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Schädigungsmuster interstitieller Lungenerkrankungen

Injury patterns in interstitial lung diseases

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Zusammenfassung

Bei interstitiellen Lungenerkrankungen (ILD) handelt es sich um eine komplexe Gruppe hunderter nicht-neoplastischer Erkrankungen mit sehr variabler klinischer Präsentation, Morphologie und Progressionstendenz. Dieser großen Zahl klinischer Entitäten steht eine nur begrenzte Anzahl morphologischer Schädigungsmuster gegenüber. Daher ist für die adäquate Einordnung eine synoptische Betrachtung der klinischen, radiologischen und morphologischen Befunde notwendig. Die ATS/ERS-Leitlinien (American Thoracic Society/European Respiratory Society) empfehlen nur für den Fall eines nicht eindeutigen Befunds in der hochauflösenden Computertomographie (CT) eine offene Lungenbiopsie. Die Abgrenzung der Schädigungsmuster kann aufgrund der Herdförmigkeit der Befunde und überlappenden Merkmale jedoch auch morphologisch problematisch sein. Um die diagnostischen Kriterien durch das Hinzuziehen molekularer Muster zu erweitern, arbeitet die Arbeitsgruppe Lungenforschung des Instituts für Pathologie der Medizinischen Hochschule Hannover, dem führenden europäischen Transplantationszentrum, die humanen Lungenexplantate frisch und standardisiert auf. Dieses Frischmaterial wird für translationale Forschungsansätze mittels funktioneller, morphologischer und molekularer Techniken untersucht, um erkrankungsspezifische Regulationsvorgänge zu identifizieren und diese diagnostisch und therapeutisch nutzbar zu machen.

Abstract

Interstitial lung diseases (ILD) consist of a complex group of hundreds of non-neoplastic pulmonary diseases with divergent clinical presentation, morphology and progression tendency. This great number of clinical entities contrasts with a limited number of injury patterns. By definition, an adequate classification requires a synopsis of the clinical, radiological and morphological findings. The ATS/ERS (American Thoracic Society/ European Respiratory Society) guidelines recommend an open lung biopsy if high-resolution computed tomography does not provide conclusive results. Due to the focal nature and overlapping features of injury patterns, microscopic categorization is not always possible. In order to broaden the diagnostic criteria by using molecular patterns the Lung Research Working Group of the Institute of Pathology of Hannover Medical School, Europe’s leading transplant center, is working up fresh explanted human lungs in a standardized manner. These fresh specimens are used for translational research by means of functional, morphological and molecular techniques in order to identify disease-specific regulatory processes and to make them usable diagnostically and therapeutically.

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Literatur

  1. Ackermann M, Gaumann A, Mentzer SJ, Hinrichs JB, Warnecke G, Hoeper MM, Braubach P, Kuehnel M, Maegel L, Jonigk D (2017) Plexiform Vasculopathy in chronic Thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 196:e48–e51. https://doi.org/10.1164/rccm.201703-0591IM

    Article  PubMed  Google Scholar 

  2. Baumgartner KB, Samet JM, Coultas DB, Stidley CA, Hunt WC, Colby TV, Waldron JA (2000) Occupational and environmental risk factors for idiopathic pulmonary fibrosis: a multicenter case-control study. Collaborating Centers. Am J Epidemiol 152:307–315

    Article  CAS  Google Scholar 

  3. Carrington CB, Addington WW, Goff AM, Madoff IM, Marks A, Schwaber JR, Gaensler EA (1969) Chronic eosinophilic pneumonia. N Engl J Med 280:787–798. https://doi.org/10.1056/NEJM196904102801501

    Article  CAS  PubMed  Google Scholar 

  4. Carrington CB, Liebow AA (1966) Limited forms of angiitis and granulomatosis of Wegener’s type. Am J Med 6(6):90214–90212. https://doi.org/10.1016/0002-9343

    Article  Google Scholar 

  5. Cottin V (2016) Idiopathic interstitial pneumonias with connective tissue diseases features: a review. Respirology 21:245–258. https://doi.org/10.1111/resp.12588

