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.     

Increasing prevalence of bronchial hyperresponsiveness in three selected areas in East Germany. Bitterfeld Study Group.

The prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergic rhinitis in children was lower in East Germany compared to West Germany. The reasons for this difference are still not understood. This study tested the hypothesis that prevalence of BHR increased in East German children after reunification. Two consecutive cross-sectional surveys of schoolchildren aged 8-14 yrs from three communities in East Germany were carried out in 1992-1993 and 1995-1996. A subsample of 530 and 790 children with complete lung function and cold air challenge data was analysed. The prevalence of BHR increased from 6.4%, in 1992-1993 to 11.6% in 1995-1996 (odds ratio (OR): 2.0, 95% confidence interval (CI): 1.3-3.0, adjusted for age, sex, season, community and parental education). No changes were found for asthma, allergic rhinitis or allergic sensitization. In contrast, physician diagnosed bronchitis, pneumonia and frequent colds decreased significantly. The observed increase in the prevalence of BHR was reduced (OR: 1.5, 95% CI: 0.95-2.3) after adjustment for several indoor factors. In conclusion, while the prevalence of nonallergic respiratory diseases seems to decrease, the prevalence of bronchial hyperresponsiveness might be a first indicator of the suspected increase of asthma prevalence in East Germany. The present results give indirect evidence, that less respiratory infections may be associated with higher bronchial hyperresponsiveness.     

Risk factors for bronchial hyperresponsiveness in late childhood and early adolescence.

The prevalence of asthma and bronchial hyperresponsiveness (BHR) tends to decrease in male children but increase in female children in the transition from childhood to adolescence. Hormonal factors may be involved in the natural history of asthma during this period. In a prospective study of Montreal school children, the authors examined the determinants of BHR according to the child's pubertal status; 156 male children and 168 female children without a prior diagnosis of asthma were followed for an average of 4.6 yrs. Average age at follow-up was 13.4 yrs and 59% had reached puberty. The prevalence of BHR at follow-up was similar among pre- and postpubertal male children (25.0% versus 29.2%),while BHR was more common among post- compared with prepubertal female children (33.1% versus 14.2%). There were no differences in the determinants (measured in childhood) of BHR at follow-up according to pubertal status. The major determinant of BHR was a positive skin test to dust-mite antigen. BHR was also linked to exposure to gas cooking and the presence of exercise-induced bronchospasm. In conclusion, the results of this study do not support a change in asthma phenotype with the onset of puberty. Pre- and postpuberty, the major determinant of bronchial hyperresponsiveness was skin sensitivity to mite allergen.     

Risk factors of bronchial hyperresponsiveness in children with wheezing-associated respiratory infection

The objectives of this study were to identify possible risk factors of bronchial hyperesponsiveness (BHR) in children up to 5 years of age with wheezing-associated respiratory infection (WARI), and to study the prevalence of BHR. Children up to 5 years of age with WARI were enrolled in the study. The parents or caregivers of children were asked about their demographic data and clinical histories. Physical examination and clinical score assessment were performed. Pulmonary function tests, i.e., tidal breathing flow volume (TBFV), were performed to measure tidal breathing parameters before and after salbutamol nebulization. If volume at peak tidal expiratory flow/expiratory tidal volume and time to peak expiratory flow/total expiratory time increased > or = 20%, or tidal expiratory flow at 25% of tidal volume/peak tidal expiratory flow increased > or = 20% after nebulization therapy, BHR was diagnosed. The number in the positive BHR group was used to calculate the prevalence of BHR, and clinical features were compared with those of the negative BHR group. Categorical data were analyzed for statistical significance (P < 0.05) by chi-square test or Fisher's exact test, or Student's t-test, as appropriate. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for those with statistical significance. One hundred and six wheezing children underwent pulmonary function tests before and after salbutamol nebulization. With the aforementioned criteria, 41 cases (38.7%) were diagnosed with BHR. History of reactive airway disease, (OR, 6.31; 95% CI, 1.68-25), maternal history of asthma (OR, 3.45; 95% CI, 1.34-9), breastfeeding less than 3 months (OR, 3.18; 95% CI, 1.26-8.12), and passive smoking (OR, 3; 95% CI, 1.15-7.62) were significant risk factors of BHR. The eosinophil count was significantly higher in the BHR (+) group particularly, in children 1-5 years of age (P < or = 0.01). Patchy infiltrates were more commonly found in patients with negative BHR but not statistically significant. In conclusion, a history of reactive airway disease, maternal history, breastfeeding less than 3 months, and passive smoking were significant risk factors for BHR.     

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.     

