Farmer's Lung

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Background

Farmer's lung is a type of hypersensitivity pneumonitis. Hypersensitivity pneumonitis, also known as extrinsic allergic alveolitis, is an immunologically mediated inflammatory disease of the lung involving the terminal airways. The condition is associated with intense or repeated exposure to inhaled biologic dusts. The classic presentation of farmer's lung results from inhalational exposure to thermophilic Actinomyces species and occasionally from exposure to various Aspergillus species.

The effect of these antigens in farmers was described as early as 1713. In Britain in 1932, Campbell described a disorder of the lung caused by inhalation of dust from moldy hay. In 1964, Ramazzini and Wright[1] described workers getting "diseases of the chest."

Thermophilic actinomycetes species include Saccharopolyspora rectivirgula (formerly Micropolyspora faeni), Thermoactinomyces vulgaris, Thermoactinomyces viridis, and Thermoactinomyces sacchari, among others.[2] These organisms flourish in areas of high humidity and prefer temperatures of 40-60°C.

The thermophilic actinomycetes are ubiquitous organisms usually found in contaminated ventilation systems and in decaying compost, hay, and sugar cane (bagasse). Exposure to large quantities of contaminated hay is the most common source of inhalational exposure for farmers who develop farmer's lung; therefore, grain farmers are not at risk for the development of the disease. Farmer's lung is often a disease of dairy farmers who handle contaminated hay during the winter months. Most cases of farmer's lung occur in cold, damp climates in late winter and early spring when farmers use stored hay to feed their livestock.

Exposure to the causative antigens depends on the type of farming, industry, and climate in the area. Note that farming practices are changing with time and that new antigens may be introduced or disappear from a region (eg, the disappearance of bagassosis in Louisiana sugar cane workers,[3] the appearance of Pseudomonas fluorescens in machine operator's lung). The dynamic nature of this disease and the changing environment may lead to new challenges for the clinician.

In addition to the inhalational exposure to the organic dusts responsible for the hypersensitivity reaction in farmer's lung disease, allergens, chemicals, toxic gases, and infectious agents must also be considered as potential triggers of airway symptoms in symptomatic farmers. Farming is currently ranked as one of the top 3 most hazardous occupations, along with construction and mining.[4, 5]

Pathophysiology

The pathogenesis of farmer's lung depends on the intensity, frequency, and duration of exposure and on host response to the causative antigen. Both humoral and cell-mediated immune responses seem to play a role in pathogenesis. During acute episodes, acute neutrophilic infiltration is followed by lymphocytic infiltration of the airways. Levels of interleukins 1 and 8 and tumor necrosis factor-alpha are increased.[6] These cytokines have proinflammatory and chemotactic properties. They cause the recruitment of additional inflammatory mediators, resulting in direct cellular damage and changes in the complement pathway, which provide the necessary stimuli to increase vascular permeability and migration of leukocytes to the lung.[7, 8]

If the acute exposure is large, a dramatic increase in inflammation leads to increased vascular permeability, which can alter the alveolar capillary units, thus promoting hypoxemia and decreased lung compliance. If the exposure is prolonged and continuous, collagen deposition and destruction of the lung parenchyma occur with resultant decreased lung volumes.

Strong evidence suggests the involvement of immune complex–induced tissue injury (type III hypersensitivity). The timing of development of symptoms after exposure supports this conclusion. The presence of antigen-specific immunoglobulin and complement activation and deposition in the lung also supports immune-complex or type III hypersensitivity in the pathogenesis of farmer's lung.

Cell-mediated, delayed-type hypersensitivity (type IV hypersensitivity) also plays a major role in the pathogenesis of this syndrome. The presence of lymphocytes, macrophages, and granulomas in the alveolar spaces and the interstitium supports this conclusion.

