2016 Section 5 Green Book

Reprinted by permission of Laryngoscope. 2013; 123 Suppl 2:S15-S27.

The Laryngoscope V C 2013 The American Laryngological, Rhinological and Otological Society, Inc.

TRIOLOGICAL SOCIETY CANDIDATE THESIS

Subclassification of Chronic Rhinosinusitis

Joseph K. Han, MD

Objectives/Hypothesis: There are variants of chronic rhinosinusitis (CRS). Therefore, the objectives of this study were to phenotype the subclasses of CRS as well as characterize their polyps with histology and cellular–intracellular biomarkers. Study Design: Prospective case-control study. Methods: Demographic data, quality-of-life (QoL) questionnaires, nasal endoscopy (NE), and computed tomography (CT) scores were obtained. CRS was divided into seven subclasses: aspirin-exacerbated respiratory disease (AERD), asthmatic si- nusitis with and without allergy, nonasthmatic sinusitis with and without allergy, allergic fungal sinusitis (AFS), and cystic fi- brosis (CF). Histopathologic and immunohistochemistry of nasal polyps were recorded. CD3, CD4, CD8, CD19, CD45, and CD56 data were collected. Interleukin (IL)4, IL5, IL13, IL17, and interferon (IFN)- c were measured. Results: Eight-four subjects were in this study. Two QoL questionnaires were inadequate at distinguishing the control group from CRS. NE and CT were able to differentiate between the control group and all CRS subclasses ( P < .01). Asthmatic sinusitis, AERD, and AFS had high NE and CT scores, nasal polyps, eosinophils, mast cell, and hypercellularity. Asthmatic si- nusitis, nonasthmatic sinusitis, and AERD had higher CD4 cells than control group ( P < .05). Even though asthmatic sinusitis and AFS are mediated by Th2, AFS had differing levels of Th2 cytokines. Each nonasthmatic sinusitis had purulence and low CT score. Each nonasthmatic sinusitis had higher CD4 cells and IFN- c than control ( P < .05). CF is associated with purulence, high CT score, high polymorphonuclear leukocytes, high plasma cells, and high mast cells. Conclusions: Well-characterized and distinct groups of CRS have been defined for targeted treatment and research studies. Key Words: Sinusitis, phenotype, asthma, allergy, aspirin triad, nasal polyp, subclassification, interleukin, inflammation, and cystic fibrosis. Level of Evidence: 2b Laryngoscope , 123:S15–S27, 2013

INTRODUCTION Developing a universal treatment for chronic rhino- sinusitis (CRS) has been elusive for many decades. When endoscopic sinus surgery (ESS) became available as a treatment for CRS, there was hope that ESS would cure many patients of their chronic ailments. Despite removing structural obstruction or chronic infection associated with CRS with ESS, sinus symptoms still per- sisted. 1 Antifungal treatment was hoped by some to cure all CRS. However, a prospective, randomized, controlled study evaluating topical antifungal medication to nasal saline demonstrated that topical antifungal irrigation From the Division of Rhinology and Endoscopic Sinus and Skull Base Surgery, Department of Otolaryngology–Head and Neck Surgery, Eastern Virginia Medical School, Norfolk, Virginia, U.S.A. Editor’s Note: This Manuscript was accepted for publication December 13, 2012. This work was funded by Richmond Eye and Ear Foundation, American Academy of Otolaryngic Allergy Foundation, and the Allergy Foundation. The author has no other funding, financial relationships, or con- flicts of interest to disclose. Send correspondence to Joseph K. Han, MD, Division of Rhinology and Endoscopic Sinus and Skull Base Surgery, Department of Otolaryn- gology–Head and Neck Surgery, Eastern Virginia Medical School, River Pavilion Suite 1100, 600 Gresham Drive, Norfolk, VA 23507. E-mail: hanjk@evms.edu

had similar results to the control group and did not pro- vide a cure for all CRS. 2 The best explanation as to why there is no single treatment for CRS is because there is no common pathophysiology for CRS. The most effective treatment for the difficult CRS patients is ESS followed by individualized long-term medical management that should be dictated by the patients’ disease process. To determine the proper medical management for CRS patients, the inflammatory process of the sinuses should define the treatment plan. In other words, a spe- cific kind of medication should be used for a specific kind of sinus inflammation. An example is the use of macrolides for the treatment for CRS. Macrolides gained some interest as a treatment for CRS because of their anti-inflammatory properties. However, the use of mac- rolides for CRS patients has not been universally beneficial. A prospective, randomized, controlled study evaluating the use of macrolides for CRS has demon- strated some statistical improvement between the study and control group. 3 However, when the CRS patients were divided into patients with low- and high-serum im- munoglobulin E (IgE), the low-IgE patients had a better response to the macrolides than the high-IgE patients. This finding is consistent with another study evaluating macrolides for CRS. In this study, patients with nasal polyps, asthma, and allergy did not have a good response

DOI: 10.1002/lary.23979

Han: Subclassification of Chronic Sinusitis

Laryngoscope 123: March 2013

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