Hypersensitivity pneumonitis

Pathogenesis and clinical presentation

The development of the disease is based on two types of immune reactions. Type III mechanisms are associated with immune complex formation, whereas type IV mechanisms involve a cell-mediated response. The latter triggers a delayed-type hypersensitivity reaction, resulting in granulomatous inflammation directly within the pulmonary interstitium.

Clinical symptoms manifest on average 6 hours after inhalation of the causative antigen. Patients present with fever, chills, cough, and dyspnea. Notably, wheezing (wheeze) is not a typical symptom, and laboratory tests show no eosinophilia.

Radiological features on HRCT by stage

Changes on high-resolution computed tomography (HRCT / HRCT) strictly depend on the phase of disease progression:

• Acute phase: the most typical manifestation is the ground-glass opacity pattern (ground-glass opacity). With continued antigen exposure, this pattern may persist into the subacute and chronic stages.
• Subacute phase: characterized by the appearance of poorly defined centrilobular nodules approximately 5 mm in diameter with a diffuse distribution. Mosaic attenuation (mosaic attenuation) develops—areas of pulmonary lobules with decreased vascularization. A critical finding on expiratory scans is air trapping (air trapping), which reflects concomitant bronchiolitis due to antigen deposition in the small airways. Occasionally, thin-walled cysts (3–25 mm) can be detected, the pathogenesis of which is not fully understood.
• Chronic phase: signs of fibrosis come to the forefront (often against the background of active disease). Intralobular and interlobular interstitial thickening, traction bronchiectasis, and honeycombing (honeycombing) destruction are identified. The involvement has an axial and bronchocentric distribution with frequent predominance in the middle and upper lung zones.

Features depending on etiology

The course of hypersensitivity pneumonitis may vary depending on the source of the inhaled antigen:

• «Farmer's lung» (farmer’s lung): in such patients, emphysema often becomes a more pronounced radiological sign than fibrosis or honeycombing. It is detected in approximately one-third of patients, even in those who have never smoked.
• «Bird breeder's lung» (bird breeder’s disease): in this case, the main and most severe complication is progressive pulmonary fibrosis.

Differential diagnosis

Chronic and subacute forms of HP must be differentiated from other interstitial lung diseases:

• With respiratory bronchiolitis (RB-ILD): the combination of centrilobular nodules, ground-glass opacity, and small airway disease signs in HP closely resembles respiratory bronchiolitis. The primary criterion to rule out the latter is the absence of a smoking history.
• With usual interstitial pneumonia (UIP) / IPF: chronic HP can mimic UIP or NSIP patterns. Findings favoring pneumonitis include upper- and mid-lung predominance of changes, abundant ground-glass opacities, bronchocentric (rather than subpleural) distribution of fibrosis, and the presence of air trapping.
• Salisbury model (2018): for accurate diagnosis, a model is used where the predominance of mosaic attenuation and air trapping over reticulation, combined with a diffuse axial distribution, yields a 90% specificity (however, the positive predictive value drops when the disease prevalence in the population is low).

Class and exam questions

What else to study on this topic

• Patterns of usual (UIP) and non-specific (NSIP) interstitial pneumonia
• Pulmonary Langerhans cell histocytosis (PLCH): radiological evolution from nodules to cysts
• Lymphangioleiomyomatosis (LAM): cystic lung disease in women
• Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)
• Salisbury model: criteria and limitations in diagnostic imaging

Other topics in the «Chest Radiology» section

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