Epidemiology

Frequency

United States

Farmer's lung is one of the most frequent types of hypersensitivity pneumonitis. Note the following:

International

The prevalence of farmer's lung in the United Kingdom has been reported to be 420-3000 cases per 100,000 at-risk persons. Note the following:

Mortality/Morbidity

The mortality rate from farmer's lung is reportedly 0-20%. Note the following:

History

The clinical syndrome of farmer's lung, as with other types of hypersensitivity pneumonitis, is categorized as acute, subacute, or chronic.

Acute farmer's lung develops after large exposure to moldy hay or contaminated compost. Symptoms often spontaneously resolve within 12 hours to days if antigen exposure is eliminated or avoided. Acute farmer's lung manifests as new onset of fever, chills, nonproductive cough, chest tightness, dyspnea, headache, and malaise. If the inhalational exposure is large, patients may develop acute respiratory failure.

Subacute farmer's lung manifests as chronic cough, dyspnea, anorexia, and weight loss. Subacute disease is insidious in onset and may occur over weeks to months.

Chronic farmer's lung results from prolonged and continuous exposure to the antigen. Patients may have irreversible lung damage.  Patients may experience severe dyspnea at rest or with exertion.

Physical

In acute farmer's lung, physical findings are as follows:

In subacute farmer's lung, physical findings are as follows:

In chronic farmer's lung, physical findings are as follows:

Causes

Thermophilic actinomycetes species include the following:

Laboratory Studies

No single diagnostic or clinical laboratory study is specific to the diagnosis of farmer's lung. The most important diagnostic tool is a detailed environmental history. Note the following:

Imaging Studies

Chest radiography

Findings are normal between acute attacks. Findings are abnormal during acute and subacute stages of disease.

Diffuse air-space consolidation is typical of acute farmer's lung (with acute antigen exposure). Nodular or reticulonodular pattern is characteristic of the subacute phase. Linear radiodensities may be discovered and indicate areas of fibrosis from previous attacks.

Pulmonary apices are often spared on plain chest radiography.

High-resolution computed tomography

High resolution CT scanning is a superior diagnostic modality compared with plain radiography. A normal finding on high-resolution CT scans eliminates the possibility of active acute or chronic farmer's lung.

Pulmonary fibrosis with honeycombing is observed in chronic disease. Peri-bronchovascular distribution of nodules with ground-glass attenuation may be observed.

 

Other Tests

Pulmonary function tests

Spirometry findings may be normal between attacks and before the development of chronic disease. Acute, subacute, and chronic forms of farmer's lung have a restrictive ventilatory pattern with reduced forced vital capacity (FVC), reduced total lung capacity (TLC), and preserved airflow.

Mild-to-severe hypoxemia at rest or during minimal exercise may be present with active disease. Decreased diffusion capacity is present with active disease.

Procedures

Bronchoscopy

Open lung biopsy

Histologic Findings

Chronic interstitial inflammation is present with infiltration of plasma cells, mast cells, histiocytes, and lymphocytes. Small and poorly organized nonnecrotizing granulomas are present, usually adjacent to bronchioles. Interstitial fibrosis is often present in chronic disease. Changes consistent with bronchiolitis obliterans may be evident. Guidelines for diagnosis of farmer's lung are as follows:

Medical Care

Systemic corticosteroid administration and avoidance measures constitute the primary treatment for farmer's lung.

Diet

No dietary restrictions are needed.

Activity

Patients may decrease activity because of cough and dyspnea on exertion. In a patient with acute farmer's lung, pulmonary function improves once antigen exposure is eliminated. Between episodes of acute disease, activity may be unlimited.

Medication Summary

Systemic corticosteroids (combined with avoidance measures) are the primary agents used to treat farmer's lung.

Nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, cromolyn, nedocromil) or systemic immune modulators are not indicated for treatment at this time.

Prednisone (Deltasone, Orasone, Meticorten)

Clinical Context:  Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Prescribed for severe symptoms or significant lung dysfunction despite antigen avoidance.

