Diagnosis and treatment of fibrotic hypersensitivity pneumonia: Where we stand and where we need to go

American Journal of Respiratory and Critical Care Medicine

Volumn 196, Issue 6, 2017, Pages 690-699

  Salisbury, Margaret L ^a   Myers, Jeffrey L ^a   Belloli, Elizabeth A ^a   Kazerooni, Ella A ^a   Martinez, Fernando J ^b   Flaherty, Kevin R ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; CORTICOSTEROID; CYTOTOXIC AGENT; STEROID; IMMUNOSUPPRESSIVE AGENT;

ALLERGIC PNEUMONITIS; CLINICAL FEATURE; DISEASE CLASSIFICATION; HIGH RESOLUTION COMPUTER TOMOGRAPHY; HISTOPATHOLOGY; HUMAN; LUNG FIBROSIS; PRIORITY JOURNAL; RADIODIAGNOSIS; REVIEW; ACUTE DISEASE; ALGORITHM; BIOPSY; BRONCHOSCOPY; CHRONIC DISEASE; CLASSIFICATION; LUNG TRANSPLANTATION; PATHOLOGY; RESPIRATORY CARE; X-RAY COMPUTED TOMOGRAPHY;

ACUTE DISEASE; ALGORITHMS; ALVEOLITIS, EXTRINSIC ALLERGIC; BIOPSY; BRONCHOSCOPY; CHRONIC DISEASE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LUNG TRANSPLANTATION; PULMONARY FIBROSIS; RESPIRATORY THERAPY; TOMOGRAPHY, X-RAY COMPUTED;

EID: 85029671011     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201608-1675PP     Document Type: Review

References (92)

1. Bang KM, Weissman DN, Pinheiro GA, Antao VC, Wood JM, Syamlal G. Twenty-three years of hypersensitivity pneumonitis mortality surveillance in the United States. Am J Ind Med 2006;49:997–1004.
2. Solaymani-Dodaran M, West J, Smith C, Hubbard R. Extrinsic allergic alveolitis: incidence and mortality in the general population. QJM 2007;100:233–237.
3. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, et al.; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. 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.
4. Kern RM, Singer JP, Koth L, Mooney J, Golden J, Hays S, Greenland J, Wolters P, Ghio E, Jones KD, et al. Lung transplantation for hypersensitivity pneumonitis. Chest 2015;147:1558–1565.
5. Morell F, Villar A, Montero MA, Muñoz X, Colby TV, Pipvath S, Cruz MJ, Raghu G. Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study. Lancet Respir Med 2013;1:685–694.
6. Swensen SJ, Aughenbaugh GL, Myers JL. Diffuse lung disease: diagnostic accuracy of CT in patients undergoing surgical biopsy of the lung. Radiology 1997;205:229–234.
7. Thomeer MJ, Costabe U, Rizzato G, Poletti V, Demedts M. Comparison of registries of interstitial lung diseases in three European countries. Eur Respir J Suppl 2001;32:114s–118s.
8. King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, et al.; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 2014;370:2083–2092.
9. Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, et al.; INPULSIS Trial Investigators. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014;370:2071–2082.
10. Lacasse Y, Selman M, Costabel U, Dalphin JC, Morell F, Erkinjuntti-Pekkanen R, Mueller NL, Colby TV, Schuyler M, Jomphe V, et al.; HP Study Group. Classification of hypersensitivity pneumonitis: a hypothesis. Int Arch Allergy Immunol 2009;149:161–166.
11. Zacharisen MC, Schlueter DP, Kurup VP, Fink JN. The long-term outcome in acute, subacute, and chronic forms of pigeon breeder’s disease hypersensitivity pneumonitis. Ann Allergy Asthma Immunol 2002;88:175–182.
12. Ohtani Y, Saiki S, Sumi Y, Inase N, Miyake S, Costabel U, Yoshizawa Y. Clinical features of recurrent and insidious chronic bird fancier’s lung. Ann Allergy Asthma Immunol 2003;90:604–610.
