Korean Journal of Radiology

  • 제22권5호
  • /
  • Pages.811-828
  • /
  • 2021
  • /
  • 1229-6929(pISSN)
  • /
  • 2005-8330(eISSN)
대한영상의학회 (The Korean Society of Radiology)
권호 표지
DOI QR코드

DOI QR Code

Spectrum of Pulmonary Fibrosis from Interstitial Lung Abnormality to Usual Interstitial Pneumonia: Importance of Identification and Quantification of Traction Bronchiectasis in Patient Management

  • Takuya Hino (Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School) ;
  • Kyung Soo Lee (Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM)) ;
  • Joungho Han (Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM)) ;
  • Akinori Hata (Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School) ;
  • Kousei Ishigami (Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University) ;
  • Hiroto Hatabu (Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School)
  • 투고 : 2020.09.15
  • 심사 : 2020.11.16
  • 발행 : 2021.05.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Following the introduction of a novel pathological concept of usual interstitial pneumonia (UIP) by Liebow and Carrington in 1969, diffuse interstitial pneumonia has evolved into UIP, nonspecific interstitial pneumonia (NSIP), and interstitial lung abnormality (ILA); the histopathological and CT findings of these conditions reflect the required multidisciplinary team approach, involving pulmonologists, radiologists, and pathologists, for their diagnosis and management. Concomitantly, traction bronchiectasis and bronchiolectasis have been recognized as the most persistent and important indices of the severity and prognosis of fibrotic lung diseases. The traction bronchiectasis index (TBI) can stratify the prognoses of patients with ILAs. In this review, the evolutionary concepts of UIP, NSIP, and ILAs are summarized in tables and figures, with a demonstration of the correlation between CT findings and pathologic evaluation. The CT-based UIP score is being proposed to facilitate a better understanding of the spectrum of pulmonary fibrosis, from ILAs to UIP, with emphasis on traction bronchiectasis/bronchiolectasis.

키워드

과제정보

We are grateful for the librarians Myung-Ah Shim and Jaero Park for their dedicated support of manuscript formatting. Both librarians are working at the Samsung Medical Information & Media Services of Samsung Medical Center located in Seoul, South Korea.

참고문헌

  1. Liebow AA, Carrington CB. The interstitial pneumonias. In: Simon M, Potchen EJ, LeMay M, eds. Frontiers of pulmonary radiology, 1st ed. New York: Grune & Stratton, 1969:102-141 
  2. Katzenstein AL, Fiorelli RF. Nonspecific interstitial pneumonia/fibrosis. Histologic features and clinical significance. Am J Surg Pathol 1994;18:136-147  https://doi.org/10.1097/00000478-199402000-00003
  3. Nishimura K, Kitaichi M, Izumi T, Nagai S, Kanaoka M, Itoh H. Usual interstitial pneumonia: histologic correlation with high-resolution CT. Radiology 1992;182:337-342  https://doi.org/10.1148/radiology.182.2.1732946
  4. Muller NL, Coiby TV. Idiopathic interstitial pneumonias: high-resolution CT and histologic findings. Radiographics 1997;17:1016-1022  https://doi.org/10.1148/radiographics.17.4.9225401
  5. Johkoh T, Muller NL, Cartier Y, Kavanagh PV, Hartman TE, Akira M, et al. Idiopathic interstitial pneumonias: diagnostic accuracy of thin-section CT in 129 patients. Radiology 1999;211:555-560  https://doi.org/10.1148/radiology.211.2.r99ma01555
  6. American Thoracic Society; European Respiratory Society. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 2002;165:277-304  https://doi.org/10.1164/ajrccm.165.2.ats01
  7. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, 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  https://doi.org/10.1164/rccm.2009-040GL
  8. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2018;198:e44-e68  https://doi.org/10.1164/rccm.201807-1255ST
