Sinusistis JAMA 2015

Clinical Review & Education
Review
Medical Therapies for Adult Chronic Sinusitis

A Systematic Review
Luke Rudmik, MD, MSc; Zachary M. Soler, MD, MSc
IMPORTANCE Chronic sinusitis is a common inflammatory condition defined by persistent

symptomatic inflammation of the sinonasal cavities lasting longer than 3 months. It accounts
for 1% to 2% of total physician encounters and is associated with large health care
expenditures. Appropriate use of medical therapies for chronic sinusitis is necessary to
optimize patient quality of life (QOL) and daily functioning and minimize the risk of acute
inflammatory exacerbations.
OBJECTIVE To summarize the highest-quality evidence on medical therapies for adult chronic
sinusitis and provide an evidence-based approach to assist in optimizing patient care.
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EVIDENCE REVIEW A systematic review searched Ovid MEDLINE (1947-January 30, 2015),
EMBASE, and Cochrane Databases. The search was limited to randomized clinical trials
(RCTs), systematic reviews, and meta-analyses. Evidence was categorized into maintenance
and intermittent or rescue therapies and reported based on the presence or absence of nasal
polyps.
FINDINGS Twenty-nine studies met inclusion criteria: 12 meta-analyses (>60 RCTs), 13
systematic reviews, and 4 RCTs that were not included in any of the meta-analyses. Saline
irrigation improved symptom scores compared with no treatment (standardized mean
difference [SMD], 1.42 [95% CI, 1.01 to 1.84]; a positive SMD indicates improvement). Topical
corticosteroid therapy improved overall symptom scores (SMD, 0.46 [95% CI, 0.65 to
0.27]; a negative SMD indicates improvement), improved polyp scores (SMD, 0.73 [95%
CI, 1.0 to 0.46]; a negative SMD indicates improvement), and reduced polyp recurrence
after surgery (relative risk, 0.59 [95% CI, 0.45 to 0.79]). Systemic corticosteroids and oral
doxycycline (both for 3 weeks) reduced polyp size compared with placebo for 3 months after
treatment (P < .001). Leukotriene antagonists improved nasal symptoms compared with
placebo in patients with nasal polyps (P < .01). Macrolide antibiotic for 3 months was
associated with improved QOL at a single time point (24 weeks after therapy) compared with
placebo for patients without polyps (SMD, 0.43 [95% CI, 0.82 to 0.05]).
CONCLUSIONS AND RELEVANCE Evidence supports daily high-volume saline irrigation with
topical corticosteroid therapy as a first-line therapy for chronic sinusitis. A short course of
systemic corticosteroids (1-3 weeks), short course of doxycycline (3 weeks), or a leukotriene
antagonist may be considered in patients with nasal polyps. A prolonged course (3 months)
of macrolide antibiotic may be considered for patients without polyps.
Author Affiliations: Department of

Surgery, Division of Otolaryngology
Head and Neck Surgery, University of
Calgary, Calgary, Alberta (Rudmik);
Department of Otolaryngology
Head and Neck Surgery, Division of
Rhinology and Sinus Surgery, Medical
University of South Carolina,
Charleston (Soler).
Corresponding Author: Luke
Rudmik, MD, MSc, Department of
Surgery, Division of Otolaryngology
Head and Neck Surgery, Richmond
Road Diagnostic and Treatment
Centre, University of Calgary,
1820 Richmond Rd SW,
Calgary, AB, Canada, T2T 5C7
(lukerudmik@gmail.com).
JAMA. 2015;314(9):926-939. doi:10.1001/jama.2015.7544

926
Section Editors: Edward Livingston,

MD, Deputy Editor, and Mary McGrae
McDermott, MD, Senior Editor.
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hronic sinusitis, or chronic rhinosinusitis, is an inflammatory condition defined by symptomatic inflammation of the
paranasal sinuses lasting longer than 3 months (Box 1).1-3
Common presenting symptoms include nasal obstruction, facial pressure or fullness, nasal discharge (anterior or posterior), and olfactory
loss (Table 1).4-7 Furthermore, chronic sinusitis is associated with reductions in patient quality of
IL-5 interleukin 5
life (QOL),8 sleep quality,9
and daily productivity.10 It is
QOL quality of life
a common yet underrecogRCT randomized clinical trial
nized chronic inflammatory
disease affecting approximately 3% to 7% of the population11,12 and
accounting for 1% to 2% of total physician visits.13,14 Health care expenditures related to chronic sinusitis exceed $9 billion per year with
societal costs exceeding $13 billion per year.15
Although previously thought to be entirely infectious in etiology, chronic sinusitis is now recognized as an inflammatory disease
of the upper airways analogous to asthma in the lower airways.16,17
The etiology is multifactorial16,18 and includes bacterial superantigens, epithelial cell defects, bacterial biofilms, T helper 1 and 2 inflammation, tissue remodeling19 (increased fibrosis of sinonasal mucosa), and genetic variations in human leukocyte antigen haplotypes
and bitter-taste receptors. For example, healthy sinonasal-ciliated
epithelial cells express bitter-taste receptors, which are stimulated
by bacterial products and activate an innate host immune response to remove and kill bacteria by locally releasing nitric oxide.20,21
Genetic variations in bitter-taste receptors have been associated with
refractory chronic sinusitis and may represent a novel future therapeutic target.22,23
Similar to asthma, current research focuses on categorizing
chronic sinusitis into chronic sinusitis endotypes,24 which are disease classifications defined by distinct clinical features, pathophysiologic molecular mechanisms, and treatment responses.25,26 However, validated chronic sinusitis endotypes have not been defined.
Therefore, chronic sinusitis is currently classified based on the presence or absence of nasal polyps.
Medical treatments for chronic sinusitis reduce mucosal inflammation, remove mucus, and modulate environmental triggers
(Figure 1).30 This systematic review identifies the most effective
treatments for the medical management of adult chronic sinusitis
and presents the evidence supporting each therapeutic option.
Methods
Ovid MEDLINE (1947-January 30, 2015), EMBASE, the Cochrane Central register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched using the terms: chronic, *sinusitis
(using * as an unlimited truncation strategy to capture all variations
of sinusitis). The results were combined with the following chronic
sinusitis medical therapy terms: saline, antibiotic, antimicrobial, corticosteroid, steroid, antifungal, leukotriene receptor antagonist, antihistamine, immunotherapy, omalizumab, anti-IL5, macrolide. The
following search limits were then applied: randomized clinical trials
(RCTs) of humans 18 years or older, systematic reviews, and metaanalyses. Inclusion criteria required that all patients in each study
were considered to have chronic sinusitis, although diagnostic criteria were allowed to vary across individual studies. Studies were exjama.com
Review Clinical Review & Education
cluded if they focused on perioperative medications, acute sinusitis, allergic fungal sinusitis, cystic fibrosis, primary ciliary dyskinesia,
aspirin-exacerbated respiratory disease, sarcoidosis, immunodeficiency, or granulomatosis with polyangiitis. Unstructured narrative
reviews were excluded. References from all identified studies were
reviewed for additional relevant articles.
Both authors independently reviewed included studies and assigned a level of evidence31 for each study. When applicable, the
quantitative effect size and confidence interval from metaanalyses and RCTs were reported. The standardized mean difference (SMD) was used to report effect size from a meta-analysis when
studies reported outcomes using different instruments. When improvement was associated with higher scores on the outcome measure, then the SMD would be greater than 0. If improvement was
associated with lower scores on the outcome measure (ie, polyp
scores), then the SMD would be less than 0. An aggregate grade of
evidence (A-C) and recommendation (I-III) for each treatment strategy was assigned using the American Heart Association grading scale
(Box 2).32 Differences in evidence grading were resolved by discussion. The risk of bias for each meta-analysis was quantified using the
Cochrane Handbook for Systematic Reviews of Interventions.33
Results
Three hundred twenty-eight studies were screened for eligibility.
Twenty-nine studies met inclusion criteria, including 12 metaanalyses (evaluating >60 RCTs), 13 systematic reviews, and 4 individual RCTs that were not included in any of the meta-analyses (eFigure in the Supplement). The evidence for each treatment strategy
is organized into either maintenance or intermittent or rescue
therapies, with the understanding that these designations are not
necessarily mutually exclusive in clinical practice.
Maintenance Medical Therapies for Chronic Sinusitis

