Bronchial hyperresponsiveness and adult onset wheeze: the influence of atopy.

The commonly held belief that adult onset wheezing illness is primarily nonatopic in nature suggests that the role of atopy in the pathophysiology of bronchial hyperresponsiveness (BHR) in adult onset wheeze may be minimal. This study examined risk factors for BHR (BHR: provocative dose causing a 20% fall in forced expiratory volume in one second PD20 < or =16.38 micromol methacholine) among 82 subjects with adult onset wheeze and among 191 subjects who had never wheezed. Subjects were identified from a cohort of subjects aged 39-45 yrs who were known to have had no childhood wheeze and who were involved in a 30 yr follow-up survey. Risk factors for BHR were examined among all subjects with BHR and among subjects with BHR stratified according to whether or not they had ever wheezed. The prevalence of BHR was 40% (33/82) among the subjects with adult onset wheeze and 11% (21/191) among the subjects who had never wheezed. Lower baseline lung function (odds ratio (OR) = 0.94; 95% confidence interval (CI) = 0.92-0.97 per unit forced expiratory volume (FEV1)% predicted) and atopy (OR = 7.23; CI = 2.53-20.64 for all three measures of atopic compared to nonatopic) were associated with BHR, while smoking and family history showed no statistically significant relation to BHR. This pattern was also apparent in analyses stratified by symptom status. A family history of atopy increased the risk that BHR was accompanied by wheezing symptoms (OR = 4.75; CI = 1.53-14.72 for more than one affected relative compared to no affected relatives). These findings suggest that atopy is associated with bronchial hyperresponsiveness in adults known to have had no childhood wheeze. A familial factor reflecting genetic influences and/or shared environmental factors may influence whether bronchial hyperresponsiveness is associated with symptoms.     

Assessing bronchial responsiveness to hypertonic saline using the stepwise protocol of Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC II)

Measurement of bronchial responsiveness to hypertonic saline was applied in 22 study centers worldwide as part of Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC Phase Two). Because the amount of inhaled saline was difficult to standardize during the stepwise protocol with inhalation periods of increasing duration, we evaluated different statistical procedures based on inhalation time in relation to wheeze and current asthma. Data on random samples on 9 to 11-year-old children (n = 1,418) from two German centers were analyzed. The following statistical approaches were evaluated: (1) bronchial hyperreactivity (BHR) defined dichotomously as a fall in FEV1 (forced expiratory volume in 1 s) >or=15%; (2) PT15: the provocation time causing BHR using survival-analyses methods; (3) time-response-slope (continuous) of the individual FEV1-courses calculated by a linear model after comparing different mathematical models. The sensitivity and specificity of BHR versus current asthma were 47% and 87%, respectively. Analyses of the provocation time indicated an increased risk (adjusted hazard-ratio: 4.3; 95% CI: 2.8-6.5) for a fall in FEV1 >or= 15% among children with current asthma in comparison to those without. The time-response-slope differed markedly between children with and without wheeze and current asthma (P < 0.0001). BHR is meaningful and relatively easy to use, but has low sensitivity. Time-response-slopes utilize the available information from the stepwise protocol better than BHR and survival-analysis based on PT15. Response parameters based on inhalation time discriminate well between children with and without asthma and will be compared in the analyses of ISAAC Phase Two data.     

Individual allergens as risk factors for asthma and bronchial hyperresponsiveness in Chinese children.

The role of allergen sensitization in the development of asthma in the Chinese is not clear. This study aims to determine the relationship of sensitization to individual allergens, and the development of asthma and bronchial hyperresponsiveness (BHR) in schoolchildren from three Chinese cities: Hong Kong, Beijing and Guangzhou. Community-based random samples of 10-yr-old schoolchildren from three Chinese cities were recruited for study using the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Subjects were studied by parental questionnaires (n=10,902), skin-prick tests (n=3,479), and methacholine challenge tests (n=608). The prevalence rates of wheeze in the past 12 months (Hong Kong, 5.8%; Beijing, 3.8%; Guangzhou, 3.4%) and atopy (Hong Kong, 41.2%; Beijing, 23.9%; Guangzhou, 30.8%) were highest in schoolchildren from Hong Kong. Multivariate logistic regression analyses revealed that sensitization to Dermatophagoides pteronyssinus (odds ratio (OR)=4.48; 95% confidence interval (CI): 3.02-6.66), cat (2.59; 1.67-4.03), Dermatophagoides farinae (2.41; 1.65-3.51) and mixed grass pollen (2.85; 1.24-6.50) were significantly associated with current wheeze. Atopy, defined as having > or = 1 positive skin-prick tests, was not an independent risk factor for current wheeze in children from any of the three cities. Furthermore, atopy (OR=2.53; 95% CI: 1.07-5.97), sensitization to cat (3.01; 1.39-6.52) and D. farinae (3.67; 1.93-6.97) were significantly associated with BHR. The authors confirmed that sensitization to house dust mite and cat was significantly associated with current wheeze and bronchial hyperresponsiveness in Chinese schoolchildren. However, the difference in the prevalence rate of atopic sensitization cannot explain the higher prevalence of childhood asthma in Hong Kong, when compared with those children from Beijing and Guangzhou.     

