- Email: [email protected]
Understanding CT patterns in idiopathic pulmonary fibrosis
Comment
continuity of care is needed, with an eye to the prevailing epidemiology, to assess signs and symptoms over time. Access to spirometry is crucial, but inevitably, this assessment will often be marred with clinical uncertainty. Better to acknowledge this uncertainty upfront; for both doctor and patients. Chris van Weel
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Australian Primary Health Care Research Institute, Australian National University, Canberra, Australia; Department of Primary and Community Care, Raboud University Medical Centre, Nijmegen, Netherlands [email protected]
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I declare that I have no competing interests.
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1
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Tirimanna PR, van Schayck CP, den Otter JJ et al. Prevalence of asthma and COPD in general practice in 1992: has it changed since 1977? Br J Gen Pract 1996; 46: 277–281. Jones RCM, Price D, Ryan D, et al, on behalf of The Respiratory Effectiveness Group. Opportunities to diagnose chronic obstructive pulmonary disease in routine care in the UK: a retrospective study of a clinical cohort. Lancet Respir Med 2014; published online Feb 13. http://dx.doi.org/10.1016/ S2213-2600(14)70008-6.
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Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. http://www.goldcopd.org/uploads/users/files/GOLD_Report_2014_ Jan23.pdf (accessed Jan 26, 2014). Albers M, Schermer T, Heijdra Y, Molema J, Akkermans R, van Weel C. Predictive value of lung function below the normal range and respiratory symptoms for progression of chronic obstructive pulmonary disease. Thorax 2008; 63: 201– 07. Boom G, van den Schayck CP, van Rutten-van Mölken MPMH, et al. Active detection of COPD and asthma in the general population: results and economic consequences of the DIMCA programme. Am J Respir Crit Care Med 1998; 158: 1730–38. Albers M, Schermer T, Molema J, et al. Do family physicians’ records fit guideline diagnosed COPD? Family Practice 2009; 26: 81–87. Knottnerus JA. Challenges in dia-prognostic research. J Epidemiol Community Health 2002; 56: 340–41. Gillies JCM, Mercer SW, Lyon A, Scott M, Watt GCM. Distilling the essence of general practice: a learning journey in progress. Br J Gen Pract 2009; 59: e167–76. Schers H, Bor H, Hoogen HJM, van Weel C. What went and what came? Morbidity trends in general practice from the Netherlands. Eur J Gen Pract 2008; 14 (suppl 1): 13–24. Starfield B, Shi L, Macinko J. Contribution of primary care to health systems and health. Milbank Q 2005; 83: 457–502. Woolf SH. The meaning of translational research and why it matters. JAMA 2008; 299: 211–13.
No gold standard test exists for diagnosis of idiopathic pulmonary fibrosis, but the presence on a thoracic high resolution CT scan of honeycomb change, defined as dilatations of small airways giving the appearance of clumps of small cysts 3–10 mm in diameter (ie, mature and irreversible fibrosis), has a high predictive value for a pathological diagnosis of usual interstitial pneumonia.1 Together with a typical history of progressive breathlessness in an older person without significant environmental exposures, drug toxicities, or evidence of a connective tissue disease, presence of usual interstitial pneumonia signifies a diagnosis of idiopathic pulmonary fibrosis. A confident diagnosis of idiopathic pulmonary fibrosis is needed because its prognosis is worse than that of other interstitial lung diseases2 and specific treatment recommendations apply, including avoidance of interventions that cause harm.3 Many patients with suspected idiopathic pulmonary fibrosis will not have honeycombing on high-resolution CT, but will otherwise fulfil the radiological criteria for a usual interstitial pneumonia pattern with reticulation (lines) in a peripheral and basal distribution, without atypical features (eg, extensive ground glass change, bronchovascular distribution, nodules, and consolidation). In the 2011 international guidelines3 for diagnosis www.thelancet.com/respiratory Vol 2 April 2014
