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 twiceweekly, 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.) Key words: idiopathic pulmonary fibrosis; pulmonary rehabilitation; exercise; quality of life.

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.

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.

We tested whether markers of systemic oxidant stress were detectable in 29 typical IPF patients, and whether these increased after low level exercise. We obtained resting plasma for measurement of amino terminal pro brain natriuretic peptide (NT-proBNP), and plasma and urine samples for isoprostanes and total nitrite. Total antioxidant capacity (TAC) was measured in plasma, and H(2)O(2) was measured in urine. Subjects exercised at ˜50 W on a semi recumbent bicycle until limited by dyspnea. Samples were obtained immediately after exercise for measurement of the same variables. Plasma and urine samples were also obtained at rest from 6 normal individuals over 40 years of age solely to establish comparison values for NT-proBNP, nitrite, H(2)O(2) and TAC assays. Plasma NT-proBNP was high at rest and after exercise, suggesting pulmonary arterial hypertension. IPF patients' resting NT-proBNP concentrations apparently exceeded those of normal controls. IPF plasma isoprostanes at rest exceeded the normals. IPF urine isoprostanes increased significantly after exercise (P = 0.047 by signed rank test); and, plasma TAC decreased significantly after exercise (P < 0.001 by signed rank test). Neither plasma nor urine nitrite changed significantly after exercise. H(2)O(2) concentration was quite high after exercise in some IPF subjects' urine. IPF patients demonstrate systemic oxidant stress at rest detectable as increased isoprostanes in the circulation. An increase in urine isoprostanes and a decrease in plasma TAC after exercise suggest that reactive oxygen species (ROS) are produced during low level exercise done by IPF patients.

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