American Thoracic Society Documents

1 American Thoracic Society DocumentsAn Official American Thoracic Society /EuropeanRespiratory Society Statement: Update of theInternational Multidisciplinary Classification of theIdiopathic Interstitial PneumoniasWilliam D. Travis, Ulrich Costabel, David M. Hansell, Talmadge E. King, Jr., David A. Lynch, Andrew G. Nicholson,Christopher J. Ryerson, Jay H. Ryu, Moise s Selman, Athol U. Wells, Jurgen Behr, Demosthenes Bouros,Kevin K. Brown, Thomas V. Colby, Harold R. Collard, Carlos Robalo Cordeiro, Vincent Cottin, Bruno Crestani,Marjolein Drent, Rosalind F. Dudden, Jim Egan, Kevin Flaherty, Cory Hogaboam, Yoshikazu Inoue, Takeshi Johkoh,Dong Soon Kim, Masanori Kitaichi, James Loyd, Fernando J. Martinez, Jeffrey Myers, Shandra Protzko,Ganesh Raghu, Luca Richeldi, Nicola Sverzellati, Jeffrey Swigris, and Dominique Valeyre; on behalf of the ATS/ERSC ommittee on Idiopathic Interstitial PneumoniasTHIS OFFICIAL STATEMENT OF THEAMERICANTHORACICSOCIETY(ATS)AND THEEUROPEANRESPIRATORYSOCIETY(ERS)

2 WASAPPROVED BY THEATS BOARD OFDIRECTORS,JUNE2013,AND BY THEERS STEERINGCOMMITTEE,MARCH2013 CONTENTSE xecutive SummaryIntroductionMethodsSummary of Major Revisions of the IIP ClassificationGeneral Progress in IIPs since 2002 Multidisciplinary ApproachObserver Agreement in Diagnosis of IIPI mportant Differential Diagnostic ConsiderationsHypersensitivity PneumonitisCollagen Vascular DiseaseFamilial Interstitial PneumoniaCoexisting PatternsProgress in Specific IIPs since 2002 Chronic Fibrosing IIPsSmoking-related IIPsAcute or Subacute IIPsRare IIPsIdiopathic Lymphoid Interstitial PneumoniaIdiopathic Pleuroparenchymal FibroelastosisRare Histologic PatternsAcute Fibrinous and Organizing PneumoniaBronchiolocentric Patterns of Interstitial PneumoniaUnclassifiable IIPC linical Classification of Disease BehaviorBiomarkersBackground: In 2002 the American Thoracic Society /European Res-piratory Society (ATS/ERS) classification of idiopathic interstitialpneumonias(IIPs)definedseven specificentities, ,thehistorical gold standard of histologic diagnosis was replaced by a multidiscipli-nary approach.

3 Since 2002 many publications have provided new infor-mation about : The objective of this statement is to update the 2002 ATS/ERS classification of : An international multidisciplinary panel was formed anddeveloped key questions that were addressed through a review ofthe literature published between 2000 and :SubstantialprogresshasbeenmadeinIIPssin cethepreviousclassification. Nonspecific interstitial pneumonia is now better de-fined. Respiratory bronchiolitis interstitial lung disease is now com-monly diagnosed without surgical biopsy. The clinical course of idi-opathic pulmonary fibrosis and nonspecific interstitial pneumonia isrecognized to be heterogeneous. Acute exacerbation of IIPs is nowwell defined. A substantial percentage of patients with IIP are diffi-cult to classify, often due to mixed patterns of lung injury. A classifi-cation based on observed disease behavior is proposed for patientswho are difficult to classify or for entities with heterogeneity in clin-ical course.

4 A group of rare entities, including pleuroparenchymalfibroelastosis and rare histologic patterns, is introduced. The rapidlyevolving field of molecular markers is reviewed with the intent ofpromoting additional investigations that may help in determiningdiagnosis, and potentially prognosis and : This update is a supplement to the previous 2002 IIPclassification document. It outlines advances in the past decadeand potential areas for future : idiopathic interstitial pneumonia; usual interstitial pneumo-nia; nonspecific interstitial pneumonia; respiratory bronchiolitis; desqua-mative interstitial pneumonia; cryptogenic organizing pneumonia; acuteinterstitial pneumonia; lymphoid interstitial pneumonia; pleuroparenchy-mal fibroelastosis; acute fibrinous and organizing pneumoniaEXECUTIVE SUMMARYT here are several specific areas that are given special attention inthis revision of the 2002 American Thoracic Society /EuropeanRespiratory Society idiopathic interstitial pneumonia (IIP) Idiopathic nonspecific interstitial pneumonia (NSIP) isnow accepted as a specific clinicopathologic entity.