Topical Corticosteroids
Corticosteroids reduce sinonasal mucosal inflammation, decrease

vascular permeability, and reduce glycoprotein release from submucosal glands (ie, thin mucus) (eTable 1 in the Supplement). Benefits associated with this therapy have the strongest level of evidence with 6 meta-analyses quantifying the evidence from more
than 40 RCTs (Table 2). 34-39 Three meta-analyses (>3624
patients)34,37,38 evaluated patients with nasal polyps and demonstrated an association with improvements in overall symptoms
scores, polyp size, and recurrence rate after sinus surgery. RCTs included in the largest meta-analysis by Kalish et al38 were of high quality with only 6 of 40 trials having a high risk of bias (eTable 2 in the
Supplement). The degree of reduction in polyp size is associated directly with the degree of improvement in QOL.45
Two meta-analyses (>657 patients)35,36 evaluated patients without nasal polyps and determined that topical corticosteroids were associated with improved overall symptom scores and greater proportion of symptom responders. Quality assessment demonstrated a low
risk of bias for blinding; however, there was a high risk of bias for group
allocation (ie, topical corticosteroid vs placebo), which indicates a need
for higher-quality trials in patients without polyps.
In summary, an A-I grade and recommendation supports using
topical corticosteroid therapy for chronic sinusitis with and with(Reprinted) JAMA September 1, 2015 Volume 314, Number 9
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Clinical Review & Education Review
Box 1. Consensus-Based Diagnostic Criteria for Chronic Sinusitis

2 of the Following 4 Symptoms Lasting for >3 Months (PODS)a
Pressure/pain (facial)
Obstruction (nasal)
Discharge (nasal)anterior or posterior
Smell reduced
Symptom Criteria Supported by Demonstrating at Least 1 of the
Following 3 Objective Signs of Inflammation
Presenting Symptom
Frequency of Presenting
Symptom, %
Sinonasal-specific
Nasal obstruction/congestion
81-95
Nasal discharge
81-93
Facial pressure/fullness
70-85
Reduced sense of smell
66-84
Other
Nasal polyps on anterior rhinoscopy or nasal endoscopy

Edema or purulence within middle meatus
CT scan of the paranasal sinuses demonstrating inflammation
Fatigue
83-92
Headache
73-83
Difficulty sleeping
62-74
CT indicates computed tomography.
Toothache
30-67
Ear pain/fullness
39-56
One of the 2 symptoms must be either obstruction or discharge.
Source: US, European, and Canadian guidelines on chronic sinusitis1-3
out nasal polyposis. Although early evidence suggests that highvolume corticosteroid irrigations (ie, techniques that involve delivering >100 mL of solution into the nasal cavity46) (eg, budesonide
irrigations47) are more effective than low-volume corticosteroid spray
techniques (ie, meter-dosed spray, atomized, or nebulized
solutions),46 clinical trials are required before a recommendation on
optimal delivery method can be provided. Doses, durations, and potential adverse effects of available medical therapies are reported
in Table 3.
Saline Irrigations
Sinonasal saline irrigations assist in removing mucus and possible environmental triggers and assist in restoring normal mucociliary clearance. Outcomes from 2 systematic reviews 41,42 and 1 metaanalysis (399 patients)40 support an association between the use
of sinonasal saline irrigations and improved symptom scores
(Table 2). However, when saline irrigation was the only treatment,
it was associated with less improvement when directly compared
with topical corticosteroid therapy.
In summary, an A-I grade and recommendation supports using
sinonasal saline irrigation as an adjunctive therapy to intranasal corticosteroids for patients with and without nasal polyps. Isotonic and
hypertonic saline irrigations provide similar symptom improvement. High-volume (>100 mL) saline irrigation is superior to lowvolume nasal saline spray techniques.46,48
Leukotriene Pathway Antagonists

