Utility of Inhaled Nitric Oxide Vasoreactivity Challenge in Pulmonary Hypertension Associated with Interstitial Lung Disease

Background: Patients with pulmonary hypertension due to interstitial lung disease (PH-ILD) have worse exercise capacity and survival than ILD patients without PH. Vasoreactivity with inhaled nitric oxide (NO) provides prognostic and therapeutic implications in pulmonary arterial hypertension, but little is known on its value in PH-ILD. We evaluated the pulmonary hemodynamic changes following inhaled NO and their association with outcomes in PH-ILD. Methods: We measured pulmonary hemodynamics in patients with PH-ILD who underwent inhaled NO administration during right heart catheterization. We recorded baseline clinical, echocardiographic, and pulmonary function testing measures; and investigated the use of inhaled treprostinil as well as the rate of hospitalization, death and lung transplantation. Results: In 120 patients (age 67 ± 11 years, 62% women), the administration of inhaled NO resulted in a median (IQR) decrease in mean pulmonary artery pressure (mPAP) of -3 (-5, -1) mmHg, p<0.001, and PVR of -0.8 (-1.8, -0.2) Wood units, p<0.001. The % change in mPAP and PVR were -6.3 (-10.9, -1.8) % and -16.8 (-27.3, -3.3) %, respectively. Factors associated with the % drop in PVR included baseline PVR (r= 0.30, p<0.001), cardiac output (r= -0.19, p=0.04), and WHO functional class (r=0.25, p=0.01). The median (IQR) follow-up was 14.5 (7, 25) months. During this time, 40 (33%) patients died, 8 (7%) underwent lung transplantation, and 76 (63%) experienced either hospitalization due to respiratory failure, transplantation, or death. The % drop in mPAP and PVR during inhalation of NO had no significant impact on these outcomes and was not associated with clinical response to inhaled treprostinil measured by changes in six-minute walk distance (6MWD) and forced vital capacity (FVC). Conclusion: Inhaled NO caused a modest reduction in mPAP and PVR in patients with PH-ILD, but the acute hemodynamic response to inhaled NO, in our cohort, was not associated with outcomes or response to inhaled treprostinil therapy.