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01-06-2020 | Hypersensitivity Pneumonitis | STATE OF THE ART REVIEW

Fibrotic Hypersensitivity Pneumonitis: Diagnosis and Management

Authors: Francesco Varone, Bruno Iovene, Giacomo Sgalla, Mariarosaria Calvello, Angelo Calabrese, Anna Rita Larici, Luca Richeldi

Published in: Lung | Issue 3/2020

Abstract

Fibrotic hypersensitivity pneumonitis is a complex interstitial lung disease that is not entirely understood. In its chronic and fibrotic form, hypersensitivity pneumonitis is one of the main mimickers of idiopathic pulmonary fibrosis (IPF). Distinguishing between these two conditions is challenging but is of particular clinical relevance. Two approved therapies are available for IPF, and a considerable number of clinical trials are now exploring newer pharmacological options. This impressive research effort is a consequence of new pathogenetic understanding, updated diagnostic criteria and a long history of pharmacological trials. Conversely, current knowledge gaps on pathogenesis of chronic hypersensitivity pneumonitis, coupled with lack of validated diagnostic criteria, make the management of this disease an unsolved clinical challenge. This also reflects the paucity of therapeutic clinical trials in this field. In this review, we describe the current evidence and the possible future options to approach this complex disease.

Riario Sforza GG, Marinou A (2017) Hypersensitivity pneumonitis: a complex lung disease. Clin Mol Allergy 15:6. https://doi.org/10.1186/s12948-017-0062-7 CrossRefPubMedPubMedCentral

Thomeer MJ, Costabe U, Rizzato G et al (2001) Comparison of registries of interstitial lung diseases in three European countries. Eur Respir J Suppl 32:114s–118sPubMed

Hyldgaard C, Hilberg O, Muller A, Bendstrup E (2014) A cohort study of interstitial lung diseases in central Denmark. Respir Med 108:793–799. https://doi.org/10.1016/j.rmed.2013.09.002 CrossRefPubMed

Costabel U, Bonella F, Guzman J (2012) Chronic hypersensitivity pneumonitis. Clin Chest Med 33:151–163. https://doi.org/10.1016/j.ccm.2011.12.004 CrossRefPubMed

Lacasse Y, Selman M, Costabel U et al (2009) Classification of hypersensitivity pneumonitis: a hypothesis. Int Arch Allergy Immunol 149:161–166. https://doi.org/10.1159/000189200 CrossRefPubMed

Cottin V, Hirani NA, Hotchkin DL et al (2018) Presentation, diagnosis and clinical course of the spectrum of progressive-fibrosing interstitial lung diseases. Eur Respir Rev 27:180076. https://doi.org/10.1183/16000617.0076-2018 CrossRefPubMed

Perez ERF, Swigris JJ, Forssen AV et al (2013) Identifying an inciting antigen is associated with improved survival in patients with chronic hypersensitivity pneumonitis. Chest 144:1644–1651. https://doi.org/10.1378/chest.12-2685 CrossRef

Pepys J, Riddell RW, Citron KM, Clayton YM (1962) Precipitins against extracts of hay and moulds in the serum of patients with farmer’s lung, aspergillosis, asthma, and sarcoidosis. Thorax 17:366–374. https://doi.org/10.1136/thx.17.4.366 CrossRefPubMedCentral

Vasakova M, Selman M, Morell F et al (2019) Hypersensitivity pneumonitis: current concepts of pathogenesis and potential targets for treatment. Am J Respir Crit Care Med 200:301–308. https://doi.org/10.1164/rccm.201903-0541PP CrossRefPubMed

10.

Okamoto T, Miyazaki Y, Tomita M et al (2013) A familial history of pulmonary fibrosis in patients with chronic hypersensitivity pneumonitis. Respiration 85:384–390. https://doi.org/10.1159/000338123 CrossRefPubMed

11.

Barrera L, Mendoza F, Zuñiga J et al (2008) Functional diversity of T-cell subpopulations in subacute and chronic hypersensitivity pneumonitis. Am J Respir Crit Care Med 177:44–55. https://doi.org/10.1164/rccm.200701-093OC CrossRefPubMed

12.

