Evolving Concepts and Controversies in Interstitial Lung diseases: Update in 2023

Main Article Content

Paul Wawryko, MD Eunhee S. Yi, MD

Abstract

Recent studies elicited evolving concepts and controversies in interstitial lung diseases and proposed substantial changes in diagnostic and therapeutic approaches to interstitial lung diseases. Dr. Averill A. Liebow first coined the term usual interstitial pneumonia (UIP) in 1960’s as distinct pathologic pattern of fibrosis in idiopathic pulmonary fibrosis (IPF), the prototype of progressive fibrosing interstitial lung disease with poor prognosis. Advances in omics led to a better understanding of molecular pathogenesis of UIP and shed light on various types of familial pulmonary fibrosis as well as familial IPF. The concept of progressive pulmonary fibrosis was introduced to acknowledge additional types of progressive fibrosing interstitial lung diseases with the clinical and pathologic phenotypes very similar to those of UIP/IPF. As such, some authors have proposed a paradigm shift by considering UIP as a stand-alone diagnostic entity to encompass other fibrosing interstitial lung diseases that undergo the same relentless progression as IPF. Cicatricial organizing pneumonia is a variant of organizing pneumonia that can be reminiscent of UIP on histopathology but usually follows a stable clinical course unlike UIP. There has been significant disconnection in fundamental understanding as well as diagnostic criteria of lymphocytic interstitial pneumonia among pathologists, pulmonologists and radiologists, which needs to be resolved. The concept and histopathologic criteria of granulomatous and lymphocytic interstitial lung disease are also elusive and require clarification as well. In this review, these topics will be covered based on current literature.

Keywords: idiopathic pulmonary fibrosis (IPF), usual interstitial pneumonia (UIP), familial pulmonary fibrosis, progressive pulmonary fibrosis, cicatricial organizing pneumonia (CiOP), lymphocytic interstitial pneumonia (LIP), granulomatous and lymphocytic interstitial lung disease (GLILD), American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), Asociacion Latinoamericana de Torax (ALAT)

Article Details

How to Cite
WAWRYKO, Paul; YI, Eunhee S.. Evolving Concepts and Controversies in Interstitial Lung diseases: Update in 2023. Medical Research Archives, [S.l.], v. 11, n. 8, aug. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4305>. Date accessed: 02 oct. 2023. doi: https://doi.org/10.18103/mra.v11i8.4305.
Section
Research Articles

