extrinsic allergic alveolitis


Summary: A common interstitial lung disease caused by hypersensitivity reactions of PULMONARY ALVEOLI after inhalation of and sensitization to environmental antigens of microbial, animal, or chemical sources. The disease is characterized by lymphocytic alveolitis and granulomatous pneumonitis.

Top Publications

  1. 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 pubmed
    ..Reactivity to used but not unused MWF suggests a biocontaminant, probably bacteria or fungi, is the causative antigen in the development of HP in this setting. ..
  2. Patel A, Ryu J, Reed C. Hypersensitivity pneumonitis: current concepts and future questions. J Allergy Clin Immunol. 2001;108:661-70 pubmed
    Hypersensitivity pneumonitis (extrinsic allergic alveolitis) caused by inhaled allergens can progress to disabling or even fatal end-stage lung disease. The only truly effective treatment is early recognition and control of exposure...
  3. Cormier Y, Letourneau L, Racine G. Significance of precipitins and asymptomatic lymphocytic alveolitis: a 20-yr follow-up. Eur Respir J. 2004;23:523-5 pubmed
    ..Serum precipitins and asymptomatic lymphocytic alveolitis in an asymptomatic, exposed dairy farmer have no clinically meaningful long-term consequences. ..
  4. Marras T, Wallace R, Koth L, Stulbarg M, Cowl C, Daley C. Hypersensitivity pneumonitis reaction to Mycobacterium avium in household water. Chest. 2005;127:664-71 pubmed
    ..Antimycobacterial therapy may be required. The possibility of MAC hypersensitivity pneumonitis from showering raises potential implications in the investigation of patients with hypersensitivity pneumonitis. ..
  5. Nance S, Cross R, Fitzpatrick E. Chemokine production during hypersensitivity pneumonitis. Eur J Immunol. 2004;34:677-685 pubmed publisher
    ..These results suggest that IFN-gamma mediates the recruitment of CXCR3+/CD4+ T cells into the lung via production of the chemokines IP-10, Mig, and I-TAC, resulting in granuloma formation. ..
  6. Travaline J, Kelsen S. Hypersensitivity pneumonitis associated with hot tub use. Arch Intern Med. 2003;163:2250; author reply 2250-1 pubmed
  7. Kenmotsu H, Honda A, Baba T, Matsumoto Y, Shichi I, Eto T, et al. [A case of hypersensitivity pneumonitis caused by inhalation of Mycobacterium avium from a home bath with a circulating water system]. Nihon Kokyuki Gakkai Zasshi. 2005;43:689-92 pubmed
    ..We believe the case is hypersensitivity pneumonitis to MAC in an immunocompetent patient, simulating hot tub lung. Hypersensitivity pneumonitis caused by MAC is rare in Japan...
  8. Bracker A, Storey E, Yang C, Hodgson M. An outbreak of hypersensitivity pneumonitis at a metalworking plant: a longitudinal assessment of intervention effectiveness. Appl Occup Environ Hyg. 2003;18:96-108 pubmed
    ..1, df = 7, p <.0002). Measured oil mist air levels did not exceed the Occupational Safety and Health Administration's (OSHA's) permissible exposure limit (PEL), and in fact, did not exceed 0.5 mg/m(3)...
  9. Mery A, Horan R. Hot tub-related Mycobacterium avium intracellulare pneumonitis. Allergy Asthma Proc. 2002;23:271-3 pubmed

More Information


  1. Pardo A, Smith K, Abrams J, Coffman R, Bustos M, McClanahan T, et al. CCL18/DC-CK-1/PARC up-regulation in hypersensitivity pneumonitis. J Leukoc Biol. 2001;70:610-6 pubmed
    ..High levels of CCL18 were detected in the subacute rather than the chronic phase of HP. These findings suggest a role for CCL18 in the pathogenesis of HP. ..
  2. Thorne P, Adamcakova Dodd A, Kelly K, O neill M, Duchaine C. Metalworking fluid with mycobacteria and endotoxin induces hypersensitivity pneumonitis in mice. Am J Respir Crit Care Med. 2006;173:759-68 pubmed
    ..MWFs containing mycobacteria induced granulomatous lung lesions, peribronchiolar lymphocytosis, increased cell concentrations in lavage, and up-regulation of several cytokines. These findings are consistent with HP. ..
