Children with severe asthma have greater prebronchodilator airflow obstruction and bronchodilator reversibility than children with nonsevere asthma, according to a study published in Pediatric Pulmonology.
In this cross-sectional analysis, researchers examined data from children aged 6 to 17 years who were enrolled in the National Heart, Lung, and Blood Institute (N=230). Participants had physician-diagnosed asthma based on ≥12% forced expiratory volume in 1 second (FEV₁) increase following bronchodilator administration (180 µg albuterol), or evidence of bronchial hyperresponsiveness by methacholine challenge at the time of enrollment. All participants were characterized as having severe asthma (n=129) or nonsevere asthma (n=101).
Peripheral blood tests were obtained to measure total white blood cells, eosinophils, neutrophils, and serum immunoglobulin E (IgE) levels, as well as percutaneous skin testing for 16 different allergens (Severe Asthma Research Program [SARP] I/II) or serum‐specific allergen testing (SARP III). The researchers measured fractional exhaled nitric oxide (FeNO) and performed spirometry for maximum bronchodilator testing. The percent predicted values were calculated using standard reference equations. Bronchodilator reversibility was defined as a ≥12% FEV₁ from baseline.
The maximum relative increase in FEV₁ was significantly greater in children with severe asthma than in those with nonsevere asthma (FEV₁% increase 22.2±20.1 vs 12.8±11.1; P <.001), secondhand smoke exposure (odds ratio [OR], 2.81; 95% CI, 1.23‐6.43; P =.014), and FeNO (OR, 1.97; 95% CI, 1.35‐2.87; P =.0005) were associated with increased odds of airway reversibility after maximal bronchodilator, while higher prebronchodilator FEV₁% predicted (OR, 0.91; 95% CI, 0.88‐0.94; P <.001) was associated with decreased odds. In the SARP III cohort, blood neutrophils, IgE, and FEV₁% predicted were significantly associated with bronchodilator reversibility.
Limitations of this study included use of an absolute bronchodilator response vs a relative response, but the researchers stated that using the absolute change did not significantly change their overall conclusion. In addition, not all findings between SARP I-II and SARP III were replicated, which may have been driven by differences in the cohorts, such as asthma severity and smoke exposure. Limitations of stepwise logistic regression may have the potential to effect the variable selection process. The researchers were unable to use the preferred causal methods of prediction as the study was inherently exploratory.
In this study, the researchers have identified a bronchodilator phenotype of pediatric asthma that is associated with worse health outcomes. These findings demonstrate that for children with asthma, lung function, particularly FEV₁%, is a significant predictor of response to bronchodilator.
Smoke exposure, higher FeNO and IgE level, and lower peripheral blood neutrophils may also identify children with asthma who are most likely to have reversibility of airflow obstruction following maximal bronchodilator. Response to maximal bronchodilator is also associated with more asthma exacerbations and hospitalizations at baseline, as well as worse lung function and asthma control at 1 year of follow-up. The pathophysiologic role of airway remodeling in children with and without a bronchodilator response may be determined with ultra-low dose computed tomography chest imaging.
Coverstone AM, Bacharier LB, Wilson BS, et al. Clinical significance of the bronchodilator response in children with severe asthma [published online August 19, 2019]. Pediatr Pulmonol. doi:10.1002/ppul.24473