Semin Respir Crit Care Med 2008; 29(6): 631-642
DOI: 10.1055/s-0028-1101273
© Thieme Medical Publishers

Myths and Controversies in Hypersensitivity Pneumonitis

Yves Lacasse1 , Evelyne Assayag1 , Yvon Cormier1
  • 1Centre de pneumologie, Hôpital Laval, Québec, Canada
Further Information

Publication History

Publication Date:
16 February 2009 (online)

ABSTRACT

Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an antigen to which the patient has been previously sensitized. HP is an orphan disease, and current concepts on its diagnosis and management are often outdated. The objectives of this review are to summarize the modern evidence regarding the diagnostic criteria of HP, its pathophysiology, the procedures involved in the management of the disease, and its treatment strategies. Several areas for further research are identified, with priority given to (1) the establishment of a multicenter collaborative network to enhance the recognition, diagnosis, and management of the disease; (2) the development and support of population-based studies to provide additional insights into environmental and clinical characterization of HP; and (3) the exploration of the use and validity of biomarkers of both exposure and disease.

REFERENCES

  • 1 Selman M. Hypersensitivity pneumonitis. In: Schwarz MI, King Jr TE Interstitial Lung Disease. Hamilton, BC; Decker 1998: 393-422
  • 2 Terho E O. Diagnostic criteria for farmer's lung disease.  Am J Ind Med. 1986;  10 329
  • 3 Richerson H B, Bernstein I L, Fink J N et al.. Guidelines for the clinical evaluation of hypersensitivity pneumonitis. Report of the Subcommittee on Hypersensitivity Pneumonitis.  J Allergy Clin Immunol. 1989;  84 839-844
  • 4 Cormier Y, Lacasse Y. Keys to the diagnosis of hypersensitivity pneumonitis: the role of serum precipitins, lung biopsy, and high-resolution computed tomography.  Clin Pulm Med. 1996;  3 72-77
  • 5 Schuyler M, Cormier Y. The diagnosis of hypersensitivity pneumonitis.  Chest. 1997;  111 534-536
  • 6 Laupacis A, Sekar N, Stiell I G. Clinical prediction rules: a review and suggested modifications of methodological standards.  JAMA. 1997;  277 488-494
  • 7 Sullivan P A, Odencrantz J R, Petsonk E L et al.. Development and validation of a hypersensitivity pneumonitis surveillance questionnaire [abstract].  Am J Respir Crit Care Med. 1997;  155 A946
  • 8 Fox J, Anderson H, Moen T, Gruetzmacher G, Hanrahan L, Fink J. Metal working fluid-associated hypersensitivity pneumonitis: an outbreak investigation and case-control study.  Am J Ind Med. 1999;  35 58-67
  • 9 Dangman K H, Cole S R, Hodgson M J et al.. The hypersensitivity pneumonitis diagnostic index: use of non-invasive testing to diagnose hypersensitivity pneumonitis in metalworkers.  Am J Ind Med. 2002;  42 150-162
  • 10 Lacasse Y, Selman M, Costabel U et al.. Clinical diagnosis of hypersensitivity pneumonitis.  Am J Respir Crit Care Med. 2003;  168 952-958
  • 11 The BAL Cooperative Group Steering Committee . Bronchoalveolar lavage constituents in healthy individuals, idiopathic pulmonary fibrosis, and selected comparison groups.  Am Rev Respir Dis. 1990;  141 S169-S202
  • 12 Matar L D, McAdams H P, Sporn T A. Hypersensitivity pneumonitis.  AJR Am J Roentgenol. 2000;  174 1061-1066
