Pulmonary fibrosis in sarcoidosis

Main Article Content

Huda Asif
Manuel Lessa Ribeiro Neto
Daniel Culver


sarcoidosis, pulmonary, fibrosis


Sarcoidosis may progress to pulmonary fibrosis in 5% of patients with significantly increased mortality. Histopathology shows fibrosis in a lymphangitic pattern surrounding the granulomas. Th1 to Th2 shift in environment along with angiogenesis is implicated in exuberant fibrosis. Clinical features include dyspnea, cough, and frequently with pulmonary function tests showing a mixed ventilatory defect with severely decreased diffusion capacity of carbon monoxide.  Serologic markers including soluble interleukin 2 receptor, chitotriosidase and kern von den lunges 6, and chemokine ligand 18 are elevated and implicated in progression of disease. CT imaging shows fibrosis along bronchovascular bundles with reticulations, traction bronchiectasis and honeycombing predominantly in the upper and central distribution. Complications include sarcoidosis-associated pulmonary hypertension (SAPH) and chronic pulmonary aspergillosis. Treatment involves glucocorticoids and steroid-sparing agents in the presence of active granulomas. Anti-fibrotic agents such as pirfenidone and nintedanib have been shown to slow down pulmonary function decline in randomized clinical trials involving sarcoidosis-associated pulmonary fibrosis. Transplant workup is indicated in New York Heart Association class III or IV with similar success rates as in other lung transplant patients.

Abstract 970 | PDF Downloads 725


1. Lowes D, Al-Shair K, Newton PJ, Morris J, Harris C, Rautemaa-Richardson R, et al. Predictors of mortality in chronic pulmonary aspergillosis. Eur Respir J. 2017;49(2).
2. Nardi A, Brillet PY, Letoumelin P, Girard F, Brauner M, Uzunhan Y, et al. Stage IV sarcoidosis: comparison of survival with the general population and causes of death. Eur Respir J. 2011;38(6):1368-73.
3. Yeager H, Rossman MD, Baughman RP, Teirstein AS, Judson MA, Rabin DL, et al. Pulmonary and psychosocial findings at enrollment in the ACCESS study. Sarcoidosis Vasc Diffuse Lung Dis. 2005;22(2):147-53.
4. Baughman RP, Teirstein AS, Judson MA, Rossman MD, Yeager H, Jr., Bresnitz EA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med. 2001;164(10 Pt 1):1885-9.
5. Kirkil G, Lower EE, Baughman RP. Predictors of Mortality in Pulmonary Sarcoidosis. Chest. 2018;153(1):105-13.
6. Jeny F, Uzunhan Y, Lacroix M, Gille T, Brillet PY, Nardi A, et al. Predictors of mortality in fibrosing pulmonary sarcoidosis. Respir Med. 2020;169:105997.
7. Zhang C, Chan KM, Schmidt LA, Myers JL. Histopathology of Explanted Lungs From Patients With a Diagnosis of Pulmonary Sarcoidosis. Chest. 2016;149(2):499-507.
8. Broos CE, van Nimwegen M, Hoogsteden HC, Hendriks RW, Kool M, van den Blink B. Granuloma formation in pulmonary sarcoidosis. Front Immunol. 2013;4:437.
9. Tana C, Donatiello I, Caputo A, Tana M, Naccarelli T, Mantini C, et al. Clinical Features, Histopathology and Differential Diagnosis of Sarcoidosis. Cells. 2021;11(1).
10. Shigemitsu H, Oblad JM, Sharma OP, Koss MN. Chronic interstitial pneumonitis in end-stage sarcoidosis. Eur Respir J. 2010;35(3):695-7.
11. Patterson KC, Strek ME. Pulmonary fibrosis in sarcoidosis. Clinical features and outcomes. Ann Am Thorac Soc. 2013;10(4):362-70.
12. Patterson KC, Hogarth K, Husain AN, Sperling AI, Niewold TB. The clinical and immunologic features of pulmonary fibrosis in sarcoidosis. Transl Res. 2012;160(5):321-31.
13. Zissel G, Muller-Quernheim J. Specific antigen(s) in sarcoidosis: a link to autoimmunity? Eur Respir J. 2016;47(3):707-9.
