Hypersensitivity Pneumonitis: Radiologic Phenotypes Are Associated With Distinct Survival Time and Pulmonary Function Trajectory

Abstract

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with a better prognosis, on average, than idiopathic pulmonary fibrosis (IPF). We compare survival time and pulmonary function trajectory in patients with HP and IPF by radiologic phenotype.

Methods: HP (n = 117) was diagnosed if surgical/transbronchial lung biopsy, BAL, and exposure history results suggested this diagnosis. IPF (n = 152) was clinically and histopathologically diagnosed. All participants had a baseline high-resolution CT (HRCT) scan and FVC % predicted. Three thoracic radiologists documented radiologic features. Survival time is from HRCT scan to death or lung transplant. Cox proportional hazards models identify variables associated with survival time. Linear mixed models compare post-HRCT scan FVC % predicted trajectories.

Results: Subjects were grouped by clinical diagnosis and three mutually exclusive radiologic phenotypes: honeycomb present, non-honeycomb fibrosis (traction bronchiectasis and reticulation) present, and nonfibrotic. Nonfibrotic HP had the longest event-free median survival (> 14.73 years) and improving FVC % predicted (1.92%; 95% CI, 0.49-3.35; P = .009). HP with non-honeycomb fibrosis had longer survival than IPF (> 7.95 vs 5.20 years), and both groups experienced a significant decline in FVC % predicted. Subjects with HP and IPF with honeycombing had poor survival (2.76 and 2.81 years, respectively) and significant decline in FVC % predicted.

Conclusions: Three prognostically distinct, radiologically defined phenotypes are identified among patients with HP. The importance of pursuing a specific diagnosis (eg, HP vs IPF) among patients with non-honeycomb fibrosis is highlighted. When radiologic honeycombing is present, invasive diagnostic testing directed at determining the diagnosis may be of limited value given a uniformly poor prognosis.

Keywords: interstitial lung disease; prognostic model; pulmonary fibrosis.

Figure 1

Patient flow diagram detailing included subjects and exclusion criteria. *Includes those with ILD diagnosis confirmed by HRCT scan only (ie, definite usual interstitial pneumonia HRCT scan pattern) and those unwilling or unable to undergo diagnostic biopsy. **Excluded diagnoses include primary cystic lung disease, pulmonary alveolar proteinosis, airway or pulmonary vascular disease without ILD, drug-induced lung disease, infection, and other non-ILD diagnoses (congestive heart failure, etc). ***Of included patients identified from the ICD-9 search alone, 23 HP and 7 control patients had chart documentation of multidisciplinary case review, which occurred prior to creation of a searchable database of conference minutes. AIP = acute interstitial pneumonitis; COP = cryptogenic organizing pneumonia; CTD-ILD = connective tissue disease-associated ILD; DIP = desquamative interstitial pneumonia; HP = hypersensitivity pneumonitis; HRCT = high-resolution CT; ICD-9 = international classification of diseases, 9th revision; ILD = interstitial lung disease; IPF = idiopathic pulmonary fibrosis; NSIP = nonspecific interstitial pneumonia; PLCH = pulmonary Langerhans cell histiocytosis; RB-ILD = respiratory bronchiolitis-ILD.

Figure 2

Cox model-based survival estimates by clinical diagnosis and radiologic phenotype group. The plot shows that patients with HP without radiologic fibrosis have significantly longer lung transplant-free survival (median, > 14.73 y) than patients with HP (median, 7.95 y) and IPF (median, 5.20 y) with non-honeycomb fibrosis, and patients with HP (median, 2.76 y) and IPF (median, 2.81 y) with radiologic honeycombing. The group of subjects with IPF without fibrosis was small (n = 1), and median survival could not be estimated. Non-honeycomb fibrosis is defined by absence of honeycombing but presence of both traction bronchiectasis and reticulation. The honeycomb groups are defined by presence of honeycombing on high-resolution CT scan. The plot is adjusted for a typical age (61.9 y), sex (51% women), and FVC % predicted (65.6%) profile. See Figure 1 legend for expansion of abbreviations.

Figure 3

FVC trajectory by clinical diagnosis and radiologic phenotype group. The plot shows that patients with hypersensitivity pneumonitis without radiologic fibrosis have significant increase in FVC % predicted, whereas all other groups experience a significant decrease in FVC % predicted. The group of subjects with idiopathic pulmonary fibrosis without fibrosis was small (n = 1) making comparisons difficult. The plot is adjusted for a typical age (61.9 y) and sex (51% women) profile. The baseline FVC % predicted location is therefore slightly different than the unadjusted values by diagnosis and phenotype group cited in the text.