and management of idiopathic pulmonary fibrosis, honeycombing is specified as a requirement for usual interstitial pneumonia pattern on high-resolution CT, with lung biopsy sampling required when honeycombing is absent. However, lung biopsy sampling in this population of older people has substantial risks, and in practice many patients with possible usual interstitial pneumonia pattern on high-resolution CT will not undergo this invasive procedure. These patients are therefore neglected because, according to the guidelines, a confident diagnosis of idiopathic pulmonary fibrosis cannot be made without a biopsy and treatment recommendations do not apply.4 In The Lancet Respiratory Medicine, Ganesh Raghu and colleagues5 go some way towards addressing this problem. In a retrospective study of 315 patients previously screened for a randomised trial in idiopathic pulmonary fibrosis, 79 (94%) of 84 patients (mean age 64·4 years, range 47–78 years) who had a high resolution CT pattern of possible usual interstitial pneumonia (without honeycombing) had histopathological usual interstitial pneumonia after analysis of lung biopsy samples. Consideration should be given to potential selection bias, because the pathology of 102 patients who did not undergo biopsy sampling was not known, although their demographics and lung function were much the same
Mauro Fermariello/Science Photo Library
Understanding CT patterns in idiopathic pulmonary fibrosis
Published Online February 18, 2014 http://dx.doi.org/10.1016/ S2213-2600(14)70030-X See Articles page 277
249
Comment
as people who had the procedure. Furthermore, some participants might have had biopsy findings inconsistent with idiopathic pulmonary fibrosis and not been referred for consideration in the trial. Previously, Fell and colleagues showed, in a retrospective study6 of 135 participants with interstitial lung disease, that in the absence of honeycombing, age and the presence of reticulation on high-resolution CT were able to confidently predict idiopathic pulmonary fibrosis. Age 70 years or older had a positive predictive value of at least 95%, and the presence of more widespread reticulation on high-resolution CT allowed prediction of idiopathic pulmonary fibrosis in younger patients. Although further prospective studies could provide confirmation, patients who have suspected idiopathic pulmonary fibrosis without honeycombing on high-resolution CT could in future be spared the risks of lung biopsy sampling and be given a confident diagnosis of idiopathic pulmonary fibrosis on the basis of clinical and radiological findings alone. Raghu and colleagues’ findings5 will probably persuade clinicians to make more inclusive and confident diagnoses of idiopathic pulmonary fibrosis than are advocated by the 2011 guidelines. The results will also help to provide clarity about treatment options for a greater number of patients and increase the pool of patients suitable for inclusion in clinical trials of new therapies. This new inclusivity might be regarded as a throwback to a time when the umbrella term cryptogenic fibrosing alveolitis was preferred in the UK. Arguments for abandoning this terminology included concerns that it encompassed fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis with differing outcomes.7 Cryptogenic fibrosing alveolitis also encompassed the entity of fibrotic non-specific interstitial pneumonia with a better prognosis compared with typical idiopathic pulmonary fibrosis, although its pathological similarity to usual interstitial pneumonia8 and coexistence of both pathologies in individual patients9 suggest a common pathogenesis. Raghu and colleagues also present tantalising data that patients with suspected idiopathic pulmonary fibrosis and a high-resolution CT scan deemed inconsistent with usual interstitial pneumonia had histopathologically confirmed usual interstitial pneumonia in 81·7% of biopsied cases. Which criteria were met for scans deemed inconsistent (eg, ground glass change, air trapping, atypical distribution) would be interesting to 250
know. A strong argument will be made for a change of terminology if such an appearance is not inconsistent with usual interstitial pneumonia at all. Interpretation of high-resolution CT patterns should continue to be made together with a typical clinical history, and careful clinical assessment is mandatory to identify those patients who might have immunologically driven disease in which inflammation precedes fibrosis, supported by adjunctive tests such as bronchoalveolar lavage.10 In the modern era with optimal high-resolution CT imaging and thoracic radiologists familiar with interpretation of interstitial lung disease patterns through participation in multidisciplinary meetings,11 the role of lung biopsy assessment might diminish further. In future, combination of high-resolution CT with new non-invasive biomarkers and functional imaging could be used to better define phenotypes of fibrotic interstitial lung disease. Simon P Hart Hull York Medical School, Centre for Cardiovascular and Metabolic Research, Academic Respiratory Medicine, Castle Hill Hospital, Cottingham HU16 5JQ, UK [email protected] I declare that I have no conflicts of interest. 1
