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

Abstract

Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete. We sought to determine phenotypic factors associated with FEV₁ throughout childhood in the Severe Asthma Research Program 3 pediatric cohort. 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. 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. 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.