20th February 2025

Hypersensitivity pneumonitis

Overview of HP

Hypersensitivity pneumonitis (HP) is characterised by granulomatous lung inflammation due to various inhaled organic antigens. It involves immune complex and cell-mediated (types III and IV hypersensitivity reactions) tissue damage.

Exposure to organic antigens may result from various hobbies or occupations, which often provide the name for different subtypes of HP:

• Farmer’s lung – due to exposure to Saccharopolyspora rectivirgula in mouldy hay
• Bird-fancier’s lung – due to exposure to avian proteins on bird feathers and droppings
• Cheese-worker’s lung – due to exposure to Penicillium casei in cheese mould
• Malt-worker’s lung – due to exposure to Aspergillus clavatus in mouldy malt
• Mushroom-worker’s lung – due to exposure to thermophilic actinomycetes in mushroom compost
• Chemical-worker’s lung – due to exposure to trimellitic anhydride, diisocyanate and methylene diisocyanate in the manufacture of plastics, polyurethane foam and rubber
• Hot-tub lung – due to exposure to Mycobacterium avium in hot tubs

Traditionally, HP is divided into acute and chronic forms. The acute form, which develops after a short period of exposure to the antigen, causes pneumonitis. The chronic form, which requires longer exposure to the causative organism, tends to cause fibrosis and emphysema.

Signs and symptoms of HP

Acute (4-8 h after exposure): fever, dry cough, dyspnoea. Examination reveals crackles and squeaks on the chest and sometimes wheeze. If exposure ceases, symptoms often settle within a few days.

Chronic (weeks-months after exposure): cough, dyspnoea, weight loss, anorexia and reduced exercise tolerance. Cyanosis and clubbing may develop, as well as inspiratory crackles in the lower lung fields on auscultation. Chronic hypoxaemia may lead to pulmonary hypertension with right heart failure. Patients can experience acute-on-chronic exacerbations.

Diagnosis of HP

History is essential. Investigations include:

• Bloods: inflammatory markers may be raised (lymphocytosis; non specific). Certain IgG antibodies may support the diagnosis but are not specific. Eosinophilia is not usually present as HP is not a type I hypersensitivity reaction
• CXR: Acute – can be normal or may show diffuse micronodular interstitial shadowing, sometimes with ground-glass change. Chronic – reticular pattern of fibrosis with honeycombing, which can be more severe in the upper lobes. Volume loss and peribronchial thickening may also be visible.
• High-resolution CT: Acute – bilateral, patchy ground-glass opacity and numerous round centrilobular opacities may be seen. Areas of radiolucency may occur due to air trapping. Chronic – diffuse centrilobular nodules, ground-glass change and air trapping. Honeycombing and traction bronchiectasis (predominantly upper lobes)
• Lung function tests: typically restrictive with reduced gas transfer and lung volumes, but obstruction may also be noted, particularly in chronic forms
• Bronchoalveolar lavage: lymphocytosis and a CD4:CD8 ratio <1

Management of HP

Antigen exposure avoidance is key. Supportive therapies include oxygen and bronchodilators.

Corticosteroids may be useful to alleviate symptoms but do not have an effect on the long-term outcome of the condition.

Lung transplantation may be considered, although if re-exposure occurs, the patient may develop severe damage to the transplanted lung. 

See note on nintedanib – this has now been approved as a treatment option for chronic progressive fibrosing interstitial lung diseases.

References

• Chandra D, Cherian SV. Hypersensitivity Pneumonitis.  StatPearls. Treasure Island (FL)2021
• Spagnolo P, Rossi G, Cavazza A, Bonifazi M, Paladini I, Bonella F, et al. Hypersensitivity Pneumonitis: A Comprehensive Review. J Investig Allergol Clin Immunol. 2015;25(4):237-50; quiz follow 50
• Knott L. Hypersensitivity Pneumonitis 2020. Available from:  https://patient.info/doctor/extrinsic-allergic-alveolitis-pro [accessed 04/01/2022]
• Ismail T, McSharry C, Boyd G. Extrinsic allergic alveolitis. Respirology. 2006;11(3):262-8
• Hirschmann JV, Pipavath SN, Godwin JD. Hypersensitivity pneumonitis: a historical, clinical, and radiologic review. Radiographics. 2009;29(7):1921-38
• Chapman SJR, G. V.; Shrimanker, R. S.; Turnbull, C. D.; Wrightson, J. M. Oxford Handbook of Respiratory Medicine. Fourth Edition ed. Oxford, United Kingdom: Oxford University Press; 2021
• Magee AL, Montner SM, Husain A, Adegunsoye A, Vij R, Chung JH. Imaging of Hypersensitivity Pneumonitis. Radiol Clin North Am. 2016;54(6):1033-46
• NICE. Nintedanib for treating progressive fibrosing interstitial lung diseases. National Institute for Health and Care Excellence, 2021 [accessed 18/03/2024]