  3. Gordon T. Metalworking fluid--the toxicity of a complex mixture. J Toxicol Environ Health A. 2004;67:209-19 pubmed
    ..This review discusses the methodologies used to examine the toxicity of the complex nature of modern metalworking fluids and the findings that point toward bacterial endotoxin as a major contributor to their adverse effects. ..
  4. Moore J, Christensen M, Wilson R, Wallace R, Zhang Y, Nash D, et al. Mycobacterial contamination of metalworking fluids: involvement of a possible new taxon of rapidly growing mycobacteria. AIHAJ. 2000;61:205-13 pubmed
    ..The relationship of this mycobacterium to the cases of HP is unknown. ..
  5. Ferri F, Ruggieri M, Guidetti G, Azzarone G, Giammartini P, Capanni S, et al. [Prevalence of extrinsic allergic alveolitis in cattle breeders from the province of Reggio Emilia]. Med Lav. 2003;94:380-90 pubmed
    Several new cases of Extrinsic Allergic Alveolitis or Farmer's Lung (FL) in farm workers were reported to Occupational Health Services in the province of Reggio Emilia (Italy)...
  6. 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 pubmed
    Determination of specific IgG antibodies is important for the diagnosis of extrinsic allergic alveolitis (EAA)...
  7. Kampfer P, Engelhart S, Rolke M, Sennekamp J. Extrinsic allergic alveolitis (hypersensitivity pneumonitis) caused by Sphingobacterium spiritivorum from the water reservoir of a steam iron. J Clin Microbiol. 2005;43:4908-10 pubmed
    A case of extrinsic allergic alveolitis (EAA) caused by Sphingobacterium spiritivorum is described. The symptoms were associated with the use of a steam iron. The water reservoir was heavily contaminated with S...
  8. Schuyler M, Gott K, Cherne A. Experimental hypersensitivity pneumonitis: role of MCP-1. J Lab Clin Med. 2003;142:187-95 pubmed
    ..We conclude that interaction of MCP-1 with CCR2 is not necessary for the development of pulmonary inflammation in response to intratracheally administered S rectivirgula or cells able to adoptively transfer experimental HP. ..
  9. Ohashi R, Akagawa S, Kurashima A, Tsuchiya K, Miyamoto M, Masuda K, et al. [Case of pulmonary mycobacterium avium complex disease, showing hypersensitivity pneumonitis-like diffuse shadow]. Kekkaku. 2006;81:19-23 pubmed
    ..Although we did not examine the presence of Mycobacterium avium in the water of sauna bath, we suspected this case as Hot Tub Lung based on clinical features and the response to treatment...
  10. Khoor A, Leslie K, Tazelaar H, Helmers R, Colby T. Diffuse pulmonary disease caused by nontuberculous mycobacteria in immunocompetent people (hot tub lung). Am J Clin Pathol. 2001;115:755-62 pubmed
    ..These findings suggest that disease due to NTM may manifest as diffuse infiltrates in immunocompetent adults and that hot tub use may be an important risk factor for this disease pattern. ..
  11. Dai H, Guzman J, Chen B, Costabel U. Production of soluble tumor necrosis factor receptors and tumor necrosis factor-alpha by alveolar macrophages in sarcoidosis and extrinsic allergic alveolitis. Chest. 2005;127:251-6 pubmed
    ..tumor necrosis factor (TNF)-alpha plays a pivotal role in the pathogenesis of sarcoidosis and extrinsic allergic alveolitis (EAA)...
  12. Falkinham J. Mycobacterial aerosols and respiratory disease. Emerg Infect Dis. 2003;9:763-7 pubmed
    ..Disinfection may select for the predominance and growth of mycobacteria. Therefore, mycobacteria may be responsible, in part, for many outbreaks of hypersensitivity pneumonitis and other respiratory problems in the workplace and home. ..
