Hypersensitivity Pneumonitis

Over 300 antigens have been identified as triggers for hypersensitivity pneumonitis. Antigens encountered through farming, birds, and water contamination account for about 75% of cases.

Antigens are commonly categorized by type and occupation (see table Examples of Hypersensitivity Pneumonitis); farmer’s lung, caused by inhalation of hay dust containing thermophilic actinomycetes, is the prototype. Substantial overlap exists between hypersensitivity pneumonitis and chronic bronchitis in farmers, in whom chronic bronchitis is far more common, occurs independently of smoking status, is linked to thermophilic actinomycete exposure, and leads to findings similar to those of hypersensitivity pneumonitis on diagnostic testing.

The disorder seems to represent a type IV hypersensitivity reaction, in which repeated exposure to antigen in genetically susceptible people leads to acute neutrophilic and mononuclear alveolitis, followed by interstitial lymphocytic infiltration and granulomatous reaction. Fibrosis with bronchiolar obliteration occurs with continued exposure.

Circulating precipitins (antibodies sensitized to antigen) seem not to have a primary etiologic role, and clinical history of allergy (such as asthma and seasonal allergies) is not a predisposing factor. Cigarette smoking seems to delay or prevent development, perhaps through down-regulation of the lung’s immune response to inhaled antigens. However, smoking may exacerbate the disease once established.

Hypersensitivity pneumonitis has clinical similarities to other disorders that have different pathophysiologies.

• Organic dust toxic syndrome (pulmonary mycotoxicosis, grain fever), for example, is a syndrome consisting of fever, chills, myalgias, and dyspnea that does not require prior sensitization and is thought to be caused by inhalation of toxins produced by fungi or other contaminants of organic dust.

• Silo filler’s disease may lead to respiratory failure, acute respiratory distress syndrome (ARDS), and bronchiolitis obliterans or bronchitis but is caused by inhalation of toxic nitrogen oxides produced by freshly fermented corn or alfalfa silage.

• Occupational asthma causes dyspnea in people previously sensitized to an inhaled antigen, but features such as airflow obstruction, airway eosinophilia, and differences in triggering antigens distinguish it from hypersensitivity pneumonitis.

Symptoms and signs tend to depend on whether onset is

• Acute

• Chronic

• Subacute

Only a small proportion of exposed people develop symptoms and in most cases only after weeks to months of exposure and sensitization.

• High-resolution CT (HRCT)

• Pulmonary function tests

• Bronchoalveolar lavage

• Histologic examination and serologic tests

Diagnosis of hypersensitivity pneumonitis requires a high index of suspicion in patients with compatible symptoms and a compatible occupational, avocational, or domestic exposure history. Hypersensitivity pneumonitis must be considered in patients with newly identified interstitial lung disease (1). HRCT and pulmonary function tests are done routinely. Bronchoalveolar lavage and lung biopsy may be necessary if results are inconclusive. The differential diagnosis is broad and includes environmental pulmonary diseases, sarcoidosis, bronchiolitis obliterans, systemic rheumatic–associated pulmonary disease, and other interstitial lung diseases.

Clues in the history include

• Recurring atypical pneumonias

• Symptom onset after moving to a new job or home

• A hot tub, a sauna, a swimming pool, or other sources of standing water or water damage in the home or regular exposure to them elsewhere

• Having birds as pets

• Exacerbation and relief of symptoms in and away from specific settings

Examination often is not useful in making the diagnosis, although abnormal lung sounds and clubbing may be present.

Imaging tests

Imaging tests are typically done for patients with appropriate history, symptoms, and signs.

Chest x-ray is neither sensitive nor specific for detecting disease and is frequently normal in patients with acute and subacute forms. It may show reticular or nodular opacities, usually when symptoms are present. Chest x-rays of patients with chronic disease are more likely to show reticular or nodular opacities in the upper lobes with reduced lung volumes and honeycombing, similar to that of idiopathic pulmonary fibrosis.

Chronic Hypersensitivity Pneumonitis

Image

Image courtesy of Harold R. Collard, MD.

High-resolution CT is far more likely to show abnormalities and is considered standard for evaluating parenchymal changes in hypersensitivity pneumonitis. The most typical HRCT finding in acute and subacute disease is the presence of profuse, poorly defined centrilobular micronodules. Occasionally, ground-glass opacification (attenuation) is the predominant or only finding. It is usually diffuse but sometimes spares the periphery of the secondary lobule. Focal areas of hyperlucency, similar to those present in bronchiolitis obliterans, may be a prominent feature in some patients (eg, mosaic attenuation with air trapping on expiratory HRCT).

In chronic hypersensitivity pneumonitis, there are findings of lung fibrosis (eg, lobar volume loss, linear or reticular opacities, or honeycombing), and centrilobular nodules may be absent. Some nonsmoking patients with chronic hypersensitivity pneumonitis have findings of upper lobe emphysema. Mediastinal lymphadenopathy is uncommon, thereby distinguishing hypersensitivity pneumonitis from sarcoidosis.

• Corticosteroids

Treatment of acute or subacute hypersensitivity pneumonitis is with corticosteroids, usually prednisone 60 mg orally once a day for 1 to 2 weeks, then tapered over the next 2 to 4 weeks to 20 mg once a day, followed by weekly decrements of 2.5 mg until the drug is stopped. This regimen relieves initial symptoms but does not appear to alter long-term outcome. Treatment of acute or subacute hypersensitivity pneumonitis is with corticosteroids, usually prednisone 60 mg orally once a day for 1 to 2 weeks, then tapered over the next 2 to 4 weeks to 20 mg once a day, followed by weekly decrements of 2.5 mg until the drug is stopped. This regimen relieves initial symptoms but does not appear to alter long-term outcome.

Treatment of chronic hypersensitivity pneumonitis is usually with longer courses of prednisone 30 to 40 mg orally once a day with tapering dependent on clinical response. Some patients require corticosteroid-sparing agents (eg, mycophenolate, azathioprine) for long-term treatment.Treatment of chronic hypersensitivity pneumonitis is usually with longer courses of prednisone 30 to 40 mg orally once a day with tapering dependent on clinical response. Some patients require corticosteroid-sparing agents (eg, mycophenolate, azathioprine) for long-term treatment.

Pathologic changes of acute hypersensitivity pneumonitis are completely reversible if detected early and if antigen exposure is eliminated. Acute disease is self-limiting with antigen avoidance; symptoms usually lessen within hours. Chronic disease has a more complicated prognosis: fibrosis is usually irreversible but may not progress if the patient is no longer exposed to the antigen.

The most important aspect of long-term management of hypersensitivity pneumonitis is avoidance of exposure to antigens. A complete change of environment is rarely realistic, especially for farmers and other workers, in which case dust control measures (such as wetting down compost before disturbing it) or using air filters or protective masks may be effective. Fungicides may be used to prevent the growth of antigenic microorganisms (eg, in hay or on sugar cane), but the long-term safety of this approach is unknown. Extensive cleaning of wet ventilation systems, removal of moist carpets, and maintenance of low humidity are also effective in some settings. Patients must be told, however, that these measures may be inadequate if exposure continues.