Evaluation of Emerging Biomarkers to Identify Aspirin-Exacerbated Respiratory Disease 公开

Abstract

Introduction: Aspirin-Exacerbated Respiratory Disease (AERD) is a severe inflammatory syndrome with inadequate diagnostic options for the 1.4 million Americans affected by this disease. Limited access to diagnostic options is a serious problem for patients. In fact, the gold standard for the identification of AERD, diagnostic aspirin challenge, is under-utilized due to limited availability of specialized providers and concerns of precipitating a life-threatening anaphylactic reaction. The dysregulated production of immunoregulatory eicosanoids promotes chronic airway inflammation in AERD and may represent novel biomarkers for unrecognized disease. In the following study, we evaluate the expression of urinary leukotriene E4 (uLTE4) and the type-2 cannabinoid receptor (CB2R), two such eicosanoids with the potential to identify clinically unrecognized AERD among high-risk patients with nasal polyps and asthma. We then propose a trial seeking to evaluate a multi-variable screening panel to identify undiagnosed AERD.

Methods: Multi-site observational trial of consecutive adult patients with either clinically apparent AERD or high-risk disease. Study sites included Emory University and Scripps Health. Clinical and demographic information was collected with the measurement of uLTE4 and CB2R gene expression from collected urine and nasal epithelium, respectively.  

Results: A total of n=70 participants completed all study activities from June 2017 to December 2020. Significant differences in participant demographics were found for enrollment site (100 vs. 61.4%, p<0.001) and prevalence of respiratory reactions to alcohol (3.9 vs 50%, p<0.001). Mean concentration of uLTE4 was similar among cohorts with mean (SD) values of 187.8 (1689.3) vs. 138.3 (889.9) for High Risk vs. AERD cohorts, p=0.222. A significant difference in CB2R gene expression was found between cohorts with mean (SD) values of 41 (119) vs. 131 (279) for High Risk vs. AERD cohorts, p=0.0042. Further evaluation of high-risk participants with elevated CB2R gene expression resulted in a new diagnosis of AERD in one patient with previously unidentified disease. 

Conclusion: uLTE4 and CB2R represent two emerging biomarkers for the identification of unrecognized AERD among high-risk patients with nasal polyps and asthma. Future study incorporating the results of diagnostic aspirin challenge with ten emerging biomarkers has the potential to improve patient care by identifying previously unrecognized disease. 

Table of Contents

Abstract

Introduction

Methods

Results

Discussion

Conclusions

References

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About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Medicine and Surgery
关键词	Aspirin-exacerbated respiratory disease
Committee Chair / Thesis Advisor	David Guidot, Emory University
Committee Members	Matthew Magee, Emory University Annette Esper, Emory University

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