Elsevier

Clinics in Chest Medicine

Volume 25, Issue 3, September 2004, Pages 531-547
Clinics in Chest Medicine

Hypersensitivity pneumonitis: a multifaceted deceiving disorder

https://doi.org/10.1016/j.ccm.2004.04.001Get rights and content

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Antigens sources

There is a wide spectrum of causative antigens, such as mammalian and avian proteins, fungi, bacteria, and even certain small-molecular-weight chemical compounds, and new sources of airborne organic particles are continually being recognized (Table 1). A broad range of occupations increases the risk of developing HP. Outbreaks of HP have been observed in residential and office buildings [2], [3], [4], [5]. Various water sources can act as reservoirs for microorganisms associated with HP,

Bird-related hypersensitivity pneumonitis

Probably the most common form of avian-related hypersensitivity develops among individuals exposed to pigeons, parakeets (budgerigars), and other small caged birds, such as finches and canaries, in the home environment [1], [12]. The disease is induced by exposure to excreta and proteinaceous material on dried, finely dispersed dust from these birds [13]. Exposure also may occur from aerosol spread of droppings by the vent of a clothes dryer, contamination of heating vents from a garage in

Cigarette smoking and its paradoxic effect on hypersensitivity pneumonitis

Research has demonstrated that HP occurs more frequently in nonsmokers than smokers [9], [40], [41]. The putative protective mechanisms of tobacco smoke are unclear but seem to be related to its immunosuppressive effect, primarily on alveolar macrophages [42], [43]. A marked decrease in macrophage expression of the B7 costimulatory molecules (CD80 and CD86) has been observed in smokers compared with patients with active HP [44]. Likewise, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and

Laboratory abnormalities and specific tests for diagnosis

In acute and subacute episodes, slight to moderate neutrophilic leukocytosis with lymphopenia may occur. Elevated levels of C-reactive protein, erythrocyte sedimentation rate, and immunoglobulin IgG and IgM are usual but nonspecific findings. Rheumatoid factor and immune complexes also may be detected [1]. Plasma lactate dehydrogenase is elevated and decreases with improvement, which suggests that it may be useful in assessing the disease activity [51].

Serum-precipitating IgG antibodies against

Chest radiograph

Conventional radiology shows low sensitivity, mainly in patients with mild acute and subacute forms of HP [56]. In the acute form, transient diffuse or patchy ground-glass attenuation or some areas with air space consolidation can be observed. In the subacute form, the chest radiograph reveals a fine nodular or reticulonodular shadowing with some degree of ground-glass attenuation (Fig. 1). The chronic stages are characterized by a predominantly reticular pattern, which may evolve to

Bronchoalveolar lavage

HP is a lymphocytic alveolitis characterized by a remarkable increase in bronchoalveolar lavage (BAL) lymphocytes, typically T cells, often more than 50% (Fig. 3) [70], [71], [72], [73], [74]. BAL lymphocytosis (which takes place to expend alveolar macrophages that significantly decrease) occurs regardless of the clinical form and type of inhaled antigen. In this context, evaluation of BAL cell pattern may be useful to distinguish HP from other forms of interstitial lung diseases. Patients with

Histopathologic features

Experience on acute HP is scant, but morphology is characterized by interstitial infiltration of neutrophils, lymphocytes, plasma cells, and macrophages. The alveolar spaces may contain amorphous proteinaceous exudates, edema, or hemorrhage [31].

The histologic hallmark of subacute and chronic HP is a bronchiolocentric interstitial granulomatous pneumonitis (Fig. 4A) [89]. The interstitial pneumonitis is mostly mononuclear and composed predominantly of lymphocytes, plasma cells, and macrophages.

Acute hypersensitivity pneumonitis

Acute HP closely mimics a respiratory tract infection. Without a history of illness occurring within hours of exposure to an identifiable antigen, the clinical syndrome is indistinguishable from an acute respiratory infection, such as an episode of flu, or from an atypical pneumonia caused by viral or mycoplasmal agents [96].

In some types of HP, particularly in farmers, the differential diagnosis must include organic dust toxic syndrome provoked by exposure to bacterial endotoxins and fungal

Basic diagnostic criteria

Criteria for HP diagnosis include a high index of suspicion by the clinician. A detailed history of occupational and home (direct and indirect) exposures is critical. The starting points for the diagnosis of acute HP are (1) evidence of exposure, documented by history and specific antibodies (when the test is available); (2) flu-like syndrome, (3) increased BAL lymphocytes and neutrophils, and (4) partial but significant improvement after removing the patient from the suspected environment and

Management and outcome

Early diagnosis and prevention of recurrent antigen exposure are critical, and these steps are enough to improve or heal most patients while continued antigen inhalation is one of the identified causes of progression. A combination of interventions, including fluid management, improved fresh air ventilation, and medical surveillance or restriction, is important to decrease the incidence of occupational risk. Preventive maintenance checks should be performed routinely to ensure that all water

Prognosis and survival

Patients with acute bird-related HP usually have a favorable outcome [110]. By contrast, patients with the chronic form may develop diffuse lung fibrosis and eventually may die from the disease [33], [35], [111]. Patients with acute farmer's lung who stayed on the farm have subnormal values for pulmonary function but comparable values to individuals who left their farms [112]. In a 14-year follow-up of patients with farmer's lung, impairment of the pulmonary transfer factor and airway

Pathogenic mechanisms

HP is associated with various occupational and residential antigens, but only a small percentage of exposed people develop the disease. This observation strongly suggests that HP is probably the result of a double-strike process, but an unambiguous promoting cofactor has not been identified. How antigen exposure, environment, and genetics interact to induce or prevent HP is not known.

The genetic connection

The role of host genetic factors in determining susceptibility to complex polygenic diseases has become evident but difficult to evaluate. In HP, several genes are likely to be involved, but studies are scant and have focused on the major histocompatibility complex. Initial research using serologic techniques did not consistently identify major histocompatibility complex alleles or haplotypes associated to HP [1]. By using polymerase chain reaction–based major histocompatibility complex class

Disturbed lung hypersensitivity

Exaggerated local response to the offending antigen involves humoral and cellular processes [1], [124]. It has been suggested that tissue damage in acute episodes may have an immune-complex basis, which may explain the 4- to 8-hour late onset of symptoms after antigen inhalation that resembles the Arthus-type skin reaction after intradermal skin tests [1], [125]. Formation of immune complexes in the lung parenchyma can activate the complement system with the generation of C3a and C5a, C3b,

Summary

Hypersensitivity pneumonitis represents a group of immunologically mediated lung disorders provoked by recurrent exposure to various environmental agents. HP is multifaceted and may mimic almost any interstitial lung disease, some infectious diseases, and even bronchiolar disorders. In the absence of a diagnostic gold standard, diagnosis of HP requires a combination of clinical, environmental, radiologic, physiologic, and pathologic findings that represent a diagnostic challenge for clinicians

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