A letter published in Annals of Intensive Care on 17 November 2025 examines whether high-flow nasal cannula oxygen can reduce intubation in critically ill patients with severe Pneumocystis jirovecii pneumonia (PjP), while flagging methodological caveats that could shape how the evidence is interpreted. The letter, authored by Lulu Wang and Jinying Cheng, responds to a study by Reizine and colleagues that analyzed 248 ICU patients with PjP from the PRONOCYSTIS cohort over 2011 to 2021, comparing initial treatment with high-flow nasal cannula (HFNC), standard oxygen, and non-invasive ventilation (NIV).
The underlying study found that HFNC was associated with a lower intubation rate, with an inverse probability of treatment weighting-adjusted hazard ratio of 0.41 (95% confidence interval 0.24–0.69). However, no day-90 survival benefit was observed. The letter’s authors commend the study for addressing an important knowledge gap in the respiratory management of immunocompromised patients, but they argue that several analytical choices warrant closer scrutiny before the findings are translated into practice.
The first concern involves the primary endpoint. Patients who died without intubation were censored in the analysis, which the letter argues could overestimate the probability of remaining intubation-free. Death before intubation is a competing event, and a competing-risks approach such as the Fine–Gray model could yield more robust estimates. The letter also notes that patients who received alternating HFNC and NIV were grouped under NIV, which may have diluted potential differences between oxygenation strategies; a time-updated or multi-state model could better address treatment sequencing.
A second set of concerns relates to the study’s ten-year, multicenter design. Practice patterns evolved over the decade and varied across centers, and the letter suggests that sensitivity analyses incorporating center and epoch effects are needed to address this potential confounding. It further points out that the use of the 4% FiOâ‚‚ estimation formula in patients on standard oxygen could introduce systematic bias into PaOâ‚‚/FiOâ‚‚ calculations, and proposes an SpOâ‚‚/FiOâ‚‚-based sensitivity analysis to help validate the findings.
The letter also raises questions about which patients benefit most. In the original cohort, long-term corticosteroid therapy, solid tumor, and higher SOFA score independently predicted mortality. The authors suggest exploring whether HFNC’s intubation-reduction effect persists in these high-risk subgroups, particularly HIV-negative patients with malignancy or transplant recipients, which would enhance clinical targeting of the therapy.
Prevention emerges as another theme. Only 11.3% of patients in the cohort had received anti-Pneumocystis prophylaxis, which the letter describes as a missed preventive opportunity. The authors propose coupling optimized prophylaxis with standardized HFNC escalation protocols, citing examples such as ROX index thresholds, early awake prone positioning, and predefined intubation criteria, as a route to improving outcomes and safety.
In its conclusion, the letter characterizes the study as important real-world evidence supporting HFNC to reduce intubation in critically ill patients with PjP, while emphasizing that a survival benefit remains unproven. It calls for future prospective studies addressing competing risks, treatment sequencing, and heterogeneity across patient subgroups and centers.
For clinicians managing immunocompromised patients with severe PjP, the exchange highlights a recurring tension in observational critical care research: an encouraging association between an oxygenation strategy and a procedure-saving endpoint, alongside unresolved questions about competing mortality, evolving practice patterns, and subgroup effects. The letter, published as a Letter to the Editor in the open-access journal, adds a methodological roadmap for the prospective studies its authors say are needed before the intubation findings can be considered definitive.
Subject of Research: Methodological and clinical perspectives on high-flow nasal cannula use and intubation risk in severe Pneumocystis jirovecii pneumonia
Article Title: High-flow nasal cannula and intubation risk in severe PjP: methodological and clinical perspectives
Article References: Wang, L., & Cheng, J. (2025). High-flow nasal cannula and intubation risk in severe PjP: methodological and clinical perspectives. Annals of Intensive Care, 15(1), Article 179. https://doi.org/10.1186/s13613-025-01581-6
Image Credits: AI Generated
DOI: 10.1186/s13613-025-01581-6
Keywords: high-flow nasal cannula, Pneumocystis jirovecii pneumonia, intubation, ICU, immunocompromised patients, competing risks, non-invasive ventilation, PRONOCYSTIS cohort, respiratory support, prophylaxis, High-flow, nasal
News Source: Ophelia Keating. (October 30, 2026). High-Flow Nasal Cannula May Lower Intubation Risk in Severe PjP. Scienmag.