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5
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Sundaram B, Gross BH, Martinez FJ, et al. Accuracy of high-resolution CT in the diagnosis of diffuse lung disease: effect of predominance and distribution of findings. AJR Am J Roentgenol 2008; 191: 1032–39. Bjoraker JA, Ryu JH, Edwin MK, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998; 157: 199–203. 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. Wells AU. The revised ATS/ERS/JRS/ALAT diagnostic criteria for idiopathic pulmonary fibrosis (IPF)—practical implications. Respir Res 2013; 14 (suppl 1): S2. Raghu 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; published online Feb 18. http://dx.doi. org/10.1016/S2213-2600(14)70011-6. Fell CD, Martinez FJ, Liu LX, et al. Clinical predictors of a diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2010; 181: 832–37. Bradley B, Branley HM, Egan JJ, et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 2008; 63 (suppl 5): 1–58. Nicholson AG, Colby TV, du Bois RM, Hansell DM, Wells AU. The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med 2000; 162: 2213–17. Flaherty KR, Travis WD, Colby TV, et al. Histopathologic variability in usual and nonspecific interstitial pneumonias. Am J Respir Crit Care Med 2001; 164: 1722–27. Morell F, Villar A, Montero M-A, et al. Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study. Lancet Respir Med 2013; 1: 685–94. Flaherty KR, King TE Jr, Raghu G, et al. Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary approach to diagnosis? Am J Respir Crit Care Med 2004; 170: 904–10.
www.thelancet.com/respiratory Vol 2 April 2014
continuity of care is needed, with an eye to the prevailing epidemiology, to assess signs and symptoms over time. Access to spirometry is crucial, but inevitably, this assessment will often be marred with clinical uncertainty. Better to acknowledge this uncertainty upfront; for both doctor and patients. Chris van Weel
3
4
5
Australian Primary Health Care Research Institute, Australian National University, Canberra, Australia; Department of Primary and Community Care, Raboud University Medical Centre, Nijmegen, Netherlands [email protected]
6
I declare that I have no competing interests.
9
1
2
Tirimanna PR, van Schayck CP, den Otter JJ et al. Prevalence of asthma and COPD in general practice in 1992: has it changed since 1977? Br J Gen Pract 1996; 46: 277–281. Jones RCM, Price D, Ryan D, et al, on behalf of The Respiratory Effectiveness Group. Opportunities to diagnose chronic obstructive pulmonary disease in routine care in the UK: a retrospective study of a clinical cohort. Lancet Respir Med 2014; published online Feb 13. http://dx.doi.org/10.1016/ S2213-2600(14)70008-6.
7 8
10 11
Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. http://www.goldcopd.org/uploads/users/files/GOLD_Report_2014_ Jan23.pdf (accessed Jan 26, 2014). Albers M, Schermer T, Heijdra Y, Molema J, Akkermans R, van Weel C. Predictive value of lung function below the normal range and respiratory symptoms for progression of chronic obstructive pulmonary disease. Thorax 2008; 63: 201– 07. Boom G, van den Schayck CP, van Rutten-van Mölken MPMH, et al. Active detection of COPD and asthma in the general population: results and economic consequences of the DIMCA programme. Am J Respir Crit Care Med 1998; 158: 1730–38. Albers M, Schermer T, Molema J, et al. Do family physicians’ records fit guideline diagnosed COPD? Family Practice 2009; 26: 81–87. Knottnerus JA. Challenges in dia-prognostic research. J Epidemiol Community Health 2002; 56: 340–41. Gillies JCM, Mercer SW, Lyon A, Scott M, Watt GCM. Distilling the essence of general practice: a learning journey in progress. Br J Gen Pract 2009; 59: e167–76. Schers H, Bor H, Hoogen HJM, van Weel C. What went and what came? Morbidity trends in general practice from the Netherlands. Eur J Gen Pract 2008; 14 (suppl 1): 13–24. Starfield B, Shi L, Macinko J. Contribution of primary care to health systems and health. Milbank Q 2005; 83: 457–502. Woolf SH. The meaning of translational research and why it matters. JAMA 2008; 299: 211–13.
