Characterisation of atopic and non-atopic wheeze in 10 year old children
http://www.100md.com
《胸》
The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, Isle of Wight PO30 5TG, UK
Correspondence to:
Dr S H Arshad
The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, Isle of Wight PO30 5TG, UK; sha@soton.ac.uk
Received 16 May 2003
Accepted for publication 7 February 2004
ABSTRACT
Background: Wheezing occurs in both atopic and non-atopic children. The characteristics of atopic and non-atopic wheeze in children at 10 years of age were assessed and attempts made to identify whether different mechanisms underlie these states.
Methods: Children were seen at birth and at 1, 2, 4 and 10 years of age in a whole population birth cohort study (n = 1456; 1373 seen at 10 years). Information was collected prospectively on inherited and early life environmental risk factors for wheezing. Skin prick testing, spirometry, and methacholine bronchial challenge were conducted at 10 years. Wheezing at 10 years of age was considered atopic or non-atopic depending on the results of the skin prick test. Independent significant risk factors for atopic and non-atopic wheeze were determined by logistic regression.
Results: Atopic (10.9%) and non-atopic (9.7%) wheeze were equally common at 10 years of age. Greater bronchial hyperresponsiveness (p<0.001) and airways obstruction (p = 0.011) occurred in children with atopic wheeze than in those with non-atopic wheeze at 10 years. Children with atopic wheeze more often received treatment (p<0.001) or an asthma diagnosis for their disorder, although current morbidity at 10 years differed little for these states. Maternal asthma and recurrent chest infections at 2 years were independently significant factors for developing non-atopic wheeze. For atopic wheeze, sibling asthma, eczema at 1 year, rhinitis at 4 years, and male sex were independently significant.
Conclusions: Non-atopic wheeze is as common as atopic wheeze in children aged 10 years, but treatment is more frequent in those with atopic wheeze. Different risk factor profiles appear relevant to the presence of atopic and non-atopic wheeze at 10 years of age.
Keywords: asthma; atopy; wheeze; children; risk factors
Much attention has focused on the strong association between atopic tendency and childhood wheezing. Causal roles for atopic sensitisation1,2 in the pathogenesis of wheezing and asthma have been postulated as a result of numerous studies showing a higher frequency of asthmatic symptoms in atopic children than in non-atopic children.3–6 Consequently, interventional strategies to prevent atopic sensitisation by allergen avoidance in early life have been applied in an attempt to modify the development of childhood allergy, wheeze, and asthma.7–9 However, these measures have met with mixed results and have not shown definitive lasting benefit.2,7–9 Given such evidence, Pearce et al10 recently questioned the role of atopy as a causative factor in asthma. Indeed, as amply shown by Martinez et al,11 there is growing evidence for the existence of several distinct wheezing phenotypes in childhood, not all of which are closely linked to atopy. Some forms of non-atopic wheeze such as early life transient wheeze have been well characterised,11 with associations with impaired lung function in infancy and maternal smoking. The nature of non-atopic wheeze in later childhood, however, remains unclear. In particular, the significance of such disease in terms of associated morbidity and the similarities or differences of its characteristics with atopic wheezing need confirmation. An understanding of whether different risk factors underlie atopic and non-atopic wheeze in later childhood could also provide fresh insight into the mechanisms underlying childhood wheezing and asthma. Here we describe findings that characterise non-atopic wheeze at 10 years of age and assess whether this differs in risk factor profile from atopic disease. The results were derived from our unselected whole population birth cohort which has been prospectively followed for the first decade of life.
METHODS
A whole population birth cohort was established on the Isle of Wight in 1989 to study prospectively the natural history of childhood wheezing and to identify risk factors relevant to the development of childhood wheezing states. Approval for the study was obtained from the local research ethics committee.