Toward a definition of asthma for epidemiology.

Because there is no "gold standard" for defining asthma for epidemiology, we have defined current asthma as bronchial hyperresponsiveness (BHR) plus recent wheeze (in the 12 months prior to study). To describe the characteristics of groups categorized by these measurements, we studied two samples of children aged 7 to 12 yr: 210 from a population sample and 142 self-identified asthmatics. Bronchial responsiveness to histamine was measured by the rapid method, respiratory symptom history, and asthma medication use by self-administered questionnaire to parents and atopy by skin prick tests to 14 allergens. Children recorded daily Airflometer readings and symptom scores for 2 wk. Children with current asthma had more severe bronchial responsiveness, greater Airflometer variability, more symptoms, more atopy (particularly to house dust mites), and used more asthma medication than children with BHR or recent wheeze alone. Children with BHR, but not with recent wheeze, were intermediate between the current asthma and normal groups in terms of bronchial responsiveness, Airflometer variability, and atopy. Children with recent wheeze and normal responsiveness differed from the normal group only in symptoms and medication use. Our definition of current asthma discriminates a group of children that is clearly different in terms of both clinical features and physiologic measures. As such, it is the most useful definition to date for measuring the prevalence of clinically important asthma in populations.     

A birth cohort study of subjects at risk of atopy: twenty-two-year follow-up of wheeze and atopic status.

This study describes the natural history of atopic and wheezy disorders from birth to adult life in a cohort at risk of atopy. One hundred subjects born in Poole, England, were selected at birth in 1976 on the basis that at least one parent was atopic. Subjects were examined annually in the preschool years, and at the ages of 11 and 22 yr. Skin prick tests and total serum immunoglobulin E (IgE) were performed at each visit, and at 11 and 22 yr, bronchial hyperresponsiveness (BHR) to inhaled histamine was measured. Sixty-three subjects remained on follow-up at 22 yr. The annual prevalence of both wheeze and atopy increased with age. Twenty-five percent of adults showed both wheeze and BHR (asthma). Remission of wheeze was common in subjects younger than 5 yr of age and likely if wheezing occurred on less than two occasions, but wheeze at 11 yr was likely to persist. Sixty percent of the adult subjects with asthma developed sensitivity to common allergens by the age of 2 yr and were showing BHR by mid-childhood. Sensitization to dietary allergens occurred in infancy and waned after early childhood but predicted the early sensitization to inhalant allergens. In conclusion, adults with asthma can begin wheezing at any age but tend to sensitize early and have abnormal airway characteristics by the age of 11 yr.     

Symptoms, lung function, and beta2-adrenoceptor polymorphisms in a birth cohort followed for 10 years

As little is known about the natural history of bronchial responsiveness and the development of wheezing symptoms in early childhood, a cohort of children at risk of allergy, whose lung function and bronchial responsiveness had been measured in the neonatal period, was followed prospectively for 10 (SD, 0.8) years in order to determine the role of neonatal measurements on wheezing history and later lung function. A potential role for beta-2 adrenoceptor (beta2AR) polymorphisms in these relationships was also sought as a secondary objective. Of the original 73 children, wheezing history was available in 65 (89%), and 49 (67%) attended the laboratory for physiological measurements and genotyping of beta2AR. Wheezing was categorized as occurring 1) only before the fourth birthday, 2) after the fourth birthday, or 3) never. No relation was seen between neonatal and later lung function. However, neonatal bronchial responsiveness predicted subsequent FEV1 (P = 0.03). Increased neonatal bronchial responsiveness was associated with transient wheeze <4 years but not with later wheeze. Neonatal V'maxFRC was reduced in those possessing Gln27 or Arg16 alleles, but there was no effect of beta2AR polymorphisms on FEV1 at 10 years. Wheeze after 4 years of age was typical of classical asthma, as it was strongly related to atopy and bronchial responsiveness at age 10. In conclusion, we confirmed the association of neonatal bronchial responsiveness with both early wheezing and later lung function. We also showed an influence of polymorphisms at both aa16 and aa27 on neonatal lung function. Wheezing beyond 4 years, typical of classical asthma, was unrelated to early measurements of lung function or bronchial responsiveness.     