Bronchial hyperresponsiveness in two populations with different prevalences of atopy.

SETTING: Random population samples of young adults from Tartu, Estonia (n = 307) and Uppsala, Sweden (n = 498) in the framework of the European Community Respiratory Health Survey (ECRHS). OBJECTIVE: To compare the prevalence and risk factors for bronchial hyperresponsiveness (BHR) to methacholine in two centres with similar climate and ethnicity but differences in the prevalence of atopy, asthma and respiratory symptoms. DESIGN: General population-based cross-sectional survey. RESULTS: The prevalence of BHR using the cut-off points 1.5, 1.0 and 0.5 mg was 19%, 12% and 8% in Tartu and 11%, 7% and 2%, respectively, in Uppsala. Current smoking was a common risk factor for BHR in both centres. Female sex (odds ratio [OR] 2.9), sensitisation to cat (OR 5.9) and visible mould in the home (OR 2.4) were independent risk factors for BHR in Tartu. In Uppsala, BHR was significantly associated with total IgE levels (OR 2.0) and exposure to environmental tobacco smoke (OR 3.3). CONCLUSION: The high prevalence of BHR can explain the high prevalence of respiratory symptoms in Tartu and indicates that causes other than asthma and atopy can be responsible for the high prevalence of BHR in a population.     

Predictors for the severity of bronchial hyperreactivity in childhood asthma.

Bronchial hyperreactivity (BHR) is a common characteristic of asthma and is shown to be a risk factor in the development and outcome of asthma. In this study, we aimed to assess the risk factors at referral for the severity of BHR, which was determined at the end of a mean of 3 yr of follow-up in 98 children with asthma [mean (+/- SD) age, 11.0 (+/- 3.4) yr, male/female = 50/48]. We also evaluated the cross-sectional risk factors for the severity of BHR in the observed children. Information on risk factors at referral was collected from the computer records of the patients followed by an end-of-study visit. Lung function, skin-prick, and bronchial provocation tests were done and total serum IgE level was measured on this visit. The relationship between BHR and risk factors was investigated by multiple linear regression analysis. A lower level of FEV1 % at referral was found to be an important predictor of more severe BHR at the end of the follow-up. None of the other risk factors evaluated predicted the severity of current BHR. We concluded that decreased lung function at referral is associated with a more severe BHR determined at the end of a 3-yr follow-up in children with asthma.     

Bronchial hyperresponsiveness decreases through childhood

Limited knowledge exists about development of bronchial hyperresponsiveness (BHR) through adolescence. We aimed to assess changes in and risk factors for BHR in adolescence. From a Norwegian birth cohort 517 subjects underwent clinical examinations, structured interviews and methacholine challenges at age 10 and 16. BHR was divided into four categories: no BHR (cumulative methacholine dose required to reduce FEV(1) by 20% (PD(20)) >16 μmol), borderline BHR (PD(20) ≤16 and >8 μmol), mild to moderate BHR (PD(20) ≤8 and >1 μmol), and severe BHR (PD(20) ≤ 1 μmol). Logistic regression analysis was used to assess risk factors and possible confounders. The number of children with PD(20) ≤ 8 decreased from 172 (33%) to 79 (15%) from age 10-16 (p < 0.001). Most children (n = 295, 57%) remained in the same BHR (category) from age 10-16 (50% with no BHR), whereas the majority 182 (82%) of the 222 children who changed BHR category, had decreased severity at age 16. PD(20) ≤ 8 at age 10 was the major risk factor for PD(20) ≤ 8 6 years later (odds ratio 6.3), without significant confounding effect (>25% change) of gender, active rhinitis, active asthma, height, FEV(1)/FVC, or allergic sensitization. BHR decreased overall in severity through adolescence, was stable for the majority of children and only a minority (8%) had increased BHR from age 10 to 16. Mild to moderate and severe BHR at age 10 were major risk factors for PD(20) ≤ 8 at 16 years and not modified by asthma or body size.     

Why Do Only Some of the Young Adults with Bronchial Hyperreactivity Wheeze?

