Hypersensitivity Pneumonitis

Authored by , Reviewed by Dr Hayley Willacy | Last edited | Meets Patient’s editorial guidelines

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Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.

Synonym: extrinsic allergic alveolitis

In hypersensitivity pneumonitis (HP) - now the preferred term for extrinsic allergic alveolitis -  there is diffuse, granulomatous inflammation of the lung parenchyma and airways in people who have been sensitised by repeated inhalation of organic antigens in dusts (eg, from dairy or grain products, animal dander and protein and water reservoir vapourisers)[1].

There are acute, subacute and chronic forms. Acute and subacute forms cause a pneumonitis which can be recurrent. Chronic disease can cause fibrosis, emphysema and permanent lung damage[2].

See also the separate Pneumonitis and Occupational Asthma articles.

The pathogenesis is thought to involve both cell-mediated and immune complex-mediated hypersensitivity reactions[1]. There may also be a genetic predisposition[3]. It has been suggested that a possible viral trigger may initiate a flare. Radiology and pathology examinations of patients with COVID-19 virus infection revealed inflammatory reactions in the lung that resembled what is observed in hypersensitivity pneumonitis rather than in other viral pneumonia[4].

Implicated antigens include avian antigens, mammalian proteins, fungi and fungal spores, bacterial antigens and small-molecular-weight chemicals[5]. However, the provoking antigen can sometimes be difficult to identify with certainty.

It can be associated with many occupations and hobbies. Examples are[6]:

  • Farmer's lung - one of the most common forms. Due to exposure to mouldy hay. The major antigen is Saccharopolyspora rectivirgula.
  • Bird-fancier's lung - one of the most common forms. Due to exposure to avian proteins - eg, pigeons, parakeets.
  • Cheese-worker's lung - exposure to cheese mould, Penicillium casei.
  • Malt worker's lung - exposure to Aspergillus clavatus in mouldy malt.
  • Hot tub lung - exposure to Mycobacterium avium in poorly-maintained hot tubs[7].
  • Chemical worker's lung - trimellitic anhydride, diisocyanate and methylene diisocyanate act as the antigens during the manufacture of plastics, polyurethane foam and rubber.
  • Mushroom worker's lung - exposure to thermophilic actinomycetes in mushroom compost[7].
  • A large UK study of the interstitial lung disease board (2005-2016) and occupational lung disease database (2002-2016) revealed 174 cases of HP classified as 6% acute, 32% subacute and 60% chronic. The mean age was 62, distributed equally between the genders. The most common causes were cryptogenic (48%), occupational (28%, including metalworking fluid=21%) and non-occupational (24% including avian=15%, drugs=6%)[8].
  • If cases complicating COVID-19 are included, this will alter the epidemiology of this condition significantly.
  • It is usually a disease of adults but bird fancier's lung can occasionally present in children[9].
  • Pre-existing lung disease.
  • Specific occupations (including farmers, cattle workers, ventilation system workers, vets, people working with grain and flour, those whose job involves working with chemicals).
  • Bird keeping and other hobbies.
  • Regular use of hot tubs.

Acute form

  • Symptoms usually start 4-8 hours after exposure to the sensitising antigen and resolve quickly, usually within days .
  • There is a flu-like illness with fever, chest tightness, dry cough and dyspnoea. Associated symptoms include malaise, chills, headache, generalised aches and pains, anorexia and tiredness.
  • Symptoms are directly related to level of exposure, and low-level acute exposure may produce mild symptoms that last for just a few hours.
  • Signs include fever, tachypnoea and bibasal fine inspiratory crackles. Wheeze is rare .
  • In very severe cases, patients may develop life-threatening respiratory failure with cyanosis, respiratory distress at rest and high fever.

Subacute or intermittent form

  • Symptoms tend to be less severe and more gradual in onset with a productive cough, dyspnoea, fatigue, anorexia and weight loss[11].
  • There may be a history of repeated acute attacks.
  • It can present as recurrent pneumonia.
  • Signs are similar to above.
  • Severe episodes can be life-threatening.
  • After the exposure is removed it can take weeks or months for symptoms to resolve[11].

Chronic form

  • In the chronic form there are often no systemic symptoms except weight loss and gradual diminution of exercise tolerance due to dyspnoea.
  • If the source of the antigen is removed, there may only be partial improvement of symptoms[11].
  • Cyanosis and clubbing may develop.
  • Tachypnoea, obvious respiratory distress and inspiratory crackles over the lower lung fields may be present[12].
  • Eventually there may be chronic hypoxaemia and pulmonary hypertension with right heart failure.
  • There may also be acute exacerbations in those with chronic disease[13, 14].
  • Infection (bacterial, fungal, viral including tuberculosis).
  • Connective tissue disorders causing interstitial lung disease.
  • Pulmonary fibrosis (including idiopathic).
  • Asthma.
  • Sarcoidosis.
  • Histoplasmosis.
  • Drug-induced interstitial lung disease.