The interrelationship among bronchial hyperresponsiveness, the diagnosis of asthma, and asthma symptoms

Bronchial hyperresponsiveness (BHR) to inhaled histamine has often been cited as the gold standard in asthma diagnosis, but recently this has been questioned. This report assesses the relationship of BHR to asthma symptoms and asthma diagnosis in a large community-based sample of children. A total of 2,053 children 7 to 10 yr of age were randomly sampled from Auckland primary schools and assessed by a questionnaire and histamine inhalation challenge. In all, 14.3% had had asthma diagnosed, 29.6% reported having had one of the four respiratory symptoms in in the previous 12 months, and 15.9% had BHR (PD20 less than or equal to 7.8 mumol histamine). After a cumulative dose of 3.9 mumol histamine, the percent change in FEV1 from postsaline FEV1 was unimodally distributed, with those in whom asthma had been diagnosed dominating the severe end of the spectrum. However, 53% of those with BHR had no asthma diagnosis, and 41% had no current asthma symptoms. On the other hand, 48% of all subjects with diagnosed asthma and 42% of children with diagnosed asthma and current symptoms did not have BHR. Although severity of BHR tended to increase with wheezing frequency, all grades of severity (including no BHR) were found for any given frequency of wheeze. An existing diagnosis of asthma identified symptomatic children more accurately than did BHR, regardless of the criteria used for BHR or for "symptomatic" and irrespective of ethnic group. In conclusion, BHR is related to, but not identical to, clinical asthma. Bronchial challenge testing is an important tool of respiratory research, but cannot reliably or precisely separate asthmatics from nonasthmatics in the general community.     

Maternal use of folic acid supplements during pregnancy, and childhood respiratory health and atopy

Previous studies have suggested possible adverse side-effects of maternal use of folic acid-containing supplements (FACSs) during pregnancy on wheeze and asthma in early childhood. We investigated the association between maternal use of FACSs and childhood respiratory health and atopy in the first 8 yrs of life. Data on maternal use of FACSs, collected during pregnancy, were available for 3,786 children participating in the Prevention and Incidence of Asthma and Mite Allergy birth cohort study. Questionnaire data on children's respiratory and allergic symptoms were collected annually and allergic sensitisation and bronchial hyperresponsiveness (BHR) were measured at 8 yrs of age. No overall (from 1 to 8 yrs of age) associations were observed between maternal use of FACSs and (frequent) asthma symptoms, wheeze, lower respiratory tract infection, frequent respiratory tract infection and eczema. Maternal folic acid use was associated with wheeze at 1 yr of age (prevalence ratio 1.20, 95% CI 1.04-1.39), but not with wheeze at later ages. Pre-natal exposure to FACSs was not associated with sensitisation and BHR. Apart from a small increased risk of early wheeze, we observed no adverse respiratory or allergic outcomes associated with pre-natal FACSs exposure in our study population.     

Early life risk factors for current wheeze, asthma, and bronchial hyperresponsiveness at 10 years of age