  • 13 Cormier Y, Brown M, Worthy S, Racine G, Muller N L. High-resolution computed tomographic characteristics in acute farmer's lung and in its follow-up.  Eur Respir J. 2000;  16 56-60
  • 14 Remy-Jardin M, Remy J, Wallaert B, Muller N L. Subacute and chronic bird breeder hypersensitivity pneumonitis: sequential evaluation with CT and correlation with lung function tests and bronchoalveolar lavage.  Radiology. 1993;  189 111-118
  • 15 Adler B D, Padley S P, Muller N L, Remy-Jardin M, Remy J. Chronic hypersensitivity pneumonitis: high-resolution CT and radiographic features in 16 patients.  Radiology. 1992;  185 91-95
  • 16 Buschman D L, Gamsu G, Waldron Jr J A, Klein J S, King Jr T E. Chronic hypersensitivity pneumonitis: use of CT in diagnosis.  AJR Am J Roentgenol. 1992;  159 957-960
  • 17 Travis W D, Colby T V, Koss M N, Rosado-de-Christenson M L, Müller N L, King T E. Non-neoplastic Disorders of the Lower Respiratory Tract. The American Registry of Pathology (ARP) and Armed Forces Institute of Pathology. Washington, DC; 2002: 49-231
  • 18 Bertorelli L, Bocchino V, Olivieri D. Hypersensitivity pneumonitis. In: Olivieri D, du Bois RM. Interstitial Lung Diseases. European Respiratory Monograph, 2000. monograph 14: 120-136
  • 19 Boyd G, McSharry C P, Banham S W, Lynch P P. A current view of pigeon fancier's lung: a model for pulmonary extrinsic allergic alveolitis.  Clin Allergy. 1982;  12(Suppl) 53-59
  • 20 Fink J N, Ortega H G, Reynolds H Y et al.. Needs and opportunities for research in hypersensitivity pneumonitis.  Am J Respir Crit Care Med. 2005;  171 792-798
  • 21 Kaltreider H B. Hypersensitivity pneumonitis.  West J Med. 1993;  159 570-578
  • 22 Ando M, Suga M, Kohrogi H. A new look at hypersensitivity pneumonitis.  Curr Opin Pulm Med. 1999;  5 299-304
  • 23 Burrell R, Rylander R. A critical review of the role of precipitins in hypersensitivity pneumonitis.  Eur J Respir Dis. 1981;  62 332-343
  • 24 Cormier Y, Letourneau L, Racine G. Significance of precipitins and asymptomatic lymphocytic alveolitis: a 20-yr follow-up.  Eur Respir J. 2004;  23 523-525
  • 25 Trentin L, Migone N, Zambello R et al.. Mechanisms accounting for lymphocytic alveolitis in hypersensitivity pneumonitis.  J Immunol. 1990;  145 2147-2154
  • 26 Cormier Y, Israel-Assayag E. Pathogenesis of hypersensitivity pneumonitis. In: Martin Dunitz Ltd Textbook of Respiratory Cell and Molecular Biology, Wardlaw AJ, Hamid Q. London; Informa Health Care 2002: 147-158
  • 27 Suda T, Sato A, Ida M, Gemma H, Hayakawa H, Chida K. Hypersensitivity pneumonitis associated with home ultrasonic humidifiers.  Chest. 1995;  107 711-717
  • 28 Marras T K, Wallace Jr R J, Koth L L, Stulbarg M S, Cowl C T, Daley C L. Hypersensitivity pneumonitis reaction to Mycobacterium avium in household water.  Chest. 2005;  127 664-671
  • 29 Sterclova M, Vasakova M, Dutka J, Kalanin J. Extrinsic allergic alveolitis: comparative study of the bronchoalveolar lavage profiles and radiological presentation.  Postgrad Med J. 2006;  82 598-601
  • 30 Drent M, Grutters J C, Mulder P G, Velzen-Blad H, Wouters E F, van den Bosch J M. Is the different T helper cell activity in sarcoidosis and extrinsic allergic alveolitis also reflected by the cellular bronchoalveolar lavage fluid profile?.  Sarcoidosis Vasc Diffuse Lung Dis. 1997;  14 31-38
