Etiology

Generally an adult disease due to antigen exposure, HP has been reported in children and even infants. There are many types of HP, each related to the offending antigen. The most common forms in the US include farmer’s lung (from moldy hay; antigen is thermophilic actinomycetes), bird fancier or breeder lung (from the feces or urine of a wide variety of bird and animal species), and ventilation or humidifier HP (from contaminated humidifiers or air conditioners; also caused by thermophilic actinomycetes). Exposure to pigeons (pigeon breeder disease) is the most common form in Turkey and Mexico, among other countries. Most case reports of HP in children have been the result of antigens inhaled during avian exposure including family pets and feather filled bedding (pillows, quilts) or exposure to molds. HP may occur after exposure to only one bird.

Pathology and Pathogenesis

HP can present as an acute, subacute, or chronic illness. These forms can be distinguished based on the morphologic features of the pulmonary involvement and the clinical symptoms. In the acute stage, alveolar walls are infiltrated by neutrophils, lymphocytes, plasma cells, and macrophages. The alveolar lumen may contain a proteinaceous exudate mixed with inflammatory cells. Repeated or continuous exposure may result in a subacute presentation characterized by the classic noncaseating granuloma associated with HP. Often, there is an associated terminal and respiratory bronchiolitis; alveoli may have pale foamy macrophages. The chronic form demonstrates further progression of the granulomatous alveolitis, resulting in interstitial fibrosis and honeycombing, primarily affecting the upper lobes. This classification of HP has been questioned as to whether it truly reflects distinct categories of the disease. The distinction between these stages may represent variable responses to the offending antigens and there may be considerable overlap in clinical manifestations.

Exposure to avian serum proteins on feathers or bird droppings produces an inflammatory response. The immune mechanisms involved with inducing these morphologic changes may include immune complex (type III) hypersensitivity (particularly in the acute presentation), delayed cellular (type IV) hypersensitivity, and the alternate complement pathway. Only a small percentage of exposed individuals actually experience clinical symptoms, suggesting an interaction between the nature of the offending antigen, the intensity and duration of exposure, and genetic factors in determining the host response.

Clinical Manifestations

Acute attacks usually occur 4-8 hr after an exposure. Symptoms include fever, chills, cough, dyspnea, myalgia, and malaise that can persist for up to 48 hr. Physical examination usually reveals an ill-appearing, dyspneic child with bibasilar crackles, wheezing, or a normal lung examination. Chest radiographs may also be normal or may demonstrate bilateral ground-glass haziness, often sparing the lung apices and bases, with fine nodulations (Fig. 391-1). These patients may progress to the subacute presentation if exposure continues or recurs. The cough worsens, dyspnea becomes more prominent, and anorexia and weight loss may occur. The chest radiograph at this stage has a more reticulonodular appearance. Long-term exposure can lead to the chronic presentation. Dyspnea and cough are severe; clubbing may be present, as are weight loss, weakness, and hypoxemia. These patients eventually develop chronic alveolitis and fibrosis that can lead to cor pulmonale. Chest radiographs show coarse reticulonodular infiltrates and bronchiectasis primarily in the upper- and mid-lung zones. High-resolution computed tomography (HRCT) scans may be more sensitive in demonstrating bronchiectasis.

Figure 391-1 Chest radiograph shows bilateral patchy alveolar infiltrate with peripheral consolidation.

(From Wubbel C, Fulmer D, Sherman J: Chronic eosinophilic pneumonia: a case report and national survey, Chest 123:1763–1766, 2003.)

When removed from the antigenic environment (occupational exposure), the patient will improve (on weekends or days off) only to have recurrent symptoms on reexposure.

Diagnosis

The diagnosis of HP is based primarily on the clinical presentation in association with a suspicious exposure. Because the clinical presentation is nonspecific, a high index of suspicion is crucial. Children with HP will meet most of the basic diagnostic criteria that have been proposed for adults. A variety of diagnostic criteria recommendations have been proposed. Major criteria include symptoms compatible with HP, evidence of exposure (antibody studies), compatible chest x-ray or HRCT findings, bronchoalveolar lavage (BAL) lymphocytosis, histologic changes compatible with HP, and a positive antigen provocation challenge. Minor criteria include bibasilar crackles, decreased diffusion capacity, and hypoxemia. The presence of 4 major and 2 minor criteria are very suggestive of HP, especially when other diseases with similar presentations have been excluded. A number of laboratory tests may also be helpful in confirming a strong clinical suspicion. HP patients often demonstrate a modest leukocytosis with neutrophilia with a left shift, and modest elevation of the erythrocyte sedimentation rate. Serum levels of immunoglobulins (IgG, IgM, and IgA) are often elevated. Skin testing to particular antigens lacks sensitivity and specificity, as do serum precipitins to specific antigens. Both these tests may indicate exposure but are often positive in individuals without the clinical disease. In adults, BAL fluid typically demonstrates a marked lymphocytosis (often up to 70%) particularly of the CD8⁺ suppressor T cells, although in children the CD4 : CD8 ratio is not increased. BAL fluid may also contain higher levels of immunoglobulins. Pulmonary function tests classically demonstrate a restrictive pattern with impaired gas exchange (diffusion capacity). The presence of a mild obstructive pattern during the acute stage is a poor prognostic indicator. Some have advocated an inhalational challenge either in the laboratory or by re-exposure to the environment. Challenge testing can be dangerous and therefore should be undertaken only in appropriately equipped diagnostic centers. A diagnostic algorithm is proposed in Figure 391-2. Table 391-1 provides criteria for estimating the probability of HP; an individual living on a farm presenting with recurrent episodes of respiratory symptoms, inspiratory crackles and testing positive for the corresponding precipitating antibodies, would have an 81% chance of having HP, while an individual with progressive dyspnea and inspiratory crackles only would have a probability of HP of less than 1%.

Figure 391-2 Diagnostic algorithm for hypersensitivity pneumonitis. *PFT improvement: ≥ 20% increase of FVC, FEV 1, and/or DLCO in PFTs. BAL, bronchoalveolar lavage; CT, computed tomography; DLCO, carbon monoxide diffusing capacity; ELISA, enzyme-linked immunosorbent assay; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HP, hypersensitivity pneumonitis; PFT, pulmonary function test; TBB, transbroncheal biopsy.

(Modified from Morell F, Roger A, Reyes L, et al: Bird fancier’s lung: a series of 86 patients, Medicine 87:110–130, 2008.)

The differential diagnosis includes asthma, sarcoidosis, idiopathic pulmonary fibrosis and other causes of interstitial lung disease.

Treatment