Of 1536 children born between 1 January 1989 and 28 February 1990, informed consent was obtained for 1456 subjects to be enrolled. Enrolment took place at birth and information on family history of allergy (parental or sibling), household pets, parental smoking, social class (Registrar General’s classification), and birth weight were recorded. Children were followed at the ages of 1 (n = 1167; 80.2%), 2 (n = 1174; 80.6%), 4 (n = 1218; 83.7%) and 10 years (n = 1373; 94.3%). The results of cohort follow up at 1, 2, 4, and 10 years of age have been reported previously.12–15 At each follow up detailed questionnaires were completed with the parents for each child regarding the prevalence of asthma and allergy. "Current wheeze" was recorded as having occurred on at least one occasion in the previous 12 months. Exposure to relevant environmental factors (domestic pets and tobacco smoke) was noted. The method of feeding was recorded at 1 and 2 years. A history of recurrent chest infections (more than one in the past year) was assessed at 1 and 2 years of age. Investigators’ diagnoses of eczema (chronic or chronically relapsing, itchy dermatitis lasting more than 6 weeks with characteristic morphology and distribution), recurrent nasal symptoms/rhinitis (recurrent nasal discharge or blockage with attacks of sneezing and itchy eyes), and food allergy (history of vomiting, diarrhoea, colic or rash within 4 hours of ingestion of a particular food on at least two occasions) were made each time. Further additional information was collected at 10 years about disease morbidity. Consultations with a hospital asthma specialist ("specialist referral") were therefore recorded along with hospital admissions for wheezing episodes. Details of asthma treatment "ever used" such as bronchodilators, inhaled corticosteroids, other prophylactic medications (long acting ?2 agonists, sodium cromoglycate, theophyllines, leukotriene antagonists or antihistamines), and oral corticosteroid therapy were also obtained. Several measures of "current wheezing morbidity" (within the preceding 12 months) were recorded at 10 years. These included "wheeze frequency" (number of wheezing episodes), "sleep disturbance from wheezing" (occurring more or less than once per week), "exercise induced wheezing", "limitation of speech by wheezing" (severe enough to limit speech to one or two words between breaths), and "nocturnal cough" (dry cough at night not associated with cold or flu). At 10 years the parents were also asked to report suspected triggers (ever) for their child’s wheezing episodes.
At 10 years of age the questionnaire information was updated in 1373 children.15 Of these, 1043 individuals attended for further tests including skin prick testing (n = 1036), serum IgE measurement (n = 953), baseline spirometry (n = 981), and methacholine bronchial challenge (n = 784).
Skin prick testing was performed to a panel of common inhaled and food allergens (ALK, Denmark) which comprised house dust mite (Dermatophagoides pteronyssinus), grass pollen mix, tree pollen mix, cat and dog epithelia, Alternaria alternata, Cladosporium herbarum, milk, hen’s egg, soya, cod and peanut plus histamine and physiological saline which acted as positive and negative controls, respectively. An allergen skin test reaction with a mean wheal diameter of at least 3 mm more than the negative control was regarded as positive and the subject defined as atopic. Serum was analysed for total IgE and a qualitative inhalant screen (Phadiatop; Pharmacia Diagnostics, Uppsala, Sweden). The inhalant screen tested for common inhalant allergens: house dust mite (D pteronyssinus and D farinae), cat dander, dog dander, horse dander, timothy grass, Cladosporium, silver birch, olive, mugwort, and nettle. All children with past or current wheezing were invited to perform a methacholine bronchial challenge at 10 years to assess bronchial hyperresponsiveness (BHR) using a Koko dosimeter (Pds Instrumentation, Louisville, USA) with compressed air source at 8 l/min and nebuliser output of 0.8 l/min. Initial inhalation of 0.9% saline was followed 1 minute later by spirometric recordings to obtain a baseline value. Incremental concentrations from 0.0625 mg/ml to 16 mg/ml methacholine were then serially administered. The concentration causing a stable fall in forced expiratory volume in 1 second (FEV1) from the post-saline value of 20% was interpolated and expressed as PC20 FEV1. The intention was to perform bronchial challenge whenever possible in all children with wheezing histories plus a control group (n = 300) of children who had never wheezed.
Analysis of data
Data were double entered onto SPSS version 10.0 (SPSS Inc, Chicago, USA). Children were categorised at 10 years of age into the following four groups by the presence of "current wheeze" and atopic status at the 10 year skin prick test: (1) non-atopic non-wheeze; (2) non-atopic wheeze; (3) atopic non-wheeze; and (4) atopic wheeze.
Comparison of continuous variables for atopic and non-atopic wheeze was made (with transformation where necessary) using independent samples t testing. A continuous measure of BHR was estimated as the least square dose-response slope using least square regression of percentage change in FEV1 on methacholine concentration administered for each child. Inverse transformation of the resulting dose-response slope (inverse slope) was used to satisfy normality and homoscedasticity with low values of 1/(10 – slope) extrapolating to high BHR. Interval data were analysed using non-parametric tests (Mann-Whitney U test).