13. Tateishi T, Ohtani Y, Takemura T, Akashi T, Miyazaki Y, Inase N, Yoshizawa Y. Serial high-resolution computed tomography findings of acute and chronic hypersensitivity pneumonitis induced by avian antigen. J Comput Assist Tomogr 2011;35: 272–279.
14. Churg A, Sin DD, Everett D, Brown K, Cool C. Pathologic patterns and survival in chronic hypersensitivity pneumonitis. Am J Surg Pathol 2009;33:1765–1770.
15. Ohtani Y, Saiki S, Kitaichi M, Usui Y, Inase N, Costabel U, Yoshizawa Y. Chronic bird fancier’s lung: histopathological and clinical correlation: an application of the 2002 ATS/ERS consensus classification of the idiopathic interstitial pneumonias. Thorax 2005;60:665–671.
16. Pérez-Padilla R, Salas J, Chapela R, Sánchez M, Carrillo G, Pérez R, Sansores R, Gaxiola M, Selman M. Mortality in Mexican patients with chronic pigeon breeder’s lung compared with those with usual interstitial pneumonia. Am Rev Respir Dis 1993;148:49–53.
17. Sahin H, Brown KK, Curran-Everett D, Hale V, Cool CD, Vourlekis JS, Lynch DA. Chronic hypersensitivity pneumonitis: CT features comparison with pathologic evidence of fibrosis and survival. Radiology 2007;244:591–598.
18. Vourlekis JS, Schwarz MI, Cherniack RM, Curran-Everett D, Cool CD, Tuder RM, King TE Jr, Brown KK. The effect of pulmonary fibrosis on survival in patients with hypersensitivity pneumonitis. Am J Med 2004;116:662–668.
19. Chiba S, Tsuchiya K, Akashi T, Ishizuka M, Okamoto T, Furusawa H, Tateishi T, Kishino M, Miyazaki Y, Tateishi U, et al. Chronic hypersensitivity pneumonitis with a usual interstitial pneumonia-like pattern: correlation between histopathologic and clinical findings. Chest 2016;149:1473–1481.
20. Hanak V, Golbin JM, Hartman TE, Ryu JH. High-resolution CT findings of parenchymal fibrosis correlate with prognosis in hypersensitivity pneumonitis. Chest 2008;134:133–138.
21. Mooney JJ, Elicker BM, Urbania TH, Agarwal MR, Ryerson CJ, Nguyen ML, Woodruff PG, Jones KD, Collard HR, King TE, et al. Radiographic fibrosis score predicts survival in hypersensitivity pneumonitis. Chest 2013;144:586–592.
22. Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, et al.; ATS/ERS Committee on Idiopathic Interstitial Pneumonias. 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;188:733–748.
23. Flaherty KR, Andrei AC, King TE Jr, Raghu G, Colby TV, Wells A, Bassily N, Brown K, du Bois R, Flint A, et al. Idiopathic interstitial pneumonia: do community and academic physicians agree on diagnosis? Am J Respir Crit Care Med 2007;175: 1054–1060.
24. Flaherty KR, King TE Jr, Raghu G, Lynch JP III, Colby TV, Travis WD, Gross BH, Kazerooni EA, Toews GB, Long Q, et al. Idiopathic interstitial pneumonia: what is the effect of a multidisciplinary approach to diagnosis? Am J Respir Crit Care Med 2004;170:904–910.
25. Walsh SL, Wells AU, Desai SR, Poletti V, Piciucchi S, Dubini A, Nunes H, Valeyre D, Brillet PY, Kambouchner M, et al. Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study. Lancet Respir Med 2016;4:557–565.
26. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology 2008;246:697–722.
27. Kazerooni EA, Martinez FJ, Flint A, Jamadar DA, Gross BH, Spizarny DL, Cascade PN, Whyte RI, Lynch JP III, Toews G. Thin-section CT obtained at 10-mm increments versus limited three-level thin-section CT for idiopathic pulmonary fibrosis: correlation with pathologic scoring. AJR Am J Roentgenol 1997; 169:977–983.
28. Johannson KA, Elicker BM, Vittinghoff E, Assayag D, de Boer K, Golden JA, Jones KD, King TE Jr, Koth LL, Lee JS, et al. A diagnostic model for chronic hypersensitivity pneumonitis. Thorax 2016;71: 951–954.
