Chronic Obstructive Pulmonary Disease, Pollution, Pulmonary Vascular Disease, Transplantation, Pleural Disease, and Lung Cancer in AJRCCM 2002
Division of Pulmonary and Critical Care Medicine, Loyola University of Chicago Stritch School of Medicine and Hines Veterans Affairs Hospital, Hines, Illinois&5.(0c;, 百拇医药
CONTENTS&5.(0c;, 百拇医药
TOP&5.(0c;, 百拇医药
CONTENTS&5.(0c;, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...&5.(0c;, 百拇医药
AIR POLLUTION&5.(0c;, 百拇医药
PULMONARY VASCULAR DISORDERS AND...&5.(0c;, 百拇医药
LUNG TRANSPLANTATION&5.(0c;, 百拇医药
PLEURAL DISORDERS&5.(0c;, 百拇医药
LUNG CANCER&5.(0c;, 百拇医药
REFERENCES&5.(0c;, 百拇医药
Chronic Obstructive Pulmonary Disease (49)&5.(0c;, 百拇医药
Genetics (1)&5.(0c;, 百拇医药
Epidemiology (3)
1–Antrypsin Deficiency (2)&5.(0c;, 百拇医药
Risk Factors (1)&5.(0c;, 百拇医药
Cellular, Molecular, and Anatomical Abnormalities (10)&5.(0c;, 百拇医药
Lung Inflammation (1)
Pathophysiologic and Radiologic Studies (2);jx, 百拇医药
Pulmonary Vasculature (1);jx, 百拇医药
Control of Breathing and Exercise (2);jx, 百拇医药
Respiratory Muscles (3);jx, 百拇医药
Peripheral Muscles (5);jx, 百拇医药
Drug Therapy (13);jx, 百拇医药
Muscarinic Antagonists (1);jx, 百拇医药
Theophylline (2);jx, 百拇医药
Glucocorticoids (7);jx, 百拇医药
Experimental Protease Inhibitors (3);jx, 百拇医药
Other Therapies (3);jx, 百拇医药
Lung Volume Reduction Surgery (2)1-Antitrypsin Replacement Therapy (1);jx, 百拇医药
Outcome (1);jx, 百拇医药
Workshops (1);jx, 百拇医药
Air Pollution (6);jx, 百拇医药
Air Pollution—General (5);jx, 百拇医药
Diesel Exhaust (1);jx, 百拇医药
Pulmonary Vascular Disorders and Related Disorders (17)
Pulmonary Hypertension (13)w!6;/*, http://www.100md.com
Molecular and Pathophysiologic Mechanisms (6)w!6;/*, http://www.100md.com
Treatment (7)w!6;/*, http://www.100md.com
Thromboembolic Disorders (1)w!6;/*, http://www.100md.com
Diagnostic Studies (1)w!6;/*, http://www.100md.com
High Altitude (2)w!6;/*, http://www.100md.com
Sickle Cell Disease (1)w!6;/*, http://www.100md.com
Lung Transplantation (13)w!6;/*, http://www.100md.com
Lung Preservation (3)w!6;/*, http://www.100md.com
Patient Selection (3)w!6;/*, http://www.100md.com
Obliterative Bronchiolitis (5)w!6;/*, http://www.100md.com
Animal Models (3)w!6;/*, http://www.100md.com
Early Detection (2)w!6;/*, http://www.100md.com
Rejection (1)w!6;/*, http://www.100md.com
Immunology and Biochemistry (1)w!6;/*, http://www.100md.com
Pleural Disorders (7)w!6;/*, http://www.100md.com
Physiology/Pathophysiology (3)w!6;/*, http://www.100md.com
Clinical Manifestations (1)w!6;/*, http://www.100md.com
Treatment (2)w!6;/*, http://www.100md.com
Pleurodesis (1)w!6;/*, http://www.100md.com
Lung Cancer (6)
Diagnosis (4);krn, 百拇医药
Studies of Molecular Mechanisms (1);krn, 百拇医药
Review Article (1);krn, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY DISEASE;krn, 百拇医药
TOP;krn, 百拇医药
CONTENTS;krn, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...;krn, 百拇医药
AIR POLLUTION;krn, 百拇医药
PULMONARY VASCULAR DISORDERS AND...;krn, 百拇医药
LUNG TRANSPLANTATION;krn, 百拇医药
PLEURAL DISORDERS;krn, 百拇医药
LUNG CANCER;krn, 百拇医药
REFERENCES;krn, 百拇医药
Genetics;krn, 百拇医药
Because oxidative stress is believed to contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), He and coworkers (1) studied the relationship between polymorphisms of antioxidant genes and susceptibility to accelerated decline of lung function in smokers. Of 594 white smokers in the Lung Health Study, 286 experienced a rapid decline in FEV1 (-152 ml per year) and 308 did not show a decline (+15 ml per year). None of the genotypes—glutathione S-transferase (GST) M1, T1, P1, or heme oxygenase-1—had an individual effect on decline in lung function. Rapid decline in lung function was associated with the presence of all three GST polymorphisms (odds ratio, 2.83). A combination of family history of COPD with GSTP1 105IIe/IIe genotype was associated with rapid decline in lung function (odds ratio, 2.2). The authors conclude that decline of lung function in smokers is not associated with any of the genotypes for glutathione S-transferase or hemeoxygenase-1.
Epidemiologymny)$ew, 百拇医药
In the GOLD (Global Initiative For Chronic Obstructive Lung Disease) guidelines, Stage 0 includes subjects without airway obstruction (FEV1/FVC greater than 0.70) who have respiratory symptoms (productive cough). Subjects with GOLD Stage 0 are considered at increased risk for COPD. To assess the usefulness of Stage 0, Vestbo and Lange (2) analyzed data on more than 10,000 participants in the Copenhagen City Heart Study. Criteria for GOLD Stage 0 were fulfilled by 5.8% of the total population and by 7.2% of smokers at baseline. At 5 years of follow-up, 13.2% of smokers with GOLD Stage 0 had developed a decrease in FEV1/FVC to less than 0.7; this change occurred in 11.6% of smokers without respiratory symptoms. At 15 years of follow-up, a decrease in FEV1/FVC to less than 0.7 occurred in 20.5% of smokers with GOLD Stage 0 and in 18.5% of smokers without respiratory symptoms. Multivariate logistic regression analysis revealed that GOLD Stage 0 did not identify subsequent airway obstruction. The authors conclude that GOLD Stage 0 is of little help in identifying subjects at risk of COPD and that cigarette smoking itself remains the best predictor of risk.
Eleven years after the Lung Health Study, Anthonisen and coworkers (3) did spirometry on 77% of the surviving participants. Smoking habits tended to converge; 93% of those who abstained from smoking during the study were still abstinent at 11 years. Men who quit smoking at the beginning of the study had a decline in FEV1 of 30 ml per year, as compared with a decline of 66 ml per year in men continuing to smoke throughout the 11 years. Women who quit smoking at the beginning of the study had a decline in FEV1 of 22 ml per year, as compared with a decline of 54 ml per year in women continuing to smoke throughout the 11 years. When expressed as a percentage of predicted normal value, the decline in FEV1 in male and female smokers was equivalent. At 11 years, 38% of individuals who continued to smoke had an FEV1 of less than 60% of the predicted normal value, as compared with 10% in the individuals who stopped smoking permanently. The authors conclude that the loss of lung function among continuing smokers is more rapid than previously suspected.
To determine whether measures of quality of life are associated with increased mortality, Domingo-Salvany and coworkers (4) analyzed data on a cohort of 321 men with COPD 5 to 6 years after enrollment. One third of the patients had died. Compared with survivors, the patients who died were older (70 versus 63 years), had lower body mass index (25 versus 27), lower FEV1 (34 versus 51% predicted), and made more frequent use of long-term oxygen therapy (31 versus 7%). After adjusting for relevant clinical and physiologic variables, both the total St. George's Respiratory Questionnaire and the physical summary score of SF-36 were independently associated with both all-cause mortality and respiratory mortality. The total mortality hazard ratio was 1.3 for the two measures of quality of life, and 1.6 for FEV1. The authors conclude that measures of quality of life provide independent information on the health status of men with COPD and are independently associated with mortality.
1-Antrypsin Deficiency-#j[, http://www.100md.com
Rodriguez and coworkers (5) describe a new method of screening for1-antitrypsin deficiency. The technique employs dried blood spots and a LightCycler fluorimetric analyzer. Among 72 patients with COPD, 22% had neither PiZ nor PiS mutations, 7% were non-S, non-Z heterozygotes, 35% were heterozygotes who had a PiZ plus a non-S, non-Z allele, 3% had the PiSS genotype, 3% were PiSZ, and 28% were PiZZ. All patients with two normal alleles and 10 heterozygous carries had normal levels of 1-antitrypsin. Processing of 32 samples took only 40 minutes. The authors conclude that fluorimetric analysis of dried blood specimens is suitable for large-scale screening for 1-antitrypsin deficiency.
Takubo and coworkers (6) determined whether the level of1-antitrypsin influenced the pattern of emphysema induced by cigarette smoke in mice. Exposure to cigarette smoke for four months produced emphysema (an increase in the mean linear intercept) in pallid mice that have a low level of 1-antitrypsin but not in C57 mice. After six months of smoke exposure, the degree of emphysema was equivalent in the two groups of mice. The pallid mice developed more diffuse emphysema than did the C57 mice. T cell inflammation was present in the alveolar walls of the pallid mice, but not in the C57 mice after 6 months of smoking. Lung compliance increased over the 6 months in the pallid mice but not in the C57 mice. The authors conclude that cigarette smoking produces emphysema in both pallid and C57 mice, and that the emphysema is panlobular in pallid mice that have low levels of 1-antitrypsin, whereas it is centrilobular in C57 mice.
Risk Factors8+7:', 百拇医药
Birring and coworkers (7) prospectively identified 25 patients with COPD who had never smoked or who had a smoking history of less than 5 pack-years. These patients represented 5.7% of total referrals with fixed airway obstruction over 2 years. The patients had a mean age of 70 years, were mainly women (86%), and had a mean duration of respiratory symptoms of 7 years. Mean FEV1 was 58%, and the FEV1/FVC ratio was 55%. Features on high-resolution computed tomography were typical of COPD. Sputum induction revealed eosinophilia in 9 patients and neutrophilia in 13 patients. Organ-specific autoimmune disease was present in 32% of patients, especially in the patients who did not display sputum eosinophilia (46% of patients). The authors conclude that the occurrence of COPD among nonsmokers is mainly seen in women and that some patients have features of organ-specific autoimmune disease.8+7:', 百拇医药
Cellular, Molecular, and Anatomic Abnormalities
Some exacerbations of COPD are caused by infection with nontypeable Haemophilus influenzae. Abe and coworkers (8) determined whether the lymphocytes of patients experiencing frequent exacerbations have decreased ability to recognize P6 (P6 is a lipoprotein of the outer membrane that is highly conserved among strains of nontypeable H. influenzae). The in vitro lymphocyte proliferative response to P6 was 0.82 in 10 patients with COPD who had experienced an exacerbation caused by nontypeable H. influenzae in the preceding 12 months as compared with 1.42 in 26 patients with COPD who did not have such an exacerbation, and 1.61 in 12 healthy subjects. Serum antibody levels to P6 did not differ between the two groups of patients with COPD. The lymphocyte response to an unrelated antigen, tetanus toxoid, did not differ among the three groups. The authors conclude that a decrease in the proliferation of lymphocytes in response to P6 is associated with increase in the frequency of exacerbations of COPD.
Smokers who develop COPD have bronchopulmonary inflammation, characterized by increased T lymphocytes. To determine whether patients with COPD have increased expression of CXCR3 (a chemokine receptor preferentially expressed on Type-1 T lymphocytes) and its ligand, CXCL10, Saetta and coworkers (9) studied airways of subjects undergoing lung resection for localized lesions. The numbers of CXCR3+ cells in the epithelium and submucosa of the peripheral airways of seven smokers with COPD was higher than in five smokers with normal lung function and in seven nonsmokers with normal lung function. The ligand of CXCR3, the interferon-induced protein CXCL10, was present in the bronchiolar epithelium of smokers with COPD but not in the bronchiolar epithelium of the other two groups. Most of the CXCR3 cells co-expressed CD8 and produced interferon-
. The authors conclude that the T cells infiltrating the peripheral airways of smokers with COPD have increased expression of the chemokine receptor CXCR3 and a parallel increase in its ligand CXCL10.
To characterize and qualify the inflammatory processes in the small airways of smokers with COPD, Turato and coworkers (10) studied surgical specimens from 9 patients with severe COPD (FEV1, 29% predicted) and 9 patients with a similar smoking history who had mild or absent airway obstruction (FEV1, 86% predicted). Compared with the smokers who had mild or absent airway obstruction, the smokers with severe COPD had increased numbers of leukocytes in the small airways. The leukocytes were positively correlated with the radiologic score of emphysema and residual volume, and were negatively correlated with FEV1 and diffusing capacity. The inflammatory process was characterized by an increase in CD8+ and CD4+ T lymphocytes in the airway wall and an increase in macrophages in the airway epithelium. Taking all smokers together, smoking history was correlated with both the thickness of the airway wall and the thickness of smooth muscle. Structural and cellular findings in the pulmonary arteries did not differ between the two groups. The authors conclude that the small airways of smokers with severe COPD display an increased number of leukocytes, which is correlated with severity of airway obstruction, impaired diffusing capacity, hyperinflation, and radiologic emphysema.
4-Hydroxy-2-nonenal is a highly diffusible product of lipid peroxidation and a key mediator of oxidant-induced cell signaling and apoptosis. To determine the role of this aldehyde in COPD, Rahman and coworkers (11) obtained surgical lung specimens from 23 current or ex-smokers, 11 of whom had COPD (FEV1 less than 70% of predicted) and 12 of whom did not have COPD. 4-Hydroxy-2-nonenal–modified protein levels were higher in airway and alveolar epithelial cells, endothelial cells, and neutrophils of the patients with COPD than in the subjects without COPD. FEV1 was correlated with the level of the aldehyde in bronchial endothelium (r = -0.61) and neutrophils (r = -0.56). Transforming growth factor-ß1 was correlated with the level of the aldehyde in the bronchial epithelium (r = 0.62) and alveolar epithelium (r = 0.51). The authors conclude that the levels of 4-hydroxy-2-nonenal play a role in the signaling events of lung inflammation leading to an imbalance in the expression of both proinflammatory mediators and protective antioxidant genes in COPD.
The increase in alveolar macrophages in cigarette smokers may result from increased recruitment, increased proliferation, or decreased cell death. To determine whether chronic cigarette smoke influences the expression and localization of cell-cycle and apoptotic proteins in alveolar macrophages and bronchial epithelial cells, Tomita and coworkers (12) obtained bronchial biopsies from 10 healthy smokers, 7 patients with mild to moderate asthma, and 6 control subjects. The increased numbers of alveolar macrophages in the smokers resulted only in part from increased proliferation. Expression of p21CIP1/WAF1, a key protein that regulates the cell cycle and is responsive to oxidative stress, was increased in the alveolar macrophages and in bronchial biopsies from the smokers; it was found predominantly within the cytoplasm. Compared with the control subjects and patients with asthma, B cell lymphoma leukemia (Bcl)-xL, an antiapopoptotic regulator, was highly expressed in macrophages from the smokers. In in vitro studies, hydrogen peroxide induced cytoplasmic expression of p21CIP1/WAF1 and failed to induce apoptosis. The authors conclude that p21CIP1/WAF1 and B cell lymphoma leukemia proteins are increased in alveolar macrophages of cigarette smokers and that the increase in macrophages in smokers appears to result from inhibition of apoptosis. An editorial commentary by Vignola (13) accompanies this article.
The rate-limiting enzyme in the production of glutathione is-glutamylcysteine synthetase, which is downregulated by oxidant exposure. Harju and coworkers (14) studied the localization of the enzyme in 22 patients with COPD, 20 smokers without COPD, and 13 nonsmokers. Both the heavy and light subunits of -glutamylcysteine synthetase were expressed most prominently in the large airways and localized in the cytoplasm and along the plasma membrane. The heavy subunit was more heavily expressed in the central bronchial epithelium than in peripheral bronchioli or in alveolar macrophages. Alveolar macrophages of nonsmokers had higher levels of both subunits than did macrophages of smokers. Expression of the heavy subunit in the central bronchial epithelium was greater in nonsmokers than in patients with COPD; the smokers and patients with COPD did not differ. The authors conclude that heavy and light subunits of -glutamylcysteine are expressed mainly in the large airways, and that their lower concentration in smokers may contribute to progression of oxidant-induced lung injury. An editorial commentary by Hiemstra (15) accompanies this article.
Lung tissue from patients with emphysema carries an excess of adenoviral E1A DNA, which is expressed as a protein in the airway surface epithelium and associated with an increased inflammatory response. To investigate the mechanisms whereby the latent adenoviral infection amplifies the inflammatory process, Higashimoto and coworkers (16) obtained lung tissue from three patients undergoing lung resection, and transfected cultures of bronchial epithelial cells with a plasmid containing the adenovirus 5 E1A gene. When stimulated by lipopolysaccharide, the transfected epithelial cells increased intercellular adhesion molecule-1, and interleukin-8 messenger RNA and protein expression. Lipopolysaccharide also induced greater activity of intercellular adhesion molecule-1 promoter and greater binding activity of nuclear factor-
B in nuclear extracts of the transfected cells. The transfected cells displayed constitutive expression of messenger RNA and protein for transforming growth factor-ß1. The authors conclude that transfection of human bronchial epithelial cells with adenovirus E1A DNA upregulates the production of mediators that are involved in the pathogenesis of emphysema.
To better define the role of tumor necrosis factor- as a mediator of lung damaged caused by cigarette smoking, Churg and coworkers (17) studied three groups of mice. In control mice, cigarette smoke caused increases in gene expression for tumor necrosis factor-, macrophage inflammatory protein-2, and macrophage chemoattractant protein-1; these changes returned to control values by 6 hours. Exposure of knockout mice that lacked the p55/p75 receptors for tumor necrosis factor- showed no change in the gene expression of these mediators at any time. At 24 hours, the control mice, but not the knockout mice, displayed an increase in lavage neutrophils, macrophages, desmosine (a measurement of elastin breakdown), and hydroxyproline (a measure of collagen breakdown). Exposure of pure strain 129 mice (mice that produce only low levels of tumor necrosis factor-) to cigarette smoke produced no inflammatory response at 24 hours or at 7 days. The authors conclude that tumor necrosis factor- is central to smoke-induced inflammation and tissue breakdown.
Lung Inflammationq.f(fs, http://www.100md.com
To determine the relationship between local and systemic inflammatory mediators in patients with COPD, Vernooy and coworkers (18) obtained plasma and sputum from 18 patients with COPD (FEV1, 56% predicted) and 17 healthy smokers (FEV1, 99% predicted). Compared with the control group, induced sputum from the patients revealed a higher percentage of neutrophils (81 versus 62%), and higher levels of interleukin-8 (3.7 versus 2.3 pg per ml) and soluble tumor necrosis factor-receptor 55 (237 versus 109 pg per ml). The level of tumor necrosis factor- in induced sputum was equivalent in the two groups. In plasma, the patients had a higher level of soluble tumor necrosis factor-receptor 75 than did the control group (1.9 versus 1.4 ng per ml). The levels of inflammatory mediators in plasma and induced sputum were not correlated with each other. In the patients, FEV1 was correlated with the sputum levels of interleukin-8 (r = -0.84) and soluble tumor necrosis factor-receptor 55 (r = -0.52). The levels of interleukin-8, soluble tumor necrosis factor-receptor 55, and soluble tumor necrosis factor-receptor 57 were higher in the sputum of patients with COPD who were ex-smokers than in patients who were current smokers. The authors conclude that sputum levels of neutrophils, interleukin-8, and soluble tumor necrosis factor-receptor 55 are higher in patients with COPD than in healthy smokers, and that the levels of inflammatory mediators in sputum do not correlate with the levels in plasma.
Pathophysiologic and Radiologic Studies|u&, 百拇医药
Brown and coworkers (19) compared the deposition and clearance of ultrafine technetium-99m–labeled aerosol in 10 patients with COPD (FEV1, 54% predicted) and 9 healthy subjects. For an aerosol exposure of 10 µg per m3, the dose rate was greater in the patients than in the control subjects (2.9 versus 1.9 µg per hour). The central-to-peripheral index, a measure of airway deposition, was greater in the patients than in the control subjects (1.11 versus 1.01). Clearance did not differ between the patients and the control group, and the average 24-hour retention was 85%. Particles were not seen to accumulate in the liver. The authors conclude that the deposition of ultrafine particles is greater in patients with COPD than in healthy subjects.|u&, 百拇医药
Because more women than men attend specialist cough clinics, Kastelik and coworkers (20) compared the sensitivity of the cough reflex in 60 female and 50 male patients with chronic cough. The dose of inhaled capsaicin inducing two coughs was 2.2 times smaller and the dose inducing five coughs was 6 times smaller in the women than in the men. The dose of inhaled citric acid inducing cough was 2.2 times smaller and the dose inducing five coughs was 2.8 times smaller in the women than in the men. The authors conclude that female patients with chronic cough displayed greater sensitivity to cough than do male patients.
Pulmonary Vasculatureiz*){oi, 百拇医药
To characterize the hemodynamic abnormalities in patients with severe emphysema, Scharf and coworkers (21) studied 120 patients participating in the National Emphysema Treatment Trial. The patients had an FEV1 of 27% of predicted and a residual volume of 225% of predicted; 91% of the patients had a mean pulmonary artery pressure at end-expiration of greater than 20 mm Hg, and 61% had a wedge pressure at end-expiration of greater than 12 mm Hg. Cardiac index was normal. The mean pulmonary artery pressure correlated inversely with PO2 and with severity of emphysema, and directly with the wedge pressure. On multiple stepwise regression, PO2 was not an independent predictor of mean pulmonary artery pressure. Diastolic ventricular pressures were increased without evidence of systolic dysfunction. The authors conclude that patients with severe emphysema commonly display elevated pulmonary vascular pressures, that increase in pulmonary artery pressure is not related to hypoxemia, that pulmonary hypertension is not associated with impaired systemic oxygen transport, and that high cardiac diastolic pressures do not represent systolic dysfunction.
Control of Breathing and Exercise#09}, 百拇医药
To determine factors that lead to an increase in PCO2 during exercise, O'Donnell and coworkers (22) studied 20 patients with COPD (FEV1, 34% of predicted). During maximum cycle exercise, patients increased PCO2 by 7 mm Hg (range, -6 to 25 mm Hg). The change in PCO2 from rest to exercise was best correlated with the change in PCO2 while breathing 60% oxygen (an indirect test of ventilation–perfusion mismatching; r2 = 0.62) and with resting oxygen saturation (r2 = 0.30). Serial changes in PCO2 during exercise were most closely correlated with changes in end-expiratory lung volume (r = 0.56) and oxygen saturation (r = 0.82). The authors conclude that the development of hypercapnia during exercise in patients with COPD is related to the development of dynamic hyperinflation and abnormalities of ventilation–perfusion matching. An editorial commentary by Dempsey (23) accompanies this article.
Respiratory Musclessxgo, 百拇医药
Ramirez-Sarmiento and coworkers (24) studied the effect of inspiratory muscle training on the structure of the inspiratory muscles in patients with COPD. Fourteen men (FEV1, 24% predicted) were randomized to true training or sham training. Training consisted of breathing through an inspiratory threshold device while generating 40 to 50% of maximum inspiratory pressure. The training was supervised and the sessions consisted of 30 minutes a day, 5 times a week, for 5 consecutive weeks. Training produced a 29% increase in maximal inspiratory pressure and 100% increase in inspiratory muscle endurance (the length of time that a patient was able to breathe against a load requiring the generation of 80% of maximal inspiratory pressure). Biopsies from the external intercostal muscles before and after training revealed a 38% increase in the proportion of type I fibers and a 21% increase in the size of type II fibers. Training had no effect on the structure of the vastus lateralis. The authors conclude that the improvement in inspiratory muscle strength and endurance after five weeks of supervised inspiratory muscle training is accompanied by increases in the proportion of type I fibers and the size of type II fibers. An editorial commentary by Levine and colleagues (25) accompanies this article.
It has been generally believed that shortening of the diaphragm in hyperinflated patients with COPD is accompanied by a decrease in the contribution of the diaphragm to tidal breathing. Gorman and coworkers (26) used ultrasonography and magnetometry to measure diaphragmatic length at different lung volumes in 10 men with COPD (FEV1, 23% of predicted) and 10 control subjects. The length of the diaphragm was 20% shorter in the patients at residual volume and functional residual capacity, but length was similar to that of the control subjects at total lung capacity. The length of the zone of apposition was decreased by 50% at residual volume and functional residual capacity in the patients. At a given absolute lung volume, however, the length of the zone of apposition was greater in the patients. Although mean functional residual capacity was equivalent to predicted total lung capacity in the patients, tidal volume, tidal changes in the length of the zone of apposition and length of the diaphragm, and tidal volume displaced by the diaphragm were equivalent in the patients and in the control subjects. The authors conclude that, despite shortening of the diaphragm in patients with COPD, the motion and change in length of the diaphragm during tidal breathing is equivalent in patients with COPD and healthy subjects.
