Effects of 100 % oxygen during exercise in patients with interstitial lung disease.

PURPOSE: Hypoxemia limits exercise in some patients with interstitial lung disease (ILD). High levels of supplemental oxygen during exercise might allow physical training at a higher level and more effective pulmonary rehabilitation (PR). Our goals were to use graded cardiopulmonary exercise testing (CPET) to determine whether hyperoxia (FIO2≈1.0) increased exercise tolerance in patients with mild to moderate ILD. METHODS: We studied 6 patients with ILD, including idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP). The study population included 3 females and 3 males (age 69 ± 5 [SD] years; FVC 61 ± 14 %; absolute DLCO 53 ± 19 %). Subjects underwent 2 ramped (15 W/min) CPET protocols on a cycle ergometer (Jaeger Oxycon Pro™, CareFusion Respiratory Care) breathing either air or oxygen (FIO2≈1.0) from a Douglas bag in random order. RESULTS: Minute ventilation (VE) increased significantly during CPET breathing air (pre CPET, 18 ± 2 [SEM] L/min; post CPET, 47 ± 6; P = 0.01), but it did not increase significantly breathing oxygen (pre CPET, 15 ± 3 [SEM]; post CPET, 29 ± 9; P = 0.06). Likewise, carbon dioxide production (VCO2) increased significantly during CPET breathing air (pre CPET, 450 ± 93 [SEM] mL/min; post CPET, 1311 ± 200; P = 0.01), but it did not increase significantly breathing oxygen (pre CPET, 369 ± 129; post CPET, 847 ± 832; P = 0.09). Exercise time during CPET did not differ significantly (P = 0.34) in air (5.6 ± 0.9 [SEM] min) or oxygen (7.0 ± 1.8). Increases in heart rate (HR) and Borg dyspnea index (BDI) after CPET were not affected by breathing oxygen. CONCLUSION: Exercise-induced increases in VE and VCO2 were prevented by breathing pure oxygen during CPET, demonstrating both decreased ventilatory drive and more efficient exercise at achieved workloads. Hyperoxia could enhance the ability of patients with ILD to train at higher workloads, resulting in more effective rehabilitation.

Physical activity and quality of life improvements of patients with idiopathic pulmonary fibrosis completing a pulmonary rehabilitation program.

INTRODUCTION: Pulmonary rehabilitation is effective for patients with COPD, but its benefit is less clearly established in idiopathic pulmonary fibrosis (IPF), especially in regard to levels of physical activity and health-related quality of life. The objectives were to determine whether pulmonary rehabilitation increased physical activity as assessed by the International Physical Activity Questionnaire (IPAQ), and improved quality of life and symptoms as assessed by the St George respiratory questionnaire for IPF (SGRQ-I) and the Borg dyspnea index (BDI). METHODS: Subjects who met current criteria for IPF were randomized to a 3-month pulmonary rehabilitation program (n = 11) or to a control group (n = 10). The rehabilitation group participated in twice-weekly, 90-min exercise sessions (24 total sessions). The control group maintained its preceding, normal physical activity. All subjects underwent 6-min walk tests to assess the postexertion BDI. The SGRQ-I and a 5-point self-assessment of health were completed at baseline, after 3 months of intervention or observation, and after 3-month follow-up. All subjects completed the IPAQ weekly. RESULTS: Subjects in the rehabilitation group maintained significantly higher levels of physical activity throughout the 3-month rehabilitation program (rehabilitation: 51,364 ± 57,713 [mean ± SD] metabolic equivalent of task-minutes; control: 20,832 ± 37,155, P = .027 by 2-tailed Mann-Whitney test). SGRQ-I symptom domain scores improved considerably by -9 ± 22 in the rehabilitation group, whereas in the control group they worsened (16 ± 12 rehabilitation compared with control, P = .013 by 2-tailed Mann-Whitney test). During the 3-month follow-up, self-reported physical activity levels in the rehabilitation group were 14,428 ± 8,884 metabolic equivalent of task-minutes and in the control group 16,923 ± 32,620 (P = .17 by 2-tailed Mann-Whitney test), demonstrating substantial reversal of activity in the rehabilitation group. BDI scores after 6-min walk tests did not change significantly. CONCLUSIONS: A 3-month rehabilitation program significantly improved symptoms (SGRQ-I) and physical activity levels (IPAQ) in subjects with IPF while they participated actively in the program. (ClinicalTrials.gov registration NCT01118221.).

Exercise limitation in IPF patients: a randomized trial of pulmonary rehabilitation.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) have severely limited exercise capacity due to dyspnea, hypoxemia, and abnormal lung mechanics. This pilot study was designed to determine whether pulmonary rehabilitation were efficacious in improving the 6-min walk test (6-MWT) distance, exercise oxygen uptake, respiratory muscle strength [maximum inspiratory pressure (MIP)], and dyspnea in patients with IPF. Underlying physiological mechanisms and effects of the intervention were investigated. METHODS: Subjects were randomly assigned to a 3-month pulmonary rehabilitation program (n = 11) or to a control group (n = 10). All subjects initially underwent the 6-MWT and constant load exercise gas exchange studies. RESULTS: Subjects in the rehabilitation group increased treadmill exercise [metabolic equivalent of task-minutes] over the first 14 sessions. Beneficial effects on physical function resulted in those who completed rehabilitation. Subjects who completed the program increased cycle ergometer time and maintained exercise oxygen consumption (exercise VO(2)) at the baseline level over 3 months, while the control group suffered a significant decrease in exercise VO(2). Rehabilitation subjects also increased their MIP. Plasma lactate doubled and brain natriuretic peptide levels increased significantly after exercise, as did the plasma amino acids glutamic acid, arginine, histidine, and methionine. These changes were associated with significant decreases in arterial oxygen saturation and increases in 15-F(2t)-isoprostanes after exercise. CONCLUSIONS: Pulmonary rehabilitation effectively maintained exercise oxygen uptake over 3 months and lengthened constant load exercise time in patients with moderately severe IPF. Exercise endurance on cycle ergometry testing was limited by dyspnea and severe hypoxemia associated with systemic oxidant stress.

Sildenafil therapy and exercise tolerance in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a form of idiopathic interstitial pneumonia characterized by temporally and spatially heterogeneous fibroblast proliferation and poor prognosis. No therapies have been shown in randomized clinical trials (RCT) to influence survival. Twenty-nine subjects were assigned randomly in a pilot study to a double-blind, placebo-controlled, RCT to test sildenafil in patients with IPF with forced vital capacity 40-90% and diffusing capacity 30-90% of predicted. During the 6-month experimental treatment period, patients underwent 6-min walk tests and estimation of dyspnea using the Borg scale at baseline (0 months), 3 months, and 6 months. Participants had moderate impairment of pulmonary function, and there were no significant differences between placebo (n = 15) and sildenafil (n = 14)-treated groups. Sildenafil did not significantly increase 6-min walk test distance (mean distance +/- SD after 6-month protocol: placebo 355 +/- 82 m, sildenafil 324 +/- 41 m; p = 0.256) nor did it lessen dyspnea after exercise (mean Borg score after 6-month protocol: placebo 3.4 +/- 1.6, sildenafil 4.1 +/- 2.3; p = 0.492). Adverse reactions were few and minor in nature. In this trial, sildenafil did not significantly increase 6-min walk test distance or decrease the Borg dyspnea index in patients with clinically typical IPF. This trial was registered at clinicaltrials.gov as NCT00359736.