29. Lynch DA, Newell JD, Logan PM, King TE Jr, Müller NL. Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis? AJR Am J Roentgenol 1995;165:807–811.
30. Silva CI, Müller NL, Lynch DA, Curran-Everett D, Brown KK, Lee KS, Chung MP, Churg A. Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology 2008;246: 288–297.
31. Arakawa H, Webb WR, McCowin M, Katsou G, Lee KN, Seitz RF. Inhomogeneous lung attenuation at thin-section CT: diagnostic value of expiratory scans. Radiology 1998;206:89–94.
32. Chung MH, Edinburgh KJ, Webb EM, McCowin M, Webb WR. Mixed infiltrative and obstructive disease on high-resolution CT: differential diagnosis and functional correlates in a consecutive series. J Thorac Imaging 2001;16:69–75.
33. Shaw M, Collins BF, Ho LA, Raghu G. Rheumatoid arthritis–associated lung disease. Eur Respir Rev 2015;24:1–16.
34. Shi JH, Liu HR, Xu WB, Feng RE, Zhang ZH, Tian XL, Zhu YJ. Pulmonary manifestations of Sjögren’s syndrome. Respiration 2009; 78:377–386.
35. Fischer A, Swigris JJ, Groshong SD, Cool CD, Sahin H, Lynch DA, Curran-Everett D, Gillis JZ, Meehan RT, Brown KK. Clinically significant interstitial lung disease in limited scleroderma: histopathology, clinical features, and survival. Chest 2008;134: 601–605.
36. Hodnett PA, Naidich DP. Fibrosing interstitial lung disease: a practical high-resolution computed tomography-based approach to diagnosis and management and a review of the literature. Am J Respir Crit Care Med 2013;188:141–149.
37. Meyer KC, Raghu G, Baughman RP, Brown KK, Costabel U, du Bois RM, Drent M, Haslam PL, Kim DS, Nagai S, et al.; American Thoracic Society Committee on BAL in Interstitial Lung Disease. An official American Thoracic Society clinical practice guideline: the clinical utility of bronchoalveolar lavage cellular analysis in interstitial lung disease. Am J Respir Crit Care Med 2012;185:1004–1014.
38. Barrera L, Mendoza F, Zuñiga J, Estrada A, Zamora AC, Melendro EI, Ramírez R, Pardo A, Selman M. Functional diversity of T-cell subpopulations in subacute and chronic hypersensitivity pneumonitis. Am J Respir Crit Care Med 2008;177:44–55.
39. Morell F, Roger A, Reyes L, Cruz MJ, Murio C, Muñoz X. Bird fancier’s lung: a series of 86 patients. Medicine (Baltimore) 2008; 87:110–130.
40. Lacasse Y, Selman M, Costabel U, Dalphin JC, Ando M, Morell F, Erkinjuntti-Pekkanen R, Muller N, Colby TV, Schuyler M, et al.; HP Study Group. Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med 2003;168:952–958.
41. Ohshimo S, Bonella F, Cui A, Beume M, Kohno N, Guzman J, Costabel U. Significance of bronchoalveolar lavage for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009;179: 1043–1047.
42. Murayama J, Yoshizawa Y, Ohtsuka M, Hasegawa S. Lung fibrosis in hypersensitivity pneumonitis: association with CD41 but not CD81 cell dominant alveolitis and insidious onset. Chest 1993; 104:38–43.
43. Lacasse Y, Fraser RS, Fournier M, Cormier Y. Diagnostic accuracy of transbronchial biopsy in acute farmer’s lung disease. Chest 1997; 112:1459–1465.
44. Sheth JS, Belperio JA, Fishbein MC, Kazerooni EA, Lagstein A, Murray S, Myers JL, Simon RH, Sisson TH, Sundaram B, et al. Utility of transbronchial versus surgical lung biopsy in the diagnosis of suspected fibrotic interstitial lung disease. Chest 2017; 151:389–399.
45. Johannson KA, Marcoux VS, Ronksley PE, Ryerson CJ. Diagnostic yield and complications of transbronchial lung cryobiopsy for interstitial lung disease: a systematic review and metaanalysis. Ann Am Thorac Soc 2016;13:1828–1838.
