Augusta University
Otolaryngology-Head and Neck Surgery

Why and When to Target Eosinophils in the Post-Operative Management of Patients with Chronic Rhinosinusitis and Outcomes

STIL KOUNTAKIS, MD, PHD

Eosinophils are known to be present in chronic rhinosinusitis (CRS) and asthma and mediate mucosal inflammation by the secretion of cysteinyl leukotrienes (CysLT) and other inflammatory mediators and molecules. CysLTs cause vasodilation and increased vascular permeability, gland hypersecretion and mucous production, and contribute to mucosal edema. In the lower airways they cause smooth muscle contraction and wheezing. Eosinophils also secrete chemotactic factors to attract more inflammatory cells, including more eosinophils that propagate respiratory inflammation. Via secretion of IL-3, IL-5, GM-CSF and other mediators, eosinophils upregulate mRNA for GM-CSF and G-CSF and thus attract more inflammatory cells and propagate the inflammatory reaction that can eventually lead to formation of polyps. We found that higher eosinophil numbers in sinus tissue are associated with worse sinus disease and we published a disease severity classification system based on whether the patient has polyps and on the presence or absence of eosinophilia (Table 1).1

During surgery, we collect sinus and polyp tissue and work with our pathologists to determine the number of eosinophils (EOS) per high powered field (HPF). Nasal endoscopy establishes the presence or absence of polyps. We use this information to guide post-operative therapy in our patients in order to achieve the best possible outcomes. Data from all treated patients is kept in a rhinologic database and can be analyzed for outcomes on demand based on an ongoing and annually reviewed and approved Augusta University IRB protocol. In addition to normal saline irrigations and intranasal steroid sprays, eosinophilic patients (Table 1) are treated long term with intranasal steroid irrigations and leukotriene receptor antagonists to counteract effects of sinus tissue eosinophilia. Intranasal steroids inhibit T-cell activation and cytokine production resulting in reduction of leukocyte influx, including eosinophils, in nasal mucosa and hasten eosinophil apoptosis. Leukotriene receptor antagonists inhibit cysteinyl leukotrienes that can cause increased vascular permeability, vasodilation, bronchoconstriction, and serve as chemotactic factors for recruitment of more eosinophils.

We have collected years of data on numerous patients and this data was analyzed to study the effectiveness of our postoperative medical therapy. The strength of a large prospectively collected data base is that inadvertently, enough patients will stop using only one medication while staying on the rest of the medical regiment and they can be studied at these different points to determine the effect of that single medication, using the patients themselves as controls. We found that patients with eCRS with and without polyps benefited by the use of intranasal budesonide nasal irrigations (BNI) with reduction of post-operative symptom and endoscopy scores compared to when they were not using budesonide (Table 2).2

Similarly, eCRSwNP and eCRSw/oNP patients benefited from the use of a leukotriene receptor antagonist (montelukast) with reduction of post-operative symptom and endoscopy scores compared to when they were not using montelukast (Table 3).3

Conclusion

The presence of sinus tissue eosinophilia indicates more severe disease in patients with CRS and using budesonide nasal irrigations along with oral montelukast as a leukotriene receptor antagonist may help improve both subjective and objective post-surgical outcomes.

References
  1. Kountakis SE, Arango P, Bradley DT, et al. Molecular and Cellular Staging for the Severity of Chronic Rhinosinusitis. Laryngoscope 2004 Nov;114(11):1895-1905.
  2. Jang DW, Lachanas VA, Segel J, Kountakis SE. Budesonide nasal irrigations in the postoperative management of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2013 Sep;3(9):708- 11.
  3. Yelverton JC, Holmes TW, Gelves CR, Kountakis SE. Effectiveness of Leukotriene Receptor Antagonism in the Post-Operative Management of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2016 Mar;6(3):243-7.

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