Leukotriene pathway antagonists block leukotrienes D4, C4, and E4
from binding the cysteinyl leukotriene receptors located in respiratory mucosa or block the production of leukotrienes from arachidonic acid by inhibiting 5-lipoxygenase. These effects can reduce eosinophil recruitment, vasodilation, and mucus secretion. Five
RCTs49-53 evaluated an oral leukotriene antagonist, montelukast
(10 mg once daily), in patients with nasal polyposis (Table 2).49-53
Only 2 RCTs met the high-quality requirements for quantitative
meta-analysis43 (174 patients). Overall, montelukast may improve
symptoms compared with placebo; however, there was no difference between oral montelukast and topical corticosteroid therapy.
No additional improvement was seen when montelukast was added
to existing topical corticosteroid therapy.
928
Table 1. Presenting Symptoms of Chronic Sinusitis
Data sources: Bhattacharyya,4,5 Soler et al,6 and Dietz de Loos et al.7
In summary, an A-II grade and recommendation supports using

a leukotriene antagonist (montelukast) in patients with nasal polyps.
No evidence grade is assigned for use of leukotriene antagonists in
patients without nasal polyps.
Antihistamines and Allergy Immunotherapy

Antihistamines and allergy immunotherapy reduce an allergen induced IgE-mediated host response, which decreases vascular permeability, vasodilation, and nasal secretions. An estimated 20% to
60% of chronic sinusitis patients have allergic rhinitis, with the highest prevalence in those with nasal polyposis.54,55 Despite this association, it remains unclear whether allergy plays a causal role in
chronic sinusitis and whether treating allergic rhinitis improves
chronic sinusitis-specific outcomes.56 One systematic review identified 6 case series evaluating the association of allergy immunotherapy on sinusitis-specific outcomes and reported improved
allergy-specific symptoms but no consistent improvement in sinusspecific symptoms (Table 2).44
In summary, a C-II grade and recommendation is designated to
allergy immunotherapy for the specific management of chronic sinusitis. No grade of evidence is provided for the use of oral antihistamines during specific management of chronic sinusitis. Evidence
supports antihistamines and allergy immunotherapy for managing
concurrent allergic rhinitis.57
Intermittent or Rescue Medical Therapies

for Chronic Sinusitis
Systemic Corticosteroids
Patients commonly present with severe nasal polyposis or acute inflammatory exacerbations requiring intermittent or rescue systemic corticosteroid to treat acute mucosal inflammation.30 Three
systematic reviews evaluated oral corticosteroids for nasal polyposis (Table 4).58-60 Oral corticosteroids were associated with improved symptoms, QOL, and reduced polyp size compared with placebo in all 5 RCTs. However, the RCTs were of low to moderate quality,
short duration (2-3 weeks), and limited follow-up (2 weeks-6
months). Improvements were not sustained for more than 3 months
in the absence of maintenance topical corticosteroid therapy.45,73
No RCTs evaluated oral corticosteroids for chronic sinusitis without nasal polyps. The highest level of evidence for patients without
JAMA September 1, 2015 Volume 314, Number 9 (Reprinted)
jama.com
Figure 1. Proposed Mechanisms of Action for Chronic Sinusitis Medical Therapies
Respiratory pathogens
Nonmacrolide antibiotics
Macrolides
Clears respiratory
pathogens and allergens
Increases ciliary clearance
Respiratory
pathogen
Increase ciliary
clearance
NASAL MUCOSA
Cell membrane
phospholipid
SUBEPITHELIAL
MAST CELL
RESPIRATORY
EPITHELIAL CELL
Antigenpresenting
cell
Epithelial cell
Phospholipase A2
Corticosteroids
Macrolides
Activation of
NF-B pathway
Environmental
allergens
Saline irrigation
Treat bacterial infection
Corticosteroids
Inhibit NF-B
pathway
Arachidonic acid
Inhibit arachidonic
acid synthesis
Antigenpresenting
cell
TH 2-cell
activation
NF-B
5-LO
Leukotriene
synthesis
5-LO inhibitors
NF-B
Block leukotriene
synthesis
Release of
inflammatory
mediators
Release of
inflammatory
mediators
Leukotrienes
TGF-
Block binding to
TGF- receptor
Neutrophil
activation
Fibroblast activation and

submucosal collagen
deposition with fibrosis
TNF-
Doxycycline
Blocks IL-6,
IL-8, TNF-
IL-4
IL-13
Eosinophil
migration and
activation
B-cell
activation
Binds free IL-5
IL-6
IL-8
GM-CSF
IL-5
Mepolizumab
IL-2
Macrolides
TH2 cell
Recruitment of
inflammatory
cells
Leukotriene receptor
antagonists
Block cysteinyl
leukotriene receptor
binding
B cell
Eosinophil
Synthesis and
release of IgE
Neutrophil
Eosinophil
Monocyte
Neutrophil
Macrolides
Inhibit neutrophil
migration
Promote neutrophil
apoptosis
Neutrophil
IL-8
Leukotriene B4
IgE
Neutrophil migration
Release of proteases
and superoxides
Neutrophil
Eosinophil
Cysteinyl leukotriene
receptors 1 and 2
Omalizumab
Binds free IgE
Histamine release
and mast cell
migration
Antihistamine
Blocks histamine
release from
mast cells
Apoptotic
neutrophil
Mast cell
Neutrophil
Histamine
Leukotrienes
Other cytokines
GM-CSF indicates granulocyte-macrophage colony-stimulating factor; IL, interleukin; LO, lipoxygenase; NF-B, nuclear factor enhancer of B cells;
TGF, transforming growth factor; TH2, T helper 2; TNF, tumor necrosis factor.
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(Reprinted) JAMA September 1, 2015 Volume 314, Number 9
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Box 2. American Heart Association Grade of Evidence and