Separate univariate risk factor analysis was conducted to identify risk factors present in early life (the first 4 years) that were associated with either atopic or non-atopic wheeze at 10 years of age. 2 analysis (with Fisher’s exact test where indicated by low expected cell counts) was used for this purpose, comparing factors between the respective wheezing state and that of a non-atopic non-wheezer (common control). To obtain the independent effect of risk factors showing trends for significance at univariate testing (p<0.2), separate logistic regression models were created for atopic and non-atopic wheeze at 10 years. Stepwise backward (likelihood ratio) logistic regression was used for this purpose. Where more than one risk factor could explain a particular exposure of interest, only the most relevant was entered into the model.
RESULTS
At 10 years of age skin prick testing was performed in 1036 subjects (75.5% of 1373). Subjects attending for skin prick testing were more likely to have a personal or family history of allergy than those providing only questionnaire data at 10 years (table 1). The prevalence of atopy—as defined by at least one skin test allergen positive response—was 26.9% (279/1036). Among the atopic children 159 (57.0%) were male. In the 1036 subjects who underwent skin prick tests, current wheeze was present at 10 years in 20.7% (n = 214), atopic wheeze in 10.9% (n = 113), and non-atopic wheeze in 9.7% (n = 101). Among non-wheezers at 10 years, 79.8% (n = 656) were non-atopic and 20.2% (n = 166) were atopic.
Table 1 Characteristics of children at 10 years of age
The median age of onset did not differ between children with atopic and non-atopic wheeze at 10 years (median 2.0 years v 2.0 years; p = 0.954, Mann-Whitney U test). Immunological and lung function characteristics of children with atopic and non-atopic wheeze at 10 years are shown in table 2. Total IgE was significantly higher in the atopic children. Positive IgE inhalant screen was also significantly greater for children with atopic wheeze than for those with non-atopic wheeze (100% v 8.6%; p<0.001). Children with atopic wheeze did not show significantly more impairment of baseline spirometric parameters (FEV1, FVC, or PEF) but they did have significantly more evidence of airways obstruction (FEV1/FVC), lower inverse slope measure of BHR, and a higher prevalence of greater BHR (PC20 FEV1<4.0 mg/ml) than those with non-atopic wheeze (64.5% v 23.1%; p<0.001, OR 6.07 (95% CI 3.25 to 11.34)). These findings did not vary with sex stratification (results not shown).
Table 2 Mean (SE) characteristics of children with atopic and non-atopic wheeze at 10 years of age
Measures of current morbidity at 10 years of age were largely similar for children with atopic and non-atopic wheeze except for sleep disturbance from wheeze (table 3). Similarly, measures that could be regarded as indices of severity—such as hospitalisation for wheezing illness or specialist referral—did not differ significantly between atopic and non-atopic wheeze. Children with atopic wheeze were more likely to have been diagnosed as asthmatic by a physician, treated with regular medications for wheezing, and to have received oral corticosteroids. However, when stratified into social classes, children in higher social classes at 10 years (I–IIInm) who had atopic wheeze were no more likely than those with non-atopic wheeze to be diagnosed as asthmatic (31.3% v 45.2%; p = 0.172; OR 0.55; (95% CI 0.23 to 1.30)) or to have used inhaled corticosteroids (52.1% v 48.8%; p = 0.756; OR 1.14 (95% CI 0.50 to 2.63)). Other patterns of morbidity did not differ by social class and there was also little variation in morbidity/disease severity with sex stratified analysis (results not shown). Boys with atopic wheeze had a higher wheeze frequency than those with non-atopic wheeze (50.7% v 29.2%; p = 0.020; OR 2.50 (95% CI 1.15 to 5.46)) but they had less exercise induced wheeze than non-atopic children (27.8% v 49.0%; OR 0.40 (95% CI 0.19 to 0.85)). Other patterns of morbidity in boys and girls were similar to the overall trends shown in table 3.
