No abstract

In this open-label study, we evaluated the effect of upfront macitentan and riociguat combination in newly diagnosed pulmonary arterial hypertension (PAH) patients. In 15 consecutive PAH patients, we collected clinical and hemodynamic data at baseline, visit 1 (median 4 months) and visit 2 (median 12 months). Survival and transplantation status were analyzed over 36 months. Statistical analysis included student t-test and 95% confidence interval (CI) (t-statistic or Clopper-Pearson). Kaplan-Meier was used to estimate survival rate. There were 11/15 women (mean age 56 years), in World Health Organization (WHO) functional class (FC) III (n = 14) or IV (n = 1). The 6 min walk distance increased from 281.6 m (baseline) to 315.7 m (visit 1) and visit 2 (313.9 m), representing a 34- and 32-m change (P < 0.05), respectively, associated with Borg score improvements. Brain natriuretic peptide decreased: 318.2 pg/mL (baseline) to 122.0 pg/mL (visit 1) and 98.6 pg/mL (visit 2) (P < 0.05). WHO FC improved in eight patients (53%, 95% CI 27%–79%). Pulmonary vascular resistance (9.2 to 5.7 Wood Units) and mean pulmonary artery pressure (47.3 to 38.9 mmHg) decreased; cardiac index increased (2.3 to 3.0 L/min/m2) (baseline to visit 2, all P < 0.05). All patients had intermediate and high risk score (baseline); at 1-year follow-up, dual therapy led to reduction to low risk score in 7/15 (47%) patients. There were no unexpected or serious side effects. Three patients died due to unrelated causes; one patient received a lung transplant. Transplant-free survival rate (36 months) was 85%. Preliminary evidence is provided for effectiveness of initial macitentan and riociguat combination therapy in PAH.

The Coronavirus disease (COVID-19) pandemic of 2019 has resulted in significant morbidity and mortality, especially from severe acute respiratory distress syndrome (ARDS). As of September 2022, more than 6.5 million patients have died globally, and up to 5% required intensive care unit treatment. COVID-19-associated ARDS (CARDS) differs from the typical ARDS due to distinct pathology involving the pulmonary vasculature endothelium, resulting in diffuse thrombi in the pulmonary circulation and impaired gas exchange. The National Institute of Health and the Society of Critical Care Medicine recommend lung-protective ventilation, prone ventilation, and neuromuscular blockade as needed. Further, a trial of pulmonary vasodilators is suggested for those who develop refractory hypoxemia. A review of the prior literature on inhaled pulmonary vasodilators in ARDS suggests only a transient improvement in oxygenation, with no mortality benefit. This narrative review aims to highlight the fundamental principles in ARDS management, delineate the fundamental differences between CARDS and ARDS, and describe the comprehensive use of inhaled pulmonary vasodilators. In addition, with the differing pathophysiology of CARDS from the typical ARDS, we sought to evaluate the current evidence regarding the use of inhaled pulmonary vasodilators in CARDS.

All participants gave informed consent on Fred Hutch IRB-approved protocols for the use of their medical data and protected health identifiers in research.

Background: Diffuse alveolar hemorrhage (DAH) occurs in patients with both primary and secondary antiphospholipid antibody syndrome (APS). We sought to determine the differences in clinical presentation, management, and outcomes of DAH in these patients. Methods:We performed a medical records review study and reviewed 30 patients with DAH in the setting of primary and secondary antiphospholipid syndrome seen at our institution between January 1, 1997, and December 31, 2018. We analyzed their demographics, clinical presentation, laboratory values, imaging studies, lung pathology results, management, and outcomes. Results:The patients in the secondary APS cohort were younger (median age, 48.5 vs 58 years) and comprised more females (75% vs 17%) compared with those with primary APS (p < 0.05). Two thirds of patients in the secondary APS group were anemic compared with less than one fourth in the primary APS group (p = 0.005). At the time of the first episode of DAH, the patients in the secondary APS required invasive and noninvasive ventilation, antibiotics, and combination immunosuppressive therapy (includes a combination of glucocorticoids with immunosuppressants or intravenous immunoglobulins or plasma exchange) more often compared with those with primary APS. There was only one in-hospital death (3% in-hospital mortality). Oneyear and 5-year mortality rates were 20% and 27%, respectively, with no significant difference between the primary and secondary APS groups.Conclusions: Diffuse alveolar hemorrhage in the setting of APS, especially secondary APS, can be severe. However, in-hospital mortality is uncommon with current management strategies.