Hill, Nicholas S.

Abstract The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched “Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics” (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.

Guidelines for the treatment of pulmonary arterial hypertension (PAH) recommend sequential add‐on therapy for patients who deteriorate or fail to improve clinically. However, it is not known whether these patients also benefit from transitioning from inhaled prostacyclins to parenteral prostacyclins. We sought to characterize PAH patients receiving inhaled treprostinil who were transitioned to parenteral treprostinil. We conducted a multicenter retrospective study at 7 PAH centers and collected reasons, methods, safety, and outcome of patients transitioned from inhaled treprostinil to parenteral treprostinil. Twenty‐six patients with pulmonary hypertension in group 1, 4, or 5 transitioned from inhaled treprostinil to parenteral treprostinil (10 intravenous, 16 subcutaneous). Twenty‐four patients were also on one or two oral therapies. Reasons for transition were clinical deterioration, lack of clinical improvement, and pregnancy (19, 6, and 1 patients, respectively). Transitions occurred in hospital, clinic, or home (17, 7, and 2 patients, respectively). Parenteral infusion was started after the last inhaled treatment at maintenance dose (13 patients), after the inhaled therapy was downtitrated to 18 μg (6 patients), or with an overlap of inhaled downtitration with parenteral uptitration (7 patients). The transition was safe; side effects included symptoms of prostacyclin overdose. Patients were followed for 3–18 months. At 3 months, 8 patients improved, 17 maintained their functional class, and 1 continued to deteriorate. In conclusion, selected PAH patients can be safely transitioned from inhaled treprostinil to parenteral treprostinil using a variety of methodologies in different settings with the expectation that patients will improve or at least remain clinically stable.

Abstract Noninvasive positive pressure ventilation (NPPV) is usually applied using pressure support ventilation (PSV). Proportional assist ventilation (PAV) is a newer mode that delivers assisted ventilation in proportion to patient effort. We hypothesized that PAV for NPPV would support gas exchange and avoid intubation as well as PSV and be more comfortable and tolerable for patients. Adult patients with acute respiratory insufficiency were randomized to receive NPPV with PAV delivered using the Respironics Vision ventilator or PSV using a Puritan-Bennett 7200ae critical care ventilator. Each mode was adjusted to relieve dyspnea and improve gas exchange until patients met weaning or intubation criteria, died, or refused to continue. Twenty-one and 23 patients were entered into the PAV and PSV groups, respectively, and had similar diagnoses and baseline characteristics, although pH was slightly lower in the PAV group (7.30 versus 7.35, p = 0.02). Mortality and intubation rates were similar, but refusal rate was lower, reduction in respiratory rate was more rapid, and there were fewer complications in the PAV group. We conclude that use of the PAV mode is feasible for noninvasive therapy of acute respiratory insufficiency. Compared with PSV delivered with the Puritan-Bennett 7200ae, PAV is associated with more rapid improvements in some physiologic variables and is better tolerated.