5 It hasbecome evident that clinical progression is highly het-erogeneous, with several studies suggesting that a subsetof patients demonstrate progression to end-stage fibro-sis; criteria to define this group at the time of diagnosiswould be document has an online supplement, which is accessible from this issue stable of contents at J Respir Crit Care Med Vol 188, Iss. 6, pp 733 748, Sep 15, 2013 Copyright 2013 by the American Thoracic SocietyDOI: address: New information has accumulated on smoking-related inter-stitial lung disease, including patients with combined emphy-sema and interstitial fibrosis. In clinical practice, respiratorybronchiolitis interstitial lungdisease is increasingly diag-nosed without surgical lung biopsy in smokers on the basisof clinical and imaging features (ground-glass opacities andcentrilobular nodules) and bronchoalveolar lavage (smok-er s macrophages and absence of lymphocytosis).

6 3. The natural progression of idiopathic pulmonary fibrosis(IPF) is acknowledged to be heterogeneous with somepatients remaining stable for prolonged periods, othersshowing more rapid steady progression, and still otherssuccumbing to acute Acute exacerbation is better defined and recognized tooccur in chronic fibrosing IIPs (IPF and NSIP).5. Some patients with IIP are difficult to classify, oftenbecause of mixed patterns of lung It is recognized that there is a need to provide a clinicalalgorithm for classifying and managing IIP cases. This isparticularly applicable when no biopsy is available andhigh-resolution computed tomography is not Pleuroparenchymal fibroelastosis is recognized as a specificrare entity, usually idiopathic. Other less well-defined his-tologic patterns, such as bronchiolocentric inflammationand fibrosis, are also A rapidly emerging field of molecular markers holdspromise for improving diagnostic approaches.

7 Thesemarkers may also be useful in predicting prognosis andresponse to different therapies. Incorporation of geneticand molecular studies may revolutionize the approachto diagnosis and classification of the objective of this statement is to update the 2002 AmericanThoracicSociety/EuropeanRespirat orySociety(ATS/ERS)clas-sification of idiopathic interstitial pneumonias (IIPs) (1). Focus isplaced on describing changes to previously described clinical enti-ties, describing new clinical entities, and describing new histologicpatterns. This update is not intended as a stand-alone documentand should be used as a supplement to the original 2002 IIP classi-fication. In 2002, the ATS/ERS IIP classification (1) defined sevendisease categories, and proposed standardized terminology anddiagnostic criteria. In addition, the historical gold standard ofhistologic diagnosis was replaced by a dynamic integrated ap-proach using multidisciplinary discussion (MDD).

8 The 2002 IIPclassification was used in 75% (157 of 208) of all clinical publica-tions on the topic of IIPs between 2004 and 2011. The new infor-mation from these publications is incorporated in this project was performed under supervision by the ATS Docu-ments Development and Implementation Committee in collab-oration with the ERS (Table E1 in the online supplement). Aninternational multidisciplinary panel was assembled. The panelconsisted of 34 experts in interstitial lung diseases (19 pulmonol-ogists, 4 radiologists, 5 pathologists, 2 experts in evidence-basedmedicine, and 4 molecular biologists). Several meetings wereheld by members of the international multidisciplinary panel(Table E2), who disclosed conflicts of interest, which were vettedaccording to ATS and ERS questions were developed that the committee believedimportant for the classification of IIPs (seeAPPENDIX 1in theonline supplement).

9 A literature search was performed to iden-tify new publications that pertained to these key questions,assisted by two librarians experienced in literature searches forpulmonary diseases. Literature retrieved from Medline searchesbetween 2000 and 2011 was used to produce this committee was divided into subgroups assigned to spe-cific sections of the document. These subgroups reviewed the rel-evant literature and produced the first draft of their respectivesections. These sections were compiled by the committee chairand a complete first draft was edited by the writing subcommit-tee. This document was reviewed and edited by all committeemembers before final review by the writing revised document was approved by all OF MAJOR REVISIONS OF THEIIP CLASSIFICATIONIn the revision of the IIP classification, the main entities are pre-served (Table 1).

10 However, there are several important , cryptogenic fibrosing alveolitis is removed, leaving idiopathicpulmonary fibrosis (IPF) as the sole clinical term for this , idiopathic nonspecific interstitial pneumonia (NSIP) is nowaccepted as a distinct clinical entity with removal of the term pro-visional (2). Third, major IIPs are distinguished from rare IIPs andunclassifiable cases. Fourth, rare histologic patterns of acute fibri-nous and organizing pneumonia (AFOP) and interstitial pneumo-nias with a bronchiolocentric distribution are recognized. Fifth, themajor IIPs are grouped into chronic fibrosing (IPF and NSIP; Fig-ures 1 and 2), smoking-related (respiratory bronchiolitis interstitiallung disease [RB-ILD] and desquamative interstitial pneumonia[DIP]; Figure 3), and acute/subacute IIPs (cryptogenic organizingpneumonia [COP] and acute interstitial pneumonia [AIP]; Figure 4and Table 2).