Peripheral Muscleso]}!n+, 百拇医药
To determine the role of apoptosis of skeletal muscle in causing weight loss in patients with COPD, Agusti and coworkers (27) obtained biopsies from the quadriceps femoris in 7 patients with COPD who had a low body mass index (less than 20 kg per m2), 8 patients with COPD who had a normal body weight, 8 healthy volunteers, and 6 subjects requiring orthopedic surgery (to assess effects of inactivity). The percentage of cells positive for TUNEL (transferase-mediated dUTP nick and labeling) was 57% in patients with COPD and low body weight, 17% in patients with COPD and normal body weight, 6% in the orthopedic patients, and 4% in healthy subjects. A similar pattern was seen with another marker of apoptosis: the immunodetection of poly-(ADP-ribose)-polymerase proteolytic fragments (PARP). In the patients with COPD, body mass index was inversely related to apoptosis, as measured by TUNEL (r = -0.65). Body mass index was also related to peak oxygen consumption during exercise (r = 0.74) and to FEV1 (r = 0.66). Markers of skeletal muscle apoptosis were not related to any variables of lung function. The authors conclude that apoptosis of skeletal muscle is increased in patients with COPD who have a low body mass index and is associated with impaired exercise tolerance independently of the effect on lung function. An editorial commentary by Lewis (28) accompanies this article.
To compare the relative efficacy of strength versus endurance training, Ortega and coworkers (29) studied 47 patients with COPD. Strength training consisted of a series of weight-lifting exercises, and endurance training consisted of leg exercises on an ergocycle at 70% of peak work rate. Improvements in dyspnea and quality of life were still evident at three months after completing the training program. Compared with patients undergoing strength training alone, improvements in submaximal exercise capacity were greater in patients undergoing either endurance training or the combination of endurance training and strength training. Increases in the strength of muscle groups (chest pull, neck press, leg flexion and extension) were equivalent in patients undergoing strength training alone and patients undergoing the combination of strength training plus endurance training: the increases in strength in both of these groups was higher than in patients undergoing endurance training alone. Increase in walking distance was restricted to the group undergoing strength training. The authors conclude that a combination of strength training plus endurance training achieves maximal muscle training in patients with COPD.
To determine whether muscle mass is a better predictor of survival than is body mass index, Marquis and coworkers (30) followed 142 patients with COPD (FEV1, 42% of predicted) for an average of 41 months. Only the cross-sectional area of midthigh muscle (obtained by computed tomography) and FEV1 were significant predictors of mortality. Mortality was not related to body mass index, thigh circumference, age, sex, daily use of glucocorticoids, diffusing capacity, PO2, PCO2, or peak work rate during exercise. Compared with the patients who had an FEV1 of at least 50% of predicted plus a midthigh muscle area of at least 70 cm2, the patients who had an FEV1 of less than 50% of predicted and a muscle area of at least 70 cm2 had a mortality odds ratio of 3.37. Compared with the patients who had an FEV1 of at least 50% of predicted plus a midthigh muscle area of at least 70 cm2, the patients who had an FEV1 of less than 50% of predicted and muscle area of less than 70 cm2 had a mortality odds ratio of 13.16. Anthropometric measurements could not predict midthigh muscle area. The authors conclude that midthigh cross-sectional muscle area is a better predictor of mortality in patients with COPD than is body mass index. An editorial commentary by Mador (31) accompanies this article.
Drug Therapy+yvo, 百拇医药
Muscarinic antagonists.+yvo, 百拇医药
The Lung Health Study involved 5,887 smokers who did not regard themselves as ill but who had mild to moderate impairment of lung function. Anthonisen and coworkers (32) analyzed the data to assess factors influencing morbidity and mortality. Over 5 years, 149 (2.5%) participants died, largely from lung cancer and cardiovascular disease. A total of 12.8% of participants were hospitalized: 75% of hospitalizations resulted from cancer, cardiovascular disease, and nonmalignant respiratory disease. Death and hospitalizations for cardiovascular disease and coronary artery disease tended to be more common in individuals assigned to the smoking intervention plus ipratropium bromide arm of the study than among individuals in the smoking intervention plus placebo arm (the difference approached statistical significance). Nine individuals in the smoking intervention plus ipratropium arm were hospitalized for supraventricular tachycardia as compared with two individuals in the smoking intervention plus placebo arm. The authors conclude that use of ipratropium bromide was associated with an increased tendency for cardiovascular disease and supraventricular tachycardia.
Theophylline./, http://www.100md.com
Culpitt and coworkers (33) asked, "Does theophylline decrease airway inflammation in patients with COPD?" In a double-blind randomized trial, 25 patients with COPD were treated with low-dose theophylline (plasma level 9 to 11 mg per liter) for 4 weeks. Theophylline produced decreases of about 22% in induced sputum inflammatory cells, neutrophils, interleukin-8, myeloperoxidase, and lactoferrin. Neutrophils from subjects treated with theophylline displayed a decrease in chemotaxis to N-formyl-met-leu-phe of about 28% and to interleukin-8 of about 60%. Theophylline produced a 34% decrease in the chemotaxis of healthy donor neutrophils to induced sputum. The authors conclude that administration of theophylline to patients with COPD produces a decrease in sputum neutrophils, sputum chemotactic activity, and chemotaxis of peripheral blood neutrophils to chemotactic stimuli. An editorial commentary by Rabe (34) accompanies this article./, http://www.100md.com
Glucocorticoids.
In 199 patients with an acute exacerbation of COPD, Maltais and coworkers (35) did a double-blind randomized trial of nebulized budesonide (2 mg every 6 hours), oral prednisolone (30 mg every 12 hours), and placebo. Compared with placebo, the postbronchodilator FEV1 was 0.10 liter higher with budesonide and 0.16 liter higher with prednisolone; the difference between budesonide and prednisolone was not significant. Adverse effects were equivalent with the three therapies, although hyperglycemia was more common with prednisolone than with budesonide. The authors conclude that nebulized budesonide is as effective as oral prednisolone in the management of acute exacerbations of COPD.h, 百拇医药
To determine the effect of stopping high-dose inhaled glucocorticoids in patients with COPD, van der Valk and coworkers (36) did a double-blind randomized study in 244 patients who had received inhaled fluticasone propionate (1,000 µg daily) for 4 months. Over the subsequent 6 months, 57% of the 121 patients in the placebo group developed at least one exacerbation as compared with 47% of the 123 patients in the fluticasone group. The hazard ratio of a first exacerbation was 1.5 in the placebo versus the fluticasone group. Measures of quality of life, in terms of total score, activity domain, and symptom domain were higher in the fluticasone group than in the placebo group. The authors conclude that the discontinuation of inhaled glucocorticoids in patients with COPD leads to an increased risk of exacerbation and a deterioration in the quality of life.
The effect of inhaled glucocorticoids on the profile of inflammatory cells in the airways of patients with COPD is not known. Accordingly, Hattotuwa and coworkers (37) did a double-blind randomized trial of inhaled fluticasone propionate (500 µg twice daily) versus placebo in 31 patients with COPD. Bronchial biopsies at three months revealed no difference between the groups in the primary endpoints: number of CD8+ cells, CD68+ cells, and neutrophils (which are considered important in COPD). Patients receiving fluticasone showed a reduction in the ratio of CD8 to CD4 cells in the epithelium and a reduction in the number of mast cells in the subepithelium. Patients receiving fluticasone had an improvement in symptoms and fewer exacerbations. The authors conclude that inhaled fluticasone propionate has no effect on the major inflammatory cell types in the airways of patients with COPD, although it reduces the ratio of CD8 to CD4 cells in the epithelium and the number of mast cells in the subepithelium. An editorial commentary by Pauwels (38) accompanies this article.
In 691 patients with COPD, Mahler and coworkers (39) did a randomized controlled comparison of inhaled salmeterol (50 µg), fluticasone propionate (500 µg), the combination of salmeterol and fluticasone, and placebo. Agents were inhaled via a Diskus device twice daily for 24 weeks. At the endpoint, the increase in predose FEV1 was greater with the fluticasone-salmeterol combination (156 ml) than with salmeterol (107 ml) and placebo (-4 ml). The increase in 2-hour postdose FEV1 was greater with the fluticasone–salmeterol combination (261 ml) than with fluticasone (138 ml) and placebo (28 ml). Improvements in dyspnea were also greater with the combination therapy. The authors conclude that combination of fluticasone propionate and salmeterol delivered via a Diskus device achieves greater improvement in lung function and dyspnea than either agent on its own..d\, 百拇医药
To determine the relationship between use of glucocorticoids, bone mineral density, and fracture, Walsh and coworkers (40) studied patients who had taken continuous or frequent courses of oral glucocorticoids for asthma, COPD or idiopathic pulmonary fibrosis over the preceding six months. Of 117 patients, 48% were women, 58% had osteoporosis, and 61% had a vertebral fracture. The presence of a vertebral fracture was related to bone mineral density of the femoral neck (measured by X-ray absorptiometry): odds ratio was 1.6 for a reduction of 1 SD in density. Between the highest and lowest quartile dose of prednisolone, the risk of vertebral fracture increased 4.4-fold; adding bone density of the femoral neck did not alter the relationship. The authors conclude the risk of vertebral fracture is strongly related to the cumulative dose of prednisolone and that this effect is independent of its more modest effect on bone mineral density.
To determine whether the use of inhaled glucocorticoids are associated with the development of a hip fracture, Hubbard and coworkers (41) did a case–control study of 16,341 cases of hip fracture in a general practice research database and 29,889 control subjects. After adjusting for potential confounders, conditional logistic regression revealed an association between hip fracture and inhaled glucocorticoids (odds ratio, 1.26). After adjusting for annual courses of oral glucocorticoids, the odds ratio was reduced to 1.19. Hip fractures displayed a dose–response relationship to inhaled glucocorticoids. The authors conclude that use of inhaled glucocorticoids is associated with the development of hip fracture in older subjects.h?||, 百拇医药
Experimental protease inhibitors.h?||, 百拇医药
In a rat model of emphysema, the retinoid, all-trans-retinoic acid, reverses anatomic and physiologic signs of emphysema. Mao and coworkers (42) tested the feasibility of this agent in 20 patients with severe emphysema using a double-blind crossover design over 6 months. The treatment was generally well tolerated. Side effects included skin changes, transient headaches, hyperlipidemia, and musculoskeletal pains. Pulmonary function and computed tomographic images did not change. Plasma drug levels varied appreciably among subjects and decreased over time in 35% of the participants. The authors conclude that it is feasible to undertake a trial of therapy with all-trans-retinoic acid in patients with emphysema.
ONO-6818 is a novel oral agent that inhibits neutrophil elastase. To investigate its effect, Kuraki and coworkers (43) studied four groups of rats. Oral administration of ONO-6818 1 hour before application of human neutrophil elastase ameliorated the increases in lung myeloperoxidase activity, hemoglobin, and neutrophil counts in bronchoalveolar fluid at 6 hours. Eight weeks later, the rats treated with ONO-6818 had less severe increases in functional residual capacity, total lung capacity, lung compliance, and mean linear intercept. The authors conclude that the induction of emphysema by human neutrophil elastase is inhibited by the oral neutrophil elastase inhibitor, ONO-6818, mainly through minimizing lung hemorrhage and the accumulation of neutrophils in the lung.rza^p, 百拇医药
To determine whether an orally active inhibitor of serine elastase, ZD 0892, decreases emphysematous lung destruction, Wright and coworkers (44) exposed guinea pigs to cigarette smoke. Acute exposure to smoke caused increased lavage neutrophils and increased desmosine and hydroxyproline (measures of elastin and collagen breakdown). These changes were reduced by the elastase inhibitor. Exposure to cigarette smoke every day for six months produced emphysema and caused increases in lavage neutrophils, desmosine, and hydroxyproline, and in plasma tumor necrosis factor-. The elastase inhibitor returned the lavage levels of neutrophils, desmosine and hydroxyproline to control values, decreased tumor necrosis factor- by 30%, and decreased the airspace enlargement by 45%. Exposure of animals to smoke plus the elastase inhibitor for two months, preceded by exposure to smoke for four months, did not protect against the development of emphysema. Mice exposed to smoke showed increases in gene expression of neutrophil chemoattractant macrophage inflammatory protein-, macrophage chemoattractant protein-1, and tumor necrosis factor-; these changes were prevented or decreased by the elastase inhibitor. The authors conclude that a serine elastase inhibitor ameliorates the inflammatory and destructive effects of cigarette smoke and that these effects are mediated in part by neutrophils and the production of tumor necrosis factor-.
Other Therapies^9*j0', 百拇医药
Lung volume reduction surgery.^9*j0', 百拇医药
The mismatch between the size of the lungs and the size of the chest cavity in patients with emphysema is thought to be an important determinant of the reduced forced vital capacity (FVC) and FEV1 in this condition. In 13 patients undergoing lung volume reduction surgery, Fessler and coworkers (45) found that the ratio of residual volume to total lung capacity—a measure of the mismatch between lung size and chest size—was the only independent predictor of the increase in FVC after surgery. Of the increase in FEV1 after surgery, 70% was attributable to the increase in FVC and the remainder to the increase in FEV1/FVC ratio. In another group of 78 patients undergoing lung volume reduction surgery, the ratio of residual volume to total lung capacity was again correlated with the increase in FVC after surgery; the ratio, however, did not predict the increase in FEV1. The authors conclude that the ratio of residual volume to total lung capacity is the major determinant of the increase in forced vital capacity achieved by lung volume reduction surgery.
In 12 patients with severe emphysema (FEV1, 0.69 liters; 23% predicted) undergoing lung volume reduction surgery, Mineo and coworkers (46) assessed right ventricular function before and 6 months after the surgery. Surgery produced a 59% increase in FEV1, a 23% decrease in the ratio of residual volume to total lung capacity, a 12% increase in cardiac index during rest, and a 9% increase in right-ventricular stroke volume. During submaximal exercise, cardiac index increased by 22%, right-ventricular stroke volume increased by 28%, and right-ventricular ejection fraction increased by 20% after surgery. The improvement in ejection fraction during exercise was correlated with the decrease in the ratio of residual volume to total lung capacity after surgery (r = -0.68). The authors conclude that lung volume reduction surgery produces an improvement in right ventricular performance in patients with emphysema, especially during exercise.(0c;:@l, 百拇医药
1-Antitrypsin replacement therapy.
In 12 patients with -antitrypsin deficiency, Stockley and coworkers (47) studied the effect of four infusions of Prolastin at weekly intervals on airway inflammation. The serum level of -antitrypsin rose and was maintained above the protective threshold. One week after the first infusion, the level of -antitrypsin in expectorated sputum increased from 0.17 to 0.43 µm (equivalent to the value in normal subjects). Chemoattractant B4 and elastase activity in the sputum samples decreased. The authors conclude that short-term therapy with Prolastin restores airway concentrations of 1-antitrypsin to normal and it decreases the level leukotriene B4 (a major mediator of neutrophil recruitment and augmentation) in airway secretions./s|w, 百拇医药
Outcome/s|w, 百拇医药
To determine whether COPD interferes with a person's ability to work, Sin and coworkers (48) analyzed data from 12,436 participants in NHANES III (Third National Health and Nutrition Examination Survey) study, 8.6% of whom reported COPD. Compared with participants without COPD, those reporting COPD were 3.9% less likely to be in the labor force. The decreased likelihood of being in the labor force was proportional to disease severity: 3.4%, 3.9%, and 14.4% for subjects with mild, moderate and severe COPD, respectively. The decrease in ability to work was estimated to cause a loss of $9.9 billion in the United States. The authors conclude that a self-report of COPD is associated with a considerable reduction in a person's ability to work.
Workshops/*30r;k, 百拇医药
In a summary report from a NHLBI workshop, Croxton and colleagues (49) review future directions for research on COPD./*30r;k, 百拇医药
AIR POLLUTION/*30r;k, 百拇医药
TOP/*30r;k, 百拇医药
CONTENTS/*30r;k, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY.../*30r;k, 百拇医药
AIR POLLUTION/*30r;k, 百拇医药
PULMONARY VASCULAR DISORDERS AND.../*30r;k, 百拇医药
LUNG TRANSPLANTATION/*30r;k, 百拇医药
PLEURAL DISORDERS/*30r;k, 百拇医药
LUNG CANCER/*30r;k, 百拇医药
REFERENCES/*30r;k, 百拇医药
Air Pollution–General/*30r;k, 百拇医药
To determine whether concentrated ambient air particles induce pulmonary inflammation in normal rats and in rats with chronic bronchitis, Saldiva and coworkers (50) exposed four groups of rats (some healthy and some with chronic bronchitis secondary to sulfur dioxide) to filtered air or to concentrated ambient air particles for five hours a day for three consecutive days. Concentrated ambient air particles caused an increase in neutrophils in the bronchoalveolar fluid of both the normal rats and the rats with chronic bronchitis. The particles caused an increase in the numerical density of neutrophils in the alveolar walls only in normal rats; the density was greater in the central regions than in the peripheral regions of the lung. A dose-dependent relationship was found between many components of concentrated ambient air particles (especially vanadium and bromine) and neutrophils and lymphocytes in bronchoalveolar fluid. The authors conclude that short-term exposure to concentrated ambient air particles induces a significant inflammatory reaction in the lungs of rats.
Particulate air pollution is associated with cardiovascular morbidity and mortality. To investigate this association, Nemmar and coworkers (51) studied the effect of intravenous and intratracheal administration of ultrafine (60 nm) polystyrene particles on thrombus formation in a hamster model. Intravenous administration of unmodified particles had no effect on thrombus formation. Intravenous administration of amine-polystyrene particles enhanced thrombosis at high but not at low concentrations. High concentrations of carboxylate-polystyrene particles inhibited thrombus formation. Intratracheal instillation of amino-polystyrene particles caused an increase in thrombus formation, whereas unmodified particles and carboxylate-polysterene particles had no effect. Unmodified particles did not alter the aggregation of platelets in human plasma induced by ADP, whereas carboxylate-polystyrene particles weakly enhanced platelet aggregation. Amine-polystyrene particles were sufficient to induce platelet aggregation on their own and strongly enhanced aggregation induced by ADP. The authors conclude that the presence of ultrafine particles in the circulation increases the tendency toward thrombosis, resulting in part from platelet activation and depending on the surface charge of the particles.
To determine whether antioxidant vitamins could modulate the adverse effect of air pollution on lung function in children, Romieu and coworkers (52) did a double-blind randomized study in 158 children with asthma who lived in Mexico City. During the 31-month study, the average maximum level of ozone was 102 ppb and the mean 24-hour average level of particulates with a mass median diameter of less than 10 µm (PM10) was 57 µg per m3. Pulmonary function was measured twice weekly. In the placebo group, the children with moderate and severe asthma showed an inverse relationship between the level of ozone (on the day before spirometry) and peak expiratory flow (-15 ml per second per 10 ppb), forced expiratory flow (FEF25–75, -13.3 ml per second per 10 ppb), and FEV1 (-4.6 ml per 10 ppb). In children treated with vitamin E (50 mg daily) and vitamin C (250 mg daily), no association was seen between ozone and lung function. The authors conclude that antioxidant supplements might modulate the impact of exposure to ozone on the small airways of children with moderate to severe asthma.
To determine whether exposure to ambient air pollutants affects the growth of lung function in children, Gauderman and coworkers (53) studied 2,081 fourth-grade children (average age, 9.9 years). Exposure to acid vapor, nitrogen dioxide, particles with an aerodynamic diameter of less than 2.5 µm (PM2.5), and elemental carbon were associated with significant deficits in the growth of lung function. Across the range of acid exposure, for example, the average annual growth rates of MMEF and FEV1 were reduced by 11% and 5%, respectively. Exposure to acid vapor was associated with a decrease in the ratio of MMEF to FVC, whereas exposure to ozone was associated with a reduced rate of growth in PEF. Children spending more time outdoors experienced greater deficits in lung function. The authors conclude that exposure to ambient levels of air pollutants has a detrimental effect on growth of lung function in children.no, 百拇医药
To determine the relationship between exposure to air pollution related to traffic and the development of asthmatic symptoms, allergic diseases, and respiratory infections, Brauer and coworkers (54) studied a birth cohort of 4,146 children. Outdoor concentrations of traffic-related air pollutants were modeled for the home of each subject. Adjusted odds ratios for wheezing, physician-diagnosed asthma, infections of the ear, nose or throat, and serious colds at 2 years of age were associated with air pollutants; some of the associations reached borderline statistical significance. The authors conclude that traffic-related air pollution may be associated with the prevalence of respiratory illness at 2 years of age.
Diesel Exhaust1a, 百拇医药
Takano and coworkers (55) determined whether diesel exhaust particles enhance lung inflammation caused by endotoxin in mice. Instillation of diesel exhaust particles into the trachea of mice synergistically enhanced the lung inflammation caused by endotoxin, which was characterized by neutrophil sequestration, interstitial edema, and alveolar hemorrhage. Given alone, diesel exhaust particles increased the lung expression of Toll-like receptor 4 and nuclear localization of the p50 subunit of nuclear factor-B. In the presence of endotoxin, diesel exhaust particles further activated the nuclear translocation of the p65 subunit of nuclear factor-B in the lung, and increased the lung expression of intercellular adhesion molecule-1, interleukin-1ß, macrophage chemoattractant protein-1, keratinocyte chemoattractant, macrophage inflammatory protein-1, and Toll-like receptors. The combined exposure to diesel exhaust particles and endotoxin decreased the nuclear localization of CCAAT/enhancer binding protein B. The authors conclude that diesel exhaust particles enhance neutrophilic lung inflammation related to endotoxin and that the enhancement is mediated through the induction of proinflammatory molecules, such as expression of Toll-like receptors and activation of p65-containing dimers of nuclear factor-B.
PULMONARY VASCULAR DISORDERS AND RELATED DISORDERSimpg(2?, 百拇医药
TOPimpg(2?, 百拇医药
CONTENTSimpg(2?, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...impg(2?, 百拇医药
AIR POLLUTIONimpg(2?, 百拇医药
PULMONARY VASCULAR DISORDERS AND...impg(2?, 百拇医药
LUNG TRANSPLANTATIONimpg(2?, 百拇医药
PLEURAL DISORDERSimpg(2?, 百拇医药
LUNG CANCERimpg(2?, 百拇医药
REFERENCESimpg(2?, 百拇医药
Pulmonary Hypertensionimpg(2?, 百拇医药
Molecular and pathophysiologic mechanisms.impg(2?, 百拇医药
The CX3E chemokine, fractalkine, is produced by endothelial cells, promotes leukocyte recruitment, and is unique because it exists both in a soluble form (chemotactic protein) and in a membrane-anchored form on endothelial cells (cell-adhesion molecule). To assess the role of fractalkine in the recruitment of cells to the lungs of patients with pulmonary hypertension, Balabanian and coworkers (56) studied seven patients with pulmonary arterial hypertension and eight patients with chronic thromboembolic pulmonary hypertension. The fractalkine receptor (CX3CR1) was upregulated in circulating T lymphocytes (mostly in the CD4+ subset) in patients with pulmonary arterial hypertension. The abnormal response of T lymphocytes to fractalkine was not secondary to high vascular pressure because it did not occur in patients with chronic thromboembolic hypertension. Concentrations of soluble fractalkine were higher in patients with pulmonary arterial hypertension than in patients with chronic thromboembolic hypertension and control subjects. Messenger RNA and the protein product of fractalkine were expressed in pulmonary artery endothelial cells of patients with pulmonary arterial hypertension. The authors conclude that inflammatory mechanisms involving the chemokine fractalkine and its receptor contribute to the injury of pulmonary arterial hypertension. An editorial commentary by Williams (57) accompanies this article.
Endothelin-1 has been implicated in pulmonary hypertension because of its dual vasoconstrictor and mitogenic actions. The effects of endothelin-1 are mediated via two distinct receptors: endothelinA and endothelinB. Davie and coworkers (58) examined the distribution of these receptors in the pulmonary arteries, and studied their role in mediating the proliferative actions of endothelin-1. EndothelinB receptors were more frequent in the distal arteries than in the proximal arteries: 36% versus 3%. The density of receptors in distal arteries and lung parenchyma was twice as great in 22 patients with pulmonary hypertension than in 13 control subjects. Endothelin-1 stimulated DNA synthesis and attenuated the antiproliferative action of cicaprost and forskolin on pulmonary artery smooth muscle cells; these effects were mediated by both the endothelinA and endothelinB receptors. The stimulation of smooth muscle proliferation by serum was attenuated by inhibiting either the release of endothelin-1 (with phosphoramidon) or the action of endothelin-1 (with PD 145,065). Cicaprost inhibited the release of endothelin-1 from the smooth muscle cells and increased the intracellular concentration of cyclic AMP, whereas stimulation of the endothelinB receptor decreased the concentration of cyclic AMP. The authors conclude that the distributions of endothelinA and endothelinB receptors differ in human pulmonary arteries, and that both receptors promote the proliferation of smooth muscle cells and may contribute to vascular remodeling in pulmonary hypertension.
The plexiform lesions of primary pulmonary hypertension contain macrophages and lymphocytes. Because RANTES (regulated upon activation, normal T cell expressed and secreted) is an important chemoattractant for monocytes and T cells, Dorfmuller and coworkers (59) determined whether this chemokine promotes cell recruitment in the lungs of patients with pulmonary hypertension. The expression of RANTES was eight times greater in lung samples from 10 patients with severe pulmonary hypertension than in the lungs of 7 control subjects. The major source of RANTES was the endothelial cells within the pulmonary artery wall. The expression of RANTES was associated with infiltrates of CD45+ inflammatory cells. The authors conclude that inflammatory mechanisms play a role in the natural history of pulmonary hypertension.arc{s?, 百拇医药
In the hepatopulmonary syndrome, dilatation of pulmonary vessels is related to increased production of nitric oxide secondary to increased expression of inducible nitric oxide synthase by macrophages in the pulmonary vessels and less so to endothelial nitric oxide synthase. To investigate the role of translocation of gut bacteria in this syndrome, Rabiller and coworkers (60) administered a 5-week course of norfloxacin to rats with cirrhosis induced by ligation of the common bile duct. Norfloxacin decreased the incidence of gram-negative translocation from 70 to 0%, and it decreased the proportion of pulmonary microvessels containing more than 10 macrophages from 52 to 21%. Features of dilated pulmonary vessels (increased alveolar-to-arterial oxygen difference and cerebral uptake of labeled macro aggregates) were decreased to a level that fell between sham-operated rats and untreated cirrhotic rats. Norfloxacin decreased the expression and activity of inducible nitric oxide-synthase to normal, but not that of endothelial nitric oxide synthase. The authors conclude that norfloxacin decreases the severity of hepatopulmonary syndrome in cirrhotic rats by inhibiting translocation of gut bacteria and decreasing the production of nitric oxide by macrophages in pulmonary vessels.
