In the United States, bird-breeder’s lung, farmer’s lung, and ventilator hypersensitivity pneumonitis occur most often. Many diseases are related to specific adult occupations (e.g., pigeon-breeder’s lung, farmer’s lung disease, disease associated with oil mist exposure in metalworkers and popcorn factories), but children living in environments rich with these antigens occasionally also can be afflicted with these respiratory illnesses. Table 231.1 lists some of the most common offenders in children including avian proteins, molds, bacteria, and medications. For children, most of the exposures occur in the home setting and include exposure to family businesses (chicken or turkey farms), family pets, moldy homes or home settings such as basement showers, or outdoor exposures (riding schools and associated barn chores). As outlined, many fungi have been associated with hypersensitivity pneumonitis, especially thermophilic actinomycetes.

The name hypersensitivity pneumonitis and the association of the condition with the inhalation of a foreign antigen suggest that this disease entity is mediated by immunologic phenomena. Gell and Coombs divided immune tissue injury into four types of hypersensitivity reactions. Immunoglobulin E (IgE)–mediated, or type I, hypersensitivity may seem a likely cause of the lung disease observed clinically, yet no evidence exists to support this hypothesis. Serum IgE levels are normal in affected
individuals; in fact, antigen-specific IgE levels rarely are elevated. Patients affected with hypersensitivity pneumonitis usually are not atopic. After antigen inhalation, rales, not wheezing, are the typical auscultatory findings, and evidence of bronchospasm is exceedingly rare. Pulmonary symptoms of dyspnea and cough rarely respond to the administration of traditional histamine blockers or mast cell stabilizers such as cromolyn sodium. All the information suggests that type I, IgE-mediated hypersensitivity plays little or no role in the pathogenesis of hypersensitivity pneumonitis.

No data conclusively support a role for type II hypersensitivity, or cytotoxic reactions, in hypersensitivity pneumonitis. Other data using rabbits as experimental models for hypersensitivity pneumonitis, however, suggest that types III (Arthus reaction or immune-complex) and IV (cell-mediated or delayed) hypersensitivity play roles in the pathogenesis of this disease entity. The role of immune complex-mediated reactions in the pathogenesis of hypersensitivity pneumonitis is supported most significantly by the Arthus-type reactions that are documented histologically after intradermal skin testing with the suspected offending antigen. Circulating serum immune complexes (i.e., serum precipitins) suggest that type III hypersensitivity reactions play a significant role in the early clinical response to antigen. The absence of immune complexes at sites of inflammation (i.e., lung biopsy) suggests that type III responses do not mediate this disease.

Evidence of type IV or cell-mediated hypersensitivity has been derived primarily from work with hypersensitivity pneumonitis induced in guinea pigs and rabbits. In these models, evidence of local T-lymphocyte activation has included enhanced local lymphokine production and increased numbers of local activated T cells recovered in bronchoalveolar lavage (BAL) fluid. Affected patients have evidence of granuloma formation at lung biopsy (as high as 70% in one review of patients with farmer’s lung). The mechanisms for formation of granulomas include pulmonary macrophage and a T-helper-1–cell response that increases interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma production locally.

In summary, most immunologic investigations suggest that hypersensitivity pneumonitis probably is mediated by a combination of immunologic events, including immune complex formation and cell-mediated hypersensitivity.

The clinical presentation of hypersensitivity pneumonitis is variable and traditionally is separated into three somewhat distinct clinical entities: acute, subacute, and chronic. The acute form of hypersensitivity pneumonitis frequently is related to intermittent, intense inhalation of the offending antigen, with symptoms precipitated 4 to 6 hours after contact with antigen. Typical clinical symptoms include elevated temperature in the range of 38.3° to 40.0°C (101° to 104°F), dry cough, dyspnea, and malaise. Constitutional symptoms can persist for weeks after exposure, but they usually resolve within 24 hours. The patient appears ill on physical examination, and lung auscultation typically documents bilateral bibasilar rales. Wheezing or evidence of reversible reactive airway disease is an uncommon finding and provides evidence against the diagnosis of hypersensitivity pneumonitis.

The subacute presentation of hypersensitivity pneumonitis lacks the characteristic findings of fever, malaise, and dyspnea that are noted in the acute form of the disorder. Clinically, the patient may complain of persistent anorexia or weight loss and malaise. Pulmonary symptoms such as progressive shortness of breath or insidious onset of dyspnea on exertion may be late manifestations. The chronic form of hypersensitivity pneumonitis usually is related to long-term, low-dose antigen exposure. Clinical findings include a normal physical examination, with the exception of pulmonary rales detected on auscultation of the chest. Wheezing rarely accompanies chronic hypersensitivity pneumonitis. Lung disease related to the chronic form of the disorder usually is poorly responsive to traditional therapeutic intervention. Initial pulmonary findings include severe restrictive impairment (coupled with a diffusion defect), pulmonary fibrosis (determined radiographically and histologically, with noncaseating granulomas noted), and progressive nonreversible obstructive disease that is characterized by hyperinflation and sometimes is associated histologically with evidence of obliterative bronchiolitis and emphysema.