Daily Respiratory Research Analysis
A multicenter double-blind RCT found that nocturnal CPAP did not mitigate airway hyperresponsiveness in people with obesity and asthma, challenging a purely mechanical explanation. A large three-nation analysis of COVID-19 ARDS showed tracheostomy was associated with lower 60-day mortality, despite substantial international variability in timing and use. A French nationwide matched cohort study found no increase in preterm birth or other adverse outcomes after maternal RSVpreF vaccination, suppo
Summary
A multicenter double-blind RCT found that nocturnal CPAP did not mitigate airway hyperresponsiveness in people with obesity and asthma, challenging a purely mechanical explanation. A large three-nation analysis of COVID-19 ARDS showed tracheostomy was associated with lower 60-day mortality, despite substantial international variability in timing and use. A French nationwide matched cohort study found no increase in preterm birth or other adverse outcomes after maternal RSVpreF vaccination, supporting pregnancy vaccination safety.
Research Themes
- Ventilatory strategies and obesity-asthma pathophysiology
- Tracheostomy practice and outcomes in COVID-19 ARDS
- Maternal RSVpreF vaccine safety in pregnancy
Selected Articles
1. A randomized trial of continuous positive airway pressure for the asthma of obesity.
In a double-blind multicenter RCT, nocturnal CPAP did not attenuate airway hyperresponsiveness in people with obesity and asthma, though numerical improvements in respiratory resistance were observed in obese controls without asthma. These findings argue against a purely mechanical, low-lung-volume explanation for obesity-asthma AHR and suggest differential physiologic responses by phenotype.
Impact: High-quality randomized evidence provides a negative but practice-informing result, refining pathophysiologic understanding of obesity-asthma and guiding the use of CPAP beyond mechanical hypotheses.
Clinical Implications: Routine nocturnal CPAP should not be expected to reduce AHR in obese asthma; management should prioritize established anti-inflammatory therapies and weight loss, while CPAP may benefit select obese individuals without asthma-related AHR.
Key Findings
- Nocturnal CPAP did not mitigate airway hyperresponsiveness in participants with obesity and asthma.
- Obese controls without asthma showed numerical improvement in respiratory resistance at 19 Hz with CPAP 10 cmH2O.
- Findings argue against a purely mechanical low-lung-volume mechanism for obesity-asthma AHR.
Methodological Strengths
- Double-blind randomized controlled design across two centers
- Registered trial with clear mechanistic endpoints
Limitations
- Sample size and intervention duration not specified in the abstract, potentially limiting power to detect effects
- No detailed phenotyping of asthma inflammatory endotypes in the abstract
Future Directions: Larger, longer-duration trials with endotype-driven stratification should test CPAP effects, interactions with weight-loss and anti-inflammatory therapies, and mechanistic readouts of airway mechanics and inflammation.
BACKGROUND: People with obesity and asthma often experience poor asthma control and frequent exacerbations, and exhibit airway hyperresponsiveness (AHR) that may be mitigated by elevating lung volume. Our objective was to determine if nocturnal continuous positive airway pressure (CPAP) mitigates AHR in people with obesity, both with and without asthma. METHODS: We performed a double-blinded randomized controlled trial at two centers. Participants with BMI ≥ 30 kg/m RESULTS: The change in resistance at 19 Hz improved numerically in controls assigned to CPAP 10 cmH CONCLUSIONS: AHR in obese asthma is not simply related to the mechanical effects of obesity causing a reduction in lung volume. Subclinical abnormalities in airway responsiveness in people with obesity but without asthma might improve with nocturnal CPAP. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov (NCT02953431, last update June 21, 2024).
2. Incidence, timing, and outcomes of tracheostomy in COVID-19 acute respiratory distress syndrome patients across three nations-an individual patient data analysis.
Across Argentina, Spain, and the Netherlands (n=5,781), tracheostomy incidence and timing varied substantially (40% in Spain vs 18% in the Netherlands), but receipt of tracheostomy was consistently associated with lower 60-day mortality in both unmatched and propensity-matched analyses. These data support tracheostomy as a beneficial strategy during prolonged ventilation in COVID-19 ARDS while highlighting practice variation.
Impact: Large-scale, cross-national IPD analysis with propensity matching provides robust, practice-informing evidence on tracheostomy benefits and timing variation in COVID-19 ARDS.
Clinical Implications: For prolonged invasive ventilation in COVID-19 ARDS, tracheostomy may confer survival benefits; centers should develop standardized criteria and timing protocols, while accounting for local resources and patient selection.
Key Findings
- Tracheostomy incidence varied by country: 24% (Argentina), 40% (Spain), 18% (Netherlands).
- Median time to tracheostomy differed: 16 days in Spain, 20 in Argentina, 21 in the Netherlands.
- Tracheostomy was associated with lower 60-day mortality in both unmatched and propensity-matched analyses.
Methodological Strengths
- Large multicountry individual patient data with propensity score matching
- Sensitivity analysis correcting for death risk and tracheostomy probability
Limitations
- Observational post hoc design cannot exclude residual confounding or selection bias
- Practice pattern heterogeneity across countries may limit generalizability of timing recommendations
Future Directions: Prospective, standardized protocols to test optimal timing and selection for tracheostomy in ARDS, with patient-centered outcomes and cost-effectiveness across diverse health systems.