STUDY OBJECTIVES: We sought to identify early life factors (ie, first 4 years) associated with wheeze, asthma, and bronchial hyperresponsiveness (BHR) at age 10 years, comparing their relative influence for these conditions. METHODS: Children were seen at birth, and at 1, 2, 4, and 10 years of age in a whole-population birth cohort study (1,456 subjects). Information was collected prospectively on genetic and environmental risk factors. Skin-prick testing was performed at 4 years of age. Current wheeze (in the last 12 months) and currently diagnosed asthma (CDA) [ie, current wheeze and ever-diagnosed asthmatic subject] were recorded at 10 years of age when BHR was measured at bronchial challenge. Independent significant risk factors for these outcomes were identified by logistic regression. RESULTS: Independent significance for current wheeze occurred with maternal asthma (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.27 to 3.41) and paternal asthma (OR, 2.12; 95% CI 1.29 to 3.51), recurrent chest infections at 2 years (OR, 3.98; 95% CI, 2.36 to 6.70), atopy at 4 years of age (OR, 3.69; 95% CI, 2.36 to 5.76), eczema at 4 years of age (OR, 2.15; 95% CI, 1.24 to 3.73), and parental smoking at 4 years of age (OR, 2.18; 95% CI, 1.25 to 3.81). For CDA, significant factors were maternal asthma (OR, 2.26; 95% CI, 1.24 to 3.73), paternal asthma (OR, 2.30; 95% CI, 1.17 to 4.52), and sibling asthma (OR, 2.00; 95% CI, 1.16 to 3.43), recurrent chest infections at 1 year of age (OR, 2.67; 95% CI, 1.12 to 6.40) and 2 years of age (OR, 4.11; 95% CI, 2.06 to 8.18), atopy at 4 years of age (OR, 7.22; 95% CI, 4.13 to 12.62), parental smoking at 1 year of age (OR, 1.99; 95% CI, 1.15 to 3.45), and male gender (OR, 1.72; 95% CI, 1.01 to 2.95). For BHR, atopy at 4 years of age (OR, 5.38; 95% CI, 3.06 to 9.47) and high social class at birth (OR, 2.03; 95% CI, 1.16 to 3.53) proved to be significant. CONCLUSIONS: Asthmatic heredity, predisposition to early life atopy, plus early passive smoke exposure and recurrent chest infections are important influences for the occurrence of wheeze and asthma at 10 years of age. BHR at 10 years of age has a narrower risk profile, suggesting that factors influencing wheezing symptom expression may differ from those predisposing the patient to BHR.     

Serum eosinophil cationic protein (S-ECP) in a population with low prevalence of atopy

The study is a part of the European Community Respiratory Health Survey. A random sample (n = 351) of 20-44-year olds and persons of the same age with asthma-like symptoms or current asthma medication according to a postal questionnaire (n = 95) were studied. Interview was taken, methacholine challenge was done and ECP, total and specific IgE were measured from serum. The median S-ECP value was 8.0 micrograms/l in the random sample. The geometric mean of S-ECP was higher in subjects with, than without atopy (10.2 vs 8.9 micrograms/l, P < 0.01) and in subjects with bronchial hyperresponsiveness (BHR) than in subjects without BHR (9.9 vs 8.0 micrograms/l, P < 0.01). The levels correlated weakly to forced expiratory volume in one second (FEV1) (r = 0.13, P < 0.01) and were not independently correlated with respiratory symptoms, asthma or FEV1 after adjusting for BHR, IgE, sensitisation and smoking. Our results indicate that the level of eosinophil activation is low in a population with a low prevalence of atopy, even when BHR is common.     

Asthma survey items as predictors of respiratory problems in children 2 yrs later: a longitudinal study.

The study compared the ability of characteristics defined by an asthma survey (wheeze versus cough and asthma diagnosis versus no diagnosis) to predict later respiratory problems in a cohort of 108 schoolchildren who had reported either recent wheeze or recurrent cough in a 1987 asthma survey. The children recorded daily respiratory symptoms and peak flow from April 1989 until May 1990. The frequency and severity of lower respiratory symptom episodes and peak flow dips were compared in the wheeze and cough groups and in the diagnosed versus nondiagnosed children. The independent effects of initial wheeze, atopy, diagnosis and bronchial hyperresponsiveness (BHR) on the longitudinal outcome measures were assessed using multiple linear regression. Children with initial wheeze had more chronic symptoms and peak flow variability than those with cough alone, but wheeze had only a weak effect on frequency and severity of acute lower respiratory episodes. Children with both wheeze and atopy had more acute symptomatic episodes and more chronic symptoms than did the other children. Children with diagnosed asthma (versus no diagnosis) had significantly more frequent and severe lower respiratory exacerbations, more days symptomatic and greater peak flow variability. The predictive effects of diagnosis were independent of (and stronger than the effects of) wheeze, atopy and BHR, or combinations of these variables. The results suggest that among children who report respiratory symptoms, survey-reported wheeze on its own is a weaker marker of significant respiratory disease than is a doctor's diagnosis of asthma.     

