Tuberculosis, Lung Infections, Interstitial Lung Disease, and Journalology in AJRCCM 2002

http://www.100md.com 《美国呼吸和危急护理医学》2003年第3期

     Division of Pulmonary and Critical Care Medicine, Loyola University of Chicago Stritch School of Medicine and Hines Veterans Affairs Hospital, Hines, Illinoisg$si, 百拇医药

    CONTENTSg$si, 百拇医药

    Tuberculosis (20)g$si, 百拇医药

    Studies of Molecular Mechanisms in Tuberculosis (7)g$si, 百拇医药

    Epidemiology of Tuberculosis (7)g$si, 百拇医药

    Diagnosis of Tuberculosis (1)g$si, 百拇医药

    Treatment of Tuberculosis (5)g$si, 百拇医药

    Nontuberculous Lung Infection (12)g$si, 百拇医药

    Human Immunodeficiency Virus Infection (2)g$si, 百拇医药

    Highly Active Antiretroviral Therapy (2)g$si, 百拇医药

    Lung Infections (10)g$si, 百拇医药

    Host Defenses (5)g$si, 百拇医药

    Pneumonia (3)g$si, 百拇医药

    Antimicrobial Therapy (2)g$si, 百拇医药

    Interstitial Lung Disease (39)g$si, 百拇医药

    Idiopathic Pulmonary Fibrosis (14)g$si, 百拇医药

    Genetics (2)

    Histopathological Subtypes (1)pa., 百拇医药

    Serum Markers (1)pa., 百拇医药

    Clinical Assessment (2)pa., 百拇医药

    Cellular and Molecular Mechanisms, in vivo (3)pa., 百拇医药

    Cellular and Molecular Mechanisms, ex vivo (1)pa., 百拇医药

    Animal Models (1)pa., 百拇医药

    Treatment (1)pa., 百拇医药

    Statements and Workshops (2)pa., 百拇医药

    Progressive Systemic Sclerosis (3)pa., 百拇医药

    Sarcoidosis (3)pa., 百拇医药

    Genetics (2)pa., 百拇医药

    Molecular Mechanisms (1)pa., 百拇医药

    Histiocytosis X (2)pa., 百拇医药

    Lymphangioleiomyomatosis (2)pa., 百拇医药

    Eosinophilic Pneumonia (3)pa., 百拇医药

    Acute Interstitial Pneumonitis (2)pa., 百拇医药

    Niemann-Pick Disease (1)pa., 百拇医药

    Lymphoproliferative Disorders (1)pa., 百拇医药

    Idiopathic Pulmonary Alveolar Proteinosis (1)

    Pulmonary Drug Toxicity (2)n, http://www.100md.com

    Calcium Deposition in the Lung (1)n, http://www.100md.com

    Rodent Model of Bleomycin Fibrosis (4)n, http://www.100md.com

    Occupational Lung Disease (12)n, http://www.100md.com

    Social Issues, Health Policy, Economics, and Journalology (6)n, http://www.100md.com

    Journalology (6)n, http://www.100md.com

    TUBERCULOSISn, http://www.100md.com

    Studies of Molecular Mechanisms in Tuberculosisn, http://www.100md.com

    Dendritic cells are the most potent antigen-presenting cells, and they play a central role in initiating the primary immune response. To study their role in granulomatous inflammation, Tsuchiya and coworkers (1) studied pulmonary granulomas elicited by Bacillus Calmette-Guerin (BCG) in rats. At the borders of the pulmonary granulomas, numerous large, pleiomorphic cells stained positive for OX62, an antibody specific for dendritic cells. Ultrastructural morphology was characteristic of dendritic cells. The cells showed intense surface expression of major histocompatibility complex class II, B7–1 and B7–2, and the absence of T cell markers and monocyte/macrophage-specific markers. The cells produced potent stimulation of allogenic T cells and syngeneic T cells specific for purified protein derivative in the absence of exogenous peptides. The authors conclude that dendritic cells participate in the formation of pulmonary granulomas elicited by BCG in rats, suggesting that dendritic cells play a pivotal role in T cell–mediated granulomatous immune responses. An editorial commentary by Dreher and Nicod (2) accompanies this article.

    Although nitric oxide may contribute to host defense against tuberculosis, its expression in human tuberculous lungs has not been systematically characterized. In surgically resected lungs of eight patients with tuberculosis, Choi and coworkers (3) found increased levels of inducible nitric oxide synthase, endothelial nitric oxide synthase, and nitrotyrosine (a marker of nitric oxide expression) in the inflammatory zone of tuberculous granulomas and in the nongranulomatous pneumonitis zone; the level of neuronal nitric oxide synthase was not elevated. Tumor necrosis factor-{alpha}9, 百拇医药

    was increased and principally localized to the necrotic areas of granulomas, and localized to a lesser degree in the inflammatory and fibrotic areas. The nitric oxide isoforms and tumor necrosis factor-{alpha}9, 百拇医药

    were expressed by the epithelioid macrophages and giant cells within the granulomas and in alveolar macrophages and epithelial cells in areas of pneumonitis. The authors conclude that nitric oxide and isoenzymes of nitric oxide synthase are present in specialized areas of tuberculous granulomas. An editorial commentary by Nathan (4) accompanies this article.

    Because CD8⁺ T cells play an important role in host defense against Mycobacterium tuberculosis, it is thought that a successful tuberculosis vaccine will need to elicit sustained responses of CD8⁺ T cells. To determine whether a potent CD4⁺ T cell antigen, Mtb39, is also a CD8⁺ T cell antigen, Lewinsohn and coworkers (5) used a replication-deficient adenovirus to introduce Mtb39 into the cytoplasm of dendritic cells derived from human monocytes. Mtb39-specific CD8⁺ T lymphocytes were detected in three healthy individuals with latent tuberculosis infection who also displayed strong responses against Mtb39-specific CD4⁺ T cells. A Mtb39-specific CD8⁺ T cell line was generated using Mtb39-expressing dendritic cells. All seven of the generated T cell clones were HLA-B44 restricted, recognized dendritic cells with Mtb, and were cytolytic. The authors conclude that infection of dendritic cells with adenoviral vectors expressing Mtb proteins allows for the measurement of antigen-specific CD8⁺ T cell responses from peripheral blood monocytes. An editorial commentary by Lalvani (6) accompanies this article.

    In a pulmonary perspective, Lazarevic and Flynn (7) discuss CD8⁺ T cells in tuberculosis.0'9du.{, http://www.100md.com

    Epidemiology of Tuberculosis0'9du.{, http://www.100md.com

    Nitta and coworkers (8) studied the extent of transmission of multidrug-resistant tuberculosis in Los Angeles County. Of 102 multidrug-resistant cases, 71 had cavitary lesions on chest radiography, 94 had acid-fast bacilli in their sputa, and 15 were infected with HIV. Four molecular clusters of two cases each and one closely related pair were identified among the 102 cases; contact investigation identified all clusters but one. Among 946 contacts cross-matched with the Tuberculosis Registry of the County, one secondary case caused by drug-resistant Mycobacterium bovis was found. The authors conclude that a very high proportion of pulmonary multidrug-resistant cases of tuberculosis in Los Angeles County are infectious, and molecular strain-typing indicates limited spread of disease. An editorial commentary by Daley (9) accompanies this article.

    To determine the occurrence and consequences of a delay in the diagnosis of active pulmonary tuberculosis among hospitalized patients, Greenaway and coworkers (10) studied 429 patients admitted to17 hospitals in Canada with a new diagnosis of active tuberculosis. Initiation of appropriate therapy was delayed one week or more in 127 patients (30%). After adjusting for atypical characteristics, a delay in starting therapy was associated with the following: admission to a hospital that has a low rate of admissions for tuberculosis (0.2 to 3.3 per 10,000 admissions), odds ratio, 7.4; admission to a hospital that has an intermediate rate of admissions for tuberculosis (3.4 to 9.9 per 10,000 admissions), odds ratio, 2.3; potentially preventable (late) admission to an intensive care unit, odds ratio, 16.8; and death, odds ratio, 3.3. After adjusting for characteristics of workers and ventilation in patient rooms, tuberculin conversions were higher in hospitals that had an overall tuberculosis mortality above 10% (odds ratio, 2.5). The authors conclude that a patient admitted to hospital because of active tuberculosis is more likely to have a poor outcome when the patient is admitted to a hospital that has a low rate of admissions for tuberculosis. An editorial commentary by Sepkowitz (11) accompanies this article.

    Investigation of the contacts of active cases of tuberculosis is important in the control of tuberculosis. Based on a model of the variables that are most likely to predict a positive tuberculin skin test among contacts of tuberculosis cases, Gerald and coworkers (12) developed a decision tree for contact investigation. Several decision trees were developed based on data collected in 292 consecutive cases and their 2,941 contacts. The decision trees were then tested with prospective data collected in 366 new cases of tuberculosis and their 3,162 contacts. The decision trees had sensitivities of 87 to 94%, specificities of 22 to 28%, and false-negative rates of 7 to 10%. The use of a decision tree was estimated to decrease the number of contacts investigated by 17 to 25%. The authors conclude that the use of a decision tree in the investigation of contacts of cases of active tuberculosis would substantially reduce the number of contacts investigated and save resources. An editorial commentary by Weis (13) accompanies this article.

    To determine the transmission dynamics of tuberculosis in Tarrant County, Texas, Weis and coworkers (14) did a prospective epidemiological study of 159 patients with culture-proven tuberculosis. Patients whose isolates had identical or closely linked patterns on restriction fragment length polymorphism (RFLP) analysis were considered a cluster. Of the 159 patients, 76 (48%) were in 19 clusters, suggesting that recent transmission accounted for 36% of tuberculosis morbidity. Independent predictors for clustering were birth in the United States, continuous residence in Tarrant County, a history of homelessness, and a history of visiting or working in bars. Four homeless shelters and five bars were associated with specific clusters. Patients in some clusters recognized more photographs of patients in their cluster than did patients outside their cluster. The authors conclude that homeless shelters and bars are important sites of tuberculosis transmission and that recognizing individuals by photograph combined with molecular fingerprinting help identify epidemiologic links among patients.

