Heterogeneity of Mild to Moderate Persistent Asthma in Children: Confirmation by Latent Class Analysis and Association With 1-Year Outcomes

Abstract

To identify latent classes of childhood asthma and determine if latent class assignments predict subsequent lung function abnormalities and exacerbation rate at 12 months of follow-up.2593 children aged 5 to 18 years enrolled in NHLBI clinical trials on mild-to-moderate asthma and who had documented adherence to article or electronic diaries.Latent class analyses were performed on the subjects on the basis of data that had been obtained as part of the clinical trials, which included questionnaires, asthma documentation and characterization by spirometry, asthma control questionnaires, total immunoglobulin E, blood eosinophils, and allergy tests. Primary outcomes included pulmonary function and the exacerbation rate over 1 year of follow-up.Five latent classes were identified. Class 1 was as follows: multiple allergic sensitizations with partially reversible airflow limitation. Class 2 was as follows: multiple sensitization with reversible airflow limitation; Class 3 was as follows: lesser sensitization with reversible airflow limitation. Class 4 was as follows: multiple sensitization with normal lung function. Class 5 was as follows: lesser sensitization with normal lung function. Lesser sensitization means mostly nonsensitivity or monosensitivity. Latent class 2 was the largest group (35.7%), followed by class 4 (27.6%), class 5 (15.0%), class 3 (12.1%), and class 1 (9.4%). Children in class 1 had lower pulmonary function at the end of the first year, with lesser treatment response. Children in class 2 revealed improvement in lung function with treatment, and seemed to respond to any controller therapy, whereas those in class 4 and 5 had a greater response to inhaled corticosteroids. Exacerbations occurred in 52.5% of class 1, 43.0% of class 4, 41.6% of class 2, 36.8% of class 3, and 34.1% of class 5; class 1 had significantly increased exacerbations, compared with that of the other classes. Inhaled corticosteroids treatment significantly reduced exacerbations in classes 1, 2, and 4 but not in classes 3 and 5. Lung function deficits persisted despite treatment of class 1.Exacerbation rates were highest in children with multiple sensitization and partially reversible airflow limitation. Sensitization and lung function measures in children may be useful for predicting future risk in clinical settings.Because these children were all enrolled in asthma clinical trials, the results may not be generalizable to the overall pediatric asthma population, but the results do reveal that children with asthma may benefit from comanagement with an allergist to better predict those at the most risk and need for more than conventional medications.