History

  • Good history-taking is essential to aid diagnosis. A high index of suspicion is needed.
  • Sensitisation can occur after a period of exposure to the antigen, varying from weeks to years.
  • Be alert to occupation, pets, hobbies and environmental factors in those who present with chronic cough and respiratory symptoms or acute symptoms with no obvious infectious trigger[15].
  • Also remember that water damage to the patient's home or school may precipitate symptoms as well as the use of a hot tub, sauna or swimming pool[11].

Investigations

  • Blood tests: inflammatory markers may be raised but are nonspecific. There may be serum antibodies detectable in some patients but there are no detectable antibodies in many. The presence of antibodies is nonspecific, as they may also occur in those who have been exposed but have no disease. Despite the pitfalls of false positives and false negatives, analysis of antigen-specific IgG antibodies can be useful as supportive evidence for diagnosis. The antibody titre level may also be helpful[16].
  • CXR: in the acute form this may be normal in some or show diffuse micronodular interstitial shadowing. In the subacute form, there may be micronodular or reticular opacities in the mid/upper lung fields. In the chronic form, there may be features of fibrosis with loss of lung volume[17].
  • CT scanning: high-resolution CT is a good way to evaluate the stage of disease and usually shows typical changes[17].
  • Lung function testing: this can be normal but can sometimes help to determine the degree of respiratory impairment. Spirometry shows a restrictive defect in acute and subacute forms but there may be a mixed restrictive/obstructive picture in the chronic form. Oxygen saturation may be reduced with further desaturation on exercise. There may also be reduced capacity of the lungs to diffuse carbon monoxide[18].
  • Inhalation challenge test (provocation testing): temperature, circulating neutrophil and lymphocytes, lung function and exercise tests are performed after inhaling the suspected allergen. This can produce symptoms and should only be performed in specialised centres[1].
  • Bronchoalveolar lavage: analysis of the lymphocyte count and CD4/CD8 cell ratio in bronchoalveolar lavage fluid may aid diagnosis. There is usually a lymphocytosis and the CD4/CD8 ratio is reduced to less than 1[17].
  • Transbronchial or open lung biopsy: this may show characteristic histopathological features.
  • In acute severe cases with significant respiratory distress and/or the presence of cyanosis, consider immediate referral to hospital for further assessment.
  • Supplemental oxygen should be given to treat hypoxaemia.
  • In less severe acute cases, or in the chronic form, avoidance of exposure to the allergen, along with investigations to confirm or refute the diagnosis should be carried out, usually in conjunction with a respiratory specialist.
  • Once the diagnosis is made it is important to avoid allergen exposure. This may require a change of job. Before such a drastic step, consultation with a respiratory consultant or specialist in occupational medicine may be prudent.
  • In the acute form, simply avoiding further exposure will usually result in recovery without medication.
  • Corticosteroids may be indicated for the treatment of severe acute and subacute forms and for chronic forms that are severe or progressive . However, steroids don't seem to alter the long-term outcome . Exposure to the offending antigen still needs to be avoided as well .
  • In advanced chronic disease, pulmonary fibrosis can still progress and death can occur despite aggressive corticosteroid therapy .
  • Azathioprine and mycophenolate mofetil have been used as steroid-sparing agents and also in resistant cases.
  • Other treatments tried are rituximab and leflunomide have also been reported in small studies to be of benefit. 
  • In chronic HP with progressive fibrosis, antifibrotic agents have been suggested.
  • Lung transplantation has also improved medium-term survival rates in chronic HP.

These can include:

  • Early recognition and control of exposure are key to outcome.
  • In acute and subacute forms, most patients recover lung function completely when exposure to the antigen stops. However, this may take several years for subacute forms.
  • Bird fancier's lung has a worse prognosis than farmer's lung[19].
  • The chronic form may be progressive and irreversible and result in debilitating fibrotic lung disease with high mortality rates[20].
  • Health and Safety measures at work, including wearing appropriate protective equipment and having adequate air filters and ventilation.
  • Avoiding pastimes which provoke the illness.
  • Adequate maintenance of hot tubs/indoor swimming pools, humidifiers, heating, ventilation and air-conditioning equipment.

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Further reading and references

  • Ito T, Sugino K, Satoh D, et al; Bird fancier's lung which developed in a pigeon breeder presenting organizing pneumonia. Intern Med. 201049(23):2605-8. Epub 2010 Dec 1.