    Diagnosis of Tuberculosisz$, 百拇医药

    The number of bacilli found by acid-fast staining in tissue sections can be much fewer than the number expected based on sputum smear data or the patient's clinical condition. Fukunaga and coworkers (15) determined whether use of fixative fluid, organic solvent, or both might contribute to the low numbers. When mycobacteria were smeared on glass slides and examined microscopically, formalin caused a decrease in the sensitivity of acid-fast staining to 0.5% and xylene caused a decrease in the sensitivity to 0.2%. In tissue sections from 30 patients with tuberculosis lesions, M. tuberculosis DNA was detected in 83% of the cases by the real-time polymerase chain reaction and in only 40% of the cases by acid-fast microscopy. The number of bacilli revealed by microscopy was much lower than the number revealed by the polymerase chain reaction technique. The authors conclude that acid-fast microscopy of formalin-fixed and paraffin-embedded tissue causes tuberculosis bacilli to be frequently missed or underestimated.

    Treatment of Tuberculosisk, http://www.100md.com

    In 346 patients from northern India being treated for tuberculosis, Sharma and coworkers (16) determined the role of risk factors, including the major histocompatibility complex (MHC) class II alleles, in the development of hepatotoxicity. Drug-induced hepatotoxicity occurred in 56 patients (16%). Patients with a high alcohol intake had threefold higher odds of developing hepatotoxicity. Multivariate logistic regression analysis revealed the following independent risk factors: older age (odds ratio, 1.2), moderate or far advanced disease (odds ratio, 2.0), serum albumin of less than 3.5 g per dl (odds ratio, 2.3), absence of HLA-DQA1*0102 (odds ratio, 4.0), and the presence of HLA-DQB1*0201 (odds ratio, 1.9). The authors conclude that advancing age, moderate or far advanced disease, hypoalbuminemia, and the presence or absence of specific HLA-DQ alleles are associated with the development of hepatotoxicity during treatment with antituberculosis drugs. An editorial commentary by Bothamley (17) accompanies this article.

    Once-weekly administration of rifapentine (a derivative of rifamycin) 600 mg in combination with isoniazid results in a higher relapse rate than does administration of rifampin plus isoniazid twice a week. To determine the safety and tolerability of higher doses of rifapentine, Bock and coworkers (18) did a randomized double-blind trial of rifapentine at three doses (600, 900, and 1,200 mg) plus isoniazid (15 mg per kg) once weekly in 150 patients with culture-positive tuberculosis (HIV seronegative). Treatment was discontinued in 6% of the 600-mg group, 4% of the 900-mg group, and 6% of the 1,200-mg group. Only one discontinuation, in the 1,200-mg arm, was attributed to therapy. The authors conclude that rifapentine 900 mg given once a week is safe, well tolerated, and is being evaluated in Phase III trials, whereas rifapentine 1,200 mg requires further evaluation.y[v!, 百拇医药

    Studies of the early bactericidal activity of antituberculosis drugs have historically focused on the log fall in the viable count in sputum over the first 48 hours of therapy. Gillespie and coworkers (19) present a mathematical model that suggests that the viable count in sputum follows an exponential decay curve with the equation: V = S + Me^-kt, where V is the viable count, M is the population of bacteria susceptible to the test drug, S is the population susceptible only to sterilizing agents, t is the day of sputum collection as related to the start of therapy, k is the rate constant for the bacteria killed each day, and e is the Napierian constant. Data from clinical trials were shown to fit the model. Based on the model, the authors propose that further studies of early bactericidal activity be performed by measuring daily quantitative counts for at least 5 days, and that the bactericidal activity of antituberculosis drugs should be based on the time to reduce the viable count to 50%. An editorial commentary by O'Brien (20) accompanies this article.

    NONTUBERCULOUS LUNG INFECTIONzl4, 百拇医药

    Human Immunodeficiency Virus Infectionzl4, 百拇医药

    Highly active antiretroviral therapy.zl4, 百拇医药

    To determine whether the introduction of highly active antiretroviral therapy has altered the epidemiology and outcomes of intensive care among HIV-infected patients, Morris and coworkers (21) analyzed data on all HIV-infected patients admitted to their intensive care units between 1996 and 1999. An average of 89 patients were admitted each year, and survival to hospital discharge was 71%. On univariate analysis, improved survival was associated with previous highly active antiretroviral therapy (odds ratio, 1.8), a non-AIDS indication for admission (odds ratio, 3.7), a lower APACHE (acute physiology and chronic health evaluation) score (odds ratio, 5.4), and higher serum albumin (odds ratio, 4.4). Decreased survival was associated with Pneumocystis carinii pneumonia (odds ratio, 0.24), mechanical ventilation (odds ratio, 0.19), and pneumothorax (odds ratio, 0.08). On mutivariate analysis, all variables except the prior use of highly active antiretroviral therapy and pneumothorax were significant independent predictors of outcome. The authors conclude that the improved survival in HIV-infected patients admitted to an intensive care unit since the introduction of highly active antiretroviral therapy has been achieved through an increased likelihood of admission for diagnoses not associated with AIDS and improvement in variables such as serum albumin. An editorial commentary by Masur (22) accompanies this article.

    Lung Infectionsx, http://www.100md.com

    Host defenses.x, http://www.100md.com

    Neutrophils play a critical role in the defense against infection with Aspergillus. A subset of the CXC chemokine family, ELR+ CXC chemokines, are potent chemoattractants for neutrophils. Mehrad and coworkers (23) determined whether mice that overexpressed the ELR+ CXC chemokine, KC, would have a better outcome when exposed to invasive aspergillosis than do wild-type mice. A transgenic line of mice were developed that overexpressed KC solely in the lungs, and it was possible to tightly regulate expression by exposure to analogs of tetracycline. Compared with wild-type mice, the transgenic mice had greater induction of KC in the lung, an earlier and higher peak of neutrophil influx to the lungs, a 74% decrease in fungal burden, and a threefold greater survival. Compared with wild-type mice, the transgenic mice also had 1.8 times more monocytes-macrophages in the lungs, and greater expression of interferon-{gamma}

    and interleukin-12 in response to infection. The authors conclude that overexpression of the ELR+ CXC chemokine, KC (a potent neutrophil chemoattractant), in the lungs causes improved host defense and survival in mice with invasive aspergillosis. An editorial commentary by Huffnagle (24) accompanies this article.l\, http://www.100md.com

    Gram-positive inflammation is presumed to result from components of the bacterial cell wall, such as lipoteichoic acid and peptidoglycan. To study the effect of these components of the wall of Staphylococcus aureus and the modulating influence of interleukin-6, Leemans and coworkers (25) administered the cell-wall components to two groups of mice. In wild-type mice, lipoteichoic acid and peptidoglycan induced acute pulmonary inflammation in a dose-dependent manner, characterized by neutrophilic influx and production of interleukin-6 in bronchoalveolar fluid. Compared with wild-type mice, instillation of 10 µg of lipoteichoic acid caused increases in neutrophil influx, tumor necrosis factor-{alpha}

    , macrophage inflammatory protein-1{alpha}+(a!, http://www.100md.com

    , and cytokine-induced neutrophil chemoattractant in mice deficient in the gene for interleukin-6. Instillation of 100 µg of lipoteichnoic acid, however, tended to attenuate cytokine and chemokine release in the interleukin-6–deficient mice. Compared with wild-type mice, instillation of peptidoglycan induced less neutrophil influx into the lungs of the interleukin-6–deficient mice. The authors conclude that interleukin-6 plays an anti-inflammatory role in the acute inflammation caused by lipoteichoic acid and a proinflammatory role in the inflammation caused by peptidoglycan.+(a!, http://www.100md.com

    The migration of neutrophils into airspaces in response to Streptococcus pneumoniae is primarily independent of CD18, whereas only 20 to 30% of neutrophil migration in response to Escherichia coli is independent of CD18. Tasaka and coworkers (26) studied the role of very late antigen-4 on neutrophil migration during acute bacterial pneumonia in mice. In wild-type mice, expression of very late antigen-4 on the neutrophils that emigrated into airspaces was less than on circulating neutrophils. Messenger RNA for vascular cell adhesion molecule-1, the major endothelial ligand for very late antigen-4, was increased more during E. coli pneumonia than during S. pneumoniae pneumonia. The adhesion molecule was not detected in the capillaries, the major site of neutrophil emigration. Mice given antibodies to both CD18 and to very late antigen-4 displayed a similar level of neutrophil emigration, as did mice receiving an antibody to CD18 alone. In hematopoietically reconstituted mice that had both wild-type and CD18-deficient neutrophils in their blood, the migration of CD18-deficient neutrophils in response to S. pneumoniae was less in animals pretreated with an antibody to very late antigen-4 than in animals receiving a control antibody. The authors conclude that most but not all of the CD18-independent emigration of neutrophils induced by bacteria in the lungs is mediated through mechanisms that do not involve very late antigen-4.

    Application of exogenous CC chemokine ligand 2 (JE, monocyte chemotactic protein-1) induces monocyte accumulation in airspaces, and the combination of CC chemokine ligand 2 and endotoxin (E. coli) provokes enhanced monocyte accumulation, extensive neutrophil influx, and loss of the pulmonary endothelial–epithelial barrier. Maus and coworkers (27) studied the role of the CC chemokine receptor 2 (the receptor for CC chemokine ligand 2) in alveolar leukocyte traffic. The accumulation of monocytes in response to alveolar CC chemokine ligand 2 (alone or in combination with endotoxin) was almost completely inhibited in knockout mice with disruption of the gene for CC chemokine receptor 2 and in wild-type mice treated with MC21 (a monoclonal antibody that blocks CC chemokine receptor 2). Both approaches of interfering with CC chemokine receptor 2 also markedly decreased the accumulation of alveolar neutrophils when the mice were challenged with the combination of CC chemokine ligand 2 and endotoxin. In wild-type mice, administration of an anti–Gr-1 monoclonal antibody (which selectively depletes neutrophils) or antileukinate (an inhibitor of the CXC receptor) markedly decreased the accumulation of alveolar monocyte when the mice were challenged with the combination of CC chemokine ligand 2 and endotoxin. Treating wild-type mice with MC21 (an inhibitor of CC chemokine receptor 2) or with anti–Gr-1 (a selective depletor of neutrophils) prevented the vascular leakage that normally occurs with the combination of CC chemokine receptor 2 and endotoxin. The authors conclude that CC chemokine receptor 2 plays a central role in the recruitment of alveolar monocytes in response to CC chemokine ligand 2, alone or in combination with endotoxin, and that the interdependence of monocytes and neutrophils contribute to vascular permeability.

