Risk Factors For Bronchial Hyperresponsiveness Research Articles

Prevalence, Risk Factors and Cutoff Values for Bronchial Hyperresponsiveness to Provocholine in 7-Year-Old Children

BackgroundA US Food and Drug Administration (FDA)-approved drug methacholine chloride (Provocholine®) was recently introduced to Korea where it is now widely used in clinical practice. We aimed to evaluate the prevalence, risk factors and cutoff value of bronchial hyperresponsiveness (BHR) to Provocholine in 7-year-old children.MethodsSix hundred and thirty-three children from the Panel Study on Korean Children who visited 16 regional hospitals were evaluated. Skin prick tests, spirometry and bronchial provocation tests for Provocholine as well as a detailed history and physical examinations were performed. The bronchial provocation test was reliably performed on 559 of these children.ResultsThe prevalence of ever-diagnosed asthma via medical records was 7.7%, and that of current asthma (wheezy episode in the last 12 months + diagnosed asthma by physicians) was 3.2%. The prevalence of BHR to Provocholine was 17.2% and 25.8%, respectively, for a PC20 < 8 and < 16 mg/mL. The risk factors for BHR (PC20 < 16 mg/mL) were atopic dermatitis diagnosis and current dog ownership, whereas those for current asthma were allergy rhinitis diagnosis, a history of bronchiolitis before the age of 3, recent use of analgesics/antipyretics and maternal history of asthma. The BHR prevalence trend showed an increase along with the increased immunoglobulin E (IgE) quartile. The cutoff value of PC20 for the diagnosis of current asthma in children at age 7 was 5.8 mg/mL (sensitivity: 47.1%, specificity: 87.4%).ConclusionsBHR to Provocholine (PC20 < 8 mg/mL) was observed in 17.2% of 7-year-olds children from the general population and the cutoff value of PC20 for the diagnosis of current asthma was 5.8 mg/mL in this age group. The risk factors for BHR and current asthma showed discrepancies suggesting different underlying mechanisms. Bronchial provocation testing with Provocholine will be a useful clinical tool in the future.

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.

Risk factors for bronchial hyperresponsiveness in teenagers differ with sex and atopic status

Sex-related differences in bronchial hyperresponsiveness (BHR) have been reported in adolescents, but the mechanisms remain obscure. To investigate the risk factors for BHR in the Raine Study, a community-based longitudinal birth cohort. At 14 years of age, children underwent a respiratory assessment including a questionnaire, lung function testing,methacholine challenge, and determination of atopic status. A total of 1779 children provided data for assessment, with 1510 completing lung function and methacholine challenge testing. Current asthma was present in 152 (10.4%), 762 (50.5%) were atopic, and 277 (18.6%) had BHR. BHR was more common in girls, whereas atopy was more common in boys, with no sex differences in asthma or current wheeze. Independent risk factors for BHR were being female (odds ratio [OR], 3.45; P< .001), atopy at 14 years (OR, 1.27; P= .004), and current asthma (OR, 2.15; P= .005). Better lung function was protective against BHR (forced expiratory flow between 25% and 75% of forced vital capacity/forced vital capacity, OR, 0.09; P< .001). Risk factors differed with sex and atopic status. Early-life factors were generally not independent risk factors for BHR at 14 years of age, with theexception of being smaller at birth in boys (birth length, OR, 6 × 10(-9); P= .017) and maternal asthma in girls (OR, 1.84; P= .041). Current asthma was not a risk for BHR in nonatopic children. Bronchial hyperresponsiveness was more common and more severe in girls. These differences could not be explained by differences in lung function or atopic status.

Nasal Polyps: An Independent Risk Factor for Bronchial Hyperresponsiveness in Patients with Allergic Rhinitis

Many studies were conducted to figure out the relationship between allergic rhinitis (AR) and lower airway diseases. This study was designed to elucidate the clinical parameters that could predict the coexistence of bronchial hyperresponsiveness (BHR) in AR and suggest a guideline for lower airway evaluation in these patients. One hundred seventy-three patients newly diagnosed with AR were evaluated for the lower airway with the methacholine bronchoprovocation test. BHR was more prevalent in patients with nasal polyps (p = 0.01), in patients complaining of moderate to severe symptoms (p = 0.023), with higher serum total IgE levels (p = 0.001), and with blood eosinophil count (p = 0.008). No statistically significant difference was observed between intermittent and persistent AR patients (p = 0.364). Blood eosinophil count that could predict BHR was calculated as 320 cells/μL (p = 0.004). Instead of a routine lower airway evaluation for all AR patients, we recommend lower airway evaluation for the selected patients with nasal polyps, moderate to severe symptoms, and high blood eosinophil count.

