Diagnosis and Management of Overlap Syndrome (COPD-OSA): Evidence, Challenges and Prospects

The overlap syndrome (OVS), characterized by the co-existence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), presents a significant clinical challenge due to its association with serious cardiopulmonary consequences and increased mortality. The complex pathophysiology and absence of standardized treatments often lead to underdiagnosis, aggravating its disease burden. Therefore, early and precise diagnosis is crucial. Beyond monitoring carbon dioxide levels as a key indicator of ventilatory limitation, a comprehensive diagnostic approach should integrate subjective assessments and objective examinations. Advances in precision medicine are shifting research focus towards biomarkers, including systemic inflammation ratios and vascular injury markers, to facilitate early detection and risk stratification. In terms of treatment, non-invasive ventilation (NIV) remains the cornerstone for maintaining airway patency, though its effectiveness is constrained by suboptimal adherence and inherent limitations. This has prompted the exploration of pharmacological strategies as alternatives or adjuncts, yet their application requires careful risk-benefit evaluation. For instance, benzodiazepines may worsen upper airway muscle tone and blunt hypercapnic arousal responses. Promising directions include novel pharmacotherapies inspired by recent advances in OSA treatment, alongside weight-loss agents that act through weight management and metabolic regulation. Adjunctive strategies such as mild intermittent hypoxia (IH) conditioning are being investigated to enhance positive airway pressure (PAP) therapy, while targeted agents like thioredoxin (TRX) demonstrate potential by mitigating oxidative stress and neutrophilic inflammation. However, the clinical translation of these innovations faces a major bottleneck the scarcity of large-scale randomized controlled trials (RCTs) to confirm their efficacy and safety. This review synthesizes current evidence to address these gaps and inform the future precision management of OVS.