14. Banoei MM, Iupe I, Bazaz RD, Campos M, Vogel HJ, Winston BW, et al. Metabolomic and metallomic profile differences between Veterans and Civilians with Pulmonary Sarcoidosis. Sci Rep. 2019;9(1):19584.
15. el-Zaatari FA, Naser SA, Markesich DC, Kalter DC, Engstand L, Graham DY. Identification of Mycobacterium avium complex in sarcoidosis. J Clin Microbiol. 1996;34(9):2240-5.
16. Fang C, Huang H, Xu Z. Immunological Evidence for the Role of Mycobacteria in Sarcoidosis: A Meta-Analysis. PLoS One. 2016;11(8):e0154716.
17. Sarcoidosis. Bonella F, Culver DA, Israël-Biet D, editors2022. 364 p.
18. Kraaijvanger R, Janssen Bonas M, Vorselaars ADM, Veltkamp M. Biomarkers in the Diagnosis and Prognosis of Sarcoidosis: Current Use and Future Prospects. Front Immunol. 2020;11:1443.
19. Ramstein J, Broos CE, Simpson LJ, Ansel KM, Sun SA, Ho ME, et al. IFN-gamma-Producing T-Helper 17.1 Cells Are Increased in Sarcoidosis and Are More Prevalent than T-Helper Type 1 Cells. Am J Respir Crit Care Med. 2016;193(11):1281-91.
20. Gerke AK, Hunninghake G. The immunology of sarcoidosis. Clin Chest Med. 2008;29(3):379-90, vii.
21. Kunkel SL, Lukacs NW, Strieter RM, Chensue SW. Th1 and Th2 responses regulate experimental lung granuloma development. Sarcoidosis Vasc Diffuse Lung Dis. 1996;13(2):120-8.
22. Katchar K, Eklund A, Grunewald J. Expression of Th1 markers by lung accumulated T cells in pulmonary sarcoidosis. J Intern Med. 2003;254(6):564-71.
23. Patterson KC, Franek BS, Muller-Quernheim J, Sperling AI, Sweiss NJ, Niewold TB. Circulating cytokines in sarcoidosis: phenotype-specific alterations for fibrotic and non-fibrotic pulmonary disease. Cytokine. 2013;61(3):906-11.
24. Keane MP. The role of chemokines and cytokines in lung fibrosis. European Respiratory Review. 2008;17(109):151-6.
25. Loke WS, Herbert C, Thomas PS. Sarcoidosis: Immunopathogenesis and Immunological Markers. Int J Chronic Dis. 2013;2013:928601.
26. Shigehara K, Shijubo N, Ohmichi M, Takahashi R, Kon S, Okamura H, et al. IL-12 and IL-18 are increased and stimulate IFN-gamma production in sarcoid lungs. J Immunol. 2001;166(1):642-9.
27. Kimura T, Ishii Y, Yoh K, Morishima Y, Iizuka T, Kiwamoto T, et al. Overexpression of the transcription factor GATA-3 enhances the development of pulmonary fibrosis. Am J Pathol. 2006;169(1):96-104.
28. Chen Y, Chen J, Dong J, Liu W. Antifibrotic effect of interferon gamma in silicosis model of rat. Toxicol Lett. 2005;155(3):353-60.
29. McLeod JJ, Baker B, Ryan JJ. Mast cell production and response to IL-4 and IL-13. Cytokine. 2015;75(1):57-61.
30. Ando M, Miyazaki E, Fukami T, Kumamoto T, Tsuda T. Interleukin-4-producing cells in idiopathic pulmonary fibrosis: an immunohistochemical study. Respirology. 1999;4(4):383-91.
31. Harris WT, Kelly DR, Zhou Y, Wang D, MacEwen M, Hagood JS, et al. Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease. PLoS One. 2013;8(8):e70196.
32. Phan SH. The myofibroblast in pulmonary fibrosis. Chest. 2002;122(6 Suppl):286S-9S.
33. Kikuchi N, Ishii Y, Morishima Y, Yageta Y, Haraguchi N, Itoh K, et al. Nrf2 protects against pulmonary fibrosis by regulating the lung oxidant level and Th1/Th2 balance. Respir Res. 2010;11:31.