Recommendation Grading Scale
A-I: conditions for which there is evidence and/or general agreement that a given treatment is useful and effective; data derived
from multiple randomized clinical trials (RCTs)
A-II: conditions for which there is conflicting evidence and/or
divergence of opinion about the usefulness/efficacy of a
treatment; data derived from multiple randomized studies
A-III: conditions for which there is evidence and/or general agreement that the treatment is not useful/effective and in some cases
may be harmful; data derived from multiple RCTs
B-I: conditions for which there is evidence and/or general agreement that a given treatment is useful and effective; data derived
from a single randomized trial or nonrandomized studies
B-II: conditions for which there is conflicting evidence and/or
divergence of opinion about the usefulness/efficacy of a
procedure/treatment, data derived from a single randomized trial
or nonrandomized studies
B-III: conditions for which there is evidence and/or general agreement that the treatment is not useful/effective and in some cases
may be harmful; data derived from a single randomized trial or
nonrandomized studies
C-I: conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective;
consensus opinion of experts
C-II: conditions for which there is conflicting evidence and/or
divergence of opinion about usefulness/efficacy of a procedure or
treatment; consensus opinion of experts
C-III: conditions for which there is evidence and/or general agreement that the procedure/treatment is not useful/effective and in
some cases may be harmful; consensus opinion of experts
Source: American Heart Association32
polyps comes from prospective case series without control groups

and heterogeneous concurrent medical therapy protocols. These
studies report that oral corticosteroids are associated with improved olfactory and symptom scores.74-77
In summary, an A-I grade and recommendation supports the use
of intermittent short-course (1-3 weeks) oral corticosteroids for symptomatic nasal polyposis. A C-II grade and recommendation supports the use of oral corticosteroids for chronic sinusitis without nasal polyps. Because of the adverse effects associated with oral
corticosteroids,78 patients and physicians should participate in an
open discussion about the risks, benefits, and alternative treatments to facilitate a shared decision-making process.
Short-term Oral Antibiotics (Nonmacrolide)

Short-term courses of antibiotics are intended to eradicate active
infection through several potential mechanisms such as inhibiting
bacterial cell wall formation, inhibiting bacterial folate synthesis, and
promoting bacterial DNA fragmentation (eTable 1 in the Supplement). One systematic review evaluated short-term oral antibiotics for chronic sinusitis61 (Table 4). Three RCTs compared 2 different antibiotics (cefotiam vs cefixime79; amoxicillin/clavulanate vs
ciprofloxacin80; and cefaclor vs amoxicillin81) for 3 weeks or less without a placebo group and showed no difference between antibiotics. Heterogeneity between studies precluded quantitative meta930
analysis. One RCT evaluated 200 mg of doxycycline once, followed

by 100 mg daily for 20 days (n = 14) compared with methylprednisolone (n = 14) and placebo (n = 19) for nasal polyposis.73 Doxycycline was associated with an improved polyp score 12 weeks after discontinuing treatment compared with placebo (P = .015).
Methylprednisolone was associated with a larger improvement in
polyp score at 2 weeks compared with doxycycline and placebo;
however, there was no difference in polyp score between methylprednisolone and doxycycline 12 weeks after discontinuing the treatment. This suggests that doxycycline does not provide as large of
an early improvement but provides a similar longer-term improvement in polyp reduction. The only symptom that improved in the
doxycycline group was postnasal drainage at 2 weeks.
In summary, a B-I grade and recommendation supports a shortcourse of doxycycline (200 mg once then 100 mg daily for 20 days)
for nasal polyposis. An A-II recommendation supports the use of
short-course oral antibiotics (<3 weeks) for chronic sinusitis without nasal polyps; however, they are probably only relevant when purulence is present on examination.2
Long-term Macrolide Therapy

Analogous to their use in lower airway disease,82 extended courses
of low-dose macrolide antibiotics have been evaluated as therapy
of chronic sinusitis.83 The direct antibacterial effects, ability to improve cilia function, and immunomodulatory properties of macrolides may improve clinical outcomes (Figure 1 and eTable 1 in the
Supplement).27,84
Two systemic reviews61,62 and 1 meta-analysis63 evaluated prolonged macrolide therapy for chronic sinusitis (Table 4). Three
months of macrolide antibiotic were associated with improved symptom response, QOL, and mucociliary clearance compared with placebo for patients without nasal polyps in a single RCT.85 Although
the meta-analysis demonstrated improvement in QOL at a single time
point after starting macrolide therapy (24 weeks), the pooled RCTs
contained a heterogeneous patient population (patients with and
without nasal polyps) and the clinical significance of the improvement was questionable. Furthermore, the QOL improvement was
not sustained 12 weeks after completing the macrolide therapy. Although not statistically significant, there may be an association in
sustained QOL improvement in patients with low serum IgE
(<200 g/L; to convert to mg/L, multiply by 0.001) (P = .06). The
only RCT that included patients with nasal polyposis showed no difference between macrolide therapy and placebo.86
In summary, an A-II grade and recommendation is designated
for long-term use (>12 weeks) of macrolide therapy in patients without nasal polyps. Given the negative results from 1 RCT, a B-III grade
and recommendation against use is designated to long-term macrolide therapy for patients with nasal polyps.
Anti-IgE Therapy
Anti-IgE therapy involves delivery of a recombinant DNA-derived humanized IgG monoclonal antibody that binds free IgE and inhibits
binding to mast cell and basophil receptors.87 However, the influence of IgE-mediated inflammation on the underlying pathophysiology of chronic sinusitis is unclear.88
Two RCTs64,65 that evaluated anti-IgE monoclonal antibody included patients with serum IgE levels from 15 kU/mL through
700 kU/mL and compared omalizumab (0.016 mg/kg per IU total
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Thus, this review placed a B-III grade of evidence and recommendation against the use of long-term macrolide for nasal polyposis. This is
in contrast to a C grade of evidence and recommendation for its use in
patients with nasal polyps by the European and British guidelines.
This review has limitations. First, the quality of included studies used to generate evidence-based conclusions was limited. Several medical therapies lacked level 1 evidence and several RCTs contained moderate to high risk of bias (eTable 2 in the Supplement).
Second, some studies used different diagnostic criteria for chronic
sinusitis and included mixed cohorts of sinusitis patients (eg, with
and without nasal polyps), limiting the ability to make specific conclusions. Third, some of the meta-analyses included the same RCTs
(ie, a RCT may be included in more than 1 meta-analysis).
Evidence-Based Medical Therapy Approach: Chronic