  13. Systrom D, Wittram C. Case records of the Massachusetts General Hospital. Case 9-2005. A 67-year-old man with acute respiratory failure. N Engl J Med. 2005;352:1238-46 pubmed
  14. Agarwal R, Nath A. Hot-tub lung: hypersensitivity to Mycobacterium avium but not hypersensitivity pneumonitis. Respir Med. 2006;100:1478 pubmed
  15. Tong Z, Chen B, Dai H, Bauer P, Guzman J, Costabel U. Extrinsic allergic alveolitis: inhibitory effects of pentoxifylline on cytokine production by alveolar macrophages. Ann Allergy Asthma Immunol. 2004;92:234-9 pubmed
    ..b>Extrinsic allergic alveolitis (EAA) is a granulomatous disease that is driven by T-cell and alveolar macrophage (AM)-derived ..
  16. Apostolakos M, Rossmoore H, Beckett W. Hypersensitivity pneumonitis from ordinary residential exposures. Environ Health Perspect. 2001;109:979-81 pubmed
    ..We propose that hypersensitivity pneumonitis may occur in North America, as it does in Japan, from domestic exposures alone. ..
  17. Hanak V, Kalra S, Aksamit T, Hartman T, Tazelaar H, Ryu J. Hot tub lung: presenting features and clinical course of 21 patients. Respir Med. 2006;100:610-5 pubmed
    ..Although corticosteroids may be helpful in the treatment of severely affected patients, others can be managed by avoidance of additional exposure alone. ..
  18. Fink J, Ortega H, Reynolds H, Cormier Y, Fan L, Franks T, et al. Needs and opportunities for research in hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2005;171:792-8 pubmed
  19. Rickman O, Ryu J, Fidler M, Kalra S. Hypersensitivity pneumonitis associated with Mycobacterium avium complex and hot tub use. Mayo Clin Proc. 2002;77:1233-7 pubmed
    ..Hypersensitivity to MAC, rather than an infection, is the likely underlying mechanism in these 2 cases of hot tub lung. ..
  20. Marchetti N, Criner K, Criner G. Characterization of functional, radiologic and lung function recovery post-treatment of hot tub lung. A case report and review of the literature. Lung. 2004;182:271-7 pubmed
    ..Prednisone therapy offered minimal further improvement while anti-MAC therapy provided no further improvement. These results are suggestive of a hypersensitivity pneumonitis rather than an infectious etiology. ..
  21. Lacasse Y, Selman M, Costabel U, Dalphin J, Ando M, Morell F, et al. Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2003;168:952-8 pubmed
    ..The rule retained its accuracy when validated in a separate cohort of 261 patients. The diagnosis of HP can often be made or rejected with confidence, especially in areas of high or low prevalence, respectively, without BAL or biopsy. ..
  22. Reboux G, Dalphin J. [Hypersensitivity pneumonitis: a technical note on precipitins]. Rev Mal Respir. 2003;20:140-3 pubmed
  23. Gordon T, Nadziejko C, Galdanes K, Lewis D, Donnelly K. Mycobacterium immunogenum causes hypersensitivity pneumonitis-like pathology in mice. Inhal Toxicol. 2006;18:449-56 pubmed
    ..immunogenum is an unrecognized class of microorganisms capable of causing hypersensitivity pneumonitis and plays a role in the outbreaks of hypersensitivity pneumonitis in automotive plants. ..
  24. Dangman K, Cole S, Hodgson M, Kuhn C, Metersky M, Schenck P, et al. The hypersensitivity pneumonitis diagnostic index: use of non-invasive testing to diagnose hypersensitivity pneumonitis in metalworkers. Am J Ind Med. 2002;42:150-62 pubmed
    ..The HP diagnostic index could provide a useful tool in future HP outbreaks, which are increasingly being recognized in metalworking facilities. ..
  25. Shelton B, Flanders W, Morris G. Mycobacterium sp. as a possible cause of hypersensitivity pneumonitis in machine workers. Emerg Infect Dis. 1999;5:270-3 pubmed
    ..Retrospective review of samples submitted to our laboratory showed an association between presence of mycobacteria and HP. ..
  26. Bernstein D, Lummus Z, Santilli G, Siskosky J, Bernstein I. Machine operator's lung. A hypersensitivity pneumonitis disorder associated with exposure to metalworking fluid aerosols. Chest. 1995;108:636-41 pubmed
    ..Observed precipitin responses to a variety of microbial contaminants in metalworking fluid strongly suggest a causative role for microbial antigens in the induction and elicitation of this manifestation of hypersensitivity pneumonitis. ..
