Vincent Cottin1,2, David M Hansell3, Nicola Sverzellati4, Derek Weycker5, Katerina M Antoniou6, Mark Atwood5, Gerry Oster5, Klaus-Uwe Kirchgaessler7, Harold R Collard8, Athol U Wells3. 1. 1 Department of Respiratory Medicine, National Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Lyon, France. 2. 2 Université Claude Bernard, Lyon, France. 3. 3 Interstitial Lung Disease Unit, Royal Brompton Hospital, London, United Kingdom. 4. 4 Department of Surgical Sciences, Ospedale Maggiore di Parma, Parma, Italy. 5. 5 Policy Analysis Inc., Brookline, Massachusetts. 6. 6 Department of Thoracic Medicine, University of Crete, Heraklion, Greece. 7. 7 Roche, Basel, Switzerland; and. 8. 8 Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, California.
Abstract
RATIONALE: Patients with idiopathic pulmonary fibrosis and emphysema may have artificially preserved lung volumes. OBJECTIVES: In this post hoc analysis, we investigated the relationship between baseline emphysema and fibrosis extents, as well as pulmonary function changes, over 48 weeks. METHODS: Data were pooled from two phase III, randomized, double-blind, placebo-controlled trials of IFN-γ-1b in idiopathic pulmonary fibrosis (GIPF-001 [NCT00047645] and GIPF-007 [NCT00075998]). Patients with Week 48 data, baseline high-resolution computed tomographic images, and FEV1/FVC ratios less than 0.8 or greater than 0.9 (<0.7 or >0.9 in GIPF-007), as well as randomly selected patients with ratios of 0.8-0.9 and 0.7-0.8, were included. Changes from baseline in pulmonary function at Week 48 were analyzed by emphysema extent. The relationship between emphysema and fibrosis extents and change in pulmonary function was assessed using multivariate linear regression. MEASUREMENTS AND MAIN RESULTS:Emphysema was identified in 38% of patients. A negative correlation was observed between fibrosis and emphysema extents (r = -0.232; P < 0.001). In quartile analysis, patients with the greatest emphysema extent (28 to 65%) showed the smallest FVC decline, with a difference of 3.32% at Week 48 versus patients with no emphysema (P = 0.047). In multivariate analyses, emphysema extent greater than or equal to 15% was associated with significantly reduced FVC decline over 48 weeks versus no emphysema or emphysema less than 15%. No such association was observed for diffusing capacity of the lung for carbon monoxide or composite physiologic index. CONCLUSIONS: FVC measurements may not be appropriate for monitoring disease progression in patients with idiopathic pulmonary fibrosis and emphysema extent greater than or equal to 15%.
RCT Entities:
RATIONALE: Patients with idiopathic pulmonary fibrosis and emphysema may have artificially preserved lung volumes. OBJECTIVES: In this post hoc analysis, we investigated the relationship between baseline emphysema and fibrosis extents, as well as pulmonary function changes, over 48 weeks. METHODS: Data were pooled from two phase III, randomized, double-blind, placebo-controlled trials of IFN-γ-1b in idiopathic pulmonary fibrosis (GIPF-001 [NCT00047645] and GIPF-007 [NCT00075998]). Patients with Week 48 data, baseline high-resolution computed tomographic images, and FEV1/FVC ratios less than 0.8 or greater than 0.9 (<0.7 or >0.9 in GIPF-007), as well as randomly selected patients with ratios of 0.8-0.9 and 0.7-0.8, were included. Changes from baseline in pulmonary function at Week 48 were analyzed by emphysema extent. The relationship between emphysema and fibrosis extents and change in pulmonary function was assessed using multivariate linear regression. MEASUREMENTS AND MAIN RESULTS:Emphysema was identified in 38% of patients. A negative correlation was observed between fibrosis and emphysema extents (r = -0.232; P < 0.001). In quartile analysis, patients with the greatest emphysema extent (28 to 65%) showed the smallest FVC decline, with a difference of 3.32% at Week 48 versus patients with no emphysema (P = 0.047). In multivariate analyses, emphysema extent greater than or equal to 15% was associated with significantly reduced FVC decline over 48 weeks versus no emphysema or emphysema less than 15%. No such association was observed for diffusing capacity of the lung for carbon monoxide or composite physiologic index. CONCLUSIONS: FVC measurements may not be appropriate for monitoring disease progression in patients with idiopathic pulmonary fibrosis and emphysema extent greater than or equal to 15%.
Authors: Justin M Oldham; Ayodeji Adegunsoye; Satinderpal Khera; Elyse Lafond; Imre Noth; Mary E Strek; Michael Kadoch; Jonathan H Chung Journal: Ann Am Thorac Soc Date: 2018-06
Authors: Carlos Machahua; Ana Montes-Worboys; Lurdes Planas-Cerezales; Raquel Buendia-Flores; Maria Molina-Molina; Vanesa Vicens-Zygmunt Journal: Respir Res Date: 2018-11-08
Authors: Samuel Y Ash; Rola Harmouche; James C Ross; Alejandro A Diaz; Farbod N Rahaghi; Gonzalo Vegas Sanchez-Ferrero; Rachel K Putman; Gary M Hunninghake; Jorge Onieva Onieva; Fernando J Martinez; Augustine M Choi; Russell P Bowler; David A Lynch; Hiroto Hatabu; Surya P Bhatt; Mark T Dransfield; J Michael Wells; Ivan O Rosas; Raul San Jose Estepar; George R Washko Journal: Radiology Date: 2018-06-05 Impact factor: 29.146