Is hypersensitivity pneumonitis divided into inflammatory and fibrotic phases according to the duration of antigen exposure?

Hypersensitivity Pneumonitis Classification: Not Based on Exposure Duration

Hypersensitivity pneumonitis is no longer classified by duration of antigen exposure (acute, subacute, chronic) but rather by the presence or absence of fibrosis on imaging or histopathology—specifically as either fibrotic or nonfibrotic disease—because fibrosis is the primary determinant of prognosis and survival, not exposure timing. 1

Why the Old Classification System Was Abandoned

The historical categorization of HP into acute, subacute, or chronic forms based on disease duration at presentation has been explicitly rejected by major international guidelines because:

• These temporal categories were vaguely defined and inconsistently applied across studies, with arbitrary and variable delineation that lacked clinical utility 1
• Duration-based categories did not correlate with outcomes—some patients classified as "acute" progressed to respiratory failure while others with "chronic" disease recovered completely, making the temporal distinction clinically meaningless 1
• The presence of radiographic or histopathological fibrosis emerged as the single most important prognostic factor, far outweighing any consideration of exposure duration 1

The Current Evidence-Based Classification

The 2020 ATS/JRS/ALAT guideline committee unanimously decided to categorize HP as either:

Nonfibrotic HP (Purely Inflammatory)

• Characterized by inflammatory changes without radiographic or histopathological evidence of fibrosis 1
• Favorable prognosis with possibility of complete recovery after antigen avoidance 1
• Patients who achieve complete antigen avoidance experience no recurrence or development of fibrosis 2
• Clinical improvement typically occurs within 2 weeks to 3.4 months after antigen cessation 3

Fibrotic HP (Mixed Inflammatory Plus Fibrotic or Purely Fibrotic)

• Defined by presence of extensive reticulation, traction bronchiectasis, and/or honeycombing on HRCT imaging 1
• Significantly reduced survival, particularly with UIP-like patterns 1
• All-cause 5-year mortality rate of approximately 48% 2
• Fibrotic HP patients have 4.35 times increased risk of death compared to nonfibrotic HP (HR 4.35; 95% CI 2.22-8.33) 1

Critical Prognostic Factors (Not Exposure Duration)

The factors that actually determine outcomes in HP are:

• Presence and extent of fibrosis on imaging (HR 1.54 per unit increase in fibrosis score; 95% CI 1.25-1.88) 1
• Pulmonary fibrosis on CT increases mortality risk 2.43-fold (HR 2.43; 95% CI 1.36-4.35) after adjusting for age and lung function 1
• UIP-like pattern on imaging correlates with particularly poor survival 1, 3
• BAL lymphocytosis <30-50% predicts worse outcomes in fibrotic disease 1, 2
• Honeycombing on HRCT is an independent negative prognostic factor 2
• Unidentified inciting antigen (occurs in 30-50% of cases) independently shortens survival (HR 2.07; 95% CI 1.02-4.24) 1, 3

Why This Distinction Matters Clinically

The fibrotic versus nonfibrotic classification has direct therapeutic and prognostic implications:

• Nonfibrotic HP: Antigen avoidance alone may be sufficient; corticosteroids reverse functional decline from -0.35% to +0.84% monthly (P<0.01) 3
• Fibrotic HP: Corticosteroids show no significant benefit on FVC% (P=0.96) or DLCO% (P=0.59); steroid-sparing immunosuppressants are needed 3
• Patients with mixed features are categorized by the predominance of inflammatory versus fibrotic features 1

Common Pitfall to Avoid

Do not assume that "acute" presentation means inflammatory disease or that "chronic" symptoms mean fibrotic disease. The speed of symptom onset and duration of exposure do not reliably predict the presence or absence of fibrosis 1. A patient with sudden symptom onset may already have established fibrosis on imaging, while someone with years of low-level exposure may have purely inflammatory disease. Always obtain HRCT imaging to definitively classify the disease phenotype 1, 3.

The pathologic literature does describe acute, subacute, and chronic histopathologic patterns 4, 5, 6, but these are descriptive morphologic observations rather than a clinically useful classification system for guiding management decisions 1.