Children with Asthma Have Fixed Airway Obstruction through Childhood Unaffected by Exacerbations

Abstract

Children with asthma may have a disease course with or without exacerbations, but the relationship between exacerbations and lung function development is poorly understood. To compare lung function trajectories from birth till adolescence in asthmatic children with and without exacerbations. Children with asthma from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) birth cohort had lung function and bronchial reactivity assessed repeatedly from 1 month to 13 years. Exacerbations were diagnosed at the COPSAC clinic defined as symptoms requiring hospitalization, oral or high-dose inhaled corticosteroid treatment. Mixed models were applied to analyze lung function trajectories. Children with asthma with exacerbations (N= 50) had a trajectory of increased, fixed airway obstruction compared with children without exacerbations (N= 47): z-score difference in airway resistance (sRawz) (95% confidence interval [CI]):+0.34 (+0.03;+0.66), P= .03, and maximal mid-expiratory flow (MMEFz):-0.41 (-0.69;-0.13), P= .004, but no differences in forced expiratory volume (FEVz):-0.14 (-0.41;+0.13), P= .29, or bronchial reactivity to methacholine (PDz):+0.08 (-0.26;+0.42), P= .65. This did not change comparing lung function trajectories before and after exacerbations: z-score difference (95% CI) sRawz:-0.04 (-0.35; 0.27), P= .80; MMEFz: 0.01 (-0.02; 0.04), P= .55; FEVz: 0.02 (-0.02; 0.05), P= .42; and PDz:-0.01 (-0.06; 0.05), P= .88. Children with asthma with exacerbations compared with children with asthma without exacerbations are characterized by increased airway obstruction since infancy through childhood. The airway obstruction is a fixed trajectory without progression due to exacerbations, suggesting that exacerbations are a consequence rather than a cause of diminished airway caliber in childhood.