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A study published this month in the New England Journal of Medicine (NEJM), the SOHO trial, brings an important reflection to current clinical practice.

This was a multicenter, randomized clinical trial including more than 1,100 patients with acute hypoxemic respiratory failure, comparing high-flow nasal oxygen (HFNC) versus standard oxygen therapy.

_{Fonte: Frat JP, Quenot JP, Guitton C, et al. SOHO Trial Group and the REVA Network. High-Flow or Standard Oxygen in Acute Hypoxemic Respiratory Failure. N Engl J Med. 2026 Mar 17. doi: 10.1056/NEJMoa2516087.}

🔍 Key findings

👉 No reduction in 28-day mortality with HFNC (14.6% vs 14.6%)
👉 A modest reduction in intubation (~6%), with borderline confidence intervals

⚠️ Critical question

Are we treating surrogate outcomes rather than clinically meaningful endpoints?

HFNC demonstrated clear physiological benefits:

• ↓ Respiratory rate
• ↓ PaCO₂
• ↑ Comfort and relief of dyspnea

However:

➡️ No impact on mortality
➡️ Time to intubation was essentially identical
➡️ Reduction in intubation was small and borderline

⚖️ Critical interpretation: why no mortality benefit?

Some key hypotheses:

1. 📉 Low event rate
The study was powered to detect a 6% absolute reduction in mortality, but the observed mortality was lower than expected, reducing statistical power.
➡️ Could there be a small but clinically relevant effect?

2. 💉 Improved contemporary care

• High use of corticosteroids
• Protective ventilation strategies
• Better overall supportive care
  ➡️ The isolated effect of HFNC may have been diluted

3. 🫁 Intubation is not necessarily a “negative” outcome
Reducing intubation does not automatically translate into better prognosis

➡️ Possible explanations:

• HFNC may delay intubation without changing outcomes
• It may select different patients for invasive ventilation

4. ⚠️ Safety signal?
Pneumothorax was numerically higher in the HFNC group (1.8% vs 0.7%)
➡️ Small difference, but biologically plausible
➡️ Possibly related to sustained inspiratory effort (P-SILI?)

🔄 Conflict with previous evidence

This trial directly challenges:

• Frat et al., 2015 (reported mortality benefit)
• COVID-19 era data (suggested reduced intubation rates)

👉 What changed?

• More heterogeneous populations
• Improved global care
• Possible overestimation of prior effects

🧩 What does this change in practice?

This study does not “overturn” HFNC, but it reshapes its role:

✔️ HFNC remains useful for:

• Patient comfort
• Reducing respiratory effort
• Initial respiratory support strategy

❗ But it should NOT be considered:

• A mortality-reducing therapy
• A universally superior strategy

 💬 Take-home message

HFNC improves how the patient feels, but not necessarily how the patient evolves.

What are your thoughts on these findings?

Read the full study here: Frat JP, Quenot JP, Guitton C, et al. SOHO Trial Group and the REVA Network. High-Flow or Standard Oxygen in Acute Hypoxemic Respiratory Failure. N Engl J Med. 2026 Mar 17. doi: 10.1056/NEJMoa2516087.