34. Keane MP, Belperio JA, Moore TA, Moore BB, Arenberg DA, Smith RE, et al. Neutralization of the CXC chemokine, macrophage inflammatory protein-2, attenuates bleomycin-induced pulmonary fibrosis. J Immunol. 1999;162(9):5511-8.
35. Keane MP, Belperio JA, Arenberg DA, Burdick MD, Xu ZJ, Xue YY, et al. IFN-gamma-inducible protein-10 attenuates bleomycin-induced pulmonary fibrosis via inhibition of angiogenesis. J Immunol. 1999;163(10):5686-92.
36. Strieter RM, Polverini PJ, Kunkel SL, Arenberg DA, Burdick MD, Kasper J, et al. The functional role of the ELR motif in CXC chemokine-mediated angiogenesis. J Biol Chem. 1995;270(45):27348-57.
37. Keane MP, Arenberg DA, Lynch JP, 3rd, Whyte RI, Iannettoni MD, Burdick MD, et al. The CXC chemokines, IL-8 and IP-10, regulate angiogenic activity in idiopathic pulmonary fibrosis. J Immunol. 1997;159(3):1437-43.
38. Burdick MD, Murray LA, Keane MP, Xue YY, Zisman DA, Belperio JA, et al. CXCL11 attenuates bleomycin-induced pulmonary fibrosis via inhibition of vascular remodeling. Am J Respir Crit Care Med. 2005;171(3):261-8.
39. Antoniou KM, Tzouvelekis A, Alexandrakis MG, Sfiridaki K, Tsiligianni I, Rachiotis G, et al. Different angiogenic activity in pulmonary sarcoidosis and idiopathic pulmonary fibrosis. Chest. 2006;130(4):982-8.
40. Cassetta L, Cassol E, Poli G. Macrophage polarization in health and disease. ScientificWorldJournal. 2011;11:2391-402.
41. Standiford TJ. Macrophage Polarization in Sarcoidosis: An Unexpected Accomplice? Am J Respir Cell Mol Biol. 2019;60(1):9-10.
42. Yao Y, Xu XH, Jin L. Macrophage Polarization in Physiological and Pathological Pregnancy. Front Immunol. 2019;10:792.
43. Prasse A, Pechkovsky DV, Toews GB, Jungraithmayr W, Kollert F, Goldmann T, et al. A vicious circle of alveolar macrophages and fibroblasts perpetuates pulmonary fibrosis via CCL18. Am J Respir Crit Care Med. 2006;173(7):781-92.
44. Sverrild A, Backer V, Kyvik KO, Kaprio J, Milman N, Svendsen CB, et al. Heredity in sarcoidosis: a registry-based twin study. Thorax. 2008;63(10):894-6.
45. Sato H, Williams HR, Spagnolo P, Abdallah A, Ahmad T, Orchard TR, et al. CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis. Eur Respir J. 2010;35(2):324-30.
46. Judson MA. The Clinical Features of Sarcoidosis: A Comprehensive Review. Clin Rev Allergy Immunol. 2015;49(1):63-78.
47. Baughman RP, Shipley RT, Loudon RG, Lower EE. Crackles in interstitial lung disease. Comparison of sarcoidosis and fibrosing alveolitis. Chest. 1991;100(1):96-101.
48. Kouranos V, Wells A, Walsh S. Why do people die from pulmonary sarcoidosis? Curr Opin Pulm Med. 2018;24(5):527-35.
49. Kouranos V, Ward S, Kokosi MA, Castillo D, Chua F, Judge EP, et al. Mixed Ventilatory Defects in Pulmonary Sarcoidosis: Prevalence and Clinical Features. Chest. 2020;158(5):2007-14.
50. Rissmiller R, James WE. Pulmonary function testing and sarcoidosis: A review. Lung Breath J. 2018;2(2):1-5.
51. Crapo RO, Forster RE, 2nd. Carbon monoxide diffusing capacity. Clin Chest Med. 1989;10(2):187-98.
52. Ramos-Casals M, Retamozo S, Siso-Almirall A, Perez-Alvarez R, Pallares L, Brito-Zeron P. Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis. Expert Rev Clin Immunol. 2019;15(4):391-405.
53. Enyedi A, Csongradi A, Altorjay IT, Beke GL, Varadi C, Enyedi EE, et al. Combined application of angiotensin converting enzyme and chitotriosidase analysis improves the laboratory diagnosis of sarcoidosis. Clin Chim Acta. 2020;500:155-62.