Sinusitis With Nasal Polyposis
An evidence-based but nonvalidated approach for the medical management of patients with nasal polyposis is provided in Figure 2. The
goal is to reduce the size or eliminate nasal polyps because they can
obstruct the nasal cavity and impair the sense of smell, restrict the
ability to breathe through the nose, and obstruct physiologic drainage of the sinuses.45,96 Patients with symptomatic nasal polyps after initial medical therapy (ie, topical corticosteroid with saline irrigations) may warrant a short-course of oral corticosteroids. Because
the expected benefit of systemic corticosteroids is relatively brief
(<3 months), it should be emphasized that this treatment ought to
be combined with maintenance topical corticosteroid therapy.
Systemic antibiotic therapy is not recommended for managing
nasal polyposis. However, during periods of acute exacerbation with
superimposed infection a broad-spectrum antibiotic may be necessary to help patients return to their baseline health state. Alternatively, an endoscopic-directed sinus swab of purulent secretions
within the middle meatus may guide a culture-directed course of oral
antibiotics. Due to the demonstrated effects on reducing the size
of nasal polyps, a short-course of doxycycline (200 mg once followed by 100 mg for 21 days) or a leukotriene antagonist may be considered to further reduce polyp burden.
Patients with chronic sinusitis who experience persistent symptomsdespitecomprehensivemedicaltherapymayconsiderendoscopic
sinus surgery. All 4 multidisciplinary practice guidelines recommend
(C-I grade of evidence and recommendation) consideration of endoscopic sinus surgery for select patients with chronic sinusitis who have
persistentsymptomsdespitetrialsofappropriatemedicaltherapy.1,2,95
ARTICLE INFORMATION
Author Contributions: Drs Rudmik and Soler had
full access to all of the data in the study and take
responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: All authors.
Acquisition, analysis, or interpretation of data: All
authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important
intellectual content: All authors.
Administrative, technical, or material support: All
authors.
Study supervision: Rudmik.
Conflict of Interest Disclosures: Both authors
have completed and submitted the ICMJE Form for
jama.com
Evidence-Based Approach: Medical Therapy for Chronic

Sinusitis Without Nasal Polyps
The initial approach to managing chronic sinusitis without nasal polyps is similar to that of nasal polyposis with several notable differences (Figure 2). First, patients without polyps benefit to a greater degree from prolonged courses of macrolide therapy compared with
patients with nasal polyps. Evidence-based long-term macrolide protocols may require 3 months of clarithromycin 250 to 500 mg once
daily, roxithromycin 150 mg daily, or azithromycin 500 mg once per
week.63,97 Potential adverse effects of prolonged macrolide therapy
should be considered, including rhabdomyolysis98 and prolonged QT
interval with cardiovascular death,99 along with prolonged bleeding
risk and sedation with co-administration with warfarin and benzodiazepines, respectively (Table 3).100,101 The estimated risk of death attributable to macrolide is 1 event per every 4100 prescriptions among
patients with high cardiovascular risk and 1 event per 100 000 among
patients with low cardiovascular risk.99 Second, there is a lack of consistent evidence supporting the routine use of short-course systemic corticosteroids (C-II grade of evidence with recommendation)
in patients without polyps, whereas evidence is stronger in patients
with polyps. Lastly, there is no research evaluating the use of leukotriene antagonists for patients without nasal polyps.
Future Directions
Given the high prevalence and large economic burden of chronic
sinusitis,15 future research should improve the quality of evidence
for individual therapies and validate treatment pathways to optimize the quality of care. Furthermore, the studies included in this
review considered chronic sinusitis as a single clinical entity with subgroups defined only by polyp status. Future research should develop personalized therapies that target precise features of the patients abnormal immune-environment interaction to maximally
improve outcomes.
Conclusion
Evidence supports daily high-volume saline irrigation with topical corticosteroid therapy as a first-line therapy for chronic sinusitis. A short
course of systemic corticosteroids (1-3 weeks), short course of doxycycline (3 weeks), or a leukotriene antagonist may be considered in
patients with nasal polyps. A prolonged course (3 months) of macrolide antibiotic may be considered for patients without polyps.
Disclosure of Potential Conflicts of Interest. Dr Soler

reports receiving consulting fees from Brainlab and
Olympus and receiving grant support from the
National Institutes of Health and the National
Institute on Deafness and Other Communication
Disorders. No other disclosures were reported.
Additional Contributions: We thank Timothy L.
Smith, MD, MPH (Oregon Health and Science
University), and Rodney J. Schlosser, MD (Medical
University of South Carolina), for their academic
mentorship and support of this project. No one
received compensation for their contribution.
Submissions:We encourage authors to
submit papers for consideration as a Review.
Please contact Edward Livingston, MD,
at Edward.livingston@jamanetwork.org
or Mary McGrae McDermott, MD, at

mdm608@northwestern.edu.
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42. van den Berg JW, de Nier LM, Kaper NM, et al.
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SA, Soler ZM. Systematic review of immunotherapy
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46. Thomas WW III, Harvey RJ, Rudmik L, Hwang
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34. Joe SA, Thambi R, Huang J. A systematic

review of the use of intranasal steroids in the
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[in German]. Laryngorhinootologie. 2007;86(4):
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CD009274.
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Impact of topical nasal steroid therapy on
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Anti-inflammatory properties of montelukast, a
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montelukast and mometasone furoate in the
prevention of recurrent nasal polyps. Ther Adv
Respir Dis. 2012;6(1):5-10.
jama.com
jama.com
Study Design
(LOEa)
Systematic review
(2a)
Poetker et al,60 2013
Systematic review
(2a)
Meta-analysis (1a)
Soler et al,61 2013
Pynnonen et al,63
2013
RCT (2b)
RCT (2b)
RCT (2b)
RCT (2b)
Pinto et al,64 2010
Gevaert et al,65 2013
Gevaert et al,66 200)
Gevaert et al,67 2011
Immunomodulation
Systematic review
(3a)
Piromchai et al,62
2011
Long-term Antibiotics
Soler et al,61 2013
Systematic review
(2a)
Systematic review
(3a)
Lal and Hwang,59