  • 31 Murayama J, Yoshizawa Y, Ohtsuka M, Hasegawa S. Lung fibrosis in hypersensitivity pneumonitis: association with CD4 + but not CD8 + cell dominant alveolitis and insidious onset.  Chest. 1993;  104 38-43
  • 32 Ohtani Y, Hisauchi K, Sumi Y et al.. Sequential changes in bronchoalveolar lavage cells and cytokines in a patient progressing from acute to chronic bird Fancier's lung disease.  Intern Med. 1999;  38 896-899
  • 33 Warren C P. Extrinsic allergic alveolitis: a disease commoner in non-smokers.  Thorax. 1977;  32 567-569
  • 34 Blanchet M R, Israel-Assayag E, Cormier Y. Modulation of airway inflammation and resistance in mice by a nicotinic receptor agonist.  Eur Respir J. 2005;  26 21-27
  • 35 Karlsson M R, Rugtveit J, Brandtzaeg P. Allergen-responsive CD4 + CD25 + regulatory T cells in children who have outgrown cow's milk allergy.  J Exp Med. 2004;  199 1679-1688
  • 36 Ling E M, Smith T, Nguyen X D et al.. Relation of CD4 + CD25 + regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease.  Lancet. 2004;  363 608-615
  • 37 Bacchetta R, Passerini L, Gambineri E et al.. Defective regulatory and effector T cell functions in patients with FOXP3 mutations.  J Clin Invest. 2006;  116 1713-1722
  • 38 Monkare S, Ikonen M, Haahtela T. Radiologic findings in farmer's lung: prognosis and correlation to lung function.  Chest. 1985;  87 460-466
  • 39 Seal R ME, Thomas G O, Griffiths J J. Farmer's lung.  Proc R Soc Med. 1963;  56 271-273
  • 40 Cook P G, Wells I P, McGavin C R. The distribution of pulmonary shadowing in farmer's lung.  Clin Radiol. 1988;  39 21-27
  • 41 Mindell H J. Roentgen findings in farmer's lung.  Radiology. 1970;  97 341-346
  • 42 Emanuel D A, Kryda M J. Farmer's lung disease.  Clin Rev Allergy. 1983;  1 509-532
  • 43 Hodgson M J, Parkinson D K, Karpf M. Chest x-rays in hypersensitivity pneumonitis: a metaanalysis of secular trend.  Am J Ind Med. 1989;  16 45-53
  • 44 Lynch D A, Rose C S, Way D, King Jr T E. Hypersensitivity pneumonitis: sensitivity of high-resolution CT in a population-based study.  AJR Am J Roentgenol. 1992;  159 469-472
  • 45 Lynch D A, Newell J D, Logan P M, King Jr T E, Muller N L. Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis?.  AJR Am J Roentgenol. 1995;  165 807-811
  • 46 Hapke E J, Seal R M, Thomas G O, Hayes M, Meek J C. Farmer's lung: a clinical, radiographic, functional, and serological correlation of acute and chronic stages.  Thorax. 1968;  23 451-468
  • 47 Lalancette M, Carrier G, Laviolette M et al.. Farmer's lung: long-term outcome and lack of predictive value of bronchoalveolar lavage fibrosing factors.  Am Rev Respir Dis. 1993;  148 216-221
  • 48 Lacasse Y, Selman M, Costabel U et al.. Clinical manifestations of hypersensitivity pneumonitis from various origins [abstract].  Am J Respir Crit Care Med. 2003;  167 A359
  • 49 Cormier Y, Belanger J, Tardif A, LeBlanc P, Laviolette M. Relationships between radiographic change, pulmonary function, and bronchoalveolar lavage fluid lymphocytes in farmer's lung disease.  Thorax. 1986;  41 28-33
  • 50 Cormier Y, Belanger J, Durand P. Factors influencing the development of serum precipitins to farmer's lung antigen in Quebec dairy farmers.  Thorax. 1985;  40 138-142