54. Ungprasert P, Carmona EM, Crowson CS, Matteson EL. Diagnostic Utility of Angiotensin-Converting Enzyme in Sarcoidosis: A Population-Based Study. Lung. 2016;194(1):91-5.
55. Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol. 2012;12(3):180-90.
56. Eurelings LEM, Miedema JR, Dalm V, van Daele PLA, van Hagen PM, van Laar JAM, et al. Sensitivity and specificity of serum soluble interleukin-2 receptor for diagnosing sarcoidosis in a population of patients suspected of sarcoidosis. PLoS One. 2019;14(10):e0223897.
57. Schimmelpennink MC, Quanjel M, Vorselaars A, Wiertz I, Veltkamp M, Van Moorsel C, et al. Value of serum soluble interleukin-2 receptor as a diagnostic and predictive biomarker in sarcoidosis. Expert Rev Respir Med. 2020;14(7):749-56.
58. Bennett D, Cameli P, Lanzarone N, Carobene L, Bianchi N, Fui A, et al. Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis. Respir Res. 2020;21(1):6.
59. Morales AT, Cignarella AG, Jabeen IS, Barkin JS, Mirsaeidi M. An update on IgG4-related lung disease. Eur J Intern Med. 2019;66:18-24.
60. Bergantini L, Bianchi F, Cameli P, Mazzei MA, Fui A, Sestini P, et al. Prognostic Biomarkers of Sarcoidosis: A Comparative Study of Serum Chitotriosidase, ACE, Lysozyme, and KL-6. Dis Markers. 2019;2019:8565423.
61. Jee AS, Sahhar J, Youssef P, Bleasel J, Adelstein S, Nguyen M, et al. Review: Serum biomarkers in idiopathic pulmonary fibrosis and systemic sclerosis associated interstitial lung disease - frontiers and horizons. Pharmacol Ther. 2019;202:40-52.
62. M E, J A, Y A. Circulating lung biomarkers in idiopathic lung fibrosis and interstitial lung diseases associated with connective tissue diseases: Where do we stand? Semin Arthritis Rheum. 2020.
63. Tang J, Cai S, Ye C, Dong L. Biomarkers in IgG4-related disease: A systematic review. Semin Arthritis Rheum. 2019.
64. Mirsaeidi M, Banoei MM, Nienow CK, Abassi T, Hakim A, Schraufnagel D, et al. Plasma metabolomic profile in fibrosing pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2016;33(1):29-38.
65. Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999;160(2):736-55.
66. Grenier P, Chevret S, Beigelman C, Brauner MW, Chastang C, Valeyre D. Chronic diffuse infiltrative lung disease: determination of the diagnostic value of clinical data, chest radiography, and CT and Bayesian analysis. Radiology. 1994;191(2):383-90.
67. Culver DA, Baughman RP. It's time to evolve from Scadding: phenotyping sarcoidosis. Eur Respir J. 2018;51(1).
68. Criado E, Sanchez M, Ramirez J, Arguis P, de Caralt TM, Perea RJ, et al. Pulmonary sarcoidosis: typical and atypical manifestations at high-resolution CT with pathologic correlation. Radiographics. 2010;30(6):1567-86.
69. Muller NL, Miller RR. Ground-glass attenuation, nodules, alveolitis, and sarcoid granulomas. Radiology. 1993;189(1):31-2.
70. Baughman RP, Winget DB, Bowen EH, Lower EE. Predicting respiratory failure in sarcoidosis patients. Sarcoidosis Vasc Diffuse Lung Dis. 1997;14(2):154-8.
71. Abehsera M, Valeyre D, Grenier P, Jaillet H, Battesti JP, Brauner MW. Sarcoidosis with pulmonary fibrosis: CT patterns and correlation with pulmonary function. AJR Am J Roentgenol. 2000;174(6):1751-7.
72. Nunes H, Brillet PY, Valeyre D, Brauner MW, Wells AU. Imaging in sarcoidosis. Semin Respir Crit Care Med. 2007;28(1):102-20.
73. Brauner MW, Grenier P, Mompoint D, Lenoir S, de Cremoux H. Pulmonary sarcoidosis: evaluation with high-resolution CT. Radiology. 1989;172(2):467-71.
