Forced Vital Capacity in Patients with Idiopathic Pulmonary Fibrosis

Imperial College, London, UK.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 09/2011; 184(12):1382-9. DOI: 10.1164/rccm.201105-0840OC
Source: PubMed


Forced vital capacity (FVC) is an established measure of pulmonary function in idiopathic pulmonary fibrosis (IPF). Evidence regarding its measurement properties and minimal clinically important difference (MCID) in this population is limited.
To assess the reliability, validity, and responsiveness of FVC and estimate the MCID in patients with IPF.
The study population included all 1,156 randomized patients in two clinical trials of IFN-γ1b. FVC and other measures of functional status were measured at screening or baseline and 24-week intervals thereafter. Reliability was assessed based on two proximal measures of FVC, validity was assessed based on correlations between FVC and other measures of functional status, and responsiveness was assessed based on the relationship between 24-week changes in FVC and other measures of functional status. Distribution-based and anchor-based methods were used to estimate the MCID.
Correlation of percent-predicted FVC between measurements (mean interval, 18 d) was high (r = 0.93; P < 0.001). Correlations between FVC and other parameters were generally weak, with the strongest observed correlation between FVC and carbon monoxide diffusing capacity (r = 0.38; P < 0.001). Correlations between change in FVC and changes in other parameters were slightly stronger (range, r = 0.16-0.37; P < 0.001). Importantly, 1-year risk of death was more than twofold higher (P < 0.001) in patients with a 24-week decline in FVC between 5% and 10%. The estimated MCID was 2-6%.
FVC is a reliable, valid, and responsive measure of clinical status in patients with IPF, and a decline of 2-6%, although small, represents a clinically important difference.

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    • "Such changes were also found to impact on quality of life (QoL; Figure  2) [41]. In a larger study of 1156 patients with IPF [39], the MCID in FVC was defined as 2–6% (equivalent to a 3–9% relative change) and changes from baseline in % predicted FVC reflected changes in global health status (Figure  3) [39]. "
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    ABSTRACT: Pompe disease/glycogen storage disease type II, is a rare, lysosomal storage disorder associated with progressive proximal myopathy, causing a gradual loss of muscular function and respiratory insufficiency. Studies of patients with late-onset Pompe disease have used endpoints such as the 6-minute walking test (6MWT) and forced vital capacity (FVC) to assess muscular and respiratory function during disease progression or treatment. However, the relevance of these markers to late-onset Pompe disease and the minimal clinically important difference (MCID) for these endpoints in late-onset Pompe disease have not yet been established. A literature search was carried out to identify studies reporting the MCID (absolute and relative) for the 6MWT and FVC in other diseases. The MCIDs determined in studies of chronic respiratory diseases were used to analyze the results of clinical studies of enzyme replacement therapy in late-onset Pompe disease. In 9 of the 10 late-onset Pompe disease studies reviewed, changes from baseline in the 6MWT were above or within the MCID established in respiratory diseases. Clinical improvement was perceived by patients in 6 of the 10 studies. In 6 of the 9 late-onset Pompe disease studies, the changes from baseline in percentage change in predicted FVC were above or within the MCID established for respiratory diseases and the difference was perceived as either an improvement or stabilization by patients." with "In 6 of the 9 late-onset Pompe disease studies that reported FVC, the changes from baseline in percentage predicted FVC were above or within the MCID established in respiratory diseases and the difference was perceived as either an improvement or stabilization by patients. However, applying the 6MWT and FVC MCIDs from studies of chronic respiratory diseases to late-onset Pompe disease has several important limitations. Outcome measures in muscular dystrophies include composite measures of muscle function and gait, as well as Rasch-designed and validated tools to assess disease-related quality of life and activities of daily living. Given that the relevance to patients with late-onset Pompe disease of the 6MWT or FVC MCIDs established for chronic respiratory diseases is unclear, these measures should be evaluated specifically in late-onset Pompe disease and alternative outcome measures more specific to neuromuscular disease considered.
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    • "Desaturation during the 6MWT has been shown to be predictive of mortality in ILD [1]. Recent studies in idiopathic pulmonary fibrosis (IPF) have shown that small changes in FVC are associated with clinically significant changes in health status and mortality [2] [3]. It is not known if small changes in FVC are clinically important in a range of ILDs. "
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    • "Forced vital capacity (FVC) is the most commonly used physiological measurement and primary endpoint in clinical trials in IPF. In fact, changes in a patient’s FVC over time (whether analyzed continuously or categorically as above or below a threshold value) have been correlated with survival time in multiple large cohorts of patients with IPF [1,50]. Recently, in a 12-month, phase 2 trial, BIBF 1120 - an intracellular tyrosine kinase inhibitor - has been shown to reduce by 68% the annual rate of decline in FVC as compared with placebo in patients with IPF (0.06 liters vs. 0.19 liters) [51]. "
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