Introduction Overweight children with asthma may display impaired response to inhaled corticosteroids (ICS), possibly due to non-eosinophilic inflammation or weight-related lung compression; these mechanisms may differentially affect response to ICS and leukotriene receptor antagonists (LTRAs). We assessed whether weight status modified the response to low-dose ICS and LTRA Step-2 monotherapy.
Methods A historical cohort study from clinical data linked to administrative databases was conducted among children aged 2–18 years with specialist-diagnosed asthma who were initiating or continuing a Step-2 monotherapy from 2000 to 2007 at the Montreal Children’s Hospital Asthma Centre. The outcome was time-to-management failure defined as any step-up in therapy, acute care visit, hospitalisation or oral corticosteroids for asthma, whichever occurred first. The independent and joint effects of weight status (body mass index [BMI] percentile) and time-varying treatment on time-to-management failure were estimated with marginal structural Cox models. The likelihood ratio test (LRT) and relative excess risk due to interaction (RERI) were computed to assess treatment effect modification by weight status on the multiplicative and additive scales.
Results Of the 433 and 85 visits with a low-dose ICS and LTRA prescription, respectively, 388 management failures occurred over 14 529 visit-weeks of follow-up. Children using LTRA compared with low-dose ICS tended to have an overall higher risk of early management failure (HR 1.52; 95% CI 0.72 to 3.22). Irrespective of treatment, the hazard of management failure increased by 5% (HR 1.05; 95% CI 1.01 to 1.10) for every 10-unit increase in BMI percentile. An additional hazard reduction of 17% (HR 0.83; 95% CI 0.70 to 0.99) was observed for every 10-unit increase in BMI percentile among LTRA users, but not for ICS (HR 0.95; 95% CI 0.86 to 1.04). The LRT indicated a departure from exact multiplicativity (p<0.0001), and the RERIs for ICS and LTRA were −0.05 (95% CI −0.14 to 0.05) and −0.52 (95% CI −1.76 to 0.71).
Conclusions Weight status was associated with earlier time-to-management failure in children prescribed Step-2 therapy. This hypothesis-generating study suggests that LTRA response increases in children with higher BMI percentiles, although further research is warranted to confirm findings.
- inhaled corticosteroids
- leukotriene receptor antagonists
- management failure
- weight status
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Presented at Part of this work was recently presented at the European Respiratory Society (ERS) Congress in Milan, Italy on 12 September 2017. An abstract will be published in an ERS journal supplement.
Correction notice This article has been corrected since it first published online. The open access licence type has been amended.
Contributors CL conceived the research question, designed the study, performed the data analysis and wrote the manuscript. CL, TAB, FMD, TS, BM and GB contributed to the study design and interpretation of findings, as well as critically reviewed and approved the manuscript. FMD was responsible for all data acquisition collected and provided access to the data. CL was granted full access to all study data and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding Funded by the Fonds de la Recherche du Québec en Santé (FRQ-S).
Competing interests FMD has received research funds from Merck Canada, unrestricted funds from Boehringer Ingelheim, Takeda, Novartis and GlaxoSmithKline, and was a consultant to Merck and Boehringer Ingelheim.
Patient consent for publication Not required.
Ethics approval The institutional Research Ethics Boards of the CHU Sainte-Justine, the Montreal Children’s Hospital, the Commission d’accès à l’information and the Régie de l’assurance maladie du Québec (RAMQ) approved this study.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available due to privacy and confidentiality laws.
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