Risk factors for asthma among young adults in Melbourne, Australia

Abstract Asthma is more prevalent in Australia than in Europe or North America. As part of the European Community Respiratory Health Survey (ECRHS), we investigated exposure to risk factors for asthma among young adults in Melbourne. During this study, 553 randomly selected and 204 symptomatic participants aged between 20 and 44 years completed a detailed respiratory questionnaire, of whom 675 underwent measurement of bronchial hyperreactivity (BHR) by methacholine challenge and 745 had skin prick tests for atopy. Current asthma, defined as BHR and wheeze in the preceding 12 months, was present in 25.5% of those tested. A family history of asthma was a risk factor for current asthma (maternal asthma odds ratio [OR] 2.4, paternal asthma OR 2.1). Current smokers were 1.7 times more likely to have current asthma. A serious respiratory infection before 5 years of age increased the risk of current asthma 2.3-fold. Atopy on skin testing was also strongly associated with current asthma (OR 5.9). The greatest risks were associated with positive skin tests to Cladosporium , house dust mite, cat and rye grass pollen. We conclude that female gender, maternal asthma, smoking, hayfever, early respiratory infection, occupational exposure and atopy are important risk factors for asthma in young adults.     

Bronchial hyperresponsiveness to 4.5% hypertonic saline indicates a past history of asthma-like symptoms in children

SUMMARY. To evaluate the importance of a past history of asthma-like symptoms over a period of 2 years and current bronchial hyperreactivity (BHR), 538 randomly selected schoolchildren, initially aged 7-8 years, were examined. At yearly intervals, three standardized questionnaires, including items from the ISAAC panel, were answered by parents. Following the last questionnaire, BHR to 4.5% hypertonic saline (HS) was recorded. In survey 1, lifetime prevalence of asthma was 4.9%. During the 12-month period, prevalence of wheeze and dyspnea ranged between 9.3 and 5.2% (Survey 1) and 5.9% and 4.4% (Survey 2). Among children with wheeze or dyspnea in Survey 3, BHR (defined as a fall of baseline FEV(1) > or = 15%) was significantly more frequent (50.0% and 60.7%, respectively) than among children without these symptoms (12.8%, P < 0.001, and 12.8%, P < 0.001, respectively). The negative predictive value of BHR to have neither wheeze nor dyspnea was about 88% and did not vary throughout the study (Survey 1, 87%; Survey 2, 88%; Survey 3, 88%). The relative risk of showing BHR was significantly increased in children with wheeze (survey 2, odds ratio (OR) 3.0 (95% confidence interval (CI) 1.0-8.7)) or dyspnea (Survey 1: OR 5.9 (95% CI 1.9-18.5), Survey 3: 5.2 (1.7-16.2), but not in children with dry cough or nocturnal cough (data not shown). Wheeze and dyspnea occurred repeatedly in the same individuals with BHR in a high percentage of children (83.3% and 76.5%, respectively). In conclusion, there is a strong association between recent and previous dyspnea and current BHR, and it indicates intraindividual persistence of symptom history.     

Comparison of percentage fall in FVC at the provocative concentration of methacholine causing a 20% fall in FEV(1) between patients with asymptomatic bronchial hyperresponsiveness and mild asthma

BACKGROUND: A significant proportion of individuals who have no symptoms of asthma or other respiratory diseases show bronchial hyperresponsiveness (BHR). BHR is usually assessed by measuring the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)). The percentage fall in FVC at the PC(20) (DeltaFVC) has been suggested to reflect maximal airway response and to be a more useful index of disease severity in asthma than PC(20). The aim of this study was to investigate whether asymptomatic BHR would differ from symptomatic BHR with regard to DeltaFVC. METHODS: Methacholine bronchial challenge tests were conducted in children with no past or current symptoms of asthma, allergic rhinitis, or other respiratory diseases, who were identified among siblings of children with asthma. Forty-three children with asymptomatic BHR (PC(20) < 16 mg/mL) were recruited, and 43 children with mild asthma who were matched for age, sex, and PC(20) were selected (mild asthma group). The DeltaFVC on methacholine concentration-response curves was retrospectively analyzed in the two groups. RESULTS: There were no differences in the frequency of atopy, blood eosinophil counts, serum IgE levels, and spirometric values between the asymptomatic BHR and mild asthma groups. Mean (+/- SD) DeltaFVC was significantly (p = 0.005) lower in the asymptomatic BHR group (14.5 +/- 3.6%) than in the mild asthma group (16.9 +/- 4.3%). CONCLUSIONS: Our results suggest that children with asymptomatic BHR have a lower level of maximal airway response than mild asthmatics with a similar degree of BHR. This may be a possible explanation for the lack of symptoms in subjects with asymptomatic BHR.     

