The obese-asthma phenotype in children: An exacerbating situation?

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The obese-asthma phenotype in children: An exacerbating situation? Cristina Longo, MSc, Gillian Bartlett, PhD, Tibor Schuster, PhD, Francine M. Ducharme, MSc, MD, Brenda MacGibbon, PhD, Tracie A. Barnett, PhD Journal of Allergy and Clinical Immunology Volume 141, Issue 4, Pages 1239-1249.e4 (April 2018) DOI: 10.1016/j.jaci.2017.10.052 Copyright © 2018 Terms and Conditions

Journal of Allergy and Clinical Immunology 2018 141, 1239-1249 Journal of Allergy and Clinical Immunology 2018 141, 1239-1249.e4DOI: (10.1016/j.jaci.2017.10.052) Copyright © 2018 Terms and Conditions

Fig 1 Study population flowchart. Journal of Allergy and Clinical Immunology 2018 141, 1239-1249.e4DOI: (10.1016/j.jaci.2017.10.052) Copyright © 2018 Terms and Conditions

Fig 2 Marginal probability of remaining exacerbation-free for obesity after initiation of step 3 maintenance therapy. The MSM estimates the marginal probability of remaining exacerbation-free had all patients been, contrary to fact, obese (red line) or nonobese (blue line) throughout follow-up. Survival curves were generated from the obesity MSM rather than the raw empiric data, which might have been misspecified. Journal of Allergy and Clinical Immunology 2018 141, 1239-1249.e4DOI: (10.1016/j.jaci.2017.10.052) Copyright © 2018 Terms and Conditions

Fig 3 Marginal probability of remaining exacerbation-free after initiation of step 3 asthma maintenance therapy regimens by treatment status. The MSM estimates the marginal probability of remaining exacerbation-free had all patients been, contrary to fact, fully adherent to ICS monotherapy (red line), fully adherent to combination therapy (blue line), or completely nonadherent (gray line) throughout follow-up. Survival curves were generated from the treatment MSM rather than the raw empiric data, which might have been misspecified. Journal of Allergy and Clinical Immunology 2018 141, 1239-1249.e4DOI: (10.1016/j.jaci.2017.10.052) Copyright © 2018 Terms and Conditions

Fig 4 Conditional and marginal HRs for obesity and step 3 maintenance therapies for children with mild-to-moderate asthma, as well as their stratified effects. Average HRs ignore the time-varying effect demonstrated in the conditional model for obesity. Marginal and conditional models were adjusted for age, sex, ethnicity, income, global assessment of severity score, number of exacerbations in previous year, exposure to smoke, asthma-related comorbidities, percent predicted FEV1, and season. Journal of Allergy and Clinical Immunology 2018 141, 1239-1249.e4DOI: (10.1016/j.jaci.2017.10.052) Copyright © 2018 Terms and Conditions

Fig 5 Marginal probability of remaining exacerbation-free for treatment groups by obesity status. The MSM estimates the probability of remaining exacerbation-free had all patients been, contrary to fact, obese and fully nonadherent (no use) to both step 3 maintenance therapies (black), nonobese and fully nonadherent (no use) to both step 3 maintenance therapies (gray), obese and fully adherent to ICS monotherapy (bright red), nonobese and fully adherent to ICS monotherapy (dark red), obese and fully adherent to combination therapy (bright blue), and nonobese and fully adherent to combination therapy (dark blue). Survival curves were generated from the obesity-by-treatment joint MSM, rather than the raw empiric data, which might have been misspecified. Journal of Allergy and Clinical Immunology 2018 141, 1239-1249.e4DOI: (10.1016/j.jaci.2017.10.052) Copyright © 2018 Terms and Conditions

Fig E1 Scaled Schoenfeld residual versus time plots with bootstrapped intervals (blue dotted lines) demonstrating the time-varying nature of the HR for obesity in the conditional (A) and marginal (B) Cox model. Bootstrap aggregation or bagging (blue line) averages the HRs over the bootstrap samples as a means of reducing variance arising from within-subject correlation, a feature of the Andersen-Gill formulation of the Cox model. The conditional HR becomes protective at approximately 250 days, whereas the IPCW marginal model corrects for this spurious protective effect. DOS, Depletion of susceptibles. Journal of Allergy and Clinical Immunology 2018 141, 1239-1249.e4DOI: (10.1016/j.jaci.2017.10.052) Copyright © 2018 Terms and Conditions