    Pneumonia.]@06g3%, 百拇医药

    In 52 patients (aged 70 years and older) admitted from a nursing home to the ICU with presumed pneumonia, El-Solh and coworkers (28) determined the causes of failure to respond to antibiotic therapy. All patients had failed to respond to 72 hours of antibiotic therapy before admission and required mechanical ventilation. Microbial investigations (including blood culture, serology, pleural fluid, and bronchoalveolar specimens) revealed a diagnosis in 24 (46%) patients. The most common isolates were methicillin-resistant Staphylococcus aureus (33%), enteric gram-negative bacilli (24%), and Pseudomonas aeruginosa (14%). In 20 cases of definite pneumonia, invasive bronchial sampling directed a change in antibiotics in 8 patients (40%) and discontinuation of antibiotics in 2 patients (10%). The overall hospital mortality was 42%. Mortality did not differ between patients with verified and nonverified pneumonia, or between patients who did or did not have their antibiotics changed on the basis of bronchial sampling. The authors conclude that patients admitted to an ICU from a nursing home because of suspected pneumonia and who have failed prior antibiotics should receive antimicrobial therapy directed at nosocomial pathogens.

    Kaplan and coworkers (29) did an observational cohort study to better define the incidence, patterns of care, and outcome among elderly patients admitted to hospital with community-acquired pneumonia. The study sample consisted of all Medicare recipients 65 years or older admitted to hospital with a diagnostic code for community-acquired pneumonia. Among 623,718 hospital admissions (18.3 per 1,000 of that population), 10.6% died. Between 65–69 years to older than 90 years, the incidence of community-acquired pneumonia rose fivefold, and the mortality doubled. Mortality was higher in men (odds ratio, 1.21). Mean length of stay in hospital was 7.6 days, and costs per admission were $6,949. Among the 22.4% of patients admitted to an ICU, length of stay was 11.3 days and costs were $14,294. Among the 7.2% of patients requiring mechanical ventilation, length of stay was 15.7 days and costs were $23,961. Overall hospital costs were $4.4 billion, and $2.1 billion was incurred by cases managed in intensive care units. The authors conclude that community-acquired pneumonia is common and frequently fatal in elderly subjects, and that it frequently necessitates admission to the ICU and results in considerable expenditure.

    To compare features of community-acquired pneumonia in patients admitted to an ICU or managed outside of the ICU, Angus and coworkers (30) studied a prospective cohort of patients. Compared with 1,169 patients who were not admitted to the ICU, 170 patients requiring ICU admission were more likely to be admitted from home and to have comorbid conditions. Reasons for admission to the ICU were: respiratory failure (57%) hemodynamic monitoring (32%), and shock (16%). Compared with patients who were not admitted to the ICU, the patients requiring ICU admission had longer hospital stays (23 versus 9 days), higher hospital costs ($21,144 versus $5,785), more nonpulmonary organ dysfunction, and higher hospital mortality (18 versus 5%). Among four sets of criteria for severe pneumonia, the revised criteria of the American Thoracic Society were the best discriminator for ICU admission (areas under a receiver operating characteristic curve, 0.68), although discrimination was still relatively weak. The authors conclude that many patients with community-acquired pneumonia are admitted to the ICU and that available criteria are not robust in guiding clinical care.

    Antimicrobial therapy.^+, http://www.100md.com

    To make better informed decisions about the dosage of antibiotic therapy, Herkner and coworkers (31) developed an approach to measure drug levels in human lung tissue. Flexible microdialysis catheters were inserted to sample lung interstitial fluid in five patients undergoing lung surgery for tumors. A single dose of cefpirome was given intravenously. Over the first 4 hours, the concentration of cefpirome in lung interstitial fluid was 66% of the corresponding plasma value, and it exceeded the minimal inhibitory concentrations of most relevant bacteria. Patients tolerated the catheters and adverse events were not seen. The authors conclude that closed chest microdialysis is a feasible and safe technique for measuring antibiotic concentration in human lung tissue.^+, http://www.100md.com

    Macrolide antibiotics inhibit the production of intercellular adhesion molecule-1, which plays a vital role in the accumulation of immune effector cells at sites of local inflammation, and is also known as a receptor for a major subgroup of rhinoviruses, RV14. To study the effects of erythromycin on rhinovirus infection, Suzuki and coworkers (32) infected cultures of human tracheal epithelial cells with the major rhinovirus subgroup, RV14, and the minor subgroup, RV2. Infection with RV14 caused upregulation of the expression of messenger RNA and protein of intercellular adhesion molecule-1, and increased production of cytokines. Erythromycin caused decreases in the titers of RV14 in the supernatant, messenger RNA for RV14, susceptibility to infection with RV14, and production of intercellular adhesion molecule-1 and cytokines. Erythromycin decreased the activation of nuclear factor-{kappa}

    B by RV14, and the number of acidic endosomes in the epithelial cells. Erythromycin also reduced the titers of RV2 in supernatant, messenger RNA for RV2, susceptibility to infection with RV2 and cytokine production, although the effects on the receptor were small. The authors conclude that erythromycin inhibits infection caused by the major rhinovirus subgroup through reducing intercellular adhesion molecule-1 and blocking the entry of rhinovirus RNA into endosomes..oo'5, http://www.100md.com

    INTERSTITIAL LUNG DISEASE.oo'5, http://www.100md.com

    Idiopathic Pulmonary Fibrosis.oo'5, http://www.100md.com

    Genetics..oo'5, http://www.100md.com

    Mutations in the gene for surfactant protein-C (SFTPC) are associated with familial interstitial pneumonitis. In a kindred of 97 members that included 11 adults and 3 children with pulmonary fibrosis, Thomas and coworkers (33) used a candidate gene approach. A heterozygous exon 5 + 128 T"->".oo'5, http://www.100md.com

    A transversion of the gene for surfactant protein-C was found (the abnormality may hinder processing of the precursor protein for surfactant protein-C). Immunostaining of lung tissue revealed aberrant subcellular localization of the precursor protein. Electron microscopy revealed atypical alveolar type II cells, with numerous abnormal lamellar bodies. The authors conclude that a large kindred of familial pulmonary fibrosis displayed a mutation in the gene for surfactant protein-C and that damage to type II cells may underlie the pulmonary fibrosis associated with this mutation. An editorial commentary by Whitsett (34) accompanies this article.

    Histopathological subtypes.:j, 百拇医药

    Nicholson and coworkers (35) studied 53 patients with idiopathic pulmonary fibrosis to determine whether four individual histological features can predict prognosis. The four histological features were: fibroblastic foci, interstitial mononuclear cell infiltrate, established fibrosis, and intra-alveolar macrophages. Interobserver agreement between pathologists was moderate to good ({kappa}:j, 百拇医药

    , 0.56 to 0.76). Mortality was independently associated with a high score for fibroblastic foci and a low diffusing capacity (as percent predicted). On univariate analysis, increasing interstitial mononuclear cell infiltrate or fibroblastic foci had the strongest correlations with the declines in FVC or diffusing capacity at 6 months. On multivariate analysis, increase in fibroblastic foci was associated with greater decline in FVC and diffusing capacity at both 6 and 12 months, and increase in a score for mononuclear cell infiltrate was linked to functional decline at 6 months. The authors conclude that the described method of histological analysis is reproducible and provides a means of predicting progression of disease in patients with idiopathic pulmonary fibrosis.

    Serum markers.;)6+e, 百拇医药

    To determine the relative accuracy of serum markers for interstitial lung disease, Ohnishi and coworkers (36) studied 21 patients with idiopathic pulmonary fibrosis, 12 patients with collagen vascular disease, and 82 control subjects. Receiver operating characteristic curves revealed that KL-6 provided the best discrimination. A KL-6 value of 465 U per ml had a sensitivity of 94% and a specificity of 96%. A surfactant protein-A level of 48.2 ng per ml had a sensitivity of 82% and a specificity of 87%. A surfactant protein-D level of 116 ng per ml had a sensitivity of 70% and a specificity of 95%. A monocyte chemoattractant protein-1 level of 1,080 pg per ml had a sensitivity of 52% and a specificity of 93%. The authors conclude that the glycoprotein KL-6 is the most discriminating serum marker for diagnosing interstitial lung disease.;)6+e, 百拇医药

    Clinical assessment.;)6+e, 百拇医药

    To define the clinical course and outcome of patients with idiopathic pulmonary fibrosis admitted to the intensive care unit, Saydain and coworkers (37) analyzed data on 38 patients. Predicted mortality by APACHE (Acute Physiology and Chronic Health Evaluation) score was 12%, but actual mortality in the intensive care unit was 45%. Predicted hospital mortality was 26% and actual mortality was 61%. Pulmonary function and echocardiography did not differ between survivors and nonsurvivors. Mechanical ventilation was used in 50% of patients, and sepsis developed in 24% of patients. Multiple organ failure developed in 14% of survivors and 43% of the nonsurvivors. Of patients surviving admission to hospital, 92% died at a median of 2 months after discharge. The authors conclude that patients with idiopathic pulmonary fibrosis requiring admission to an intensive care unit have poor short-term and long-term prognosis.

    To determine whether the variability of breathing pattern is altered in patients with restrictive lung disease and to determine whether any such alteration is related to dyspnea, Brack and coworkers (38) measured ventilation nonobtrusively in 10 patients with restrictive lung disease and in 7 healthy subjects. Compared with the healthy subjects, the random fraction of breath variability was reduced in the patients: 27 times for expiratory time, 12 times for tidal volume, and 6 times for inspiratory time. Conversely, the nonrandom, correlated fraction for tidal volume was increased almost threefold in the patients. On a separate occasion, dyspnea was measured while the patients and control subjects voluntarily copied different tidal volumes and frequencies. Small variations from the average resting tidal volume caused marked increases in dyspnea in the patients, and the relationship was parabolic (r² = 0.97). The authors conclude that patients with restrictive lung disease adopt a tightly constrained breathing pattern, probably as a strategy for avoiding dyspnea.

    Cellular and molecular mechanisms, in vivo.9, 百拇医药

    Vascular endothelial growth factor is involved in the development and maintenance of vascular function, and inhibition of its receptor causes endothelial cell apoptosis and emphysema. Koyama and coworkers (39) determined whether its level is altered in patients with lung disease. The level of vascular endothelial growth factor in bronchoalveolar fluid was 256 pg per ml in 16 healthy nonsmokers, 27 pg per ml in 11 healthy smokers, 62 pg per ml in 14 patients with idiopathic pulmonary fibrosis, 78 pg per ml in 21 patients with pulmonary fibrosis associated with connective tissue disease, and 133 pg per ml in 14 patients with sarcoidosis. The isoform in the healthy nonsmokers was VEGF165. The authors conclude that vascular endothelial growth factor is decreased in the bronchoalveolar fluid of healthy nonsmokers, and in patients with idiopathic pulmonary fibrosis, pulmonary fibrosis associated with connective tissue disease, and sarcoidosis.