Urban Residence Is Associated With Bronchial Hyperresponsiveness in Italian General Population Samples

The role of different risk factors for bronchial hyperresponsiveness (BHR), such as gender, atopy, IgE, and environmental factors (smoking, occupational exposure, infections), has been described. Indoor and outdoor pollution play an important role too, but few studies have analyzed the association with BHR. The aim of this study was to assess the effect of urban residence on BHR. We studied two general population samples enrolled in two cross-sectional epidemiological studies performed in Northern Italy (Po Delta, rural area) and Central Italy (Pisa, urban area). We analyzed 2,760 subjects (age range, 8 to 74 years). We performed analysis of variance and logistic regression analysis using ln slope of the dose-response curve of the methacholine challenge test as dependent variable, and sex, age, smoking habits, respiratory symptoms, skin-prick test results, IgE value, residence, and airway caliber as independent variables. The mean value of ln slope of the dose-response curve adjusted for initial airways caliber (by baseline FEV(1) percentage of predicted value) was significantly higher in female subjects, in smokers, in subjects with respiratory symptoms, in younger and older ages, in subjects with high values of IgE, and in subjects with positive skin-prick test results. After controlling for the independent effects of all these variables, living in urban area was an independent risk factor for having BHR (odds ratio, 1.41; 95% confidence interval, 1.13 to 1.76). Living in urban area is a risk factor for increased bronchial responsiveness.

Risk Factors for Bronchial Hyperresponsiveness in Children with Allergic Rhinitis

Risk Factors for Bronchial Hyperresponsiveness in Children with Allergic Rhinitis

Atopy and Sensitization to Inhalant Allergens may be Risk Factor for Bronchial Hyperresponsiveness but not Pulmonary Function

Atopy and Sensitization to Inhalant Allergens may be Risk Factor for Bronchial Hyperresponsiveness but not Pulmonary Function

The Relationship Between Allergen Sensitization and Bronchial Hyperresponsiveness in Children Aged 6-8 Years

RATIONALE: The identification of risk factors for bronchial hyperresponsiveness (BHR) is important in furthering the understanding of the cause of asthma. BHR is known to be related to atopy. We investigated the relations of BHR to sensitization to the five allergen groups in children aged 6-8 years.

Perinatal risk factors for bronchial hyperresponsiveness and atopy after a follow-up of 20 years

Background Perinatal risk factors are associated with lung function and respiratory symptoms in adult life. Whether the same holds for distinctive asthma features, such as bronchial hyperresponsiveness (BHR) and atopy, has scarcely been studied. Objective We sought to identify the perinatal risk factors for the development of BHR and atopy. Methods BHR and atopy were measured after 20 years' follow-up in 597 of 3162 babies born from 1975 through 1978. Factors directly related to delivery of these children were studied in association with the presence of BHR and atopy. Results Twenty-five percent had BHR, and 47% had atopy. Delivery duration of longer than 12 hours was associated with the development of atopy (odds ratio [OR], 2.24; 95% CI, 1.30-3.86), and severe respiratory infection in the first year of life was associated with the development of BHR (OR, 2.69; 95% CI, 1.41-5.16). Nonatopic subjects born after induced labor and current smokers were more likely to have BHR (ORs of 2.41 [95% CI, 1.07-5.41] and 2.50 [95% CI, 1.12-5.59], respectively). Prenatal smoke exposure and childhood pet keeping decreased the risk for atopy, especially in BHR-positive subjects (ORs of 0.51 [95% CI, 0.27-0.99] and 0.46 [95% CI, 0.24-0.88], respectively). Conclusions It has been shown that events before or during birth still have an effect on respiratory health 20 years later. We put forward that an extreme hormonal status during delivery primes the fetal immune system toward atopy development. Furthermore, a severe respiratory infection in the first year of life appears associated with BHR development, and prenatal smoke exposure might be protective for the development of atopy, yet explanatory mechanisms are lacking thus far.

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 Pitkäranta, 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.

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.

S and Z alpha1-antitrypsin alleles are risk factors for bronchial hyperresponsiveness in young farmers: an example of gene/environment interaction.