BACKGROUND: Tracheostomy is often performed to facilitate weaning in invasively ventilated patients. There are studies regarding tracheostomy in acute respiratory distress syndrome (ARDS) patients, but its practice in ARDS patients due to coronavirus disease 2019 (COVID-19) remains uncertain. The aim of the study was to compare incidences of tracheostomy among three nations and to analyze outcomes associated with tracheostomy in COVID-19 ARDS patients. METHODS: Post hoc analysis of patient-level data on tracheostomy in patients with COVID-19 ARDS from nationwide ventilation studies in Argentina, Spain, and the Netherlands. The primary endpoint was incidence and timing of tracheostomy. A propensity matched analysis was used to correct for factors with a known association with mortality, and a sensitivity analysis was performed to correct for the risk of death and the chance of receiving a tracheostomy. All three studies included patients that were admitted to a participating intensive care unit (ICU); aged >18 years; receiving ventilatory support; confirmed to have COVID-19 pneumonia. Patients were excluded from participation when there was an alternate cause for pneumonia. For the current analysis, we additionally excluded patients not having ARDS. RESULTS: The analysis included 5,781 invasively ventilated patients: 1,469 (25%) patients from Argentina, 3,349 (58%) patients from Spain, and 963 (17%) patients from the Netherlands. Tracheostomies were performed 24% in Argentina {median 20 [16-24] days}, 40% in Spain {median 16 [12-21] days}, and 18% in the Netherlands {median 21 [17-27] days}. In unmatched and matched analyses 60-day mortality was lower in patients that received a tracheostomy. CONCLUSIONS: Both the incidence and timing of tracheostomy in COVID-19 ARDS patients differed among the three nations. Tracheostomy was associated with lower mortality rates.
3. Maternal and Neonatal Outcomes After Respiratory Syncytial Virus Prefusion F Protein Vaccination During Pregnancy: Analysis From the 2024-2025 Immunization Campaign in France.
Using France’s national health database and 1:1 matching, RSVpreF vaccination in pregnancy showed no increased risks of preterm birth, near-term delivery after vaccination, stillbirth, SGA, cesarean, postpartum hemorrhage, preeclampsia, or major cardiovascular events. These real-world findings support maternal RSVpreF vaccine safety during widespread rollout.
Impact: Large, matched nationwide cohort data directly address prominent safety concerns in pregnancy RSV vaccination programs and can inform maternal immunization policy.
Clinical Implications: Clinicians can reassure pregnant patients regarding RSVpreF vaccine safety, while maintaining vigilance through pharmacovigilance systems and shared decision-making, especially when comparing with infant mAb strategies.
Key Findings
- No increased risk of preterm birth after RSVpreF vaccination (IRR 0.97, 95% CI 0.89–1.06).
- No excess risk for delivery within 1 or 3 weeks after vaccination; 1-week risk was lower (IRR 0.81, 95% CI 0.72–0.90).
- No increases in stillbirth, SGA, cesarean delivery, postpartum hemorrhage, preeclampsia, or major cardiovascular events.
Methodological Strengths
- Nationwide database covering ~99% of the population with large matched cohort
- Rigorous 1:1 matching and robust-variance Poisson regression for time-to-event outcomes
Limitations
- Observational retrospective design susceptible to residual confounding and coding misclassification
- Short campaign window may limit detection of very rare adverse events
Future Directions: International comparative studies and head-to-head effectiveness and safety evaluations versus infant monoclonal antibodies, alongside enhanced pharmacovigilance for rare events.
OBJECTIVE: To assess the safety of the respiratory syncytial virus prefusion F protein (RSVpreF) vaccine in pregnant women during the 2024-2025 French immunization campaign, with a particular focus on the risk of preterm birth. METHODS: Using the national health care database, which covers almost 99% of the population in France, we included all women who gave birth after 22 weeks of gestation between September 16 and December 31, 2024. Women vaccinated with RSVpreF were matched 1:1 with unvaccinated women on the basis of gestational age at vaccination, maternal age at pregnancy onset, region of residence, week of conception, history of preterm birth, influenza vaccination during the same pregnancy, and multiple pregnancy. Outcomes included preterm birth, delivery within 1 and 3 weeks after vaccination, stillbirth, small-for-gestational-age (SGA) birth weight, cesarean delivery, hemorrhage, preeclampsia, and major cardiovascular events, including maternal death. Time-to-event analyses were conducted with Poisson regression models with robust variance to estimate weighted incidence rate ratios (IRRs) and their 95% CIs for each outcome. RESULTS: Among the 29,032 women vaccinated during the study period, 24,891 (85.7%) were successfully matched to 24,891 unvaccinated women in a control group. In the matched cohort, the mean±SD maternal age was 30.9±5.0 years, 3.2% had a history of preterm birth, 0.6% had multiple pregnancies, and 21.8% had received influenza vaccination. No significant increase in the risk of the following outcomes was observed: preterm birth (weighted IRR 0.97, 95% CI, 0.89-1.06), delivery within 1 week (weighted IRR 0.81, 95% CI, 0.72-0.90) or within 3 weeks (weighted IRR 0.97, 95% CI, 0.93-1.00), stillbirth (weighted IRR 0.77, 95% CI, 0.45-1.32), cesarean delivery (weighted IRR 1.00, 95% CI, 0.96-1.03), SGA birth weight (weighted IRR 1.01, 95% CI, 0.96-1.07), postpartum hemorrhage (weighted IRR 1.03, 95% CI, 0.97-1.10), preeclampsia (weighted IRR 1.02, 95% CI, 0.85-1.22), or major adverse cardiovascular event (weighted IRR 0.60, 95% CI, 0.26-1.40) outcomes. Among women vaccinated at or before 32 weeks of gestation, no significant increase in the risk of preterm birth was observed (weighted IRR 1.13, 95% CI, 0.98-1.31). CONCLUSION: This large observational study found no major safety concerns associated with RSVpreF vaccination during pregnancy. Further research, including international comparisons and evaluations of effectiveness relative to monoclonal antibodies against RSV, will be needed to fully characterize the benefit-risk balance of RSVpreF. Ongoing surveillance remains essential, particularly to monitor rare adverse events.