Profiling Persistent Asthma Phenotypes in Adolescents: A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies

Abstract

We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13-17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included (n = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact (n = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 (n = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 (n = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms (p < 0.001). Class 3 (n = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month (p = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.

Keywords: adolescents; asthma; clustering; latent class analysis; longitudinal studies; phenotypes.

Figure 1

Longitudinal changes in the three CARAT scores (T, UA, and LA), in classes 1 (n = 89), class 2 (n = 31) and class 3 (n = 43). Error bars indicating standard error of the mean. CARAT: Control of Allergic Rhinitis and Asthma Test; T0: baseline assessment; T: total; UA: Upper airways; LA: Lower airways. * significant overall longitudinal changes (p < 0.05). T0: baseline assessment; T1: 1-week; T2: 1-month; T3: 4-month follow-up.

Figure 2

Longitudinal changes in the rate of exacerbations and unscheduled healthcare visits per month, among the three classes. Error bars indicating standard error of the mean. Number of subjects with exacerbations: class 1 (T0: n = 81; T3: n = 33), class 2 (T0: n = 3; T3: n = 10) and class 3 (T0: n = 3; T3: n = 16). Number of subjects with unscheduled healthcare visits: class 1 (T0: n = 49; T3: n = 12), class 2 (T0: n = 0; T3: n = 2) and class 3 (T0: n = 0; T3: n = 3). * significant for p < 0.01. T0: baseline assessment; T3: 4-month follow-up.