Study background and disease burden
Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide and is closely linked to cigarette smoking and other environmental exposures. Patients with COPD are at heightened risk for developing additional respiratory comorbidities, including lung infections and malignancies, which often necessitate diagnostic procedures such as flexible bronchoscopy. Bronchoscopy allows direct visualization and sampling of the airways but carries increased risks in COPD patients, chiefly due to compromised baseline lung function and vulnerability to oxygen desaturation during sedation and airway manipulation. Episodes of hypoxaemia can complicate the procedure and contribute to adverse outcomes, prolong recovery, and increase healthcare resource utilization. Therefore, optimizing oxygen delivery during bronchoscopy in COPD patients is an unmet clinical need to improve procedural safety and patient outcomes.
Study design
The PROSA 2 trial was an investigator-initiated, single-centre, open-label randomised controlled study conducted to examine whether high-flow nasal oxygen (HFNO) could better prevent oxygen desaturation than conventional low-flow oxygen therapy during bronchoscopy under conscious sedation in patients with COPD. A total of 600 patients with a median age of 69 years (interquartile range 62–76) were randomized to receive either high-flow oxygen (n=295) or low-flow oxygen (n=305).
The low-flow oxygen group was supplied with oxygen starting at 4 L/min via nasal cannula, titrated up to 12 L/min to maintain peripheral oxygen saturation (SpO2) above 90%. The high-flow group received heated, humidified oxygen starting at 60 L/min with an inspired oxygen fraction (FiO2) of 0.6, increased to 80 L/min if necessary to sustain SpO2 above 90%. The primary endpoint was the cumulative duration of hypoxaemia during the procedure, defined by SpO2 below 90%. Secondary endpoints included the number of hypoxaemic events and patient comfort assessments.
Key findings
The PROSA 2 trial demonstrated a significant advantage of high-flow oxygen over conventional low-flow oxygen in reducing hypoxaemia during bronchoscopy in COPD patients. Specifically, cumulative hypoxaemia time was reduced by 53% in the high-flow group compared to the low-flow group: median 1.8% (95% CI 1.5–2.2) versus 3.8% (95% CI 3.2–4.5) of the monitored procedural time (p < 0.001).
Additionally, the high-flow group experienced fewer hypoxaemic events, with a median of 3.0 events (IQR 1.0–6.0) compared to 6.0 events (IQR 3.0–10.0) in the low-flow group (p < 0.001). The odds of encountering hypoxaemia during the procedure were five-fold higher in the low-flow group (OR 5.1, 95% CI 3.2–8.2; p < 0.001). Thus, HFNO markedly decreased the frequency and duration of oxygen desaturation episodes.
Crucially, patient comfort was comparable between groups, suggesting that HFNO did not adversely impact the tolerability of the procedure despite the higher oxygen flow rates.
Safety endpoints were not compromised; no significant adverse events related to oxygen delivery methods were reported, underscoring the feasibility of HFNO in this clinical context.
Expert commentary
The PROSA 2 trial adds to growing evidence supporting high-flow nasal oxygen’s role beyond intensive care and procedural sedation, highlighting its utility in high-risk respiratory populations such as COPD. Mechanistically, HFNO provides several physiological benefits—including improved oxygenation through stable FiO2 delivery, positive airway pressure, dead space washout, and better mucosal hydration—which can mitigate hypoventilation effects during conscious sedation and airway instrumentation.
From a clinical standpoint, reducing hypoxaemia during bronchoscopy may decrease the need for procedure interruption, escalation of airway support, or post-procedural complications. However, as this was a single-centre, open-label trial, generalizability to other clinical settings warrants further multi-centre validation. Additionally, the study did not explore long-term clinical outcomes such as hospitalization rates or respiratory function post-procedure.
Nonetheless, current guidelines increasingly recognize HFNO as an effective adjunct in procedural sedation for patients at risk of respiratory compromise. Integration into routine bronchoscopy practice for COPD patients appears justified based on the PROSA 2 findings.
Further research might explore optimal HFNO settings tailored to patient severity, cost-effectiveness, and impact on clinical endpoints beyond oxygen saturation metrics.
Conclusion
The PROSA 2 randomised trial conclusively demonstrates that high-flow nasal oxygen significantly reduces both the duration and frequency of hypoxaemia during bronchoscopy in patients with COPD compared to standard low-flow oxygen. This intervention is feasible, safe, and maintains patient comfort, addressing a critical unmet need for improved periprocedural respiratory management in this vulnerable population. Adopting HFNO for sedation-supported bronchoscopy in COPD could enhance procedural safety, reduce hypoxaemic complications, and potentially improve overall clinical outcomes. Continued research and clinical guideline updates are warranted to establish HFNO as the standard of care in this setting.
References
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