    Article  PubMed  Google Scholar 

  6. Feinstein MB, DeSouza SA, Moreira AL, Stover DE, Heelan RT, Iyriboz TA, Taur Y, Travis WD (2015) A comparison of the pathological, clinical and radiographical, features of cryptogenic organising pneumonia, acute fibrinous and organising pneumonia and granulomatous organising pneumonia. J Clin Pathol 68:441–447. https://doi.org/10.1136/jclinpath-2014-202626

    Article  PubMed  Google Scholar 

  7. Ferri C, Manfredi A, Sebastiani M, Colaci M, Giuggioli D, Vacchi C, Casa DG, Cerri S, Torricelli P, Luppi F (2016) Interstitial pneumonia with autoimmune features and undifferentiated connective tissue disease. Autoimmun Rev 15:61–70. https://doi.org/10.1016/j.autrev.2015.09.003

    Article  CAS  PubMed  Google Scholar 

  8. Frankel SK, Cool CD, Lynch DA, Brown KK (2004) Idiopathic pleuroparenchymal fibroelastosis: description of a novel clinicopathologic entity. Chest 126:2007–2013. https://doi.org/10.1378/chest.126.6.2007

    Article  PubMed  Google Scholar 

  9. García-Sancho C, Buendía-Roldán I, Fernández-Plata MR, Navarro C, Pérez-Padilla R, Vargas MH, Loyd JE, Selman M (2011) Familial pulmonary fibrosis is the strongest risk factor for idiopathic pulmonary fibrosis. Respir Med 105:1902–1907. https://doi.org/10.1016/J.RMED.2011.08.022

    Article  PubMed  Google Scholar 

  10. Guiot J, Henket M, Corhay JL, Moermans C, Louis R (2017) Sputum biomarkers in IPF: Evidence for raised gene expression and protein level of IGFBP-2, IL-8 and MMP-7. PLoS ONE 12:e171344. https://doi.org/10.1371/journal.pone.0171344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Homolka J (1987) Idiopathic pulmonary fibrosis: a historical review. CMAJ 137:1003–1005

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Hutchinson J, Fogarty A, Hubbard R, McKeever T (2015) Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review. Eur Respir J 46:795–806. https://doi.org/10.1183/09031936.00185114

    Article  PubMed  Google Scholar 

  13. Izykowski N, Kuehnel M, Hussein K, Mitschke K, Gunn M, Janciauskiene S, Haverich A, Warnecke G, Laenger F, Maus U, Jonigk D (2016) Organizing pneumonia in mice and men. J Transl Med 14:169. https://doi.org/10.1186/s12967-016-0933-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jonigk D, Izykowski N, Rische J, Braubach P, Kühnel M, Warnecke G, Lippmann T, Kreipe H, Haverich A, Welte T, Gottlieb J, Laenger F (2015) Molecular profiling in lung biopsies of human pulmonary Allografts to predict chronic lung Allograft dysfunction. Am J Pathol 185:3178–3188. https://doi.org/10.1016/j.ajpath.2015.08.016

    Article  CAS  PubMed  Google Scholar 

  15. Jonigk D, Merk M, Hussein K, Maegel L, Theophile K, Muth M, Lehmann U, Bockmeyer CL, Mengel M, Gottlieb J, Welte T, Haverich A, Golpon H, Kreipe H, Laenger F (2011) Obliterative airway remodeling: molecular evidence for shared pathways in transplanted and native lungs. Am J Pathol 178:599–608. https://doi.org/10.1016/j.ajpath.2010.10.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jonigk D, Modde F, Bockmeyer CL, Becker JU, Lehmann U (2011) Optimized RNA extraction from non-deparaffinized, laser-microdissected material. Methods Mol Biol 755:67–75. https://doi.org/10.1007/978-1-61779-163-5_5

    Article  CAS  PubMed  Google Scholar 

  17. Jonigk D, Rath B, Borchert P, Braubach P, Maegel L, Izykowski N, Warnecke G, Sommer W, Kreipe H, Blach R, Anklamm A, Haverich A, Eder M, Stadler M, Welte T, Gottlieb J, Kuehnel M, Laenger F (2017) Comparative analysis of morphological and molecular motifs in bronchiolitis obliterans and alveolar fibroelastosis after lung and stem cell transplantation. J Pathol Clin Res 3:17–28. https://doi.org/10.1002/cjp2.60

