Sildenafil Therapy and Exercise Tolerance in Idiopathic Pulmonary Fibrosis

Abstract

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.

An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management

“…There were no differences in serious adverse events or mortality over 24 weeks. A second study randomized 29 subjects with IPF to sildenafil or placebo (273). Unlike the first study, there was no requirement for advanced disease; the average DL CO in this study group was 42% predicted.…”

Physical Activity and Quality of Life Improvements of Patients With Idiopathic Pulmonary Fibrosis Completing a Pulmonary Rehabilitation Program

“…8 Inclusion and exclusion criteria were identical to those described elsewhere. 9,10 To screen and define cases, we consistently used the following diagnostic scheme. Three major criteria were required, including exclusion of other known causes of ILD, abnormal pulmonary function tests, and bibasilar, reticular abnormalities with minimal ground glass opacities on high-resolution computed tomography.…”

Pulmonary hypertension in chronic interstitial lung diseases

“…Supplemental oxygen is indicated for prevention and therapy of PH due to hypoxia; however, there are no data supporting the beneficial effect of oxygen on survival in this group of patients. There is no clear evidence that specific therapies utilised in pulmonary arterial hypertension (PAH) can be an effective treatment for PH in IPF patients, and welldesigned prospective studies are needed before routine use of these agents can be recommended and a firm conclusion made [16,[37][38][39][40][41][42][43]. The Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (STEP-IPF study) [44] intended to evaluate the effects of sildenafil in a population with advanced IPF, defined by the severity of lung function abnormalities (DLCO ,35% predicted).…”