The significance of nonspecific bronchial hyperreactivity (BHR) is a controversial issue in asthma. The natural history of BHR has not been investigated adequately although its importance as a cross-sectional risk factor for asthma is widely accepted. This paper investigates the risk factors for wheeze among people with BHR. Subjects were young adults who had participated in the second phase of the European Community Respiratory Health Survey in Melbourne, Australia. We compared the participants with wheeze and BHR (n = 186) to those with asymptomatic BHR (n = 66). Information was collected on sociodemographic factors, family history of asthma, and relevant environmental factors using an interviewer-administered questionnaire. Atopy to a range of aeroallergens was examined by skin prick tests. Risk factors were examined by adjusting the odds ratios (OR) by a logistic regression to control for confounding effects. Parental asthma (OR = 4.2), keeping pets during childhood (OR = 3.3), allergy to house dust mite (OR = 2.7), allergic rhinitis (OR = 2.6), and having ever smoked (OR = 2.4) were associated with an increased risk of wheeze, independent of the other factors examined. When allergic rhinitis was not included as an explanatory variable, being atopic to any of the allergens assessed was found to increase the risk of current wheeze (OR = 4.8). Allergic rhinitis may represent an intermediate stage in the natural history of BHR. Avoidance of pets during childhood, not smoking, and taking steps to minimize dust exposure are likely to prevent the progression from asymptomatic BHR to asthma.     

Sensitization to individual allergens and bronchial responsiveness in the ECRHS. European Community Respiratory Health Survey.

Little is known about the relation of bronchial responsiveness (BHR) to sensitization to individual allergens, or its variation between countries. Data were obtained for BHR, specific immunoglobulin E and confounding variables from 11,215 subjects, aged 20-44 yrs at the start of the European Community Respiratory Health Survey, in 34 centres in 15 countries. The relation of BHR to sensitization to cat, house dust mite, timothy grass and Cladosporium was estimated by means of multiple regression for each centre, and combined across centres by random effects meta-analysis, controlling for baseline lung function, height, sex, season of testing, age, smoking and age/sex and age/smoking interactions. BHR was greater, on average, in those sensitized to cat (p=0.023), house dust mite (p<0.001) and timothy grass (p=0.018), but not to Cladosporium (p=0.60), and increased with degree of sensitization (p<0.001). All relations showed heterogeneity between centres, although to a lesser extent in the relation to sensitization to house dust mite. More variation in bronchial responsiveness was explained by sensitization and degree of sensitization to the individual allergens than by atopy defined as any positive test in each centre, but the relative importance of each allergen varied. The use of atopy as a single variable in relation to bronchial hyperresponsiveness may be misleading.     

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.     

Risk factors for COPD spirometrically defined from the lower limit of normal in the BOLD project

Chronic obstructive pulmonary disease (COPD) is predicted to become the third most common cause of death and disability worldwide by 2020. The prevalence of COPD defined by the lower limit of normal was estimated using high-quality spirometry in surveys of 14 populations aged ≥ 40 yrs. The strength and consistency of associations were assessed using random effects meta-analysis. Pack-years of smoking were associated with risk of COPD at each site. After adjusting for this effect, we still observed significant associations of COPD risk with age (OR 1.52 for a 10 yr age difference, 95% CI 1.35-1.71), body mass index in obese compared with normal weight (OR 0.50, 95% CI 0.37-0.67), level of education completed (OR 0.76, 95% CI 0.67-0.87), hospitalisation with a respiratory problem before age 10 yrs (OR 2.35, 95% CI 1.42-3.91), passive cigarette smoke exposure (OR 1.24, 95% CI 1.05-1.47), tuberculosis (OR 1.78, 95%CI 1.17-2.72) and a family history of COPD (OR 1.50, 95% CI 1.19-1.90). Although smoking is the most important risk factor for COPD, other risk factors are also important. More research is required to elucidate relevant risk factors in low- and middle-income countries where the greatest impact of COPD will occur.     

Smoking and atopy as determinants of sputum eosinophilia and bronchial hyper-responsiveness in adults with normal lung function

Data concerning the determinants of sputum eosinophilia and bronchial hyper-responsiveness (BHR) in large cohorts of individuals with normal lung function are limited. Here, we assessed the occurrence of sputum eosinophilia and BHR and identified the risk factors for these variables in two populations living in North Karelia, Finland, and in Pitk?ranta, the Republic of Karelia, Russia. These areas are geographically adjacent, but differ, however, fundamentally in major cultural, socioeconomical and lifestyle aspects. The study population comprised 790 Finns and 387 Russian, aged 25-54 years, who were randomly enrolled from the population registers. A methacholine challenge test to measure BHR was successfully performed in 581 (74%) Finns and 307 (79%) Russians with virtually normal lung function (FEV1 > 70% of predicted). Of these, induced sputum samples were obtained from 41% of the Finns and from 67% of the Russians. The proportion of current smokers was 27% among the former and 42% among the latter. Sputum eosinophilia was assessed using a semi-quantitative method, and total concentrations of sputum eosinophilic cationic protein (ECP) and myeloperoxidase (MPO) were measured using an immunoassay. Risk factors for BHR and sputum eosinophilia were identified with a regression analysis. The prevalence of sputum eosinophilia was 22% among the Finns and 19% among the Russians, and the respective figures for BHR were 14% and 13%. The median ECP concentration in sputum was significantly higher among the Russians as compared with the Finns (P<0.001), whereas for MPO, the difference did not achieve significance. Current smoking was significantly associated with both sputum eosinophilia and BHR in Russia (OR 3.1, 95% CI 1.2-7.6 for sputum eosinophilia, 2.8, 1.3-6.1 for BHR) and with BHR in Finland (2.1, 1.3-3.7). Atopy showed a tendency to be another risk factor for BHR in Finland (1.6, 0.98-2.6). In conclusion, sputum eosinophilia and BHR occurred commonly among the Finns and the Russians with normal lung function. Current smoking was significantly associated with BHR in both countries and additionally with sputum eosinophilia in Russia. Atopy was identified as a risk factor, albeit of borderline significance, for BHR in Finland only, suggesting that there may be differences in the aetiology and nature of BHR between the two countries.     