References

1. Liebow, A.A. and C.B. Carrington, The interstitial pneumonias, in Frontiers of Pulmonary Radiology, M. Simon, E. Potchen, and M. Lemay, Editors. 1969, Grune and Stratton: New York. p. 102-41.
2. Katzenstein, A.L. and J.L. Myers, Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. Am J Respir Crit Care Med, 1998. 157(4 Pt 1): p. 1301-15.
3. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med, 2000. 161(2 Pt 1): p. 646-64.
4. Raghu, G., et al., Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med, 2022. 205(9): p. e18-e47.
5. Kim, S.Y., et al., Classification of usual interstitial pneumonia in patients with interstitial lung disease: assessment of a machine learning approach using high-dimensional transcriptional data. Lancet Respir Med, 2015. 3(6): p. 473-82.
6. Raghu, G., et al., Use of a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples: a prospective validation study. Lancet Respir Med, 2019. 7(6): p. 487-496.
7. Selman, M., A. Pardo, and A.U. Wells, Usual interstitial pneumonia as a stand-alone diagnostic entity: the case for a paradigm shift? Lancet Respir Med, 2023. 11(2): p. 188-196.
8. Collard, H.R., et al., Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2007. 176(7): p. 636-43.
9. Raghu, G., 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(6): p. 788-824.
10. Richeldi, L., et al., Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med, 2011. 365(12): p. 1079-87.
11. Richeldi, L., et al., Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med, 2014. 370(22): p. 2071-82.
12. Azuma, A., et al., Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med, 2005. 171(9): p. 1040-7.
13. Taniguchi, H., et al., Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J, 2010. 35(4): p. 821-9.
14. Raghu, G., et al., 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, 2015. 192(2): p. e3-19.
15. Raghu, G., et al., Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med, 2018. 198(5): p. e44-e68.
16. Hambly, N., et al., Prevalence and characteristics of progressive fibrosing interstitial lung disease in a prospective registry. Eur Respir J, 2022. 60(4).
17. Hozumi, H., et al., Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control study. BMJ Open, 2013. 3(9): p. e003132.
18. Kang, J., et al., Acute exacerbation of fibrotic hypersensitivity pneumonitis: incidence and outcomes. Respir Res, 2021. 22(1): p. 152.
19. Adegunsoye, A., et al., Computed Tomography Honeycombing Identifies a Progressive Fibrotic Phenotype with Increased Mortality across Diverse Interstitial Lung Diseases. Ann Am Thorac Soc, 2019. 16(5): p. 580-588.
20. Sandoz, E., Uber zwei falle von fotaler bronchektasie. Beitr Pathol Anat, 1907. 41: p. 496-517.
21. Marshall, R.P., et al., Adult familial cryptogenic fibrosing alveolitis in the United Kingdom. Thorax, 2000. 55(2): p. 143-6.
22. Hodgson, U., T. Laitinen, and P. Tukiainen, Nationwide prevalence of sporadic and familial idiopathic pulmonary fibrosis: evidence of founder effect among multiplex families in Finland. Thorax, 2002. 57(4): p. 338-42.
23. Barlo, N.P., et al., Surfactant protein-D predicts survival in patients with idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis, 2009. 26(2): p. 155-61.
24. Garcia-Sancho, C., et al., Familial pulmonary fibrosis is the strongest risk factor for idiopathic pulmonary fibrosis. Respir Med, 2011. 105(12): p. 1902-7.
25. Loyd, J.E., Pulmonary fibrosis in families. Am J Respir Cell Mol Biol, 2003. 29(3 Suppl): p. S47-50.
26. Fernandez, B.A., et al., A Newfoundland cohort of familial and sporadic idiopathic pulmonary fibrosis patients: clinical and genetic features. Respir Res, 2012. 13(1): p. 64.
27. Ley, B., et al., The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis: an observational cohort-control study. Lancet Respir Med, 2017. 5(8): p. 639-647.