Reeves (61) recalls early studies on pulmonary vasoconstriction in cattle at high altitude.n, http://www.100md.com
Treatment.n, http://www.100md.com
In patients with primary pulmonary hypertension, prostacyclin improves exercise tolerance within the first few weeks of treatment, even in patients who show no change in resting pulmonary hemodynamics. To determine whether the improved exercise tolerance is accompanied by improvement in the pressure-flow characteristics of the pulmonary circulation during exercise, Castelain and coworkers (62) studied seven patients with primary pulmonary hypertension before and after continuous infusion of prostacyclin for six weeks. The patients did not respond to an acute inhalation of nitric oxide. Prostacyclin produced an increase of 81 m in the six-minute walking distance. Prostacyclin caused a 28% decrease in the slope of mean pulmonary artery pressure plotted against cardiac index. The authors conclude that the improvement in exercise performance achieved by prostacyclin in patients with primary pulmonary hypertension results from blunting of the increase in pulmonary vascular resistance during exercise.
Prostacyclin requires a permanent central venous catheter, whereas the stable prostacyclin analog, treprostinil, can be given by subcutaneous infusion and has a longer half-life. In 470 patients with primary pulmonary hypertension, Simmonneau and coworkers (63) did a 12-week double-blind, placebo-controlled trial. Treprostinil increased the 6-minute walking distance by 16 m, and it improved dyspnea, signs and symptoms of pulmonary hypertension, and hemodynamics. Pain at the infusion site occurred in 85% of the treprostinil group, requiring premature discontinuation of therapy in 8% of patients. The authors conclude that chronic subcutaneous infusion of treprostinil is effective in patients with pulmonary hypertension and that its safety profile is acceptable.cpi$z, http://www.100md.com
To determine the frequency and outcome of cardiopulmonary resuscitation in patients with pulmonary artery hypertension, Hoeper and coworkers (64) analyzed data on 3,130 patients from 17 referral centers in Europe and the United States. Circulatory arrest occurred in 513 patients and cardiopulmonary resuscitation was attempted in 132 (26%) of the patients. Resuscitation efforts were primarily unsuccessful in 104 patients (79%), and only 8 patients (6%) survived for more than 90 days. Hemodynamic measures within three months before the arrest did not predict outcome. The authors conclude that cardiopulmonary resuscitation is rarely successful in patients with pulmonary artery hypertension.
In a rat model of pulmonary hypertension induced by left pneumonectomy and injection of monocrotaline, Nishimura and coworkers (65) studied the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Compared with rats treated with placebo, rats treated with simvastatin from Days 5 to 35 after induction of pulmonary hypertension had a lower mean pulmonary artery pressure (27 versus 53 mm Hg) and less pulmonary vascular remodeling with neointimal formation (scores of 0.6 versus 2.0). Expression of the gene for nitric oxide synthase in lung endothelium was decreased in the mice treated with placebo, but the levels returned toward normal in the mice treated with simvastatin. The authors conclude that simvastatin attenuates pulmonary arterial hypertension, right-ventricular hypertrophy, and neointimal formation in pneumonectomized mice treated with monocrotaline. An editorial commentary by Rubin (66) accompanies this article.-^'fw{&, 百拇医药
In a model of neonatal pulmonary hypertension in piglets, Shekerdemian and coworkers (67) studied the effect of intravenous sildenafil, a phosphodiesterase-5 inhibitor. Instilling human meconium into the trachea of piglets produced a 70% increase in pulmonary vascular resistance and a 100% increase in oxygenation index. Within 1 hour of commencing the infusion of sildenafil, pulmonary vascular resistance was reversed completely as compared with a 40% decrease in resistance after treatment with inhaled nitric oxide for 2 hours. Sildenafil also increased cardiac output by 30% without an adverse effect on oxygenation. The authors conclude that intravenous sildenafil is a selective and highly effective pulmonary vasodilator in piglets that have neonatal pulmonary hypertension.
In a pulmonary perspective, Hoeper and colleagues (68) discuss new treatments for pulmonary arterial hypertension.|\, 百拇医药
Thromboembolic Disorders|\, 百拇医药
Diagnostic studies.|\, 百拇医药
In a prospective study of 314 consecutive patients, de Monye and coworkers (69) asked, "Is the accuracy of D-dimer assays in diagnosing pulmonary embolism influenced by the location of the embolus?" Emboli were confined to subsegmental arteries in 20% of the patients. The area under a receiver operating characteristic curve for D-dimer was higher when pulmonary emboli were located in segmental or larger arteries than when emboli were located in subsegmental arteries: 0.86 versus 0.59. Sensitivity of D-dimer in excluding segmental or larger emboli was higher than for excluding subsegmental emboli: 93% versus 50%. The authors conclude that D-dimer assays are not reliable in excluding small subsegmental pulmonary emboli.|\, 百拇医药
High Altitude
In a study of inhabitants on the mountains of Kyrgyzstan, Aldashev and coworkers (70) estimated the prevalence of high-altitude pulmonary hypertension and determined whether polymorphisms of the gene for angiotensin-converting enzyme are associated with pulmonary hypertension. An electrocardiographic survey of 741 highlanders revealed features of cor pulmonale in 14% of subjects. Among an independent group of 136 male highlanders with dyspnea at altitude, 20% had a mean pulmonary artery pressure of greater than 25 mm Hg and another 26% developed an increase in pulmonary artery pressure when breathing 11% oxygen. On follow-up after 10 years, mean pulmonary artery pressure increased by 35% in the subjects who hyperresponded to 11% oxygen, by 20% in the subjects who previously displayed resting pulmonary hypertension, and by 6% in the normal subjects. Insertion/deletion (I/D) genotyping for angiotensin-converting enzyme revealed that the I/I genotype was three times more common in highlanders with pulmonary hypertension than in normal highlanders. Mean pulmonary artery pressure was higher in highlanders with the I/I genotype (27 mm Hg) than in highlanders with the I/D genotype (21 mm Hg) or the D/D genotype (18 mm Hg). The authors conclude that pulmonary hypertension is common among Kyrgyzstan highlanders, its development can be predicted by the response to acute hypoxia, and that high-altitude pulmonary hypertension is associated with insertion/deletion polymorphism of the gene for angiotensin-converting enzyme.
A polymorphism of the gene for angiotensin-converting enzyme has been identified in which the presence (insertion, I allele), as opposed to the absence (deletion, D allele), of a fragment is associated with low tissue levels of the enzyme and enhanced performance in endurance athletes. An excess of the I allele has also been noted in South American natives living above 3,000 m. To determine whether this polymorphism is associated with oxygen saturation at high altitude, Woods and coworkers (71) studied 32 individuals who ascended to 5,000 m over 12 days and 40 individuals who ascended over 18.5 days. In the slow ascent group, oxygen saturation at rest and the fall in saturation with ascent were independent of genotype for angiotensin-converting enzyme. In the rapid ascent group, oxygen saturation was associated with genotype and saturation was relatively well sustained in the II subjects. The authors conclude that the insertion allele of the gene for angiotensin-converting enzyme is associated with maintenance of oxygen saturation during rapid ascent to high altitude.
Sickle Cell Disease3ld.x, 百拇医药
To determine the mechanisms of exercise limitation in patients with sickle cell anemia, Callahan and coworkers (72) had 17 adult women with sickle cell anemia perform maximal cardiopulmonary exercise tests. Blood gases and lactate concentrations were measured every two minutes. All patients completed the test without complications and none displayed a mechanical ventilatory limitation. Three patterns of response were seen: 11 patients had a pattern consistent with pulmonary vascular disease (low peak oxygen consumption, low anaerobic threshold, gas exchange abnormalities, and high ventilatory reserve); 3 patients had a pattern consistent with peripheral vascular disease, a myopathy, or both (low peak oxygen consumption, low anaerobic threshold, no gas exchange abnormalities, and a high heart rate reserve); and 3 patients had a pattern consistent with anemia (low peak oxygen consumption, low anaerobic threshold, no gas exchange abnormalities, and a low heart rate reserve). The authors conclude that a substantial proportion of patients with sickle cell anemia develop features of pulmonary vascular disease during exercise.
LUNG TRANSPLANTATION#.\u, 百拇医药
TOP#.\u, 百拇医药
CONTENTS#.\u, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...#.\u, 百拇医药
AIR POLLUTION#.\u, 百拇医药
PULMONARY VASCULAR DISORDERS AND...#.\u, 百拇医药
LUNG TRANSPLANTATION#.\u, 百拇医药
PLEURAL DISORDERS#.\u, 百拇医药
LUNG CANCER#.\u, 百拇医药
REFERENCES#.\u, 百拇医药
Lung Preservation#.\u, 百拇医药
To gain insight into pathophysiology of preservation and reperfusion injury during lung transplantation, de Perrot and coworkers (73) studied the kinetics of cytokine release in 18 consecutive patients undergoing bilateral lung transplantation. The levels of tumor necrosis factor-, interferon-, interleukin-10, interleukin-12, and interleukin-18 were elevated during ischemia time. Interleukin-8 was predominantly increased after reperfusion; the level of interleukin-8 after two hours of reperfusion was correlated with the PO2/FIO2 ratio (r2 = 0.50), mean airway pressure (r2 = 0.60), APACHE score during the first 24 hours after surgery (r2 = 0.30), and length of stay in the intensive care unit. The authors conclude that the level of interleukin-8 is a significant predictor of graft function after lung transplantation.
The current surgical procedures for lung transplantation do not reinstitute the systemic circulation of the graft. Nowak and coworkers (74) determined whether revascularization of the bronchial arteries would decrease ischemia–reperfusion injury in the transplanted lungs of dogs. Compared with control dogs, dogs undergoing either conventional lung transplantation or bronchial artery revascularization had higher levels of lactate dehydrogenase and carboxypeptidase M (a marker for type I pneumocytes) at 2 and 4 hours of reperfusion. The levels of alkaline phosphatase (a marker enzyme for type II pneumocytes) were higher in the animals undergoing conventional transplantation (60 IU per liter) than in animals undergoing bronchial revascularization (33 IU per liter) or in control animals (13.6 IU per liter). The level of angiotensin-converting enzyme (a marker for pulmonary endothelium) was also higher in the dogs undergoing conventional transplantation (1.4 IU per liter) than in dogs undergoing bronchial revascularization (0.35 IU per liter) or in control animals (0.06 IU per liter). The authors conclude that bronchial artery revascularization protects the pulmonary endothelium and type II pneumocytes after lung transplantation.
ATP-sensitive potassium channel openers suppress the release of superoxide from neutrophils and play a central role in the suppression of reperfusion injury in cardiac muscle. To determine whether pinacidil, an ATP-sensitive potassium channel opener, attenuates ischemia–reperfusion injury of the lung, Fukuse and coworkers (75) used an ex vivo rat lung model. Heart–lung blocks preserved with pinacidil had lower shunt fraction, pulmonary artery pressure, and peak inspiratory pressure than did heart–lung blocks preserved with saline or with pinacidil combined with glibenclamide (a blocker of the channel opener). The concentrations of total adenine nucleotides and ATP in the lung after reperfusion were lower in the control group and in the glibenclamide group than in the fresh group. The control and glibenclamide groups displayed increased lipid peroxidation of the lungs after reperfusion, and decreased State 3 mitochondrial respiration and State 3/4 ratio of mitochondrial respiration. The authors conclude that ATP-sensitive potassium channel openers maintain mitochondrial respiratory function during lung preservation, prevent lipid peroxidation after reperfusion, and attenuate ischemia–reperfusion injury during lung preservation.
Patient Selectionv, 百拇医药
The breathing reserve index is the minute ventilation at the lactate threshold during incremental exercise divided by maximal voluntary ventilation. To determine whether this index would predict mortality in patients with cystic fibrosis on a waiting list for lung transplantation, Tantisira and coworkers (76) did exercise testing in 45 consecutive patients with cystic fibrosis as part of their pretransplant assessment. Fifteen patients died, 21 patients were transplanted, and 9 patients were still on the waiting list. In a multivariate model, relative risk of mortality was 17.52 for the breathing reserve index, 1.29 for resting PCO2, 0.97 for resting PO2, and 1.19 for FEV1. The authors conclude that the breathing reserve index provided the highest point estimate of mortality in patients with cystic fibrosis waiting for lung transplantation.v, 百拇医药
Deciding the right time to undertake lung transplantation in patients with cystic fibrosis is difficult, and the criteria used in guiding the decision are controversial. Mayer-Hamblett and coworkers (77) developed a mathematical model for predicting 2-year mortality using data on 14,572 patients in the National Patient Registry of the Cystic Fibrosis Foundation who were 6 years of age or older in 1996. Multivariate logistic regression revealed that age, height, FEV1, respiratory microbiology, number of hospitalizations for pulmonary exacerbations, and number of course of intravenous antibiotics in the home were significant predictors of 2-year mortality. When compared with the widely used criterion of an FEV1 of less than 30% of predicted, the mathematical model did not prove superior. The negative predictive value was 98% for the model and 97% for FEV1. The positive predictive value was 33% for the model and 28% for FEV1. Both the model and the FEV1 criterion will result in high rates of premature referral for lung transplantation. The authors conclude that a well-fitting mathematical model based on data from 14,572 patients with cystic fibrosis was not superior to the usual criterion of a FEV1 of less than 30% predicted in guiding decision on the best time to do lung transplantation. An editorial commentary by Noone and Egan (78) accompanies this article.
Obliterative Bronchiolitis#4-[50e, 百拇医药
Animal models.#4-[50e, 百拇医药
In a rat model of bronchiolitis obliterans, Liu and coworkers (79) studied the role of transforming growth factor-ß. The model consisted of heterotopic allogenic transplantation of the trachea (that is, transplantation of a trachea from a genetically dissimilar individual of same species into a location different from the usual location). Positive staining for the growth factor was evident in infiltrating mononuclear cells on the second and seventh day and in fibrous tissues on the twenty-first day. The fibrous obliteration of the airway was inhibited by transfection of the gene for soluble transforming growth factor-ß type III receptor, which functions as an antagonist for the growth factor, on the fifth day after transplantation. Delivery of an empty vector gene had no effect. The authors conclude that expression of transforming growth factor-ß in allografts plays a pivotal role in the pathogenesis of bronchiolitis obliterans.
Activation of T cells, which may be involved in causing obliterative bronchiolitis, relies in part on the interaction between CD28 and its ligands, B7–1 and B7–2. In untreated rats with tracheal allografts (grafts from genetically dissimilar individuals of same species), Tikkanen and coworkers (80) found that expression of B7–2, but not of B7–1, peaked on the tenth day after transplantation. Upregulation of B7–2 was not seen in syngeneic grafts (grafts from a genetically identical rat). Administration of cytotoxic T lymphocyte antigen 4 immunoglobulin, which selectively blocks the costimulatory pathway of CD28 and its ligand B7–1, had no effect on the epithelial injury or the airway occlusion in the tracheal allografts; nor did it affect cytokine expression. Administration of a fusion protein that blocks both the interactions between CD28 and B7–1 and between CD28 and B7–2 delayed the epithelial injury and airway occlusion; it also decreased production of tumor necrosis factor-, interleukin-2, and interferon- within the graft, and it increased production of interleukin-10. The authors conclude that interaction between CD28 and its ligand B7–2 plays a prominent role in the regulation of the proinflammatory and type 1 (Th1) helper T cell cytokine responses involved in the epithelial injury of experimental obliterative bronchiolitis.
To determine the role of growth factors in the pathogenesis of obliterative bronchiolitis in the mouse heterotopic trachea model, Aris and coworkers (81) implanted isografts and allografts in three sets of cyclosporine-treated mice. Compared with the isografts, the allografts had 1.5- to 5-fold increases in expression of transforming growth factor-ß, tumor necrosis factor-, endothelin-1, and insulin-like growth factor-1 after two to six weeks. The allografts had increased expression of fibroblast growth factor isoforms 1 and 2, and platelet-derived growth factor-B at 4 weeks, which reversed at 6 and 10 weeks. The isografts expressed more epidermal growth factors than did the allografts. Treatment with a tumor necrosis factor-–soluble receptor produced a decrease in the epithelial injury and the luminal obstruction. The authors conclude that a large number of growth factors participate in obliterative bronchiolitis in mice, and that blockade of tumor necrosis factor- may ameliorate the lesion.
Early detection.%|7#, 百拇医药
To assess the role of T cell responses in predicting the development of obliterative bronchiolitis, Duncan and coworkers (82) studied 12 patients who underwent lung transplantation. All six patients who developed obliterative bronchiolitis had abnormal expansion of circulating CD4+ T cells attributable to oligoclonal proliferations. Two of six recipients who did not develop rejection had a much lesser abnormality in CD4+ cells. Expansions of CD8+ cells were common in both groups. The authors conclude that expansion of CD4+ T cells had 100% sensitivity and 80% specificity in predicting the development of obliterative bronchiolitis.%|7#, 百拇医药
In a pulmonary perspective, Estenne and Hertz (83) discusses bronchiolitis obliterans after human lung transplantation.%|7#, 百拇医药
Rejection%|7#, 百拇医药
In 22 patients who had undergone bilateral lung or heart-lung transplantation, Morlion and coworkers (84) studied the reliability of Internet-based monitoring of lung function and its sensitivity in detecting infection or rejection of the allograft. The patients performed forced expiratory maneuvers into a mircrospirometer in their home, and the flow–volume loops were transmitted across the Internet to the hospital. Over a median of 473 days, 13,833 measurements were obtained. Patient compliance for one measurement a day was 84%, and compliance for two measurements a day was 55%. Agreement between home and hospital spirometry was within 4% for FEV1 and 6% for midexpiratory flow rate (FEF25–75). Coefficients of variation were 3.2% for FEV1 and 7.5% for FEF25–75. Home spirometry had a sensitivity of 63% for detecting acute graft dysfunction (diagnosed by biopsy or lavage). The authors conclude that transmission across the Internet of home spirometry in lung transplant recipients is accurate and reproducible, although it has only mild sensitivity (because a substantial number of acute complications do not alter pulmonary function).
Immunology and Biochemistry+#6%gd, 百拇医药
To characterize the usual profile of cells obtained by bronchoalveolar lavage in patients undergoing lung transplantation, Slebos and coworkers (85) analyzed 169 lavage samples from 63 patients free of airway complications after transplantation. The total cell counts decreased from 234 x 103 cells per ml shortly after transplantation to 103 x 103 cells per ml during the second year. The differential cell counts did not change. The ratio of CD4 to CD8 cell counts increased from 0.32 shortly after transplantation to 0.62 in the second year. The authors conclude that the pattern of cells obtained by bronchoalveolar lavage changes over the first two years after lung transplantation.+#6%gd, 百拇医药
PLEURAL DISORDERS+#6%gd, 百拇医药
TOP+#6%gd, 百拇医药
CONTENTS+#6%gd, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...+#6%gd, 百拇医药
AIR POLLUTION+#6%gd, 百拇医药
PULMONARY VASCULAR DISORDERS AND...
LUNG TRANSPLANTATION:, 百拇医药
PLEURAL DISORDERS:, 百拇医药
LUNG CANCER:, 百拇医药
REFERENCES:, 百拇医药
Physiology/Pathophysiology:, 百拇医药
To determine whether the helper T lymphocytes in malignant pleural effusions undergo a shift to type 2 (Th2) helper responses, Oshikawa and coworkers (86) studied pleural fluid and sera from 17 patients with malignant effusions, 8 patients with tuberculous effusions, and 5 patients with congestive heart failure. CD4+ T cells isolated from the pleural fluid of the patients with malignant pleural effusions produced more interleukin-4 and interleukin-10 and less interferon- and interleukin-12 than did cells obtained from the other two patient groups. The concentration of ST2, which is preferentially expressed on Th2 effector cells but not on Th1 cells, was higher in the patients with malignant effusions than in the other two groups. The concentration of ST2 was positively correlated with the percentage of CD4+ T cells (r = 0.43) and inversely correlated with the concentration of interferon- (r = -0.42) in pleural fluid. The expression of messenger RNA of ST2 in CD4+ T cells was upregulated in malignant effusions. The authors conclude that CD4+ T cells in malignant pleural effusions shift to a type 2 (Th2) profile and produce soluble ST2 gene products.
During the initial fibrinopurulent phase of a pleural loculation, fibrin bridges the visceral and parietal pleural surfaces. In rabbits with a pleural injury caused by tetracycline, Idell and coworkers (87) determined whether a single-chain urokinase plasminogen activator (alone or bound to its receptor) could prevent visceral-parietal adhesions. (This plasminogen activator enhances fibrinolytic activity and is relatively resistant to local inhibitors.) Urokinase bound to its receptor maintained fibrinolytic activity over 24 hours in the rabbits. When administered on its own into the pleura at 24 and 48 hours after intrapleural tetracycline, single-chain urokinase prevented the formation of adhesions. When bound to its receptor, administration of urokinase attenuated the formation of adhesions. At 72 hours after administration of tetracycline, antigenic, but not functional, evidence of the fibrinolytic agents persisted. The fibrinolytic agents did not cause local or systemic bleeding. The authors conclude that single-chain urokinase inhibits the formation of adhesions in rabbits with pleural injury caused by tetracycline. An editorial commentary by Antony (88) accompanies this article.
Clinical Manifestationsg, 百拇医药
In a consecutive case series of 389 patients, Light and coworkers (89) determined the prevalence of pleural effusions at about 28 days after cardiac surgery. Chest X-rays revealed pleural effusions in 63% of 312 patients who had undergone coronary artery bypass grafting alone, in 62% of 37 patients who had undergone both bypass grafting and valve surgery, and in 45% of 40 patients who had undergone value surgery alone. The prevalence of effusions occupying more than 25% of the hemithorax was 9.7%. The primary symptom associated with larger effusions was dyspnea; chest pain and fever were distinctly uncommon. The effusions usually resolved after one or two thoracenteses, and almost all effusions had resolved within one year of surgery. The authors conclude that about 10% of patients undergoing coronary artery surgery develop a pleural effusion that occupies more than 25% of a hemithorax.g, 百拇医药
Treatment
Because of controversy about the management of a first episode of a primary spontaneous pneumothorax, Noppen and coworkers (90) did a randomized prospective comparison of manual aspiration versus chest tube drainage in 60 patients. Immediate success was achieved in 59% of the patients treated by manual aspiration and in 64% of the patients treated by chest tube drainage. Success at one week was 93% in the manual aspiration group and 85% in the chest-tube group. Hospitalization was required in 52% of the manual aspiration group and in 100% of the chest-tube group. When evaluated after a minimum of one year, 26% of the manual aspiration group and 27% of the chest-tube group had experienced a recurrence. No complications were associated with manual aspiration. The authors conclude that manual aspiration is as effective as chest-tube drainage in managing a first episode of a primary spontaneous pneumothorax. An editorial commentary by Light (91) accompanies this article.1t/, http://www.100md.com
Pleurodesis
When used for pleurodesis, transforming growth factor-ß causes large transient pleural effusions. Lee and coworkers (92) investigated the role of vascular endothelial growth factor in causing the effusions. (Vascular endothelial growth factor is a cytokine that increases the permeability of microvessels and leads to formation of pleural effusions and ascites.) Injection of transforming growth factor-ß into the pleural cavity of rabbits caused a dose-dependent increase in vascular endothelial growth factor; the levels were higher than those achieved by talc or doxycycline. The volume of pleural fluid was correlated with the level of vascular endothelial growth factor (r = 0.79). In in vitro studies, transforming growth factor-ß, but not talc or doxycycline, induced a significant increase in vascular endothelial growth factor; the increase was decreased by an antibody to transforming growth factor-ß. The authors conclude that transforming growth factor-ß causes mesothelial cells to produce vascular endothelial growth factor, which is accompanied by proportional increases in pleural fluid.
LUNG CANCER;?jk, 百拇医药
TOP;?jk, 百拇医药
CONTENTS;?jk, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...;?jk, 百拇医药
AIR POLLUTION;?jk, 百拇医药
PULMONARY VASCULAR DISORDERS AND...;?jk, 百拇医药
LUNG TRANSPLANTATION;?jk, 百拇医药
PLEURAL DISORDERS;?jk, 百拇医药
LUNG CANCER;?jk, 百拇医药
REFERENCES;?jk, 百拇医药
Diagnosis;?jk, 百拇医药
To determine the usefulness of screening for lung cancer with low-dose spiral computed tomography and sputum cytology, Swensen and coworkers (93) enrolled 1,520 individuals in a prospective cohort study. The subjects were aged 50 years or older and had a 20-pack-year smoking history. One year after baseline screening, 2,244 uncalcified lung nodules were identified in 1,000 participants (66%). Twenty-five cases of lung cancer were diagnosed: 23 cases by computed tomography and 2 cases by sputum cytology. Twenty-two patients underwent curative resection. Of the non–small cell cancers detected by computed tomography, the mean size was 17 mm and 12 (57%) were stage IA at diagnosis. Seven benign nodules were resected. The authors conclude that screening with computed tomography can detect lung cancers at an early stage. An editorial commentary by Heffner and Silvestri (94) accompanies this article.