    The role of inflammatory mechanisms in of the pathogenesis of idiopathic pulmonary fibrosis is debated by Gauldie (40) and Strieter (41), with rebuttals from each (42, 43).hj{3q, 百拇医药

    Cellular and molecular mechanisms, ex vivo.hj{3q, 百拇医药

    Infection with the Epstein-Barr virus has been linked to idiopathic pulmonary fibrosis. Replication of the virus is associated with a rearrangement of genomes for Epstein-Barr virus, termed the WZhet recombinant fragment. To determine whether WZhet genomes are associated with idiopathic pulmonary fibrosis, Kelly and coworkers (44) studied 39 patients with idiopathic pulmonary fibrosis, 26 lung transplant recipients, and 24 healthy subjects. Of lung biopsies from patients with idiopathic pulmonary fibrosis that contained DNA of the Epstein-Barr virus, 11 of 18 (61%) were positive for WZhet. WZhet was positive in the buffy coat of peripheral blood in 59% of patients with idiopathic pulmonary fibrosis, as compared with 4% of the healthy subjects and none of the lung transplant recipients. The presence of WZhet in lung tissue was correlated with the level in peripheral blood. The presence of WZhet was not related to immunosuppressive therapy. The authors conclude that a rearranged form of Epstein-Barr virus DNA, the WZhet recombinant fragment, is common in patients with idiopathic pulmonary fibrosis, and that it provides a marker for tracking Epstein-Barr virus in this disease.

    Animal models.?.;[^|}, http://www.100md.com

    Using fluorescence-activated cell sorting technology, Maus and coworkers (45) characterized the molecular pathways involved in the phenotyping of leukocyte traffic into the alveolar space of intact mice. The instillation of monocyte chemoattractant JE/monocyte chemotactic protein-1 combined with E. coli lipopolysaccharide into the trachea induced self-limiting alveolar inflammation involving migration of both monocytes and neutrophils. Challenge with JE/monocyte chemotactic protein-1 alone provoked the migration of only monocytes and it did not cause inflammation; this recruitment of monocytes was strictly dependent on CD11b/CD18, CD54 and CD-49d, partly dependent on CD11a, and not dependent on CD106. The recruitment of monocytes in response to the combination of JE-monocyte chemotactic protein-1 and E. coli lipopolysaccharide was associated with additional engagement of CD11a and CD106. Neutrophils comigrating under these conditions involved CD11b, CD18 and CD54, but not CD49d, CD106, or CD11a. The authors conclude that the molecular pathways involved in the migration of monocytes into the alveolar space in response to monocyte chemoattractant JE/monocyte chemotactic protein-1 differ depending whether or not there was accompanying inflammation.

    Treatment.4?{-g/, 百拇医药

    Because nuclear factor-{kappa}4?{-g/, 百拇医药

    B promotes the transcription of genes encoding chemokines and cytokines involved in chronic inflammation, preventing the activation of this transcription factor may lessen the lung injury of idiopathic pulmonary fibrosis. Conron and coworkers (46) infected alveolar macrophages from patients with inflammatory lung disease with adenovirus constructs that express a defective ß subunit of I{kappa}4?{-g/, 百拇医药

    B kinase and a defective nuclear factor-{kappa}4?{-g/, 百拇医药

    B–inducing kinase. Constitutive and cytokine induced activation of nuclear factor-{kappa}4?{-g/, 百拇医药

    B by alveolar macrophages was found to require the catalytically active subunit of I{kappa}4?{-g/, 百拇医药

    B kinase, but was not dependent on signaling by nuclear factor-{kappa}4?{-g/, 百拇医药

    B–inducing kinase. The authors conclude that the I{kappa}

    B kinase subunit is a potential target for gene therapy in diseases that involve transcription of nuclear factor-{kappa}|, http://www.100md.com

    B.|, http://www.100md.com

    Statements and workshops.|, http://www.100md.com

    The American Thoracic Society and the European Respiratory Society (47) present a multidisciplinary consensus classification of the idiopathic interstitial pneumonias.|, http://www.100md.com

    In a summary report from a NHLBI workshop, Crystal and colleagues (48) review future directions for research on idiopathic pulmonary fibrosis.|, http://www.100md.com

    Progressive Systemic Sclerosis|, http://www.100md.com

    To determine whether the better prognosis of idiopathic pulmonary fibrosis associated with systemic sclerosis is related to histopathologic findings, Bouros and coworkers (49) studied 80 patients with this condition. Nonspecific interstitial pneumonia was observed in 77.5%, usual interstitial pneumonia in 7.5%, end-stage lung disease in 7.5%, and other patterns in the remaining 7.5%. Five-year mortality was 91% in patients with nonspecific interstitial pneumonia and 82% in patients with usual interstitial pneumonia or the end-stage pattern. Mortality was associated with a low initial diffusing capacity and a low FVC. The authors conclude that idiopathic pulmonary fibrosis associated with systemic sclerosis has the histopathologic pattern of nonspecific interstitial pneumonia, but that the histopathologic pattern does not predict prognosis. An editorial commentary by King (50) accompanies this article.

    To determine whether the alveolar concentration of nitric oxide is elevated in patients with pulmonary involvement of scleroderma, Girgis and coworkers (51) studied 20 patients and 20 healthy control subjects. Exhaled nitric oxide was measured at multiple flow rates and the output of nitric oxide was plotted against expiratory flow rate: the slope of the relationship was taken as a measure of alveolar concentration and the intercept was taken as a measure of flux in the conducting airways. The alveolar concentration of nitric oxide was higher in the patients than in the control subjects: 4.7 versus 1.8 ppb. Flux in the conducting airways was lower in the patients than in the control subjects: 0.6 versus 1.2 nl per second. The alveolar concentration of nitric oxide was negatively correlated with diffusing capacity (r = -0.66). The authors conclude that patients who have scleroderma with lung involvement have an increased alveolar concentration of nitric oxide.5i[}**, http://www.100md.com

    Sarcoidosis

    Genetics.cy9#[, http://www.100md.com

    To determine whether polymorphisms in the genes of the interleukin-1 family are involved in the pathogenesis of sarcoidosis and idiopathic pulmonary fibrosis, Hutrova and coworkers (52) studied 95 patients with sarcoidosis, 54 patients with idiopathic pulmonary fibrosis, and 199 healthy subjects. The interleukin-1{alpha}cy9#[, http://www.100md.com

    -889 1.1 genotype was overrepresented in the patients as compared with the healthy subjects: 60% versus 44%. The distribution of genotypes for interleukin-1ß -511, interleukin-1ß +3953, and interleukin-1 receptor antagonist VNTR did not differ between the patients with sarcoidosis and the healthy subjects. None of the polymorphisms was associated with interstitial pulmonary fibrosis. The authors conclude that interleukin-1{alpha}cy9#[, http://www.100md.com

    -889 1.1 polymorphism is associated with the development of sarcoidosis.cy9#[, http://www.100md.com

    In two well-defined groups of patients with sarcoidosis (96 British patients and 354 control subjects, and 100 Dutch patients and 222 control subjects), Grutters and coworkers (53) studied five potential functional polymorphisms in the promoter region of the gene for tumor necrosis factor-{alpha}

    . The two populations of patients with sarcoidosis displayed an increase in the rare -857T allele (which involves a change from C to T at position -857 in the promoter region). This allele was carried by 25.5% of the patients with sarcoidosis and by 14.1% of the control subjects; the allele frequency of this polymorphism was 13.5% in the sarcoidosis patients and 7.3% in the control subjects. The rare -307A allele was increased in the subgroup of patients with Lofgren's syndrome, although linkage disequilibrium was not excluded. The authors conclude that patients with sarcoidosis display an increase in the rare -857T allele in the promoter region of the gene for tumor necrosis factor-{alpha}|96xeqx, 百拇医药

    .|96xeqx, 百拇医药

    Molecular mechanisms.|96xeqx, 百拇医药

    In bronchoalveolar fluid from 30 patients with different stages of sarcoidosis and 18 healthy subjects, Capelli and coworkers (54) measured the levels of two macrophage-derived CC chemokines that induce lymphocyte migration. Macrophage inflammatory protein-1{alpha}

     was increased in patients with Stage II and Stage III disease, whereas macrophage inflammatory protein-1ß was increased in all stages. Expression of CCR5, the receptor for both chemokines, was increased in both lymphocytes and macrophages of all patients. The concentration of macrophage inflammatory protein-1ß was correlated with the number of CD4 lymphocytes (r = 0.64) and with the number of CD8 lymphocytes (r = 0.62). The concentration of macrophage inflammatory protein-1{alpha}2, 百拇医药

    was correlated only with the number of CD8 lymphocytes (r = 0.45). The percentage of neutrophils was negatively related to expression of CCR5 in both alveolar macrophages (r = -0.53) and lymphocytes (r = -0.43). The authors conclude that lymphocytes and alveolar macrophages of patients with sarcoidosis display increased levels of two CC chemokines, macrophage inflammatory protein-1{alpha}2, 百拇医药

    and macrophage inflammatory protein-1ß, associated with increased expression of CCR5, the specific receptor for these chemokines.

    Histiocytosis X7)k@f, 百拇医药

    Pulmonary Langerhans cell histiocytosis (also called histiocytosis x) is characterized by destructive granulomas containing large numbers of activated Langerhans cells. The extent to which the granulomas are bronchocentric is unknown, and the mode of cyst formation has not been defined. To investigate these issues, Kambouchner and coworkers (55) studied serial sections obtained from seven patients. The granulomatous process exclusively affected the small airways in an acinar distribution. The lesions extended, without interruption, along the bronchiolar axis, forming continuous sleeve-like structures around the distant airways. The granulomatous reaction progressed along the bronchiolar axis over time, extending the abnormalities in both proximal and distal directions. Cystic lesions resulted from destruction of the bronchiolar wall and progressive dilation of the lumen, subsequently circumscribed by fibrous tissue. The authors conclude that it may be more accurate to classify pulmonary Langerhans cell histiocytosis as a bronchiolitis rather than as an interstitial lung disease because the lesions affect and progressively destroy the distal airways. An editorial commentary by Myers and Aubry (56) accompanies this article.