Garcia de Alba C, Buendia-Roldan I, Salgado A et al (2015) Fibrocytes contribute to inflammation and fibrosis in chronic hypersensitivity pneumonitis through paracrine effects. Am J Respir Crit Care Med 191:427–436. https://doi.org/10.1164/rccm.201407-1334OC CrossRefPubMed

13.

Baur X, Richter G, Pethran A et al (1992) Increased prevalence of IgG-lnduced sensitization and hypersensitivity pneumonitis (humidifier lung) in nonsmokers exposed to aerosols of a contaminated air conditioner. Respiration 59:211–214. https://doi.org/10.1159/000196060 CrossRefPubMed

14.

Blanchet M-R, Israël-Assayag E, Cormier Y (2004) Inhibitory effect of nicotine on experimental hypersensitivity pneumonitis in vivo and in vitro. Am J Respir Crit Care Med 169:903–909. https://doi.org/10.1164/rccm.200210-1154OC CrossRefPubMed

15.

Selman M, Buendía-Roldán I (2012) Immunopathology, diagnosis, and management of hypersensitivity pneumonitis. Semin Respir Crit Care Med 33:543–554. https://doi.org/10.1055/s-0032-1325163 CrossRefPubMed

16.

Walsh SLF, Wells AU, Desai SR et al (2016) Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study. Lancet Respir Med 4:557–565. https://doi.org/10.1016/S2213-2600(16)30033-9 CrossRefPubMed

17.

Lacasse Y, Selman M, Costabel U et al (2003) Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med 168:952–958. https://doi.org/10.1164/rccm.200301-137OC CrossRefPubMed

18.

Reich JM (1993) Chirping rales in bird-fancier’s lung. Chest 104:326–327. https://doi.org/10.1378/chest.104.1.326b CrossRefPubMed

19.

Vasakova M, Morell F, Walsh S et al (2017) Hypersensitivity pneumonitis: perspectives in diagnosis and management. Am J Respir Crit Care Med 196:680–689. https://doi.org/10.1164/rccm.201611-2201PP CrossRefPubMed

20.

Millerick-May ML, Mulks MH, Gerlach J et al (2016) Hypersensitivity pneumonitis and antigen identification: an alternate approach. Respir Med 112:97–105. https://doi.org/10.1016/j.rmed.2015.09.001 CrossRefPubMed

21.

Rodrigo MJ, Benavent MI, Cruz MJ et al (2000) Detection of specific antibodies to pigeon serum and bloom antigens by enzyme linked immunosorbent assay in pigeon breeder’s disease. Occup Env Med 57:159–164. https://doi.org/10.1136/oem.57.3.159 CrossRef

22.

Van Hoeyveld E, Dupont L, Bossuyt X (2006) Quantification of IgG antibodies to aspergillus fumigatus and pigeon antigens by immunoCAP technology: an alternative to the precipitation technique? Clin Chem 52:1785–1793. https://doi.org/10.1373/clinchem.2006.067546 CrossRefPubMed

23.

Suhara K, Miyazaki Y, Okamoto T et al (2015) Utility of immunological tests for bird-related hypersensitivity pneumonitis. Respir Investig 53:13–21. https://doi.org/10.1016/j.resinv.2014.08.001 CrossRefPubMed

24.

Fenoglio C-MM, Reboux G, Sudre B et al (2007) Diagnostic value of serum precipitins to mould antigens in active hypersensitivity pneumonitis. Eur Respir J 29:706–712. https://doi.org/10.1183/09031936.00001006 CrossRefPubMed

25.

Millon L, Rognon B, Valot B et al (2016) Common peptide epitopes induce cross-reactivity in hypersensitivity pneumonitis serodiagnosis. J Allergy Clin Immunol 138:1738–1741.e6. https://doi.org/10.1016/j.jaci.2016.06.037 CrossRefPubMed

26.

Rognon B, Barrera C, Monod M et al (2016) Identification of antigenic proteins from Lichtheimia corymbifera for farmer’s lung disease diagnosis. PLoS ONE 11:e0160888. https://doi.org/10.1371/journal.pone.0160888 CrossRefPubMedPubMedCentral

27.

