Childhood wheezing phenotypes influence asthma, lung function and exhaled nitric oxide fraction in adolescence

The objective of this study was to examine the associations of childhood wheezing phenotypes with asthma, lung function and exhaled nitric oxide fraction (FeNO) in adolescence. In a population-based, prospective cohort study of 6841 children, we used latent class analysis to identify wheezing phenotypes during the first 7 years of life. Physician-diagnosed asthma, spirometry and FeNO were assessed at 14-15 years. Compared with never/infrequent wheeze, intermediate-onset and persistent wheeze were consistently strongest associated with higher risk of asthma (risk ratio (95% CI) 10.9 (8.97-13.16) and 9.13 (7.74-10.77), respectively), lower forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio (mean difference in standard deviation units (SDU) (95% CI) -0.34 (-0.54 -0.14) and -0.50 (-0.62 -0.38), respectively), lower forced expiratory flow at 25-75% of FVC (FEF25-75%) (mean difference in SDU (95% CI) -0.30 (-0.49 -0.10) and -0.42 (-0.54--0.30), respectively) and increased FEV1 bronchodilator reversibility (mean difference in SDU (95% CI) 0.12 (0.02-0.22) and 0.13 (0.06-0.19), respectively). Prolonged early and persistent wheeze were associated with a decline in FEV1/FVC ratio and FEF25-75% between 8-9 and 14-15 years. Intermediate-onset, late-onset and persistent wheeze were associated with higher FeNO ratios (ratio of geometric means (95% CI) 1.90 (1.59-2.29), 1.57 (1.39-1.77) and 1.37 (1.22-1.53), respectively, compared with never/infrequent wheeze). Early-onset wheezing phenotypes persisting after 18 months of age show the strongest associations with asthma, lower lung function, even worsening from mid-childhood, and higher FeNO levels in adolescence.