    Lymphangioleiomyomatosis&idech], 百拇医药

    Telomerase synthesizes nucleotide hexameric repeats (telomeres) at the end of chromosomes, replacing base sequences that are lost during each mitotic cycle and protecting the ends against the action of exonucleases and ligases. To evaluate the role of telomerase activity in the proliferation of lymphangioleiomyomatosis (LAM) cells (abnormal smooth muscle cells), Kumaki and coworkers (57) studied 22 women with LAM (14 untreated and 8 treated with progesterone or tamoxifen). Signals for telomerase protein and messenger RNA were observed in 5 to 20% of LAM cells (mostly of the spindle-shaped type) in 21 of the 22 patients. Signals were less intense in the treated group. Telomerase colocalized in the same cells with {alpha}&idech], 百拇医药

    -smooth muscle actin, but only rarely with HMB-45 antibody (a marker for epithelioid LAM cells). The authors conclude that telomerase is present in 5 to 20% of LAM cells, and mostly in those of the proliferative spindle-shaped type.

    Mast cells produce basic fibroblast growth factor, which is a potent mitogenic factor for proliferation of smooth muscle cells, myofibroblasts, and fibroblasts. Inoue and coworkers (58) studied involvement of this growth factor in lung sections from 14 patients with idiopathic pulmonary fibrosis, 9 patients with LAM, and 10 control subjects without lung disease. The lungs from the two patient groups contained more smooth muscle cells and myofibroblast-like cells than did the control lungs. Mast cells containing basic fibroblast growth factor were abundant in both patient groups, and were associated with collagen, elastic fibers, smooth muscle cells, and myofibroblast-like cells. Fibroblast growth factor receptor 1 (Flg) was expressed on epithelial cells, endothelial cells, smooth muscle cells, myofibroblast-like cells, and macrophages in idiopathic pulmonary fibrosis. The fibroblast growth factor receptor was expressed on epithelial cells adjacent to aggregates of smooth muscle cells and myofibroblast-like cells in LAM. Fibroblast growth factor receptor 2 (Bek) was expressed on smooth muscle cells and myofibroblast-like cells in both idiopathic pulmonary fibrosis and LAM, and also on neutrophils in idiopathic pulmonary fibrosis. The authors conclude that basic fibroblast growth factor derived from mast cells appears to exert proliferative fibrogenic effects on smooth muscle cells and myofibroblast-like cells in patients with idiopathic pulmonary fibrosis and LAM.

    Eosinophilic Pneumonia*, 百拇医药

    Thymus- and activation-regulated chemokine (TARC/CCL17) is a high-affinity ligand for CC chemokine receptor-4 (CCR4), which recruits CCR4-expressing type 2 (Th2) helper T cells. Miyazaki and coworkers (59) found that 25 patients with eosinophilic pneumonia had a median level of TARC in bronchoalveolar fluid of 240 pg per ml, whereas most patients with other interstitial lung diseases (11 with hypersensitivity pneumonitis, 20 with sarcoidosis, 18 with idiopathic pulmonary fibrosis) had a level of less than 7 pg per ml. Patients with eosinophilic pneumonia also had increased levels of interleukin-4, interleukin-5, and interleukin-13 in bronchoalveolar fluid. The concentration of TARC was correlated with the levels of interleukin-5 (r = 0.89) and interleukin-13 (r = 0.84) in bronchoalveolar fluid. On serial measurements, a fall in the level TARC preceded decreases in the level of interleukin-5 and in the number of eosinophils. The authors conclude that the level of TARC (thymus- and activation-regulated chemokine) is elevated in parallel with type 2 (Th2) cytokines, interleukin-5, and interleukin-13 in the bronchoalveolar fluid of patients with eosinophilic pneumonia.

    Idiopathic acute eosinophilic pneumonia is characterized by acute febrile respiratory failure associated with diffuse radiographic infiltrates and pulmonary eosinophilia. Philit and coworkers (60) describe a series of 22 patients with this rare clinical entity. Within the first month after the onset of symptoms, the patients presented with severe hypoxemia (Pa_O2/FI_O2 ratio, 156 mm Hg). Fourteen patients (64%) required mechanical ventilation, 12 patients met the criteria for acute lung injury, and 8 patients met the criteria for the acute respiratory distress syndrome. Radiographic studies revealed diffuse bilateral infiltrates. Bronchoalveolar lavage revealed 54% eosinophils. All patients recovered: 6 recovered without glucocorticoids and 12 received glucocorticoids. No patient relapsed. The authors conclude that idiopathic acute eosinophilic pneumonia should be considered in the differential diagnosis of acute respiratory distress syndrome, finding more than 25% eosinophilia on lavage obviates the need for lung biopsy, and a response to glucocorticoids should not be used as a diagnostic criterion. An editorial commentary by du Bois (61) accompanies this article.

    Acute Interstitial Pneumonitis@hh, http://www.100md.com

    Acute interstitial pneumonitis causes acute alveolar damage, and its sudden onset resembles the acute respiratory distress syndrome. Ichikado and coworkers (62) studied whether the findings on high-resolution computed tomography could predict prognosis in 10 nonsurvivors and 21 survivors of acute interstitial pneumonia. Two independent observers unaware of patient outcome graded the findings: interobserver agreement was good ({kappa}@hh, http://www.100md.com

    0.75). Compared with nonsurvivors, survivors displayed less ground-glass attenuation or consolidation associated with traction bronchiolectasis or bronchiectasis, less architectural distortion, and more ground glass attenuation or consolidation without traction bronchiolectasis. Overall scores were lower in survivors than in nonsurvivors: 223 versus 324. A score of less than 245 had a positive predictive value of 80% and a negative predictive value of 90% for survival. The authors conclude that findings on computed tomography help in predicting the prognosis in acute interstitial pneumonitis irrespective of the underlying physiologic abnormality. An editorial commentary by Hansell (63) accompanies this article.

    Niemann-Pick Disease*}e, 百拇医药

    Niemann-Pick disease is a lipid storage disorder caused by a lack or deficiency of acid sphingomyelinase. Patients with Type B disease often survive into adulthood and can develop progressive pulmonary infiltrates. Nicholson and coworkers (64) describe a patient who presented with extensive endogenous lipoid pneumonia and severe hypoxemia after cardiac surgery. Bilateral whole lung lavage produced a decrease in the pulmonary infiltrates and an increase in PO₂ of 15 mm Hg while breathing room air. The authors conclude that whole-lung lavage may be useful in treating pulmonary involvement caused by Neimann-Pick Type B disease.*}e, 百拇医药

    Lymphoproliferative Disorders*}e, 百拇医药

    Kurosa and coworkers (65) determined whether pulmonary lymphoproliferative lesions display selective oligoclonal expansion of tumor-infiltrating T lymphocytes. Denaturing gradient gel electrophoresis revealed some oligoclonal bands for T cell antigen receptor-V{gamma}

    gene in 6 of 15 patients with low-grade mucosa-associated lymphoid tissue (MALT), in all of 5 patients with HIV-related lymphocytic interstitial pneumonia, and in 1 of 3 patients with HIV-negative lymphocytic interstitial pneumonia. The authors conclude that oligoclonal expansions occur in some pulmonary lymphoproliferative disorders.1vif7tp, 百拇医药

    Idiopathic Pulmonary Alveolar Proteinosis1vif7tp, 百拇医药

    In a state of the art review article, Seymour and Presneill (66) discuss the first 44 years of progress on pulmonary alveolar proteinosis.1vif7tp, 百拇医药

    Pulmonary Drug Toxicity1vif7tp, 百拇医药

    Idiopathic pneumonia syndrome, a noninfectious diffuse lung injury, is reported to occur in 39 to 64% of patients who undergo high-dose chemotherapy and bone marrow transplantation. Bhalla and Folz (67) developed a murine model that mimics the human disease. Using an autologous bone transplant regimen, mice developed pulmonary injury as early as the following day. The injury was characterized by intense infiltrates of activated macrophages and a decrease in lung compliance. The cellular influx was preceded by acute elevation in monocyte chemotactic protein-1 and macrophage inflammatory protein-1{alpha}

    . The conditioning regimen caused substantial oxidative stress, as manifested by increase in lung lipid peroxidation and oxidized glutathione. Administration of N-acetylcysteine, an antioxidant, markedly decreased the lung injury. The authors conclude that the early stages of idiopathic pneumonia syndrome in mice treated with high-dose chemotherapy and bone marrow transplantation consists of severe oxidative stress, associated with the recruitment of alveolar macrophages and a decrease in lung compliance. An editorial commentary by Haddad (68) accompanies this article.;+04m-, 百拇医药

    Calcium Deposition in the Lung;+04m-, 百拇医药

    In a state of the art review article, Chan and colleagues (69) discuss calcium deposition with or without bone formation in the lung.;+04m-, 百拇医药

    Rodent Model of Bleomycin Fibrosis;+04m-, 百拇医药

    To determine the role of leukotrienes in pulmonary fibrosis, Peters-Golden (70) studied lung fibrosis caused by bleomycin in mice. In wild-type mice, bleomycin caused a fivefold increase in the levels of cyteinyl-leukotrienes, and the levels remained high for 21 days. In mice deficient in leukotrienes (achieved by targeted deletion of the gene for 5-lipoxygenase), bleomycin caused less collagen formation and a 60% decrease in lung hydroxyproline. Unlike the wild-type mice, the knockout mice did not develop increases in lung inflammatory cells after bleomycin, and they displayed greater expression of the antifibrotic cytokine, interferon-{gamma}

    , and higher levels of the antiinflammatory and antifibrotic molecule, prostaglandin E₂. The authors conclude that leukotrienes participate both directly and indirectly in pulmonary fibrosis caused by bleomycin. An editorial commentary by Zeldin (71) accompanies this article.4#, 百拇医药

    Because N-acetylcysteine ameliorates pulmonary fibrosis caused by bleomycin, Wang and coworkers (72) studied the effect of bilirubin, another powerful antioxidant, in this setting. Intravenous infusions were used to maintain a serum bilirubin of 3 to 10 mg per dl in rats. Mortality from pulmonary fibrosis caused by bleomycin was lower in rats with hyperbilirubinemia than in control animals. Rats with hyperbilirubinemia had lower levels of hydroxyproline in the lung, lower concentrations of transforming growth factor-ß₁ in bronchoalveolar fluid, and decreased numbers of polymorphonuclear leukocytes and lymphocytes in bronchoalveolar fluid. Rats with hyperbilirubinemia had higher levels of oxidative metabolites of bilirubin in the urine. The authors conclude that the antioxidant action of bilirubin attenuates the pulmonary fibrosis caused by bleomycin, partly by inhibiting lung inflammation and the production of transforming growth factor-ß₁.

