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Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT
Correspondence
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.1 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.2 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)3 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, nonspecific 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, www.thelancet.com/respiratory Vol 2 May 2014
if 50 patients with possible usual interstitial pneumonia on highresolution 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 highresolution 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.3 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.
*Kerri A Johannson, Kaissa de Boer, Paul J Wolters, Jeffrey A Golden, Joyce S Lee, Harold R Collard [email protected] Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, USA
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Raghu G, Lynch D, Godwin JD, et al. Diagnosis of idiopathic pulmonary fibrosis with highresolution CT in patients with little or no radiological evidence of honeycombing: secondary analysis of a randomised, controlled trial. Lancet Respir Med 2014; 2: 277–84. Raghu G, Behr J, Brown KK, et al. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med 2013; 158: 641–49. Raghu 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: 788–824.
Authors’ reply Kerri 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. We had reminded the reader of the clinical profile of patients with suspected idiopathic pulmonary fibrosis. In essence, our findings relate to patients directly assessed thoroughly by experts familiar with all the clinical and radiological features of interstitial lung disease, idiopathic interstitial pneumonias, and hypersensitivity pneumonitis. We had also alerted the reader, in our discussion section, that patients showing an HRCT pattern of “possible UIP” (who might have had an alternative diagnosis ascertained by surgical lung biopsy) would not have been referred to this study. Johannson and colleagues discuss the potential number of patients excluded from our study with possible UIP pattern on HRCT, but who had a diagnosis other than UIP on biopsy. To our knowledge, no studies to date have definitively addressed the question of sensitivity e5
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.1 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.2 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)3 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, nonspecific 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, www.thelancet.com/respiratory Vol 2 May 2014
if 50 patients with possible usual interstitial pneumonia on highresolution 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 highresolution 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.3 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.
*Kerri A Johannson, Kaissa de Boer, Paul J Wolters, Jeffrey A Golden, Joyce S Lee, Harold R Collard [email protected] Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA, USA
1
2
3
Raghu G, Lynch D, Godwin JD, et al. Diagnosis of idiopathic pulmonary fibrosis with highresolution CT in patients with little or no radiological evidence of honeycombing: secondary analysis of a randomised, controlled trial. Lancet Respir Med 2014; 2: 277–84. Raghu G, Behr J, Brown KK, et al. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med 2013; 158: 641–49. Raghu 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: 788–824.
Authors’ reply Kerri 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. We had reminded the reader of the clinical profile of patients with suspected idiopathic pulmonary fibrosis. In essence, our findings relate to patients directly assessed thoroughly by experts familiar with all the clinical and radiological features of interstitial lung disease, idiopathic interstitial pneumonias, and hypersensitivity pneumonitis. We had also alerted the reader, in our discussion section, that patients showing an HRCT pattern of “possible UIP” (who might have had an alternative diagnosis ascertained by surgical lung biopsy) would not have been referred to this study. Johannson and colleagues discuss the potential number of patients excluded from our study with possible UIP pattern on HRCT, but who had a diagnosis other than UIP on biopsy. To our knowledge, no studies to date have definitively addressed the question of sensitivity e5