Millon L, Reboux G, Barrera C et al (2014) Immunoproteomics for serological diagnosis of hypersensitivity pneumonitis caused by environmental microorganisms. Curr Protein Pept Sci 15:430–436CrossRef

28.

Ramírez-Venegas A, Sansores RH, Pérez-Padilla R, Carrillo GSM (1998) Utility of a provocation test for diagnosis of chronic pigeon breeder’s disease. Am J Respir Crit Care Med 158:862–869. https://doi.org/10.1164/ajrccm.158.3.9710036 CrossRefPubMed

29.

Hendrick DJ, Marshall R, Faux JA, Krall JM (1980) Positive “alveolar” responses to antigen inhalation provocation tests: their validity and recognition. Thorax 35:415–427. https://doi.org/10.1136/thx.35.6.415 CrossRefPubMedPubMedCentral

30.

Muñoz X, Sánchez-Ortiz M, Torres F et al (2014) Diagnostic yield of specific inhalation challenge in hypersensitivity pneumonitis. Eur Respir J 44:1658–1665. https://doi.org/10.1183/09031936.00060714 CrossRefPubMed

31.

Morell F, Villar A, Montero M-ÁÁ et al (2013) Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study. Lancet Respir Med 1:685–694. https://doi.org/10.1016/S2213-2600(13)70191-7 CrossRefPubMed

32.

Ochi J, Ohtani Y, Takemura T et al (2017) Histological variability and consequences in chronic bird-related hypersensitivity pneumonitis. Respirology 22:1350–1356. https://doi.org/10.1111/resp.13070 CrossRefPubMed

33.

Yoshizawa Y, Miyake S, Sumi Y et al (1995) 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 96:122–129CrossRef

34.

Wuyts W, Sterclova M, Vasakova M (2015) Pitfalls in diagnosis and management of hypersensitivity pneumonitis. Curr Opin Pulm Med 21:490–498. https://doi.org/10.1097/MCP.0000000000000199 CrossRefPubMed

35.

Soumagne T, Pana-Katatali H, Degano B, Dalphin J-C (2015) Combined pulmonary fibrosis and emphysema in hypersensitivity pneumonitis. BMJ Case Rep. https://doi.org/10.1136/bcr-2015-211560 CrossRefPubMedPubMedCentral

36.

Johannson KA, Elicker BM, Vittinghoff E et al (2016) A diagnostic model for chronic hypersensitivity pneumonitis. Thorax 71:951–954. https://doi.org/10.1136/thoraxjnl-2016-208286 CrossRefPubMedPubMedCentral

37.

Salisbury ML, Myers JL, Belloli EA et al (2017) Diagnosis and treatment of fibrotic hypersensitivity pneumonia. Where we stand and where we need to go. Am J Respir Crit Care Med 196:690–699. https://doi.org/10.1164/rccm.201608-1675PP CrossRefPubMedPubMedCentral

38.

Morisset J, Johannson KA, Jones KD et al (2017) Identification of diagnostic criteria for chronic hypersensitivity pneumonitis: an international modified Delphi survey. Am J Respir Crit Care Med 197:1036–1044. https://doi.org/10.1164/rccm.201710-1986OC CrossRefPubMed

39.

Lynch DA, Newell JD, Logan PM et al (1995) Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis? Am J Roentgenol 165:807–811. https://doi.org/10.2214/ajr.165.4.7676971 CrossRef

40.

Silva CIS, Müller NL, Lynch DA et al (2008) Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology 246:288–297. https://doi.org/10.1148/radiol.2453061881 CrossRefPubMed

41.

Silva CIS, Churg A, Müller NL (2007) Hypersensitivity pneumonitis: spectrum of high-resolution CT and pathologic findings. Am J Roentgenol 188:334–344. https://doi.org/10.2214/AJR.05.1826 CrossRef

42.

Salisbury ML, Gross BH, Chughtai A et al (2018) Development and validation of a radiological diagnosis model for hypersensitivity pneumonitis. Eur Respir J 52:1800443. https://doi.org/10.1183/13993003.00443-2018 CrossRefPubMedPubMedCentral

43.

