Daily Respiratory Research Analysis
Three practice-informing trials stand out today: a double-blind phase 3b trial shows that as-needed albuterol–budesonide halves severe exacerbations in mild asthma; two phase 3 trials of the PDE4B inhibitor nerandomilast slow FVC decline in idiopathic pulmonary fibrosis over 52 weeks; and a multicenter randomized trial finds navigational bronchoscopy noninferior to transthoracic needle biopsy with far fewer pneumothoraces for peripheral lung nodules.
Summary
Three practice-informing trials stand out today: a double-blind phase 3b trial shows that as-needed albuterol–budesonide halves severe exacerbations in mild asthma; two phase 3 trials of the PDE4B inhibitor nerandomilast slow FVC decline in idiopathic pulmonary fibrosis over 52 weeks; and a multicenter randomized trial finds navigational bronchoscopy noninferior to transthoracic needle biopsy with far fewer pneumothoraces for peripheral lung nodules.
Research Themes
- Anti-inflammatory reliever therapy in mild asthma
- Antifibrotic innovation in idiopathic pulmonary fibrosis
- Diagnostic pathway optimization for peripheral pulmonary nodules
Selected Articles
1. As-Needed Albuterol-Budesonide in Mild Asthma.
In this double-blind, event-driven phase 3b trial (n=2,516), as-needed albuterol–budesonide reduced severe exacerbations by about half versus albuterol alone in mild asthma, with similar adverse events and lower systemic steroid exposure. The trial stopped early for efficacy at interim analysis.
Impact: This provides high-level evidence that an anti-inflammatory reliever strategy benefits patients with mild asthma, a large population with frequent SABA-only use.
Clinical Implications: Clinicians can consider as-needed albuterol–budesonide instead of SABA-only for mild asthma to reduce severe exacerbations and systemic steroid exposure.
Key Findings
- Severe exacerbations: 5.1% with albuterol–budesonide vs 9.1% with albuterol alone (on-treatment; HR 0.53; 95% CI 0.39–0.73; P<0.001).
- Intention-to-treat analysis: 5.3% vs 9.4% (HR 0.54; 95% CI 0.40–0.73; P<0.001).
- Annualized severe exacerbation rate reduced (0.15 vs 0.32; rate ratio 0.47; 95% CI 0.34–0.64).
- Lower mean annual systemic glucocorticoid dose (23.2 vs 61.9 mg/year).
- Adverse events were similar between groups.
Methodological Strengths
- Multicenter, double-blind, randomized, event-driven phase 3b design.
- Efficacy signal robust across on-treatment and ITT analyses with prespecified interim stopping.
Limitations
- Fully virtual, decentralized design may affect generalizability and adherence assessment.
- Trial stopped early for efficacy, which can overestimate effect sizes.
Future Directions: Head-to-head comparisons with maintenance low-dose ICS, real-world effectiveness across diverse health systems, and long-term safety are warranted.
2. Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis.
In a 52-week, double-blind phase 3 trial (n=1,177), nerandomilast attenuated FVC decline in IPF versus placebo, including in patients already receiving nintedanib or pirfenidone. Diarrhea was the most frequent adverse event; serious adverse events were balanced.
Impact: This is a large, well-controlled phase 3 trial of a novel PDE4B inhibitor showing clinically meaningful preservation of lung function in IPF, a disease with high unmet need.
Clinical Implications: Nerandomilast could be considered as an add-on or alternative antifibrotic option to slow lung function decline in IPF; monitoring for gastrointestinal adverse effects is required.
Key Findings
- Adjusted mean FVC change at week 52: −114.7 mL (18 mg), −138.6 mL (9 mg), −183.5 mL (placebo).
- Adjusted differences vs placebo: +68.8 mL (18 mg; 95% CI 30.3–107.4; P<0.001) and +44.9 mL (9 mg; 95% CI 6.4–83.3; P=0.02).
- 77.7% were on nintedanib or pirfenidone at enrollment; benefit observed across background therapy strata.
- Diarrhea occurred in 41.3% (18 mg), 31.1% (9 mg), 16.0% (placebo); serious adverse events were similar across groups.
Methodological Strengths
- Large, multicenter, double-blind randomized design with 52-week follow-up.
- Stratification by background antifibrotic therapy and clinically meaningful primary endpoint (FVC).
Limitations
- Primary endpoint was FVC change; effects on mortality or acute exacerbations were not established.
- Gastrointestinal side effects (notably diarrhea) were more frequent with nerandomilast.
Future Directions: Evaluate long-term outcomes (mortality, exacerbations), head-to-head comparisons with existing antifibrotics, and biomarker-driven responder analyses.
3. Navigational Bronchoscopy or Transthoracic Needle Biopsy for Lung Nodules.
In a multicenter randomized noninferiority trial (n=234 analyzed), navigational bronchoscopy achieved noninferior 12-month diagnostic accuracy compared with transthoracic needle biopsy for 10–30 mm peripheral nodules, while markedly reducing pneumothorax (3.3% vs 28.3%) and need for chest tube or admission.
Impact: The trial supports a safer first-line diagnostic strategy for peripheral pulmonary nodules without sacrificing accuracy, with substantial reductions in pneumothorax risk.
Clinical Implications: For intermediate/high-risk 10–30 mm peripheral nodules, navigational bronchoscopy may be preferred to minimize pneumothorax and downstream resource use while maintaining diagnostic accuracy.
Key Findings
- Diagnostic accuracy at 12 months: 79.0% (navigational bronchoscopy) vs 73.6% (transthoracic biopsy); absolute difference 5.4 percentage points (95% CI −6.5 to 17.2); noninferiority P=0.003.
- Pneumothorax: 3.3% with navigational bronchoscopy vs 28.3% with transthoracic biopsy; chest tube/admission required in 0.8% vs 11.5%, respectively.
- Randomized, multicenter comparison in 10–30 mm peripheral nodules and intermediate/high malignancy risk.
Methodological Strengths
- Randomized, multicenter, parallel-group noninferiority design with 12-month confirmation of diagnosis.
- Clinically meaningful safety endpoints captured (pneumothorax, chest tube, admission).
Limitations
- Operator and center expertise may influence outcomes and limit generalizability.
- Sample size, while adequate for noninferiority, may limit subgroup analyses.
Future Directions: Cost-effectiveness, patient-reported outcomes, and integration with robotic or advanced guidance systems merit evaluation; validation across diverse practice settings is needed.