Risk Factors for Lung Function Decline in Pediatric Asthma under Treatment: A Retrospective, Multicenter, Observational Study

Abstract

Background: Childhood asthma is a major risk for low lung function in later adulthood, but what factors in asthma are associated with the poor lung function during childhood is not known. Objective: To identify clinical factors in children with asthma associated with low or declining lung function during the treatment. Methods: We enrolled children with asthma who had been treated throughout three age periods, i.e., 6−9, 10−12, and 13−15 years old, at seven specialized hospitals in Japan. Clinical information and lung function measurements were retrieved from the electronic chart systems. To characterize the lung function trajectories during each age period, we evaluated the forced expiratory volume 1 (FEV1) with % predicted values and individual changes by the slope (S) from linear regression. We defined four trajectory patterns: normal (Group N) and low (Group L), showing %FEV1 ≥80% or <80% throughout all three periods; upward (Group U) and downward (Group D), showing S ≥ 0 or S < 0%. Logistic regression analysis was performed to compare factors associated with the unfavorable (D/L) versus favorable (N/U) groups. Results: Among 273 eligible patients, 197 (72%) were classified into Group N (n = 150)/U (n = 47), while 76 (28%) were in Group D (n = 66)/L (n = 10). A history of poor asthma control, long-acting beta2 agonist use, and a lower height Z-score during 13−15 years were associated with an unfavorable outcome (Group D/L). Conversely, inhaled corticosteroid (ICS) use during 10−12 years and high-dose ICS use during 13−15 years were associated with a favorable outcome (Group N/U). Conclusion: We identified several factors that are associated with unfavorable lung function changes in pediatric asthma. Attention should be paid to the possible relationship between yearly changes in lung function and poor asthma control, use of ICS (and its dose) and use of LABA.

Keywords: asthma; asthma control; childhood and adolescence; inhaled corticosteroids; lung function; risk factors.

Figure 1

Flow of the subjects and classification of lung function trajectories in the retrospective study. Numbers in parenthesis indicate the number of patients at each age.

Figure 2

Annual changes in %FEV1 in lung function trajectory groups. p < 0.0001 with Kruskal–Wallis test. **** p < 0.0001, *** p < 0.001, and * p < 0.05 with Dunn’s multiple comparison test. n.s.: not significant.