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. (J Allergy Clin Immunol 2023;151:138-46.)

Automated summary

This study aimed to identify phenotypic factors associated with FEV1 in children with asthma. The results showed that baseline FENO, response to triamcinolone acetonide, and bronchodilator reversibility were associated with FEV1. Additionally, age, obesity, and exacerbation frequency predicted FEV1 over time. There was also a significant interaction between age and sex, with boys experiencing more significant effects of exacerbation frequency on FEV1 compared to girls.