Weekly Respiratory Research Analysis
This week’s respiratory literature features practice-changing randomized trials and strong translational and population evidence. A phase 3 NEJM trial showed inhaled molgramostim (GM‑CSF) improved gas transfer and quality-of-life in autoimmune pulmonary alveolar proteinosis. A large multicenter BMJ randomized trial found lateral positioning during sedation markedly reduced hypoxemia and airway rescues, a simple safety intervention with broad applicability. Translational genetic and biomarker ana
Summary
This week’s respiratory literature features practice-changing randomized trials and strong translational and population evidence. A phase 3 NEJM trial showed inhaled molgramostim (GM‑CSF) improved gas transfer and quality-of-life in autoimmune pulmonary alveolar proteinosis. A large multicenter BMJ randomized trial found lateral positioning during sedation markedly reduced hypoxemia and airway rescues, a simple safety intervention with broad applicability. Translational genetic and biomarker analyses implicate IL‑6 as a key driver in pleural infection, supporting trials of IL‑6 inhibition.
Selected Articles
1. Phase 3 Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis.
In a 48‑week double‑blind phase 3 RCT (n=164), once‑daily inhaled molgramostim (300 μg) significantly improved DLCO at 24 and 48 weeks versus placebo and produced clinically meaningful improvement in SGRQ total score at 24 weeks, with similar adverse event rates between groups.
Impact: Largest rigorous RCT demonstrating a targeted inhaled biologic improves physiology and patient‑reported outcomes in a rare pulmonary disease, filling an important therapeutic gap.
Clinical Implications: Molgramostim could become a disease‑directed therapy for autoimmune PAP, potentially reducing need for whole‑lung lavage and improving gas exchange and quality of life; adoption will require guideline updates and payer considerations.
Key Findings
- Primary: LS mean DLCO change at week 24: +9.8 percentage points with molgramostim vs +3.8 with placebo (difference 6.0 pp; P<0.001).
- Secondary: DLCO improvement persisted at 48 weeks and SGRQ total score improved at 24 weeks; adverse event rates similar between arms.
2. Effect of lateral versus supine positioning on hypoxaemia in sedated adults: multicentre randomised controlled trial.
A pragmatic multicenter RCT (n=2,143 analyzed) randomized sedated adults to lateral versus supine positioning and found lateral positioning significantly reduced incidence and severity of hypoxaemia (lateral group hypoxaemia incidence 5.4%), decreased need for airway rescue interventions, and did not compromise safety.
Impact: A simple, low‑cost, immediately implementable intervention that reduces peri‑procedural hypoxaemia across diverse settings — high potential for rapid uptake and policy/guideline change.
Clinical Implications: Adopt lateral positioning as a standard option during procedural sedation to reduce hypoxaemia and airway rescues, especially where monitoring or rescue resources are limited; tailor to patient-specific contraindications.
Key Findings
- Large RCT showing significant reduction in hypoxaemia incidence with lateral positioning (5.4% in lateral group).
- Reduced severity of desaturation and fewer airway rescue interventions without increased adverse events.
3. The role of interleukin-6 signalling in pleural infection: observational and genetic analyses.
Paired pleural fluid and serum measures (n=76) showed pleural IL‑6 ~5,000‑fold higher than serum, correlating with severity and LOS; two‑sample Mendelian randomization using IL6R variants (1,601 cases vs 830,709 controls) predicted a large protective effect of IL‑6 pathway inhibition on pleural infection incidence (OR 0.23 per SD CRP decrease).
Impact: Convergent biomarker and genetic causal evidence nominate IL‑6 as a tractable target in pleural infection — a direct translational signal that can inform randomized therapeutic trials.
Clinical Implications: Measure pleural IL‑6 to help risk‑stratify patients and consider clinical trials of IL‑6 pathway inhibitors (e.g., tocilizumab) for empyema/pleural infection; efforts to quantify mtDNA/other DAMPs may complement targeting strategies.
Key Findings
- Pleural IL‑6 median ~72,752 pg/mL vs serum 15 pg/mL (~5,000‑fold higher) and correlated with severity and length of stay.
- Mendelian randomization using IL6R variants predicted a protective effect of IL‑6 inhibition on pleural infection incidence (OR 0.23 per SD CRP decrease).