Oxygen therapy in emergency settings for chronic obstructive pulmonary disease: a systematic literature review

Abstract Background Oxygen therapy is fundamental in the management of chronic obstructive pulmonary disease (COPD) and acute exacerbations chronic obstructive pulmonary disease (AECOPD), yet excessive oxygen delivery may worsen hypercapnia and acidosis. High-flow nasal cannula (HFNC) allows precise oxygen titration, high flow rates (30–60 L/min), and heated humidification. This systematic review evaluated the clinical and physiological effects of HFNC compared with conventional oxygen therapy (COT) and non-invasive positive pressure ventilation (NIPPV) in stable COPD and AECOPD. Methods This systematic review followed PRISMA guidelines and was registered in PROSPERO ID: CRD420251007399. PubMed, Scopus and WILEY, as primary search engines, and Google Scholar, as a secondary searching database, were searched up to January 2026. Randomized controlled trials enrolling adults with spirometry-confirmed COPD (Forced Expiratory Volume (FEV₁)/Forced Vital Capacity (FVC) < 0.70) were included. Outcomes included gas exchange, respiratory rate, dyspnea, exacerbation outcomes, and mortality. Risk of bias was assessed using the Cochrane Risk of Bias tool. Results Nine randomized controlled trials involving more than 1,400 patients were included. HFNC improved oxygenation compared with COT, with higher peripheral oxygen saturation (SpO₂) values (95% vs. 93%, p = 0.046) and greater increases in partial pressure of arterial oxygen (PaO₂) (up to 75 to 155 mmHg, p < 0.001). Respiratory rate was consistently reduced with HFNC (median 18 vs. 22 breaths/min, p = 0.018), and partial pressure of arterial carbon dioxide (PaCO₂) remained stable or decreased in patients with compensated hypercapnia. HFNC demonstrated comparable gas exchange to NIPPV, with similar intubation rates (2.8% in both groups) and fewer treatment interruptions. HFNC reduced treatment failure (10% vs. 19.4%) and need for escalation to NIPPV (8.1% vs. 16.3%) and was associated with lower 3-month readmission rates (20% vs. 28.1%). Mortality rates were similar across groups, ranging from 8.2% to 8.3%, except in studies evaluating uncontrolled oxygen therapy. Conclusions HFNC improves oxygenation, respiratory rate, and overall comfort in patients with COPD and AECOPD. It can be used as an alternative to COT and for selected patients intolerant to NIPPV without severe acidosis. NIPPV remains the standard of care in patients with significant hypercapnia or acidosis. Evidence for mortality and intubation is limited. HFNC should be applied with careful patient selection. Further trials are needed to assess long-term outcomes. Trial registration CRD420251007399.