Several studies have found an association between the rare Pi-alleles and asthma or bronchial hyperresponsiveness (BHR). This study deals with the effect of Pi-type on BHR among 2,308 young Danish people living in rural areas with a mean +/- SD age of 19.7+/-2.4 yrs. Interviews, pulmonary function testing, bronchial histamine provocation and skin-prick tests were performed. Serum alpha1-antitrypsin levels were determined and phenotyping was performed by means of isoelectric focusing and the subjects categorized into four groups: 1) MM and MX; 2) MS; 3) MZ; and 4) rare, i.e. SZ, SS and ZZ. Among the farmers, a significant positive trend for sensitization towards house dust mites was found, ranging from 12% in the MM group to 22% in the rare Pi-group. A positive test for trend was found within the Pi-groups in a one-sided test for doctor-diagnosed asthma with a peak prevalence of 40% for these symptoms among smokers in the rare Pi-group. On multiple logistic regression analysis, an increased odds ratio (OR) for BHR was found among farming school attendants with the rare Pi-alleles. The OR (95% confidence interval) was 1.71 (0.84-3.49) for MS, 1.93 (1.10-3.39) for MZ and 4.34 (1.19-15.8) for the rare Pi-group. Such a relationship was not found among the conscripts. These results show that a gene/environment interaction may exist between the farming occupation and the rare Pi-alleles, leading to a higher proportion of bronchial hyperresponsiveness related to the rare Pi-alleles in farming school attendants, in contrast to what is found among other young people living in rural areas.

Cotinine excretion as a predictor of peak flow variability.

Environmental tobacco smoke (ETS) is suspected to be an important risk factor for bronchial hyperresponsiveness. In order to test the effect of ETS, we measured expiratory flow rates and urine cotinine excretion (UCE) within a narrow time window in two consecutive years. Maternal smoking habits and medical history were ascertained by standardized questionnaires. The percentage ratio of the amplitude over the mean (AVAM) of the diurnal peak flow rates of children (complete values from at least five consecutive days) was calculated as an indicator of bronchial responsiveness. The association of UCE and log10AVAM was analyzed by multiple linear regression. Complete data were available for a sample of 417 children. The median of UCE in children of parents who smoked (3.2 ng/mg and 2.9 ng/mg creatinine, Surveys 1 and 2, respectively) was higher than the median in children of nonsmoking parents (0 ng/mg in both surveys). With increasing UCE the log10AVAM rose in the first and second surveys, as well as in the longitudinal analysis (p = 0.003). This association, however, showed up only in boys (p = 0.0001) and not in girls (p = 0.31). Our data suggest that there is a need both for further analysis of the gender difference and for more support of strategies against passive smoking as far as children are concerned, since airway hyperresponsiveness is a risk factor for chronic airway impairment.

Factors associated with bronchial hyperresponsiveness in Australian adults and children

To accurately assess putative risk factors for bronchial hyperresponsiveness (BHR), we have used multivariate models to analyse data from 4,366 children living in four regions and from 878 adults. A standard protocol was used to measure bronchial responsiveness to histamine. The prevalence of BHR was high at 7-9 yrs (16-18%), decreased significantly at 11-14 yrs (7-8%), and then increased in adults (12-14%). Atopy was the most important risk factor for BHR at all ages. In children, parental asthma, early respiratory illness and being born in Australia also had a significant influence, and eating fish more than once a week had a protective effect. No effect of parental smoking, gender or race was found. In adults, BHR was associated with being female and with smoking history. It appears that many factors have a significant influence on the presence of BHR, with environmental factors, particularly atopy, birthplace and diet, being the most important.

Longitudinal changes in atopy during a 4-year period: Relation to bronchial hyperresponsiveness and respiratory symptoms in a population sample of Australian schoolchildren

A total of 380 schoolchildren living in Belmont, New South Wales, a coastal town where the predominant aeroallergens are house dust mites, were studied on three occasions at 2-year intervals. At each study, atopy was measured by skin prick tests to 13 allergens, bronchial responsiveness was measured by histamine inhalation test, and respiratory illness history was assessed by a self-administered questionnaire to parents. The age of the group was 8 to 10 years at enrollment. We found that skin wheals <4 mm were not associated with respiratory or allergic illness, and therefore, we defined atopy as the presence of a skin wheal of ≥4 mm. In the sample, 24% of the children were atopic at 8 to 10 years (early-onset atopy), and an additional 15% became atopic during the study (late-onset atopy). Both early- and late-onset atopy had a close association with hay fever. Late-onset atopy was strongly associated with inconsistent reporting of symptoms. Early-onset atopy was an important risk factor for bronchial hyperresponsiveness (BHR), diagnosed asthma, and continuing symptoms of wheeze, and was a particularly important risk factor for BHR with current wheeze in late childhood years. We conclude that atopy acquired at an early age is an important predictive factor for respiratory symptoms occurring with BHR and continuing into late childhood.