|Topic:||12. Diffuse Parenchymal Lung Diseases: ILD, Sarcoidosis, IPF, LAM / Adult / Clinical Studies / Clinical Problems (CP)|
|Authors:||R.L. Perez, G.W. Vicary, C.W. Barber, S. Furmanek, T. Wiemken, B. Mattingly, A. Persaud, B. Guinn, J. Roman; Louisville, KY/US|
Rationale: A 10% decline in forced vital capacity (FVC) from baseline is considered a marker of significant disease progression in Idiopathic Pulmonary Fibrosis (IPF), and has been used as a primary end-point in clinical trials. Impairments in airflow caused by peri-bronchiolar fibrosis, airway inflammation, and tissue traction have also been reported in IPF, yet alterations in airflow are not adequately considered when using FVC alone. Interestingly, associations between the FEV1/FVC ratio and survival in IPF have noted in previous work. Thus, we hypothesized that incorporating FEV1 as the measure of airflow and change in FVC from predicted baseline into a single formula might unveil a more sensitive marker of disease progression. We tested whether a 10% decline in FEV1/(predicted FVC – actual FVC), henceforth FEV1/dFVC, detects IPF progression earlier than the standard accepted 10% decline in FVC alone. Methods: First, we obtained the datasets for the Prednisone, Azathioprine, N-acetylcysteine in IPF (PANTHER) Trial from the NIH-NHLBI-sponsored Biologic Specimen and Data Repository Information Coordinating Center (BioLincc). Second, we selected all patients who showed a 10% decline FVC during the course of the study (60 weeks) and compared time to 10% change in baseline FVC to time to 10% change in baseline FEV1/dFVC ratio. The analysis was completed in R with marginal homogeneity determined by Stuart-Maxwell test. Results: Of the 250 total patients enrolled in the PANTHER trial, 85 had their FVC drop 10% during the course of the study (60 Weeks) and were selected for analysis. FEV1/dFVC detected a drop earlier in 58% of patients. Additionally, a 10% decline in FEV1/dFVC ratio was detected an average of 14.9 weeks earlier (visit 1) when compared to FVC alone. Furthermore, at 30 weeks, twice as many patients showed a 10% decline in FEV1/dFVC ratio when compared to FVC alone (figure). Conclusion: A 10% decline in FEV1/dFVC ratio may be a marker of disease progression in IPF earlier than FVC alone. This marker may allow earlier detection of IPF progression in clinical trials, and may identify those in need of intervention earlier.