    Instilling bleomycin into the lungs of mice causes DNA damage and apoptosis within hours, and inflammation and fibrosis several weeks later. Ghosh and coworkers (73) evaluated the role of p53 tumor suppression protein, which mediates cellular responses to DNA damage, including the induction of apoptosis. Transgenic mice with a dominant-negative mutant form of human p53 expressed from the promoter for surfactant protein C displayed more severe lung damage, increased collagen deposition, and more pronounced eosinophilia after exposure to bleomycin than did control mice. The authors conclude that compromised function of p53 tumor suppressor protein in alveolar epithelium impairs the recovery of the lung after exposure to bleomycin.3{)lw, 百拇医药

    OCCUPATIONAL LUNG DISEASE3{)lw, 百拇医药

    Crystalline silica stimulates macrophages to release interleukin-1ß, tumor necrosis factor-{alpha}3{)lw, 百拇医药

    , and nitric oxide, and it induces apoptosis of macrophages. In a model of murine silicosis,Srivastava and coworkers (74) investigated the mechanisms of lung inflammation and apoptosis. In in-vitro experiments, silica induced the production of nitric oxide and apoptosis in a macrophage cell line. Both the release of nitric oxide and apoptosis were inhibited by a neutralizing antibody to interleukin-1ß or an inhibitor of nitric oxide synthase (N^G–nitro-L-arginine-methyl ester, L-NAME). In in vivo experiments, three groups of mice were exposed to silica (250 mg per cubic meter) for 5 hours a day over 10 days. Compared with inducible nitric oxide synthase knockout (iNOS^-/-) mice, wild-type mice developed more inflammation and apoptosis. Wild-type mice developed lung inflammation, apoptosis, and more and larger silicotic lesions than did interleukin-1ß^-/- knockout mice. The authors conclude that apoptosis dependent on interleukin-1ß and mediated by nitric oxide plays a role in the evolution of murine silicosis.

    The cytokine tumor necrosis factor-{alpha}jaj.8, http://www.100md.com

    plays a central role in the pathophysiology of silicosis. Corbett and coworkers (75) investigated the role of single nucleotide polymorphisms (SNPs) in the promoter region of tumor necrosis factor-{alpha}jaj.8, http://www.100md.com

    in determining susceptibility to silicosis in black South African gold miners. No differences were seen for any loci in the promoter region between 112 patients with nonsevere silicosis and 120 miners without silicosis. Nine miners with severe silicosis were more likely than control subjects to have -238A (33 versus 5%) and -376A (33 versus 5%); these alleles were in linkage disequilibrium, indicating that they were not independent. Miners with severe silicosis were also more likely to have the -308A allele, but the result was confounded by ethnicity. The authors conclude that polymorphisms of the promoter region of tumor necrosis factor-{alpha}jaj.8, http://www.100md.com

    are associated with severe silicosis, and that the polymorphism influences the severity of the disease rather than its frequency.

    Some 1 to 8% of beryllium workers have beryllium hypersensitivity on immunologic testing, and 42 to 83% of workers with hypersensitivity have manifestations of chronic beryllium disease. Rossman and coworkers (76) studied three different human leukocyte antigen (HLA) Class II isotypes in 25 patients with established chronic beryllium disease, 30 subjects with beryllium hypersensitivity but without clinical disease, and 82 beryllium workers who did not have beryllium hypersensitivity. HLA-DPB1-E⁶⁹ was a marker for beryllium hypersensitivity, but it did not distinguish between subjects who did or did not develop symptoms of chronic beryllium disease. Chronic beryllium disease was significantly associated with HLA-DQB1-G⁸⁶ and HLA-DRB1-S¹¹. The authors conclude that HLA-DPB1-E⁶⁹ is a marker for susceptibility to beryllium hypersensitivity but not a marker for progression to disease, and that HLA amino acid epitodes on HLA-DRB1 and HLA-DQB1 may be associated with progression of disease.

    Vermiculite is a silicate material that is used extensively in the insulation and building industry. Wright and coworkers (77) describe the case of a 65-year-old accountant who developed extensive fibrocalcific pleural plaques, end-stage pulmonary fibrosis, and rapidly progressive respiratory failure. The patient's only exposure to asbestos was during a summer job 50 years earlier in a California vermiculite expansion plant. Electron microscopy revealed over 8 million asbestos fibers per gram of dry lung, and 68% were tremolite asbestos. Additional asbestiform fibers of a composition not matching any of the standard varieties were also present in high concentration. Analysis of a sample of vermiculite from Libby, Montana—a major source of U.S. vermiculite—showed a similar mix of asbestiform fibers. The authors conclude that brief but intense exposure to asbestos can cause severe fibrotic disease after a long latency period, and that the risk of vermiculite-induced injury needs to be considered among former workers of the more 200 expansion plants.

    Rom and coworkers (78) describe a firefighter who was exposed to high concentrations of dust from the World Trade Center for over 2 weeks and who subsequently developed acute eosinophilic pneumonia. The patient presented with cough, blackish sputum, and dyspnea, and had a PO₂ of 53 mm Hg. Computed tomography revealed patchy ground glass density, thickened bronchial walls, and bilateral pleural effusions. Bronchoalveolar lavage revealed 70% eosinophilia and increased levels of interleukin-5. Mineralogical analysis revealed 305 commercial asbestos fibers per 10⁶ macrophages; fly ash and degraded glass were also found. The patient responded to oxygen and glucocorticoids. An editorial commentary by Beckett (79) accompanies this article.kzl4!20, 百拇医药

    To determine the prevalence of sensitization to allergens in the workplace and the prevalence of occupational asthma among growers of greenhouse flowers or ornamental plants, Monso and coworkers (80) studied 39 growers. Thirteen of 38 growers (34%) were sensitized to flowers or molds, but sensitization was not related to characteristics of the greenhouses. Poor ventilation was a marginal risk factor for wheezing. Occupational asthma was confirmed by bronchial provocation in three workers (7.7%), all of whom were sensitized to workhouse flowers or molds. None of the nonsensitized workers had occupational asthma. The authors conclude that occupational asthma occurs in 8% of growers of greenhouse flowers, ornamental plants, or both, and in a quarter of workers sensitized to flowers or molds.

    Peripheral blood monocytes of patients with diisocyanate asthma produce monocyte chemoattractant protein-1 in response to diisocyanate human serum albumin. To determine the diagnostic usefulness of this response, Bernstein and coworkers (81) studied 54 workers exposed to diisocyanate. A diagnosis of diisocyanate asthma was confirmed by a specific inhalation challenge in 19 (35%) of the workers. The assay for production of monocyte chemoattractant protein-1 (in response to diisocyanate-human serum albumin) had a diagnostic sensitivity of 79% and a specificity of 91%. Diisocyanate-specific IgG had a sensitivity of 47% and a specificity of 74%. Diisocyanate-specific IgE had a sensitivity of 21% and a specificity of 89%. The authors conclude that an in vitro assay for production of chemoattractant protein-1 in response to diisocyanate-human serum albumin is superior to specific IgE and IgG antibodies in the diagnosis of diisocyanate asthma. An editorial commentary by Hendrick (82) accompanies this article.

    To determine the influence of occupational exposure on the incidence of respiratory symptoms and asthma, Eagan and coworkers (83) undertook an 11-year community cohort study in 2,819 Norwegian subjects. At baseline, the prevalence of exposure to quartz was 3.7%, to asbestos 5.0%, and to dust or fumes 28.3%. After adjusting for sex, age, educational level, and smoking, the odds ratios for the development of respiratory symptoms or asthma in subjects exposed to dust or fumes varied between 1.4 and 2.1. After adjusting for the confounding variables, 14% of the incidence of asthma and 6 to 19% of the incidence of respiratory symptoms were attributable to exposure to dust or fumes. The authors conclude that airborne occupational exposure increases the incidence of asthma and respiratory symptoms.(a!4'\, http://www.100md.com

    To investigate the relationship between pesticides and wheeze in farmers, Hoppin and coworkers (84) analyzed data from 20,468 certified pesticide applicators in Iowa and North Carolina. The applicators, ranging in age from 16 to 88 years, completed self-administered questionnaires. In the previous year, 19% reported wheezing. After controlling for age, state, smoking, and history of asthma or atopy, the odds ratios for wheeze were elevated for paraquat, three organophosphates (parathion, malathion, and chlorpyrifos), and one thiocarbamate (S-ethyl-dipropylthiocarbamate, EPTC). The herbicides, atrazine and alachlor, but not 2, 4-D, were associated with wheeze. Inclusion of crops and animals into the model did not alter the odds ratios. The authors conclude that specific pesticides are independent contributors to wheeze in farmers. An editorial commentary by Ernst (85) accompanies this article.

    SOCIAL ISSUES, HEALTH POLICY, ECONOMICS, AND JOURNALOLOGY5:2tn, 百拇医药

    Journalology5:2tn, 百拇医药

    In an occasional essay, Hoppin (86) discusses how he reviews an original scientific article.5:2tn, 百拇医药

    In an editorial, Tobin (87) discusses the rigor of peer review and the standing of a journal.5:2tn, 百拇医药

    In an editorial, Tobin (88) discusses the policy of AJRCCM on duplicate publication.5:2tn, 百拇医药

    In an editorial, Tobin (89) discusses the expansion of web-based publishing in the Journal.5:2tn, 百拇医药

    In an editorial, Tobin (90) discusses the Journal's policy on abbreviations.5:2tn, 百拇医药

    In an editorial, Tobin (91) discusses the Journal in 2002.5:2tn, 百拇医药

    REFERENCES5:2tn, 百拇医药

    Tsuchiya T, Chida K, Suda T, Schneeberger EE, Nakamura H. Dendritic cell involvementin pulmonary granuloma formation elicited by bacillus calmette-guerin in rats. Am J Respir Crit Care Med 2002;165:1640–1646.5:2tn, 百拇医药

    Dreher D, Nicod LP. Dendritic cells in the mycobacterial granuloma are involved in acquired immunity. Am J Respir Crit Care Med 2002;165:1577–1578.06g3%, 百拇医药

    Choi HS, Rai PR, Chu HW, Cool C, Chan ED. Analysis of nitric oxide synthase and nitrotyrosine expression in human pulmonary tuberculosis. Am J Respir Crit Care Med 2002;166:178–186.06g3%, 百拇医药

    Nathan C. Inducible nitric oxide synthase in the tuberculous human lung. Am J Respir Crit Care Med 2002;166:130–131.06g3%, 百拇医药

    Lewinsohn DA, Lines RA, Lewinsohn DM. Human dendritic cells presenting adenovirally expressed antigen elicit Mycobacterium tuberculosis–specific CD8+ T cells. Am J Respir Crit Care Med 2002;166:843–848.06g3%, 百拇医药

    Lalvani A. CD8 cytotoxic T cells and the development of new tuberculosis vaccines. Am J Respir Crit Care Med 2002;166:789–790.06g3%, 百拇医药

    Lazarevic V, Flynn J. CD8(+) T cells in tuberculosis. Am J Respir Crit Care Med 2002;166:1116–1121.06g3%, 百拇医药

    Nitta AT, Knowles LS, Kim J, Lehnkering EL, Borenstein LA, Davidson PT, Harvey SM, De Koning ML. Limited transmission of multidrug-resistant tuberculosis despite a high proportion of infectious cases in Los Angeles County, California. Am J Respir Crit Care Med 2002;165:812–817.