Table 3 Morbidity and treatment of children with atopic and non-atopic wheeze at 10 years of age
Figure 1 shows parental reporting of suspected triggers (ever) for their child’s wheezing. Infections, exercise, and stress did not differ significantly in frequency between children with atopic wheeze and those with non-atopic wheeze.
s113–7.(R J Kurukulaaratchy, M Fe)
Correspondence to:
Dr S H Arshad
The David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, Isle of Wight PO30 5TG, UK; sha@soton.ac.uk
Received 16 May 2003
Accepted for publication 7 February 2004
ABSTRACT
Background: Wheezing occurs in both atopic and non-atopic children. The characteristics of atopic and non-atopic wheeze in children at 10 years of age were assessed and attempts made to identify whether different mechanisms underlie these states.
Methods: Children were seen at birth and at 1, 2, 4 and 10 years of age in a whole population birth cohort study (n = 1456; 1373 seen at 10 years). Information was collected prospectively on inherited and early life environmental risk factors for wheezing. Skin prick testing, spirometry, and methacholine bronchial challenge were conducted at 10 years. Wheezing at 10 years of age was considered atopic or non-atopic depending on the results of the skin prick test. Independent significant risk factors for atopic and non-atopic wheeze were determined by logistic regression.
Results: Atopic (10.9%) and non-atopic (9.7%) wheeze were equally common at 10 years of age. Greater bronchial hyperresponsiveness (p<0.001) and airways obstruction (p = 0.011) occurred in children with atopic wheeze than in those with non-atopic wheeze at 10 years. Children with atopic wheeze more often received treatment (p<0.001) or an asthma diagnosis for their disorder, although current morbidity at 10 years differed little for these states. Maternal asthma and recurrent chest infections at 2 years were independently significant factors for developing non-atopic wheeze. For atopic wheeze, sibling asthma, eczema at 1 year, rhinitis at 4 years, and male sex were independently significant.
Conclusions: Non-atopic wheeze is as common as atopic wheeze in children aged 10 years, but treatment is more frequent in those with atopic wheeze. Different risk factor profiles appear relevant to the presence of atopic and non-atopic wheeze at 10 years of age.
Keywords: asthma; atopy; wheeze; children; risk factors
Much attention has focused on the strong association between atopic tendency and childhood wheezing. Causal roles for atopic sensitisation1,2 in the pathogenesis of wheezing and asthma have been postulated as a result of numerous studies showing a higher frequency of asthmatic symptoms in atopic children than in non-atopic children.3–6 Consequently, interventional strategies to prevent atopic sensitisation by allergen avoidance in early life have been applied in an attempt to modify the development of childhood allergy, wheeze, and asthma.7–9 However, these measures have met with mixed results and have not shown definitive lasting benefit.2,7–9 Given such evidence, Pearce et al10 recently questioned the role of atopy as a causative factor in asthma. Indeed, as amply shown by Martinez et al,11 there is growing evidence for the existence of several distinct wheezing phenotypes in childhood, not all of which are closely linked to atopy. Some forms of non-atopic wheeze such as early life transient wheeze have been well characterised,11 with associations with impaired lung function in infancy and maternal smoking. The nature of non-atopic wheeze in later childhood, however, remains unclear. In particular, the significance of such disease in terms of associated morbidity and the similarities or differences of its characteristics with atopic wheezing need confirmation. An understanding of whether different risk factors underlie atopic and non-atopic wheeze in later childhood could also provide fresh insight into the mechanisms underlying childhood wheezing and asthma. Here we describe findings that characterise non-atopic wheeze at 10 years of age and assess whether this differs in risk factor profile from atopic disease. The results were derived from our unselected whole population birth cohort which has been prospectively followed for the first decade of life.
METHODS
A whole population birth cohort was established on the Isle of Wight in 1989 to study prospectively the natural history of childhood wheezing and to identify risk factors relevant to the development of childhood wheezing states. Approval for the study was obtained from the local research ethics committee.