2011
Short-term Antibiotics
Systematic review
(2a)
Martinez-Devesa and
Patiar,58 2011
Systemic Corticosteroids
Source
NA
Sample Size

NA
NA
NA
NA
2 (1b)
2 (1b)
1 (1b)
4 (1b) and
2 (4)
5 (2b), 2 (3b),
and 11 (4)
30 patients
24 patients
24 patients
14 patients
124 patients
NA
NA
NA
NA
1 (3b) and 6 (4) NA
3 (2b)
No. of Studies
(LOEa)
Nasal polyps
Nasal polyps
Nasal polyps
Nasal polyps
no polyps; mixed
polyp groups
Both polyp groups
No polyps
Both polyp groups
Both polyp groups
No polyps
Nasal polyps
Population
Treated
Table 4. Highest-Level Evidence for Intermittent or Rescue Therapies for Chronic Sinusitis
Anti-IL-5 (mepolizumab
750 mg for 2 doses 28 d apart)
vs placebo
Anti-IL-5 (reslizumab 1 or
3 mg/kg single infusion) vs
placebo
Anti-IgE (omalizumab max

375 mg monthly for 4 mo) vs
placebo
Anti-IgE (omalizumab
0.016 mg/kg per IU total serum
IgE/mL monthly for 6 mo) vs
placebo
Oral macrolide vs placebo
Oral antibiotic vs placebo; oral

antibiotic vs oral antibiotic
Oral corticosteroid vs placebo
Oral corticosteroids added to

other multimodality treatment
strategies
Oral corticosteroid vs placebo
Study Groups
Polyp score and radiographic
Polyp score, nasal patency,

symptom score, and
inflammatory markers
Polyp score, radiographic,

QOL, symptoms, and nasal
mucosal inflammation
Radiographic, QOL, nasal

patency, olfaction, and nasal
mucosal inflammation
QOL
Symptom, QOL, endoscopy,

mucus transport, and
olfaction

mucus transport, and
olfaction
Symptom, endoscopy, polyp

size, cure, and radiographic

and radiographic
Symptom, radiographic,
endoscopy, and nasal
secretions

radiographic, and adverse
events
Primary End Point
(continued)
Mepolizumab was associated with a greater change in polyp

score from baseline (mean change, 1.30 vs 0.0 [on a 0-4
scale]; P = .028) compared with placebo at 8 wk; significant
improvements were also seen in mean CT score
No difference in efficacy outcomes but was not designed with

sufficient power
Omalizumab was associated with improved polyp scores

(mean reduction, 2.67 vs 0.12 [on a 0-4 scale]; P = .02)
after 16 wk of treatment compared with placebo; significant
improvements were also seen in CT score, individual symptoms,
and QOL
No differences in the median changes in CT score (11.9% vs

5.9% reduction; P = .391), QOL score (mean reduction, 5.5 vs
2.3; P = .60), olfaction score (mean reduction, 3 vs 4
; P = .31), nasal endoscopy score (mean reduction, 0 vs 0.5;
P = .58), eosinophils in nasal lavage (mean reduction, 2 vs 9;
P = .47), and total symptom scores (mean reduction, 1 vs 0;
P = .21) between omalizumab and placebo, respectively
Macrolide for 3 mo was associated with improved QOL

compared with placebo at a single time point after starting
therapy (24 wk) (SMD, 0.43 [95% CI, 0.82 to 0.05]); the
clinical significance of this improvement is questionable
Macrolide for 3 mo was superior to placebo for patients with no

polyps, particularly those with low IgE; macrolide therapy was
no different than placebo in mixed group of patients with and
without polyps
Roxithromycin for 3 mo was superior to placebo for patients

without polyps; no difference in outcomes 12 wk after stopping
therapy
Uncontrolled trials demonstrate mixed outcomes in patients

without polyps; a level 1b study demonstrated that doxycycline
therapy was superior to placebo for reducing polyp size up to
12 wk after completing the therapy (P = .015)
Oral corticosteroids improve short-term symptoms, QOL, and

endoscopy scores for nasal polyps compared with placebo;
inadequate evidence to support the use of oral corticosteroids
for patients without polyps
Inadequate evidence to support the use of oral corticosteroids

for patients without polyps
Oral corticosteroids improve short-term symptoms, QOL,

and endoscopy compared with placebo
Conclusions

933
934
Systematic review
(2a)
Systematic review
(2a)
Systematic review
(2a)
Rudmik et al,41 2013
Soler et al,61 2013
Wei et al,69 2013
Meta-analysis (1a)
Meta-analysis (1a)
Sacks et al,71 2011
Wang et al,72 2014

5 (1b)
5 (1b)
3 (1b) and
3 (2b)
2 (2b)
2 (1b), 1 (2b),
2 (2c), and
4 (4)
2 (1b), 1 (2b),
1 (2c), 2 (3a),
and 4 (4)
5 (2b), 2 (3b),
and 7 (4)
No. of Studies
(LOEa)
300 patients
327 patients
284 patients
NA
NA
NA
NA
Sample Size
Topical
amphotericin B
vs placebo
Topical
amphotericin B
vs placebo
Topical
amphotericin B
vs placebo
No polyps
No polyps
No polyps
No polyps
Population
Treated
No polyps
No polyps
No polyps
QOL and endoscopy
Symptom, QOL,
and adverse effects
Symptom, endoscopy,
and radiologic
Symptom, QOL,
and endoscopy
Symptom, QOL,
and endoscopy
QOL and endoscopy score
QOL, endoscopy score,

and bacterial culture rates
Primary End Point
Topical amphotericin B was no different than placebo for

no polyps
Topical amphotericin failed to improve QOL (SMD, 0.18

[95% CI, 0.05 to 0.42]) and endoscopy scores (SMD, 0.00
[95% CI, 0.26 to 0.26]); placebo improved symptom scores
compared with topical amphotericin B (SMD, 0.35 [95% CI,
0.07 to 0.63])
Topical amphotericin B was no different than placebo in all 3

