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Hypersensitivity pneumonitis 

Hypersensitivity pneumonitis
Chapter:
Hypersensitivity pneumonitis
Author(s):

Stephen Chapman

, Grace Robinson

, John Stradling

, Sophie West

, and John Wrightson

DOI:
10.1093/med/9780198703860.003.0028
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date: 27 October 2021

Causes

Definition

Group of lung diseases typically caused by inhalation of organic antigen to which the individual has been previously sensitized. Disease following inhalation of inorganic antigens and drug ingestion is also reported. Hypersensitivity pneumonitis (HP; previously termed extrinsic allergic alveolitis) is often divided into ‘acute’ and ‘chronic’ forms, based on the time course of presentation. Acute HP often follows a short period of exposure to a high concentration of antigen and is usually reversible. Chronic HP typically follows a period of chronic exposure to a low antigen dose and is less reversible. These two presentations may overlap, and ‘subacute’ forms of the disease are recognized.

Epidemiology

Exact prevalence unknown. At least 8% of budgerigar and pigeon keepers and up to 5% of farmers may develop HP. HP is thought to be more common in non-smokers (mechanism unclear; may reflect inhibition of alveolar macrophage function by smoke).

Causes

Many different antigens have been reported to cause HP, ranging from the relatively common (bird fancier’s lung and farmer’s lung in the UK; summer-house HP in Japan) to the more unusual and exotic (shell lung—proteins on mollusc shells; pituitary snuff-taker’s disease; sericulturist’s lung—silkworm larvae proteins; sax lung—yeast on saxophone mouthpieces). Important examples are listed in Table 28.1.

Table 28.1 Causes of HP—examples

Antigen

Sources

Diseases

Organisms

Thermophilic actinomycetes (Micropolyspora faeni, Thermoactinomyces vulgaris), Aspergillus spp.

Mouldy hay; sugar cane; compost; mushrooms; contaminated water in humidifiers and air conditioners

Farmer’s lung; bagassosis; compost lung; mushroom worker’s lung; humidifier lung

Aspergillus clavatus

Mouldy barley

Malt worker’s lung

Trichosporon cutaneum

House dust

Summer-house HP (Japan)

M. avium complex

Hot tub mist, ceiling mould

Hot tub lung

Animal protein

Bird proteins

Bloom on bird feathers and droppings

Bird fancier’s lung

Rat proteins

Rat droppings

Rat lung

Chemical

Toluene diisocyanate

Paints

Isocyanate HP

Pathophysiology

Pathogenesis of HP is not fully understood and may involve T-cell-mediated immunity and granuloma formation (type IV hypersensitivity) and/or antibody-antigen immune complex formation (type III hypersensitivity). It is not an atopic disease and is not characterized by a rise in tissue eosinophils or IgE (type I hypersensitivity); this may, in part, be due to the small particle size of offending antigens, which tend to be deposited more distally in the airspaces than the larger particles associated with asthma. Lung histology specimens typically reveal an interstitial inflammatory infiltrate, often with accompanying bronchiolitis and OP. Non-caseating granulomata are often present and typically are ill-defined and single (compared with sarcoidosis where granulomata are well defined and are grouped subpleurally or near bronchi). Chronic HP is characterized by fibrosis and often by the absence of granulomata and airways involvement, particularly if antigen exposure has ceased.

Diagnosis

Clinical features

Acute HP

  • Breathlessness, dry cough, and systemic symptoms (fever, chills, arthralgia, myalgia, headache) occur 4–8h after exposure to antigen

  • Examination: crackles and squeaks on auscultation, fever; wheeze may occur, leading to a misdiagnosis of asthma

  • In the absence of ongoing exposure, symptoms settle spontaneously within 1–3 days. Episodes may be recurrent.

Chronic HP

  • Slowly progressive exertional breathlessness, dry cough, sometimes systemic symptoms (weight loss) over the course of months to years. May be history of acute episodes

  • Examination: crackles and squeaks on auscultation, clubbing rare; may be features of cor pulmonale.

