Factors associated with increased bronchial responsiveness in adolescents and young adults: The importance of adjustment for prechallenge FEV1

doi:10.1016/S0091-6749(96)80153-9

Journal of Allergy and Clinical Immunology

Volume 97, Issue 3, March 1996, Pages 761-767

https://doi.org/10.1016/S0091-6749(96)80153-9 Get rights and content

Background: Asymptomatic increased bronchial responsiveness (BR) appears to be a major risk factor for later development of asthma, but risk factors for increased BR are not well established.

Objective: The relationship of age, gender, house dust mite allergy, number of blood eosinophils, and FEV₁ to the degree of nonspecific BR was studied in a population sample of 665 adolescents and young adults, aged 13 to 23 years.

Methods: Case history, especially concerning smoking habits and respiratory symptoms, was obtained by interview and a self-administered questionnaire. Pulmonary function, number of blood eosinophils, BR to inhaled histamine, and skin test reactivity to house dust mites were measured with standard techniques. BR was analyzed as both a continuous variable (doseresponse slope) and a categorical variable (cutoff: PC₂₀ 16 mg/ml).

Results: Increasing number of blood eosinophils, sensitivity to house dust mite, and former or current symptoms of asthma were associated with increasing levels of BR, independently of the level of FEV₁. Adjustment for prechallenge FEV₁ revealed a strong association between lower prechallenge FEV₁ and increasing level of BR (p<0.0001), whereas the previously observed association between female gender and higher level of BR vanished. Repeating the analyses after exclusion of subjects with former or current asthma (n=85) showed an unchanged relationship between house dust mite allergy and level of BR whether or not prechallenge FEV₁ was included in the regression model, whereas gender only influenced the level of BR when no adjustment was made for prechallenge FEV₁. On the contrary, the number of blood eosinophils was only significantly associated with BR after adjustment for baseline FEV₁. Comparable findings were observed when patients with former or current symptoms of asthma and subjects with a prechallenge FEV₁ less than 80% of predicted value (n=46) were excluded from the analyses.

Conclusions: This analysis suggests that adjustment for prechallenge level of FEV₁ should be considered in studies concerned with risk factors for symptomatic and asymptomatic bronchial hyperresponsiveness.

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Cited by (33)