outcomes (all P > .11)
There is insufficient evidence to support the use of topical

antibiotic therapy for patients without polyps
Evidence does not support the routine use of topical antibiotic

therapy for chronic sinusitis
Evidence does not support the routine use of topical antibiotic

therapy chronic sinusitis; single level 1b study demonstrated
that high-volume mupirocin irrigations were superior to
placebo when sinus cultures were positive for
Staphylococcus aureus
Nebulized and spray-delivered topical antibiotics failed to

improve outcomes in level 2b studies; lower-quality studies
demonstrate a potential benefit of topical antibiotic therapy for
chronic sinusitis without polyps
Conclusions
Level of evidence scale was from the Oxford Centre for Evidence-based Medicine.31
Tobramycin and neomycin
Fosfomycin, N-chlorotaurine,
bacitracin, tobramycin,
mupirocin, and neomycin
Neomycin, tobramycin-saline,
bacitracin, gentamycin, and
mupirocin
Neomycin, tobramycin,
ceftazidime, N-chlorotaurine,
dibekacin, fosfomycin,
mupirocin, and amphotericin B
Study Groups
Abbreviations: CT, computed tomography; IL, interleukin; INS, intranasal steroid; LOE, level of evidence; NA, not
applicable; QOL, quality of life; RCT, randomized clinical trial; SMD, standardized mean difference.
Meta-analysis (1a)
Isaacs et al,70 2011
Topical Antifungals
Systematic review
(2a)
Study Design
(LOEa)
Lim et al,68 2008
Topical Antibiotics
Source
Table 4. Highest-Level Evidence for Intermittent or Rescue Therapies for Chronic Sinusitis (continued)

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Table 5. Comparison of Guideline Recommendations for Medical Therapies in the Management of Chronic Sinusitis
Recommendation Levela
Grade of Evidence and
Recommendation: Current Review
EPOS Guidelines 20122
Canadian Sinusitis
Guidelines 20111
BSACI Guidelines 200895
Nasal Polyps
Nasal Polyps No Polyps
No Polyps
Maintenance Therapies
Topical corticosteroid
A-I
A-I
++
++
++
++
++
++
Saline irrigations
A-I
A-I
++
++
++
LTA
A-II
None
None
None
NE
Systemic antihistamineb
None
None
None
None
++
++
Allergy immunotherapy
C-II
C-II
None
None
NE
NE
Intermittent or Rescue Therapies

Systemic corticosteroid
A-I
C-II
++
++
++
Short-term antibiotic
B-Ic
A-II
Long-term macrolide
B-III
A-II
++
Anti-IgE monoclonal antibody
A-II
None
None
NE
NE
NE
NE
Anti-IL-5 monoclonal antibody
A-II
None
None
NE
NE
NE
NE
Topical antibiotic
None
A-III
None
NE
NE
Topical antifungal
None
A-III
None
NE
NE
Abbreviations: BSACI, British Society for Allergy and Clinical Immunology;

EPOS, European Position Paper on Sinusitis; LTA, leukotriene antagonist; NE,
not evaluated.
a
Recommendation level symbols indicate the following: + +, strong

recommendation for use; +, weak recommendation for use; , strong
recommendation against use; , weak recommendation against use; none,
represents the topic was evaluated but lack of evidence resulted in no
recommendation provided.
serum IgE/mL; max dose of 375 mg) to placebo (Table 4). Both studies lacked statistical power and contained moderate estimates of bias
making it challenging to draw definitive conclusions from the reported associations between improved radiologic (ie, computerized tomography scan) and polyp scores at 16 weeks of omalizumab compared with placebo.
to anti-IgE therapy for chronic sinusitis with nasal polyposis and
asthma. No evidence grade and recommendation is assigned for antiIgE therapy for patients without nasal polyps.
AntiInterleukin 5 Therapy
Anti-interleukin 5 (IL-5) therapy involves delivering a humanized
IgG monoclonal antibody that binds free IL-5 and impairs
eosinophilic-mediated inflammation.89 Two RCTs evaluated antiIL-5 therapy (reslizumab and mepolizumab) for nasal polyposis
(Table 4).66,67 Both studies were small (n 30), lacked long-term
follow-up, and contained moderate to high estimates of bias.
Reslizumab (1 or 3 mg/kg) did not improve symptom scores compared with placebo but slightly reduced blood eosinophil levels.
Mepolizumab (2 injections of 750 mg received 28 days apart) was
associated with improved polyp scores in approximately 50% of
patients compared with placebo but the study did not evaluate
patient-reported outcomes.
for anti-IL-5 monoclonal antibody therapy in patients with nasal polyposis. No grade of evidence or recommendation is assigned for antiIL-5 therapy for patients without nasal polyps.
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Antihistamines are not indicated as sinusitis-specific treatment but should be

considered in patients with concurrent allergic rhinitis.
Short-term antibiotic use in patients with nasal polyps limited to doxycycline

200 mg once then 100 mg daily for 20 days.73
Topical Antibacterials
Four systematic reviews41,61,68,69 evaluated topical antibiotics for
chronic sinusitis without nasal polyps (Table 4). All RCTs contained
small sample sizes, evaluated different topical antibiotics, and used
different application techniques. Three RCTs demonstrated no difference in clinical outcomes compared with placebo. One RCT demonstrated improved short-term symptom improvement using a highvolume (240 mL divided between 2 nasal cavities) mupirocin
irrigation compared with placebo in a specific cohort of patients with
a sinus culture positive for Staphylococcus aureus.90 There was no
difference in sinus-specific QOL with mupirocin irrigation compared with placebo.
In summary, the routine use of topical antibiotics during the management of chronic sinusitis without nasal polyps is not recommended and has an A-III grade designation. High-volume topical mupirocin irrigations may be appropriate therapy in select cases of
recalcitrant disease with a sinus culture positive for S aureus. No grade
of evidence or recommendation is designated for the use of topical
antibiotics for nasal polyposis.
Topical Antifungals
Fungi colonize the nasal mucosa in 96% of both chronic sinusitis
patients and healthy controls.91,92 This created a hypothesis that
an abnormal immunological response to fungi may cause chronic
sinusitis and eradication of fungi may resolve sinus disease.93,94
Topical amphotericin B binds ergosterol (a component of the fungal cell membrane) and creates a transmembrane ion channel
leading to fungal death.
935
Figure 2. Evidence-Based Approach to Medical Therapy for Chronic Sinusitis

