Idiopathic Pulmonary Fibrosis

Abstract

Rationale and Hypothesis: Idiopathic pulmonary fibrosis is a fatal disease with a variable rate of progression. We hypothesized that changes in distance walked and quantity of desaturation during a six-minute-walk test (6MWT) would add prognostic information to changes in FVC or diffusing capacity for carbon monoxide. Methods: One hundred ninety-seven patients with idiopathic pulmonary fibrosis were evaluated. Desaturation during the 6MWT was associated with increased mortality even if a threshold of 88% was not reached. Baseline walk distance predicted subsequent walk distance but was not a reliable predictor of subsequent mortality in multivariate survival models. The predictive ability of serial changes in physiology varied when patients were stratified by the presence/absence of desaturation р 88% during a baseline 6MWT. For patients with a baseline saturation р 88% during a 6MWT, the strongest observed predictor of mortality was serial change in diffusing capacity for carbon monoxide. For patients with saturation Ͼ 88% during their baseline walk test, serial decreases in FVC and increases in desaturation area significantly predicted subsequent mortality, whereas decreases in walk distance and in diffusing capacity for carbon monoxide displayed less consistent statistical evidence of increasing mortality in our patients. Conclusion: These data highlight the importance of stratifying patients by degree of desaturation during a 6MWT before attributing prognostic value to serial changes in other physiologic variables.Keywords: idiopathic pulmonary fibrosis; six-minute-walk test; prognosis; pulmonary function; survival Idiopathic pulmonary fibrosis (IPF) is a uniformly fatal disease with a variable rate of progression. Identification of readily available baseline and short-term serial predictors of survival is critical for physicians and patients considering options such as lung transplantation and for the investigation of novel treatments. Recent studies have suggested several demographic (age, smoking), physiologic (diffusion capacity for carbon monoxide [Dl CO ], FVC, and desaturation), radiologic (high-resolution computed tomography [HRCT] fibrosis score), and histopathologic (fibroblastic foci) features are associated with survival (1-7). Serial change in FVC adds additional prognostic information to data obtained at baseline (8-11).(Received in original form April 6, 2006; accepted in final form June 30, 2006 ) Supported by National Institutes of Health NHLBI grants P50HL-56402, NHLBI, 2 K24 HL04212, 1 K23 HL68713, and 1K23 HL077719.Correspondence and requests for reprints should be addressed to Kevin R. A central feature in the pathophysiology of IPF is impaired gas exchange, which worsens with exercise (12, 13). This exerciseinduced widening of alveolar arterial O 2 gradient and fall in Pa O 2 is believed to be secondary to multiple abnormalities, including V /Q mismatch, decreased Pv O 2 and venous admixture (12-16). The six-min-walk test (6MWT) is a safe procedure for patients with IPF. Baseline des...

Principles of Rehabilitation and Reactivation: Interstitial Lung Disease, Sarcoidosis and Rheumatoid Disease with Respiratory Involvement

“…There is a strong relationship between reduced exercise capacity and increased mortality, particularly in IPF [10]. Exercise capacity is frequently a stronger predictor of prognosis than resting respiratory function [11,12]. There are multiple contributors to exercise limitation in ILD, with gas exchange limitation and circulatory limitation playing important roles.…”

Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis: A Review

“…Undoubtedly, this mechanism plays a role, but it is unlikely to account for all cases of PH, for example the presence of PH in normoxemic IPF patients. Furthermore, intermittent nocturnal hypoxia and also exercise-induced desaturation, which are often present in IPF patients [8,35], might represent important factors in the development of disproportionate PH in these patients and need to be appropriately evaluated [36]. Interestingly, Pouwels-Fry et al [37] demonstrated that oxygen did not improve an exercise-induced increase in pulmonary artery pressure in IPF patients, suggesting that hypoxic vasoconstriction is not the only mechanism contributing to the acute increase in pulmonary pressure during exercise.…”

“…The most commonly used exercise tests are the 6-min walk test (6MWT) and cardiopulmonary exercise testing. Impaired gas exchange which worsens with exercise is a common feature in the pathophysiology of IPF and appears to have prognostic value as well [7,8,63]. When PH is present in the setting of IPF, common physiological abnormalities during exercise include decreased maximal oxygen consumption, increased dead space with progressive exercise and a low anaerobic threshold [64,65].…”

“…It is a fatal disorder with a median survival of 2.5–5 years, as no effective treatment exists to date. Poor prognosis has been associated with older age, male gender, lower forced vital capacity, lower diffusing capacity, desaturation during exercise and the extent of fibrosis on imaging studies [6,7,8]. Pulmonary hypertension (PH) is recognized as a severe complication of IPF [6,9].…”

Long-Term Intersession Variability for Single-Breath Diffusing Capacity

“…Defining intra-individual variability for D l CO is clinically important. Serial measurements of D l CO are commonly performed to assess disease activity in response to therapeutic interventions [11,12,13] and to monitor the effects of drug or toxin exposures [14,15,16]. …”