Photodynamic therapy has curative potential for patients with early lung cancer that is centrally located. In 18 patients with biopsy-proven squamous cell carcinomas that had been considered appropriate candidates for photodynamic therapy on the basis of conventional bronchoscopy and high-resolution computed tomography, Miyazu and coworkers (95) evaluated the usefulness of endobronchial ultrasonography in making the selection. Endobronchial bronchoscopy revealed intracartilaginous lesions in nine patients, and photodynamic therapy has achieved complete remission (median follow-up, 32 months). Extracartilaginous lesions were found in the remaining nine patients, and they were treated by surgery, chemotherapy, or radiotherapy. The depth of tumor invasion estimated by endobronchial ultrasonography was comparable to the depth on histopathology in six patients undergoing surgical resection. The authors conclude that endobronchial ultrasonography is a useful technique in selecting patients with early, centrally located lung cancer for photodynamic therapy.
Transbronchial needle aspiration is an important method for bronchoscopic sampling of mediastinal adenopathy, but the optimal number of aspirates is not known. Chin and coworkers (96) studied 79 patients with known or suspected lung carcinoma and mediastinal adenopathy (57% of the cases were positive for malignancy). Among the patients in whom the procedure identified involvement of the mediastinal nodes, 42% had a cytologically positive sample on the first aspirate. All positive results were achieved with seven or fewer aspirates. A positive diagnosis was obtained in 71% of the cases handled with rapid on-site cytologic examination versus in 25% of the cases without on-site evaluation. The authors conclude that seven or fewer transbronchial needle aspirates achieve an optimal yield in patients with a suspected lung cancer and mediastinal adenopathy.34, http://www.100md.com
Studies of Molecular Mechanisms34, http://www.100md.com
Heat shock proteins derived from animals with cancers elicit protective immunity against autologous cancer. To determine whether heat shock protein-70 derived from human lung cancer is complexed with tumor-specific antigens, Michils and coworkers (97) collected peripheral blood monocytes from patients with lung cancer 10 days after surgery. When the monocytes were stimulated with heat shock protein-70 derived from autologous tumor, the stimulation index was 1.96 times higher in the patients with lung cancer than in the control subjects. Heat shock protein-70 derived from heterologous tumor or from autologous tumor-free lung tissue did not cause significant stimulation. Six patients were again studied at three months after surgery, and the stimulation index had decreased by 54%. Heat shock protein-70 derived from lung carcinoma was associated with T cell antigens, and the T cell reactivity was transient and restricted solely to antigens complexed to heat shock protein-70 derived from autologous tumors. The authors conclude that heat shock protein-70 derived from human lung carcinoma acts to chaperone antigens that are specific for the tumor from which the protein was purified and are responsible for a transient cellular immune response.
Review Article*:q}%[, http://www.100md.com
In a state of the art review article, Spiro and Porter (98) discuss current advances in staging and nonsurgical treatment of lung cancer.*:q}%[, http://www.100md.com
REFERENCES*:q}%[, http://www.100md.com
TOP*:q}%[, http://www.100md.com
CONTENTS*:q}%[, http://www.100md.com
CHRONIC OBSTRUCTIVE PULMONARY...*:q}%[, http://www.100md.com
AIR POLLUTION*:q}%[, http://www.100md.com
PULMONARY VASCULAR DISORDERS AND...*:q}%[, http://www.100md.com
LUNG TRANSPLANTATION*:q}%[, http://www.100md.com
PLEURAL DISORDERS*:q}%[, http://www.100md.com
LUNG CANCER*:q}%[, http://www.100md.com
REFERENCES*:q}%[, http://www.100md.com
He JQ, Ruan J, Connett JE, Anthonisen NR, Pare PD, Sandford AJ. Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung function in smokers. Am J Respir Crit Care Med 2002;166:323–328.*:q}%[, http://www.100md.com
Vestbo J, Lange P. Can GOLD Stage 0 provide information of prognostic value in chronic obstructive pulmonary disease? Am J Respir Crit Care Med 2002;166:329–332.
Anthonisen NR, Connett JE, Murray RP. Smoking and lung function of Lung Health Study participants after 11 years. Am J Respir Crit Care Med 2002;166:675–679.q]zgc[m, http://www.100md.com
Domingo-Salvany A, Lamarca R, Ferrer M, Garcia-Aymerich J, Alonso J, Felez M, Khalaf A, Marrades RM, Monso E, Serra-Batlles J, et al. Health-related quality of life and mortality in male patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:680–685.q]zgc[m, http://www.100md.com
Rodriguez F, Jardi R, Costa X, Cotrina M, Galimany R, Vidal R, Miravitlles M. Rapid screening for1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease using dried blood specimens. Am J Respir Crit Care Med 2002;166:814–817.q]zgc[m, http://www.100md.com
Takubo Y, Guerassimov A, Ghezzo H, Triantafillopoulos A, Bates JH, Hoidal JR, Cosio MG.1-Antitrypsin determines the pattern of emphysema and function in tobacco smoke-exposed mice: parallels with human disease. Am J Respir Crit Care Med 2002;166:1596–1603.
Birring SS, Brightling CE, Bradding P, Entwisle JJ, Vara DD, Grigg J, Wardlaw AJ, Pavord ID. Clinical, radiologic, and induced sputum features of chronic obstructive pulmonary disease in nonsmokers: a descriptive study. Am J Respir Crit Care Med 2002;166:1078–1083.s7, http://www.100md.com
Abe Y, Murphy TF, Sethi S, Faden HS, Dmochowski J, Harabuchi Y, Thanavala YM. Lymphocyte proliferative response to P6 of Haemophilus influenzae is associated with relative protection from exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;165:967–971.s7, http://www.100md.com
Saetta M, Mariani M, Panina-Bordignon P, Turato G, Buonsanti C, Baraldo S, Bellettato CM, Papi A, Corbetta L, Zuin R, et al. Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;165:1404–1409.s7, http://www.100md.com
Turato G, Zuin R, Miniati M, Baraldo S, Rea F, Beghe B, Monti S, Formichi B, Boschetto P, Harari S, et al. Airway inflammation in severe chronic obstructive pulmonary disease: relationship with lung function and radiologic emphysema. Am J Respir Crit Care Med 2002;166:105–110.
Rahman I, van Schadewijk AA, Crowther AJ, Hiemstra PS, Stolk J, MacNee W, De Boer WI. 4-Hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:490–495.8y/5(, http://www.100md.com
Tomita K, Caramori G, Lim S, Ito K, Hanazawa T, Oates T, Chiselita I, Jazrawi E, Chung KF, Barnes PJ, et al. Increased p21(CIP1/WAF1) and B cell lymphoma leukemia-x(L) expression and reduced apoptosis in alveolar macrophages from smokers. Am J Respir Crit Care Med 2002;166:724–731.8y/5(, http://www.100md.com
Vignola AM. p21(CIP1/WAF1) and the immunologic fate of macrophages in smokers: at the crossroad between proliferation, survival, and death. Am J Respir Crit Care Med 2002;166:637–638.8y/5(, http://www.100md.com
Harju T, Kaarteenaho-Wiik R, Soini Y, Sormunen R, Kinnula VL. Diminished immunoreactivity of gamma-glutamylcysteine synthetase in the airways of smokers' lung. Am J Respir Crit Care Med 2002;166:754–759.8y/5(, http://www.100md.com
Hiemstra PS. The adaptive response of smokers to oxidative stress: moving from culture to tissue. Am J Respir Crit Care Med 2002;166:635–636.
Higashimoto Y, Elliott WM, Behzad AR, Sedgwick EG, Takei T, Hogg JC, Hayashi S. Inflammatory mediator mRNA expression by adenovirus E1A-transfected bronchial epithelial cells. Am J Respir Crit Care Med 2002;166:200–207.n85[kh&, http://www.100md.com
Churg A, Dai J, Tai H, Xie C, Wright JL. Tumor necrosis factor- is central to acute cigarette smoke-induced inflammation and connective tissue breakdown. Am J Respir Crit Care Med 2002;166:849–854.n85[kh&, http://www.100md.com
Vernooy JH, Kucukaycan M, Jacobs JA, Chavannes NH, Buurman WA, Dentener MA, Wouters EF. Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med 2002;166:1218–1224.n85[kh&, http://www.100md.com
Brown JS, Zeman KL, Bennett WD. Ultrafine particle deposition and clearance in the healthy and obstructed lung. Am J Respir Crit Care Med 2002;166:1240–1247.n85[kh&, http://www.100md.com
Kastelik JA, Thompson RH, Aziz I, Ojoo JC, Redington AE, Morice AH. Sex-related differences in cough reflex sensitivity in patients with chronic cough. Am J Respir Crit Care Med 2002;166:961–964.
Scharf SM, Iqbal M, Keller C, Criner G, Lee S, Fessler HE. Hemodynamic characterization of patients with severe emphysema. Am J Respir Crit Care Med 2002;166:314–322.#;'d@$, 百拇医药
O'Donnell DE, D'Arsigny C, Fitzpatrick M, Webb KA. Exercise hypercapnia in advanced chronic obstructive pulmonary disease: the role of lung hyperinflation. Am J Respir Crit Care Med 2002;166:663–668.#;'d@$, 百拇医药
Dempsey JA. Exercise carbon dioxide retention in chronic obstructive pulmonary disease: a case for ventilation/perfusion mismatch combined with hyperinflation. Am J Respir Crit Care Med 2002;166:634–635.#;'d@$, 百拇医药
Ramirez-Sarmiento A, Orozco-Levi M, Guell R, Barreiro E, Hernandez N, Mota S, Sangenis M, Broquetas JM, Casan P, Gea J. Inspiratory muscle training in patients with chronic obstructive pulmonary disease: structural adaptation and physiologic outcomes. Am J Respir Crit Care Med 2002;166:1491–1497.#;'d@$, 百拇医药
Levine S, Nguyen T, Kaiser LR, Shrager JB. Evaluating respiratory muscle adaptations: a new approach. Am J Respir Crit Care Med 2002;166:1418–1419.#;'d@$, 百拇医药
Gorman RB, McKenzie DK, Pride NB, Tolman JF, Gandevia SC. Diaphragm length during tidal breathing in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:1461–1469.
Agusti AG, Sauleda J, Miralles C, Gomez C, Togores B, Sala E, Batle S, Busquets X. Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:485–489.t+9w.|!, http://www.100md.com
Lewis MI. Apoptosis as a potential mechanism of muscle cachexia in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:434–436.t+9w.|!, http://www.100md.com
Ortega F, Toral J, Cejudo P, Villagomez R, Sanchez H, Castillo J, Montemayor T. Comparison of effects of strength and endurance training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:669–674.t+9w.|!, http://www.100md.com
Marquis K, Debigare R, Lacasse Y, LeBlanc P, Jobin J, Carrier G, Maltais F. Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:809–813.t+9w.|!, http://www.100md.com
Mador MJ. Muscle mass, not body weight, predicts outcome in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:787–789.t+9w.|!, http://www.100md.com
Anthonisen NR, Connett JE, Enright PL, Manfreda J. Hospitalizations and mortality in the Lung Health Study. Am J Respir Crit Care Med 2002;166:333–339.
Culpitt SV, De Matos C, Russell RE, Donnelly LE, Rogers DF, Barnes PJ. Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;165:1371–1376.mr9, http://www.100md.com
Rabe KF. On theophylline, leukocytes, and chicken soup. Am J Respir Crit Care Med 2002;165:1351–1352.mr9, http://www.100md.com
Maltais F, Ostinelli J, Bourbeau J, Tonnel AB, Jacquemet N, Haddon J, Rouleau M, Boukhana M, Martinot JB, Duroux P. Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Am J Respir Crit Care Med 2002;165:698–703.mr9, http://www.100md.com
Van Der Valk P, Monninkhof E, van der PJ, Zielhuis G, van Herwaarden C. Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE study. Am J Respir Crit Care Med 2002;166:1358–1363.mr9, http://www.100md.com
Hattotuwa KL, Gizycki MJ, Ansari TW, Jeffery PK, Barnes NC. The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study. Am J Respir Crit Care Med 2002;165:1592–1596.
Pauwels R. Inhaled glucocorticosteroids and chronic obstructive pulmonary disease: how full is the glass? Am J Respir Crit Care Med 2002;165:1579–1580.0]impg, 百拇医药
Mahler DA, Wire P, Horstman D, Chang CN, Yates J, Fischer T, Shah T. Effectiveness of fluticasone propionate and salmeterol combination delivered via the diskus device in the treatment of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:1084–1091.0]impg, 百拇医药
Walsh LJ, Lewis SA, Wong CA, Cooper S, Oborne J, Cawte SA, Harrison T, Green DJ, Pringle M, Hubbard R, et al. The impact of oral corticosteroid use on bone mineral density and vertebral fracture. Am J Respir Crit Care Med 2002;166:691–695.0]impg, 百拇医药
Hubbard RB, Smith CJ, Smeeth L, Harrison TW, Tattersfield AE. Inhaled corticosteroids and hip fracture: a population-based case-control study. Am J Respir Crit Care Med 2002;166:1563–1566.0]impg, 百拇医药
Mao JT, Goldin JG, Dermand J, Ibrahim G, Brown MS, Emerick A, McNitt-Gray MF, Gjertson DW, Estrada F, Tashkin DP, et al. A pilot study of all-trans-retinoic acid for the treatment of human emphysema. Am J Respir Crit Care Med 2002;165:718–723.
Kuraki T, Ishibashi M, Takayama M, Shiraishi M, Yoshida M. A novel oral neutrophil elastase inhibitor (ONO-6818) inhibits human neutrophil elastase-induced emphysema in rats. Am J Respir Crit Care Med 2002;166:496–500.zfh^ejz, 百拇医药
Wright JL, Farmer SG, Churg A. Synthetic serine elastase inhibitor reduces cigarette smoke-induced emphysema in guinea pigs. Am J Respir Crit Care Med 2002;166:954–960.zfh^ejz, 百拇医药
Fessler HE, Scharf SM, Permutt S. Improvement in spirometry following lung volume reduction surgery: application of a physiologic model. Am J Respir Crit Care Med 2002;165:34–40.zfh^ejz, 百拇医药
Mineo TC, Pompeo E, Rogliani P, Dauri M, Turani F, Bollero P, Magliocchetti N. Effect of lung volume reduction surgery for severe emphysema on right ventricular function. Am J Respir Crit Care Med 2002;165:489–494.zfh^ejz, 百拇医药
Stockley RA, Bayley DL, Unsal I, Dowson LJ. The effect of augmentation therapy on bronchial inflammation in 1-antitrypsin deficiency. Am J Respir Crit Care Med 2002;165:1494–1498.zfh^ejz, 百拇医药
Sin DD, Stafinski T, Ng YC, Bell NR, Jacobs P. The impact of chronic obstructive pulmonary disease on work loss in the United States. Am J Respir Crit Care Med 2002;165:704–707.
Croxton TL, Weinmann GG, Senior RM, Hoidal JR. Future research directions in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;165:838–844.c{s?, 百拇医药
Saldiva PH, Clarke RW, Coull BA, Stearns RC, Lawrence J, Murthy GG, Diaz E, Koutrakis P, Suh H, Tsuda A, et al. Lung inflammation induced by concentrated ambient air particles is related to particle composition. Am J Respir Crit Care Med 2002;165:1610–1617.c{s?, 百拇医药
Nemmar A, Hoylaerts MF, Hoet PH, Dinsdale D, Smith T, Xu H, Vermylen J, Nemery B. Ultrafine particles affect experimental thrombosis in an in vivo hamster model. Am J Respir Crit Care Med 2002;166:998–1004.c{s?, 百拇医药
Romieu I, Sienra-Monge JJ, Ramirez-Aguilar M, Tellez-Rojo MM, Moreno-Macias H, Reyes-Ruiz NI, Rio-Navarro BE, Ruiz-Navarro MX, Hatch G, Slade R, et al. Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. Am J Respir Crit Care Med 2002;166:703–709.c{s?, 百拇医药
Gauderman WJ, Gilliland GF, Vora H, Avol E, Stram D, McConnell R, Thomas D, Lurmann F, Margolis HG, Rappaport EB, et al. Association between air pollution and lung function growth in southern California children: results from a second cohort. Am J Respir Crit Care Med 2002;166:76–84.
Brauer M, Hoek G, Van Vliet P, Meliefste K, Fischer PH, Wijga A, Koopman LP, Neijens HJ, Gerritsen J, Kerkhof M, et al. Air pollution from traffic and the development of respiratory infections and asthmatic and allergic symptoms in children. Am J Respir Crit Care Med 2002;166:1092–1098.n, http://www.100md.com
Takano H, Yanagisawa R, Ichinose T, Sadakane K, Yoshino S, Yoshikawa T, Morita M. Diesel exhaust particles enhance lung injury related to bacterial endotoxin through expression of proinflammatory cytokines, chemokines, and intercellular adhesion molecule-1. Am J Respir Crit Care Med 2002;165:1329–1335.n, http://www.100md.com
Balabanian K, Foussat A, Dorfmuller P, Durand-Gasselin I, Capel F, Bouchet-Delbos L, Portier A, Marfaing-Koka A, Krzysiek R, Rimaniol AC, et al. CX(3)C chemokine fractalkine in pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:1419–1425.n, http://www.100md.com
Williams TJ. Stalking the chemokine. Am J Respir Crit Care Med 2002;165:1350–1351.n, http://www.100md.com
Davie N, Haleen SJ, Upton PD, Polak JM, Yacoub MH, Morrell NW, Wharton J. ET(A) and ET(B) receptors modulate the proliferation of human pulmonary artery smooth muscle cells. Am J Respir Crit Care Med 2002;165:398–405.
Dorfmuller P, Zarka V, Durand-Gasselin I, Monti G, Balabanian K, Garcia G, Capron F, Coulomb-Lhermine A, Marfaing-Koka A, Simonneau G, et al. Chemokine RANTES in severe pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:534–539.cpi$z, http://www.100md.com
Rabiller A, Nunes H, Lebrec D, Tazi KA, Wartski M, Dulmet E, Libert JM, Mougeot C, Moreau R, Mazmanian M, et al. Prevention of gram-negative translocation reduces the severity of hepatopulmonary syndrome. Am J Respir Crit Care Med 2002;166:514–517.cpi$z, http://www.100md.com
Reeves JT. High adventure in pulmonary hypertension: acute and chronic hypoxia are not the same. Am J Respir Crit Care Med 2002;166:1537–1538.cpi$z, http://www.100md.com
Castelain V, Chemla D, Humbert M, Sitbon O, Simonneau G, Lecarpentier Y, Herve P. Pulmonary artery pressure-flow relations after prostacyclin in primary pulmonary hypertension. Am J Respir Crit Care Med 2002;165:338–340.cpi$z, http://www.100md.com
Simonneau G, Barst RJ, Galie N, Naeije R, Rich S, Bourge RC, Keogh A, Oudiz R, Frost A, Blackburn SD, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2002;165:800–804.
Hoeper MM, Galie N, Murali S, Olschewski H, Rubenfire M, Robbins IM, Farber HW, McLaughlin V, Shapiro S, Pepke-Zaba J, et al. Outcome after cardiopulmonary resuscitation in patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:341–344.-^'fw{&, 百拇医药
Nishimura T, Faul JL, Berry GJ, Vaszar LT, Qiu D, Pearl RG, Kao PN. Simvastatin attenuates smooth muscle neointimal proliferation and pulmonary hypertension in rats. Am J Respir Crit Care Med 2002;166:1403–1408.-^'fw{&, 百拇医药
Rubin LJ. Therapy of pulmonary hypertension: the evolution from vasodilators to antiproliferative agents. Am J Respir Crit Care Med 2002;166:1308–1309.-^'fw{&, 百拇医药
Shekerdemian LS, Ravn HB, Penny DJ. Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension. Am J Respir Crit Care Med 2002;165:1098–1102.-^'fw{&, 百拇医药
Hoeper MM, Galie N, Simonneau G, Rubin LJ. New treatments for pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:1209–1216.-^'fw{&, 百拇医药
De Monye W, Sanson BJ, Mac Gillavry MR, Pattynama PM, Buller HR, van den Berg-Huysmans AA, Huisman MV. Embolus location affects the sensitivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism. Am J Respir Crit Care Med 2002;165:345–348.
Aldashev AA, Sarybaev AS, Sydykov AS, Kalmyrzaev BB, Kim EV, Mamanova LB, Maripov R, Kojonazarov BK, Mirrakhimov MM, Wilkins MR, et al. Characterization of high-altitude pulmonary hypertension in the Kyrgyz: association with angiotensin-converting enzyme genotype. Am J Respir Crit Care Med 2002;166:1396–1402.|\, 百拇医药
Woods DR, Pollard AJ, Collier DJ, Jamshidi Y, Vassiliou V, Hawe E, Humphries SE, Montgomery HE. Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene and arterial oxygen saturation at high altitude. Am J Respir Crit Care Med 2002;166:362–366.|\, 百拇医药
Callahan LA, Woods KF, Mensah GA, Ramsey LT, Barbeau P, Gutin B. Cardiopulmonary responses to exercise in women with sickle cell anemia. Am J Respir Crit Care Med 2002;165:1309–1316.|\, 百拇医药
De Perrot M, Sekine Y, Fischer S, Waddell TK, McRae K, Liu M, Wigle DA, Keshavjee S. Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation. Am J Respir Crit Care Med 2002;165:211–215.|\, 百拇医药
Nowak K, Kamler M, Bock M, Motsch J, Hagl S, Jakob H, Gebhard MM. Bronchial artery revascularization affects graft recovery after lung transplantation. Am J Respir Crit Care Med 2002;165:216–220.
Fukuse T, Hirata T, Omasa M, Wada H. Effect of adenosine triphosphate-sensitive potassium channel openers on lung preservation. Am J Respir Crit Care Med 2002;165:1511–1515.6.v&&%-, http://www.100md.com
Tantisira KG, Systrom DM, Ginns LC. An elevated breathing reserve index at the lactate threshold is a predictor of mortality in patients with cystic fibrosis awaiting lung transplantation. Am J Respir Crit Care Med 2002;165:1629–1633.6.v&&%-, http://www.100md.com
Mayer-Hamblett N, Rosenfeld M, Emerson J, Goss CH, Aitken ML. Developing cystic fibrosis lung transplant referral criteria using predictors of 2-year mortality. Am J Respir Crit Care Med 2002;166:1550–1555.6.v&&%-, http://www.100md.com
Noone PG, Egan TM. Cystic fibrosis: when to refer for lung transplantation-is the answer clear? Am J Respir Crit Care Med 2002;166:1531–1532.6.v&&%-, http://www.100md.com
Liu M, Suga M, Maclean AA, St George JA, Souza DW, Keshavjee S. Soluble transforming growth factor-beta type III receptor gene transfection inhibits fibrous airway obliteration in a rat model of Bronchiolitis obliterans. Am J Respir Crit Care Med 2002;165:419–423.6.v&&%-, http://www.100md.com
Tikkanen JM, Lemstrom KB, Koskinen PK. Blockade of CD28/B7–2 costimulation inhibits experimental obliterative bronchiolitis in rat tracheal allografts: suppression of helper T cell type1-dominated immune response. Am J Respir Crit Care Med 2002;165:724–729.
Aris RM, Walsh S, Chalermskulrat W, Hathwar V, Neuringer IP. Growth factor upregulation during obliterative bronchiolitis in the mouse model. Am J Respir Crit Care Med 2002;166:417–422.4jj@, 百拇医药
Duncan SR, Leonard C, Theodore J, Lega M, Girgis RE, Rosen GD, Theofilopoulos AN. Oligoclonal CD4(+) T cell expansions in lung transplant recipients with obliterative bronchiolitis. Am J Respir Crit Care Med 2002;165:1439–1444.4jj@, 百拇医药
Estenne M, Hertz MI. Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med 2002;166:440–444.4jj@, 百拇医药
Morlion B, Knoop C, Paiva M, Estenne M. Internet-based home monitoring of pulmonary function after lung transplantation. Am J Respir Crit Care Med 2002;165:694–697.4jj@, 百拇医药
Slebos DJ, Scholma J, Marike BH, Koeter GH, van der BW, Postma DS, Kauffman HF. Longitudinal profile of bronchoalveolar lavage cell characteristics in patients with a good outcome after lung transplantation. Am J Respir Crit Care Med 2002;165:501–507.4jj@, 百拇医药
Oshikawa K, Yanagisawa K, Ohno S, Tominaga S, Sugiyama Y. Expression of ST2 in helper T lymphocytes of malignant pleural effusions. Am J Respir Crit Care Med 2002;165:1005–1009.
Idell S, Mazar A, Cines D, Kuo A, Parry G, Gawlak S, Juarez J, Koenig K, Azghani A, Hadden W, et al. Single-chain urokinase alone or complexed to its receptor in tetracycline-induced pleuritis in rabbits. Am J Respir Crit Care Med 2002;166:920–926.3ld.x, 百拇医药
Antony VB. Fibrinolysis in the pleural space: breaking the bonds that bind. Am J Respir Crit Care Med 2002;166:909–910.3ld.x, 百拇医药
Light RW, Rogers JT, Moyers JP, Lee YC, Rodriguez RM, Alford WC Jr, Ball SK, Burrus GR, Coltharp WH, Glassford DM Jr, et al. Prevalence and clinical course of pleural effusions at 30 days after coronary artery and cardiac surgery. Am J Respir Crit Care Med 2002;166:1567–1571.3ld.x, 百拇医药
Noppen M, Alexander P, Driesen P, Slabbynck H, Verstraeten A. Manual aspiration versus chest tube drainage in first episodes of primary spontaneous pneumothorax: a multicenter, prospective, randomized pilot study. Am J Respir Crit Care Med 2002;165:1240–1244.3ld.x, 百拇医药
Light RW. Manual aspiration: the preferred method for managing primary spontaneous pneumothorax? Am J Respir Crit Care Med 2002;165:1202–1203.