    Article  CAS  PubMed  Google Scholar 

  18. Kellner M, Heidrich M, Lorbeer R‑A, Antonopoulos GC, Knudsen L, Wrede C, Izykowski N, Grothausmann R, Jonigk D, Ochs M, Ripken T, Kühnel MP, Meyer H (2016) A combined method for correlative 3D imaging of biological samples from macro to nano scale. Sci Rep 6:35606. https://doi.org/10.1038/srep35606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kellner M, Wehling J, Warnecke G, Heidrich M, Izykowski N, Vogel-Claussen J, Lorbeer R‑A, Antonopoulos G, Janciauskiene S, Grothausmann R, Knudsen L, Ripken T, Meyer H, Kreipe H, Ochs M, Jonigk D, Kühnel MP (2015) Correlating 3D morphology with molecular pathology: fibrotic remodelling in human lung biopsies. Thorax 70:1197–1198. https://doi.org/10.1136/thoraxjnl-2015-207131

    Article  PubMed  Google Scholar 

  20. Kokosi MA, Nicholson AG, Hansell DM, Wells AU (2016) Rare idiopathic interstitial pneumonias: LIP and PPFE and rare histologic patterns of interstitial pneumonias: AFOP and BPIP. Respirology 21:600–614. https://doi.org/10.1111/resp.12693

    Article  PubMed  Google Scholar 

  21. Konen E, Weisbrod GL, Pakhale S, Chung T, Paul NS, Hutcheon MA (2003) Fibrosis of the upper lobes: a newly identified late-onset complication after lung transplantation? AJR Am J Roentgenol 181:1539–1543. https://doi.org/10.2214/ajr.181.6.1811539

    Article  PubMed  Google Scholar 

  22. Larsen BT, Smith ML, Elicker BM, Fernandez JM, de Morvil GAA-O, Pereira CAC, Leslie KO (2017) Diagnostic approach to advanced fibrotic interstitial lung disease: bringing together clinical, radiologic, and histologic clues. Arch Pathol Lab Med 141:901–915. https://doi.org/10.5858/arpa.2016-0299-SA

    Article  PubMed  Google Scholar 

  23. Lederer DJ, Martinez FJ (2018) Idiopathic pulmonary fibrosis. N Engl J Med 378:1811–1823. https://doi.org/10.1056/NEJMra1705751

    Article  CAS  PubMed  Google Scholar 

  24. Lettieri CJ, Veerappan GR, Helman DL, Mulligan CR, Shorr AF (2005) Outcomes and safety of surgical lung biopsy for interstitial lung disease. Chest 127:1600–1605. https://doi.org/10.1378/chest.127.5.1600

    Article  PubMed  Google Scholar 

  25. Liebow AA, Carrington CB (1966) Hypersensitivity reactions involving the lung. Trans Stud Coll Physicians Phila 34:47–70

    CAS  PubMed  Google Scholar 

  26. Liebow AA, Steer A, Billingsley JG (1965) Desquamative interstitial pneumonia. Am J Med 39:369–404

    Article  CAS  Google Scholar 

  27. Miles LA, Parmer RJ (2016) Angry macrophages patrol for fibrin. Blood 127:1079–1080. https://doi.org/10.1182/blood-2016-01-687673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Milstone AP, Brumble LM, Loyd JE, Ely EW, Roberts JR, Pierson RN, Dummer JS (2000) Active CMV infection before lung transplantation: risk factors and clinical implications. J Heart Lung Transplant 19:744–750

    Article  CAS  Google Scholar 

  29. Parish JM, Muhm JR, Leslie KO (2003) Upper lobe pulmonary fibrosis associated with high-dose chemotherapy containing BCNU for bone marrow transplantation. Mayo Clin Proc 78:630–634. https://doi.org/10.4065/78.5.630

