Factors Associated with Persistence of Severe Asthma from Late Adolescence to Early Adulthood

Abstract

Rationale: Asthma severity in children generally starts mild but may progress and stay severe for unknown reasons.

Objectives: Identify factors in childhood that predict persistence of severe asthma in late adolescence and early adulthood.

Methods: The Childhood Asthma Management Program is the largest and longest asthma trial in 1041 children aged 5-12 years with mild to moderate asthma. We evaluated 682 participants from the program with analyzable data in late adolescence (age 17-19) and early adulthood (age 21-23).

Measurements: Severe asthma was defined using criteria from the American Thoracic Society and the National Asthma Education and Prevention Program to best capture severe asthma. Logistic regression with stepwise elimination was used to analyze clinical features, biomarkers, and lung function predictive of persistence of severe asthma.

Main results: In late adolescence and early adulthood 12% and 19% of the patents had severe asthma, respectively; only 6% were severe at both time periods. For every 5% decrease in post bronchodilator FEV1/FVC in childhood, the odds of persistence of severe asthma increased 2.36-fold (95% CI: 1.70-3.28; p <0.0001), for participants with maternal smoking during pregnancy odds of persistence of severe asthma increased 3.17-fold (95% CI: 1.18-8.53, p=0.02). Reduced growth lung function trajectory was significantly associated with persistence of severe asthma compared to normal growth.

Conclusions: Lung function and maternal smoking during pregnancy were significant predictors of severe asthma from late adolescence to early adulthood. Interventions to preserve lung function early may prevent disease progression.

Keywords: adolescence; asthma; lung function; pediatric; severity.

Figure 1.

Study participant flowchart. CAMP = Childhood Asthma Management Program.

Figure 2.

Sankey diagram of asthma severity changes, demonstrating the proportion of patients with each category of asthma severity over time: at baseline in childhood, late adolescence, and early adulthood. Asthma severity was dynamic from childhood to early adulthood. The data are presented as the mean (SD). ^†“Stayed Severe” refers to patients with a persistence of severe asthma from late adolescence to early adulthood.

Figure 3.

Forest plot of relevant childhood factors and the persistence of severe asthma from late adolescence to early adulthood. By using univariate logistic regression models, significant predictors of severe asthma from late adolescence to early adulthood were found to be as follows: male sex (odds ratio, 2.59; 95% confidence interval [CI], 1.22–5.51; P = 0.0133), hay fever (odds ratio, 0.42; 95% CI, 0.22–0.82; P = 0.0107), prebronchodilator FEV₁/FVC ratio (odds ratio for increase of 5%, 0.58; 95% CI, 0.48–0.71; P < 0.0001), postbronchodilator FEV₁/FVC ratio (odds ratio for increase of 5%, 0.49; 95% CI, 0.38–0.63; P < 0.0001), M.D. baseline diagnosis of mild versus moderate asthma (0.50; 95% CI, 0.26–0.95; P = 0.0347), and age at randomization (odds for 1-yr increase, 0.84; 95% CI, 0.72–0.99; P = 0.0350). The variables that were analyzed but are not included in the figure include the enrollment clinic. M.D. = Doctor of Medicine; PC₂₀ = provocative concentration resulting in a 20% decrease in the FEV₁.

Figure 4.

Asthma severity by lung function trajectory pattern. The distribution of participants with remitting, intermittent, persistent, and severe asthma is different between participants with normal lung growth patterns and those with reduced lung growth patterns. Lung function trajectory patterns were as follows: “normal growth” (FEV₁ growth curve almost always at or above the 25th percentile) versus “reduced growth” (FEV₁ growth curve almost always below the 25th percentile) and “early decline” (earlier-than-expected decrease in the FEV₁) versus “no decline” (see Reference 18).