No gold standard test exists for diagnosis of idiopathic pulmonary fibrosis, but the presence on a thoracic high resolution CT scan of honeycomb change, defined as dilatations of small airways giving the appearance of clumps of small cysts 3–10 mm in diameter (ie, mature and irreversible fibrosis), has a high predictive value for a pathological diagnosis of usual interstitial pneumonia.1 Together with a typical history of progressive breathlessness in an older person without significant environmental exposures, drug toxicities, or evidence of a connective tissue disease, presence of usual interstitial pneumonia signifies a diagnosis of idiopathic pulmonary fibrosis. A confident diagnosis of idiopathic pulmonary fibrosis is needed because its prognosis is worse than that of other interstitial lung diseases2 and specific treatment recommendations apply, including avoidance of interventions that cause harm.3 Many patients with suspected idiopathic pulmonary fibrosis will not have honeycombing on high-resolution CT, but will otherwise fulfil the radiological criteria for a usual interstitial pneumonia pattern with reticulation (lines) in a peripheral and basal distribution, without atypical features (eg, extensive ground glass change, bronchovascular distribution, nodules, and consolidation). In the 2011 international guidelines3 for diagnosis www.thelancet.com/respiratory Vol 2 April 2014
and management of idiopathic pulmonary fibrosis, honeycombing is specified as a requirement for usual interstitial pneumonia pattern on high-resolution CT, with lung biopsy sampling required when honeycombing is absent. However, lung biopsy sampling in this population of older people has substantial risks, and in practice many patients with possible usual interstitial pneumonia pattern on high-resolution CT will not undergo this invasive procedure. These patients are therefore neglected because, according to the guidelines, a confident diagnosis of idiopathic pulmonary fibrosis cannot be made without a biopsy and treatment recommendations do not apply.4 In The Lancet Respiratory Medicine, Ganesh Raghu and colleagues5 go some way towards addressing this problem. In a retrospective study of 315 patients previously screened for a randomised trial in idiopathic pulmonary fibrosis, 79 (94%) of 84 patients (mean age 64·4 years, range 47–78 years) who had a high resolution CT pattern of possible usual interstitial pneumonia (without honeycombing) had histopathological usual interstitial pneumonia after analysis of lung biopsy samples. Consideration should be given to potential selection bias, because the pathology of 102 patients who did not undergo biopsy sampling was not known, although their demographics and lung function were much the same
Mauro Fermariello/Science Photo Library
Understanding CT patterns in idiopathic pulmonary fibrosis
Published Online February 18, 2014 http://dx.doi.org/10.1016/ S2213-2600(14)70030-X See Articles page 277
249
Comment
as people who had the procedure. Furthermore, some participants might have had biopsy findings inconsistent with idiopathic pulmonary fibrosis and not been referred for consideration in the trial. Previously, Fell and colleagues showed, in a retrospective study6 of 135 participants with interstitial lung disease, that in the absence of honeycombing, age and the presence of reticulation on high-resolution CT were able to confidently predict idiopathic pulmonary fibrosis. Age 70 years or older had a positive predictive value of at least 95%, and the presence of more widespread reticulation on high-resolution CT allowed prediction of idiopathic pulmonary fibrosis in younger patients. Although further prospective studies could provide confirmation, patients who have suspected idiopathic pulmonary fibrosis without honeycombing on high-resolution CT could in future be spared the risks of lung biopsy sampling and be given a confident diagnosis of idiopathic pulmonary fibrosis on the basis of clinical and radiological findings alone. Raghu and colleagues’ findings5 will probably persuade clinicians to make more inclusive and confident diagnoses of idiopathic pulmonary fibrosis than are