Lee GYC, Melkerneker D, Thompson PJ, Light RW, Lane KB. Transforming growth factor beta induces vascular endothelial growth factor elaboration from pleural mesothelial cells in vivo and in vitro. Am J Respir Crit Care Med 2002;165:88–94.#.\u, 百拇医药
Swensen SJ, Jett JR, Sloan JA, Midthun DE, Hartman TE, Sykes AM, Aughenbaugh GL, Zink FE, Hillman SL, Noetzel GR, et al. Screening for lung cancer with low-dose spiral computed tomography. Am J Respir Crit Care Med 2002;165:508–513.#.\u, 百拇医药
Heffner JE, Silvestri G. CT screening for lung cancer: is smaller better? Am J Respir Crit Care Med 2002;165:433–434.#.\u, 百拇医药
Miyazu Y, Miyazawa T, Kurimoto N, Iwamoto Y, Kanoh K, Kohno N. Endobronchial ultrasonography in the assessment of centrally located early-stage lung cancer before photodynamic therapy. Am J Respir Crit Care Med 2002;165:832–837.#.\u, 百拇医药
Chin R Jr, McCain TW, Lucia MA, Cappellari JO, Adair NE, Lovato JF, Dunagan DP, Brooks MA, Clark HP, Haponik EF. Transbronchial needle aspiration in diagnosing and staging lung cancer: how many aspirates are needed? Am J Respir Crit Care Med 2002;166:377–381.#.\u, 百拇医药
Michils A, Dutry D, de Beyl VZ, Remmelink M. de MV, Rocmans P. Peripheral blood mononuclear cell proliferation to heat shock protein-70 derived from autologous lung carcinoma. Am J Respir Crit Care Med 2002;166:749–753.#.\u, 百拇医药
Spiro SG, Porter JC. Lung cancer–where are we today? Current advances in staging and nonsurgical treatment. Am J Respir Crit Care Med 2002;166:1166–1196.(Martin J. Tobin)
CONTENTS&5.(0c;, 百拇医药
TOP&5.(0c;, 百拇医药
CONTENTS&5.(0c;, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...&5.(0c;, 百拇医药
AIR POLLUTION&5.(0c;, 百拇医药
PULMONARY VASCULAR DISORDERS AND...&5.(0c;, 百拇医药
LUNG TRANSPLANTATION&5.(0c;, 百拇医药
PLEURAL DISORDERS&5.(0c;, 百拇医药
LUNG CANCER&5.(0c;, 百拇医药
REFERENCES&5.(0c;, 百拇医药
Chronic Obstructive Pulmonary Disease (49)&5.(0c;, 百拇医药
Genetics (1)&5.(0c;, 百拇医药
Epidemiology (3)
1–Antrypsin Deficiency (2)&5.(0c;, 百拇医药Risk Factors (1)&5.(0c;, 百拇医药
Cellular, Molecular, and Anatomical Abnormalities (10)&5.(0c;, 百拇医药
Lung Inflammation (1)
Pathophysiologic and Radiologic Studies (2);jx, 百拇医药
Pulmonary Vasculature (1);jx, 百拇医药
Control of Breathing and Exercise (2);jx, 百拇医药
Respiratory Muscles (3);jx, 百拇医药
Peripheral Muscles (5);jx, 百拇医药
Drug Therapy (13);jx, 百拇医药
Muscarinic Antagonists (1);jx, 百拇医药
Theophylline (2);jx, 百拇医药
Glucocorticoids (7);jx, 百拇医药
Experimental Protease Inhibitors (3);jx, 百拇医药
Other Therapies (3);jx, 百拇医药
Lung Volume Reduction Surgery (2)
1-Antitrypsin Replacement Therapy (1);jx, 百拇医药Outcome (1);jx, 百拇医药
Workshops (1);jx, 百拇医药
Air Pollution (6);jx, 百拇医药
Air Pollution—General (5);jx, 百拇医药
Diesel Exhaust (1);jx, 百拇医药
Pulmonary Vascular Disorders and Related Disorders (17)
Pulmonary Hypertension (13)w!6;/*, http://www.100md.com
Molecular and Pathophysiologic Mechanisms (6)w!6;/*, http://www.100md.com
Treatment (7)w!6;/*, http://www.100md.com
Thromboembolic Disorders (1)w!6;/*, http://www.100md.com
Diagnostic Studies (1)w!6;/*, http://www.100md.com
High Altitude (2)w!6;/*, http://www.100md.com
Sickle Cell Disease (1)w!6;/*, http://www.100md.com
Lung Transplantation (13)w!6;/*, http://www.100md.com
Lung Preservation (3)w!6;/*, http://www.100md.com
Patient Selection (3)w!6;/*, http://www.100md.com
Obliterative Bronchiolitis (5)w!6;/*, http://www.100md.com
Animal Models (3)w!6;/*, http://www.100md.com
Early Detection (2)w!6;/*, http://www.100md.com
Rejection (1)w!6;/*, http://www.100md.com
Immunology and Biochemistry (1)w!6;/*, http://www.100md.com
Pleural Disorders (7)w!6;/*, http://www.100md.com
Physiology/Pathophysiology (3)w!6;/*, http://www.100md.com
Clinical Manifestations (1)w!6;/*, http://www.100md.com
Treatment (2)w!6;/*, http://www.100md.com
Pleurodesis (1)w!6;/*, http://www.100md.com
Lung Cancer (6)
Diagnosis (4);krn, 百拇医药
Studies of Molecular Mechanisms (1);krn, 百拇医药
Review Article (1);krn, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY DISEASE;krn, 百拇医药
TOP;krn, 百拇医药
CONTENTS;krn, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...;krn, 百拇医药
AIR POLLUTION;krn, 百拇医药
PULMONARY VASCULAR DISORDERS AND...;krn, 百拇医药
LUNG TRANSPLANTATION;krn, 百拇医药
PLEURAL DISORDERS;krn, 百拇医药
LUNG CANCER;krn, 百拇医药
REFERENCES;krn, 百拇医药
Genetics;krn, 百拇医药
Because oxidative stress is believed to contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), He and coworkers (1) studied the relationship between polymorphisms of antioxidant genes and susceptibility to accelerated decline of lung function in smokers. Of 594 white smokers in the Lung Health Study, 286 experienced a rapid decline in FEV1 (-152 ml per year) and 308 did not show a decline (+15 ml per year). None of the genotypes—glutathione S-transferase (GST) M1, T1, P1, or heme oxygenase-1—had an individual effect on decline in lung function. Rapid decline in lung function was associated with the presence of all three GST polymorphisms (odds ratio, 2.83). A combination of family history of COPD with GSTP1 105IIe/IIe genotype was associated with rapid decline in lung function (odds ratio, 2.2). The authors conclude that decline of lung function in smokers is not associated with any of the genotypes for glutathione S-transferase or hemeoxygenase-1.
Epidemiologymny)$ew, 百拇医药
In the GOLD (Global Initiative For Chronic Obstructive Lung Disease) guidelines, Stage 0 includes subjects without airway obstruction (FEV1/FVC greater than 0.70) who have respiratory symptoms (productive cough). Subjects with GOLD Stage 0 are considered at increased risk for COPD. To assess the usefulness of Stage 0, Vestbo and Lange (2) analyzed data on more than 10,000 participants in the Copenhagen City Heart Study. Criteria for GOLD Stage 0 were fulfilled by 5.8% of the total population and by 7.2% of smokers at baseline. At 5 years of follow-up, 13.2% of smokers with GOLD Stage 0 had developed a decrease in FEV1/FVC to less than 0.7; this change occurred in 11.6% of smokers without respiratory symptoms. At 15 years of follow-up, a decrease in FEV1/FVC to less than 0.7 occurred in 20.5% of smokers with GOLD Stage 0 and in 18.5% of smokers without respiratory symptoms. Multivariate logistic regression analysis revealed that GOLD Stage 0 did not identify subsequent airway obstruction. The authors conclude that GOLD Stage 0 is of little help in identifying subjects at risk of COPD and that cigarette smoking itself remains the best predictor of risk.
Eleven years after the Lung Health Study, Anthonisen and coworkers (3) did spirometry on 77% of the surviving participants. Smoking habits tended to converge; 93% of those who abstained from smoking during the study were still abstinent at 11 years. Men who quit smoking at the beginning of the study had a decline in FEV1 of 30 ml per year, as compared with a decline of 66 ml per year in men continuing to smoke throughout the 11 years. Women who quit smoking at the beginning of the study had a decline in FEV1 of 22 ml per year, as compared with a decline of 54 ml per year in women continuing to smoke throughout the 11 years. When expressed as a percentage of predicted normal value, the decline in FEV1 in male and female smokers was equivalent. At 11 years, 38% of individuals who continued to smoke had an FEV1 of less than 60% of the predicted normal value, as compared with 10% in the individuals who stopped smoking permanently. The authors conclude that the loss of lung function among continuing smokers is more rapid than previously suspected.
To determine whether measures of quality of life are associated with increased mortality, Domingo-Salvany and coworkers (4) analyzed data on a cohort of 321 men with COPD 5 to 6 years after enrollment. One third of the patients had died. Compared with survivors, the patients who died were older (70 versus 63 years), had lower body mass index (25 versus 27), lower FEV1 (34 versus 51% predicted), and made more frequent use of long-term oxygen therapy (31 versus 7%). After adjusting for relevant clinical and physiologic variables, both the total St. George's Respiratory Questionnaire and the physical summary score of SF-36 were independently associated with both all-cause mortality and respiratory mortality. The total mortality hazard ratio was 1.3 for the two measures of quality of life, and 1.6 for FEV1. The authors conclude that measures of quality of life provide independent information on the health status of men with COPD and are independently associated with mortality.
1-Antrypsin Deficiency-#j[, http://www.100md.comRodriguez and coworkers (5) describe a new method of screening for
1-antitrypsin deficiency. The technique employs dried blood spots and a LightCycler fluorimetric analyzer. Among 72 patients with COPD, 22% had neither PiZ nor PiS mutations, 7% were non-S, non-Z heterozygotes, 35% were heterozygotes who had a PiZ plus a non-S, non-Z allele, 3% had the PiSS genotype, 3% were PiSZ, and 28% were PiZZ. All patients with two normal alleles and 10 heterozygous carries had normal levels of 1-antitrypsin. Processing of 32 samples took only 40 minutes. The authors conclude that fluorimetric analysis of dried blood specimens is suitable for large-scale screening for 1-antitrypsin deficiency.Takubo and coworkers (6) determined whether the level of
1-antitrypsin influenced the pattern of emphysema induced by cigarette smoke in mice. Exposure to cigarette smoke for four months produced emphysema (an increase in the mean linear intercept) in pallid mice that have a low level of 1-antitrypsin but not in C57 mice. After six months of smoke exposure, the degree of emphysema was equivalent in the two groups of mice. The pallid mice developed more diffuse emphysema than did the C57 mice. T cell inflammation was present in the alveolar walls of the pallid mice, but not in the C57 mice after 6 months of smoking. Lung compliance increased over the 6 months in the pallid mice but not in the C57 mice. The authors conclude that cigarette smoking produces emphysema in both pallid and C57 mice, and that the emphysema is panlobular in pallid mice that have low levels of 1-antitrypsin, whereas it is centrilobular in C57 mice.Risk Factors8+7:', 百拇医药
Birring and coworkers (7) prospectively identified 25 patients with COPD who had never smoked or who had a smoking history of less than 5 pack-years. These patients represented 5.7% of total referrals with fixed airway obstruction over 2 years. The patients had a mean age of 70 years, were mainly women (86%), and had a mean duration of respiratory symptoms of 7 years. Mean FEV1 was 58%, and the FEV1/FVC ratio was 55%. Features on high-resolution computed tomography were typical of COPD. Sputum induction revealed eosinophilia in 9 patients and neutrophilia in 13 patients. Organ-specific autoimmune disease was present in 32% of patients, especially in the patients who did not display sputum eosinophilia (46% of patients). The authors conclude that the occurrence of COPD among nonsmokers is mainly seen in women and that some patients have features of organ-specific autoimmune disease.8+7:', 百拇医药
Cellular, Molecular, and Anatomic Abnormalities
Some exacerbations of COPD are caused by infection with nontypeable Haemophilus influenzae. Abe and coworkers (8) determined whether the lymphocytes of patients experiencing frequent exacerbations have decreased ability to recognize P6 (P6 is a lipoprotein of the outer membrane that is highly conserved among strains of nontypeable H. influenzae). The in vitro lymphocyte proliferative response to P6 was 0.82 in 10 patients with COPD who had experienced an exacerbation caused by nontypeable H. influenzae in the preceding 12 months as compared with 1.42 in 26 patients with COPD who did not have such an exacerbation, and 1.61 in 12 healthy subjects. Serum antibody levels to P6 did not differ between the two groups of patients with COPD. The lymphocyte response to an unrelated antigen, tetanus toxoid, did not differ among the three groups. The authors conclude that a decrease in the proliferation of lymphocytes in response to P6 is associated with increase in the frequency of exacerbations of COPD.
Smokers who develop COPD have bronchopulmonary inflammation, characterized by increased T lymphocytes. To determine whether patients with COPD have increased expression of CXCR3 (a chemokine receptor preferentially expressed on Type-1 T lymphocytes) and its ligand, CXCL10, Saetta and coworkers (9) studied airways of subjects undergoing lung resection for localized lesions. The numbers of CXCR3+ cells in the epithelium and submucosa of the peripheral airways of seven smokers with COPD was higher than in five smokers with normal lung function and in seven nonsmokers with normal lung function. The ligand of CXCR3, the interferon-induced protein CXCL10, was present in the bronchiolar epithelium of smokers with COPD but not in the bronchiolar epithelium of the other two groups. Most of the CXCR3 cells co-expressed CD8 and produced interferon-
. The authors conclude that the T cells infiltrating the peripheral airways of smokers with COPD have increased expression of the chemokine receptor CXCR3 and a parallel increase in its ligand CXCL10.To characterize and qualify the inflammatory processes in the small airways of smokers with COPD, Turato and coworkers (10) studied surgical specimens from 9 patients with severe COPD (FEV1, 29% predicted) and 9 patients with a similar smoking history who had mild or absent airway obstruction (FEV1, 86% predicted). Compared with the smokers who had mild or absent airway obstruction, the smokers with severe COPD had increased numbers of leukocytes in the small airways. The leukocytes were positively correlated with the radiologic score of emphysema and residual volume, and were negatively correlated with FEV1 and diffusing capacity. The inflammatory process was characterized by an increase in CD8+ and CD4+ T lymphocytes in the airway wall and an increase in macrophages in the airway epithelium. Taking all smokers together, smoking history was correlated with both the thickness of the airway wall and the thickness of smooth muscle. Structural and cellular findings in the pulmonary arteries did not differ between the two groups. The authors conclude that the small airways of smokers with severe COPD display an increased number of leukocytes, which is correlated with severity of airway obstruction, impaired diffusing capacity, hyperinflation, and radiologic emphysema.
4-Hydroxy-2-nonenal is a highly diffusible product of lipid peroxidation and a key mediator of oxidant-induced cell signaling and apoptosis. To determine the role of this aldehyde in COPD, Rahman and coworkers (11) obtained surgical lung specimens from 23 current or ex-smokers, 11 of whom had COPD (FEV1 less than 70% of predicted) and 12 of whom did not have COPD. 4-Hydroxy-2-nonenal–modified protein levels were higher in airway and alveolar epithelial cells, endothelial cells, and neutrophils of the patients with COPD than in the subjects without COPD. FEV1 was correlated with the level of the aldehyde in bronchial endothelium (r = -0.61) and neutrophils (r = -0.56). Transforming growth factor-ß1 was correlated with the level of the aldehyde in the bronchial epithelium (r = 0.62) and alveolar epithelium (r = 0.51). The authors conclude that the levels of 4-hydroxy-2-nonenal play a role in the signaling events of lung inflammation leading to an imbalance in the expression of both proinflammatory mediators and protective antioxidant genes in COPD.
The increase in alveolar macrophages in cigarette smokers may result from increased recruitment, increased proliferation, or decreased cell death. To determine whether chronic cigarette smoke influences the expression and localization of cell-cycle and apoptotic proteins in alveolar macrophages and bronchial epithelial cells, Tomita and coworkers (12) obtained bronchial biopsies from 10 healthy smokers, 7 patients with mild to moderate asthma, and 6 control subjects. The increased numbers of alveolar macrophages in the smokers resulted only in part from increased proliferation. Expression of p21CIP1/WAF1, a key protein that regulates the cell cycle and is responsive to oxidative stress, was increased in the alveolar macrophages and in bronchial biopsies from the smokers; it was found predominantly within the cytoplasm. Compared with the control subjects and patients with asthma, B cell lymphoma leukemia (Bcl)-xL, an antiapopoptotic regulator, was highly expressed in macrophages from the smokers. In in vitro studies, hydrogen peroxide induced cytoplasmic expression of p21CIP1/WAF1 and failed to induce apoptosis. The authors conclude that p21CIP1/WAF1 and B cell lymphoma leukemia proteins are increased in alveolar macrophages of cigarette smokers and that the increase in macrophages in smokers appears to result from inhibition of apoptosis. An editorial commentary by Vignola (13) accompanies this article.
The rate-limiting enzyme in the production of glutathione is
-glutamylcysteine synthetase, which is downregulated by oxidant exposure. Harju and coworkers (14) studied the localization of the enzyme in 22 patients with COPD, 20 smokers without COPD, and 13 nonsmokers. Both the heavy and light subunits of -glutamylcysteine synthetase were expressed most prominently in the large airways and localized in the cytoplasm and along the plasma membrane. The heavy subunit was more heavily expressed in the central bronchial epithelium than in peripheral bronchioli or in alveolar macrophages. Alveolar macrophages of nonsmokers had higher levels of both subunits than did macrophages of smokers. Expression of the heavy subunit in the central bronchial epithelium was greater in nonsmokers than in patients with COPD; the smokers and patients with COPD did not differ. The authors conclude that heavy and light subunits of -glutamylcysteine are expressed mainly in the large airways, and that their lower concentration in smokers may contribute to progression of oxidant-induced lung injury. An editorial commentary by Hiemstra (15) accompanies this article.Lung tissue from patients with emphysema carries an excess of adenoviral E1A DNA, which is expressed as a protein in the airway surface epithelium and associated with an increased inflammatory response. To investigate the mechanisms whereby the latent adenoviral infection amplifies the inflammatory process, Higashimoto and coworkers (16) obtained lung tissue from three patients undergoing lung resection, and transfected cultures of bronchial epithelial cells with a plasmid containing the adenovirus 5 E1A gene. When stimulated by lipopolysaccharide, the transfected epithelial cells increased intercellular adhesion molecule-1, and interleukin-8 messenger RNA and protein expression. Lipopolysaccharide also induced greater activity of intercellular adhesion molecule-1 promoter and greater binding activity of nuclear factor-
B in nuclear extracts of the transfected cells. The transfected cells displayed constitutive expression of messenger RNA and protein for transforming growth factor-ß1. The authors conclude that transfection of human bronchial epithelial cells with adenovirus E1A DNA upregulates the production of mediators that are involved in the pathogenesis of emphysema.To better define the role of tumor necrosis factor-
as a mediator of lung damaged caused by cigarette smoking, Churg and coworkers (17) studied three groups of mice. In control mice, cigarette smoke caused increases in gene expression for tumor necrosis factor-, macrophage inflammatory protein-2, and macrophage chemoattractant protein-1; these changes returned to control values by 6 hours. Exposure of knockout mice that lacked the p55/p75 receptors for tumor necrosis factor- showed no change in the gene expression of these mediators at any time. At 24 hours, the control mice, but not the knockout mice, displayed an increase in lavage neutrophils, macrophages, desmosine (a measurement of elastin breakdown), and hydroxyproline (a measure of collagen breakdown). Exposure of pure strain 129 mice (mice that produce only low levels of tumor necrosis factor-) to cigarette smoke produced no inflammatory response at 24 hours or at 7 days. The authors conclude that tumor necrosis factor- is central to smoke-induced inflammation and tissue breakdown.Lung Inflammationq.f(fs, http://www.100md.com
To determine the relationship between local and systemic inflammatory mediators in patients with COPD, Vernooy and coworkers (18) obtained plasma and sputum from 18 patients with COPD (FEV1, 56% predicted) and 17 healthy smokers (FEV1, 99% predicted). Compared with the control group, induced sputum from the patients revealed a higher percentage of neutrophils (81 versus 62%), and higher levels of interleukin-8 (3.7 versus 2.3 pg per ml) and soluble tumor necrosis factor-receptor 55 (237 versus 109 pg per ml). The level of tumor necrosis factor-
in induced sputum was equivalent in the two groups. In plasma, the patients had a higher level of soluble tumor necrosis factor-receptor 75 than did the control group (1.9 versus 1.4 ng per ml). The levels of inflammatory mediators in plasma and induced sputum were not correlated with each other. In the patients, FEV1 was correlated with the sputum levels of interleukin-8 (r = -0.84) and soluble tumor necrosis factor-receptor 55 (r = -0.52). The levels of interleukin-8, soluble tumor necrosis factor-receptor 55, and soluble tumor necrosis factor-receptor 57 were higher in the sputum of patients with COPD who were ex-smokers than in patients who were current smokers. The authors conclude that sputum levels of neutrophils, interleukin-8, and soluble tumor necrosis factor-receptor 55 are higher in patients with COPD than in healthy smokers, and that the levels of inflammatory mediators in sputum do not correlate with the levels in plasma.Pathophysiologic and Radiologic Studies|u&, 百拇医药
Brown and coworkers (19) compared the deposition and clearance of ultrafine technetium-99m–labeled aerosol in 10 patients with COPD (FEV1, 54% predicted) and 9 healthy subjects. For an aerosol exposure of 10 µg per m3, the dose rate was greater in the patients than in the control subjects (2.9 versus 1.9 µg per hour). The central-to-peripheral index, a measure of airway deposition, was greater in the patients than in the control subjects (1.11 versus 1.01). Clearance did not differ between the patients and the control group, and the average 24-hour retention was 85%. Particles were not seen to accumulate in the liver. The authors conclude that the deposition of ultrafine particles is greater in patients with COPD than in healthy subjects.|u&, 百拇医药
Because more women than men attend specialist cough clinics, Kastelik and coworkers (20) compared the sensitivity of the cough reflex in 60 female and 50 male patients with chronic cough. The dose of inhaled capsaicin inducing two coughs was 2.2 times smaller and the dose inducing five coughs was 6 times smaller in the women than in the men. The dose of inhaled citric acid inducing cough was 2.2 times smaller and the dose inducing five coughs was 2.8 times smaller in the women than in the men. The authors conclude that female patients with chronic cough displayed greater sensitivity to cough than do male patients.
Pulmonary Vasculatureiz*){oi, 百拇医药
To characterize the hemodynamic abnormalities in patients with severe emphysema, Scharf and coworkers (21) studied 120 patients participating in the National Emphysema Treatment Trial. The patients had an FEV1 of 27% of predicted and a residual volume of 225% of predicted; 91% of the patients had a mean pulmonary artery pressure at end-expiration of greater than 20 mm Hg, and 61% had a wedge pressure at end-expiration of greater than 12 mm Hg. Cardiac index was normal. The mean pulmonary artery pressure correlated inversely with PO2 and with severity of emphysema, and directly with the wedge pressure. On multiple stepwise regression, PO2 was not an independent predictor of mean pulmonary artery pressure. Diastolic ventricular pressures were increased without evidence of systolic dysfunction. The authors conclude that patients with severe emphysema commonly display elevated pulmonary vascular pressures, that increase in pulmonary artery pressure is not related to hypoxemia, that pulmonary hypertension is not associated with impaired systemic oxygen transport, and that high cardiac diastolic pressures do not represent systolic dysfunction.
Control of Breathing and Exercise#09}, 百拇医药
To determine factors that lead to an increase in PCO2 during exercise, O'Donnell and coworkers (22) studied 20 patients with COPD (FEV1, 34% of predicted). During maximum cycle exercise, patients increased PCO2 by 7 mm Hg (range, -6 to 25 mm Hg). The change in PCO2 from rest to exercise was best correlated with the change in PCO2 while breathing 60% oxygen (an indirect test of ventilation–perfusion mismatching; r2 = 0.62) and with resting oxygen saturation (r2 = 0.30). Serial changes in PCO2 during exercise were most closely correlated with changes in end-expiratory lung volume (r = 0.56) and oxygen saturation (r = 0.82). The authors conclude that the development of hypercapnia during exercise in patients with COPD is related to the development of dynamic hyperinflation and abnormalities of ventilation–perfusion matching. An editorial commentary by Dempsey (23) accompanies this article.
Respiratory Musclessxgo, 百拇医药
Ramirez-Sarmiento and coworkers (24) studied the effect of inspiratory muscle training on the structure of the inspiratory muscles in patients with COPD. Fourteen men (FEV1, 24% predicted) were randomized to true training or sham training. Training consisted of breathing through an inspiratory threshold device while generating 40 to 50% of maximum inspiratory pressure. The training was supervised and the sessions consisted of 30 minutes a day, 5 times a week, for 5 consecutive weeks. Training produced a 29% increase in maximal inspiratory pressure and 100% increase in inspiratory muscle endurance (the length of time that a patient was able to breathe against a load requiring the generation of 80% of maximal inspiratory pressure). Biopsies from the external intercostal muscles before and after training revealed a 38% increase in the proportion of type I fibers and a 21% increase in the size of type II fibers. Training had no effect on the structure of the vastus lateralis. The authors conclude that the improvement in inspiratory muscle strength and endurance after five weeks of supervised inspiratory muscle training is accompanied by increases in the proportion of type I fibers and the size of type II fibers. An editorial commentary by Levine and colleagues (25) accompanies this article.
