2016 Section 5 Green Book

The Laryngoscope

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)-

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 (

.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 (

.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-

than control (

.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:

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.

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

had similar results to the control group and did not pro-

vide a cure for all CRS.

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.

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

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

DOI: 10.1002/lary.23979

Laryngoscope 123: March 2013

Han:

Subclassification

of Chronic

Sinusitis

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