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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
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
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.eduDOI: 10.1002/lary.23979
Laryngoscope 123: March 2013
Han:
Subclassification
of Chronic
Sinusitis
Reprinted by permission of Laryngoscope. 2013; 123 Suppl 2:S15-S27.
47