28. Newton, C.A., et al., Telomere length and genetic variant associations with interstitial lung disease progression and survival. Eur Respir J, 2019. 53(4).
29. Cutting, C.C., et al., Family History of Pulmonary Fibrosis Predicts Worse Survival in Patients With Interstitial Lung Disease. Chest, 2021. 159(5): p. 1913-1921.
30. Steele, M.P., et al., Clinical and pathologic features of familial interstitial pneumonia. Am J Respir Crit Care Med, 2005. 172(9): p. 1146-52.
31. Newton, C.A., et al., Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive. Eur Respir J, 2016. 48(6): p. 1710-1720.
32. Mathai, S.K., et al., MUC5B variant is associated with visually and quantitatively detected preclinical pulmonary fibrosis. Thorax, 2019. 74(12): p. 1131-1139.
33. Hunninghake, G.M., et al., Interstitial Lung Disease in Relatives of Patients with Pulmonary Fibrosis. Am J Respir Crit Care Med, 2020. 201(10): p. 1240-1248.
34. Salisbury, M.L., et al., Development and Progression of Radiologic Abnormalities in Individuals at Risk for Familial Interstitial Lung Disease. Am J Respir Crit Care Med, 2020. 201(10): p. 1230-1239.
35. Mathai, S.K., et al., Pulmonary fibrosis in the era of stratified medicine. Thorax, 2016. 71(12): p. 1154-1160.
36. Seibold, M.A., et al., A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med, 2011. 364(16): p. 1503-12.
37. Nogee, L.M., et al., A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med, 2001. 344(8): p. 573-9.
38. van Moorsel, C.H.M., J.J. van der Vis, and J.C. Grutters, Genetic disorders of the surfactant system: focus on adult disease. Eur Respir Rev, 2021. 30(159).
39. Thomas, A.Q., et al., Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med, 2002. 165(9): p. 1322-8.
40. van Moorsel, C.H., et al., SFTPA2 Mutations in Familial and Sporadic Idiopathic Interstitial Pneumonia. Am J Respir Crit Care Med, 2015. 192(10): p. 1249-52.
41. Armanios, M.Y., et al., Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med, 2007. 356(13): p. 1317-26.
42. Tsakiri, K.D., et al., Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci U S A, 2007. 104(18): p. 7552-7.
43. Armanios, M., Telomerase and idiopathic pulmonary fibrosis. Mutat Res, 2012. 730(1-2): p. 52-8.
44. Savage, S.A. and B.P. Alter, Dyskeratosis congenita. Hematol Oncol Clin North Am, 2009. 23(2): p. 215-31.
45. Diaz de Leon, A., et al., Subclinical lung disease, macrocytosis, and premature graying in kindreds with telomerase (TERT) mutations. Chest, 2011. 140(3): p. 753-763.
46. Borie, R., et al., Prevalence and characteristics of TERT and TERC mutations in suspected genetic pulmonary fibrosis. Eur Respir J, 2016. 48(6): p. 1721-1731.
47. Juge, P.A., et al., Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis. Eur Respir J, 2017. 49(5).
48. Petrovski, S., et al., An Exome Sequencing Study to Assess the Role of Rare Genetic Variation in Pulmonary Fibrosis. Am J Respir Crit Care Med, 2017. 196(1): p. 82-93.
49. Dressen, A., et al., Analysis of protein-altering variants in telomerase genes and their association with MUC5B common variant status in patients with idiopathic pulmonary fibrosis: a candidate gene sequencing study. Lancet Respir Med, 2018. 6(8): p. 603-614.
50. Ley, B., et al., Rare Protein-Altering Telomere-related Gene Variants in Patients with Chronic Hypersensitivity Pneumonitis. Am J Respir Crit Care Med, 2019. 200(9): p. 1154-1163.
51. Cronkhite, J.T., et al., Telomere shortening in familial and sporadic pulmonary fibrosis. Am J Respir Crit Care Med, 2008. 178(7): p. 729-37.
52. Leslie, K.O., et al., Familial idiopathic interstitial pneumonia: histopathology and survival in 30 patients. Arch Pathol Lab Med, 2012. 136(11): p. 1366-76.
53. Wijsenbeek, M. and V. Cottin, Spectrum of Fibrotic Lung Diseases. N Engl J Med, 2020. 383(10): p. 958-968.
