Hypersensitivity Pneumonitis

Chapters

 

OVERVIEW1

Hypersensitivity pneumonitis (HP) is a lung disease causing inflammation of the lung tissue and results from breathing in antigens.

Hypersensitivity pneumonitis may also be referred to as extrinsic allergic alveolitis.

HP is an inflammatory and/or fibrotic disease affecting the lung parenchyma and small airways. It typically results from an immune-mediated reaction provoked by an overt or occult inhaled antigen in susceptible individuals.

Recommended Classifications for HP2

The ATS/JRS/ALAT provided clinical practice guidelines on the diagnosis of HP.

Nonfibrotic (purely inflammatory)

  • Typical nonfibrotic HP requires one HRCT abnormality indicative of diffuse parenchymal infiltration and diffuse small airway disease

Fibrotic (mixed inflammatory plus fibrotic or purely fibrotic)

  • Typical fibrotic HP requires an HRCT pattern of lung fibrosis and at least one abnormality indicative of small airway disease

Characteristics

The following features are considered characteristic of this disease:3

  • Pulmonary disease which can be accompanied by systemic manifestations such as fever or weight loss
  • Caused by inhalation of an antigen to which the patient is sensitized, causing an overreaction of the immune system
  • Defined by exposure and sensitization to an antigen, and the presence of clinical symptoms

EPIDEMIOLOGY

Estimated prevalence of 1.7 to 2.7 cases per 100,000 people.4

  • Definite prevalence is uncertain as many cases may go undetected or undiagnosed5

Survival rates range from 2 to 18 years6,7

  • Factors such as identifiable antigens and patterns on HRCT have been shown to impact mortality6,7

PATHOGENESIS

HP is believed to be caused by an exaggerated response of the immune system to repeated inhalation of environmental pathogens.1

Hypersensitivity Pneumonitis Pathogenesis Graph

Adapted from Selman M et al.5

This pathogenicity is the result of a combination of immune complex mediated (type Ill) and delayed (type IV) hypersensitivity reactions.8

  • The main reaction early on and in HP is immune complex mediated (type III) 
  • With continual exposure the primary reaction shifts to a delayed hypersensitivity (type IV) reaction  
    • Several chemokines and proinflammatory cytokines mediate a sustained CD8 cytotoxic T-cell response which results in the tissue reaction response  
    • In addition, chemokines and cytokines play a role in macrophage activation, granuloma formation, and fibrosis  

Risk Factors

Exposure History

Most common causes are exposure to birds or fungi at home or at work.1

Agents associated with HP include fungal, bacterial, protozoal, and animal proteins, as well as low-molecular-weight chemical compounds.1

The most common causes of HP are exposure to avian antigens, or to fungi/actinomyces in the home or at work.1 The time interval between the antigen exposure and disease is months to decades.1

Patients in whom the causative antigen is identified have a better prognosis.6 However, even after eliminating the antigen exposure, disease progression often occurs.1 In addition, determining the inciting antigen can be very difficult in fibrotic HP.1

Avian antigens can remain in the home long after the bird has been removed.1

Environmental Antigens Associated with HP2

Class of Antigens Specific Antigens Sources Type of Disease
Bacteria Saccharopolyspora rectivirgula
Thermoactinomyces vulgaris		 Moldy hay and grain Farmer’s lung
Fungi/Yeasts
  • Aspergillus species
  • Trichosporon cutaneum
  • Penicillium species
  • Penicillium casei
  • Alternaria species
  • Moldy hay and grain
  • Moldy compost and mushrooms
  • Contaminated houses
  • Moldy cork
  • Moldy cheese or cheese casings
  • Contaminated wood pulp or dust
  • Farmer’s lung
  • Mushroom’s worker’s lung
  • Japanese summer-type HP
  • Suberosis
  • Cheese washer’s lung
  • Woodworker’s lung
Mycobacteria Mycobacterium avium-intracellulare
  • Mold on ceiling, Tub Water
  • Mist from pool water, sprays, and fountains
  • Hot tub lung
  • Swimming pool lung
Animal Proteins
  • Proteins in avian droppings and serum on feathers
  • Avian proteins
  • Silkworm protein
  • Birds
  • Feather beds, pillows, and duvets
  • Dust from silkworm larvae and cocoons
  • Pigeon breeder’s lung, Bird financier’s lung
  • Feather duvet lung
  • Silk production HP
Chemicals Diisocyanates
Trimellitic anhydride		 Polyurethane foams, spray paints, dyes, glues Chemical worker’s lung

Occupations and hobbies that could be risk factors for HP10

  • Bird fancier  
  • Farming  
  • Cheese worker  
  • Furrier  
  • Malt worker 
  • Many others

Genetics

HP is characterized by the upregulation of genes related to inflammation, T-cell activation, and immune responses.11 Patients with avian-antigen associated HP have a higher rate of single nucleotide polymorphisms (SNPs) within HLA-DRB1 (major histocompatibility complex, class II, DR beta 1).12

Smoking

Most patients (80%-95%) with HP are nonsmokers,13 but in smokers the disease is associated with higher mortality.14 

See also

Test your Knowledge
Test your knowledge

Take the test

Lung X-Ray Example
Rad Rounds Mobile App

Download the app

Interstitial lung disease in systemic sclerosis with a focus on chest CT

Media Library

See Media