Bronchial hyperresponsiveness decreases through childhood
2012, Respiratory Medicine
Citation Excerpt :
This reflects findings from other studies, where a positive skin prick test has been associated with BHR in some32,33 but not all studies.34 Allergic sensitization to HDM has as been linked to BHR in cross sectional32,33 and longitudinal studies12 and has been reported to be a risk factor in childhood for BHR in adolescence even after adjusting for asthma.15 There was no association (in cross sectional data) between height and mild to moderate or severe BHR, even with a height range of 47 cm and 50 cm, respectively.
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 FEV₁ by 20% (PD₂₀) >16 μmol), borderline BHR (PD₂₀ ≤16 and >8 μmol), mild to moderate BHR (PD₂₀ ≤8 and >1 μmol), and severe BHR (PD₂₀ ≤ 1 μmol). Logistic regression analysis was used to assess risk factors and possible confounders.
The number of children with PD₂₀ ≤ 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. PD₂₀ ≤ 8 at age 10 was the major risk factor for PD₂₀ ≤ 8 6 years later (odds ratio 6.3), without significant confounding effect (>25% change) of gender, active rhinitis, active asthma, height, FEV₁/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 PD₂₀ ≤ 8 at 16 years and not modified by asthma or body size.
Predictive factors for airway hyperresponsiveness in children with respiratory symptoms
2011, Annals of Allergy, Asthma and Immunology
Citation Excerpt :
There are several studies in adult populations supporting our finding; however, pediatric data are limited. Ulrik27 highlighted eosinophilia as a predictor of AHR. Sekerel et al28 also determined this relationship in children and young adolescents.
Asthma diagnosis is a challenging condition, particularly in patients without obstructive pattern and reversibility on spirometry. Determination of airway hyperresponsiveness (AHR) may be helpful, but the procedure is time-consuming and not always practical.
To determine the potential factors that may predict the presence of AHR in children with asthmalike symptoms but without obstructive pattern and reversibility on spirometry.
All patients with asthmalike symptoms but without obstructive pattern and reversibility on spirometry were analyzed retrospectively between January 9, 2007, and December 30, 2009. The features of clinical history and laboratory results were analyzed with univariate and multivariate regression analysis.
A total of 111 children between 6 and 18 years of age, with a median age of 10.2 years, were analyzed, and AHR was detected in 67 patients (60.3%). Multivariate logistic regression analysis revealed coexistence of nocturnal cough and exercise-induced cough (odds ratio [OR], 22.1; 95% confidence interval [CI], 3.1–159.2; P = .004), eosinophilia (OR, 18.7; 95% CI, 1.9–178.7; P = .01), and borderline bronchodilator response in forced expiratory volume in 1 second (between 7% and 11%) (OR, 10.1; 95% CI, 2.1–49.1; P = .004) as significant risk factors for the presence of AHR, whereas exercise-induced dyspnea was found to be related to the absence of AHR (OR, 0.2; 95% CI, 0.1–0.8; P = .02).
In children with asthmalike symptoms but with normal spirometry, certain features of clinical history and laboratory results can strongly predict the presence of AHR and may help less frequent use of challenge tests.
Bronchodilation and bronchoconstriction: Predictors of future lung function in childhood asthma
2006, Journal of Allergy and Clinical Immunology
Citation Excerpt :
The interrelationships between our predictors supports this (Fig 1). The importance of adjusting for baseline severity in assessing the relationship of FEV1 to airways responsiveness has been emphasized32 and is readily applicable to bronchodilator response as well. Several previous studies in children with asthma have evaluated a broad range of airway responsiveness and FEV1, but not bronchodilator response, in relation to subsequent lung function.
Persistently low levels of lung function are associated with subsequent symptoms in patients with asthma as children.
We hypothesized that objective measures of baseline pulmonary function would be independently associated with future lung function in the Childhood Asthma Management Program and that these associations might vary with treatment.
We evaluated the association of FEV₁, airway responsiveness, and bronchodilator response at randomization as predictors of longitudinal growth in FEV₁ at the 48-month follow-up visit in the 1041 Childhood Asthma Management Program participants.
Baseline levels of airway responsiveness and bronchodilator response were significantly associated with baseline level of lung function. In multivariate models, higher bronchodilator response (β = 0.22; P < .0001), log PC₂₀ (β = 1.82; P < .0001), and FEV₁ (β = 0.58; P < .0001) at randomization were each associated with higher levels of prebronchodilator FEV₁, as a percent of predicted, after 4 years. Similar associations were noted for prebronchodilator forced vital capacity and FEV₁/forced vital capacity ratio. Baseline bronchodilator response was a particularly powerful predictor of lung function improvements while on inhaled corticosteroids, whereas airway responsiveness was a better predictor in subjects not randomized to any controller medications.
We conclude that baseline bronchodilator response, airway responsiveness, and level of FEV₁ are independent predictors of subsequent level of FEV₁ in childhood asthma and may have treatment-specific prognostic significance for persistence of symptoms into early adulthood.
In asthma, bronchodilator and bronchoconstrictor responses are independent predictors of future lung function and should not be used interchangeably; bronchodilator response may indicate good response to inhaled corticosteroids.
Sensitization to aeroallergens and airway hyperresponsiveness at 7 years of age
2006, Chest
Citation Excerpt :
Gender and race were controlled for in the adjusted analyses, as these are factors that have been shown to be associated with asthma in numerous studies. Other variables included in the adjusted analyses were family income and parental history of asthma, which have been shown to be associated with development of asthma28,29; age and height, which are both important factors that influence FEV1 and have also been shown to effect airway responsiveness in children30; and prechallenge FEV1.31 We also controlled for specific allergen levels in the home and presence of a pet in the home, when relevant.
To investigate the relationship between current and early life factors and airway responsiveness to inhaled methacholine in children with a median age of 7.0 years.
Study subjects were a subset of a prospective birth cohort of children in the Boston area at high risk for atopy.
One hundred thirty-one children underwent both skin-prick testing to a panel of aeroallergens and a methacholine challenge test between 6.5 years and 8.8 years of age. Telephone questionnaires were performed at set intervals, and home dust samples were collected in the first year of life.
Of the 131 participating children, 51% (67 patients) had at least one positive skin-prick test response and 28% (37 patients) had airway hyperresponsiveness (AHR) [provocative concentration of methacholine causing a 20% fall in FEV₁ of < 4 mg/mL]. After adjusting for relevant covariates, AHR was strongly associated with sensitization to at least four aeroallergens (odds ratio [OR], 13.41; 95% confidence interval [CI], 3.03 to 59.42). In separate adjusted models, sensitization to cat (OR, 14.73; 95% CI, 3.64 to 59.55), dust mite (OR, 5.13; 95% CI, 1.94 to 13.56), cockroach (OR, 4.00; 95% CI, 1.19 to 13.50), and ragweed (OR, 10.08; 95% CI, 2.31 to 44.10) were significant predictors of AHR. However, no relationship was found with early life exposure to perennial aeroallergens or other perinatal and first-year-of-life factors.
Among young children at risk for atopy, sensitization to specific aeroallergens, but not early life exposures, is associated with increased airway responsiveness.
Sex differences in asthma, atopy, and airway hyperresponsiveness in a university population
2003, Annals of Allergy, Asthma and Immunology
A male predominance in atopy, a preadolescent male predominance in asthma, and a female predominance in airway hyperresponsiveness (AHR) have been previously documented, mostly in separate populations.
We examined gender differences in a single population of 500 randomly selected university students from a previous publication which addressed sensitivity and specificity of histamine bronchoprovocation (Cockcroft et al. J Allergy Clin Immunol. 1992;89:23–30).
In these 500 subjects (age 21.8 ± 1.5 years) we assessed gender differences in asthma, atopy, and AHR. We compared our findings with those in the literature from a PUBMED search using the keywords gender,asthma, atopy, AHR, and bronchial reactivity.
A diagnosis of asthma made by another physician was seen in 31, a male-to-female ratio of 2.9:1 (P = 0.004). Our definition of asthma increased the total to 52 and reduced the male-to-female ratio to 1.2:1. Atopy was seen in 190, male-to-female ratio of 1.5:1 (P = 0.001). Borderline to mild AHR had a female predominance with a male-to-female ratio of 1:1.5 (P = 0.02), whereas moderate AHR had a marked predominance with a male-to-female ratio of 7:1 (P = 0.03).
In our population, the associations among gender and asthma, atopy, and AHR were similar to those seen in the literature with the exception of males having more severe AHR. This may be the one factor contributing to the higher prevalence of asthma (including previous doctor-diagnosed asthma in our population) in boys and young men.
Clinical features of bronchial hyperresponsiveness
1999, Pulmonary Pharmacology and Therapeutics