Asthma in the vicinity of power stations: I. A prevalence study.

Respiratory symptoms, atopy, and bronchial reactivity were measured in primary school children living in Lake Munmorah (LM), a coastal town near two power stations, and in Nelson Bay (NB), a coastal town free from any possible major sources of outdoor air pollution. A prevalence survey and longitudinal follow-up study were performed 1 year apart. In both studies, the prevalence of ever wheezed, current wheezing, breathlessness, wheezing with exercise, diagnosed asthma, and use of drugs for asthma at LM were all approximately double the prevalence at NB (all P values less than 0.01). The prevalence of bronchial reactivity was significantly greater at LM than NB (P less than 0.01) at the first but not the second survey. By contrast, no significant differences were found between the two areas for skin test atopy or for parental history of allergic disease. Multivariate analysis supported the conclusion from the univariate analysis that there was more wheezing at LM compared to NB at both studies, when adjusted for atopy, smoking in the home, age, and sex. As expected, a positive skin test reaction to house dust mite was the predominant explanatory variable. Asthma was more common in the community near power stations (LM) than in the NB area. The absence of significant differences in skin test atopy and parental history of allergic disease argued against major genetic differences between the two groups. By contrast, the more common reporting of siblings' chest disease and asthma in Lake Munmorah supported an environmental cause.     

中国儿童呼吸道及特应性疾病患病情况调查

目的 由于支气管哮喘(简称哮喘)是一种特应性疾病，且世界各地患病率差异很大，我们对北京、广州、香港三地儿童的呼吸道疾病及特应性疾病进行了比较，以确定特应性在哮喘发生中的作用。方法在北京、广州、香港三城市的9～11岁儿童中随机抽样，应用国际儿童哮喘和过敏性疾病研究(ISAAC)第二阶段问卷，由10902名儿童的父母回答问卷并对3479名儿童进行皮肤检查及皮肤变应原点刺检查。结果近年喘息、重度喘息(说话受限)、鼻(眼)结膜炎及肢体弯曲处皮炎的患病率，香港显高于北京及广州。特应性发生率香港地区(41．2％)也高于北京(23．9％)和广州(30．8％)。表明特应性与近年喘息高度相关(0R=7．74，95％CI=5．70～10．51)。对香港地区人群进一步分析发现，由内地移居香港的儿童，其过敏症状及特应性发生率显低于香港地区出生儿童。结论香港地区学龄儿童哮喘、变态反应性疾病患病率、特应性发生率最高。特应性是中国儿童哮喘发病的重要因素。     

Candidate genetic polymorphisms for asthma in Chinese schoolchildren from Hong Kong.

BACKGROUND: Polymorphisms in several genes have been associated with asthma, atopy and bronchial hyperresponsiveness in white and Japanese populations. In this study we tested for associations of 11 polymorphisms with wheeze and asthma in 10-year-old Chinese schoolchildren. METHODS: The subjects were 107 children who had wheeze in the last 12 months and 118 without wheeze in the last 12 months. They were randomly selected from 3110 children who took part in Phase II of the International Study of Asthma and Allergies in Childhood. These schoolchildren underwent questionnaire, spirometry and methacholine challenge testing. RESULTS: The A allele of the tumor necrosis factor-alpha (TNFA) G-308A polymorphism was significantly associated with wheeze in the last 12 months (odds ratio [OR] 2.1, P = 0.04) and current asthma (OR 2.6, P = 0.006). When stratified by gender, these associations were only seen in the female study participants. In girls, the OR for the TNFA-308A allele and wheeze in the last 12 months was 3.6 (P = 0.01) and for current asthma it was 6.0 (P = 0.0006). CONCLUSION: The A allele of the TNFA G-308A polymorphism was a risk factor for asthma-related phenotypes in girls but not boys.     

