Factors Associated With Persistence of Severe Asthma From Late Adolescence to Early Adulthood

Abstract

To determine risk factors in childhood that predict severe persistent asthma in late adolescence and early adulthood.Patients aged 5 to 12 years with mild to moderate asthma and a positive methacholine challenge enrolled in the Childhood Asthma Management Program (CAMP) trial.The CAMP participants above who had data available from late adolescence to early adulthood were included. The first study visit at age 18 years was used to determine asthma activity in late adolescence, whereas the first study at age 22 years was used to determine asthma activity in early adulthood. The American Thoracic Society definition of severe asthma was used for patients on high dose inhaled corticosteroids and the National Asthma Education and Prevention Program Expert Panel Report (NAEPP EPR) 3 definition of severe asthma was used for those not receiving high dose inhaled corticosteroids. Additional criteria for intermittent and persistent asthma were included. The following factors were analyzed: secondhand smoke exposure, maternal smoking during pregnancy, body mass index percentile, hay fever, eczema, food allergy, parental asthma being sensitized and exposed to any perennial aeroallergen, bronchial hyperreactivity, prebronchodilator FEV1/FVC ratio, post bronchodilator FEV1/FVC ratio, bronchial hyperresponsiveness to methacholine challenge, log10 of serum total IgE and log10 of serum absolute eosinophil count. Characteristics were compared from baseline to late adolescence and from baseline to early adulthood.Six hundred eighty-two CAMP participants were included. Of these participants, severe asthma was present in 81 (12%) participants in late adolescence and 131 (19%) participants in early adulthood. Half of the patients with severe asthma in late adolescence continued to have severe asthma into early adulthood. About 18% of patients improved severity, 61% did not change, and 21% of patients worsened in severity from late adolescence to early adulthood. The postbronchodilator percent predicted FEV1 and pre and post bronchodilator FEV1/FVC ratio significantly decreased from childhood to late adolescence and from late adolescence to early adulthood (P < .0001), whereas prebronchodilator FEV1 values increased from childhood to late adolescence (P < .0001) and stabilized in early adulthood (P = .040). Bronchodilator reversibility and bronchial hyperresponsiveness each decreased from childhood to late adolescence (P < .0001), whereas bronchial hyperresponsiveness also significantly decreased from childhood to early adulthood (P = .0003). Patients with persistent and severe asthma had higher serum IgE in late adolescence and were more likely to have a positive aeroallergen skin test, along with sensitization and exposure to perennial allergens in childhood. Significant factors in early childhood that were associated with persistence of severe asthma from late adolescence to early adulthood included a younger age, male sex, no reported hay fever, a low prebronchodilator FEV1/FVC ratio, a low postbronchodilator FEV1/FVC ratio, and a physician diagnosis of moderate asthma during the screening period. Notably, for every 5% decrease in post bronchodilator FEV1/FVC ratio in childhood, the odds of severe asthma persistence increased by 2.36-fold (P < .0001) as well as maternal smoking during pregnancy increased odds of severe asthma persistence by 3.17-fold (P = .020). There was a strong association between a reduced-growth lung function trajectory and severe asthma persistence.Lower FEV1/FVC ratio in childhood and maternal smoking during pregnancy were the strongest predictors for severe asthma between late adolescence and early adulthood.Understanding early factors for persistence of asthma into adulthood can help develop targeted primary prevention measures such as reduction of smoking during pregnancy as well as early intervention measures with therapies to preserve lung function in childhood.URL: www.pediatrics.org/cgi/doi/10.1542/peds.10.1164/rccm.202010-3763OC