Class Summary

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Further Outpatient Care

Outpatient care includes the following:

Further Inpatient Care

Inpatient care includes the following:

Deterrence/Prevention

Complete avoidance of the antigen is indicated. Consider the following:

Complications

Complications of farmer's lung include the following:

Prognosis

The long-term prognosis of farmer's lung varies and depends on the extent of fibrosis and the amount of irreversible damage to the lung parenchyma.[19]  Consider the following:

Patient Education

Environmental control and complete avoidance of the antigen should be the goal. Complete avoidance of the environment or farm may be required to ensure prevention of chronic disease and survival.

Many farmers have thought that salting the hay can prevent the growth of molds in the hay. However, salting does not prevent the growth of molds. The use of salt does not significantly decrease the amount of Saccharopolyspora rectivirgula (the actinomycetes most commonly involved in farmer's lung disease), or Absidia corymbifera, Eurotium amstelodami, and Wallemia sebi, 3 molds responsible for farmer's lung disease in Europe. Therefore, palatable hay is not safe hay.

For patient education information, see Bronchoscopy.

Author

Laurianne G Wild, MD, FAAAAI, FACAAI, Chief and Professor of Medicine, Section of Clinical Immunology, Allergy and Rheumatology, Co-Director, Allergy and Immunology Fellowship Training Program, Tulane University School of Medicine; Director, Allergy and Immunology Clinic, Southeast Louisiana Veterans Health Care System of New Orleans

Disclosure: Nothing to disclose.

Coauthor(s)

Eduardo E Chang, MD, Fellow, Department of Allergy and Immunology, Tulane University

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP, Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba Faculty of Medicine; Site Director, Respiratory Medicine, St Boniface General Hospital, Canada

Disclosure: Nothing to disclose.

Acknowledgements

Gregg T Anders, DO Medical Director, Great Plains Regional Medical Command , Brooke Army Medical Center; Clinical Associate Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Science Center at San Antonio

Disclosure: Nothing to disclose.