Household Smoking and Bronchial Hyperresponsiveness in Children with Asthma

This study investigated whether household environmental tobacco smoke (ETS) exposure is associated with increased bronchial hyperresponsiveness (BHR) in children with asthma. Two hundred forty-nine children, ages 7-11 years, sampled from a larger group with reported asthma or multiple asthma symptoms identified in a community survey in Cape Town, underwent histamine challenge testing and had urinary cotinine measured. Parents were interviewed for information on smoking habits and a variety of covariates. Children with asthma whose mothers smoked had a lower frequency of BHR than asthmatic children of nonsmoking mothers, particularly if the mother smoked ≥15 cigarettes daily. BHR was also less common among children sharing a house with four or more smokers vs. fewer or none. BHR was unrelated to paternal smoking. In contrast, FEV₁ was lower among children whose mothers currently smoked. The findings do not support a mechanism whereby ETS exposure aggravates existing childhood asthma by increasing BHR. This association may be masked, however, by the degree to which mothers of asthmatic children adjust their smoking. The results are consistent with an adverse effect of maternal smoking on lung function in asthmatic children.     

Characterisation of asthma among adults with and without childhood farm contact.

Childhood farm contact is associated with a lower prevalence of sensitisation and allergic rhinitis. Findings have been contradictory for asthma. The aim of the present study was to investigate the differences between farm and nonfarm subjects using objective measurements. A cross-sectional questionnaire study was performed among rural adults aged 18-44 yrs, of which 37% lived on a farm during the first 3 yrs of life and were thus referred to as "farm subjects". Lung function, bronchial hyperresponsiveness (BHR) to methacholine and sensitisation were measured in a random sample. A total of 1,595 subjects were included in the analyses. Among farm subjects, sensitisation against inhalant allergens (odds ratio (OR) 0.7; 95% confidence interval 0.6-0.9), allergic rhinitis (0.5 (0.4-0.8)) and asthma diagnosis (0.7(0.4-1.1)) were less common than among nonfarm subjects. For BHR and lung function, no statistically significant differences were found between the two groups. Stratifying for sensitisation, farm subjects had a lower OR of asthma diagnosis (0.5 (0.3-1.0)) and a nonsignificantly reduced OR of BHR with sensitisation (0.8 (0.5-1.1)). The present study confirmed, using objective measurements, that farm subjects have a lower prevalence of symptoms and asthma diagnosis, while the prevalence of bronchial hyperresponsiveness does not differ.     

Lower prevalence of asthma and atopy in Turkish children living in Germany.

Ethnic origin has been reported to affect the prevalence of atopic diseases in several studies in different parts of the world. However, little is known about the prevalence of asthma and atopy in immigrants living in Europe. The objective of this study was to evaluate the prevalence of asthma and atopy in Turkish children living in Germany and to investigate the role of ethnic origin on the development of asthma and atopy in this population. In a cross-sectional survey the prevalence of physician-diagnosed asthma, atopy, skin-prick tests and bronchial hyperresponsiveness (BHR) to cold dry air challenge was assessed in 7,445 school children aged 9-11 yrs, living in Munich, south Germany. Questionnaires were distributed to the parents for self-completion and children underwent skin prick tests and cold air hyperventilation challenge. The Turkish children showed a significantly lower prevalence of asthma (5.3 versus 9.4%, p<0.05) than their German peers. Furthermore, atopy, as assessed by skin prick tests (24.7 versus 36.7%, p<0.001) and BHR (3.9 versus 7.7%, p<0.001), was less common in Turkish children. In multivariate regression models controlling for potential explanatory factors, Turkish origin still showed a significantly lower risk of developing asthma, atopic sensitization and BHR. The prevalence of childhood asthma was therefore shown to be lower in Turkish children living in Germany than in Turkey. These findings suggest that the lower prevalence of asthma and allergy in Turkish children living in Germany might be attributable to a selection bias affecting the parents of these children, as healthy individuals may have decided to come to Germany for work.     