46. Tomassetti S, Wells AU, Costabel U, Cavazza A, Colby TV, Rossi G, Sverzellati N, Carloni A, Carretta E, Buccioli M, et al. Bronchoscopic lung cryobiopsy increases diagnostic confidence in the multidisciplinary diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2016;193:745–752.
47. Coleman A, Colby TV. Histologic diagnosis of extrinsic allergic alveolitis. Am J Surg Pathol 1988;12:514–518.
48. Reyes CN, Wenzel FJ, Lawton BR, Emanuel DA. The pulmonary pathology of farmer’s lung disease. Chest 1982;81:142–146.
49. Churg A, Muller NL, Flint J, Wright JL. Chronic hypersensitivity pneumonitis. Am J Surg Pathol 2006;30:201–208.
50. Ohtani Y, Kojima K, Sumi Y, Sawada M, Inase N, Miyake S, Yoshizawa Y. Inhalation provocation tests in chronic bird fancier’s lung. Chest 2000; 118:1382–1389.
51. Akashi T, Takemura T, Ando N, Eishi Y, Kitagawa M, Takizawa T, Koike M, Ohtani Y, Miyazaki Y, Inase N, et al. Histopathologic analysis of sixteen autopsy cases of chronic hypersensitivity pneumonitis and comparison with idiopathic pulmonary fibrosis/usual interstitial pneumonia. Am J Clin Pathol 2009;131:405–415.
52. Vourlekis JS, Schwarz MI, Cool CD, Tuder RM, King TE, Brown KK. Nonspecific interstitial pneumonitis as the sole histologic expression of hypersensitivity pneumonitis. Am J Med 2002; 112:490–493.
53. Lima MS, Coletta EN, Ferreira RG, Jasinowodolinski D, Arakaki JS, Rodrigues SC, Rocha NA, Pereira CA. Subacute and chronic hypersensitivity pneumonitis: histopathological patterns and survival. Respir Med 2009;103:508–515.
54. Pérez-Padilla R, Gaxiola M, Salas J, Mejía M, Ramos C, Selman M. Bronchiolitis in chronic pigeon breeder’s disease: morphologic evidence of a spectrum of small airway lesions in hypersensitivity pneumonitis induced by avian antigens. Chest 1996;110:371–377.
55. Trahan S, Hanak V, Ryu JH, Myers JL. Role of surgical lung biopsy in separating chronic hypersensitivity pneumonia from usual interstitial pneumonia/idiopathic pulmonary fibrosis: analysis of 31 biopsies from 15 patients. Chest 2008;134:126–132.
56. Ramírez-Venegas A, Sansores RH, Pérez-Padilla R, Carrillo G, Selman M. Utility of a provocation test for diagnosis of chronic pigeon breeder’s disease. Am J Respir Crit Care Med 1998;158: 862–869.
57. Ishizuka M, Miyazaki Y, Tateishi T, Tsutsui T, Tsuchiya K, Inase N. Validation of inhalation provocation test in chronic bird-related hypersensitivity pneumonitis and new prediction score. Ann Am Thorac Soc 2015;12:167–173.
58. Muñoz X, Sánchez-Ortiz M, Torres F, Villar A, Morell F, Cruz MJ. Diagnostic yield of specific inhalation challenge in hypersensitivity pneumonitis. Eur Respir J 2014;44:1658–1665.
59. Yoshizawa Y, Miyake S, Sumi Y, Hisauchi K, Sato T, Kurup VP. A follow-up study of pulmonary function tests, bronchoalveolar lavage cells, and humoral and cellular immunity in bird fancier’s lung. J Allergy Clin Immunol 1995;96:122–129.
60. Fernández Pérez ER, Swigris JJ, Forssén AV, Tourin O, Solomon JJ, Huie TJ, Olson AL, Brown KK. Identifying an inciting antigen is associated with improved survival in patients with chronic hypersensitivity pneumonitis. Chest 2013;144:1644–1651.
61. Millerick-May ML, Mulks MH, Gerlach J, Flaherty KR, Schmidt SL, Martinez FJ, LeVeque RM, Rosenman KD. Hypersensitivity pneumonitis and antigen identification: an alternate approach. Respir Med 2016;112:97–105.