advocated by the 2011 guidelines. The results will also help to provide clarity about treatment options for a greater number of patients and increase the pool of patients suitable for inclusion in clinical trials of new therapies. This new inclusivity might be regarded as a throwback to a time when the umbrella term cryptogenic fibrosing alveolitis was preferred in the UK. Arguments for abandoning this terminology included concerns that it encompassed fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis with differing outcomes.7 Cryptogenic fibrosing alveolitis also encompassed the entity of fibrotic non-specific interstitial pneumonia with a better prognosis compared with typical idiopathic pulmonary fibrosis, although its pathological similarity to usual interstitial pneumonia8 and coexistence of both pathologies in individual patients9 suggest a common pathogenesis. Raghu and colleagues also present tantalising data that patients with suspected idiopathic pulmonary fibrosis and a high-resolution CT scan deemed inconsistent with usual interstitial pneumonia had histopathologically confirmed usual interstitial pneumonia in 81·7% of biopsied cases. Which criteria were met for scans deemed inconsistent (eg, ground glass change, air trapping, atypical distribution) would be interesting to 250
know. A strong argument will be made for a change of terminology if such an appearance is not inconsistent with usual interstitial pneumonia at all. Interpretation of high-resolution CT patterns should continue to be made together with a typical clinical history, and careful clinical assessment is mandatory to identify those patients who might have immunologically driven disease in which inflammation precedes fibrosis, supported by adjunctive tests such as bronchoalveolar lavage.10 In the modern era with optimal high-resolution CT imaging and thoracic radiologists familiar with interpretation of interstitial lung disease patterns through participation in multidisciplinary meetings,11 the role of lung biopsy assessment might diminish further. In future, combination of high-resolution CT with new non-invasive biomarkers and functional imaging could be used to better define phenotypes of fibrotic interstitial lung disease. Simon P Hart Hull York Medical School, Centre for Cardiovascular and Metabolic Research, Academic Respiratory Medicine, Castle Hill Hospital, Cottingham HU16 5JQ, UK [email protected] I declare that I have no conflicts of interest. 1
2
3
4
5
6 7
8
9
10
11
Sundaram B, Gross BH, Martinez FJ, et al. Accuracy of high-resolution CT in the diagnosis of diffuse lung disease: effect of predominance and distribution of findings. AJR Am J Roentgenol 2008; 191: 1032–39. Bjoraker JA, Ryu JH, Edwin MK, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998; 157: 199–203. 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. Wells AU. The revised ATS/ERS/JRS/ALAT diagnostic criteria for idiopathic pulmonary fibrosis (IPF)—practical implications. Respir Res 2013; 14 (suppl 1): S2. Raghu 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; published online Feb 18. http://dx.doi. org/10.1016/S2213-2600(14)70011-6. Fell CD, Martinez FJ, Liu LX, et al. Clinical predictors of a diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2010; 181: 832–37. Bradley B, Branley HM, Egan JJ, et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 2008; 63 (suppl 5): 1–58. Nicholson AG, Colby TV, du Bois RM, Hansell DM, Wells AU. The prognostic significance of the histologic pattern of interstitial pneumonia in patients presenting with the clinical entity of cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med 2000; 162: 2213–17. Flaherty KR, Travis WD, Colby TV, et al. Histopathologic variability in usual and nonspecific interstitial pneumonias. Am J Respir Crit Care Med 2001; 164: 1722–27. Morell F, Villar A, Montero M-A, et al. Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study. Lancet Respir Med 2013; 1: 685–94. Flaherty KR, King TE Jr, Raghu G, et al. Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary approach to diagnosis? Am J Respir Crit Care Med 2004; 170: 904–10.
www.thelancet.com/respiratory Vol 2 April 2014