It has been generally believed that shortening of the diaphragm in hyperinflated patients with COPD is accompanied by a decrease in the contribution of the diaphragm to tidal breathing. Gorman and coworkers (26) used ultrasonography and magnetometry to measure diaphragmatic length at different lung volumes in 10 men with COPD (FEV1, 23% of predicted) and 10 control subjects. The length of the diaphragm was 20% shorter in the patients at residual volume and functional residual capacity, but length was similar to that of the control subjects at total lung capacity. The length of the zone of apposition was decreased by 50% at residual volume and functional residual capacity in the patients. At a given absolute lung volume, however, the length of the zone of apposition was greater in the patients. Although mean functional residual capacity was equivalent to predicted total lung capacity in the patients, tidal volume, tidal changes in the length of the zone of apposition and length of the diaphragm, and tidal volume displaced by the diaphragm were equivalent in the patients and in the control subjects. The authors conclude that, despite shortening of the diaphragm in patients with COPD, the motion and change in length of the diaphragm during tidal breathing is equivalent in patients with COPD and healthy subjects.
Peripheral Muscleso]}!n+, 百拇医药
To determine the role of apoptosis of skeletal muscle in causing weight loss in patients with COPD, Agusti and coworkers (27) obtained biopsies from the quadriceps femoris in 7 patients with COPD who had a low body mass index (less than 20 kg per m2), 8 patients with COPD who had a normal body weight, 8 healthy volunteers, and 6 subjects requiring orthopedic surgery (to assess effects of inactivity). The percentage of cells positive for TUNEL (transferase-mediated dUTP nick and labeling) was 57% in patients with COPD and low body weight, 17% in patients with COPD and normal body weight, 6% in the orthopedic patients, and 4% in healthy subjects. A similar pattern was seen with another marker of apoptosis: the immunodetection of poly-(ADP-ribose)-polymerase proteolytic fragments (PARP). In the patients with COPD, body mass index was inversely related to apoptosis, as measured by TUNEL (r = -0.65). Body mass index was also related to peak oxygen consumption during exercise (r = 0.74) and to FEV1 (r = 0.66). Markers of skeletal muscle apoptosis were not related to any variables of lung function. The authors conclude that apoptosis of skeletal muscle is increased in patients with COPD who have a low body mass index and is associated with impaired exercise tolerance independently of the effect on lung function. An editorial commentary by Lewis (28) accompanies this article.
To compare the relative efficacy of strength versus endurance training, Ortega and coworkers (29) studied 47 patients with COPD. Strength training consisted of a series of weight-lifting exercises, and endurance training consisted of leg exercises on an ergocycle at 70% of peak work rate. Improvements in dyspnea and quality of life were still evident at three months after completing the training program. Compared with patients undergoing strength training alone, improvements in submaximal exercise capacity were greater in patients undergoing either endurance training or the combination of endurance training and strength training. Increases in the strength of muscle groups (chest pull, neck press, leg flexion and extension) were equivalent in patients undergoing strength training alone and patients undergoing the combination of strength training plus endurance training: the increases in strength in both of these groups was higher than in patients undergoing endurance training alone. Increase in walking distance was restricted to the group undergoing strength training. The authors conclude that a combination of strength training plus endurance training achieves maximal muscle training in patients with COPD.
To determine whether muscle mass is a better predictor of survival than is body mass index, Marquis and coworkers (30) followed 142 patients with COPD (FEV1, 42% of predicted) for an average of 41 months. Only the cross-sectional area of midthigh muscle (obtained by computed tomography) and FEV1 were significant predictors of mortality. Mortality was not related to body mass index, thigh circumference, age, sex, daily use of glucocorticoids, diffusing capacity, PO2, PCO2, or peak work rate during exercise. Compared with the patients who had an FEV1 of at least 50% of predicted plus a midthigh muscle area of at least 70 cm2, the patients who had an FEV1 of less than 50% of predicted and a muscle area of at least 70 cm2 had a mortality odds ratio of 3.37. Compared with the patients who had an FEV1 of at least 50% of predicted plus a midthigh muscle area of at least 70 cm2, the patients who had an FEV1 of less than 50% of predicted and muscle area of less than 70 cm2 had a mortality odds ratio of 13.16. Anthropometric measurements could not predict midthigh muscle area. The authors conclude that midthigh cross-sectional muscle area is a better predictor of mortality in patients with COPD than is body mass index. An editorial commentary by Mador (31) accompanies this article.
Drug Therapy+yvo, 百拇医药
Muscarinic antagonists.+yvo, 百拇医药
The Lung Health Study involved 5,887 smokers who did not regard themselves as ill but who had mild to moderate impairment of lung function. Anthonisen and coworkers (32) analyzed the data to assess factors influencing morbidity and mortality. Over 5 years, 149 (2.5%) participants died, largely from lung cancer and cardiovascular disease. A total of 12.8% of participants were hospitalized: 75% of hospitalizations resulted from cancer, cardiovascular disease, and nonmalignant respiratory disease. Death and hospitalizations for cardiovascular disease and coronary artery disease tended to be more common in individuals assigned to the smoking intervention plus ipratropium bromide arm of the study than among individuals in the smoking intervention plus placebo arm (the difference approached statistical significance). Nine individuals in the smoking intervention plus ipratropium arm were hospitalized for supraventricular tachycardia as compared with two individuals in the smoking intervention plus placebo arm. The authors conclude that use of ipratropium bromide was associated with an increased tendency for cardiovascular disease and supraventricular tachycardia.
Theophylline./, http://www.100md.com
Culpitt and coworkers (33) asked, "Does theophylline decrease airway inflammation in patients with COPD?" In a double-blind randomized trial, 25 patients with COPD were treated with low-dose theophylline (plasma level 9 to 11 mg per liter) for 4 weeks. Theophylline produced decreases of about 22% in induced sputum inflammatory cells, neutrophils, interleukin-8, myeloperoxidase, and lactoferrin. Neutrophils from subjects treated with theophylline displayed a decrease in chemotaxis to N-formyl-met-leu-phe of about 28% and to interleukin-8 of about 60%. Theophylline produced a 34% decrease in the chemotaxis of healthy donor neutrophils to induced sputum. The authors conclude that administration of theophylline to patients with COPD produces a decrease in sputum neutrophils, sputum chemotactic activity, and chemotaxis of peripheral blood neutrophils to chemotactic stimuli. An editorial commentary by Rabe (34) accompanies this article./, http://www.100md.com
Glucocorticoids.
In 199 patients with an acute exacerbation of COPD, Maltais and coworkers (35) did a double-blind randomized trial of nebulized budesonide (2 mg every 6 hours), oral prednisolone (30 mg every 12 hours), and placebo. Compared with placebo, the postbronchodilator FEV1 was 0.10 liter higher with budesonide and 0.16 liter higher with prednisolone; the difference between budesonide and prednisolone was not significant. Adverse effects were equivalent with the three therapies, although hyperglycemia was more common with prednisolone than with budesonide. The authors conclude that nebulized budesonide is as effective as oral prednisolone in the management of acute exacerbations of COPD.h, 百拇医药
To determine the effect of stopping high-dose inhaled glucocorticoids in patients with COPD, van der Valk and coworkers (36) did a double-blind randomized study in 244 patients who had received inhaled fluticasone propionate (1,000 µg daily) for 4 months. Over the subsequent 6 months, 57% of the 121 patients in the placebo group developed at least one exacerbation as compared with 47% of the 123 patients in the fluticasone group. The hazard ratio of a first exacerbation was 1.5 in the placebo versus the fluticasone group. Measures of quality of life, in terms of total score, activity domain, and symptom domain were higher in the fluticasone group than in the placebo group. The authors conclude that the discontinuation of inhaled glucocorticoids in patients with COPD leads to an increased risk of exacerbation and a deterioration in the quality of life.
The effect of inhaled glucocorticoids on the profile of inflammatory cells in the airways of patients with COPD is not known. Accordingly, Hattotuwa and coworkers (37) did a double-blind randomized trial of inhaled fluticasone propionate (500 µg twice daily) versus placebo in 31 patients with COPD. Bronchial biopsies at three months revealed no difference between the groups in the primary endpoints: number of CD8+ cells, CD68+ cells, and neutrophils (which are considered important in COPD). Patients receiving fluticasone showed a reduction in the ratio of CD8 to CD4 cells in the epithelium and a reduction in the number of mast cells in the subepithelium. Patients receiving fluticasone had an improvement in symptoms and fewer exacerbations. The authors conclude that inhaled fluticasone propionate has no effect on the major inflammatory cell types in the airways of patients with COPD, although it reduces the ratio of CD8 to CD4 cells in the epithelium and the number of mast cells in the subepithelium. An editorial commentary by Pauwels (38) accompanies this article.
In 691 patients with COPD, Mahler and coworkers (39) did a randomized controlled comparison of inhaled salmeterol (50 µg), fluticasone propionate (500 µg), the combination of salmeterol and fluticasone, and placebo. Agents were inhaled via a Diskus device twice daily for 24 weeks. At the endpoint, the increase in predose FEV1 was greater with the fluticasone-salmeterol combination (156 ml) than with salmeterol (107 ml) and placebo (-4 ml). The increase in 2-hour postdose FEV1 was greater with the fluticasone–salmeterol combination (261 ml) than with fluticasone (138 ml) and placebo (28 ml). Improvements in dyspnea were also greater with the combination therapy. The authors conclude that combination of fluticasone propionate and salmeterol delivered via a Diskus device achieves greater improvement in lung function and dyspnea than either agent on its own..d\, 百拇医药
To determine the relationship between use of glucocorticoids, bone mineral density, and fracture, Walsh and coworkers (40) studied patients who had taken continuous or frequent courses of oral glucocorticoids for asthma, COPD or idiopathic pulmonary fibrosis over the preceding six months. Of 117 patients, 48% were women, 58% had osteoporosis, and 61% had a vertebral fracture. The presence of a vertebral fracture was related to bone mineral density of the femoral neck (measured by X-ray absorptiometry): odds ratio was 1.6 for a reduction of 1 SD in density. Between the highest and lowest quartile dose of prednisolone, the risk of vertebral fracture increased 4.4-fold; adding bone density of the femoral neck did not alter the relationship. The authors conclude the risk of vertebral fracture is strongly related to the cumulative dose of prednisolone and that this effect is independent of its more modest effect on bone mineral density.
To determine whether the use of inhaled glucocorticoids are associated with the development of a hip fracture, Hubbard and coworkers (41) did a case–control study of 16,341 cases of hip fracture in a general practice research database and 29,889 control subjects. After adjusting for potential confounders, conditional logistic regression revealed an association between hip fracture and inhaled glucocorticoids (odds ratio, 1.26). After adjusting for annual courses of oral glucocorticoids, the odds ratio was reduced to 1.19. Hip fractures displayed a dose–response relationship to inhaled glucocorticoids. The authors conclude that use of inhaled glucocorticoids is associated with the development of hip fracture in older subjects.h?||, 百拇医药
Experimental protease inhibitors.h?||, 百拇医药
In a rat model of emphysema, the retinoid, all-trans-retinoic acid, reverses anatomic and physiologic signs of emphysema. Mao and coworkers (42) tested the feasibility of this agent in 20 patients with severe emphysema using a double-blind crossover design over 6 months. The treatment was generally well tolerated. Side effects included skin changes, transient headaches, hyperlipidemia, and musculoskeletal pains. Pulmonary function and computed tomographic images did not change. Plasma drug levels varied appreciably among subjects and decreased over time in 35% of the participants. The authors conclude that it is feasible to undertake a trial of therapy with all-trans-retinoic acid in patients with emphysema.
ONO-6818 is a novel oral agent that inhibits neutrophil elastase. To investigate its effect, Kuraki and coworkers (43) studied four groups of rats. Oral administration of ONO-6818 1 hour before application of human neutrophil elastase ameliorated the increases in lung myeloperoxidase activity, hemoglobin, and neutrophil counts in bronchoalveolar fluid at 6 hours. Eight weeks later, the rats treated with ONO-6818 had less severe increases in functional residual capacity, total lung capacity, lung compliance, and mean linear intercept. The authors conclude that the induction of emphysema by human neutrophil elastase is inhibited by the oral neutrophil elastase inhibitor, ONO-6818, mainly through minimizing lung hemorrhage and the accumulation of neutrophils in the lung.rza^p, 百拇医药
To determine whether an orally active inhibitor of serine elastase, ZD 0892, decreases emphysematous lung destruction, Wright and coworkers (44) exposed guinea pigs to cigarette smoke. Acute exposure to smoke caused increased lavage neutrophils and increased desmosine and hydroxyproline (measures of elastin and collagen breakdown). These changes were reduced by the elastase inhibitor. Exposure to cigarette smoke every day for six months produced emphysema and caused increases in lavage neutrophils, desmosine, and hydroxyproline, and in plasma tumor necrosis factor-
. The elastase inhibitor returned the lavage levels of neutrophils, desmosine and hydroxyproline to control values, decreased tumor necrosis factor- by 30%, and decreased the airspace enlargement by 45%. Exposure of animals to smoke plus the elastase inhibitor for two months, preceded by exposure to smoke for four months, did not protect against the development of emphysema. Mice exposed to smoke showed increases in gene expression of neutrophil chemoattractant macrophage inflammatory protein-, macrophage chemoattractant protein-1, and tumor necrosis factor-; these changes were prevented or decreased by the elastase inhibitor. The authors conclude that a serine elastase inhibitor ameliorates the inflammatory and destructive effects of cigarette smoke and that these effects are mediated in part by neutrophils and the production of tumor necrosis factor-.Other Therapies^9*j0', 百拇医药
Lung volume reduction surgery.^9*j0', 百拇医药
The mismatch between the size of the lungs and the size of the chest cavity in patients with emphysema is thought to be an important determinant of the reduced forced vital capacity (FVC) and FEV1 in this condition. In 13 patients undergoing lung volume reduction surgery, Fessler and coworkers (45) found that the ratio of residual volume to total lung capacity—a measure of the mismatch between lung size and chest size—was the only independent predictor of the increase in FVC after surgery. Of the increase in FEV1 after surgery, 70% was attributable to the increase in FVC and the remainder to the increase in FEV1/FVC ratio. In another group of 78 patients undergoing lung volume reduction surgery, the ratio of residual volume to total lung capacity was again correlated with the increase in FVC after surgery; the ratio, however, did not predict the increase in FEV1. The authors conclude that the ratio of residual volume to total lung capacity is the major determinant of the increase in forced vital capacity achieved by lung volume reduction surgery.
In 12 patients with severe emphysema (FEV1, 0.69 liters; 23% predicted) undergoing lung volume reduction surgery, Mineo and coworkers (46) assessed right ventricular function before and 6 months after the surgery. Surgery produced a 59% increase in FEV1, a 23% decrease in the ratio of residual volume to total lung capacity, a 12% increase in cardiac index during rest, and a 9% increase in right-ventricular stroke volume. During submaximal exercise, cardiac index increased by 22%, right-ventricular stroke volume increased by 28%, and right-ventricular ejection fraction increased by 20% after surgery. The improvement in ejection fraction during exercise was correlated with the decrease in the ratio of residual volume to total lung capacity after surgery (r = -0.68). The authors conclude that lung volume reduction surgery produces an improvement in right ventricular performance in patients with emphysema, especially during exercise.(0c;:@l, 百拇医药
1-Antitrypsin replacement therapy.In 12 patients with -antitrypsin deficiency, Stockley and coworkers (47) studied the effect of four infusions of Prolastin at weekly intervals on airway inflammation. The serum level of -antitrypsin rose and was maintained above the protective threshold. One week after the first infusion, the level of -antitrypsin in expectorated sputum increased from 0.17 to 0.43 µm (equivalent to the value in normal subjects). Chemoattractant B4 and elastase activity in the sputum samples decreased. The authors conclude that short-term therapy with Prolastin restores airway concentrations of 1-antitrypsin to normal and it decreases the level leukotriene B4 (a major mediator of neutrophil recruitment and augmentation) in airway secretions./s|w, 百拇医药
Outcome/s|w, 百拇医药
To determine whether COPD interferes with a person's ability to work, Sin and coworkers (48) analyzed data from 12,436 participants in NHANES III (Third National Health and Nutrition Examination Survey) study, 8.6% of whom reported COPD. Compared with participants without COPD, those reporting COPD were 3.9% less likely to be in the labor force. The decreased likelihood of being in the labor force was proportional to disease severity: 3.4%, 3.9%, and 14.4% for subjects with mild, moderate and severe COPD, respectively. The decrease in ability to work was estimated to cause a loss of $9.9 billion in the United States. The authors conclude that a self-report of COPD is associated with a considerable reduction in a person's ability to work.
Workshops/*30r;k, 百拇医药
In a summary report from a NHLBI workshop, Croxton and colleagues (49) review future directions for research on COPD./*30r;k, 百拇医药
AIR POLLUTION/*30r;k, 百拇医药
TOP/*30r;k, 百拇医药
CONTENTS/*30r;k, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY.../*30r;k, 百拇医药
AIR POLLUTION/*30r;k, 百拇医药
PULMONARY VASCULAR DISORDERS AND.../*30r;k, 百拇医药
LUNG TRANSPLANTATION/*30r;k, 百拇医药
PLEURAL DISORDERS/*30r;k, 百拇医药
LUNG CANCER/*30r;k, 百拇医药
REFERENCES/*30r;k, 百拇医药
Air Pollution–General/*30r;k, 百拇医药
To determine whether concentrated ambient air particles induce pulmonary inflammation in normal rats and in rats with chronic bronchitis, Saldiva and coworkers (50) exposed four groups of rats (some healthy and some with chronic bronchitis secondary to sulfur dioxide) to filtered air or to concentrated ambient air particles for five hours a day for three consecutive days. Concentrated ambient air particles caused an increase in neutrophils in the bronchoalveolar fluid of both the normal rats and the rats with chronic bronchitis. The particles caused an increase in the numerical density of neutrophils in the alveolar walls only in normal rats; the density was greater in the central regions than in the peripheral regions of the lung. A dose-dependent relationship was found between many components of concentrated ambient air particles (especially vanadium and bromine) and neutrophils and lymphocytes in bronchoalveolar fluid. The authors conclude that short-term exposure to concentrated ambient air particles induces a significant inflammatory reaction in the lungs of rats.
Particulate air pollution is associated with cardiovascular morbidity and mortality. To investigate this association, Nemmar and coworkers (51) studied the effect of intravenous and intratracheal administration of ultrafine (60 nm) polystyrene particles on thrombus formation in a hamster model. Intravenous administration of unmodified particles had no effect on thrombus formation. Intravenous administration of amine-polystyrene particles enhanced thrombosis at high but not at low concentrations. High concentrations of carboxylate-polystyrene particles inhibited thrombus formation. Intratracheal instillation of amino-polystyrene particles caused an increase in thrombus formation, whereas unmodified particles and carboxylate-polysterene particles had no effect. Unmodified particles did not alter the aggregation of platelets in human plasma induced by ADP, whereas carboxylate-polystyrene particles weakly enhanced platelet aggregation. Amine-polystyrene particles were sufficient to induce platelet aggregation on their own and strongly enhanced aggregation induced by ADP. The authors conclude that the presence of ultrafine particles in the circulation increases the tendency toward thrombosis, resulting in part from platelet activation and depending on the surface charge of the particles.
To determine whether antioxidant vitamins could modulate the adverse effect of air pollution on lung function in children, Romieu and coworkers (52) did a double-blind randomized study in 158 children with asthma who lived in Mexico City. During the 31-month study, the average maximum level of ozone was 102 ppb and the mean 24-hour average level of particulates with a mass median diameter of less than 10 µm (PM10) was 57 µg per m3. Pulmonary function was measured twice weekly. In the placebo group, the children with moderate and severe asthma showed an inverse relationship between the level of ozone (on the day before spirometry) and peak expiratory flow (-15 ml per second per 10 ppb), forced expiratory flow (FEF25–75, -13.3 ml per second per 10 ppb), and FEV1 (-4.6 ml per 10 ppb). In children treated with vitamin E (50 mg daily) and vitamin C (250 mg daily), no association was seen between ozone and lung function. The authors conclude that antioxidant supplements might modulate the impact of exposure to ozone on the small airways of children with moderate to severe asthma.
To determine whether exposure to ambient air pollutants affects the growth of lung function in children, Gauderman and coworkers (53) studied 2,081 fourth-grade children (average age, 9.9 years). Exposure to acid vapor, nitrogen dioxide, particles with an aerodynamic diameter of less than 2.5 µm (PM2.5), and elemental carbon were associated with significant deficits in the growth of lung function. Across the range of acid exposure, for example, the average annual growth rates of MMEF and FEV1 were reduced by 11% and 5%, respectively. Exposure to acid vapor was associated with a decrease in the ratio of MMEF to FVC, whereas exposure to ozone was associated with a reduced rate of growth in PEF. Children spending more time outdoors experienced greater deficits in lung function. The authors conclude that exposure to ambient levels of air pollutants has a detrimental effect on growth of lung function in children.no, 百拇医药
To determine the relationship between exposure to air pollution related to traffic and the development of asthmatic symptoms, allergic diseases, and respiratory infections, Brauer and coworkers (54) studied a birth cohort of 4,146 children. Outdoor concentrations of traffic-related air pollutants were modeled for the home of each subject. Adjusted odds ratios for wheezing, physician-diagnosed asthma, infections of the ear, nose or throat, and serious colds at 2 years of age were associated with air pollutants; some of the associations reached borderline statistical significance. The authors conclude that traffic-related air pollution may be associated with the prevalence of respiratory illness at 2 years of age.
Diesel Exhaust1a, 百拇医药
Takano and coworkers (55) determined whether diesel exhaust particles enhance lung inflammation caused by endotoxin in mice. Instillation of diesel exhaust particles into the trachea of mice synergistically enhanced the lung inflammation caused by endotoxin, which was characterized by neutrophil sequestration, interstitial edema, and alveolar hemorrhage. Given alone, diesel exhaust particles increased the lung expression of Toll-like receptor 4 and nuclear localization of the p50 subunit of nuclear factor-B. In the presence of endotoxin, diesel exhaust particles further activated the nuclear translocation of the p65 subunit of nuclear factor-B in the lung, and increased the lung expression of intercellular adhesion molecule-1, interleukin-1ß, macrophage chemoattractant protein-1, keratinocyte chemoattractant, macrophage inflammatory protein-1, and Toll-like receptors. The combined exposure to diesel exhaust particles and endotoxin decreased the nuclear localization of CCAAT/enhancer binding protein B. The authors conclude that diesel exhaust particles enhance neutrophilic lung inflammation related to endotoxin and that the enhancement is mediated through the induction of proinflammatory molecules, such as expression of Toll-like receptors and activation of p65-containing dimers of nuclear factor-
B.PULMONARY VASCULAR DISORDERS AND RELATED DISORDERSimpg(2?, 百拇医药
TOPimpg(2?, 百拇医药
CONTENTSimpg(2?, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...impg(2?, 百拇医药
AIR POLLUTIONimpg(2?, 百拇医药
PULMONARY VASCULAR DISORDERS AND...impg(2?, 百拇医药
LUNG TRANSPLANTATIONimpg(2?, 百拇医药
PLEURAL DISORDERSimpg(2?, 百拇医药
LUNG CANCERimpg(2?, 百拇医药
REFERENCESimpg(2?, 百拇医药
Pulmonary Hypertensionimpg(2?, 百拇医药
Molecular and pathophysiologic mechanisms.impg(2?, 百拇医药
The CX3E chemokine, fractalkine, is produced by endothelial cells, promotes leukocyte recruitment, and is unique because it exists both in a soluble form (chemotactic protein) and in a membrane-anchored form on endothelial cells (cell-adhesion molecule). To assess the role of fractalkine in the recruitment of cells to the lungs of patients with pulmonary hypertension, Balabanian and coworkers (56) studied seven patients with pulmonary arterial hypertension and eight patients with chronic thromboembolic pulmonary hypertension. The fractalkine receptor (CX3CR1) was upregulated in circulating T lymphocytes (mostly in the CD4+ subset) in patients with pulmonary arterial hypertension. The abnormal response of T lymphocytes to fractalkine was not secondary to high vascular pressure because it did not occur in patients with chronic thromboembolic hypertension. Concentrations of soluble fractalkine were higher in patients with pulmonary arterial hypertension than in patients with chronic thromboembolic hypertension and control subjects. Messenger RNA and the protein product of fractalkine were expressed in pulmonary artery endothelial cells of patients with pulmonary arterial hypertension. The authors conclude that inflammatory mechanisms involving the chemokine fractalkine and its receptor contribute to the injury of pulmonary arterial hypertension. An editorial commentary by Williams (57) accompanies this article.