Febrile respiratory illnesses in infancy and atopy are risk factors for persistent asthma and wheeze

Severe viral respiratory illnesses and atopy are risk factors for childhood wheezing and asthma. The aim of this study was to explore associations between severe respiratory infections and atopy in early childhood with wheeze and asthma persisting into later childhood. 147 children at high atopic risk were followed from birth to age 10 yrs. Data on all respiratory infections occurring in infancy were collected prospectively and viral aetiology ascertained. Atopy was measured by skin prick tests at 6 months, and 2 and 5 yrs. History of wheeze and doctor-diagnosed eczema and asthma was collected regularly until 10 yrs of age. At 10 yrs, 60% of the cohort was atopic, 25.9% had current eczema, 18.4% current asthma and 20.4% persistent wheeze. 35.8% experienced at least one lower respiratory infection (LRI) associated with fever and/or wheeze in first year of life. Children who had wheezy or, in particular, febrile LRI in infancy and were atopic by 2 yrs, were significantly more likely to have persistent wheeze (RR 3.51, 95% CI 1.83-6.70; p<0.001) and current asthma (RR 4.92, 95% CI 2.59-9.36; p<0.001) at 10 yrs. Severe viral respiratory infections in infancy and early atopy are risk factors for persistent wheeze and asthma. The strongest marker of the asthmatogenic potential of early life infections was concurrent fever. The occurrence of fever during respiratory illnesses is an important marker of risk for wheeze and asthma later in childhood, suggesting it should be measured in prospective studies of asthma aetiology.     

Respiratory symptoms and lung function in relation to atopy in children born preterm

Respiratory morbidity is a major health problem among children. The aim of this study was to compare the background of respiratory problems of children born preterm with that of children born full-term, with special reference to atopy. The study comprised two cohorts of 10-year-old children: a group of 72 children born preterm with birth weights of less than 1,501 g, and a group of 65 children born full-term with birth weights of over 2,500 g. Histories of respiratory and atopic symptoms, and of risk factors for atopy, were collected with a questionnaire. Predisposition to atopy was verified by skin-prick testing and by measuring serum total and antigen-specific IgEs. Lung function was evaluated by spirometry testing. Children born preterm had significantly more wheezing. In them, the lifetime prevalence of wheezing was 43%, vs. 17% in children born full-term (P = 0.001; odds ratio, 3.71; 95% confidence interval, 1.67-8.25). In the full-term group, wheezing was associated with atopy: 64% of wheezers were atopic; in the preterm group, 23% of wheezers were atopic (difference between groups, P = 0.024). Children born preterm expired significantly lower spirometry values of forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEV1/FVC ratio, forced expiratory flow after 50% of vital capacity has been exhaled (FEF50), and forced expiratory flow during middle half of FVC (FEF25-75). In the preterm group, wheezing, asthma, and low gestational age, but not atopy, were significantly associated with lower lung function values. Wheezers of the preterm group who still wheezed at age 10 were significantly more often atopic than those who no longer wheezed (62% vs. 9%, P = 0.006). In conclusion, we demonstrated a significant difference between groups in the association of atopy with respiratory problems. However, although atopy was not associated with a lifetime prevalence of respiratory symptoms in prematurely born children, an atopic predisposition in them was found to associate with persistence of wheezing.     

Bronchial hyperresponsiveness, atopy, and bronchoalveolar lavage eosinophils in persistent middle lobe syndrome

Most cases of middle lobe syndrome (MLS) in children are considered to be due to asthma and may recover spontaneously; however, in persistent MLS, repeated episodes of infection often institute a vicious cycle that may lead to persistent symptoms and bronchial hyperresponsiveness (BHR). The present study was undertaken to investigate whether asthma, as an underlying diagnosis, is predictive of a favorable outcome of children with persistent MLS. We evaluated 53 children with MLS who underwent an aggressive management protocol that included fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). These patients were compared to two other groups: one consisting of children with current asthma but no evidence of MLS (N = 40) and another of non-asthmatic controls (N = 42), matched for age and sex. Prevalence of sensitization (>or=1 aeroallergen) did not differ between patients with MLS and "non-asthmatics" but was significantly lower than that of "current asthmatics." A positive response to methacholine bronchial challenge was observed with increased frequency among children with MLS when compared to "current asthmatic" and non-asthmatic children. Multivariate logistic regression analysis revealed a positive correlation between an increased number of eosinophils in the BAL fluid (BALF) and a favorable outcome, whereas no correlation was detected between sensitization or BHR and BAL cellular components. In conclusion, children with MLS have an increased prevalence of BHR, even when compared to asthmatics, but exhibit prevalence of atopy similar to that of non-asthmatics. An increased eosinophilic BALF count is predictive of symptomatic but not radiographic improvement of MLS patients after aggressive anti-asthma management.