Daily Respiratory Research Analysis
A large multicenter randomized clinical trial found that intrapartum sildenafil did not reduce hypoxia-related adverse perinatal outcomes, providing definitive evidence against its use during labor. A nationwide Swedish cohort demonstrated that patients with physician-diagnosed COPD but normal spirometry (dnsCOPD) and PRISm remain symptomatic and at risk, and that the GOLD A/B/E framework predicts outcomes even in these groups. A California case-crossover study showed that the interaction of wil
Summary
A large multicenter randomized clinical trial found that intrapartum sildenafil did not reduce hypoxia-related adverse perinatal outcomes, providing definitive evidence against its use during labor. A nationwide Swedish cohort demonstrated that patients with physician-diagnosed COPD but normal spirometry (dnsCOPD) and PRISm remain symptomatic and at risk, and that the GOLD A/B/E framework predicts outcomes even in these groups. A California case-crossover study showed that the interaction of wildfire smoke and extreme heat increases hospitalizations, especially for respiratory causes and in vulnerable subgroups.
Research Themes
- Definitive negative RCT informing perinatal care
- Risk stratification in COPD beyond spirometric thresholds
- Climate-related compound exposures and respiratory morbidity
Selected Articles
1. Intrapartum Sildenafil to Improve Perinatal Outcomes: A Randomized Clinical Trial.
In this pragmatic multicenter RCT of 3257 women, intrapartum oral sildenafil did not reduce the composite of hypoxia-related adverse perinatal outcomes compared with placebo. No significant effects were seen on emergency cesarean or instrumental birth for fetal distress, nor on individual components of the composite.
Impact: This definitive negative RCT closes a long-standing clinical question and discourages off-label use of intrapartum sildenafil to prevent hypoxia-related neonatal complications.
Clinical Implications: Intrapartum sildenafil should not be used to improve perinatal outcomes in laboring patients. Guidelines and protocols should avoid recommending sildenafil for intrapartum fetal hypoxia prevention.
Key Findings
- Primary composite outcome occurred in 5.1% (sildenafil) vs 5.2% (placebo); RR 1.02 (95% CI 0.75–1.37).
- No significant effect on emergency cesarean or instrumental birth for fetal distress (RR 1.12; 95% CI 0.98–1.29).
- No heterogeneity of treatment effect across prespecified subgroups.
Methodological Strengths
- Pragmatic, multicenter, placebo-controlled randomized design with large sample size
- Clinically relevant composite outcome with blinded allocation and standardized follow-up to 28-day neonatal mortality
Limitations
- Potential dilution of effect due to low event rates and broad inclusion criteria
- Fixed dosing schedule may not account for timing relative to labor progression
Future Directions: Focus should shift to alternative strategies for intrapartum fetal monitoring and timely obstetric interventions rather than pharmacologic vasodilators.
2. Risk of exacerbations, hospitalisation, and mortality in adults with physician-diagnosed chronic obstructive pulmonary disease with normal spirometry and adults with preserved ratio impaired spirometry in Sweden: retrospective analysis of data from a nationwide cohort study.
In a nationwide cohort of 45,653 adults with physician-diagnosed COPD, 5.4% had dnsCOPD and 11.4% had PRISm. Although dnsCOPD and PRISm had lower risks of exacerbations, respiratory hospitalizations, and respiratory mortality than spirometry-confirmed COPD, they remained symptomatic, commonly treated, and the GOLD A/B/E classification predicted future events in both groups.
Impact: This study extends risk stratification beyond spirometric thresholds, showing that clinically diagnosed patients with normal spirometry or PRISm still require structured management and prognostication.
Clinical Implications: Clinicians should apply GOLD A/B/E risk stratification in dnsCOPD and PRISm, address comorbidities (obesity, cardiovascular disease, diabetes), and avoid reflexive escalation to triple therapy without risk-based justification.
Key Findings
- Prevalence: dnsCOPD 5.4%, PRISm 11.4%, sCOPD 83.3% among 45,653 patients.
- Compared with sCOPD, lower risks in dnsCOPD and PRISm: exacerbations (SHR 0.69 and 0.85), respiratory hospitalization (0.40 and 0.68), respiratory mortality (0.22 and 0.60).
- GOLD A/B/E classification predicted outcomes in dnsCOPD and PRISm; group E in these phenotypes had higher risks than sCOPD A/B.
Methodological Strengths
- Nationwide registry with >1000 clinics, large sample and real-world representativeness
- Use of standardized GOLD A/B/E risk stratification and cause-specific outcomes
Limitations
- Observational design; residual confounding cannot be excluded
- Follow-up intensity and treatment decisions not randomized; potential treatment-by-indication bias
Future Directions: Prospective studies should test risk-based treatment algorithms in dnsCOPD and PRISm and evaluate comorbidity-targeted interventions.
3. Joint Effects of Wildfire Smoke and Extreme Heat on Hospitalizations in California, 2011-2020.
Using a time-stratified case-crossover analysis of >28 million hospitalization events in California, approximately 8% of respiratory hospitalizations were attributable to the interaction between wildfire smoke and extreme heat. Joint effects were also significant for cardiovascular and renal morbidity, with disproportionate impacts in Black individuals, females (cardiovascular), and adults aged 50–64 (renal).
Impact: This study quantifies compound climate-related exposures on hospitalizations and identifies high-risk subgroups, informing targeted public health advisories and combined heat–smoke response strategies.
Clinical Implications: Healthcare systems should integrate joint heat and wildfire smoke warnings into respiratory and cardiovascular risk management, prioritize outreach to vulnerable populations, and plan surge capacity during concurrent events.
Key Findings
- Approximately 8% (95% CI 2.4%–13.8%) of respiratory hospitalizations were attributable to wildfire smoke–heat interaction over a 4-day window.
- Significant joint effects for cardiovascular (5.5%) and renal (6.2%) morbidities.
- Stronger interaction effects in Black individuals (respiratory 19.2%, cerebrovascular 15.7%), females (cardiovascular 9.8%), and adults aged 50–64 (renal 15.4%).
Methodological Strengths
- Time-stratified case-crossover design controls for time-invariant confounders
- Evaluation across multiple exposure lags and additive/multiplicative interaction scales with subgroup analyses
Limitations
- Exposure assessment based on modeled wildfire-influenced PM2.5 and ambient heat may introduce measurement error
- Findings may not generalize outside California or to non-hospital outcomes
Future Directions: Develop and test integrated early-warning and intervention systems for concurrent smoke and heat events, with tailored messaging and resource allocation for high-risk communities.