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.     

Determinants and regulating processes in bronchial hyperreactivity

Bronchial hyperresponsiveness (BHR) can be considered as a feature of asthma, although only a loose relationship is present with symptoms and severity of the disease. Epidemiology of BHR may inform about determining factors in BHR and its role as a risk factor. BHR is found already at a young age, mostly diminishes with age, and increases in many asthmatic patients after midlife. Genetic determinants are suggested by familial segregation and twin studies. Allergy, respiratory infections, and cigarette smoking are found to induce increase in BHR and to modify its degree at the long run. The mechanisms in BHR are being unraveled gradually. A chronic inflammation with an important role for eosinophils, mast cells, and others, is thought to modify bronchial mechanisms, such as smooth muscle, epithelium, and autonomic systems. Growing evidence supports that T lymphocytes are implicated and may determine many of the inflammatory cells, such as eosinophils, neutrophils, and mast cells.     

Bronchial Responsiveness,Spirometry and Mortality in a Cohort of Adults

Objective. Prospective population studies have reported that pulmonary function, measured by forced expiratory volume in one second (FEV₁), is an independent predictor for mortality. Besides, several studies found that death from all causes is higher in asthmatics than in non-asthmatics. However, none of these studies examined whether bronchial hyperresponsiveness (BHR), one of the key features in asthma, can be used as a predictor for mortality. Thus, the aim of this study was to analyze the association between BHR, FEV_1, and all-cause mortality in a population-based cohort of adults. Methods. Within the cross-sectional survey ECRHS-I Erfurt (1990–1992), 1162 adults aged 20–65 years performed lung function tests, including spirometry and BHR testing by methacholine inhalation up to a cumulative dose of 2 mg. BHR was assessed from the methacholine dose nebulized at ≥ 20% fall of FEV₁. After circa 20 years of follow-up, the association between baseline lung function, BHR, and mortality was investigated. Results. A total of 85 individuals (7.3%) died during a mean follow-up period of 17.4 years (SD = 2.4). FEV₁, but not forced vital capacity (FVC), was a predictor for mortality. In men, BHR increased the mortality risk (OR = 2.6, 95% CI: 1.3–5.3; adjusted for age and BMI). Additional adjustment for asthma did not change the results (OR = 2.4, 95% CI: 1.2–5.0). However, after an additional adjustment for pack years of cigarette smoking or airway obstruction, the association was not statistically significant anymore (OR = 1.8, 95% CI: 0.8–4.0, OR = 1.9, 95% CI: 0.9–4.3, respectively). Conclusions. BHR was associated with an increased mortality risk in men. Potential explanatory factors for this association are cigarette smoking, chronic obstructive pulmonary disease (COPD), or asthma. Thus, BHR might be an indirect predictor for all-cause mortality. FEV₁ was an independent predictor for all-cause mortality.     

Improvement in bronchial hyperresponsiveness with inhaled corticosteroids in children with asthma: importance of family history of bronchial hyperresponsiveness

The extent of improvement in bronchial hyperresponsiveness (BHR) with corticosteroids varies considerably among patients with asthma, although predictive factors for improvement are largely unknown. We tested the hypothesis that the improvement may vary according to family history of BHR. Children with atopic asthma (n = 121) received inhaled budesonide (800 micro g per day) regularly for 6 months. Methacholine provocative concentration causing a 20% fall in FEV(1) was measured before treatment and again after 3 and 6 months of treatment. A methacholine challenge test was also performed in each patient's parents, and the results were analyzed with regard to their children's response to corticosteroid therapy. When the children were classified into large (n = 40) and small (n = 40) improvement groups after 6 months of treatment, the prevalence of BHR and the bronchial responsiveness index were higher in parents of the small improvement group (28.8%, 1.145 +/- 0.104) than in parents of the large improvement group (6.3%, 1.095 +/- 0.064; both, p < 0.01). The magnitude of improvement in BHR at 6 months was lower in children with at least one parent with BHR (n = 45; 1.666 +/- 1.244 doubling doses) than in children with non-BHR parents (n = 76; 2.531 +/- 1.726, p < 0.01). Our results suggest that a family history of BHR may be an important factor in the sensitivity of BHR of individuals with asthma to inhaled corticosteroids.