  9. Lynch DA, Sverzellati N, Travis WD, Brown KK, Colby TV, Galvin JR, et al. Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper. Lancet Respir Med 2018;6:138-153  https://doi.org/10.1016/S2213-2600(17)30433-2
  10. Hatabu H, Hunninghake GM, Richeldi L, Brown KK, Wells AU, Remy-Jardin M, et al. Interstitial lung abnormalities detected incidentally on CT: a Position Paper from the Fleischner Society. Lancet Respir Med 2020;8:726-737  https://doi.org/10.1016/S2213-2600(20)30168-5
  11. Sumikawa H, Johkoh T, Fujimoto K, Arakawa H, Colby TV, Fukuoka J, et al. Pathologically proved nonspecific interstitial pneumonia: CT pattern analysis as compared with usual interstitial pneumonia CT pattern. Radiology 2014;272:549-556  https://doi.org/10.1148/radiol.14130853
  12. Putman RK, Gudmundsson G, Axelsson GT, Hida T, Honda O, Araki T, et al. Imaging patterns are associated with interstitial lung abnormality progression and mortality. Am J Respir Crit Care Med 2019;200:175-183  https://doi.org/10.1164/rccm.201809-1652OC
  13. Hida T, Nishino M, Hino T, Lu J, Putman RK, Gudmundsson EF, et al. Traction bronchiectasis/bronchiolectasis is associated with interstitial lung abnormality mortality. Eur J Radiol 2020;129:109073 
  14. Katzenstein AL, Myers JL, Mazur MT. Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study. Am J Surg Pathol 1986;10:256-267  https://doi.org/10.1097/00000478-198604000-00004
  15. Myers JL, Veal CF Jr, Shin MS, Katzenstein AL. Respiratory bronchiolitis causing interstitial lung disease. A clinicopathologic study of six cases. Am Rev Respir Dis 1987;135:880-884  https://doi.org/10.1164/arrd.1987.135.4.880
  16. Ohori NP, Sciurba FC, Owens GR, Hodgson MJ, Yousem SA. Giant-cell interstitial pneumonia and hard-metal pneumoconiosis. A clinicopathologic study of four cases and review of the literature. Am J Surg Pathol 1989;13:581-587  https://doi.org/10.1097/00000478-198907000-00006
  17. Gibbs AR, Seal RM. Primary lymphoproliferative conditions of lung. Thorax 1978;33:140-152  https://doi.org/10.1136/thx.33.2.140
  18. Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. Am J Respir Crit Care Med 1998;157:1301-1315  https://doi.org/10.1164/ajrccm.157.4.9707039
  19. Heppleston AG. The pathology of honeycomb lung. Thorax 1956;11:77-93  https://doi.org/10.1136/thx.11.2.77
  20. Genereux GP. The end-stage lung: pathogenesis, pathology, and radiology. Radiology 1975;116:279-289  https://doi.org/10.1148/116.2.279
  21. Westcott JL, Cole SR. Traction bronchiectasis in end-stage pulmonary fibrosis. Radiology 1986;161:665-669  https://doi.org/10.1148/radiology.161.3.3786716
  22. Cantin L, Bankier AA, Eisenberg RL. Bronchiectasis. AJR Am J Roentgenol 2009;193:W158-171  https://doi.org/10.2214/AJR.09.3053
  23. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Muller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology 2008;246:697-722  https://doi.org/10.1148/radiol.2462070712
  24. Kitaichi M. Pathologic features and the classification of interstitial pneumonia of unknown etiology. Bull Chest Dis Res Inst Kyoto Univ 1990;23:1-18 
  25. Nagai S, Kitaichi M, Itoh H, Nishimura K, Izumi T, Colby TV. Idiopathic nonspecific interstitial pneumonia/fibrosis: comparison with idiopathic pulmonary fibrosis and BOOP. Eur Respir J 1998;12:1010-1019  https://doi.org/10.1183/09031936.98.12051010
  26. Travis WD, Matsui K, Moss J, Ferrans VJ. Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns: survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia. Am J Surg Pathol 2000;24:19-33  https://doi.org/10.1097/00000478-200001000-00003
  27. Bjoraker JA, Ryu JH, Edwin MK, Myers JL, Tazelaar HD, Schroeder DR, et al. Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998;157:199-203  https://doi.org/10.1164/ajrccm.157.1.9704130
