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

Abstract

Rationale: Asthma in children generally starts as being mild but may progress to being severe and may stay severe for unknown reasons. Objectives: To identify factors in childhood that predict the persistence of severe asthma in late adolescence and early adulthood. Methods: The CAMP (Childhood Asthma Management Program) is, to our knowledge, the largest and longest asthma trial to date; it includes 1,041 children aged 5-12 years with mild to moderate asthma. We evaluated 682 program participants with analyzable data in late adolescence (age, 17-19 yr) and early adulthood (age, 21-23 yr). Measurements and Main Results: To best capture the cases of severe asthma, a status of severe asthma was defined by using criteria from the American Thoracic Society and the National Asthma Education and Prevention Program. Logistic regression with stepwise elimination was used to analyze the clinical features, biomarkers, and lung function that are predictive of the persistence of severe asthma. In late adolescence and early adulthood, 12% and 19% of the participants had severe asthma, respectively; only 6% at both time points had severe cases. For every 5% decrease in the postbronchodilator FEV₁/FVC ratio in childhood, the odds of the persistence of severe asthma increased by 2.36-fold (95% confidence interval [CI], 1.70-3.28; P < 0.0001); for participants with maternal smoking during pregnancy, the odds of the persistence of severe asthma increased by 3.17-fold (95% CI, 1.18-8.53; P = 0.02). A reduced-growth lung function trajectory was significantly associated with the persistence of severe asthma compared with a normal-growth lung function trajectory. Conclusions: Lung function and maternal smoking during pregnancy were significant predictors of severe asthma from late adolescence to early adulthood. Early interventions to preserve lung function may prevent disease progression.

Keywords: biomarkers; children; clinical; lung; progression.

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).