54. Cottin, V., et al., Fibrosing interstitial lung diseases: knowns and unknowns. Eur Respir Rev, 2019. 28(151).
55. Brown, K.K., et al., The natural history of progressive fibrosing interstitial lung diseases. Eur Respir J, 2020. 55(6).
56. Nasser, M., et al., Progressive fibrosing interstitial lung disease: a clinical cohort (the PROGRESS study). Eur Respir J, 2021. 57(2).
57. Flaherty, K.R., et al., Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Respir Res, 2017. 4(1): p. e000212.
58. Flaherty, K.R., et al., Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med, 2019. 381(18): p. 1718-1727.
59. Maher, T.M., et al., Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med, 2020. 8(2): p. 147-157.
60. Behr, J., et al., Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir Med, 2021. 9(5): p. 476-486.
61. Wells, A.U., et al., Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Respir Med, 2020. 8(5): p. 453-460.
62. Matteson, E.L., et al., Nintedanib in Patients With Autoimmune Disease-Related Progressive Fibrosing Interstitial Lung Diseases: Subgroup Analysis of the INBUILD Trial. Arthritis Rheumatol, 2022. 74(6): p. 1039-1047.
63. Epler, G.R. and T.V. Colby, The spectrum of bronchiolitis obliterans. Chest, 1983. 83(2): p. 161-2.
64. Epler, G.R., et al., Bronchiolitis obliterans organizing pneumonia. N Engl J Med, 1985. 312(3): p. 152-8.
65. Katzenstein, A.L., et al., Bronchiolitis obliterans and usual interstitial pneumonia. A comparative clinicopathologic study. Am J Surg Pathol, 1986. 10(6): p. 373-81.
66. Camus, P., et al., Bronchiolitis obliterans organising pneumonia in patients taking acebutolol or amiodarone. Thorax, 1989. 44(9): p. 711-5.
67. Santrach, P.J., et al., Nodular form of bleomycin-related pulmonary injury in patients with osteogenic sarcoma. Cancer, 1989. 64(4): p. 806-11.
68. Kaufman, J. and R. Komorowski, Bronchiolitis obliterans. A new clinical-pathologic complication of irradiation pneumonitis. Chest, 1990. 97(5): p. 1243-4.
69. Colby, T.V., Pathologic aspects of bronchiolitis obliterans organizing pneumonia. Chest, 1992. 102(1 Suppl): p. 38S-43S.
70. Crestani, B., et al., Bronchiolitis obliterans organizing pneumonia syndrome primed by radiation therapy to the breast. The Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires (GERM"O"P). Am J Respir Crit Care Med, 1998. 158(6): p. 1929-35.
71. Cazzato, S., et al., Bronchiolitis obliterans-organizing pneumonia: an Italian experience. Respir Med, 2000. 94(7): p. 702-8.
72. Epler, G.R., Bronchiolitis obliterans organizing pneumonia. Arch Intern Med, 2001. 161(2): p. 158-64.
73. Popper, H.H., Bronchiolitis obliterans. Organizing pneumonia. Verh Dtsch Ges Pathol, 2002. 86: p. 101-6.
74. Vasu, T.S., et al., Clinical and radiologic distinctions between secondary bronchiolitis obliterans organizing pneumonia and cryptogenic organizing pneumonia. Respir Care, 2009. 54(8): p. 1028-32.
75. Yoo, J.W., et al., Comparison between cryptogenic organizing pneumonia and connective tissue disease-related organizing pneumonia. Rheumatology (Oxford), 2011. 50(5): p. 932-8.
76. Travis, W.D., et al., 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, 2013. 188(6): p. 733-48.
77. King, T.E., Jr. and R.L. Mortenson, Cryptogenic organizing pneumonitis. The North American experience. Chest, 1992. 102(1 Suppl): p. 8S-13S.
78. Oymak, F.S., et al., Bronchiolitis obliterans organizing pneumonia. Clinical and roentgenological features in 26 cases. Respiration, 2005. 72(3): p. 254-62.
79. Sen, T. and Z.F. Udwadia, Cryptogenic organizing pneumonia: clinical profile in a series of 34 admitted patients in a hospital in India. J Assoc Physicians India, 2008. 56: p. 229-32.