62. Mannina A, Chung JH, Swigris JJ, Solomon JJ, Huie TJ, Yunt ZX, Truong TQ, Brown KK, Achcar RD, Olson AL, et al. Clinical predictors of a diagnosis of common variable immunodeficiency-related granulomatous-lymphocytic interstitial lung disease. Ann Am Thorac Soc 2016;13:1042–1049.
63. Ryerson CJ, Urbania TH, Richeldi L, Mooney JJ, Lee JS, Jones KD, Elicker BM, Koth LL, King TE Jr, Wolters PJ, et al. Prevalence and prognosis of unclassifiable interstitial lung disease. Eur Respir J 2013;42:750–757.
64. Ahluwalia N, Shea BS, Tager AM. New therapeutic targets in idiopathic pulmonary fibrosis: aiming to rein in runaway wound-healing responses. Am J Respir Crit Care Med 2014;190:867–878.
65. Selman M, Pardo A, King TE Jr. Hypersensitivity pneumonitis: insights in diagnosis and pathobiology. Am J Respir Crit Care Med 2012;186: 314–324.
66. Selman M, Pardo A, Barrera L, Estrada A, Watson SR, Wilson K, Aziz N, Kaminski N, Zlotnik A. Gene expression profiles distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis. Am J Respir Crit Care Med 2006;173:188–198.
67. Camarena A, Juárez A, Mejía M, Estrada A, Carrillo G, Falfán R, Zuñiga J, Navarro C, Granados J, Selman M. Major histocompatibility complex and tumor necrosis factor-a polymorphisms in pigeon breeder’s disease. Am J Respir Crit Care Med 2001;163:1528–1533.
68. Simonian PL, Roark CL, Diaz del Valle F, Palmer BE, Douglas IS, Ikuta K, Born WK, O’Brien RL, Fontenot AP. Regulatory role of gd T cells in the recruitment of CD41 and CD81 T cells to lung and subsequent pulmonary fibrosis. J Immunol 2006;177:4436–4443.
69. Simonian PL, Roark CL, Wehrmann F, Lanham AM, Born WK, O’Brien RL, Fontenot AP. IL-17A–expressing T cells are essential for bacterial clearance in a murine model of hypersensitivity pneumonitis. J Immunol 2009;182:6540–6549.
70. Hasan SA, Eksteen B, Reid D, Paine HV, Alansary A, Johannson K, Gwozd C, Goring KA, Vo T, Proud D, et al. Role of IL-17A and neutrophils in fibrosis in experimental hypersensitivity pneumonitis. J Allergy Clin Immunol 2013;131:1663–1673.
71. Ishizuka M, Miyazaki Y, Masuo M, Suhara K, Tateishi T, Yasui M, Inase N. Interleukin-17A and neutrophils in a murine model of bird-related hypersensitivity pneumonitis. PLoS One 2015;10: e0137978.
72. Joshi AD, Fong DJ, Oak SR, Trujillo G, Flaherty KR, Martinez FJ, Hogaboam CM. Interleukin-17–mediated immunopathogenesis in experimental hypersensitivity pneumonitis. Am J Respir Crit Care Med 2009;179:705–716.
73. Pardo A, Barrios R, Gaxiola M, Segura-Valdez L, Carrillo G, Estrada A, Mejía M, Selman M. Increase of lung neutrophils in hypersensitivity pneumonitis is associated with lung fibrosis. Am J Respir Crit Care Med 2000;161:1698–1704.
74. Bartram U, Speer CP. The role of transforming growth factor b in lung development and disease. Chest 2004;125:754–765.
75. García de Alba C, Buendia-Roldán I, Salgado A, Becerril C, Ramírez R, González Y, Checa M, Navarro C, Ruiz V, Pardo A, et al. Fibrocytes contribute to inflammation and fibrosis in chronic hypersensitivity pneumonitis through paracrine effects. Am J Respir Crit Care Med 2015;191:427–436.