Of 1536 children born between 1 January 1989 and 28 February 1990, informed consent was obtained for 1456 subjects to be enrolled. Enrolment took place at birth and information on family history of allergy (parental or sibling), household pets, parental smoking, social class (Registrar General’s classification), and birth weight were recorded. Children were followed at the ages of 1 (n = 1167; 80.2%), 2 (n = 1174; 80.6%), 4 (n = 1218; 83.7%) and 10 years (n = 1373; 94.3%). The results of cohort follow up at 1, 2, 4, and 10 years of age have been reported previously.12–15 At each follow up detailed questionnaires were completed with the parents for each child regarding the prevalence of asthma and allergy. "Current wheeze" was recorded as having occurred on at least one occasion in the previous 12 months. Exposure to relevant environmental factors (domestic pets and tobacco smoke) was noted. The method of feeding was recorded at 1 and 2 years. A history of recurrent chest infections (more than one in the past year) was assessed at 1 and 2 years of age. Investigators’ diagnoses of eczema (chronic or chronically relapsing, itchy dermatitis lasting more than 6 weeks with characteristic morphology and distribution), recurrent nasal symptoms/rhinitis (recurrent nasal discharge or blockage with attacks of sneezing and itchy eyes), and food allergy (history of vomiting, diarrhoea, colic or rash within 4 hours of ingestion of a particular food on at least two occasions) were made each time. Further additional information was collected at 10 years about disease morbidity. Consultations with a hospital asthma specialist ("specialist referral") were therefore recorded along with hospital admissions for wheezing episodes. Details of asthma treatment "ever used" such as bronchodilators, inhaled corticosteroids, other prophylactic medications (long acting ?2 agonists, sodium cromoglycate, theophyllines, leukotriene antagonists or antihistamines), and oral corticosteroid therapy were also obtained. Several measures of "current wheezing morbidity" (within the preceding 12 months) were recorded at 10 years. These included "wheeze frequency" (number of wheezing episodes), "sleep disturbance from wheezing" (occurring more or less than once per week), "exercise induced wheezing", "limitation of speech by wheezing" (severe enough to limit speech to one or two words between breaths), and "nocturnal cough" (dry cough at night not associated with cold or flu). At 10 years the parents were also asked to report suspected triggers (ever) for their child’s wheezing episodes.
At 10 years of age the questionnaire information was updated in 1373 children.15 Of these, 1043 individuals attended for further tests including skin prick testing (n = 1036), serum IgE measurement (n = 953), baseline spirometry (n = 981), and methacholine bronchial challenge (n = 784).
Skin prick testing was performed to a panel of common inhaled and food allergens (ALK, Denmark) which comprised house dust mite (Dermatophagoides pteronyssinus), grass pollen mix, tree pollen mix, cat and dog epithelia, Alternaria alternata, Cladosporium herbarum, milk, hen’s egg, soya, cod and peanut plus histamine and physiological saline which acted as positive and negative controls, respectively. An allergen skin test reaction with a mean wheal diameter of at least 3 mm more than the negative control was regarded as positive and the subject defined as atopic. Serum was analysed for total IgE and a qualitative inhalant screen (Phadiatop; Pharmacia Diagnostics, Uppsala, Sweden). The inhalant screen tested for common inhalant allergens: house dust mite (D pteronyssinus and D farinae), cat dander, dog dander, horse dander, timothy grass, Cladosporium, silver birch, olive, mugwort, and nettle. All children with past or current wheezing were invited to perform a methacholine bronchial challenge at 10 years to assess bronchial hyperresponsiveness (BHR) using a Koko dosimeter (Pds Instrumentation, Louisville, USA) with compressed air source at 8 l/min and nebuliser output of 0.8 l/min. Initial inhalation of 0.9% saline was followed 1 minute later by spirometric recordings to obtain a baseline value. Incremental concentrations from 0.0625 mg/ml to 16 mg/ml methacholine were then serially administered. The concentration causing a stable fall in forced expiratory volume in 1 second (FEV1) from the post-saline value of 20% was interpolated and expressed as PC20 FEV1. The intention was to perform bronchial challenge whenever possible in all children with wheezing histories plus a control group (n = 300) of children who had never wheezed.
Analysis of data
Data were double entered onto SPSS version 10.0 (SPSS Inc, Chicago, USA). Children were categorised at 10 years of age into the following four groups by the presence of "current wheeze" and atopic status at the 10 year skin prick test: (1) non-atopic non-wheeze; (2) non-atopic wheeze; (3) atopic non-wheeze; and (4) atopic wheeze.
Comparison of continuous variables for atopic and non-atopic wheeze was made (with transformation where necessary) using independent samples t testing. A continuous measure of BHR was estimated as the least square dose-response slope using least square regression of percentage change in FEV1 on methacholine concentration administered for each child. Inverse transformation of the resulting dose-response slope (inverse slope) was used to satisfy normality and homoscedasticity with low values of 1/(10 – slope) extrapolating to high BHR. Interval data were analysed using non-parametric tests (Mann-Whitney U test).
