Microparticles in nasal lavage fluids in chronic rhinosinusitis: Potential biomarkers for diagnosis of aspirin-exacerbated respiratory disease

Reviewed by Dr. Jake Hutto
Takahashi T, et al. J Allergy Clin Immunol. 2017 Sept; 140(3): 720-729

SUMMARY
In this study, investigators sought to identify potential biomarkers to aid in the diagnosis of various forms of chronic rhinosinusitis (CRS), including CRS without nasal polyps (CRSsNP), CRS with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD). Nasal lavage fluid (NLF) samples were obtained from 33 patients with CRSsNP, 45 patients with CRSwNP, 31 patients with AERD, and 24 control patients. Samples were then evaluated for the presence of microparticles (MP), which are submicron-sized shed membrane vesicles from injured or activated cells. MPs for various cell types, including endothelial and epithelial cells, platelets, eosinophils, mast cells, and basophils, were detected in NLF samples using flow cytometry. EndoMPs and ActEndoMPs (markers of endothelial cell injury and activation, respectively), were significantly increased in patients with CRSsNP, CRSwNP, and AERD compared to controls. Platelet MPs were significantly increased only in patients with AERD (3.5-fold, P<0.003). Eosinophil MPs were significantly increased in patients with all 3 conditions compared to controls, though mast cell MPs (MCMPs) were only significantly increased in AERD patients (4.3-fold, P<0.002). Significant differences in levels of ActEndoMPs, platelet MPs, epithelial MPs, mast cell MPs, and basophil MPs were noted in area-under-curve (AUC) analyses when comparing AERD to CRSwNP patients as well. The study provides evidence for the release of MPs from activated immune and injured structural cells in the pathophysiology of CRS, and shows that nasal lavage fluid sampling in CRS patients to detect specific MPs and their quantitative levels can help clarify the specific diagnoses of CRS in an outpatient setting, particularly for distinguishing AERD versus CRSwNP.

COMMENTARY
Chronic rhinosinusitis affects ~1-5% of the US population and costs our healthcare system nearly 3-5 billion dollars annually in office visits and treatment. The most severe form of CRS is AERD, in which patients have comorbid asthma, atopy, and/or aspirin sensitivity. Distinguishing these patients from patients with CRSwNP is important since morbidity is high in asthma exacerbations secondary to aspirin sensitivity, and the pathophysiology of the two phenotypes appears to be distinct. The gold standard for diagnosing AERD is an oral aspirin challenge, which can take many hours as symptoms are monitored for while dosages are increased every few hours. The logistics of this test make it difficult to fully utilize in an outpatient setting, and the risk of a severe reaction occurring outside of the hospital or ER setting can be dangerous. This study was the first to show that analyzing levels and types of MPs from NLF samples can provide a standardized, straightforward method to further learn the pathophysiology of CRS and clarify the diagnosis of various subtypes of CRS to help guide management. Further analyses of MPs in a large cohort of challenge-confirmed AERD are still needed to confirm the usefulness of MPs as biomarkers. Regardless, the use of MP analysis in NLF samples may provide a new tool to study prevalence, progression, and remission in patients with these conditions.

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