References

  1. Ramazzini B, Wright WC, eds. De Morbis Artificium [Diseases of Workers]. New York, NY: Hafner Publishing; 1964.
  2. Barrera C, Valot B, Rognon B, Zaugg C, Monod M, Millon L. Draft genome sequence of the principal etiological agent of farmer's lung disease, Saccharopolyspora rectivirgula. Genome Announc. 2014 Dec 18. 2(6):[View Abstract]
  3. Lehrer SB, Turer E, Weill H, Salvaggio JE. Elimination of bagassosis in Louisiana paper manufacturing plant workers. Clin Allergy. 1978 Jan. 8(1):15-20. [View Abstract]
  4. Liu S, Chen D, Fu S, et al. Prevalence and risk factors for farmer's lung in greenhouse farmers: an epidemiological study of 5,880 farmers from Northeast China. Cell Biochem Biophys. 2015 Mar. 71(2):1051-7. [View Abstract]
  5. Barrera C, Millon L, Rognon B, et al. Immunoreactive proteins of Saccharopolyspora rectivirgula for farmer's lung serodiagnosis. Proteomics Clin Appl. 2014 Dec. 8(11-12):971-81. [View Abstract]
  6. Ashitani J, Kyoraku Y, Yanagi S, Matsumoto N, Nakazato M. Elevated levels of beta-D-glucan in bronchoalveolar lavage fluid in patients with farmer's lung in Miyazaki, Japan. Respiration. 2008. 75(2):182-8. [View Abstract]
  7. Deschenes D, Provencher S, Cormier Y. Farmer's lung-induced hypersensitivity pneumonitis complicated by shock. Respir Care. 2012 Mar. 57(3):464-6. [View Abstract]
  8. Bellanger AP, Reboux G, Botterel F, et al. New evidence of the involvement of Lichtheimia corymbifera in farmer's lung disease. Med Mycol. 2010 Nov. 48(7):981-7. [View Abstract]
  9. Hanak V, Golbin JM, Ryu JH. Causes and presenting features in 85 consecutive patients with hypersensitivity pneumonitis. Mayo Clin Proc. 2007 Jul. 82(7):812-6. [View Abstract]
  10. Depierre A, Dalphin JC, Pernet D, et al. Epidemiological study of farmer's lung in five districts of the French Doubs province. Thorax. 1988 Jun. 43(6):429-35. [View Abstract]
  11. Malmberg P, Rask-Andersen A, Palmgren U, Hoglund S, Kolmodin-Hedman B, Stalenheim G. Exposure to microorganisms, febrile and airway-obstructive symptoms, immune status and lung function of Swedish farmers. Scand J Work Environ Health. 1985 Aug. 11(4):287-93. [View Abstract]
  12. Kokkarinen J, Tukiainen H, Terho EO. Mortality due to farmer's lung in Finland. Chest. 1994 Aug. 106(2):509-12. [View Abstract]
  13. Arya A, Roychoudhury K, Bredin CP. Farmer's lung is now in decline. Ir Med J. 2006 Jul-Aug. 99(7):203-5. [View Abstract]
  14. Cormier Y, Belanger J. The fluctuant nature of precipitating antibodies in dairy farmers. Thorax. 1989 Jun. 44(6):469-73. [View Abstract]
  15. Arshad M, Braun SR, Sunderrajan EV. Severe hypoxemia in farmer's lung disease with normal findings on chest roentgenogram. Chest. 1987 Feb. 91(2):274-5. [View Abstract]
  16. Monkare S, Ikonen M, Haahtela T. Radiologic findings in farmer's lung. Prognosis and correlation to lung function. Chest. 1985 Apr. 87(4):460-6. [View Abstract]
  17. Cormier Y, Brown M, Worthy S, Racine G, Muller NL. High-resolution computed tomographic characteristics in acute farmer's lung and in its follow-up. Eur Respir J. 2000 Jul. 16(1):56-60. [View Abstract]
  18. Roussel S, Reboux G, Dalphin JC, Laplante JJ, Piarroux R. Evaluation of salting as a hay preservative against farmer's lung disease agents. Ann Agric Environ Med. 2005. 12(2):217-21. [View Abstract]
  19. Barbee RA, Callies Q, Dickie HA, Rankin J. The long-term prognosis in farmer's lung. Am Rev Respir Dis. 1968 Feb. 97(2):223-31. [View Abstract]
  20. Ohtsuka Y, Munakata M, Tanimura K, et al. Smoking promotes insidious and chronic farmer's lung disease, and deteriorates the clinical outcome. Intern Med. 1995 Oct. 34(10):966-71. [View Abstract]
  21. Thorshauge H, Fallesen I, Ostergaard PA. Farmer's lung in infants and small children. Allergy. 1989 Feb. 44(2):152-5. [View Abstract]