  • 51 Fink J N. Epidemiologic aspects of hypersensitivity pneumonitis.  Monogr Allergy. 1987;  21 59-69
  • 52 Dalphin J C, Toson B, Monnet E et al.. Farmer's lung precipitins in Doubs (a department of France): prevalence and diagnostic value.  Allergy. 1994;  49 744-750
  • 53 Cormier Y, Belanger J. The fluctuant nature of precipitating antibodies in dairy farmers.  Thorax. 1989;  44 469-473
  • 54 Kawai T, Tamura M, Murao M. Summer-type hypersensitivity pneumonitis: a unique disease in Japan.  Chest. 1984;  85 311-317
  • 55 Ojanen T. Class specific antibodies in serodiagnosis of farmer's lung.  Br J Ind Med. 1992;  49 332-336
  • 56 Reynaud C, Slosman D O, Polla B S. Precipitins in bird breeder's disease: how useful are they?.  Eur Respir J. 1990;  3 1155-1161
  • 57 Fenoglio C M, Reboux G, Sudre B et al.. Diagnostic value of serum precipitins to mould antigens in active hypersensitivity pneumonitis.  Eur Respir J. 2007;  29 706-712
  • 58 Van Hoeyveld E, Dupont L, Bossuyt X. Quantification of IgG antibodies to Aspergillus fumigatus and pigeon antigens by ImmunoCAP technology: an alternative to the precipitation technique?.  Clin Chem. 2006;  52 1785-1793
  • 59 Reboux G, Dalphin J C. Hypersensitivity pneumonitis: a technical note on precipitins [in French].  Rev Mal Respir. 2003;  20 140-143
  • 60 Simpson C, Shirodaria P V, Evans J P, Simpson D I, Stanford C F. Comparison of immunodiffusion and enzyme linked immunosorbent assay in the detection of abnormal antibodies in pigeon breeder's disease.  J Clin Pathol. 1992;  45 490-493
  • 61 Aberer W, Woltsche M, Woltsche-Kahr I, Kranke B. IgG antibodies typical for extrinsic allergic alveolitis: an inter-laboratory quality assessment.  Eur J Med Res. 2001;  6 498-504
  • 62 Banales J L, Vazquez L, Mendoza F et al.. On the correct determination of reference values for serum antibodies against pigeon serum antigen using a group of healthy blood donors.  Arch Med Res. 1997;  28 289-291
  • 63 Edwards J H, Davies B H. Inhalation challenge and skin testing in farmer's lung.  J Allergy Clin Immunol. 1981;  68 58-64
  • 64 Semenzato G, Bjermer L, Costabel U, Haslam P L, Olivieri D. Clinical guidelines and indications for bronchoalveolar lavage (BAL): extrinsic allergic alveolitis.  Eur Respir J. 1990;  3 945-949
  • 65 Cormier Y, Belanger J, LeBlanc P, Laviolette M. Bronchoalveolar lavage in farmers' lung disease: diagnostic and physiological significance.  Br J Ind Med. 1986;  43 401-405
  • 66 Cormier Y, Belanger J, Laviolette M. Persistent bronchoalveolar lymphocytosis in asymptomatic farmers.  Am Rev Respir Dis. 1986;  133 843-847
  • 67 Godard P, Clot J, Jonquet O, Bousquet J, Michel F B. Lymphocyte subpopulations in bronchoalveolar lavages of patients with sarcoidosis and hypersensitivity pneumonitis.  Chest. 1981;  80 447-452
  • 68 Valenti S, Scordamaglia A, Crimi P, Mereu C. Bronchoalveolar lavage and transbronchial lung biopsy in sarcoidosis and extrinsic allergic alveolitis.  Eur J Respir Dis. 1982;  63 564-569
  • 69 Helmers R A, Dayton C S, Floerchinger C, Hunninghake G W. Bronchoalveolar lavage in interstitial lung disease: effect of volume of fluid infused.  J Appl Physiol. 1989;  67 1443-1446
  • 70 Schildge J, Nagel C, Grun C. Bronchoalveolar lavage in interstitial lung diseases: does the recovery rate affect the results?.  Respiration. 2007;  74 553-557