74. Brauner MW, Lenoir S, Grenier P, Cluzel P, Battesti JP, Valeyre D. Pulmonary sarcoidosis: CT assessment of lesion reversibility. Radiology. 1992;182(2):349-54.
75. Murdoch J, Muller NL. Pulmonary sarcoidosis: changes on follow-up CT examination. AJR Am J Roentgenol. 1992;159(3):473-7.
76. Remy-Jardin M, Giraud F, Remy J, Wattinne L, Wallaert B, Duhamel A. Pulmonary sarcoidosis: role of CT in the evaluation of disease activity and functional impairment and in prognosis assessment. Radiology. 1994;191(3):675-80.
77. Akira M, Kozuka T, Inoue Y, Sakatani M. Long-term follow-up CT scan evaluation in patients with pulmonary sarcoidosis. Chest. 2005;127(1):185-91.
78. Akira M. Radiographic Differentiation of Advanced Fibrocystic Lung Diseases. Ann Am Thorac Soc. 2017;14(3):432-40.
79. Herve A, Brillet P-Y, Bouvry D, Freynet O, Naccache J-M, Kambouchner M, et al. Honeycombing pattern: A particular form of sarcoidosis-related pulmonary fibrosis. European Respiratory Journal. 2011;38(Suppl 55):p3725.
80. Walsh SL, Wells AU, Sverzellati N, Keir GJ, Calandriello L, Antoniou KM, et al. An integrated clinicoradiological staging system for pulmonary sarcoidosis: a case-cohort study. Lancet Respir Med. 2014;2(2):123-30.
81. Akaike G, Itani M, Shah H, Ahuja J, Yilmaz Gunes B, Assaker R, et al. PET/CT in the Diagnosis and Workup of Sarcoidosis: Focus on Atypical Manifestations. Radiographics. 2018;38(5):1536-49.
82. Glaudemans AW, de Vries EF, Galli F, Dierckx RA, Slart RH, Signore A. The use of (18)F-FDG-PET/CT for diagnosis and treatment monitoring of inflammatory and infectious diseases. Clin Dev Immunol. 2013;2013:623036.
83. Kapoor V, McCook BM, Torok FS. An introduction to PET-CT imaging. Radiographics. 2004;24(2):523-43.
84. Mostard RL, van Kroonenburgh MJ, Drent M. The role of the PET scan in the management of sarcoidosis. Curr Opin Pulm Med. 2013;19(5):538-44.
85. Gerke AK. Morbidity and mortality in sarcoidosis. Curr Opin Pulm Med. 2014;20(5):472-8.
86. Mirsaeidi M, Machado RF, Schraufnagel D, Sweiss NJ, Baughman RP. Racial difference in sarcoidosis mortality in the United States. Chest. 2015;147(2):438-49.
87. Swigris JJ, Olson AL, Huie TJ, Fernandez-Perez ER, Solomon J, Sprunger D, et al. Sarcoidosis-related mortality in the United States from 1988 to 2007. Am J Respir Crit Care Med. 2011;183(11):1524-30.
88. Pabst S, Grohe C, Skowasch D. Prevalence of sarcoidosis-associated pulmonary hypertension: cumulative analysis of two PULSAR studies. Eur Respir J. 2020;55(2).
89. Savale L, Huitema M, Shlobin O, Kouranos V, Nathan SD, Nunes H, et al. WASOG statement on the diagnosis and management of sarcoidosis-associated pulmonary hypertension. Eur Respir Rev. 2022;31(163).
90. Diaz-Guzman E, Farver C, Parambil J, Culver DA. Pulmonary hypertension caused by sarcoidosis. Clin Chest Med. 2008;29(3):549-63, x.
91. Nathan SD, Shlobin OA, Barnett SD, Saggar R, Belperio JA, Ross DJ, et al. Right ventricular systolic pressure by echocardiography as a predictor of pulmonary hypertension in idiopathic pulmonary fibrosis. Respir Med. 2008;102(9):1305-10.
92. Huitema MP, Post MC, Grutters JC, Wells AU, Kouranos V, Shlobin OA, et al. Echocardiographic estimate of pulmonary artery pressure in sarcoidosis patients - real world data from a multi-national study. Sarcoidosis Vasc Diffuse Lung Dis. 2022;38(4):e2021032.
