Researchers identify factors that predict future lung function in children with asthma

Key takeaways:

• Factors associated with FEV1 included baseline fractional exhaled nitric oxide, response to a characterizing dose of triamcinolone acetonide and maximal bronchodilator reversibility.
• When assessed annually, age, obesity and exacerbation frequency predicted FEV1 over time.
• Boys with recurrent exacerbations experienced high risks for lower FEV1 during childhood.

Obesity, fractional exhaled nitric oxide and maximum bronchodilator reversibility were among the factors that precited lower FEV1 over time among children with asthma, according to a study in The Journal of Allergy and Clinical Immunology.

Also, boys with recurrent exacerbations had higher risks for lower FEV1 in childhood, Jonathan M. Gaffin, MD, MMSc, co-director of the severe asthma program at Boston Children’s Hospital, and colleagues wrote.

The Severe Asthma Research Program (SARP3) observational study involved 188 children (mean age, 11.5 years; standard deviation [SD], 2.8; 62.2% boys; 53.2% Black) — including 111 children with severe asthma and 77 children with non-severe asthma — who participated in 862 baseline and follow-up observations (median per patient, 5; interquartile range, 3-6) between November 2012 and January 2015. Median age at last follow-up was 17.2 years.

Participants had a mean pre-bronchodilator (BD) FEV1% predicted of 89.7 (SD, 16.6) and a mean post-BD FEV1% predicted of 104.3 (SD, 16).

At enrollment, 31% of participants reported no exacerbations in the previous year; 42% reported one or two, which the researchers called moderate; and 26.7% reported three or more, classified as high.

Univariate models showed significant factors related to FEV1 included baseline FeNO values, triamcinolone acetate-induced difference in post-BD FEV1% predicted (tdFEV1) and maximal BD reversibility. Also, time-varying measures of severe asthma designation, exacerbation rate and obesity were significantly related to FEV1. In fact, the researchers said they found a significant three-way interaction effect between exacerbation rate, age and sex.

Multivariate regression models confirmed these associations between FEV1 and baseline FeNO level (B= –49mL/log₂PPB, 95% CI –92 to –6), post-BD tdFEV1 (B = –8.4mL; 95% CI, –12.3 to –4.5) and maximal BD reversibility of FEV1 (B = –27 mL; 95% CI, –37 to –16), as well as with time-varying values of age, obesity and exacerbation frequency, but not with severe asthma.

Exacerbation rate did not have any effect among girls, but boys experienced yearly FEV1 decreases of 20 mL (95% CI, –39 to –2) with moderate exacerbation rates and 30 mL (95% CI, –60 to 0.3) with high exacerbation rates in the previous year. Further, the FEV1 of boys with high exacerbation rates in the previous 12 to 24 months decreased yearly by 34 mL (95% CI, –61 to –7).

Inverse probability weights in a sensitivity analysis largely confirmed these findings and also showed an inverse association between post-BD tdFEV1 and FEV1, with each percent predicted increase in the former linked to an 8.4 mL drop (95% CI, –12.3 to –4.5) in FEV1. According to the researchers, this translates to clinically meaningful, 100 mL decrease (95% CI, –146.4 to –53.6) in FEV1 through childhood for each SD in post-BD tdFEV1 (11.9%).

Predicted FEV1 had an inverse association with baseline maximal BD FEV1 (B = –27 mL/% change in post-BD FEV1; 95% CI, –37 to –16). But FEV1 also increased by 2.5 mL (95% CI, 1.1-3.8) per 1% predicted change in baseline maximal BD FEV1 reversibility. There was an association between obesity and higher FEV1 as well, but FEV1 decreased with each year in increased age.

When researchers evaluated factors that predicted maximal post-BD FEV1, they found lower levels with increasing age as well as among boys with high exacerbation frequency rates, and they observed inverse associations with maximal post-BD FEV1 and obesity in the setting of older age and with post-BD tdFEV1.

When evaluating pre-BD FEV1/forced vital capacity (FVC), age predicted decreased levels in adjusted analyses whereas lower post-BD tdFEV1 and baseline maximal BD reversibility of FEV1 precited higher levels, with the latter association appearing more pronounced at younger ages.

Based on these findings, the researchers concluded that poor lung function trajectories into adulthood are one of the risks that children with asthma experience. Also, among children and adolescents with severe and non-severe asthma, post-BD tdFEV1, FeNO, maximum BD reversibility and obesity predicted lower FEV1. Boys demonstrated novel sex-specific risks for exacerbations in lower lung function as well.

These findings could be used to develop a framework for clinically available measures that could be used to identify risks for lung function impairment over time for children with asthma as well as to develop future intervention studies designed to improve lung function in these children, according to the researchers.