    Daley CL. Transmission of multidrug-resistant tuberculosis: limited by man or nature? Am J Respir Crit Care Med 2002;165:742–743.$5em, 百拇医药

    Greenaway C, Menzies D, Fanning A, Grewal R, Yuan L, FitzGerald JM. Delay in diagnosis among hospitalized patients with active tuberculosis–predictors and outcomes. Am J Respir Crit Care Med 2002;165:927–933.$5em, 百拇医药

    Sepkowitz KA. On the contagious nature of tuberculosis (continued). Am J Respir Crit Care Med 2002;165:858–859.$5em, 百拇医药

    Gerald LB, Tang S, Bruce F, Redden D, Kimerling ME, Brook N, Dunlap N, Bailey WC. A decision tree for tuberculosis contact investigation. Am J Respir Crit Care Med 2002;166:1122–1127.$5em, 百拇医药

    Weis S. Contact investigations: how do they need to be designed for the 21st century? Am J Respir Crit Care Med 2002;166:1016–1017.$5em, 百拇医药

    Weis SE, Pogoda JM, Yang Z, Cave MD, Wallace C, Kelley M, Barnes PF. Transmission dynamics of tuberculosis in Tarrant county, Texas. Am J Respir Crit Care Med 2002;166:36–42.$5em, 百拇医药

    Fukunaga H, Murakami T, Gondo T, Sugi K, Ishihara T. Sensitivity of acid-fast staining for mycobacterium tuberculosis in formalin-fixed tissue. Am J Respir Crit Care Med 2002;166:994–997.

    Sharma SK, Balamurugan A, Saha PK, Pandey RM, Mehra NK. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. Am J Respir Crit Care Med 2002;166:916–919.uy, 百拇医药

    Bothamley GH. Treatment, tuberculosis, and human leukocyte antigen. Am J Respir Crit Care Med 2002;166:907–908.uy, 百拇医药

    Bock NN, Sterling TR, Hamilton CD, Pachucki C, Wang YC, Conwell DS, Mosher A, Samuels M, Vernon A. A prospective, randomized, double-blind study of the tolerability of rifapentine 600, 900, and 1,200 mg plus isoniazid in the continuation phase of tuberculosis treatment. Am J Respir Crit Care Med 2002;165:1526–1530.uy, 百拇医药

    Gillespie SH, Gosling RD, Charalambous BM. A reiterative method for calculating the early bactericidal activity of antituberculosis drugs. Am J Respir Crit Care Med 2002;166:31–35.uy, 百拇医药

    O'Brien RJ. Studies of the early bactericidal activity of new drugs for tuberculosis: a help or a hindrance to antituberculosis drug development? Am J Respir Crit Care Med 2002;166:3–4.uy, 百拇医药

    Morris A, Creasman J, Turner J, Luce JM, Wachter RM, Huang L. Intensive care of human immunodeficiency virus-infected patients during the era of highly active antiretroviral therapy. Am J Respir Crit Care Med 2002;166:262–267.

    Masur H. Acquired immunodeficiency syndrome in the intensive care unit: will human immunodeficiency virus-related admissions continue to decline? Am J Respir Crit Care Med 2002;166:258–259.e5+qt;q, 百拇医药

    Mehrad B, Wiekowski M, Morrison BE, Chen SC, Coronel EC, Manfra DJ, Lira SA. Transient lung-specific expression of the chemokine KC improves outcome in invasive aspergillosis. Am J Respir Crit Care Med 2002;166:1263–1268.e5+qt;q, 百拇医药

    Huffnagle GB. Investigating invasive aspergillosis. Am J Respir Crit Care Med 2002;166:1159–1160.e5+qt;q, 百拇医药

    Leemans JC, Vervoordeldonk MJ, Florquin S, van Kessel KP, Van Der PT. Differential role of interleukin-6 in lung inflammation induced by lipoteichoic acid and peptidoglycan from Staphylococcus aureus. Am J Respir Crit Care Med 2002;165:1445–1450.e5+qt;q, 百拇医药

    Tasaka S, Richer SE, Mizgerd JP, Doerschuk CM. Very late antigen-4 in CD18-independent neutrophil emigration during acute bacterial pneumonia in mice. Am J Respir Crit Care Med 2002;166:53–60.e5+qt;q, 百拇医药

    Maus U, von Grote K, Kuziel WA, Mack M, Miller EJ, Cihak J, Stangassinger M, Maus R, Schlondorff D, Seeger W, et al. The role of CC chemokine receptor 2 in alveolar monocyte and neutrophil immigration in intact mice. Am J Respir Crit Care Med 2002;166:268–273.

    El Solh AA, Aquilina AT, Dhillon RS, Ramadan F, Nowak P, Davies J. Impact of invasive strategy on management of antimicrobial treatment failure in institutionalized older people with severe pneumonia. Am J Respir Crit Care Med 2002;166:1038–1043.n#77$/, http://www.100md.com

    Kaplan V, Angus DC, Griffin MF, Clermont G, Scott WR, Linde-Zwirble WT. Hospitalized community-acquired pneumonia in the elderly: age- and sex-related patterns of care and outcome in the United States. Am J Respir Crit Care Med 2002;165:766–772.n#77$/, http://www.100md.com

    Angus DC, Marrie TJ, Obrosky DS, Clermont G, Dremsizov TT, Coley C, Fine MJ, Singer DE, Kapoor WN. Severe community-acquired pneumonia: use of intensive care services and evaluation of American and British Thoracic Society Diagnostic criteria. Am J Respir Crit Care Med 2002;166:717–723.n#77$/, http://www.100md.com

    Herkner H, Muller MR, Kreischitz N, Mayer BX, Frossard M, Joukhadar C, Klein N, Lackner E, Muller M. Closed-chest microdialysis to measure antibiotic penetration into human lung tissue. Am J Respir Crit Care Med 2002;165:273–276.n#77$/, http://www.100md.com

    Suzuki T, Yamaya M, Sekizawa K, Hosoda M, Yamada N, Ishizuka S, Yoshino A, Yasuda H, Takahashi H, Nishimura H, et al. Erythromycin inhibits rhinovirus infection in cultured human tracheal epithelial cells. Am J Respir Crit Care Med 2002;165:1113–1118.

    Thomas AQ, Lane K, Phillips J III, Prince M, Markin C, Speer M, Schwartz DA, Gaddipati R, Marney A, Johnson J, et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med 2002;165:1322–1328.z2o?o@u, 百拇医药

    Whitsett JA. Genetic basis of familial interstitial lung disease: misfolding or function of surfactant protein C? Am J Respir Crit Care Med 2002;165:1201–1202.z2o?o@u, 百拇医药

    Nicholson AG, Fulford LG, Colby TV, Du Bois RM, Hansell DM, Wells AU. The relationship between individual histologic features and disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2002;166:173–177.z2o?o@u, 百拇医药

    Ohnishi H, Yokoyama A, Kondo K, Hamada H, Abe M, Nishimura K, Hiwada K, Kohno N. Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med 2002;165:378–381.z2o?o@u, 百拇医药

    Saydain G, Islam A, Afessa B, Ryu JH, Scott JP, Peters SG. Outcome of patients with idiopathic pulmonary fibrosis admitted to the intensive care unit. Am J Respir Crit Care Med 2002;166:839–842.

    Brack T, Jubran A, Tobin MJ. Dyspnea and decreased variability of breathing in patients with restrictive lung disease. Am J Respir Crit Care Med 2002;165:1260–1264.$:[?6r*, 百拇医药

    Koyama S, Sato E, Haniuda M, Numanami H, Nagai S, Izumi T. Decreased level of vascular endothelial growth factor in bronchoalveolar lavage fluid of normal smokers and patients with pulmonary fibrosis. Am J Respir Crit Care Med 2002;166:382–385.$:[?6r*, 百拇医药

    Gauldie J. Inflammatory mechanisms are a minor component of the pathogenesis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2002;165:1205–1206.$:[?6r*, 百拇医药

    Strieter RM. Inflammatory mechanisms are not a minor component of the pathogenesis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2002;165:1206–1207.$:[?6r*, 百拇医药

    Gauldie J. Rebuttal. Am J Respir Crit Care Med 2002;165:1207–1208.$:[?6r*, 百拇医药

    Strieter RM. Rebuttal. Am J Respir Crit Care Med 2002;165:1208.$:[?6r*, 百拇医药

    Kelly BG, Lok SS, Hasleton PS, Egan JJ, Stewart JP. A rearranged form of Epstein-Barr virus DNA is associated with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2002;166:510–513.

    Maus U, Huwe J, Ermert L, Ermert M, Seeger W, Lohmeyer J. Molecular pathways of monocyte emigration into the alveolar air space of intact mice. Am J Respir Crit Care Med 2002;165:95–100.w, 百拇医药

    Conron M, Andreakos E, Pantelidis P, Smith C, Beynon HL, Dubois RM, Foxwell BM. Nuclear factor-{kappa}w, 百拇医药

    B activation in alveolar macrophages requires I{kappa}w, 百拇医药

    B kinase-ß, but not nuclear factor-{kappa}w, 百拇医药

    B inducing kinase. Am J Respir Crit Care Med 2002;165:996–1004.w, 百拇医药

    American Thoracic Society/European Respiratory Society. International multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002;165:277–304.w, 百拇医药

    Crystal RG, Bitterman PB, Mossman B, Schwarz MI, Sheppard D, Almasy L, Chapman HA, Friedman SL, King TE Jr, Leinwand LA, et al. Future research directions in idiopathic pulmonary fibrosis: summary of a National Heart, Lung, and Blood Institute working group. Am J Respir Crit Care Med 2002;166:236–246.