  22. Lacasse Y, Fraser RS, Fournier M, Cormier Y. Diagnostic accuracy of transbronchial biopsy in acute farmer's lung disease. Chest. 1997 Dec. 112(6):1459-65. [View Abstract]
  23. Takahashi T, Munakata M, Ohtsuka Y, et al. Serum KL-6 concentrations in dairy farmers. Chest. 2000 Aug. 118(2):445-50. [View Abstract]
  24. Nakagawa-Yoshida K, Ando M, Etches RI, Dosman JA. Fatal cases of farmer's lung in a Canadian family. Probable new antigens, Penicillium brevicompactum and P olivicolor. Chest. 1997 Jan. 111(1):245-8. [View Abstract]
  25. Imai K, Ashitani J, Imazu Y, et al. [Farmer's lung cases of a farmer and his son with high BAL fluid beta-D glucan levels]. Nihon Kokyuki Gakkai Zasshi. 2004 Dec. 42(12):1024-9. [View Abstract]
  26. Ando M, Suga M. Hypersensitivity pneumonitis. Curr Opin Pulm Med. 1997 Sep. 3(5):391-5. [View Abstract]
  27. 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 Sep. 152(3):997-1002. [View Abstract]
  28. Cormier Y, Belanger J. Long-term physiologic outcome after acute farmer's lung. Chest. 1985 Jun. 87(6):796-800. [View Abstract]
  29. Emanuel DA, Kryda MJ. Farmer's lung disease. Clin Rev Allergy. 1983 Dec. 1(4):509-32. [View Abstract]
  30. Fink JN, Zacharisen MC. Hypersensitivity pneumonitis. Middleton E Jr, Reed CE, Ellis EF, Adkinson NF Jr, Yunginger JW, Busse WW, eds. Allergy Principles and Practice. 5th ed. St. Louis, Mo: Mosby; 1998. 994-1004.
  31. Fink JN. Hypersensitivity pneumonitis. Clin Chest Med. 1992 Jun. 13(2):303-9. [View Abstract]
  32. Fraser RG, Pare JA. Diagnosis of Diseases of the Chest. 3rd ed. Philadelphia, Pa: WB Saunders; 1989. 1273-90.
  33. Gay J, Donham KJ, Leonard S. Iowa Agricultural Health and Safety Service Project. Am J Ind Med. 1990. 18(4):385-9. [View Abstract]
  34. Kaltreider HB. Hypersensitivity pneumonitis. West J Med. 1993 Nov. 159(5):570-8. [View Abstract]
  35. Kline JN, Schwartz DA. Agricultural dust-induced lung disease. Rom WN, ed. Environmental Occupational Medicine. Philadelphia, Pa: Lippincott Raven; 1998. 565-71.
  36. Kokkarinen JI, Tukiainen HO, Terho EO. Recovery of pulmonary function in farmer's lung. A five-year follow-up study. Am Rev Respir Dis. 1993 Apr. 147(4):793-6. [View Abstract]
  37. 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 Jul. 148(1):216-21. [View Abstract]
  38. Myers ML. Health problems and disease patterns in agriculture. Encyclopedia of Occupational Health Safety. Geneva, Switzerland: International Labour Office; 1997.
  39. Patel AM, Ryu JH, Reed CE. Hypersensitivity pneumonitis: current concepts and future questions. J Allergy Clin Immunol. 2001 Nov. 108(5):661-70. [View Abstract]
  40. Patterson R, Greenberger PA, Castile RG, et al. Diagnostic problems in hypersensitivity lung disease. Allergy Proc. 1989 Mar-Apr. 10(2):141-7. [View Abstract]
  41. Salvaggio JE. Extrinsic allergic alveolitis (hypersensitivity pneumonitis): past, present and future. Clin Exp Allergy. 1997 May. 27 Suppl 1:18-25. [View Abstract]
  42. Schuyler M, Cormier Y. The diagnosis of hypersensitivity pneumonitis. Chest. 1997 Mar. 111(3):534-6. [View Abstract]
  43. Schuyler M, Gott K, Edwards B. Experimental hypersensitivity pneumonitis: cellular requirements. Clin Exp Immunol. 1996 Jul. 105(1):169-75. [View Abstract]
  44. Wiatr E, Radzikowska E, Pawlowski J. [Pulmonary fibrosis in young patients with hypersensitivity pneumonitis]. Pneumonol Alergol Pol. 2004. 72(3-4):111-6. [View Abstract]
  45. Wild LG. Hypersensitivity pneumonitis: A childhood disease?. Pediatr Asth Allergy. 2000. 14:57-75.
  46. Wild LG, Lopez M. Hypersensitivity pneumonitis: a comprehensive review. J Investig Allergol Clin Immunol. 2001. 11(1):3-15. [View Abstract]
  47. Rognon B, Reboux G, Roussel S, et al. Western blotting as a tool for the serodiagnosis of farmer's lung disease: validation with Lichtheimia corymbifera protein extracts. J Med Microbiol. 2015 Apr. 64(Pt 4):359-68. [View Abstract]