A Longitudinal Assessment of Lung Function in a Clinical Cohort of Pediatric Patients With Severe Asthma

Abstract Rationale: Early alterations in lung function may increase children's risk for longer term respiratory morbidity. In pediatric patients with asthma, lower symptom control and more frequent exacerbations may be a marker for chronic inflammation, which may impact early lung development. We aimed to assess the impact of asthma control on long-term lung function in a clinical cohort of severe asthma patients <18 years of age. Methods: This is a retrospective review of pediatric patients followed in the severe asthma clinic from June 1, 2018 to December 31, 2023 at the Hospital for Sick Children, Toronto, Canada. Patients were included if they had a physician-diagnosis of asthma based on ICD-10 billing codes, and had at least 2 spirometry tests over a one-year period with acceptable and reproducible data per ATS criteria. Mixed effects linear regression models with random intercepts were used to assess the effect of age, sex, patient-reported severe exacerbations (requiring oral steroid, emergency department visit or hospitalization) and asthma control test score on repeated FEV1 and FVC measures. Results: 226 patients (45% female) were included, with a total of 839 spirometry tests. Mean age at first visit was 10.1 years (SD 3.9). At first spirometry, patients had a mean FEV1 z-score of -0.593 (SD 1.530), FVC z-score of 0.120 (SD 1.389) and FEV1/FVC z-score of -1.083 (SD 1.196). Two linear mixed effects models were conducted, while controlling for sex and age at first visit to examine the effects of exacerbations and control score on FEV1, FVC and FEV1/FVC z-scores. In the first model, severe exacerbations were significantly associated with lower FEV1 (β=-0.024, 95% CI -0.042, -0.005), and lower FVC (β=-0.017, 95% CI -0.032, -0.003), but not with FEV1/FVC (β=-0.011, 95% CI -0.027, 0.006). In the second model, lower control score was significantly associated with lower FEV1 (β=0.037, 95% CI 0.025, 0.050) and FEV1/FVC (β=0.034, 95% CI 0.023, 0.045), but not significantly associated with FVC (β=0.008, 95% CI -0.002, 0.019). In both models, older age at first visit was associated with lower FEV1, FVC and FEV1/FVC (p<0.01 for all). Conclusions: We determined that in children with asthma, lower symptom control scores, severe exacerbations, and older age at first visit were associated with worsened trajectories of FEV1. Patients with a higher burden of asthma symptoms and exacerbations may be at risk for lower lung function, and are a target for early, aggressive intervention to avoid permanent alterations in lung function.

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