Abstract
RATIONALE: Small airways disease (SAD) and hyperinflation are common in precapillary pulmonary hypertension (PH). Activin signaling plays an important role in airway and bronchial function. OBJECTIVE: To determine whether treatment with sotatercept, an activin signaling inhibitor, for severe precapillary PH is associated with improvements in physiologic markers of SAD and hyperinflation. METHODS: We conducted a single-center, retrospective cohort study of participants who received sotatercept for the treatment of severe precapillary PH despite background PH treatments who also had pulmonary function tests (PFT) before and after initiation of sotatercept treatment. MEASUREMENTS AND MAIN RESULTS: Forty-eight participants were included (median age 68 years, 77% female). Median BMI was 26.7 kg/m(2) (IQR 23.6-31.4). All participants were functional class III or IV. Follow-up PFTs obtained a median of 4.4 months after sotatercept initiation showed significant improvements: FEV1 +155 mL (11%, 95% confidence interval [CI], 100-215 mL; p<0.001), FVC +180 mL (10%, 95% CI, 125-245 mL; p<0.001), FEF25-75% +0.15 L/sec (16%, 95% CI, 0.03-0.28 L/sec; p=0.015), DLCO +0.79 mL/min/mmHg (10%, 95% CI, 0.30-1.25 mL/min/mmHg; p<0.01). In participants with paired lung volume measurements (n=22), RV decreased 210 mL (12%, 95% CI, -340 to -85 mL; p<0.01), RV/TLC decreased 5% (95% CI, -7% to -3%; p<0.001), and ERV increased 175 mL (29%, 95% CI, 50-385 mL; p=0.02). There was no overall change in TLC or FRC. CONCLUSIONS: In a real-world cohort of patients with severe precapillary PH from a variety of causes, sotatercept was associated with improvements in markers of SAD and hyperinflation.