Clinical significance of the bronchodilator response in children with severe asthma

Abstract

Background: Our objective was to determine those characteristics associated with reversibility of airflow obstruction and response to maximal bronchodilation in children with severe asthma through the Severe Asthma Research Program (SARP).

Methods: We performed a cross-sectional analysis evaluating children ages 6 to 17 years with nonsevere asthma (NSA) and severe asthma (SA). Participants underwent spirometry before and after 180 µg of albuterol to determine reversibility (≥12% increase in FEV₁ ). Participants were then given escalating doses up to 720 µg of albuterol to determine their maximum reversibility.

Results: We evaluated 230 children (n = 129 SA, n = 101 NSA) from five centers across the United States in the SARP I and II cohorts. SA (odds ratio [OR], 2.08, 95% confidence interval [CI], 1.05-4.13), second-hand smoke exposure (OR, 2.81, 95%CI, 1.23-6.43), and fractional exhaled nitric oxide (FeNO; OR, 1.97, 95%CI, 1.35-2.87) were associated with increased odds of airway reversibility after maximal bronchodilation, while higher prebronchodilator (BD) FEV₁ % predicted (OR, 0.91, 95%CI, 0.88-0.94) was associated with decreased odds. In an analysis using the SARP III cohort (n = 186), blood neutrophils, immunoglobulin E (IgE), and FEV₁ % predicted were significantly associated with BD reversibility. In addition, children with BD response have greater healthcare utilization. BD reversibility was associated with reduced lung function at enrollment and 1-year follow-up though less decline in lung function over 1 year compared to those without reversibility.

Conclusions: Lung function, that is FEV₁ % predicted, is a predictor of BD response in children with asthma. Additionally, smoke exposure, higher FeNO or IgE level, and low peripheral blood neutrophils are associated with a greater likelihood of BD reversibility. BD response can identify a phenotype of pediatric asthma associated with low lung function and poor asthma control.

Keywords: asthma; bronchodilator response; pediatrics.

Figure1a:

Cumulative percent change in FEV1 for increasing amounts of bronchodilator for patients with asthma enrolled in SARP I-II. 1b: Maximal lung function following bronchodilator in children with asthma enrolled in SARP I-II.

Figure1a:

Cumulative percent change in FEV1 for increasing amounts of bronchodilator for patients with asthma enrolled in SARP I-II. 1b: Maximal lung function following bronchodilator in children with asthma enrolled in SARP I-II.

Figure2a.

Maximum FEV1% predicted following bronchodilators shows a strong positive correlation with pre-BD FEV1% predicted (r=0.81, p < 0.001). Participants with lower pre-BD lung function have lower maximal FEV1% predicted while participants with higher pre-BD lung function maintain higher maximal FEV1% Predicted. 2b. Maximum FEV1/FVC (log transformed) following bronchodilators shows strong correlation with pre-BD FEV1/FVC (log transformed) (r=0.77, p < 0.0001). Participants with greater airflow limitation after maximal bronchodilation have greater pre-BD airflow limitation. 2c. Maximum percent change in FEV1 following bronchodilators shows moderate negative correlation with pre-BD FEV1% predicted using quadratic fit (r=−0.55, p < 0.001). Participants with lower pre-BD lung function had a greater bronchodilator response than participants with higher pre-BD lung function.

Figure2a.

Maximum FEV1% predicted following bronchodilators shows a strong positive correlation with pre-BD FEV1% predicted (r=0.81, p < 0.001). Participants with lower pre-BD lung function have lower maximal FEV1% predicted while participants with higher pre-BD lung function maintain higher maximal FEV1% Predicted. 2b. Maximum FEV1/FVC (log transformed) following bronchodilators shows strong correlation with pre-BD FEV1/FVC (log transformed) (r=0.77, p < 0.0001). Participants with greater airflow limitation after maximal bronchodilation have greater pre-BD airflow limitation. 2c. Maximum percent change in FEV1 following bronchodilators shows moderate negative correlation with pre-BD FEV1% predicted using quadratic fit (r=−0.55, p < 0.001). Participants with lower pre-BD lung function had a greater bronchodilator response than participants with higher pre-BD lung function.

Figure2a.

Maximum FEV1% predicted following bronchodilators shows a strong positive correlation with pre-BD FEV1% predicted (r=0.81, p < 0.001). Participants with lower pre-BD lung function have lower maximal FEV1% predicted while participants with higher pre-BD lung function maintain higher maximal FEV1% Predicted. 2b. Maximum FEV1/FVC (log transformed) following bronchodilators shows strong correlation with pre-BD FEV1/FVC (log transformed) (r=0.77, p < 0.0001). Participants with greater airflow limitation after maximal bronchodilation have greater pre-BD airflow limitation. 2c. Maximum percent change in FEV1 following bronchodilators shows moderate negative correlation with pre-BD FEV1% predicted using quadratic fit (r=−0.55, p < 0.001). Participants with lower pre-BD lung function had a greater bronchodilator response than participants with higher pre-BD lung function.