93. Baughman RP, Culver DA, Cordova FC, Padilla M, Gibson KF, Lower EE, et al. Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial. Chest. 2014;145(4):810-7.
94. Baughman RP, Judson MA, Lower EE, Highland K, Kwon S, Craft N, et al. Inhaled iloprost for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis. 2009;26(2):110-20.
95. Fisher KA, Serlin DM, Wilson KC, Walter RE, Berman JS, Farber HW. Sarcoidosis-associated pulmonary hypertension: outcome with long-term epoprostenol treatment. Chest. 2006;130(5):1481-8.
96. Mathijssen H, Huitema MP, Bakker ALM, Mager JJ, Snijder RJ, Grutters JC, et al. Safety of macitentan in sarcoidosis-associated pulmonary hypertension: a case-series. Sarcoidosis Vasc Diffuse Lung Dis. 2020;37(1):74-8.
97. Baughman RP, Shlobin OA, Gupta R, Engel PJ, Stewart JI, Lower EE, et al. Riociguat for Sarcoidosis-Associated Pulmonary Hypertension: Results of a 1-Year Double-Blind, Placebo-Controlled Trial. Chest. 2022;161(2):448-57.
98. Denning DW. Sarcoidosis and aspergillosis: a tough combination. Eur Respir J. 2017;49(6).
99. Uzunhan Y, Nunes H, Jeny F, Lacroix M, Brun S, Brillet PY, et al. Chronic pulmonary aspergillosis complicating sarcoidosis. Eur Respir J. 2017;49(6).
100. Li H, Rui Y, Zhou W, Liu L, He B, Shi Y, et al. Role of the Aspergillus-Specific IgG and IgM Test in the Diagnosis and Follow-Up of Chronic Pulmonary Aspergillosis. Front Microbiol. 2019;10:1438.
101. Takeda T, Itano H, Kakehashi R, Fukita S, Saitoh M, Takeda S. Direct transbronchial administration of liposomal amphotericin B into a pulmonary aspergilloma. Respir Med Case Rep. 2014;11:7-11.
102. Wijsenbeek MS, Culver DA. Treatment of Sarcoidosis. Clin Chest Med. 2015;36(4):751-67.
103. Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2011;183(5):573-81.
104. Atzeni F, Talotta R, Salaffi F, Cassinotti A, Varisco V, Battellino M, et al. Immunogenicity and autoimmunity during anti-TNF therapy. Autoimmun Rev. 2013;12(7):703-8.
105. El Jammal T, Jamilloux Y, Gerfaud-Valentin M, Valeyre D, Seve P. Refractory Sarcoidosis: A Review. Ther Clin Risk Manag. 2020;16:323-45.
106. Hade EM, Smith RM, Culver DA, Crouser ED. Design, rationale, and baseline characteristics of a pilot randomized clinical trial of nicotine treatment for pulmonary sarcoidosis. Contemp Clin Trials Commun. 2020;20:100669.
107. Valeyre D, Soler P, Clerici C, Pre J, Battesti JP, Georges R, et al. Smoking and pulmonary sarcoidosis: effect of cigarette smoking on prevalence, clinical manifestations, alveolitis, and evolution of the disease. Thorax. 1988;43(7):516-24.
108. Villa G, Amass T, Giua R, Lanini I, Chelazzi C, Tofani L, et al. Validation of END-of-life ScorING-system to identify the dying patient: a prospective analysis. BMC Anesthesiol. 2020;20(1):63.
109. Churg A, Muller NL, Wright JL. Respiratory bronchiolitis/interstitial lung disease: fibrosis, pulmonary function, and evolving concepts. Arch Pathol Lab Med. 2010;134(1):27-32.
110. Ebrahimpour A, Shrestha S, Bonnen MD, Eissa NT, Raghu G, Ghebre YT. Nicotine Modulates Growth Factors and MicroRNA to Promote Inflammatory and Fibrotic Processes. J Pharmacol Exp Ther. 2019;368(2):169-78.
111. Collins BF, Raghu G. Antifibrotic therapy for fibrotic lung disease beyond idiopathic pulmonary fibrosis. Eur Respir Rev. 2019;28(153).