76. Mercer PF, Williams AE, Scotton CJ, José RJ, Sulikowski M, Moffatt JD, Murray LA, Chambers RC. Proteinase-activated receptor-1, CCL2, and CCL7 regulate acute neutrophilic lung inflammation. Am J Respir Cell Mol Biol 2014;50:144–157.
77. de Gracia J, Morell F, Bofill JM, Curull V, Orriols R. Time of exposure as a prognostic factor in avian hypersensitivity pneumonitis. Respir Med 1989;83:139–143.
78. Tsutsui T, Miyazaki Y, Kuramochi J, Uchida K, Eishi Y, Inase N. The amount of avian antigen in household dust predicts the prognosis of chronic bird-related hypersensitivity pneumonitis. Ann Am Thorac Soc 2015;12:1013–1021.
79. Craig TJ, Hershey J, Engler RJ, Davis W, Carpenter GB, Salata K. Bird antigen persistence in the home environment after removal of the bird. Ann Allergy 1992;69:510–512.
80. Kokkarinen JI, Tukiainen HO, Terho EO. Effect of corticosteroid treatment on the recovery of pulmonary function in farmer’s lung. Am Rev Respir Dis 1992;145:3–5.
81. Okamoto T, Miyazaki Y, Ogura T, Chida K, Kohno N, Kohno S, Taniguchi H, Akagawa S, Mochizuki Y, Yamauchi K, et al. Nationwide epidemiological survey of chronic hypersensitivity pneumonitis in Japan. Respir Investig 2013;51:191–199.
82. Morisset J, Johannson KA, Vittinghoff E, Aravena C, Elicker BM, Jones KD, Fell CD, Manganas H, Dubé BP, Wolters PJ, et al. Use of mycophenolate mofetil or azathioprine for the management of chronic hypersensitivity pneumonitis. Chest 2017; 151:619–625.
83. Keir GJ, Maher TM, Ming D, Abdullah R, de Lauretis A, Wickremasinghe M, Nicholson AG, Hansell DM, Wells AU, Renzoni EA. Rituximab in severe, treatment-refractory interstitial lung disease. Respirology 2014;19:353–359.
84. Raghu G, Anstrom KJ, King TE Jr, Lasky JA, Martinez FJ; Idiopathic Pulmonary Fibrosis Clinical Research Network. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med 2012;366:1968–1977.
85. Oku H, Shimizu T, Kawabata T, Nagira M, Hikita I, Ueyama A, Matsushima S, Torii M, Arimura A. Antifibrotic action of pirfenidone and prednisolone: different effects on pulmonary cytokines and growth factors in bleomycin-induced murine pulmonary fibrosis. Eur J Pharmacol 2008;590:400–408.
86. Miyazaki Y, Tateishi T, Akashi T, Ohtani Y, Inase N, Yoshizawa Y. Clinical predictors and histologic appearance of acute exacerbations in chronic hypersensitivity pneumonitis. Chest 2008;134:1265–1270.
87. Olson AL, Huie TJ, Groshong SD, Cosgrove GP, Janssen WJ, Schwarz MI, Brown KK, Frankel SK. Acute exacerbations of fibrotic hypersensitivity pneumonitis: a case series. Chest 2008;134:844–850.
88. Knippenberg S, Ueberberg B, Maus R, Bohling J, Ding N, Tort Tarres M, Hoymann HG, Jonigk D, Izykowski N, Paton JC, et al. Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin. Thorax 2015;70:636–646.
89. Shulgina L, Cahn AP, Chilvers ER, Parfrey H, Clark AB, Wilson EC, Twentyman OP, Davison AG, Curtin JJ, Crawford MB, et al. Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial. Thorax 2013;68:155–162.
90. Lubin M, Chen H, Elicker B, Jones KD, Collard HR, Lee JS. A comparison of health-related quality of life in idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. Chest 2014;145: 1333–1338.
91. Koschel DS, Cardoso C, Wiedemann B, Höffken G, Halank M. Pulmonary hypertension in chronic hypersensitivity pneumonitis. Lung 2012;190:295–302.
92. Adegunsoye A, Oldham JM, Demchuk C, Montner S, Vij R, Strek ME. Predictors of survival in coexistent hypersensitivity pneumonitis with autoimmune features. Respir Med 2016;114: 53–60.