  28. Katzenstein AL, Mukhopadhyay S, Myers JL. Diagnosis of usual interstitial pneumonia and distinction from other fibrosing interstitial lung diseases. Hum Pathol 2008;39:1275-1294  https://doi.org/10.1016/j.humpath.2008.05.009
  29. Li X, Chen C, Xu J, Liu J, Yi X, Sun X, et al. Nonspecific interstitial pneumonia and usual interstitial pneumonia: comparison of the clinicopathologic features and prognosis. J Thorac Dis 2014;6:1476-1481 
  30. Flaherty KR, Travis WD, Colby TV, Toews GB, Kazerooni EA, Gross BH, et al. Histopathologic variability in usual and nonspecific interstitial pneumonias. Am J Respir Crit Care Med 2001;164:1722-1727  https://doi.org/10.1164/ajrccm.164.9.2103074
  31. du Bois R, King TE Jr. Challenges in pulmonary fibrosis x 5: the NSIP/UIP debate. Thorax 2007;62:1008-1012  https://doi.org/10.1136/thx.2004.031039
  32. Nunes H, Schubel K, Piver D, Magois E, Feuillet S, Uzunhan Y, et al. Nonspecific interstitial pneumonia: survival is influenced by the underlying cause. Eur Respir J 2015;45:746-755  https://doi.org/10.1183/09031936.00148613
  33. Silva CI, Muller NL, Lynch DA, Curran-Everett D, Brown KK, Lee KS, et al. Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology 2008;246:288-297  https://doi.org/10.1148/radiol.2453061881
  34. Kligerman SJ, Groshong S, Brown KK, Lynch DA. Nonspecific interstitial pneumonia: radiologic, clinical, and pathologic considerations. Radiographics 2009;29:73-87  https://doi.org/10.1148/rg.291085096
  35. Kim TS, Lee KS, Chung MP, Han J, Park JS, Hwang JH, et al. Nonspecific interstitial pneumonia with fibrosis: high-resolution CT and pathologic findings. AJR Am J Roentgenol 1998;171:1645-1650  https://doi.org/10.2214/ajr.171.6.9843306
  36. Mink SN, Maycher B. Comparative manifestations and diagnostic accuracy of high-resolution computed tomography in usual interstitial pneumonia and nonspecific interstitial pneumonia. Curr Opin Pulm Med 2012;18:530-534  https://doi.org/10.1097/MCP.0b013e3283568026
  37. Travis WD, Hunninghake G, King TE Jr, Lynch DA, Colby TV, Galvin JR, et al. Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Respir Crit Care Med 2008;177:1338-1347  https://doi.org/10.1164/rccm.200611-1685OC
  38. MacDonald SL, Rubens MB, Hansell DM, Copley SJ, Desai SR, du Bois RM, et al. Nonspecific interstitial pneumonia and usual interstitial pneumonia: comparative appearances at and diagnostic accuracy of thin-section CT. Radiology 2001;221:600-605  https://doi.org/10.1148/radiol.2213010158
  39. Hunninghake GW, Zimmerman MB, Schwartz DA, King TE Jr, Lynch J, Hegele R, et al. Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2001;164:193-196  https://doi.org/10.1164/ajrccm.164.2.2101090
  40. Sverzellati N, Wells AU, Tomassetti S, Desai SR, Copley SJ, Aziz ZA, et al. Biopsy-proved idiopathic pulmonary fibrosis: spectrum of nondiagnostic thin-section CT diagnoses. Radiology 2010;254:957-964  https://doi.org/10.1148/radiol.0990898
  41. Lee HY, Lee KS, Jeong YJ, Hwang JH, Kim HJ, Chung MP, et al. High-resolution CT findings in fibrotic idiopathic interstitial pneumonias with little honeycombing: serial changes and prognostic implications. AJR Am J Roentgenol 2012;199:982-989  https://doi.org/10.2214/AJR.11.8192
  42. Lynch DA, Newell JD, Logan PM, King TE Jr, Muller NL. Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis? AJR Am J Roentgenol 1995;165:807-811  https://doi.org/10.2214/ajr.165.4.7676971
  43. Quadrelli S, Molinari L, Ciallella L, Spina JC, Sobrino E, Chertcoff J. Radiological versus histopathological diagnosis of usual interstitial pneumonia in the clinical practice: does it have any survival difference? Respiration 2009;79:32-37  https://doi.org/10.1159/000225987