  • 71 Reyes C N, Wenzel F J, Lawton B R, Emanuel D A. The pulmonary pathology of farmer's lung disease.  Chest. 1982;  81 142-146
  • 72 Kawanami O, Basset F, Barrios R, Lacronique J G, Ferrans V J, Crystal R G. Hypersensitivity pneumonitis in man: light- and electron-microscopic studies of 18 lung biopsies.  Am J Pathol. 1983;  110 275-289
  • 73 Coleman A, Colby T V. Histologic diagnosis of extrinsic allergic alveolitis.  Am J Surg Pathol. 1988;  12 514-518
  • 74 Vourlekis J S, Schwarz M I, Cool C D, Tuder R M, King T E, Brown K K. Nonspecific interstitial pneumonitis as the sole histologic expression of hypersensitivity pneumonitis.  Am J Med. 2002;  112 490-493
  • 75 Jacobs R L. Hypersensitivity pneumonia: UIP/IPF histopathologic presentation.  J Allergy Clin Immunol. 2002;  110 532-533
  • 76 Ohtani Y, Saiki S, Kitaichi M et al.. 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
  • 77 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;  161 646-664
  • 78 Jacobs R L, Andrews C P, Coalson J J. Hypersensitivity pneumonitis: beyond classic occupational disease-changing concepts of diagnosis and management.  Ann Allergy Asthma Immunol. 2005;  95 115-128
  • 79 Cormier Y. Hypersensitivity pneumonitis: restrictive diagnostic criteria or a different disease?.  Ann Allergy Asthma Immunol. 2005;  95 99
  • 80 Lacasse Y, Fraser R S, Fournier M, Cormier Y. Diagnostic accuracy of transbronchial biopsy in acute farmer's lung disease.  Chest. 1997;  112 1459-1465
  • 81 Qureshi R A, Ahmed T A, Grayson A D, Soorae A S, Drakeley M J, Page R D. Does lung biopsy help patients with interstitial lung disease?.  Eur J Cardiothorac Surg. 2002;  21 621-626
  • 82 Rena O, Casadio C, Leo F et al.. Videothoracoscopic lung biopsy in the diagnosis of interstitial lung disease.  Eur J Cardiothorac Surg. 1999;  16 624-627
  • 83 Temes R T, Joste N E, Qualls C R et al.. Lung biopsy: is it necessary?.  J Thorac Cardiovasc Surg. 1999;  118 1097-1100
  • 84 Kramer M R, Berkman N, Mintz B, Godfrey S, Saute M, Amir G. The role of open lung biopsy in the management and outcome of patients with diffuse lung disease.  Ann Thorac Surg. 1998;  65 198-202
  • 85 Neuhaus S J, Matar K S. The efficacy of open lung biopsy.  Aust N Z J Surg. 1997;  67 181-184
  • 86 Lachapelle K J, Morin J E. Benefit of open lung biopsy in patients with respiratory failure.  Can J Surg. 1995;  38 316-321
  • 87 Bove P, Ranger W, Pursel S, Glover J, Bove K, Bendick P. Evaluation of outcome following open lung biopsy.  Am Surg. 1994;  60 564-570
  • 88 Shah S S, Tsang V, Goldstraw P. Open lung biopsy: a safe, reliable and accurate method for diagnosis in diffuse lung disease.  Respiration. 1992;  59 243-246
  • 89 Wagner J D, Stahler C, Knox S, Brinton M, Knecht B. Clinical utility of open lung biopsy for undiagnosed pulmonary infiltrates.  Am J Surg. 1992;  164 104-107
  • 90 Walker W A, Cole Jr F H, Khandekar A, Mahfood S S, Watson D C. Does open lung biopsy affect treatment in patients with diffuse pulmonary infiltrates?.  J Thorac Cardiovasc Surg. 1989;  97 534-540
  • 91 Warner D O, Warner M A, Divertie M B. Open lung biopsy in patients with diffuse pulmonary infiltrates and acute respiratory failure.  Am Rev Respir Dis. 1988;  137 90-94