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View full text

Factors associated with increased bronchial responsiveness in adolescents and young adults: The importance of adjustment for prechallenge FEV11

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy

Chest

Lancet

J Allergy Clin Immunol

Bronchial reactivity to inhaled histamine: a method and clinical survey

Clin Allergy

Factors associated with bronchial hyperresponsiveness in Australian adults and children

Eur Respir J

Towards a definition of asthma for epidemiology

Am Rev Respir Dis

Histamine dose-response curves in asthma: relevance of the distinction between PC20 and reactivity in characterizing clinical state

Thorax

The relationship between airway responsiveness to histamine and pulmonary function in a random population sample

Am Rev Respir Dis

Comparison of stayers, dropouts and newcomers in a longitudinal population study of asthma and bronchial hyperresponsiveness: Introduction of bias?

J Asthma

American Thoracic Society Executive Committee. Standardization project

Am Rev Respir Dis

The presence of airway reactivity before development of asthma

Am Rev Respir Dis

The skin prick test. Methodological studies and clinical applications

T˦lling af cirkulerende eosinophile celler i t˦llekammer

Ugeskr Laeger

Factors associated with increased bronchial responsiveness in adolescents and young adults: The importance of adjustment for prechallenge FEV₁1

Histamine dose-response curves in asthma: relevance of the distinction between PC₂₀ and reactivity in characterizing clinical state