Diagnosis of Idiopathic Pulmonary Fibrosis with High-Resolution CT

It was with great interest that we read the Article by Ganesh Raghu and colleagues published in The Lancet Respiratory Medicine.1Raghu G Lynch D Godwin JD et al.Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT in patients with little or no radiological evidence of honeycombing: secondary analysis of a randomised, controlled trial.Lancet Respir Med. 2014; 2: 277-284Summary Full Text Full Text PDF Scopus (134) Google Scholar In this retrospective subgroup analysis of a clinical trial population of patients with idiopathic pulmonary fibrosis, the investigators analysed patients with surgical lung biopsy specimens that were centrally screened for inclusion in the main trial.2Raghu G Behr J Brown KK et al.Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial.Ann Intern Med. 2013; 158: 641-649Crossref PubMed Scopus (375) Google Scholar The authors report that a possible usual interstitial pneumonia on high-resolution CT (a pattern that is not diagnostic of idiopathic pulmonary fibrosis according to current guidelines)3Raghu G Collard HR Egan JJ et al.An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management.Am J Respir Crit Care Med. 2011; 183: 788-824Crossref PubMed Scopus (5169) Google Scholar has a positive predictive value of 94% for the presence of a histological pattern of usual interstitial pneumonia. On the basis of this finding, they conclude that a possible usual interstitial pneumonia pattern on high-resolution CT is sufficient to make the diagnosis of idiopathic pulmonary fibrosis in clinically appropriate cases, obviating the need for surgical lung biopsy.We believe selection bias severely limits any conclusions that can be drawn from this study. The most fundamental issue is that patients with possible usual interstitial pneumonia included in this analysis were only those with surgical lung biopsies that led their local physician to believe they had idiopathic pulmonary fibrosis (ie, these patients were thought to have usual interstitial pneumonia on surgical lung biopsy). The patients with possible usual interstitial pneumonia and a surgical lung biopsy suggesting an alternative diagnosis (eg, chronic hypersensitivity pneumonitis, non-specific interstitial pneumonia) were never referred for central screening. If there were a significant number of these cases, the true positive predictive value of usual interstitial pneumonia pattern on high-resolution CT would be substantially reduced. For example, if 50 patients with possible usual interstitial pneumonia on high-resolution CT were never referred for central screening, and only five (10%) of those had usual interstitial pneumonia on biopsy, the overall positive predictive value would be 63%. Although the authors acknowledge this bias in their discussion, we do not believe the conclusions reflect this limitation. On the basis of the data presented, we believe one can only conclude that the positive predictive value of a possible usual interstitial pneumonia pattern on high-resolution CT in predicting histological usual interstitial pneumonia is 94% in a patient population already diagnosed with idiopathic pulmonary fibrosis by a local physician based on surgical lung biopsy.We are concerned that readers will interpret these findings as evidence that patients with possible usual interstitial pneumonia on high-resolution CT and a compatible clinical history do not need a surgical lung biopsy to establish the diagnosis of idiopathic pulmonary fibrosis, and that this behaviour will lead to misdiagnosis. Until additional studies are done using a broader population of patients, clinicians and researchers should follow the diagnostic recommendations of the 2011 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines for idiopathic pulmonary fibrosis.3Raghu G Collard HR Egan JJ et al.An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management.Am J Respir Crit Care Med. 2011; 183: 788-824Crossref PubMed Scopus (5169) Google ScholarKAJ and KdB report non-financial support from Intermune, outside of the submitted work. HRC reports personal fees from Bayer, FibroGen, Gilead, Intermune, Mesoblast, Moerae matrix, Pfizer, Promedior, and Takeda; and grants from Boehringer Ingelheim, Genentech, National Heart, Lung, and Blood Institute, and University of California, San Francisco. The other authors declare that they have no competing interests. It was with great interest that we read the Article by Ganesh Raghu and colleagues published in The Lancet Respiratory Medicine.1Raghu G Lynch D Godwin JD et al.Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT in patients with little or no radiological evidence of honeycombing: secondary analysis of a randomised, controlled trial.Lancet Respir Med. 2014; 2: 277-284Summary Full Text Full Text PDF Scopus (134) Google Scholar In this retrospective subgroup analysis of a clinical trial population of patients with idiopathic pulmonary fibrosis, the investigators analysed patients with surgical lung biopsy specimens that were centrally screened for inclusion in the main trial.2Raghu G Behr J Brown KK et al.Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial.Ann Intern Med. 2013; 158: 641-649Crossref PubMed Scopus (375) Google Scholar The authors report that a possible usual interstitial pneumonia on high-resolution CT (a pattern that is not diagnostic of idiopathic pulmonary fibrosis according to current guidelines)3Raghu G Collard HR Egan JJ et al.An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management.Am J Respir Crit Care Med. 2011; 183: 788-824Crossref PubMed Scopus (5169) Google Scholar has a positive predictive value of 94% for the presence of a histological pattern of usual interstitial pneumonia. On the basis of this finding, they conclude that a possible usual interstitial pneumonia pattern on high-resolution CT is sufficient to make the diagnosis of idiopathic pulmonary fibrosis in clinically appropriate cases, obviating the need for surgical lung biopsy. We believe selection bias severely limits any conclusions that can be drawn from this study. The most fundamental issue is that patients with possible usual interstitial pneumonia included in this analysis were only those with surgical lung biopsies that led their local physician to believe they had idiopathic pulmonary fibrosis (ie, these patients were thought to have usual interstitial pneumonia on surgical lung biopsy). The patients with possible usual interstitial pneumonia and a surgical lung biopsy suggesting an alternative diagnosis (eg, chronic hypersensitivity pneumonitis, non-specific interstitial pneumonia) were never referred for central screening. If there were a significant number of these cases, the true positive predictive value of usual interstitial pneumonia pattern on high-resolution CT would be substantially reduced. For example, if 50 patients with possible usual interstitial pneumonia on high-resolution CT were never referred for central screening, and only five (10%) of those had usual interstitial pneumonia on biopsy, the overall positive predictive value would be 63%. Although the authors acknowledge this bias in their discussion, we do not believe the conclusions reflect this limitation. On the basis of the data presented, we believe one can only conclude that the positive predictive value of a possible usual interstitial pneumonia pattern on high-resolution CT in predicting histological usual interstitial pneumonia is 94% in a patient population already diagnosed with idiopathic pulmonary fibrosis by a local physician based on surgical lung biopsy. We are concerned that readers will interpret these findings as evidence that patients with possible usual interstitial pneumonia on high-resolution CT and a compatible clinical history do not need a surgical lung biopsy to establish the diagnosis of idiopathic pulmonary fibrosis, and that this behaviour will lead to misdiagnosis. Until additional studies are done using a broader population of patients, clinicians and researchers should follow the diagnostic recommendations of the 2011 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines for idiopathic pulmonary fibrosis.3Raghu G Collard HR Egan JJ et al.An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management.Am J Respir Crit Care Med. 2011; 183: 788-824Crossref PubMed Scopus (5169) Google Scholar KAJ and KdB report non-financial support from Intermune, outside of the submitted work. HRC reports personal fees from Bayer, FibroGen, Gilead, Intermune, Mesoblast, Moerae matrix, Pfizer, Promedior, and Takeda; and grants from Boehringer Ingelheim, Genentech, National Heart, Lung, and Blood Institute, and University of California, San Francisco. The other authors declare that they have no competing interests. Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT in patients with little or no radiological evidence of honeycombing: secondary analysis of a randomised, controlled trialIn the appropriate clinical setting, for patients with possible usual interstitial pneumonia pattern on high resolution CT, surgical lung biopsy sampling might not be necessary to reach a diagnosis of idiopathic pulmonary fibrosis if high-resolution CT scans are assessed by experts at regional sites familiar with patterns of usual interstitial pneumonia and management of idiopathic interstitial pneumonia. Full-Text PDF Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT – Authors' replyKerri Johannson and colleagues discuss a limitation of our study that was acknowledged in the discussion section of our report.1 Nevertheless, our conclusions seem to have been misunderstood; at no place in the report did we make a recommendation that surgical lung biopsy was not necessary for all patients showing the pattern of “possible usual interstitial pneumonia (UIP)” on high-resolution CT (HRCT) of the chest. We emphasise that our study findings should not be extrapolated to all patients showing the HRCT pattern of “possible UIP” interpreted by general pulmonologists and radiologists. Full-Text PDF