Aerobic Exercise in Patients With Pulmonary Hypertension

We propose a randomized trial to determine the safety and effectiveness of aerobic exercise for patients who have primary pulmonary hypertension (PH) or PH secondary to interstitial lung disease (ILD). This project will be the first in a series of studies aimed at establishing exercise prescription and general rehabilitation guidelines for patients who have advanced lung diseases.

An essential treatment for almost all cardiovascular and pulmonary disorders is aerobic exercise training. The effectiveness of exercise rehabilitation has been established and exercise rehabilitation has become a standard of care for patients with chronic obstructive pulmonary disease (COPD). However, fundamental information about the mechanisms underlying exercise training and its therapeutic benefits remains lacking for patients who have advanced lung disease in general and specifically for those with PH.

Subjects will be over the age of 21 years. The patients will be enrolled from sites within a reasonable travel distance from the greater Washington area and will receive their exercise training at Inova Fairfax Hospital or at the National Institutes of Health (NIH) main campus. Exercise-based rehabilitation is already common for patients who have PH at the Inova Fairfax Hospital. Their pulmonary rehabilitation program is well established, and their staff is experienced in providing exercise therapy for patients with PH and advanced lung diseases. The Rehabilitation Medicine Department (RMD) at The NIH Clinical Center has established a pulmonary rehabilitation program for this protocol as well as to provide rehabilitation services for NIH clinic patients.

There will be two primary treatment arms. Patients with PH will be randomized to either aerobic exercise training plus education (AET) or education only (Ed-only) treatments. A comparison group of patients with ILD who do not have secondary PH (ILD-only) will also undergo the AET arm. Exercise training will consist of a 10-week regimen of supervised treadmill or over ground walking three times a week. Exercise session duration will be 30 minutes and will progress to 45 minutes per session over the 10 weeks. The intensity of the exercise will be between 70 and 80% of the heart rate reserve.

There will also be two secondary studies. First, the subjects with PH initially randomized to the education only arm will complete an aerobic exercise training program after participation in education. In addition, we will also compare baseline tests among patients with PH, patients with ILD-only and healthy controls.

The study outcome measures will be assessed at NIH, RMD. These will include pre- and post-exercise training comparisons of symptom limited treadmill exercise tests to assess heart rate, pulse oximetry, EKG, maximum oxygen consumption, bioelectrical impedance cardiography, and near infrared spectroscopy measurements of muscle oxygenation. We will also assess accelerometry based activity, 6-minute walk distance, and a number of other quality of life and functional measures questionnaires including: International Physical Activity Questionnaire, Fatigue Severity Scale, SF-36v2 Health Survey, Human Activity Profile, Stages of Exercise Change, Exercise Self-Efficacy, Profile of Mood States, Cambridge Pulmonary Hypertension Outcome Review.

This study represents a unique opportunity to assess the effects of exercise on patients with advanced lung disease and may open up valuable new treatment options for these patients.