Association between long-term oxygen therapy provided outside the guidelines and mortality in patients with COPD.

Introduction: Hypoxaemia is a frequent complication of chronic obstructive pulmonary disease (COPD). To prevent its consequences, supplemental oxygen therapy is recommended by international respiratory societies. However, despite clear recommendations, some patients receive long-term oxygen therapy (LTOT), while they do not meet prescription criteria. While evidence suggests that acute oxygen supply at high oxygenation targets increases COPD mortality, its chronic effects on COPD mortality remain unclear. Thus, the study will aim to evaluate through a systematic review and individual patient data meta-analysis (IPD-MA), the association of LTOT prescription outside the guidelines on survival over time in COPD.

Methods: Systematic review and IPD-MA will be conducted according to Preferred Reporting Items for a Systematic Review and Meta-Analyses IPD guidelines. Electronic databases (PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, OpenGrey and BioRxiv/MedRxix) will be scanned to identify relevant studies (cohort of stable COPD with arterial oxygen tension data available, with indication of LTOT filled out at the moment of the study and with a survival follow-up). The anticipated search dates are January-February 2022. The main outcome will be the association between LTOT and time to all-cause mortality according to hypoxaemia severity, after controlling for potential covariates and all available clinical characteristics. Quantitative data at the level of the individual patient will be used in a one-step approach to develop and validate a prognostic model with a Cox regression analysis. The one-step IPD-MA will be conducted to study the association and the moderators of association between supplemental oxygen therapy and mortality. Multilevel survival analyses using Cox-mixed effects models will be performed.

Ethics And Dissemination: As a protocol for a systematic review, a formal ethics committee review is not required. Only studies with institutional approval from an ethics committee and anonymised IPD will be included. Results will be disseminated through peer-reviewed publications and presentations in conferences.

Prospero Registration Number: CRD42020209823.