  44. Yagihashi K, Huckleberry J, Colby TV, Tazelaar HD, Zach J, Sundaram B, et al. Radiologic-pathologic discordance in biopsy-proven usual interstitial pneumonia. Eur Respir J 2016;47:1189-1197  https://doi.org/10.1183/13993003.01680-2015
  45. Chung JH, Chawla A, Peljto AL, Cool CD, Groshong SD, Talbert JL, et al. CT scan findings of probable usual interstitial pneumonitis have a high predictive value for histologic usual interstitial pneumonitis. Chest 2015;147:450-459  https://doi.org/10.1378/chest.14-0976
  46. Raghu G, Lynch D, Godwin JD, Webb R, Colby TV, Leslie KO, 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;2:277-284  https://doi.org/10.1016/S2213-2600(14)70011-6
  47. Brownell R, Moua T, Henry TS, Elicker BM, White D, Vittinghoff E, et al. The use of pretest probability increases the value of high-resolution CT in diagnosing usual interstitial pneumonia. Thorax 2017;72:424-429  https://doi.org/10.1136/thoraxjnl-2016-209671
  48. Flaherty KR, Toews GB, Lynch JP 3rd, Kazerooni EA, Gross BH, Strawderman RL, et al. Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse reactions, response to therapy, and survival. Am J Med 2001;110:278-282  https://doi.org/10.1016/S0002-9343(00)00711-7
  49. Parambil JG, Myers JL, Ryu JH. Histopathologic features and outcome of patients with acute exacerbation of idiopathic pulmonary fibrosis undergoing surgical lung biopsy. Chest 2005;128:3310-3315  https://doi.org/10.1378/chest.128.5.3310
  50. Collard HR, Ryu JH, Douglas WW, Schwarz MI, Curran-Everett D, King TE Jr, et al. Combined corticosteroid and cyclophosphamide therapy does not alter survival in idiopathic pulmonary fibrosis. Chest 2004;125:2169-2174  https://doi.org/10.1378/chest.125.6.2169
  51. Pereira CA, Malheiros T, Coletta EM, Ferreira RG, Rubin AS, Otta JS, et al. Survival in idiopathic pulmonary fibrosis-cytotoxic agents compared to corticosteroids. Respir Med 2006;100:340-347  https://doi.org/10.1016/j.rmed.2005.05.008
  52. Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006;354:2655-2666  https://doi.org/10.1056/NEJMoa055120
  53. Keir GJ, Maher TM, Ming D, Abdullah R, de Lauretis A, Wickremasinghe M, et al. Rituximab in severe, treatment-refractory interstitial lung disease. Respirology 2014;19:353- 359  https://doi.org/10.1111/resp.12214
  54. Mason DP, Brizzio ME, Alster JM, McNeill AM, Murthy SC, Budev MM, et al. Lung transplantation for idiopathic pulmonary fibrosis. Ann Thorac Surg 2007;84:1121-1128  https://doi.org/10.1016/j.athoracsur.2007.04.096
  55. King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 2014;370:2083-2092  https://doi.org/10.1056/NEJMoa1402582
  56. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014;370:2071-2082  https://doi.org/10.1056/NEJMoa1402584
  57. Collins BF, Raghu G. Antifibrotic therapy for fibrotic lung disease beyond idiopathic pulmonary fibrosis. Eur Respir Rev 2019;28:190022 
  58. Lamas DJ, Kawut SM, Bagiella E, Philip N, Arcasoy SM, Lederer DJ. Delayed access and survival in idiopathic pulmonary fibrosis: a cohort study. Am J Respir Crit Care Med 2011;184:842-847  https://doi.org/10.1164/rccm.201104-0668OC
  59. Maher TM, Strek ME. Antifibrotic therapy for idiopathic pulmonary fibrosis: time to treat. Respir Res 2019;20:205 
  60. Rosas IO, Ren P, Avila NA, Chow CK, Franks TJ, Travis WD, et al. Early interstitial lung disease in familial pulmonary fibrosis. Am J Respir Crit Care Med 2007;176:698-705  https://doi.org/10.1164/rccm.200702-254OC
  61. Copley SJ, Wells AU, Hawtin KE, Gibson DJ, Hodson JM, Jacques AE, et al. Lung morphology in the elderly: comparative CT study of subjects over 75 years old versus those under 55 years old. Radiology 2009;251:566-573  https://doi.org/10.1148/radiol.2512081242
  62. Lederer DJ, Enright PL, Kawut SM, Hoffman EA, Hunninghake G, van Beek EJ, et al. Cigarette smoking is associated with subclinical parenchymal lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA)-lung study. Am J Respir Crit Care Med 2009;180:407-414  https://doi.org/10.1164/rccm.200812-1966OC