    Article  PubMed  Google Scholar 

  30. Peca D, Boldrini R, Johannson J, Shieh JT, Citti A, Petrini S, Salerno T, Cazzato S, Testa R, Messina F, Onofri A, Cenacchi G, Westermark P, Ullman N, Cogo P, Cutrera R, Danhaive O, Danhaive O (2015) Clinical and ultrastructural spectrum of diffuse lung disease associated with surfactant protein C mutations. Eur J Hum Genet 23:1033–1041. https://doi.org/10.1038/ejhg.2015.45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier J‑F, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE, Kondoh Y, Myers J, Müller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schünemann HJ, ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis (2011) An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 183:788–824. https://doi.org/10.1164/rccm.2009-040GL

    Article  PubMed  PubMed Central  Google Scholar 

  32. Raghu G, Rochwerg B, Zhang Y, Garcia CAC, Azuma A, Behr J, Brozek JL, Collard HR, Cunningham W, Homma S, Johkoh T, Martinez FJ, Myers J, Protzko SL, Richeldi L, Rind D, Selman M, Theodore A, Wells AU, Hoogsteden H, Schünemann HJ, American Thoracic Society, European Respiratory society, Japanese Respiratory Society, Latin American Thoracic Association (2015) An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med 192:e3–e19. https://doi.org/10.1164/rccm.201506-1063ST

    Article  PubMed  Google Scholar 

  33. Raghu G, Selman M (2015) Nintedanib and Pirfenidone. New antifibrotic treatments indicated for idiopathic pulmonary fibrosis offer hopes and raises questions. Am J Respir Crit Care Med 191:252–254. https://doi.org/10.1164/rccm.201411-2044ED

    Article  CAS  PubMed  Google Scholar 

  34. Rosenbaum JN, Butt YM, Johnson KA, Meyer K, Batra K, Kanne JP, Torrealba JR (2015) Pleuroparenchymal fibroelastosis: a pattern of chronic lung injury. Hum Pathol 46:137–146. https://doi.org/10.1016/j.humpath.2014.10.007

    Article  PubMed  Google Scholar 

  35. Rossi G, Cavazza A, Colby TV (2015) Pathology of Sarcoidosis. Clin Rev Allergy Immunol 49:36–44. https://doi.org/10.1007/s12016-015-8479-6

    Article  CAS  PubMed  Google Scholar 

  36. Sato M, Hwang DM, Ohmori-Matsuda K, Chaparro C, Waddell TK, Singer LG, Hutcheon MA, Keshavjee S (2012) Revisiting the pathologic finding of diffuse alveolar damage after lung transplantation. J Heart Lung Transplant 31:354–363. https://doi.org/10.1016/j.healun.2011.12.015

    Article  PubMed  Google Scholar 

  37. Sato M, Waddell TK, Wagnetz U, Roberts HC, Hwang DM, Haroon A, Wagnetz D, Chaparro C, Singer LG, Hutcheon MA, Keshavjee S (2011) Restrictive allograft syndrome (RAS): a novel form of chronic lung allograft dysfunction. J Heart Lung Transplant 30:735–742. https://doi.org/10.1016/j.healun.2011.01.712

    Article  PubMed  Google Scholar 

  38. Snetselaar R, van Moorsel CHM, Kazemier KM, van der Vis JJ, Zanen P, van Oosterhout MFM, Grutters JC (2015) Telomere length in interstitial lung diseases. Chest 148:1011–1018. https://doi.org/10.1378/chest.14-3078

    Article  PubMed  Google Scholar 

  39. Spagnolo P, Lee JC, Sverzellati N, Rossi G, Cottin V (2018) The lung in rheumatoid arthritis—focus on interstitial lung disease. Arthritis Rheumatol. https://doi.org/10.1002/art.40574

    Article  PubMed  Google Scholar 

  40. Takeuchi Y, Miyagawa-Hayashino A, Chen F, Kubo T, Handa T, Date H, Haga H (2015) Pleuroparenchymal fibroelastosis and non-specific interstitial pneumonia: frequent pulmonary sequelae of haematopoietic stem cell transplantation. Histopathology 66:536–544. https://doi.org/10.1111/his.12553