Separate univariate risk factor analysis was conducted to identify risk factors present in early life (the first 4 years) that were associated with either atopic or non-atopic wheeze at 10 years of age. 2 analysis (with Fisher’s exact test where indicated by low expected cell counts) was used for this purpose, comparing factors between the respective wheezing state and that of a non-atopic non-wheezer (common control). To obtain the independent effect of risk factors showing trends for significance at univariate testing (p<0.2), separate logistic regression models were created for atopic and non-atopic wheeze at 10 years. Stepwise backward (likelihood ratio) logistic regression was used for this purpose. Where more than one risk factor could explain a particular exposure of interest, only the most relevant was entered into the model.
RESULTS
At 10 years of age skin prick testing was performed in 1036 subjects (75.5% of 1373). Subjects attending for skin prick testing were more likely to have a personal or family history of allergy than those providing only questionnaire data at 10 years (table 1). The prevalence of atopy—as defined by at least one skin test allergen positive response—was 26.9% (279/1036). Among the atopic children 159 (57.0%) were male. In the 1036 subjects who underwent skin prick tests, current wheeze was present at 10 years in 20.7% (n = 214), atopic wheeze in 10.9% (n = 113), and non-atopic wheeze in 9.7% (n = 101). Among non-wheezers at 10 years, 79.8% (n = 656) were non-atopic and 20.2% (n = 166) were atopic.
Table 1 Characteristics of children at 10 years of age
The median age of onset did not differ between children with atopic and non-atopic wheeze at 10 years (median 2.0 years v 2.0 years; p = 0.954, Mann-Whitney U test). Immunological and lung function characteristics of children with atopic and non-atopic wheeze at 10 years are shown in table 2. Total IgE was significantly higher in the atopic children. Positive IgE inhalant screen was also significantly greater for children with atopic wheeze than for those with non-atopic wheeze (100% v 8.6%; p<0.001). Children with atopic wheeze did not show significantly more impairment of baseline spirometric parameters (FEV1, FVC, or PEF) but they did have significantly more evidence of airways obstruction (FEV1/FVC), lower inverse slope measure of BHR, and a higher prevalence of greater BHR (PC20 FEV1<4.0 mg/ml) than those with non-atopic wheeze (64.5% v 23.1%; p<0.001, OR 6.07 (95% CI 3.25 to 11.34)). These findings did not vary with sex stratification (results not shown).
Table 2 Mean (SE) characteristics of children with atopic and non-atopic wheeze at 10 years of age
Measures of current morbidity at 10 years of age were largely similar for children with atopic and non-atopic wheeze except for sleep disturbance from wheeze (table 3). Similarly, measures that could be regarded as indices of severity—such as hospitalisation for wheezing illness or specialist referral—did not differ significantly between atopic and non-atopic wheeze. Children with atopic wheeze were more likely to have been diagnosed as asthmatic by a physician, treated with regular medications for wheezing, and to have received oral corticosteroids. However, when stratified into social classes, children in higher social classes at 10 years (I–IIInm) who had atopic wheeze were no more likely than those with non-atopic wheeze to be diagnosed as asthmatic (31.3% v 45.2%; p = 0.172; OR 0.55; (95% CI 0.23 to 1.30)) or to have used inhaled corticosteroids (52.1% v 48.8%; p = 0.756; OR 1.14 (95% CI 0.50 to 2.63)). Other patterns of morbidity did not differ by social class and there was also little variation in morbidity/disease severity with sex stratified analysis (results not shown). Boys with atopic wheeze had a higher wheeze frequency than those with non-atopic wheeze (50.7% v 29.2%; p = 0.020; OR 2.50 (95% CI 1.15 to 5.46)) but they had less exercise induced wheeze than non-atopic children (27.8% v 49.0%; OR 0.40 (95% CI 0.19 to 0.85)). Other patterns of morbidity in boys and girls were similar to the overall trends shown in table 3.
Table 3 Morbidity and treatment of children with atopic and non-atopic wheeze at 10 years of age
Figure 1 shows parental reporting of suspected triggers (ever) for their child’s wheezing. Infections, exercise, and stress did not differ significantly in frequency between children with atopic wheeze and those with non-atopic wheeze.
s113–7.(R J Kurukulaaratchy, M Fe)