Walsh SLF, Sverzellati N, Devaraj A et al (2012) Chronic hypersensitivity pneumonitis: high resolution computed tomography patterns and pulmonary function indices as prognostic determinants. Eur Radiol 22:1672–1679. https://doi.org/10.1007/s00330-012-2427-0 CrossRefPubMed

44.

Jacob J, Bartholmai BJ, Rajagopalan S et al (2017) Automated computer-based CT stratification as a predictor of outcome in hypersensitivity pneumonitis. Eur Radiol 27:3635–3646. https://doi.org/10.1007/s00330-016-4697-4 CrossRefPubMed

45.

Churg A, Bilawich A, Wright JL (2018) Pathology of chronic hypersensitivity pneumonitis what is it? What are the diagnostic criteria? Why do we care? Arch Pathol Lab Med 142:109–119. https://doi.org/10.5858/arpa.2017-0173-RA CrossRefPubMed

46.

Joshua J, Mooney LLK (2014) Surgical lung biopsy over bronchoalveolar lavage in chronic hypersensitivity pneumonitis. Am Thorac Soc 189(3):371–372

47.

Hodnett PA ND (2014) Reply to surgical lung biopsy over bronchoalveolar lavage in chronic hypersensitivity pneumonitis. Am Thorac Soc

48.

Meyer KC, Raghu G, Baughman RP et al (2012) 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 185:1004–1014. https://doi.org/10.1164/rccm.201202-0320ST CrossRefPubMed

49.

Vourlekis JS, Schwarz MI, Cherniack RM et al (2004) The effect of pulmonary fibrosis on survival in patients with hypersensitivity pneumonitis. Am J Med 116:662–668. https://doi.org/10.1016/j.amjmed.2003.12.030 CrossRefPubMed

50.

Adams TN, Newton CA, Batra K et al (2018) Utility of bronchoalveolar lavage and transbronchial biopsy in patients with hypersensitivity pneumonitis. Lung 196:617–622. https://doi.org/10.1007/s00408-018-0139-1 CrossRefPubMedPubMedCentral

51.

Spagnolo P, Rossi G, Cavazza A et al (2015) Hypersensitivity pneumonitis: a comprehensive review. J Investig Allergol Clin Immunol 25:237–250PubMed

52.

Romagnoli M, Colby TV, Berthet J-P et al (2019) Poor concordance between sequential transbronchial lung cryobiopsy and surgical lung biopsy in the diagnosis of diffuse interstitial lung diseases. Am J Respir Crit Care Med 199:1249–1256. https://doi.org/10.1164/rccm.201810-1947OC CrossRefPubMed

53.

Lacasse Y, Fraser RS, Fournier M, Cormier Y (1997) Diagnostic accuracy of transbronchial biopsy in acute farmer’s lung disease. Chest 112:1459–1465. https://doi.org/10.1378/chest.112.6.1459 CrossRefPubMed

54.

Troy LK, Grainge C, Corte TJ et al (2020) Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study. Lancet Respir Med 8:171–181. https://doi.org/10.1016/S2213-2600(19)30342-X CrossRefPubMed

55.

Takemura T, Akashi T, Ohtani Y et al (2008) Pathology of hypersensitivity pneumonitis. Curr Opin Pulm Med 14:440–454. https://doi.org/10.1097/MCP.0b013e3283043dfa CrossRefPubMed

56.

Coleman A, Colby TV (1988) Histologic diagnosis of extrinsic allergic alveolitis. Am J Surg Pathol 12:514–518CrossRef

57.

Vourlekis JS, Schwarz MI, Cool CD et al (2002) Nonspecific interstitial pneumonitis as the sole histologic expression of hypersensitivity pneumonitis. Am J Med 112:490–493. https://doi.org/10.1016/S0002-9343(02)01046-X CrossRefPubMed

58.

Churg A, Myers J, Suarez T et al (2004) Airway-centered interstitial fibrosis: a distinct form of aggressive diffuse lung disease. Am J Surg Pathol 28:62–68CrossRef

59.

Trahan S, Hanak V, Ryu JH, Myers JL (2008) Role of surgical lung biopsy in separating chronic hypersensitivity pneumonia from usual interstitial pneumonia/idiopathic pulmonary fibrosis. Chest 134:126–132. https://doi.org/10.1378/chest.08-0033 CrossRefPubMed

60.