    Article  PubMed  Google Scholar 

  41. von der Thüsen JH, Hansell DM, Tominaga M, Veys PA, Ashworth MT, Owens CM, Nicholson AG (2011) Pleuroparenchymal fibroelastosis in patients with pulmonary disease secondary to bone marrow transplantation. Mod Pathol 24:1633–1639. https://doi.org/10.1038/modpathol.2011.114

    Article  PubMed  Google Scholar 

  42. Tobin RW, Pope CE, Pellegrini CA, Emond MJ, Sillery J, Raghu G (1998) Increased prevalence of gastroesophageal reflux in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 158:1804–1808. https://doi.org/10.1164/ajrccm.158.6.9804105

    Article  CAS  PubMed  Google Scholar 

  43. Travis WD, Costabel U, Hansell DM, King TE, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, Behr J, Bouros D, Brown KK, Colby TV, Collard HR, Cordeiro CR, Cottin V, Crestani B, Drent M, Dudden RF, Egan J, Flaherty K, Hogaboam C, Inoue Y, Johkoh T, Kim DS, Kitaichi M, Loyd J, Martinez FJ, Myers J, Protzko S, Raghu G, Richeldi L, Sverzellati N, Swigris J, Valeyre D (2013) An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. https://doi.org/10.1164/rccm.201308-1483ST

    Article  PubMed  PubMed Central  Google Scholar 

  44. Wang Y, Kuan PJ, Xing C, Cronkhite JT, Torres F, Rosenblatt RL, DiMaio JM, Kinch LN, Grishin NV, Garcia CK (2009) Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet 84:52–59. https://doi.org/10.1016/j.ajhg.2008.11.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yan Z, Kui Z, Ping Z (2014) Reviews and prospectives of signaling pathway analysis in idiopathic pulmonary fibrosis. Autoimmun Rev 13:1020–1025. https://doi.org/10.1016/j.autrev.2014.08.028

    Article  CAS  PubMed  Google Scholar 

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Danksagung

Die Autoren bedanken sich bei Regina Engelhardt, Anette Müller-Brechlin, Christina Petzold, Enrico Calvino Iglesias, Tim Klein, Svea Schwarze, Edith Plucinski, Fabian Foltan und Laurien Czichon für ihre exzellente technische Unterstützung; bei der Klinik für Herz‑, Thorax‑, Transplantations- und Gefäßchirurgie (MHH; Prof. Dr. A. Haverich), der Klinik für Pneumologie (MHH; Prof. Dr. T. Welte) und dem Institut für diagnostische und interventionelle Radiologie (MHH; Prof. Dr. F. Wacker) für die fortgesetzt gute und kollegiale Zusammenarbeit.

Förderung

Diese Publikation wurde durch den europäischen Forschungsrat (European Research Council [ERC]) durch das Horizon 2020 Foschungs- und Innovationsprogramm (consolidator grant XHaLe [no. 19281137 – Danny Jonigk]) sowie durch die Deutsche Forschungsgemeinschaft (DFG; SFB 738/3, Projekt B09 – Danny Jonigk und Florian Laenger) gefördert.

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Authors and Affiliations

  1. Institut für Pathologie, Medizinische Hochschule Hannover (MHH), Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland

    F. Länger, H. Stark, P. Braubach, K. Hussein, K. Teiken, L. Maegel, M. Kuehnel &  D. Jonigk FRCPath

  2. Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Deutsches Zentrum für Lungenforschung (DZL), Hannover, Deutschland

    F. Länger, H. Stark, P. Braubach, K. Teiken, L. Maegel, M. Kuehnel &  D. Jonigk FRCPath

  3. Institut für Pathologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland

    M. Ackermann

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F. Länger, H. Stark, P. Braubach, M. Ackermann, K. Hussein, K. Teiken, L. Maegel, M. Kuehnel und D. Jonigk geben an, dass kein Interessenkonflikt besteht.

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Länger, F., Stark, H., Braubach, P. et al. Schädigungsmuster interstitieller Lungenerkrankungen. Pathologe 39 (Suppl 2), 262–271 (2018). https://doi.org/10.1007/s00292-018-0503-1

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