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Comparative Study
. 2013 Nov;144(5):1644-1651.
doi: 10.1378/chest.12-2685.

Identifying an inciting antigen is associated with improved survival in patients with chronic hypersensitivity pneumonitis

Evans R Fernández Pérez  1 , Jeffrey J Swigris  2 , Anna V Forssén  3 , Olga Tourin  4 , Joshua J Solomon  2 , Tristan J Huie  2 , Amy L Olson  2 , Kevin K Brown  2
Affiliations
Comparative Study

Identifying an inciting antigen is associated with improved survival in patients with chronic hypersensitivity pneumonitis

Evans R Fernández Pérez et al. Chest. 2013 Nov.

Abstract

Background: The cornerstone of hypersensitivity pneumonitis (HP) management is having patients avoid the inciting antigen (IA). Often, despite an exhaustive search, an IA cannot be found. The objective of this study was to examine whether identifying the IA impacts survival in patients with chronic HP.

Methods: We used the Kaplan-Meier method to display, and the log-rank test to compare, survival curves of patients with well-characterized chronic HP stratified on identification of an IA exposure. A Cox proportional hazards (PH) model was used to identify independent predictors in time-to-death analysis.

Results: Of 142 patients, 67 (47%) had an identified IA, and 75 (53%) had an unidentified IA. Compared with survivors, patients who died (n = 80, 56%) were older, more likely to have smoked, had lower total lung capacity % predicted and FVC % predicted, had higher severity of dyspnea, were more likely to have pulmonary fibrosis, and were less likely to have an identifiable IA. In a Cox PH model, the inability to identify an IA (hazard ratio [HR], 1.76; 95% CI, 1.01-3.07), older age (HR, 1.04; 95% CI, 1.01-1.07), the presences of pulmonary fibrosis (HR, 2.43; 95% CI, 1.36-4.35), a lower FVC% (HR, 1.36; 95% CI, 1.10-1.68), and a history of smoking (HR, 2.01; 95% C1, 1.15-3.50) were independent predictors of shorter survival. After adjusting for mean age, presence of fibrosis, mean FVC%, mean diffusing capacity of the lung for carbon monoxide (%), and history of smoking, survival was longer for patients with an identified IA exposure than those with an unidentified IA exposure (median, 8.75 years vs 4.88 years; P = .047).

Conclusions: Among patients with chronic HP, when adjusting for a number of potentially influential predictors, including the presence of fibrosis, the inability to identify an IA was independently associated with shortened survival.

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Figures

Figure 1.
Figure 1.
A, Survival time estimate of chronic hypersensitivity cohort based on the presence or absence of pulmonary fibrosis (n = 142, number of events = 80). Median survival time for those with pulmonary fibrosis was 4.9 y (95% CI, 2.9-7.5) and median survival time for those without pulmonary fibrosis was 16.9 y (95% CI, 14.9-22.5). B, Survival time estimate of chronic hypersensitivity pneumonitis (HP) cohort based on presence or absence of identified IA exposure (n = 142, number of events = 80). Median survival time for those with identified IA exposure was 18.2 y (95% CI, 14.4-not available [NA]*), and median survival time for those with unidentified IA exposure was 9.3 y (95% CI, 5.9-14.5). C, Survival time estimate of chronic HP cohort for those with identified IA exposure adjusted for mean age of 55 y, former cigarette smoking, and pulmonary fibrosis (n = 67, number of events = 27). Median survival times for nonfibrosis and nonsmoking (NA; 95% CI, 20.6-NA), nonfibrosis and smoking (20.6 y; 95% CI, 14.39-NA), fibrosis and nonsmoking (12.8 y; 95% CI, 8.0-NA), fibrosis and smoking (8.0 y; 95% CI, 6.1-NA). D, Survival time estimate of chronic HP cohort for those with unidentified IA exposure adjusted for mean age of 60 y, former cigarette smoking, and pulmonary fibrosis (n = 75, number of events 53). Median survival times for nonfibrosis and nonsmoking (15.5 y; 95% CI, 12.9-NA), nonfibrosis and smoking (13.5 y; 95% CI, 9.10-20.5), fibrosis and nonsmoking (5.8 y; 95% CI, 2.64-13.9), fibrosis and smoking (2.9 y; 95% CI, 2.0-9.1). *Median or the 95% CI was not calculable because an insufficient number of subjects reached the event at the final time point for assessment. IA = inciting antigen.
Figure 2.
Figure 2.
Survival time estimate of chronic HP cohort for those with or without pulmonary fibrosis and with or without IA adjusted to former cigarette smoking, mean age of 58 y, mean FVC % predicted of 64%, and mean diffusing capacity of the lung for carbon monoxide % predicted of 55%. Median survival times for nonfibrosis and unidentified IA (11.8 y; 95% CI, 7.13-15.7), nonfibrosis and identified IA (14.5 y; 95% CI, 12.33-not available [NA]*), fibrosis and unidentified IA (4.88 y; 95% CI, 2.82-12.3), fibrosis and identified IA (8.75 y; 95% CI, 5.83-15.7). *Median or 95% CI was not calculable because an insufficient number of subjects reached the event at the final time point for assessment. See Figure 1 legend for expansion of abbreviation.
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