Endothelin-1 has been implicated in pulmonary hypertension because of its dual vasoconstrictor and mitogenic actions. The effects of endothelin-1 are mediated via two distinct receptors: endothelinA and endothelinB. Davie and coworkers (58) examined the distribution of these receptors in the pulmonary arteries, and studied their role in mediating the proliferative actions of endothelin-1. EndothelinB receptors were more frequent in the distal arteries than in the proximal arteries: 36% versus 3%. The density of receptors in distal arteries and lung parenchyma was twice as great in 22 patients with pulmonary hypertension than in 13 control subjects. Endothelin-1 stimulated DNA synthesis and attenuated the antiproliferative action of cicaprost and forskolin on pulmonary artery smooth muscle cells; these effects were mediated by both the endothelinA and endothelinB receptors. The stimulation of smooth muscle proliferation by serum was attenuated by inhibiting either the release of endothelin-1 (with phosphoramidon) or the action of endothelin-1 (with PD 145,065). Cicaprost inhibited the release of endothelin-1 from the smooth muscle cells and increased the intracellular concentration of cyclic AMP, whereas stimulation of the endothelinB receptor decreased the concentration of cyclic AMP. The authors conclude that the distributions of endothelinA and endothelinB receptors differ in human pulmonary arteries, and that both receptors promote the proliferation of smooth muscle cells and may contribute to vascular remodeling in pulmonary hypertension.
The plexiform lesions of primary pulmonary hypertension contain macrophages and lymphocytes. Because RANTES (regulated upon activation, normal T cell expressed and secreted) is an important chemoattractant for monocytes and T cells, Dorfmuller and coworkers (59) determined whether this chemokine promotes cell recruitment in the lungs of patients with pulmonary hypertension. The expression of RANTES was eight times greater in lung samples from 10 patients with severe pulmonary hypertension than in the lungs of 7 control subjects. The major source of RANTES was the endothelial cells within the pulmonary artery wall. The expression of RANTES was associated with infiltrates of CD45+ inflammatory cells. The authors conclude that inflammatory mechanisms play a role in the natural history of pulmonary hypertension.arc{s?, 百拇医药
In the hepatopulmonary syndrome, dilatation of pulmonary vessels is related to increased production of nitric oxide secondary to increased expression of inducible nitric oxide synthase by macrophages in the pulmonary vessels and less so to endothelial nitric oxide synthase. To investigate the role of translocation of gut bacteria in this syndrome, Rabiller and coworkers (60) administered a 5-week course of norfloxacin to rats with cirrhosis induced by ligation of the common bile duct. Norfloxacin decreased the incidence of gram-negative translocation from 70 to 0%, and it decreased the proportion of pulmonary microvessels containing more than 10 macrophages from 52 to 21%. Features of dilated pulmonary vessels (increased alveolar-to-arterial oxygen difference and cerebral uptake of labeled macro aggregates) were decreased to a level that fell between sham-operated rats and untreated cirrhotic rats. Norfloxacin decreased the expression and activity of inducible nitric oxide-synthase to normal, but not that of endothelial nitric oxide synthase. The authors conclude that norfloxacin decreases the severity of hepatopulmonary syndrome in cirrhotic rats by inhibiting translocation of gut bacteria and decreasing the production of nitric oxide by macrophages in pulmonary vessels.
Reeves (61) recalls early studies on pulmonary vasoconstriction in cattle at high altitude.n, http://www.100md.com
Treatment.n, http://www.100md.com
In patients with primary pulmonary hypertension, prostacyclin improves exercise tolerance within the first few weeks of treatment, even in patients who show no change in resting pulmonary hemodynamics. To determine whether the improved exercise tolerance is accompanied by improvement in the pressure-flow characteristics of the pulmonary circulation during exercise, Castelain and coworkers (62) studied seven patients with primary pulmonary hypertension before and after continuous infusion of prostacyclin for six weeks. The patients did not respond to an acute inhalation of nitric oxide. Prostacyclin produced an increase of 81 m in the six-minute walking distance. Prostacyclin caused a 28% decrease in the slope of mean pulmonary artery pressure plotted against cardiac index. The authors conclude that the improvement in exercise performance achieved by prostacyclin in patients with primary pulmonary hypertension results from blunting of the increase in pulmonary vascular resistance during exercise.
Prostacyclin requires a permanent central venous catheter, whereas the stable prostacyclin analog, treprostinil, can be given by subcutaneous infusion and has a longer half-life. In 470 patients with primary pulmonary hypertension, Simmonneau and coworkers (63) did a 12-week double-blind, placebo-controlled trial. Treprostinil increased the 6-minute walking distance by 16 m, and it improved dyspnea, signs and symptoms of pulmonary hypertension, and hemodynamics. Pain at the infusion site occurred in 85% of the treprostinil group, requiring premature discontinuation of therapy in 8% of patients. The authors conclude that chronic subcutaneous infusion of treprostinil is effective in patients with pulmonary hypertension and that its safety profile is acceptable.cpi$z, http://www.100md.com
To determine the frequency and outcome of cardiopulmonary resuscitation in patients with pulmonary artery hypertension, Hoeper and coworkers (64) analyzed data on 3,130 patients from 17 referral centers in Europe and the United States. Circulatory arrest occurred in 513 patients and cardiopulmonary resuscitation was attempted in 132 (26%) of the patients. Resuscitation efforts were primarily unsuccessful in 104 patients (79%), and only 8 patients (6%) survived for more than 90 days. Hemodynamic measures within three months before the arrest did not predict outcome. The authors conclude that cardiopulmonary resuscitation is rarely successful in patients with pulmonary artery hypertension.
In a rat model of pulmonary hypertension induced by left pneumonectomy and injection of monocrotaline, Nishimura and coworkers (65) studied the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Compared with rats treated with placebo, rats treated with simvastatin from Days 5 to 35 after induction of pulmonary hypertension had a lower mean pulmonary artery pressure (27 versus 53 mm Hg) and less pulmonary vascular remodeling with neointimal formation (scores of 0.6 versus 2.0). Expression of the gene for nitric oxide synthase in lung endothelium was decreased in the mice treated with placebo, but the levels returned toward normal in the mice treated with simvastatin. The authors conclude that simvastatin attenuates pulmonary arterial hypertension, right-ventricular hypertrophy, and neointimal formation in pneumonectomized mice treated with monocrotaline. An editorial commentary by Rubin (66) accompanies this article.-^'fw{&, 百拇医药
In a model of neonatal pulmonary hypertension in piglets, Shekerdemian and coworkers (67) studied the effect of intravenous sildenafil, a phosphodiesterase-5 inhibitor. Instilling human meconium into the trachea of piglets produced a 70% increase in pulmonary vascular resistance and a 100% increase in oxygenation index. Within 1 hour of commencing the infusion of sildenafil, pulmonary vascular resistance was reversed completely as compared with a 40% decrease in resistance after treatment with inhaled nitric oxide for 2 hours. Sildenafil also increased cardiac output by 30% without an adverse effect on oxygenation. The authors conclude that intravenous sildenafil is a selective and highly effective pulmonary vasodilator in piglets that have neonatal pulmonary hypertension.
In a pulmonary perspective, Hoeper and colleagues (68) discuss new treatments for pulmonary arterial hypertension.|\, 百拇医药
Thromboembolic Disorders|\, 百拇医药
Diagnostic studies.|\, 百拇医药
In a prospective study of 314 consecutive patients, de Monye and coworkers (69) asked, "Is the accuracy of D-dimer assays in diagnosing pulmonary embolism influenced by the location of the embolus?" Emboli were confined to subsegmental arteries in 20% of the patients. The area under a receiver operating characteristic curve for D-dimer was higher when pulmonary emboli were located in segmental or larger arteries than when emboli were located in subsegmental arteries: 0.86 versus 0.59. Sensitivity of D-dimer in excluding segmental or larger emboli was higher than for excluding subsegmental emboli: 93% versus 50%. The authors conclude that D-dimer assays are not reliable in excluding small subsegmental pulmonary emboli.|\, 百拇医药
High Altitude
In a study of inhabitants on the mountains of Kyrgyzstan, Aldashev and coworkers (70) estimated the prevalence of high-altitude pulmonary hypertension and determined whether polymorphisms of the gene for angiotensin-converting enzyme are associated with pulmonary hypertension. An electrocardiographic survey of 741 highlanders revealed features of cor pulmonale in 14% of subjects. Among an independent group of 136 male highlanders with dyspnea at altitude, 20% had a mean pulmonary artery pressure of greater than 25 mm Hg and another 26% developed an increase in pulmonary artery pressure when breathing 11% oxygen. On follow-up after 10 years, mean pulmonary artery pressure increased by 35% in the subjects who hyperresponded to 11% oxygen, by 20% in the subjects who previously displayed resting pulmonary hypertension, and by 6% in the normal subjects. Insertion/deletion (I/D) genotyping for angiotensin-converting enzyme revealed that the I/I genotype was three times more common in highlanders with pulmonary hypertension than in normal highlanders. Mean pulmonary artery pressure was higher in highlanders with the I/I genotype (27 mm Hg) than in highlanders with the I/D genotype (21 mm Hg) or the D/D genotype (18 mm Hg). The authors conclude that pulmonary hypertension is common among Kyrgyzstan highlanders, its development can be predicted by the response to acute hypoxia, and that high-altitude pulmonary hypertension is associated with insertion/deletion polymorphism of the gene for angiotensin-converting enzyme.
A polymorphism of the gene for angiotensin-converting enzyme has been identified in which the presence (insertion, I allele), as opposed to the absence (deletion, D allele), of a fragment is associated with low tissue levels of the enzyme and enhanced performance in endurance athletes. An excess of the I allele has also been noted in South American natives living above 3,000 m. To determine whether this polymorphism is associated with oxygen saturation at high altitude, Woods and coworkers (71) studied 32 individuals who ascended to 5,000 m over 12 days and 40 individuals who ascended over 18.5 days. In the slow ascent group, oxygen saturation at rest and the fall in saturation with ascent were independent of genotype for angiotensin-converting enzyme. In the rapid ascent group, oxygen saturation was associated with genotype and saturation was relatively well sustained in the II subjects. The authors conclude that the insertion allele of the gene for angiotensin-converting enzyme is associated with maintenance of oxygen saturation during rapid ascent to high altitude.
Sickle Cell Disease3ld.x, 百拇医药
To determine the mechanisms of exercise limitation in patients with sickle cell anemia, Callahan and coworkers (72) had 17 adult women with sickle cell anemia perform maximal cardiopulmonary exercise tests. Blood gases and lactate concentrations were measured every two minutes. All patients completed the test without complications and none displayed a mechanical ventilatory limitation. Three patterns of response were seen: 11 patients had a pattern consistent with pulmonary vascular disease (low peak oxygen consumption, low anaerobic threshold, gas exchange abnormalities, and high ventilatory reserve); 3 patients had a pattern consistent with peripheral vascular disease, a myopathy, or both (low peak oxygen consumption, low anaerobic threshold, no gas exchange abnormalities, and a high heart rate reserve); and 3 patients had a pattern consistent with anemia (low peak oxygen consumption, low anaerobic threshold, no gas exchange abnormalities, and a low heart rate reserve). The authors conclude that a substantial proportion of patients with sickle cell anemia develop features of pulmonary vascular disease during exercise.
LUNG TRANSPLANTATION#.\u, 百拇医药
TOP#.\u, 百拇医药
CONTENTS#.\u, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...#.\u, 百拇医药
AIR POLLUTION#.\u, 百拇医药
PULMONARY VASCULAR DISORDERS AND...#.\u, 百拇医药
LUNG TRANSPLANTATION#.\u, 百拇医药
PLEURAL DISORDERS#.\u, 百拇医药
LUNG CANCER#.\u, 百拇医药
REFERENCES#.\u, 百拇医药
Lung Preservation#.\u, 百拇医药
To gain insight into pathophysiology of preservation and reperfusion injury during lung transplantation, de Perrot and coworkers (73) studied the kinetics of cytokine release in 18 consecutive patients undergoing bilateral lung transplantation. The levels of tumor necrosis factor-
, interferon-, interleukin-10, interleukin-12, and interleukin-18 were elevated during ischemia time. Interleukin-8 was predominantly increased after reperfusion; the level of interleukin-8 after two hours of reperfusion was correlated with the PO2/FIO2 ratio (r2 = 0.50), mean airway pressure (r2 = 0.60), APACHE score during the first 24 hours after surgery (r2 = 0.30), and length of stay in the intensive care unit. The authors conclude that the level of interleukin-8 is a significant predictor of graft function after lung transplantation.The current surgical procedures for lung transplantation do not reinstitute the systemic circulation of the graft. Nowak and coworkers (74) determined whether revascularization of the bronchial arteries would decrease ischemia–reperfusion injury in the transplanted lungs of dogs. Compared with control dogs, dogs undergoing either conventional lung transplantation or bronchial artery revascularization had higher levels of lactate dehydrogenase and carboxypeptidase M (a marker for type I pneumocytes) at 2 and 4 hours of reperfusion. The levels of alkaline phosphatase (a marker enzyme for type II pneumocytes) were higher in the animals undergoing conventional transplantation (60 IU per liter) than in animals undergoing bronchial revascularization (33 IU per liter) or in control animals (13.6 IU per liter). The level of angiotensin-converting enzyme (a marker for pulmonary endothelium) was also higher in the dogs undergoing conventional transplantation (1.4 IU per liter) than in dogs undergoing bronchial revascularization (0.35 IU per liter) or in control animals (0.06 IU per liter). The authors conclude that bronchial artery revascularization protects the pulmonary endothelium and type II pneumocytes after lung transplantation.
ATP-sensitive potassium channel openers suppress the release of superoxide from neutrophils and play a central role in the suppression of reperfusion injury in cardiac muscle. To determine whether pinacidil, an ATP-sensitive potassium channel opener, attenuates ischemia–reperfusion injury of the lung, Fukuse and coworkers (75) used an ex vivo rat lung model. Heart–lung blocks preserved with pinacidil had lower shunt fraction, pulmonary artery pressure, and peak inspiratory pressure than did heart–lung blocks preserved with saline or with pinacidil combined with glibenclamide (a blocker of the channel opener). The concentrations of total adenine nucleotides and ATP in the lung after reperfusion were lower in the control group and in the glibenclamide group than in the fresh group. The control and glibenclamide groups displayed increased lipid peroxidation of the lungs after reperfusion, and decreased State 3 mitochondrial respiration and State 3/4 ratio of mitochondrial respiration. The authors conclude that ATP-sensitive potassium channel openers maintain mitochondrial respiratory function during lung preservation, prevent lipid peroxidation after reperfusion, and attenuate ischemia–reperfusion injury during lung preservation.
Patient Selectionv, 百拇医药
The breathing reserve index is the minute ventilation at the lactate threshold during incremental exercise divided by maximal voluntary ventilation. To determine whether this index would predict mortality in patients with cystic fibrosis on a waiting list for lung transplantation, Tantisira and coworkers (76) did exercise testing in 45 consecutive patients with cystic fibrosis as part of their pretransplant assessment. Fifteen patients died, 21 patients were transplanted, and 9 patients were still on the waiting list. In a multivariate model, relative risk of mortality was 17.52 for the breathing reserve index, 1.29 for resting PCO2, 0.97 for resting PO2, and 1.19 for FEV1. The authors conclude that the breathing reserve index provided the highest point estimate of mortality in patients with cystic fibrosis waiting for lung transplantation.v, 百拇医药
Deciding the right time to undertake lung transplantation in patients with cystic fibrosis is difficult, and the criteria used in guiding the decision are controversial. Mayer-Hamblett and coworkers (77) developed a mathematical model for predicting 2-year mortality using data on 14,572 patients in the National Patient Registry of the Cystic Fibrosis Foundation who were 6 years of age or older in 1996. Multivariate logistic regression revealed that age, height, FEV1, respiratory microbiology, number of hospitalizations for pulmonary exacerbations, and number of course of intravenous antibiotics in the home were significant predictors of 2-year mortality. When compared with the widely used criterion of an FEV1 of less than 30% of predicted, the mathematical model did not prove superior. The negative predictive value was 98% for the model and 97% for FEV1. The positive predictive value was 33% for the model and 28% for FEV1. Both the model and the FEV1 criterion will result in high rates of premature referral for lung transplantation. The authors conclude that a well-fitting mathematical model based on data from 14,572 patients with cystic fibrosis was not superior to the usual criterion of a FEV1 of less than 30% predicted in guiding decision on the best time to do lung transplantation. An editorial commentary by Noone and Egan (78) accompanies this article.
Obliterative Bronchiolitis#4-[50e, 百拇医药
Animal models.#4-[50e, 百拇医药
In a rat model of bronchiolitis obliterans, Liu and coworkers (79) studied the role of transforming growth factor-ß. The model consisted of heterotopic allogenic transplantation of the trachea (that is, transplantation of a trachea from a genetically dissimilar individual of same species into a location different from the usual location). Positive staining for the growth factor was evident in infiltrating mononuclear cells on the second and seventh day and in fibrous tissues on the twenty-first day. The fibrous obliteration of the airway was inhibited by transfection of the gene for soluble transforming growth factor-ß type III receptor, which functions as an antagonist for the growth factor, on the fifth day after transplantation. Delivery of an empty vector gene had no effect. The authors conclude that expression of transforming growth factor-ß in allografts plays a pivotal role in the pathogenesis of bronchiolitis obliterans.
Activation of T cells, which may be involved in causing obliterative bronchiolitis, relies in part on the interaction between CD28 and its ligands, B7–1 and B7–2. In untreated rats with tracheal allografts (grafts from genetically dissimilar individuals of same species), Tikkanen and coworkers (80) found that expression of B7–2, but not of B7–1, peaked on the tenth day after transplantation. Upregulation of B7–2 was not seen in syngeneic grafts (grafts from a genetically identical rat). Administration of cytotoxic T lymphocyte antigen 4 immunoglobulin, which selectively blocks the costimulatory pathway of CD28 and its ligand B7–1, had no effect on the epithelial injury or the airway occlusion in the tracheal allografts; nor did it affect cytokine expression. Administration of a fusion protein that blocks both the interactions between CD28 and B7–1 and between CD28 and B7–2 delayed the epithelial injury and airway occlusion; it also decreased production of tumor necrosis factor-, interleukin-2, and interferon- within the graft, and it increased production of interleukin-10. The authors conclude that interaction between CD28 and its ligand B7–2 plays a prominent role in the regulation of the proinflammatory and type 1 (Th1) helper T cell cytokine responses involved in the epithelial injury of experimental obliterative bronchiolitis.
To determine the role of growth factors in the pathogenesis of obliterative bronchiolitis in the mouse heterotopic trachea model, Aris and coworkers (81) implanted isografts and allografts in three sets of cyclosporine-treated mice. Compared with the isografts, the allografts had 1.5- to 5-fold increases in expression of transforming growth factor-ß, tumor necrosis factor-
, endothelin-1, and insulin-like growth factor-1 after two to six weeks. The allografts had increased expression of fibroblast growth factor isoforms 1 and 2, and platelet-derived growth factor-B at 4 weeks, which reversed at 6 and 10 weeks. The isografts expressed more epidermal growth factors than did the allografts. Treatment with a tumor necrosis factor-–soluble receptor produced a decrease in the epithelial injury and the luminal obstruction. The authors conclude that a large number of growth factors participate in obliterative bronchiolitis in mice, and that blockade of tumor necrosis factor- may ameliorate the lesion.Early detection.%|7#, 百拇医药
To assess the role of T cell responses in predicting the development of obliterative bronchiolitis, Duncan and coworkers (82) studied 12 patients who underwent lung transplantation. All six patients who developed obliterative bronchiolitis had abnormal expansion of circulating CD4+ T cells attributable to oligoclonal proliferations. Two of six recipients who did not develop rejection had a much lesser abnormality in CD4+ cells. Expansions of CD8+ cells were common in both groups. The authors conclude that expansion of CD4+ T cells had 100% sensitivity and 80% specificity in predicting the development of obliterative bronchiolitis.%|7#, 百拇医药
In a pulmonary perspective, Estenne and Hertz (83) discusses bronchiolitis obliterans after human lung transplantation.%|7#, 百拇医药
Rejection%|7#, 百拇医药
In 22 patients who had undergone bilateral lung or heart-lung transplantation, Morlion and coworkers (84) studied the reliability of Internet-based monitoring of lung function and its sensitivity in detecting infection or rejection of the allograft. The patients performed forced expiratory maneuvers into a mircrospirometer in their home, and the flow–volume loops were transmitted across the Internet to the hospital. Over a median of 473 days, 13,833 measurements were obtained. Patient compliance for one measurement a day was 84%, and compliance for two measurements a day was 55%. Agreement between home and hospital spirometry was within 4% for FEV1 and 6% for midexpiratory flow rate (FEF25–75). Coefficients of variation were 3.2% for FEV1 and 7.5% for FEF25–75. Home spirometry had a sensitivity of 63% for detecting acute graft dysfunction (diagnosed by biopsy or lavage). The authors conclude that transmission across the Internet of home spirometry in lung transplant recipients is accurate and reproducible, although it has only mild sensitivity (because a substantial number of acute complications do not alter pulmonary function).
Immunology and Biochemistry+#6%gd, 百拇医药
To characterize the usual profile of cells obtained by bronchoalveolar lavage in patients undergoing lung transplantation, Slebos and coworkers (85) analyzed 169 lavage samples from 63 patients free of airway complications after transplantation. The total cell counts decreased from 234 x 103 cells per ml shortly after transplantation to 103 x 103 cells per ml during the second year. The differential cell counts did not change. The ratio of CD4 to CD8 cell counts increased from 0.32 shortly after transplantation to 0.62 in the second year. The authors conclude that the pattern of cells obtained by bronchoalveolar lavage changes over the first two years after lung transplantation.+#6%gd, 百拇医药
PLEURAL DISORDERS+#6%gd, 百拇医药
TOP+#6%gd, 百拇医药
CONTENTS+#6%gd, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...+#6%gd, 百拇医药
AIR POLLUTION+#6%gd, 百拇医药
PULMONARY VASCULAR DISORDERS AND...
LUNG TRANSPLANTATION:, 百拇医药
PLEURAL DISORDERS:, 百拇医药
LUNG CANCER:, 百拇医药
REFERENCES:, 百拇医药
Physiology/Pathophysiology:, 百拇医药
To determine whether the helper T lymphocytes in malignant pleural effusions undergo a shift to type 2 (Th2) helper responses, Oshikawa and coworkers (86) studied pleural fluid and sera from 17 patients with malignant effusions, 8 patients with tuberculous effusions, and 5 patients with congestive heart failure. CD4+ T cells isolated from the pleural fluid of the patients with malignant pleural effusions produced more interleukin-4 and interleukin-10 and less interferon- and interleukin-12 than did cells obtained from the other two patient groups. The concentration of ST2, which is preferentially expressed on Th2 effector cells but not on Th1 cells, was higher in the patients with malignant effusions than in the other two groups. The concentration of ST2 was positively correlated with the percentage of CD4+ T cells (r = 0.43) and inversely correlated with the concentration of interferon- (r = -0.42) in pleural fluid. The expression of messenger RNA of ST2 in CD4+ T cells was upregulated in malignant effusions. The authors conclude that CD4+ T cells in malignant pleural effusions shift to a type 2 (Th2) profile and produce soluble ST2 gene products.
During the initial fibrinopurulent phase of a pleural loculation, fibrin bridges the visceral and parietal pleural surfaces. In rabbits with a pleural injury caused by tetracycline, Idell and coworkers (87) determined whether a single-chain urokinase plasminogen activator (alone or bound to its receptor) could prevent visceral-parietal adhesions. (This plasminogen activator enhances fibrinolytic activity and is relatively resistant to local inhibitors.) Urokinase bound to its receptor maintained fibrinolytic activity over 24 hours in the rabbits. When administered on its own into the pleura at 24 and 48 hours after intrapleural tetracycline, single-chain urokinase prevented the formation of adhesions. When bound to its receptor, administration of urokinase attenuated the formation of adhesions. At 72 hours after administration of tetracycline, antigenic, but not functional, evidence of the fibrinolytic agents persisted. The fibrinolytic agents did not cause local or systemic bleeding. The authors conclude that single-chain urokinase inhibits the formation of adhesions in rabbits with pleural injury caused by tetracycline. An editorial commentary by Antony (88) accompanies this article.
Clinical Manifestationsg, 百拇医药
In a consecutive case series of 389 patients, Light and coworkers (89) determined the prevalence of pleural effusions at about 28 days after cardiac surgery. Chest X-rays revealed pleural effusions in 63% of 312 patients who had undergone coronary artery bypass grafting alone, in 62% of 37 patients who had undergone both bypass grafting and valve surgery, and in 45% of 40 patients who had undergone value surgery alone. The prevalence of effusions occupying more than 25% of the hemithorax was 9.7%. The primary symptom associated with larger effusions was dyspnea; chest pain and fever were distinctly uncommon. The effusions usually resolved after one or two thoracenteses, and almost all effusions had resolved within one year of surgery. The authors conclude that about 10% of patients undergoing coronary artery surgery develop a pleural effusion that occupies more than 25% of a hemithorax.g, 百拇医药
Treatment
Because of controversy about the management of a first episode of a primary spontaneous pneumothorax, Noppen and coworkers (90) did a randomized prospective comparison of manual aspiration versus chest tube drainage in 60 patients. Immediate success was achieved in 59% of the patients treated by manual aspiration and in 64% of the patients treated by chest tube drainage. Success at one week was 93% in the manual aspiration group and 85% in the chest-tube group. Hospitalization was required in 52% of the manual aspiration group and in 100% of the chest-tube group. When evaluated after a minimum of one year, 26% of the manual aspiration group and 27% of the chest-tube group had experienced a recurrence. No complications were associated with manual aspiration. The authors conclude that manual aspiration is as effective as chest-tube drainage in managing a first episode of a primary spontaneous pneumothorax. An editorial commentary by Light (91) accompanies this article.1t/, http://www.100md.com
Pleurodesis
When used for pleurodesis, transforming growth factor-ß causes large transient pleural effusions. Lee and coworkers (92) investigated the role of vascular endothelial growth factor in causing the effusions. (Vascular endothelial growth factor is a cytokine that increases the permeability of microvessels and leads to formation of pleural effusions and ascites.) Injection of transforming growth factor-ß into the pleural cavity of rabbits caused a dose-dependent increase in vascular endothelial growth factor; the levels were higher than those achieved by talc or doxycycline. The volume of pleural fluid was correlated with the level of vascular endothelial growth factor (r = 0.79). In in vitro studies, transforming growth factor-ß, but not talc or doxycycline, induced a significant increase in vascular endothelial growth factor; the increase was decreased by an antibody to transforming growth factor-ß. The authors conclude that transforming growth factor-ß causes mesothelial cells to produce vascular endothelial growth factor, which is accompanied by proportional increases in pleural fluid.