  27. Wright R, Dyer Z, Liebhaber M, Kell D, Harber P. Hypersensitivity pneumonitis from Pezizia domiciliana. A case of El Niño lung. Am J Respir Crit Care Med. 1999;160:1758-61 pubmed
    ..Open lung biopsy revealed extrinsic allergic alveolitis (hypersensitivity pneumonitis)...
  28. Ahmad S, Graham D. Pneumonitis with antiandrogens. Ann Intern Med. 2003;139:528-9; author reply 529 pubmed
  29. Dalphin J, Manzoni P, Ranfaing E, Reboux G. [Bronchial involvement in hypersensitivity pneumonitis]. Presse Med. 2009;38:1647-53 pubmed publisher
    ..Chronic bronchitis, an obstructive defect at lung function tests and emphysema as long-term outcome are frequent consequences of this bronchial involvement. ..
  30. Vasakova M, Sterclova M, Kolesar L, Slavcev A, Pohunek P, Sulc J, et al. Cytokine gene polymorphisms and BALF cytokine levels in interstitial lung diseases. Respir Med. 2009;103:773-9 pubmed publisher
    ..The TNF-alpha BALF values correlated with IL-1R pst 1970 gene polymorphisms. ..
  31. Belhassen García M, Hernández Cabrera M, Pérez Arellano J. [Hypersensitivity pneumonitis associated with Mycobacterium chelonae]. Arch Bronconeumol. 2008;44:226-7 pubmed
  32. Nordness M, Zacharisen M, Fink J. Toxic and other non-IgE-mediated effects of fungal exposures. Curr Allergy Asthma Rep. 2003;3:438-46 pubmed
    ..However, if mold is discovered in a home, school, or office setting, the source should be investigated and appropriate remediation undertaken to minimize structural damage and potential allergic sensitization. ..
  33. Yoshizawa Y. [Hypersensitivity pneumonitis]. Nihon Rinsho. 2005;63 Suppl 5:156-64 pubmed
  34. Venkatesh P, Wild L. Hypersensitivity pneumonitis in children: clinical features, diagnosis, and treatment. Paediatr Drugs. 2005;7:235-44 pubmed
    Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is a form of immune-mediated inflammatory lung disease involving the distal portions of the lungs associated with intense or repeated exposure to a variety of finely ..
  35. Palmer B, Mack D, Martin A, Maier L, Fontenot A. CD57 expression correlates with alveolitis severity in subjects with beryllium-induced disease. J Allergy Clin Immunol. 2007;120:184-91 pubmed
    ..These findings suggest that CD57 is a marker of lung inflammation and potentially, disease severity. ..
  36. Zompatori M, Calabrò E, Chetta A, Chiari G, Marangio E, Olivieri D. [Chronic hypersensitivity pneumonitis or idiopathic pulmonary fibrosis? Diagnostic role of high resolution Computed Tomography (HRCT)]. Radiol Med. 2003;106:135-46 pubmed
    In the diagnosis of extrinsic allergic alveolitis, high-resolution computed tomography (HRCT) is more sensitive and more specific than radiography; however, the accuracy of HRCT is not absolute...
  37. van Heemst R, Sander I, Rooyackers J, de Jong L, Djamin R, Aerts J, et al. Hypersensitivity pneumonitis caused by occupational exposure to phytase. Eur Respir J. 2009;33:1507-9 pubmed publisher
    ..After treatment and cessation of phytase contact the patient became symptom free and lung function normalised. Phytase should be considered as a cause of occupational hypersensitivity pneumonitis in the animal feed industry. ..
  38. Navarro C, Ruiz V, Gaxiola M, Carrillo G, Selman M. Angiogenesis in hypersensitivity pneumonitis. Arch Physiol Biochem. 2003;111:365-8 pubmed
    ..By RT-PCR the VEGF RNA was increased compared with those in normal lung. Our results suggest that abnormal expression of VEGF may contribute to impair the lung repair in HP. ..
  39. Chung M, Edinburgh K, Webb E, McCowin M, Webb W. 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 pubmed
    ..67, p = 0.05), and DLCO (r = -0.75, p = 0.02). Findings of lung infiltration on inspiratory HRCT scans and air trapping on expiratory CT correlated respectively with PFT measures of restrictive and obstructive lung disease. ..
