Chest
Volume 152, Issue 3, September 2017, Pages 502-509
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Original Research: Diffuse Lung Disease
Pathologic Findings and Prognosis in a Large Prospective Cohort of Chronic Hypersensitivity Pneumonitis

Preliminary results of this study were presented as an abstract at the annual meeting of the American Thoracic Society, May 19-21, 2014, San Diego, CA (abstract: A6402).
https://doi.org/10.1016/j.chest.2017.02.011Get rights and content

Background

The ability of specific histopathologic features to predict mortality or lung transplantation in patients with chronic hypersensitivity pneumonitis (HP) is unknown.

Methods

Patients with chronic HP diagnosed by surgical lung biopsy were identified from an ongoing longitudinal cohort. The surgical lung biopsy slides were evaluated prospectively by an experienced thoracic pathologist using a standardized checklist to differentiate the major pathologic patterns and score the presence of specific histopathologic features. Cox proportional hazard analysis was used to identify independent predictors of transplant-free survival, and Kaplan-Meier analysis was used to visualize outcomes.

Results

One hundred nineteen patients were identified. Patients with a fibrotic nonspecific interstitial pneumonia (f-NSIP) pattern, bronchiolocentric fibrosis (BF) pattern, or usual interstitial pneumonia (UIP) pattern had significantly worse transplant-free survival than did those with a cellular NSIP (c-NSIP) pattern or peribronchiolar inflammation with poorly formed granulomas (PI-PFG) pattern. No survival difference among patients with an f-NSIP pattern, a BF pattern, or a UIP pattern was found. Fibroblastic foci were identified in a subset of biopsy samples from all pathologic patterns. Peribronchiolar fibrosis was noted in all UIP cases. Independent predictors of time to death or transplantation included the presence of fibroblast foci or dense collagen fibrosis.

Conclusions

Histopathologic patterns of c-NSIP and PI-PFG had a better transplant-free survival than did patterns of UIP, f-NSIP, and BF. The presence of fibroblast foci or dense collagen fibrosis correlated with progression to death or lung transplantation. Identification of fibroblast foci on biopsy samples, regardless of the underlying histopathologic pattern, may be a clinically useful predictor of survival in patients with HP.

Section snippets

Study Population

Patients with chronic HP and surgical lung biopsy samples were identified from a longitudinal cohort of patients followed at the University of California, San Francisco (UCSF) Interstitial Lung Disease Clinic from February 2003 to June 2013. The diagnosis of HP was based on consensus agreement by experts at a multidisciplinary conference after thorough review of all clinical, radiological, and pathologic data according to American Thoracic Society/European Respiratory Society guidelines.7, 12,

Clinical Characteristics

A total of 159 patients with a diagnosis of chronic HP who underwent surgical lung biopsy were identified from the UCSF Interstitial Lung Disease database. Of the 159 patients identified, 40 lacked pathologic scoring data in the database and were excluded, resulting in a study cohort of 119 patients. Baseline demographics are shown in Table 1. Antigen exposure categories included down, microbial, bird, soil/compost, and indoor hot tub (e-Table 1). Serum precipitant testing was not routinely

Discussion

This study of 119 prospectively enrolled patients with chronic HP and variable antigen exposure was designed to examine the frequencies of classifiable pathologic patterns and whether the histologic features were predictive of death or transplantation, or both. Our findings both extend and provide novel observations regarding the relationship between pathologic findings and clinical outcome. New observations include the finding that the pathologic patterns of c-NSIP and PI-PFG were associated

Conclusions

This study represents a prospective cohort of carefully scored lung biopsy samples from patients with chronic HP. In addition to major pathologic patterns, the clinical relevance of secondary histopathologic features was examined. Despite the finding that UIP and BF were not common in chronic HP, the presence of fibroblast foci could be identified in a subset of patients in all major pathologic patterns and predicted a poor outcome. Thus, the identification of fibroblast foci should be noted in

Acknowledgments

Author contributions: P. W. had full access to the data and takes responsibility for the integrity of the data and the accuracy of the data analysis. P. W. contributed to study design, data collection and analysis, statistical analysis, and writing, review, and approval of the final manuscript. K. D. J. and A. U. contributed to histopathologic slide review and assessment and review and approval of the final manuscript. B. M. E. and A. U. contributed to CT data collection and review in

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    FUNDING/SUPPORT: This study was supported by departmental sources and the Nina Ireland Program for Lung Health.

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