Determinants of lung function across childhood in the Severe Asthma Research Program (SARP) 3

Background: Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete. Objective: We sought to determine phenotypic factors associated with FEV₁ throughout childhood in the Severe Asthma Research Program 3 pediatric cohort. Methods: Lung function was measured at baseline and annually. Multivariate linear mixed-effects models were constructed to assess the effect of baseline and time-varying predictors of prebronchodilator FEV₁ at each assessment for up to 6 years. All models were adjusted for age, predicted FEV₁ by Global Lung Function Initiative reference equations, race, sex, and height. Secondary outcomes included postbronchodilator FEV₁ and prebronchodilator FEV₁/forced vital capacity. Results: A total of 862 spirometry assessments were performed for 188 participants. Factors associated with FEV₁ include baseline FENO (B, −49 mL/log₂ PPB; 95% CI, −92 to −6), response to a characterizing dose of triamcinolone acetonide (B, −8.4 mL/1% change FEV₁ posttriamcinolone; 95% CI, −12.3 to −4.5), and maximal bronchodilator reversibility (B, −27 mL/1% change postbronchodilator FEV₁; 95% CI, −37 to −16). Annually assessed time-varying factors of age, obesity, and exacerbation frequency predicted FEV₁ over time. Notably, there was a significant age and sex interaction. Among girls, there was no exacerbation effect. For boys, however, moderate (1-2) exacerbation frequency in the previous 12 months was associated with −20 mL (95% CI, −39 to −2) FEV₁ at each successive year. High exacerbation frequency (≥3) 12 to 24 months before assessment was associated with −34 mL (95% CI, −61 to −7) FEV₁ at each successive year. Conclusions: In children with severe and nonsevere asthma, several clinically relevant factors predict FEV₁ over time. Boys with recurrent exacerbations are at high risk of lower FEV₁ through childhood.