LUNG CANCER;?jk, 百拇医药
TOP;?jk, 百拇医药
CONTENTS;?jk, 百拇医药
CHRONIC OBSTRUCTIVE PULMONARY...;?jk, 百拇医药
AIR POLLUTION;?jk, 百拇医药
PULMONARY VASCULAR DISORDERS AND...;?jk, 百拇医药
LUNG TRANSPLANTATION;?jk, 百拇医药
PLEURAL DISORDERS;?jk, 百拇医药
LUNG CANCER;?jk, 百拇医药
REFERENCES;?jk, 百拇医药
Diagnosis;?jk, 百拇医药
To determine the usefulness of screening for lung cancer with low-dose spiral computed tomography and sputum cytology, Swensen and coworkers (93) enrolled 1,520 individuals in a prospective cohort study. The subjects were aged 50 years or older and had a 20-pack-year smoking history. One year after baseline screening, 2,244 uncalcified lung nodules were identified in 1,000 participants (66%). Twenty-five cases of lung cancer were diagnosed: 23 cases by computed tomography and 2 cases by sputum cytology. Twenty-two patients underwent curative resection. Of the non–small cell cancers detected by computed tomography, the mean size was 17 mm and 12 (57%) were stage IA at diagnosis. Seven benign nodules were resected. The authors conclude that screening with computed tomography can detect lung cancers at an early stage. An editorial commentary by Heffner and Silvestri (94) accompanies this article.
Photodynamic therapy has curative potential for patients with early lung cancer that is centrally located. In 18 patients with biopsy-proven squamous cell carcinomas that had been considered appropriate candidates for photodynamic therapy on the basis of conventional bronchoscopy and high-resolution computed tomography, Miyazu and coworkers (95) evaluated the usefulness of endobronchial ultrasonography in making the selection. Endobronchial bronchoscopy revealed intracartilaginous lesions in nine patients, and photodynamic therapy has achieved complete remission (median follow-up, 32 months). Extracartilaginous lesions were found in the remaining nine patients, and they were treated by surgery, chemotherapy, or radiotherapy. The depth of tumor invasion estimated by endobronchial ultrasonography was comparable to the depth on histopathology in six patients undergoing surgical resection. The authors conclude that endobronchial ultrasonography is a useful technique in selecting patients with early, centrally located lung cancer for photodynamic therapy.
Transbronchial needle aspiration is an important method for bronchoscopic sampling of mediastinal adenopathy, but the optimal number of aspirates is not known. Chin and coworkers (96) studied 79 patients with known or suspected lung carcinoma and mediastinal adenopathy (57% of the cases were positive for malignancy). Among the patients in whom the procedure identified involvement of the mediastinal nodes, 42% had a cytologically positive sample on the first aspirate. All positive results were achieved with seven or fewer aspirates. A positive diagnosis was obtained in 71% of the cases handled with rapid on-site cytologic examination versus in 25% of the cases without on-site evaluation. The authors conclude that seven or fewer transbronchial needle aspirates achieve an optimal yield in patients with a suspected lung cancer and mediastinal adenopathy.34, http://www.100md.com
Studies of Molecular Mechanisms34, http://www.100md.com
Heat shock proteins derived from animals with cancers elicit protective immunity against autologous cancer. To determine whether heat shock protein-70 derived from human lung cancer is complexed with tumor-specific antigens, Michils and coworkers (97) collected peripheral blood monocytes from patients with lung cancer 10 days after surgery. When the monocytes were stimulated with heat shock protein-70 derived from autologous tumor, the stimulation index was 1.96 times higher in the patients with lung cancer than in the control subjects. Heat shock protein-70 derived from heterologous tumor or from autologous tumor-free lung tissue did not cause significant stimulation. Six patients were again studied at three months after surgery, and the stimulation index had decreased by 54%. Heat shock protein-70 derived from lung carcinoma was associated with T cell antigens, and the T cell reactivity was transient and restricted solely to antigens complexed to heat shock protein-70 derived from autologous tumors. The authors conclude that heat shock protein-70 derived from human lung carcinoma acts to chaperone antigens that are specific for the tumor from which the protein was purified and are responsible for a transient cellular immune response.
Review Article*:q}%[, http://www.100md.com
In a state of the art review article, Spiro and Porter (98) discuss current advances in staging and nonsurgical treatment of lung cancer.*:q}%[, http://www.100md.com
REFERENCES*:q}%[, http://www.100md.com
TOP*:q}%[, http://www.100md.com
CONTENTS*:q}%[, http://www.100md.com
CHRONIC OBSTRUCTIVE PULMONARY...*:q}%[, http://www.100md.com
AIR POLLUTION*:q}%[, http://www.100md.com
PULMONARY VASCULAR DISORDERS AND...*:q}%[, http://www.100md.com
LUNG TRANSPLANTATION*:q}%[, http://www.100md.com
PLEURAL DISORDERS*:q}%[, http://www.100md.com
LUNG CANCER*:q}%[, http://www.100md.com
REFERENCES*:q}%[, http://www.100md.com
He JQ, Ruan J, Connett JE, Anthonisen NR, Pare PD, Sandford AJ. Antioxidant gene polymorphisms and susceptibility to a rapid decline in lung function in smokers. Am J Respir Crit Care Med 2002;166:323–328.*:q}%[, http://www.100md.com
Vestbo J, Lange P. Can GOLD Stage 0 provide information of prognostic value in chronic obstructive pulmonary disease? Am J Respir Crit Care Med 2002;166:329–332.
Anthonisen NR, Connett JE, Murray RP. Smoking and lung function of Lung Health Study participants after 11 years. Am J Respir Crit Care Med 2002;166:675–679.q]zgc[m, http://www.100md.com
Domingo-Salvany A, Lamarca R, Ferrer M, Garcia-Aymerich J, Alonso J, Felez M, Khalaf A, Marrades RM, Monso E, Serra-Batlles J, et al. Health-related quality of life and mortality in male patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:680–685.q]zgc[m, http://www.100md.com
Rodriguez F, Jardi R, Costa X, Cotrina M, Galimany R, Vidal R, Miravitlles M. Rapid screening for
1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease using dried blood specimens. Am J Respir Crit Care Med 2002;166:814–817.q]zgc[m, http://www.100md.comTakubo Y, Guerassimov A, Ghezzo H, Triantafillopoulos A, Bates JH, Hoidal JR, Cosio MG.
1-Antitrypsin determines the pattern of emphysema and function in tobacco smoke-exposed mice: parallels with human disease. Am J Respir Crit Care Med 2002;166:1596–1603.Birring SS, Brightling CE, Bradding P, Entwisle JJ, Vara DD, Grigg J, Wardlaw AJ, Pavord ID. Clinical, radiologic, and induced sputum features of chronic obstructive pulmonary disease in nonsmokers: a descriptive study. Am J Respir Crit Care Med 2002;166:1078–1083.s7, http://www.100md.com
Abe Y, Murphy TF, Sethi S, Faden HS, Dmochowski J, Harabuchi Y, Thanavala YM. Lymphocyte proliferative response to P6 of Haemophilus influenzae is associated with relative protection from exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;165:967–971.s7, http://www.100md.com
Saetta M, Mariani M, Panina-Bordignon P, Turato G, Buonsanti C, Baraldo S, Bellettato CM, Papi A, Corbetta L, Zuin R, et al. Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;165:1404–1409.s7, http://www.100md.com
Turato G, Zuin R, Miniati M, Baraldo S, Rea F, Beghe B, Monti S, Formichi B, Boschetto P, Harari S, et al. Airway inflammation in severe chronic obstructive pulmonary disease: relationship with lung function and radiologic emphysema. Am J Respir Crit Care Med 2002;166:105–110.
Rahman I, van Schadewijk AA, Crowther AJ, Hiemstra PS, Stolk J, MacNee W, De Boer WI. 4-Hydroxy-2-nonenal, a specific lipid peroxidation product, is elevated in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:490–495.8y/5(, http://www.100md.com
Tomita K, Caramori G, Lim S, Ito K, Hanazawa T, Oates T, Chiselita I, Jazrawi E, Chung KF, Barnes PJ, et al. Increased p21(CIP1/WAF1) and B cell lymphoma leukemia-x(L) expression and reduced apoptosis in alveolar macrophages from smokers. Am J Respir Crit Care Med 2002;166:724–731.8y/5(, http://www.100md.com
Vignola AM. p21(CIP1/WAF1) and the immunologic fate of macrophages in smokers: at the crossroad between proliferation, survival, and death. Am J Respir Crit Care Med 2002;166:637–638.8y/5(, http://www.100md.com
Harju T, Kaarteenaho-Wiik R, Soini Y, Sormunen R, Kinnula VL. Diminished immunoreactivity of gamma-glutamylcysteine synthetase in the airways of smokers' lung. Am J Respir Crit Care Med 2002;166:754–759.8y/5(, http://www.100md.com
Hiemstra PS. The adaptive response of smokers to oxidative stress: moving from culture to tissue. Am J Respir Crit Care Med 2002;166:635–636.
Higashimoto Y, Elliott WM, Behzad AR, Sedgwick EG, Takei T, Hogg JC, Hayashi S. Inflammatory mediator mRNA expression by adenovirus E1A-transfected bronchial epithelial cells. Am J Respir Crit Care Med 2002;166:200–207.n85[kh&, http://www.100md.com
Churg A, Dai J, Tai H, Xie C, Wright JL. Tumor necrosis factor-
is central to acute cigarette smoke-induced inflammation and connective tissue breakdown. Am J Respir Crit Care Med 2002;166:849–854.n85[kh&, http://www.100md.comVernooy JH, Kucukaycan M, Jacobs JA, Chavannes NH, Buurman WA, Dentener MA, Wouters EF. Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med 2002;166:1218–1224.n85[kh&, http://www.100md.com
Brown JS, Zeman KL, Bennett WD. Ultrafine particle deposition and clearance in the healthy and obstructed lung. Am J Respir Crit Care Med 2002;166:1240–1247.n85[kh&, http://www.100md.com
Kastelik JA, Thompson RH, Aziz I, Ojoo JC, Redington AE, Morice AH. Sex-related differences in cough reflex sensitivity in patients with chronic cough. Am J Respir Crit Care Med 2002;166:961–964.
Scharf SM, Iqbal M, Keller C, Criner G, Lee S, Fessler HE. Hemodynamic characterization of patients with severe emphysema. Am J Respir Crit Care Med 2002;166:314–322.#;'d@$, 百拇医药
O'Donnell DE, D'Arsigny C, Fitzpatrick M, Webb KA. Exercise hypercapnia in advanced chronic obstructive pulmonary disease: the role of lung hyperinflation. Am J Respir Crit Care Med 2002;166:663–668.#;'d@$, 百拇医药
Dempsey JA. Exercise carbon dioxide retention in chronic obstructive pulmonary disease: a case for ventilation/perfusion mismatch combined with hyperinflation. Am J Respir Crit Care Med 2002;166:634–635.#;'d@$, 百拇医药
Ramirez-Sarmiento A, Orozco-Levi M, Guell R, Barreiro E, Hernandez N, Mota S, Sangenis M, Broquetas JM, Casan P, Gea J. Inspiratory muscle training in patients with chronic obstructive pulmonary disease: structural adaptation and physiologic outcomes. Am J Respir Crit Care Med 2002;166:1491–1497.#;'d@$, 百拇医药
Levine S, Nguyen T, Kaiser LR, Shrager JB. Evaluating respiratory muscle adaptations: a new approach. Am J Respir Crit Care Med 2002;166:1418–1419.#;'d@$, 百拇医药
Gorman RB, McKenzie DK, Pride NB, Tolman JF, Gandevia SC. Diaphragm length during tidal breathing in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:1461–1469.
Agusti AG, Sauleda J, Miralles C, Gomez C, Togores B, Sala E, Batle S, Busquets X. Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:485–489.t+9w.|!, http://www.100md.com
Lewis MI. Apoptosis as a potential mechanism of muscle cachexia in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:434–436.t+9w.|!, http://www.100md.com
Ortega F, Toral J, Cejudo P, Villagomez R, Sanchez H, Castillo J, Montemayor T. Comparison of effects of strength and endurance training in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:669–674.t+9w.|!, http://www.100md.com
Marquis K, Debigare R, Lacasse Y, LeBlanc P, Jobin J, Carrier G, Maltais F. Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:809–813.t+9w.|!, http://www.100md.com
Mador MJ. Muscle mass, not body weight, predicts outcome in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:787–789.t+9w.|!, http://www.100md.com
Anthonisen NR, Connett JE, Enright PL, Manfreda J. Hospitalizations and mortality in the Lung Health Study. Am J Respir Crit Care Med 2002;166:333–339.
Culpitt SV, De Matos C, Russell RE, Donnelly LE, Rogers DF, Barnes PJ. Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;165:1371–1376.mr9, http://www.100md.com
Rabe KF. On theophylline, leukocytes, and chicken soup. Am J Respir Crit Care Med 2002;165:1351–1352.mr9, http://www.100md.com
Maltais F, Ostinelli J, Bourbeau J, Tonnel AB, Jacquemet N, Haddon J, Rouleau M, Boukhana M, Martinot JB, Duroux P. Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Am J Respir Crit Care Med 2002;165:698–703.mr9, http://www.100md.com
Van Der Valk P, Monninkhof E, van der PJ, Zielhuis G, van Herwaarden C. Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE study. Am J Respir Crit Care Med 2002;166:1358–1363.mr9, http://www.100md.com
Hattotuwa KL, Gizycki MJ, Ansari TW, Jeffery PK, Barnes NC. The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study. Am J Respir Crit Care Med 2002;165:1592–1596.
Pauwels R. Inhaled glucocorticosteroids and chronic obstructive pulmonary disease: how full is the glass? Am J Respir Crit Care Med 2002;165:1579–1580.0]impg, 百拇医药
Mahler DA, Wire P, Horstman D, Chang CN, Yates J, Fischer T, Shah T. Effectiveness of fluticasone propionate and salmeterol combination delivered via the diskus device in the treatment of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;166:1084–1091.0]impg, 百拇医药
Walsh LJ, Lewis SA, Wong CA, Cooper S, Oborne J, Cawte SA, Harrison T, Green DJ, Pringle M, Hubbard R, et al. The impact of oral corticosteroid use on bone mineral density and vertebral fracture. Am J Respir Crit Care Med 2002;166:691–695.0]impg, 百拇医药
Hubbard RB, Smith CJ, Smeeth L, Harrison TW, Tattersfield AE. Inhaled corticosteroids and hip fracture: a population-based case-control study. Am J Respir Crit Care Med 2002;166:1563–1566.0]impg, 百拇医药
Mao JT, Goldin JG, Dermand J, Ibrahim G, Brown MS, Emerick A, McNitt-Gray MF, Gjertson DW, Estrada F, Tashkin DP, et al. A pilot study of all-trans-retinoic acid for the treatment of human emphysema. Am J Respir Crit Care Med 2002;165:718–723.
Kuraki T, Ishibashi M, Takayama M, Shiraishi M, Yoshida M. A novel oral neutrophil elastase inhibitor (ONO-6818) inhibits human neutrophil elastase-induced emphysema in rats. Am J Respir Crit Care Med 2002;166:496–500.zfh^ejz, 百拇医药
Wright JL, Farmer SG, Churg A. Synthetic serine elastase inhibitor reduces cigarette smoke-induced emphysema in guinea pigs. Am J Respir Crit Care Med 2002;166:954–960.zfh^ejz, 百拇医药
Fessler HE, Scharf SM, Permutt S. Improvement in spirometry following lung volume reduction surgery: application of a physiologic model. Am J Respir Crit Care Med 2002;165:34–40.zfh^ejz, 百拇医药
Mineo TC, Pompeo E, Rogliani P, Dauri M, Turani F, Bollero P, Magliocchetti N. Effect of lung volume reduction surgery for severe emphysema on right ventricular function. Am J Respir Crit Care Med 2002;165:489–494.zfh^ejz, 百拇医药
Stockley RA, Bayley DL, Unsal I, Dowson LJ. The effect of augmentation therapy on bronchial inflammation in 1-antitrypsin deficiency. Am J Respir Crit Care Med 2002;165:1494–1498.zfh^ejz, 百拇医药
Sin DD, Stafinski T, Ng YC, Bell NR, Jacobs P. The impact of chronic obstructive pulmonary disease on work loss in the United States. Am J Respir Crit Care Med 2002;165:704–707.
Croxton TL, Weinmann GG, Senior RM, Hoidal JR. Future research directions in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2002;165:838–844.c{s?, 百拇医药
Saldiva PH, Clarke RW, Coull BA, Stearns RC, Lawrence J, Murthy GG, Diaz E, Koutrakis P, Suh H, Tsuda A, et al. Lung inflammation induced by concentrated ambient air particles is related to particle composition. Am J Respir Crit Care Med 2002;165:1610–1617.c{s?, 百拇医药
Nemmar A, Hoylaerts MF, Hoet PH, Dinsdale D, Smith T, Xu H, Vermylen J, Nemery B. Ultrafine particles affect experimental thrombosis in an in vivo hamster model. Am J Respir Crit Care Med 2002;166:998–1004.c{s?, 百拇医药
Romieu I, Sienra-Monge JJ, Ramirez-Aguilar M, Tellez-Rojo MM, Moreno-Macias H, Reyes-Ruiz NI, Rio-Navarro BE, Ruiz-Navarro MX, Hatch G, Slade R, et al. Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. Am J Respir Crit Care Med 2002;166:703–709.c{s?, 百拇医药
Gauderman WJ, Gilliland GF, Vora H, Avol E, Stram D, McConnell R, Thomas D, Lurmann F, Margolis HG, Rappaport EB, et al. Association between air pollution and lung function growth in southern California children: results from a second cohort. Am J Respir Crit Care Med 2002;166:76–84.
Brauer M, Hoek G, Van Vliet P, Meliefste K, Fischer PH, Wijga A, Koopman LP, Neijens HJ, Gerritsen J, Kerkhof M, et al. Air pollution from traffic and the development of respiratory infections and asthmatic and allergic symptoms in children. Am J Respir Crit Care Med 2002;166:1092–1098.n, http://www.100md.com
Takano H, Yanagisawa R, Ichinose T, Sadakane K, Yoshino S, Yoshikawa T, Morita M. Diesel exhaust particles enhance lung injury related to bacterial endotoxin through expression of proinflammatory cytokines, chemokines, and intercellular adhesion molecule-1. Am J Respir Crit Care Med 2002;165:1329–1335.n, http://www.100md.com
Balabanian K, Foussat A, Dorfmuller P, Durand-Gasselin I, Capel F, Bouchet-Delbos L, Portier A, Marfaing-Koka A, Krzysiek R, Rimaniol AC, et al. CX(3)C chemokine fractalkine in pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:1419–1425.n, http://www.100md.com
Williams TJ. Stalking the chemokine. Am J Respir Crit Care Med 2002;165:1350–1351.n, http://www.100md.com
Davie N, Haleen SJ, Upton PD, Polak JM, Yacoub MH, Morrell NW, Wharton J. ET(A) and ET(B) receptors modulate the proliferation of human pulmonary artery smooth muscle cells. Am J Respir Crit Care Med 2002;165:398–405.
Dorfmuller P, Zarka V, Durand-Gasselin I, Monti G, Balabanian K, Garcia G, Capron F, Coulomb-Lhermine A, Marfaing-Koka A, Simonneau G, et al. Chemokine RANTES in severe pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:534–539.cpi$z, http://www.100md.com
Rabiller A, Nunes H, Lebrec D, Tazi KA, Wartski M, Dulmet E, Libert JM, Mougeot C, Moreau R, Mazmanian M, et al. Prevention of gram-negative translocation reduces the severity of hepatopulmonary syndrome. Am J Respir Crit Care Med 2002;166:514–517.cpi$z, http://www.100md.com
Reeves JT. High adventure in pulmonary hypertension: acute and chronic hypoxia are not the same. Am J Respir Crit Care Med 2002;166:1537–1538.cpi$z, http://www.100md.com
Castelain V, Chemla D, Humbert M, Sitbon O, Simonneau G, Lecarpentier Y, Herve P. Pulmonary artery pressure-flow relations after prostacyclin in primary pulmonary hypertension. Am J Respir Crit Care Med 2002;165:338–340.cpi$z, http://www.100md.com
Simonneau G, Barst RJ, Galie N, Naeije R, Rich S, Bourge RC, Keogh A, Oudiz R, Frost A, Blackburn SD, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2002;165:800–804.
Hoeper MM, Galie N, Murali S, Olschewski H, Rubenfire M, Robbins IM, Farber HW, McLaughlin V, Shapiro S, Pepke-Zaba J, et al. Outcome after cardiopulmonary resuscitation in patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:341–344.-^'fw{&, 百拇医药
Nishimura T, Faul JL, Berry GJ, Vaszar LT, Qiu D, Pearl RG, Kao PN. Simvastatin attenuates smooth muscle neointimal proliferation and pulmonary hypertension in rats. Am J Respir Crit Care Med 2002;166:1403–1408.-^'fw{&, 百拇医药
Rubin LJ. Therapy of pulmonary hypertension: the evolution from vasodilators to antiproliferative agents. Am J Respir Crit Care Med 2002;166:1308–1309.-^'fw{&, 百拇医药
Shekerdemian LS, Ravn HB, Penny DJ. Intravenous sildenafil lowers pulmonary vascular resistance in a model of neonatal pulmonary hypertension. Am J Respir Crit Care Med 2002;165:1098–1102.-^'fw{&, 百拇医药
Hoeper MM, Galie N, Simonneau G, Rubin LJ. New treatments for pulmonary arterial hypertension. Am J Respir Crit Care Med 2002;165:1209–1216.-^'fw{&, 百拇医药
De Monye W, Sanson BJ, Mac Gillavry MR, Pattynama PM, Buller HR, van den Berg-Huysmans AA, Huisman MV. Embolus location affects the sensitivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism. Am J Respir Crit Care Med 2002;165:345–348.
Aldashev AA, Sarybaev AS, Sydykov AS, Kalmyrzaev BB, Kim EV, Mamanova LB, Maripov R, Kojonazarov BK, Mirrakhimov MM, Wilkins MR, et al. Characterization of high-altitude pulmonary hypertension in the Kyrgyz: association with angiotensin-converting enzyme genotype. Am J Respir Crit Care Med 2002;166:1396–1402.|\, 百拇医药
Woods DR, Pollard AJ, Collier DJ, Jamshidi Y, Vassiliou V, Hawe E, Humphries SE, Montgomery HE. Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene and arterial oxygen saturation at high altitude. Am J Respir Crit Care Med 2002;166:362–366.|\, 百拇医药
Callahan LA, Woods KF, Mensah GA, Ramsey LT, Barbeau P, Gutin B. Cardiopulmonary responses to exercise in women with sickle cell anemia. Am J Respir Crit Care Med 2002;165:1309–1316.|\, 百拇医药
De Perrot M, Sekine Y, Fischer S, Waddell TK, McRae K, Liu M, Wigle DA, Keshavjee S. Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation. Am J Respir Crit Care Med 2002;165:211–215.|\, 百拇医药
Nowak K, Kamler M, Bock M, Motsch J, Hagl S, Jakob H, Gebhard MM. Bronchial artery revascularization affects graft recovery after lung transplantation. Am J Respir Crit Care Med 2002;165:216–220.
Fukuse T, Hirata T, Omasa M, Wada H. Effect of adenosine triphosphate-sensitive potassium channel openers on lung preservation. Am J Respir Crit Care Med 2002;165:1511–1515.6.v&&%-, http://www.100md.com
Tantisira KG, Systrom DM, Ginns LC. An elevated breathing reserve index at the lactate threshold is a predictor of mortality in patients with cystic fibrosis awaiting lung transplantation. Am J Respir Crit Care Med 2002;165:1629–1633.6.v&&%-, http://www.100md.com
Mayer-Hamblett N, Rosenfeld M, Emerson J, Goss CH, Aitken ML. Developing cystic fibrosis lung transplant referral criteria using predictors of 2-year mortality. Am J Respir Crit Care Med 2002;166:1550–1555.6.v&&%-, http://www.100md.com
Noone PG, Egan TM. Cystic fibrosis: when to refer for lung transplantation-is the answer clear? Am J Respir Crit Care Med 2002;166:1531–1532.6.v&&%-, http://www.100md.com
Liu M, Suga M, Maclean AA, St George JA, Souza DW, Keshavjee S. Soluble transforming growth factor-beta type III receptor gene transfection inhibits fibrous airway obliteration in a rat model of Bronchiolitis obliterans. Am J Respir Crit Care Med 2002;165:419–423.6.v&&%-, http://www.100md.com
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Aris RM, Walsh S, Chalermskulrat W, Hathwar V, Neuringer IP. Growth factor upregulation during obliterative bronchiolitis in the mouse model. Am J Respir Crit Care Med 2002;166:417–422.4jj@, 百拇医药
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