  • 92 Venn G E, Kay P H, Midwood C J, Goldstraw P. Open lung biopsy in patients with diffuse pulmonary shadowing.  Thorax. 1985;  40 931-935
  • 93 Kokkarinen J I, Tukiainen H O, Terho E O. Effect of corticosteroid treatment on the recovery of pulmonary function in farmer's lung.  Am Rev Respir Dis. 1992;  145 3-5
  • 94 Cormier Y, Desmeules M. Treatment of hypersensitivity pneumonitis (HP): comparison between contact avoidance and corticosteroids.  Can Respir J. 1994;  1 223-228
  • 95 Monkare S. Influence of corticosteroid treatment on the course of farmer's lung.  Eur J Respir Dis. 1983;  64 283-293
  • 96 Kokkarinen J I, Tukiainen H O, Terho E O. Recovery of pulmonary function in farmer's lung: a five-year follow-up study.  Am Rev Respir Dis. 1993;  147 793-796
  • 97 Carlsen K H, Leegaard J, Lund O D, Skjaervik H. Allergic alveolitis in a 12-year-old boy: treatment with budesonide nebulizing solution.  Pediatr Pulmonol. 1992;  12 257-259
  • 98 Hoglund S. Prevention of respiratory problems in agriculture.  Am J Ind Med. 1986;  10 245-247
  • 99 American Thoracic Society . Respiratory health hazards in agriculture.  Am J Respir Crit Care Med. 1998;  158 S1-S76
  • 100 Yoshida K, Ando M, Sakata T, Araki S. Prevention of summer-type hypersensitivity pneumonitis: effect of elimination of Trichosporon cutaneum from the patients' homes.  Arch Environ Health. 1989;  44 317-322
  • 101 Jacobs R L, Andrews C P, Jacobs F O. Hypersensitivity pneumonitis treated with an electrostatic dust filter.  Ann Intern Med. 1989;  110 115-118
  • 102 Bouchard S, Morin F, Bedard G, Gauthier J, Paradis J, Cormier Y. Farmer's lung and variables related to the decision to quit farming.  Am J Respir Crit Care Med. 1995;  152 997-1002
  • 103 Cormier Y, Belanger J. Long-term physiologic outcome after acute farmer's lung.  Chest. 1985;  87 796-800
  • 104 Braun S R, doPico G A, Tsiatis A, Horvath E, Dickie H A, Rankin J. Farmer's lung disease: long-term clinical and physiologic outcome.  Am Rev Respir Dis. 1979;  119 185-191
  • 105 Dalphin J C, Pernet D, Reboux G et al.. Influence of mode of storage and drying of fodder on thermophilic actinomycete aerocontamination in dairy farms of the Doubs region of France.  Thorax. 1991;  46 619-623
  • 106 Baron V S, Greer G G. Comparison of six commercial hay preservatives under simulated storage conditions.  Can J Animal Science. 1988;  68 429-437
  • 107 Nuutinen J, Terho E O, Husman K, Kotimaa M, Harkonen R, Nousiainen H. Protective value of powered dust respirator helmet for farmers with farmer's lung.  Eur J Respir Dis Suppl. 1987;  152 212-220
  • 108 Hendrick D J, Marshall R, Faux J A, Krall J M. Protective value of dust respirators in extrinsic allergic alveolitis: clinical assessment using inhalation provocation tests.  Thorax. 1981;  36 917-921
  • 109 Gourley C A, Braidwood G D. The use of dust respirators in the prevention of recurrence of farmer's lung.  Trans Soc Occup Med. 1971;  21 93-95
  • 110 Kusaka H, Ogasawara H, Munakata M et al.. Two-year follow up on the protective value of dust masks against farmer's lung disease.  Intern Med. 1993;  32 106-111

Yves LacasseM.D. M.Sc. 

Centre de pneumologie, Hôpital Laval

2725 Chemin Ste-Foy, Québec, Québec, G1V 4G5, Canada

Email: yves.lacasse@med.ulaval.ca

    >