Approach

Consensus recommendations categorize HP into nonfibrotic and fibrotic clinical phenotypes, based on the presence or absence of fibrosis on high-resolution computed tomography (HRCT).[3][33]​ However, no one test is pathognomonic.​

Clinicians should instead conduct a thorough history to identify inciting antigens, including occupational exposure, and to establish the type, extent, and temporal relationship of exposure(s) to symptoms.[33] Note that a substantial minority of patients will be unable to provide a history of exposure. A 2020 Delphi expert group suggests inquiring about occult exposures (e.g., feather pillows/cushions/duvets or mold beneath floorboards).[34]

Clinical improvement with antigen avoidance or therapy usually supports the diagnosis, but a lack of improvement is not sufficient alone to exclude the diagnosis. Possible corroborative tests include abnormal chest x-ray or computed tomography (CT), a high titer antibody against the suspected antigen, and abnormal pulmonary function tests (PFTs).[3][33]​​​​

Clinical assessment

Common symptoms of both nonfibrotic and fibrotic HP include dyspnea and cough.[3][33]​​ There may also be mid inspiratory squeaks and cyanosis on physical exam. Systemic symptoms include weight loss, flu-like symptoms (e.g, malaise, chills, and low-grade fever), chest tightness, and wheezing.[24] Onset may be acute (developing over days to weeks; more usually associated with nonfibrotic HP), or insidious (developing and worsening over months to years; more frequently seen with fibrotic HP). Episodes may be recurrent. Patients with fibrotic HP are more likely to be older and have unknown exposure to a causative antigen.[35] Recurrent flu-like illness or interstitial lung disease should raise a high index of suspicion for HP.

Laboratory

Complete blood count, erythrocyte sedimentation rate (ESR), and albumin are of limited value but may indicate an inflammatory process and/or chronic disease process. In acute settings, there may be nonspecific findings such as an elevated ESR and leukocytosis with a left shift. In chronic conditions, there are often nonspecific findings such as low albumin and anemia.[36][37]​ High titers against serum antigen-specific immunoglobulin G (IgG) or immunoglobulin A (IgA) are corroborative.

Imaging

The chest x-ray in acute presentations and nonfibrotic disease is generally characterized by patchy, nodular infiltrates, while in later stages there is fibrosis and peribronchial thickening.[38] However, chest x-ray may be normal between episodes in nonfibrotic disease, and the chest x-ray findings are nonspecific; therefore, patients with suspected HP require a HRCT.[33]

In nonfibrotic HP, the HRCT findings include bilateral, diffuse ground-glass opacities and mosaic attenuation, plus at least one of the following features suggestive of small airways disease:

  • ill-defined, small (<5 mm) centrilobular nodules

  • air trapping.

Nonspecific features that are compatible with nonfibrotic HP include: uniform and subtle ground glass opacities, airspace consolidation, and lung cysts.

In fibrotic HP, the HRCT findings most commonly consist of signs of lung fibrosis (e.g., irregular linear opacities or coarse reticulation) with lung distortion and possible septal thickening. The pattern of fibrosis may be mid-zone predominant, mid- to lower-zone, or distributed throughout the lung with relative basal sparing. Traction bronchiectasis and honeycombing may also be present.

The "three-density pattern" (formerly called the "headcheese sign") is specific to fibrotic HP, with sharply demarcated areas of:

  • high attenuation (ground-glass opacity)

  • regions of decreased attenuation and vascularity

  • normal lung.[3]

Physiologic

PFTs are typically abnormal, demonstrating either restriction or obstruction, or both, and diffusing lung capacity of carbon monoxide (DLCO) is reduced. PFTs and DLCO may be normal between acute attacks.

Bronchoalveolar lavage may occasionally be necessary to confirm the diagnosis or exclude differentials.[3][33][39]​​

Compared with patients with nonfibrotic HP, those with fibrotic HP usually have a lower vital capacity and diffusion capacity, and a lower percentage of lymphocytes in their bronchoalveolar lavage fluid.[3]

Antigen-specific inhalation challenges are rarely used and potentially dangerous.[33]

Biopsy

Lung biopsy may occasionally be performed when a multidisciplinary team cannot make a diagnosis based on clinical, laboratory, or imaging data (e.g., patients with atypical features or no history of exposure).[40] Transbronchial lung cryobiopsy is an option where surgical lung biopsy is not suitable. ​Typical histologic features include bronchocentric infiltrate consisting of lymphocytes, plasma cells, neutrophils, foamy macrophages, and noncaseating granulomas. In later stages, interstitial fibrosis predominates.

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