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Immunological Characteristics as Potential Treatment Targets in Refractory CRS With Nasal Polyps

Article

The aim of this study was to assess cytokine levels in patients with refractory chronic rhinosinusitis with nasal polyps and to identify inflammatory markers associated with certain subtypes.

Investigators characterized the immunological profiles of patients with refractory chronic rhinosinusitis (CRS) with nasal polyps requiring revision surgery, then compared them with the characteristics of patients with nonrefractory CRS with nasal polyps and with healthy controls.

The study, published in Allergy, Asthma & Immunology Research, noted that although functional endoscopic sinus surgery (FESS) is effective for patients with CRS with nasal polyps that do not respond to pharmaceutical therapy, the condition has a high recurrence rate and revision surgery is sometimes necessary. The aim of the study was to assess cytokine levels in patients with refractory CRS with nasal polyps and to identify inflammatory markers associated with certain subtypes.

From February 2014 to April 2017, surgeons collected sinonasal tissues from patients with CRS with nasal polyps and from healthy controls. Study participants also underwent endoscopic examinations, computed tomography scans, and bacterial cultures. Patients who had undergone FESS once and did not have recurrent polyps were categorized as having primary nasal polyps, and those whose nasal polyps were uncontrolled with medications after undergoing FESS 2 or more times were defined as having refractory nasal polyps.

Those who had undergone revision surgery were younger, had more extensive disease, and had a higher bacterial infection rate, as well as more frequent use of antibiotics, compared with those with primary CRS with nasal polyps.

Protein assay tests and immunochemical staining were performed on the tissue samples, revealing that those with refractory nasal polyps had higher levels of Th1 cytokine (interferon-γ), B-cell activating factor (BAFF), and Th17-associated mediators than those with primary nasal polyps.

A component consisting of interferon-γ, BAFF, and interleukin-17A accounted for 26.3% of the variance between refractory and primary nasal polyp tissues. This component can be used to discriminate between refractory and primary nasal polyps in both the eosinophilic and noneosinophilic subtypes.

“These findings demonstrated that BAFF- and Th17/Th1-related markers are the main biomarkers for characterizing [refractory nasal polyps] regardless of tissue eosinophilia,” the study authors wrote.

Based on analysis of immunological profiles of patients with refractory nasal polyps with and without asthma, eosinophilic inflammation appeared to affect recurrence in those with asthma.

The study authors wrote that their results supported those of a previous study showing an association of neutrophil-related infiltration and Th17 cytokines with steroid resistance and more severe disease in inflammatory disease of the airway. In suggesting a mechanism for their findings, they speculated that recurrent infections, which may be common in the population of patients requiring revision surgery, cause upregulation of Th17-related inflammation and BAFF.

The investigators concluded that inhibition of Th1, Th17, eosinophilic markers, and autoantibodies “may provide a new treatment strategy” for CRS with nasal polyps, especially in refractory cases.

References

Ryu G, Kim DK, Dhong HJ, et al. Immunological characteristics in refractory chronic rhinosinusitis with nasal polyps undergoing revision surgeries. Allergy Asthma Immunol Res. 2019;11(5):664-676. doi: 10.4168/aair.2019.11.5.664.

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