Endotracheal intubation, while life-saving, carries significant risks including immediate complications [1,2] (e.g., trauma, hemodynamic instability, hypoxia, airway injury) and subsequent hazards [[2], [3], [4]] (e.g., difficulty swallowing, ventilator-associated pneumonia, prolonged sedation). Consequently, non-invasive ventilation (NIV) [5] and high-flow nasal cannula (HFNC) [6] are frequently employed to prevent intubation in patients with acute respiratory failure (ARF) not yet requiring invasive support.

NIV delivers positive pressure to improve oxygenation, augment alveolar ventilation, and reduce respiratory muscle workload, particularly effective in hypercapnic failure [7]. However, its use is often limited by poor patient tolerance [8] (mask discomfort, claustrophobia), risk of skin injury, impaired secretion clearance, and aspiration risk, especially in patients with altered mental status or copious secretions.

HFNC provides heated, humidified oxygen at high flows (up to 60 L/min), generating low-level positive airway pressure, improving oxygenation, reducing anatomical dead space, and enhancing mucociliary clearance [9,10]. Its key advantage over NIV is superior patient tolerance, facilitating communication, oral intake, and nursing care. However, HFNC lacks active pressure support, potentially limiting its efficacy in severe hypoxemia or hypercapnia.

Theoretically, combining NIV and HFNC could synergize their complementary mechanisms, NIV's superior pressure support and alveolar recruitment with HFNC's comfort, dead space washout, and secretion management, while mitigating the drawbacks of prolonged NIV use. This strategy has shown promise in reducing reintubation rates after extubation in high-risk populations, as evidenced by recent meta-analyses [11,12]. However, no meta-analysis has specifically evaluated the efficacy of NIV + HFNC combination therapy as the initial ventilatory strategy for preventing intubation or mortality in patients presenting with ARF. Furthermore, results from individual randomized controlled trials (RCTs) [13,14] evaluating this initial strategy have been inconsistent. Therefore, we conducted this meta-analysis to compare the efficacy of combined NIV + HFNC versus NIV alone or HFNC alone as the initial ventilatory approach for preventing intubation and mortality in adults with ARF.