  63. Guckel C, Hansell DM. Imaging the 'dirty lung'--has high resolution computed tomography cleared the smoke? Clin Radiol 1998;53:717-722  https://doi.org/10.1016/S0009-9260(98)80312-7
  64. Gochuico BR, Avila NA, Chow CK, Novero LJ, Wu HP, Ren P, et al. Progressive preclinical interstitial lung disease in rheumatoid arthritis. Arch Intern Med 2008;168:159-166  https://doi.org/10.1001/archinternmed.2007.59
  65. Miller ER, Putman RK, Vivero M, Hung Y, Araki T, Nishino M, et al. Histopathology of interstitial lung abnormalities in the context of lung nodule resections. Am J Respir Crit Care Med 2018;197:955-958  https://doi.org/10.1164/rccm.201708-1679LE
  66. Hatabu H, Hunninghake GM, Lynch DA. Interstitial lung abnormality: recognition and perspectives. Radiology 2019;291:1-3  https://doi.org/10.1148/radiol.2018181684
  67. Washko GR, Lynch DA, Matsuoka S, Ross JC, Umeoka S, Diaz A, et al. Identification of early interstitial lung disease in smokers from the COPDGene Study. Acad Radiol 2010;17:48-53  https://doi.org/10.1016/j.acra.2009.07.016
  68. Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med 2011;364:897-906  https://doi.org/10.1056/NEJMoa1007285
  69. Hunninghake GM, Hatabu H, Okajima Y, Gao W, Dupuis J, Latourelle JC, et al. MUC5B promoter polymorphism and interstitial lung abnormalities. N Engl J Med 2013;368:2192-2200  https://doi.org/10.1056/NEJMoa1216076
  70. Doyle TJ, Washko GR, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. Interstitial lung abnormalities and reduced exercise capacity. Am J Respir Crit Care Med 2012;185:756-762  https://doi.org/10.1164/rccm.201109-1618OC
  71. Araki T, Putman RK, Hatabu H, Gao W, Dupuis J, Latourelle JC, et al. Development and progression of interstitial lung abnormalities in the Framingham Heart Study. Am J Respir Crit Care Med 2016;194:1517-1522  https://doi.org/10.1164/rccm.201512-2523OC
  72. Putman RK, Hatabu H, Araki T, Gudmundsson G, Gao W, Nishino M, et al. Association between interstitial lung abnormalities and all-cause mortality. JAMA 2016;315:672-681  https://doi.org/10.1001/jama.2016.0518
  73. Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet 2017;389:1941-1952  https://doi.org/10.1016/S0140-6736(17)30866-8
  74. Silva CI, Muller NL, Hansell DM, Lee KS, Nicholson AG, Wells AU. Nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis: changes in pattern and distribution of disease over time. Radiology 2008;247:251-259  https://doi.org/10.1148/radiol.2471070369
  75. Tsushima K, Sone S, Yoshikawa S, Yokoyama T, Suzuki T, Kubo K. The radiological patterns of interstitial change at an early phase: over a 4-year follow-up. Respir Med 2010;104:1712-1721  https://doi.org/10.1016/j.rmed.2010.05.014
  76. Sverzellati N, Guerci L, Randi G, Calabro E, La Vecchia C, Marchiano A, et al. Interstitial lung diseases in a lung cancer screening trial. Eur Respir J 2011;38:392-400  https://doi.org/10.1183/09031936.00201809
  77. Jin GY, Lynch D, Chawla A, Garg K, Tammemagi MC, Sahin H, et al. Interstitial lung abnormalities in a CT lung cancer screening population: prevalence and progression rate. Radiology 2013;268:563-571  https://doi.org/10.1148/radiol.13120816
  78. Putman RK, Rosas IO, Hunninghake GM. Genetics and early detection in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2014;189:770-778  https://doi.org/10.1164/rccm.201312-2219PP
  79. Hunninghake GM. Interstitial lung abnormalities: erecting fences in the path towards advanced pulmonary fibrosis. Thorax 2019;74:506-511  https://doi.org/10.1136/thoraxjnl-2018-212446
  80. Antoniou KM, Tzilas V, Vasarmidi E, Symvoulakis EK, Tzouvelekis A, Bouros D. Interstitial lung abnormalities: ignotum per ignotius. Lancet Respir Med 2019;7:376-378  https://doi.org/10.1016/S2213-2600(19)30052-9