  • Creamer AW, Barratt SL; Prognostic factors in chronic hypersensitivity pneumonitis. Eur Respir Rev. 2020 May 1529(156). pii: 29/156/190167. doi: 10.1183/16000617.0167-2019. Print 2020 Jun 30.

  • Kumar R, Singh M; Bird fancier's lung: clinical-radiological presentation in 15 cases. Pneumonol Alergol Pol. 201583(1):39-44. doi: 10.5603/PiAP.2015.0005.

  1. Chandra D et al; Hypersensitivity Pneumonitis., StatPearls, 2020.

  2. Magee AL, Montner SM, Husain A, et al; Imaging of Hypersensitivity Pneumonitis. Radiol Clin North Am. 2016 Nov54(6):1033-1046. doi: 10.1016/j.rcl.2016.05.013. Epub 2016 Aug 11.

  3. Woda BA; Hypersensitivity pneumonitis: an immunopathology review. Arch Pathol Lab Med. 2008 Feb132(2):204-5.

  4. Song YG, Shin HS; COVID-19, A Clinical Syndrome Manifesting as Hypersensitivity Pneumonitis. Infect Chemother. 2020 Mar52(1):110-112. doi: 10.3947/ic.2020.52.1.110. Epub 2020 Mar 10.

  5. Selman M; Hypersensitivity pneumonitis: a multifaceted deceiving disorder. Clin Chest Med. 2004 Sep25(3):531-47, vi.

  6. Lacasse Y, Cormier Y; Hypersensitivity pneumonitis. Orphanet J Rare Dis. 2006 Jul 31:25.

  7. Hypersensitivity pneumonitis; Haz-Map, 2018.

  8. Walters GI, Mokhlis JM, Moore VC, et al; Characteristics of hypersensitivity pneumonitis diagnosed by interstitial and occupational lung disease multi-disciplinary team consensus. Respir Med. 2019 Aug155:19-25. doi: 10.1016/j.rmed.2019.06.026. Epub 2019 Jun 29.

  9. Stauffer Ettlin M, Pache JC, Renevey F, et al; Bird breeder's disease: a rare diagnosis in young children. Eur J Pediatr. 2006 Jan165(1):55-61. Epub 2005 Nov 4.

  10. Wang LJ, Cai HR, Xiao YL, et al; Clinical characteristics and outcomes of hypersensitivity pneumonitis: a population-based study in China. Chin Med J (Engl). 2019 Jun 5132(11):1283-1292. doi: 10.1097/CM9.0000000000000256.

  11. Ismail T, McSharry C, Boyd G; Extrinsic allergic alveolitis. Respirology. 2006 May11(3):262-8.

  12. Lacasse Y, Selman M, Costabel U, et al; Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med. 2003 Oct 15168(8):952-8. Epub 2003 Jul 3.

  13. Miyazaki Y, Tateishi T, Akashi T, et al; Clinical predictors and histologic appearance of acute exacerbations in chronic hypersensitivity pneumonitis. Chest. 2008 Dec134(6):1265-70. Epub 2008 Aug 8.

  14. Olson AL, Huie TJ, Groshong SD, et al; Acute exacerbations of fibrotic hypersensitivity pneumonitis: a case series. Chest. 2008 Oct134(4):844-50.

  15. Mohr LC; Hypersensitivity pneumonitis. Curr Opin Pulm Med. 2004 Sep10(5):401-11.

  16. McSharry C, Dye GM, Ismail T, et al; Quantifying serum antibody in bird fanciers' hypersensitivity pneumonitis. BMC Pulm Med. 2006 Jun 266:16.

  17. Magee AL, Montner SM, Husain A, et al; Imaging of Hypersensitivity Pneumonitis. Radiol Clin North Am. 2016 Nov54(6):1033-1046. doi: 10.1016/j.rcl.2016.05.013. Epub 2016 Aug 11.

  18. Riario Sforza GG, Marinou A; Hypersensitivity pneumonitis: a complex lung disease. Clin Mol Allergy. 2017 Mar 715:6. doi: 10.1186/s12948-017-0062-7. eCollection 2017.

  19. Chan AL, Juarez MM, Leslie KO, et al; Bird fancier's lung: a state-of-the-art review. Clin Rev Allergy Immunol. 2012 Aug43(1-2):69-83. doi: 10.1007/s12016-011-8282-y.

  20. Solaymani-Dodaran M, West J, Smith C, et al; Extrinsic allergic alveolitis: incidence and mortality in the general population. QJM. 2007 Apr100(4):233-7. Epub 2007 Feb 16.

Has anyone been diagnosed with pleuroparnchymal fibroelastosis (PPFE). Pulmonologist and radiologist think I might have it. Not much written on it - fairly new to the medical community, I believe....

CherylH
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