    Bouros D, Wells AU, Nicholson AG, Colby TV, Polychronopoulos V, Pantelidis P, Haslam PL, Vassilakis DA, Black CM, Du Bois RM. Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome. Am J Respir Crit Care Med 2002;165:1581–1586.%, 百拇医药

    King TE Jr. Nonspecific interstitial pneumonia and systemic sclerosis. Am J Respir Crit Care Med 2002;165:1578–1579.%, 百拇医药

    Girgis RE, Gugnani MK, Abrams J, Mayes MD. Partitioning of alveolar and conducting airway nitric oxide in scleroderma lung disease. Am J Respir Crit Care Med 2002;165:1587–1591.%, 百拇医药

    Hutyrova B, Pantelidis P, Drabek J, Zurkova M, Kolek V, Lenhart K, Welsh KI, Du Bois RM, Petrek M. Interleukin-1 gene cluster polymorphisms in sarcoidosis and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2002;165:148–151.%, 百拇医药

    Grutters JC, Sato H, Pantelidis P, Lagan AL, McGrath DS, Lammers JW, van den Bosch JM, Wells AU, Du Bois RM, Welsh KI. Increased frequency of the uncommon tumor necrosis factor-857T allele in British and Dutch patients with sarcoidosis. Am J Respir Crit Care Med 2002;165:1119–1124.

    Capelli A, Di Stefano A, Lusuardi M, Gnemmi I, Donner CF. Increased macrophage inflammatory protein-1{alpha}6*#, 百拇医药

    and macrophage inflammatory protein-1ß levels in bronchoalveolar lavage fluid of patients affected by different stages of pulmonary sarcoidosis. Am J Respir Crit Care Med 2002;165:236–241.6*#, 百拇医药

    Kambouchner M, Basset F, Marchal J, Uhl JF, Hance AJ, Soler P. Three-dimensional characterization of pathologic lesions in pulmonary Langerhans cell histiocytosis. Am J Respir Crit Care Med 2002;166:1483–1490.6*#, 百拇医药

    Myers JL, Aubry MC. Pulmonary Langerhans cell histiocytosis: what was the question? Am J Respir Crit Care Med 2002;166:1419–1421.6*#, 百拇医药

    Kumaki F, Takeda K, Yu ZX, Moss J, Ferrans VJ. Expression of human telomerase reverse transcriptase in lymphangioleiomyomatosis. Am J Respir Crit Care Med 2002;166:187–191.6*#, 百拇医药

    Inoue Y, King TE Jr, Barker E, Daniloff E, Newman LS. Basic fibroblast growth factor and its receptors in idiopathic pulmonary fibrosis and lymphangioleiomyomatosis. Am J Respir Crit Care Med 2002;166:765–773.

    Miyazaki E, Nureki S, Fukami T, Shigenaga T, Ando M, Ito K, Ando H, Sugisaki K, Kumamoto T, Tsuda T. Elevated levels of thymus- and activation-regulated chemokine in bronchoalveolar lavage fluid from patients with eosinophilic pneumonia. Am J Respir Crit Care Med 2002;165:1125–1131.px^0v, 百拇医药

    Philit F, Etienne-Mastroianni B, Parrot A, Guerin C, Robert D, Cordier JF. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med 2002;166:1235–1239.px^0v, 百拇医药

    Du Bois RM. Rare lung diseases: orphans no more? Am J Respir Crit Care Med 2002;166:1157–1158.px^0v, 百拇医药

    Ichikado K, Suga M, Muller NL, Taniguchi H, Kondoh Y, Akira M, Johkoh T, Mihara N, Nakamura H, Takahashi M, et al. Acute interstitial pneumonia: comparison of high-resolution computed tomography findings between survivors and nonsurvivors. Am J Respir Crit Care Med 2002;165:1551–1556.px^0v, 百拇医药

    Hansell DM. Acute interstitial pneumonia: clues from the white stuff. Am J Respir Crit Care Med 2002;165:1465–1466.px^0v, 百拇医药

    Nicholson AG, Wells AU, Hooper J, Hansell DM, Kelleher A, Morgan C. Successful treatment of endogenous lipoid pneumonia due to Niemann-Pick Type B disease with whole-lung lavage. Am J Respir Crit Care Med 2002;165:128–131.

    Kurosu K, Yumoto N, Rom WN, Takiguchi Y, Jaishree J, Nakata K, Tatsumi K, Mikata A, Kuriyama T, Weiden MD. Oligoclonal T cell expansions in pulmonary lymphoproliferative disorders: demonstration of the frequent occurrence of oligoclonal T cells in human immunodeficiency virus-related lymphoid interstitial pneumonia. Am J Respir Crit Care Med 2002;165:254–259.%v]x8, http://www.100md.com

    Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med 2002;166:215–235.%v]x8, http://www.100md.com

    Bhalla KS, Folz RJ. Idiopathic pneumonia syndrome after syngeneic bone marrow transplant in mice. Am J Respir Crit Care Med 2002;166:1579–1589.%v]x8, http://www.100md.com

    Haddad IY. Idiopathic pneumonia after marrow transplantation: when are antioxidants effective? Am J Respir Crit Care Med 2002;166:1532–1534.%v]x8, http://www.100md.com

    Chan ED, Morales DV, Welsh CH, McDermott MT, Schwarz MI. Calcium deposition with or without bone formation in the lung. Am J Respir Crit Care Med 2002;165:1654–1669.%v]x8, http://www.100md.com

    Peters-Golden M, Bailie M, Marshall T, Wilke C, Phan SH, Toews GB, Moore BB. Protection from pulmonary fibrosis in leukotriene-deficient mice. Am J Respir Crit Care Med 2002;165:229–235.

    Zeldin DC. The 5-lipoxygenase pathway: a new therapeutic target for the treatment of pulmonary fibrosis. Am J Respir Crit Care Med 2002;165:146–147.'(y\, http://www.100md.com

    Wang HD, Yamaya M, Okinaga S, Jia YX, Kamanaka M, Takahashi H, Guo LY, Ohrui T, Sasaki H. Bilirubin ameliorates bleomycin-induced pulmonary fibrosis in rats. Am J Respir Crit Care Med 2002;165:406–411.'(y\, http://www.100md.com

    Ghosh S, Mendoza T, Ortiz LA, Hoyle GW, Fermin CD, Brody AR, Friedman M, Morris GF. Bleomycin sensitivity of mice expressing dominant-negative p53 in the lung epithelium. Am J Respir Crit Care Med 2002;166:890–897.'(y\, http://www.100md.com

    Srivastava KD, Rom WN, Jagirdar J, Yie TA, Gordon T, Tchou-Wong KM. Crucial role of interleukin-1beta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice. Am J Respir Crit Care Med 2002;165:527–533.'(y\, http://www.100md.com

    Corbett EL, Mozzato-Chamay N, Butterworth AE, De Cock KM, Williams BG, Churchyard GJ, Conway DJ. Polymorphisms in the tumor necrosis factor-alpha gene promoter may predispose to severe silicosis in black South African miners. Am J Respir Crit Care Med 2002;165:690–693.

    Rossman MD, Stubbs J, Lee CW, Argyris E, Magira E, Monos D. Human leukocyte antigen Class II amino acid epitopes: susceptibility and progression markers for beryllium hypersensitivity. Am J Respir Crit Care Med 2002;165:788–794.rr[8n, 百拇医药

    Wright RS, Abraham JL, Harber P, Burnett BR, Morris P, West P. Fatal asbestosis 50 years after brief high intensity exposure in a vermiculite expansion plant. Am J Respir Crit Care Med 2002;165:1145–1149.rr[8n, 百拇医药

    Rom WN, Weiden M, Garcia R, Yie TA, Vathesatogkit P, Tse DB, McGuinness G, Roggli V, Prezant D. Acute eosinophilic pneumonia in a New York City firefighter exposed to World Trade Center dust. Am J Respir Crit Care Med 2002;166:797–800.rr[8n, 百拇医药

    Beckett WS. A New York City firefighter: overwhelmed by World Trade Center dust. Am J Respir Crit Care Med 2002;166:785–786.rr[8n, 百拇医药

    Monso E, Magarolas R, Badorrey I, Radon K, Nowak D, Morera J. Occupational asthma in greenhouse flower and ornamental plant growers. Am J Respir Crit Care Med 2002;165:954–960.rr[8n, 百拇医药

    Bernstein DI, Cartier A, Cote J, Malo JL, Boulet LP, Wanner M, Milot J, L'Archeveque J, Trudeau C, Lummus Z. Diisocyanate antigen-stimulated monocyte chemoattractant protein-1 synthesis has greater test efficiency than specific antibodies for identification of diisocyanate asthma. Am J Respir Crit Care Med 2002;166:445–450.

    Hendrick DJ. Diagnostic tests for occupational asthma. Am J Respir Crit Care Med 2002;166:436–437.m&{&%x?, 百拇医药

    Eagan TM, Gulsvik A, Eide GE, Bakke PS. Occupational airborne exposure and the incidence of respiratory symptoms and asthma. Am J Respir Crit Care Med 2002;166:933–938.m&{&%x?, 百拇医药

    Hoppin JA, Umbach DM, London SJ, Alavanja MC, Sandler DP. Chemical predictors of wheeze among farmer pesticide applicators in the Agricultural Health Study. Am J Respir Crit Care Med 2002;165:683–689.m&{&%x?, 百拇医药

    Ernst P. Pesticide exposure and asthma. Am J Respir Crit Care Med 2002;165:563–564.m&{&%x?, 百拇医药

    Hoppin FG Jr. How I review an original scientific article. Am J Respir Crit Care Med 2002;166:1019–1023.m&{&%x?, 百拇医药

    Tobin MJ. Rigor of peer review and the standing of a journal. Am J Respir Crit Care Med 2002;166:1013–1014.m&{&%x?, 百拇医药

    Tobin MJ. AJRCCM's policy on duplicate publication: infrequently asked questions. Am J Respir Crit Care Med 2002;166:433–434.m&{&%x?, 百拇医药

    Tobin MJ. The official copy of AJRCCM is posted but not printed. Am J Respir Crit Care Med 2002;166:905–906.m&{&%x?, 百拇医药

    Tobin MJ. Compliance (COMmunicate PLease wIth Less Abbreviations, Noun Clusters, and Exclusiveness). Am J Respir Crit Care Med 2002;166:1534–1536.m&{&%x?, 百拇医药

    Tobin MJ. The Journal in 2002. Am J Respir Crit Care Med 2002;166:1153–1156.(Martin J. Tobin)

    百拇医药网 http://www.100md.com/html/DirDu/2005/05/02/60/73/65.htm