112. Margaritopoulos GA, Trachalaki A, Wells AU, Vasarmidi E, Bibaki E, Papastratigakis G, et al. Pirfenidone improves survival in IPF: results from a real-life study. BMC Pulm Med. 2018;18(1):177.
113. Noble PW, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, et al. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. Eur Respir J. 2016;47(1):243-53.
114. Gupta R, Baughman R, Judson M, Reeves R, Lower E, Wells A. Pirfenidone for Fibrotic Sarcoidosis: Physiology of Study Patients. A38 GRANULOMATOUS LUNG DISEASE: American Thoracic Society; 2020. p. A1554-A.
115. Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. 2019;381(18):1718-27.
116. Cottin V, Richeldi L, Rosas I, Otaola M, Song JW, Tomassetti S, et al. Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases. Respir Res. 2021;22(1):84.
117. Baughman RP, Judson MA, Culver DA, Birring SS, Parambil J, Zeigler J, et al. Roflumilast (Daliresp(R)) to reduce acute pulmonary events in fibrotic sarcoidosis: a multi-center, double blind, placebo controlled, randomized clinical trial. Sarcoidosis Vasc Diffuse Lung Dis. 2021;38(3):e2021035.
118. Martinez FJ, Calverley PM, Goehring UM, Brose M, Fabbri LM, Rabe KF. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet. 2015;385(9971):857-66.
119. Shlobin OA, Nathan SD. Management of end-stage sarcoidosis: pulmonary hypertension and lung transplantation. Eur Respir J. 2012;39(6):1520-33.
120. [Available from: https://www.cdc.gov/nchs/icd/icd9.htm.
121. Arcasoy SM, Christie JD, Pochettino A, Rosengard BR, Blumenthal NP, Bavaria JE, et al. Characteristics and outcomes of patients with sarcoidosis listed for lung transplantation. Chest. 2001;120(3):873-80.
122. Orens JB, Estenne M, Arcasoy S, Conte JV, Corris P, Egan JJ, et al. International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2006;25(7):745-55.
123. Shah L. Lung transplantation in sarcoidosis. Semin Respir Crit Care Med. 2007;28(1):134-40.
124. Judson MA. Lung transplantation for pulmonary sarcoidosis. Eur Respir J. 1998;11(3):738-44.
125. Taimeh Z, Hertz MI, Shumway S, Pritzker M. Lung transplantation for pulmonary sarcoidosis. Twenty-five years of experience in the USA. Thorax. 2016;71(4):378-9.
126. Kruit A, Grutters JC, Ruven HJ, van Moorsel CH, Weiskirchen R, Mengsteab S, et al. Transforming growth factor-beta gene polymorphisms in sarcoidosis patients with and without fibrosis. Chest. 2006;129(6):1584-91.
127. Pabst S, Franken T, Schonau J, Stier S, Nickenig G, Meyer R, et al. Transforming growth factor-{beta} gene polymorphisms in different phenotypes of sarcoidosis. Eur Respir J. 2011;38(1):169-75.
128. Voorter CE, Drent M, van den Berg-Loonen EM. Severe pulmonary sarcoidosis is strongly associated with the haplotype HLA-DQB1*0602-DRB1*150101. Hum Immunol. 2005;66(7):826-35.
129. Typiak M, Rebala K, Dudziak M, Slominski JM, Dubaniewicz A. Polymorphism of FCGR2A, FCGR2C, and FCGR3B Genes in the Pathogenesis of Sarcoidosis. Adv Exp Med Biol. 2016;905:57-68.
130. Tong X, Ma Y, Niu X, Yan Z, Liu S, Peng B, et al. The BTNL2 G16071A gene polymorphism increases granulomatous disease susceptibility: A meta-analysis including FPRP test of 8710 participants. Medicine (Baltimore). 2016;95(30):e4325.
131. Mirsaeidi M, Vu A, Zhang W, Arbieva Z, Zhang C, Abbasi T, et al. Annexin A11 is associated with pulmonary fibrosis in African American patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2016;33(4):418-22.
132. Mirsaeidi M, Gidfar S, Vu A, Schraufnagel D. Annexins family: insights into their functions and potential role in pathogenesis of sarcoidosis. J Transl Med. 2016;14:89.

Most read articles by the same author(s)