Childhood wheeze phenotypes show less than expected growth in FEV1 across adolescence

Abstract. Rationale: Better characterization of childhood wheeze phenotypes using newer statistical methods provides a basis for addressing the heterogeneity of childhood asthma. Outcomes of these phenotypes beyond childhood are unknown. Objectives: To determine if adolescent respiratory symptoms, lung function and changes in lung function over adolescence differ by childhood wheeze phenotypes defined through Latent Class Analysis. Methods: A prospective birth cohort (Melbourne Atopy Cohort Study) followed 620 high allergy-risk children, recording respiratory symptoms and spirometry at 12 and 18 years. Regression analyses identified relationships between wheeze phenotypes (Never/Infrequent ; Early Transient ; Early Persistent ; Intermediate Onset ; Late Onset ) and: lung function, change in lung function (12-18yrs), respiratory symptoms, and asthma. Baseline : Never/Infrequent wheeze. Measurements and Main Results: Deficits in expected growth of lung function, measured by change in pre-bronchodilator Forced Expiratory Volume over 1 second (FEV1) between 12 and 18 years were found for: Early Persistent (reduced 290mls; 95 CI 82,498); Intermediate Onset (reduced 210mls; 62,359); and Late Onset wheeze; (reduced 255mls; 69,442 ). Intermediate Onset wheezers had persistent FEV1 deficit post bronchodilator at 18 years (reduced 198mls; 46,350). Current asthma risk was increased for all phenotypes except Early Transient, which was also not associated with lung function deficits at 12 or 18 years. Conclusions: Persistent wheeze phenotypes in childhood were associated with reduced growth in pre-bronchodilator FEV1 over adolescence. Intermediate Onset wheezers showed irreversible airflow limitation by 18 years. Conversely, Early Transient wheeze was a benign condition with no sequelae for respiratory health by age 18.