Soumagne T, Chardon M-L, Dournes G et al (2017) Emphysema in active farmer’s lung disease. PLoS ONE 12:e0178263. https://doi.org/10.1371/journal.pone.0178263 CrossRefPubMedPubMedCentral

61.

Richeldi L, du Bois RM, Raghu G et al (2014) Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 370:2071–2082. https://doi.org/10.1056/NEJMoa1402584 CrossRefPubMed

62.

King TE, Bradford WZ, Castro-Bernardini S et al (2014) A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 370:2083–2092. https://doi.org/10.1056/NEJMoa1402582 CrossRefPubMed

63.

Fernandez Perez ER, Kong AM, Raimundo K et al (2018) Epidemiology of hypersensitivity pneumonitis among an insured population in the united states: a claims-based cohort analysis. Ann Am Thorac Soc 15:460–469. https://doi.org/10.1513/AnnalsATS.201704-288OC CrossRefPubMed

64.

Molyneaux PL, Maher TM (2017) Time for an international consensus on hypersensitivity pneumonitis: a call to arms. Am J Respir Crit Care Med 196:665–666CrossRef

65.

Takei R, Yamano Y, Kataoka K et al (2020) Usefulness of new diagnostic criteria for chronic hypersensitivity pneumonitis established on the basis of a Delphi survey: a Japanese cohort study. Respir Investig 58:52–58. https://doi.org/10.1016/j.resinv.2019.10.001 CrossRefPubMed

66.

Barnett J, Molyneaux PL, Rawal B et al (2019) Variable utility of mosaic attenuation to distinguish fibrotic hypersensitivity pneumonitis from idiopathic pulmonary fibrosis. Eur Respir J. https://doi.org/10.1183/13993003.00531-2019 CrossRefPubMedPubMedCentral

67.

Miyazaki Y, Tsutsui T, Inase N (2016) Treatment and monitoring of hypersensitivity pneumonitis. Expert Rev Clin Immunol 12:953–962. https://doi.org/10.1080/1744666X.2016.1182426 CrossRefPubMed

68.

Kokkarinen JI, Tukiainen HO, Terho EO (1992) Effect of corticosteroid treatment on the recovery of pulmonary function in farmer’s lung. Am Rev Respir Dis 145:3–5. https://doi.org/10.1164/ajrccm/145.1.3 CrossRefPubMed

69.

Richeldi L, Varone F, Bergna M et al (2018) Pharmacological management of progressive-fibrosing interstitial lung diseases: a review of the current evidence. Eur Respir Rev. https://doi.org/10.1183/16000617.0074-2018 CrossRefPubMed

70.

Morisset J, Johannson KA, Vittinghoff E et al (2017) Use of mycophenolate mofetil or azathioprine for the management of chronic hypersensitivity pneumonitis. Chest 151:619–625. https://doi.org/10.1016/j.chest.2016.10.029 CrossRefPubMed

71.

Adegunsoye A, Oldham JM, Fernández Pérez ER et al (2017) Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis. ERJ Open Res 3:00016–02017. https://doi.org/10.1183/23120541.00016-2017 CrossRefPubMedPubMedCentral

72.

Kern RM, Singer JP, Koth L et al (2015) Lung transplantation for hypersensitivity pneumonitis. Chest 147:1558–1565. https://doi.org/10.1378/chest.14-1543 CrossRefPubMed

73.

Flaherty KR, Brown KK, Wells AU et al (2017) 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 4:e000212. https://doi.org/10.1136/bmjresp-2017-000212 CrossRefPubMedPubMedCentral

Title: Fibrotic Hypersensitivity Pneumonitis: Diagnosis and Management
Authors: Francesco Varone
Bruno Iovene
Giacomo Sgalla
Mariarosaria Calvello
Angelo Calabrese
Anna Rita Larici
Luca Richeldi
Publication date: 01-06-2020
Publisher: Springer US
Keywords: Hypersensitivity Pneumonitis
Idiopathic Pulmonary Fibrosis
Published in: Lung / Issue 3/2020
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-020-00360-3

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