80. Lee, J.W., et al., Cryptogenic organizing pneumonia: serial high-resolution CT findings in 22 patients. AJR Am J Roentgenol, 2010. 195(4): p. 916-22.
81. Cohen, A.J., T.E. King, Jr., and G.P. Downey, Rapidly progressive bronchiolitis obliterans with organizing pneumonia. Am J Respir Crit Care Med, 1994. 149(6): p. 1670-5.
82. Nizami, I.Y., et al., Idiopathic bronchiolitis obliterans with organizing pneumonia. An acute and life-threatening syndrome. Chest, 1995. 108(1): p. 271-7.
83. Terada, T., Autopsy findings of fatal cryptogenic organizing pneumonia. Int J Clin Exp Pathol, 2013. 6(6): p. 1128-31.
84. Lee, J.S., et al., Organizing pneumonia: prognostic implication of high-resolution computed tomography features. J Comput Assist Tomogr, 2003. 27(2): p. 260-5.
85. Roberton, B.J. and D.M. Hansell, Organizing pneumonia: a kaleidoscope of concepts and morphologies. Eur Radiol, 2011. 21(11): p. 2244-54.
86. Yousem, S.A., R.H. Lohr, and T.V. Colby, Idiopathic bronchiolitis obliterans organizing pneumonia/cryptogenic organizing pneumonia with unfavorable outcome: pathologic predictors. Mod Pathol, 1997. 10(9): p. 864-71.
87. Yousem, S.A., Cicatricial variant of cryptogenic organizing pneumonia. Hum Pathol, 2017. 64: p. 76-82.
88. Churg, A., J.L. Wright, and A. Bilawich, Cicatricial organising pneumonia mimicking a fibrosing interstitial pneumonia. Histopathology, 2018. 72(5): p. 846-854.
89. Mengoli, M.C., et al., Incidental iatrogenic form of collagenized organizing pneumonia. Hum Pathol, 2018. 73: p. 192-193.
90. Roden, A.C., et al., Late Complications of COVID-19. Arch Pathol Lab Med, 2022. 146(7): p. 791-804.
91. Woge, M.J., et al., Cicatricial organizing pneumonia: a clinicopathologic and radiologic study on a cohort diagnosed by surgical lung biopsy at a single institution. Hum Pathol, 2020. 101: p. 58-63.
92. Carrington, C.B. and A.A. Liebow, Lymphocytic interstitial pneumonia. Am J Pathol, 1966. 48: p. 36a.
93. American Thoracic, S. and S. European Respiratory, 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(2): p. 277-304.
94. Isaacson, P. and D.H. Wright, Extranodal malignant lymphoma arising from mucosa-associated lymphoid tissue. Cancer, 1984. 53(11): p. 2515-24.
95. Nicholson, A.G., et al., Pulmonary B-cell non-Hodgkin's lymphomas. The value of immunohistochemistry and gene analysis in diagnosis. Histopathology, 1995. 26(5): p. 395-403.
96. Katzenstein, A.L. and R.F. Fiorelli, Nonspecific interstitial pneumonia/fibrosis. Histologic features and clinical significance. Am J Surg Pathol, 1994. 18(2): p. 136-47.
97. Travis, W.D., et al., Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Respir Crit Care Med, 2008. 177(12): p. 1338-47.
98. Fraune, C., et al., Lymphoid Interstitial Pneumonia (LIP) Revisited: A Critical Reappraisal of the Histologic Spectrum of "Radiologic" and "Pathologic" LIP in the Context of Diffuse Benign Lymphoid Proliferations of the Lung. Am J Surg Pathol, 2023. 47(3): p. 281-295.
99. Bates, C.A., et al., Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol, 2004. 114(2): p. 415-21.
100. Rao, N., A.C. Mackinnon, and J.M. Routes, Granulomatous and lymphocytic interstitial lung disease: a spectrum of pulmonary histopathologic lesions in common variable immunodeficiency--histologic and immunohistochemical analyses of 16 cases. Hum Pathol, 2015. 46(9): p. 1306-14.
101. Hurst, J.R., et al., British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders. J Allergy Clin Immunol Pract, 2017. 5(4): p. 938-945.
102. Prasse, A., G. Kayser, and K. Warnatz, Common variable immunodeficiency-associated granulomatous and interstitial lung disease. Curr Opin Pulm Med, 2013. 19(5): p. 503-9.
103. Larsen, B.T., et al., GLILD Revisited: Pulmonary Pathology of Common Variable and Selective IgA Immunodeficiency. Am J Surg Pathol, 2020. 44(8): p. 1073-1081.