  40. Yamamoto Y, Osanai S, Fujiuchi S, Yamazaki K, Nakano H, Ohsaki Y, et al. Extrinsic allergic alveolitis induced by the yeast Debaryomyces hansenii. Eur Respir J. 2002;20:1351-3 pubmed
    ..The diagnosis of extrinsic allergic alveolitis (EAA) was confirmed by radiographic findings, pathological evidence of alveolitis and reproductive ..
  41. Suga M. [Hypersensitivity pneumonitis]. Nihon Naika Gakkai Zasshi. 2003;92:1212-7 pubmed
  42. D Alessandro A, Folletti I, Muzi G, Murgia N, Brugnami G, Abritti G. [Use of sputum in the follow-up of hypersensitivity pneumonia]. G Ital Med Lav Ergon. 2003;25 Suppl:284-5 pubmed
  43. Merkus P, van Toorenenbergen A. Birds or zebras?. Allergy. 2002;57:566-9 pubmed
  44. Huang W, Lu Y, Lin Z, Su W. Sauna lung: hypersensitivity pneumonitis due to Exophiala jeanselmei. Respirology. 2010;15:573-6 pubmed publisher
    ..Immunoblotting assays from the patient's serum confirmed the major antigenic stimulus. The patient recovered fully after systemic corticosteroid treatment and cessation of further exposure. ..
  45. Jimenez Alvarez L, Zuniga J, Gaxiola M, Checa M, Becerril C, Mendoza F, et al. Inflammatory response and dynamics of lung T cell subsets in Th1, Th2 biased and Th2 deficient mice during the development of hypersensitivity pneumonitis. Exp Mol Pathol. 2010;88:407-15 pubmed publisher
    ..These results confirm a predominant role of the Th1 response in HP and suggest that the control of inflammation by Th2 biased mice may be related with the increase of NKT DN cells and regulatory NK and gammadelta T cells. ..
  46. Shirai T, Ikeda M, Morita S, Asada K, Suda T, Chida K. Elevated alveolar nitric oxide concentration after environmental challenge in hypersensitivity pneumonitis. Respirology. 2010;15:721-2 pubmed publisher
    ..It suggested a diagnosis of environmentally induced HP. The clinical value of measuring alveolar NO as an acute-phase reactant in HP is demonstrated in this patient. ..
  47. Aebischer C, Frey U, Schöni M. Hypersensitivity pneumonitis in a five-year-old boy: an unusual antigen source. Pediatr Pulmonol. 2002;33:77-8 pubmed
  48. Cordeiro C, Jones J, Alfaro T, Ferreira A. Bronchoalveolar lavage in occupational lung diseases. Semin Respir Crit Care Med. 2007;28:504-13 pubmed
  49. Guillot M, Bertoletti L, Deygas N, Raberin H, Faure O, Vergnon J. [Dry sausage mould hypersensitivity pneumonitis: three cases]. Rev Mal Respir. 2008;25:596-600 pubmed
    ..Exposure to dry sausage mould occurs in work places where salami is made and should be considered as a possible cause of hypersenstitivity pneumonitis. ..
  50. Thonhofer R, Maercker C, Popper H. Expression of sarcoidosis related genes in lung lavage cells. Sarcoidosis Vasc Diffuse Lung Dis. 2002;19:59-65 pubmed
    ..inflammatory messages, we compared gene expression in sarcoidosis with that of tuberculosis and extrinsic allergic alveolitis. After normalization genes up- or downregulated for a factor of at least 1.8 were further analyzed...
  51. Thornburg A, Abonour R, Smith P, Knox K, Twigg H. Hypersensitivity pneumonitis-like syndrome associated with the use of lenalidomide. Chest. 2007;131:1572-4 pubmed
  52. Ndiaye M, Soumah M, Sow M. [Actualities in extrinsic allergic alveolities or hypersensitivity pneumonitis]. Dakar Med. 2007;52:31-6 pubmed
    Significant advances have been noticed in the pathogenesis and the diagnosis of extrinsic allergic alveolitis during the last few years...
  53. Cardoso L, Oliveira S, Goes A, Oliveira R, Pacífico L, Marinho F, et al. Schistosoma mansoni antigens modulate the allergic response in a murine model of ovalbumin-induced airway inflammation. Clin Exp Immunol. 2010;160:266-74 pubmed publisher