Pulmonology

Triple-therapy COPD mortality signal in ETHOS/IMPACT likely driven by ICS withdrawal

This Thorax reanalysis argues that ETHOS and IMPACT mortality differences favoring triple therapy stem from inhaled corticosteroid (ICS) withdrawal in dual-therapy arms. Patients randomized to LAMA/LABA comparators had protocol-mandated cessation of maintenance ICS, which was associated with excess deaths. The data suggest that triple therapy’s apparent mortality benefit is at least partly an artifact of comparator design, not intrinsic triple superiority. Guideline claims of mortality reduction with triple therapy should be interpreted cautiously, especially when contemplating ICS withdrawal in stable patients. 1

Ensifentrine improves FEV1 and symptoms in Chinese patients with moderate-to-severe COPD

In this 24-week phase III trial, 525 Chinese participants with symptomatic moderate-to-severe COPD were randomized 5:3 to nebulized ensifentrine or placebo. Ensifentrine increased average FEV1 AUC0–12h versus placebo by 110 mL (95% CI, 69–151 mL; P<0.0001), with consistent benefit across severity and maintenance-therapy strata. Treatment improved dyspnea (Transition Dyspnea Index) and health status scores on Evaluating Respiratory Symptoms and St. George’s Respiratory Questionnaire compared with placebo. Ensifentrine tended to reduce moderate-to-severe exacerbation rates and prolong time to first exacerbation, with similar adverse event rates to placebo. 2

Sotatercept reduces pulmonary vascular resistance in CpcPH-HFpEF

CADENCE randomized 164 adults with CpcPH-HFpEF to sotatercept 0.3 mg/kg, 0.7 mg/kg, or placebo every three weeks for 24 weeks. Baseline median pulmonary vascular resistance (PVR) was 5.2 Wood units, indicating substantial pre-capillary load. Placebo-adjusted Hodges-Lehmann PVR shifts were -1.02 Wood units (95% CI, -1.81 to -0.23; P=0.004) for 0.3 mg/kg and -0.75 (95% CI, -1.52 to 0.03; P=0.024) for 0.7 mg/kg. Both sotatercept doses also reduced mean pulmonary arterial and wedge pressures and modestly improved 6-minute walk distance, particularly at 0.3 mg/kg. 3

EBRT outperforms bronchoscopic strategies for survival in malignant central airway obstruction

Using TriNetX data, 11,478 patients with malignant central airway obstruction receiving EBRT were propensity-matched 1:1 to stenting, debulking, or stent-plus-EBRT cohorts. EBRT yielded longer median survival than stenting (1029 vs 627 days; HR 0.776; P<0.0001) and debulking (1068 vs 692 days; HR 0.762; P<0.0001). Compared with stent plus EBRT, EBRT alone had better median survival (1003 vs 545 days; HR 0.706; P<0.0001) and lower mortality odds. At six months, EBRT showed substantially lower mortality than all comparators, with benefits persisting at one year before convergence by five years. 4