The Role of Oxygen Therapy in Acute Exacerbations of Chronic Pulmonary Diseases

Abstract: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a major cause of hospitalization, respiratory failure, and mortality worldwide. The pathophysiological complexity of AECOPD, characterized by ventilation-perfusion mismatch, alveolar hypoventilation, dynamic hyperinflation, respiratory muscle dysfunction, and carbon dioxide retention, underscores the pivotal role of oxygen therapy in respiratory support. However, oxygen administration in AECOPD extends beyond the correction of hypoxemia, as excessive oxygen supplementation may precipitate oxygen-induced hypercapnia and worsen clinical outcomes. Consequently, individualized oxygen delivery strategies that balance adequate oxygenation with ventilatory support have become an essential component of contemporary AECOPD management. This review summarizes the physiological rationale, mechanisms of action, clinical evidence, advantages, and limitations of the three principal oxygen delivery modalities currently used in AECOPD, namely conventional oxygen therapy (COT), noninvasive ventilation (NIV), and high-flow nasal cannula (HFNC). COT remains the preferred initial strategy for patients with isolated hypoxemia when oxygen is carefully titrated to achieve guideline-recommended oxygen saturation targets. NIV continues to represent the first-line respiratory support modality for acute hypercapnic respiratory failure because of its well-established ability to improve alveolar ventilation, reduce respiratory muscle workload, correct respiratory acidosis, and decrease intubation and mortality. HFNC has emerged as an important complementary modality by providing stable oxygen delivery, anatomical dead-space washout, low-level positive airway pressure, and heated humidification, thereby improving oxygenation, secretion clearance, and patient comfort. Nevertheless, current evidence does not support replacing NIV with HFNC in patients with moderate-to-severe hypercapnic respiratory failure. Future respiratory support strategies should move beyond a one-size-fits-all approach toward precision oxygen therapy guided by pathophysiological phenotyping, respiratory mechanics, neural respiratory drive, and dynamic physiological monitoring. Integrating evidence-based respiratory support modalities with individualized physiological assessment may further optimize outcomes and represents the future direction of AECOPD management.