  81. Hoyer N, Thomsen LH, Wille MMW, Wilcke T, Dirksen A, Pedersen JH, et al. Increased respiratory morbidity in individuals with interstitial lung abnormalities. BMC Pulm Med 2020;20:67 
  82. Hoyer N, Wille MMW, Thomsen LH, Wilcke T, Dirksen A, Pedersen JH, et al. Interstitial lung abnormalities are associated with increased mortality in smokers. Respir Med 2018;136:77-82  https://doi.org/10.1016/j.rmed.2018.02.001
  83. Whittaker Brown SA, Padilla M, Mhango G, Powell C, Salvatore M, Henschke C, et al. Interstitial lung abnormalities and lung cancer risk in the National Lung Screening Trial. Chest 2019;156:1195-1203  https://doi.org/10.1016/j.chest.2019.06.041
  84. Putman RK, Hunninghake GM, Dieffenbach PB, Barragan-Bradford D, Serhan K, Adams U, et al. Interstitial lung abnormalities are associated with acute respiratory distress syndrome. Am J Respir Crit Care Med 2017;195:138-141  https://doi.org/10.1164/rccm.201604-0818LE
  85. Wolters PJ, Collard HR, Jones KD. Pathogenesis of idiopathic pulmonary fibrosis. Annu Rev Pathol 2014;9:157-179  https://doi.org/10.1146/annurev-pathol-012513-104706
  86. Chilosi M, Poletti V, Murer B, Lestani M, Cancellieri A, Montagna L, et al. Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis: the role of deltaN-p63. Lab Invest 2002;82:1335-1345  https://doi.org/10.1097/01.LAB.0000032380.82232.67
  87. Mohning MP, Richards JC, Huie TJ. Idiopathic pulmonary fibrosis: the radiologist's role in making the diagnosis. Br J Radiol 2019;92:20181003 
  88. Watadani T, Sakai F, Johkoh T, Noma S, Akira M, Fujimoto K, et al. Interobserver variability in the CT assessment of honeycombing in the lungs. Radiology 2013;266:936-944  https://doi.org/10.1148/radiol.12112516
  89. Staats P, Kligerman S, Todd N, Tavora F, Xu L, Burke A. A comparative study of honeycombing on high resolution computed tomography with histologic lung remodeling in explants with usual interstitial pneumonia. Pathol Res Pract 2015;211:55-61  https://doi.org/10.1016/j.prp.2014.08.013
  90. Piciucchi S, Tomassetti S, Ravaglia C, Gurioli C, Gurioli C, Dubini A, et al. From "traction bronchiectasis" to honeycombing in idiopathic pulmonary fibrosis: a spectrum of bronchiolar remodeling also in radiology? BMC Pulm Med 2016;16:87 
  91. Johkoh T, Muller NL, Colby TV, Ichikado K, Taniguchi H, Kondoh Y, et al. Nonspecific interstitial pneumonia: correlation between thin-section CT findings and pathologic subgroups in 55 patients. Radiology 2002;225:199-204  https://doi.org/10.1148/radiol.2251011555
  92. Jacob J, Aksman L, Mogulkoc N, Procter AJ, Gholipour B, Cross G, et al. Serial CT analysis in idiopathic pulmonary fibrosis: comparison of visual features that determine patient outcome. Thorax 2020;75:648-654  https://doi.org/10.1136/thoraxjnl-2019-213865
  93. Sumikawa H, Johkoh T, Colby TV, Ichikado K, Suga M, Taniguchi H, et al. Computed tomography findings in pathological usual interstitial pneumonia: relationship to survival. Am J Respir Crit Care Med 2008;177:433-439  https://doi.org/10.1164/rccm.200611-1696OC
  94. Yamauchi H, Bando M, Baba T, Kataoka K, Yamada Y, Yamamoto H, et al. Clinical course and changes in high-resolution computed tomography findings in patients with idiopathic pulmonary fibrosis without honeycombing. PLoS One 2016;11:e0166168 
  95. Edey AJ, Devaraj AA, Barker RP, Nicholson AG, Wells AU, Hansell DM. Fibrotic idiopathic interstitial pneumonias: HRCT findings that predict mortality. Eur Radiol 2011;21:1586-1593  https://doi.org/10.1007/s00330-011-2098-2
  96. Walsh SL, Sverzellati N, Devaraj A, Wells AU, Hansell DM. Chronic hypersensitivity pneumonitis: high resolution computed tomography patterns and pulmonary function indices as prognostic determinants. Eur Radiol 2012;22:1672-1679 https://doi.org/10.1007/s00330-012-2427-0