Investigations

  • Imaging: acute HP

    • CXR Diffuse, small (1–3mm) nodules or infiltrates, sometimes ground-glass change, apical sparing. Normal in up to 20% of cases

    • HRCT Patchy or diffuse ground-glass change and poorly defined micronodules. Areas of increased lucency/mosaic attenuation (enhanced on expiratory HRCT) occur due to air trapping from bronchiolar involvement

    • Both CXR and HRCT appearances may quickly normalize following removal from antigen exposure

  • Imaging: chronic HP

    • CXR Typically upper and mid-zone reticulation, reduced lung volumes

    • HRCT Diffuse centrilobular nodules, ground-glass change, mosaic attenuation from air trapping, may be honeycombing and traction bronchiectasis (may mimic appearance of UIP, although upper lobe predominance is typical in HP)

  • PFTs Typically restrictive pattern with reduced gas transfer and lung volumes; mild obstruction is also sometimes observed. May be normal. Hypoxia may occur

  • Bloods Acute HP associated with neutrophilia but not eosinophilia. Inflammatory markers often increased

  • Serum antibody (IgG) precipitin Results are presented either as an ELISA or as a number of precipitin lines, referring to the number of different epitopes an individual responds to. Precipitins to organic antigens are found in 90% of patients but are also present in up to 10% of asymptomatic farmers and 50% of pigeon breeders. Precipitin levels often fall in the absence of ongoing antigen exposure

  • BAL Lymphocytosis (often >50%) is a characteristic finding, particularly in the setting of ongoing antigen exposure but is not, in itself, diagnostic and may be found in asymptomatic exposed individuals

  • Transbronchial or surgical lung biopsy may be required in cases of diagnostic uncertainty. TBB often fails to provide sufficient tissue for adequate histological analysis

  • Inhalation antigen challenge may be unpleasant and is not recommended routinely.

Diagnosis

is based on the combination of history of antigen exposure and typical clinical and HRCT features. Atypical presentations require further investigation to support the diagnosis such as BAL lymphocytosis or characteristic histological features on lung biopsy (a bronchiolocentric granulomatous lymphocytic pneumonitis). The underlying causative antigen cannot be identified in up to 40% of cases.

Differential diagnosis

  • Atypical pneumonia

  • IIPs (particularly IPF, NSIP, RB-ILD)

  • Sarcoidosis

  • Vasculitis

  • Occupational asthma (e.g. from isocyanates)

  • Drug-induced lung disease (including pesticides)

  • Organic dust toxic syndrome (follows very high levels of exposure to agricultural dusts; symptoms transient; benign course)

  • Silo-filler’s disease (variable respiratory manifestations following exposure to nitrogen dioxide in silos; ranges from mild bronchitis to fatal bronchospasm).

Management

Management

centres on antigen avoidance, which is frequently difficult. If complete removal from antigen is unrealistic (e.g. farmers), measures to reduce exposure may be of benefit (such as respiratory protection with high-performance, positive-pressure masks; avoidance of particularly heavy exposure; improved ventilation and use of air filters; drying of hay prior to storage).

In acute HP, symptoms typically resolve following cessation of antigen exposure, and treatment is usually not required. Removal from exposure may also result in symptomatic and physiological improvement in chronic HP, although this is less certain and established pulmonary fibrosis is often irreversible.

When treatment is required, corticosteroids are frequently used, although there is a lack of randomized controlled evidence to support this. Steroids may hasten the resolution of impaired pulmonary function in acute HP, although their effect on long-term outcome is unclear; they appear to be of benefit in some cases of chronic HP. A typical regimen is prednisolone 0.5mg/kg until symptoms and radiological changes have resolved, and then slowly reduce dose over several months to a maintenance dose of approximately 10mg daily. Courses of 3–6 months may be sufficient in subacute HP, although more prolonged courses are usually required for progressive or chronic disease.

Prognosis

is highly variable. Prognosis is usually excellent following removal from antigen exposure in acute HP, although progression to respiratory failure and death may very rarely occur after short-term exposures of very high intensity. Recurrent episodes of acute HP do not necessarily progress to chronic HP and fibrosis, and chronic HP may develop in the absence of previous acute HP episodes. Development of chronic HP with ongoing exposure may eventually lead to cor pulmonale and death, although again this is variable and many patients do not exhibit disease progression despite chronic exposure. Persistent low-dose exposure (e.g. budgerigar in the house) may be more likely to progress to the chronic fibrotic form of HP than intermittent high-dose exposure (e.g. pigeon fanciers), which predisposes more to episodes of acute HP.