Chronic sinusitis
(see Box 1)
Topical intranasal corticosteroids (daily)

and saline irrigations (daily)
No
Active mucopurulence present?
Yes
Short-course antibiotic
Culture-directed or broad
spectrum when indicated
Reassess in 1 to 3 months
Persistent symptomsa
or acute exacerbation
Resolved or mild symptomsb
Continue treatment
Yes
Nasal polyps present?
No
Short course of systemic corticosteroidc for
Long-term antibiotic (macrolide)d
14-21 days
Prednisone 30-50 mg daily (taper when indicated)
Prednisolone 20-60 mg daily (taper when indicated)
Consider
Short course of doxycycline 200 mg once followed
by 100 mg daily for 21 days
Culture-directed antibiotic (in the presence
of mucopurulent discharge on examination)
Clarithromycin 250-500 mg daily for 3 months

Roxithromycin 150 mg daily for 3 months
Consider
Short course of systemic corticosteroidc
Culture-directed short-course antibiotic (only in the
presence of mucopurulent discharge on examination)
Persistent symptomsa
No
Persistent symptoms implies that

the patient is still experiencing
chronic sinusitisspecific symptoms
that are negatively effecting quality
of life and daily productivity or
functioning.
Mild symptoms implies that the

patient is still experiencing chronic
sinusitisspecific symptoms but
they are not negatively effecting
quality of life and daily productivity
or functioning.
Patient and physician should

participate in an open discussion
about the known benefits and the
potential adverse effects of
systemic corticosteroids to help
inform patient decision making.
Risk of cardiac arrhythmia and

cardiovascular death; risk of
rhabdomyolysis in patients
currently taking an oral
3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase
inhibitor.
Continue treatment
Yes
Does patient have concurrent
allergic rhinitis?
No
Yes
Consider
Systemic antihistamine
Leukotriene pathway antagonist
Allergy immunotherapy
Consider endoscopic sinus surgery
Resolved or mild symptomsb
Three meta-analyses (327 patients)70-72 demonstrated no benefitoftopicalamphotericinBcomparedwithplaceboforpatientswithout nasal polyps. Therefore, use of topical antifungals for chronic sinusitis without nasal polyps is not recommended and has an A-III grade
designation. No grade of evidence can be made for nasal polyposis.
Discussion
Basedonavailableevidence,medicaltherapyforchronicsinusitisshould
begin with daily application of a topical intranasal corticosteroid in conjunction with high-volume saline irrigation. Subsequent therapies are
based on the patients polyp status and severity of symptoms or QOL
impairment. Although there have been several published guidelines
evaluating adult chronic sinusitis,1-3,95 only 3 include specific treatment
936
recommendations.1,2,95 Table 5 summarizes the overall grades of evidence from this review and how they compare with published guidelines from Europe, Canada, and the United Kingdom.
First, there were differences regarding use of leukotriene antagonists for treating nasal polyposis. The outcomes from 2 RCTs
evaluating leukotriene antagonists demonstrated mixed results;
therefore, available evidence is consistent with an A-II grade of evidence and recommendation. This differs from the A grade of evidence and recommendation against the use of leukotriene antagonists (ie, equivalent to an A-III grade) to treat nasal polyposis made
in the European guidelines.
Second, there were differences pertaining to the use of long-term
macrolide therapy in patients with nasal polyps. The only RCT evaluating long-term macrolide therapy, which included patients with nasal polyposis, demonstrated no difference compared with placebo.
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Thus, this review placed a B-III grade of evidence and recommendation against the use of long-term macrolide for nasal polyposis. This is
in contrast to a C grade of evidence and recommendation for its use in
patients with nasal polyps by the European and British guidelines.
This review has limitations. First, the quality of included studies used to generate evidence-based conclusions was limited. Several medical therapies lacked level 1 evidence and several RCTs contained moderate to high risk of bias (eTable 2 in the Supplement).
Second, some studies used different diagnostic criteria for chronic
sinusitis and included mixed cohorts of sinusitis patients (eg, with
and without nasal polyps), limiting the ability to make specific conclusions. Third, some of the meta-analyses included the same RCTs
(ie, a RCT may be included in more than 1 meta-analysis).
Evidence-Based Medical Therapy Approach: Chronic

Sinusitis With Nasal Polyposis
An evidence-based but nonvalidated approach for the medical management of patients with nasal polyposis is provided in Figure 2. The
goal is to reduce the size or eliminate nasal polyps because they can
obstruct the nasal cavity and impair the sense of smell, restrict the
ability to breathe through the nose, and obstruct physiologic drainage of the sinuses.45,96 Patients with symptomatic nasal polyps after initial medical therapy (ie, topical corticosteroid with saline irrigations) may warrant a short-course of oral corticosteroids. Because
the expected benefit of systemic corticosteroids is relatively brief
(<3 months), it should be emphasized that this treatment ought to
be combined with maintenance topical corticosteroid therapy.
Systemic antibiotic therapy is not recommended for managing
nasal polyposis. However, during periods of acute exacerbation with
superimposed infection a broad-spectrum antibiotic may be necessary to help patients return to their baseline health state. Alternatively, an endoscopic-directed sinus swab of purulent secretions
within the middle meatus may guide a culture-directed course of oral
antibiotics. Due to the demonstrated effects on reducing the size
of nasal polyps, a short-course of doxycycline (200 mg once followed by 100 mg for 21 days) or a leukotriene antagonist may be considered to further reduce polyp burden.
Patients with chronic sinusitis who experience persistent symptomsdespitecomprehensivemedicaltherapymayconsiderendoscopic
sinus surgery. All 4 multidisciplinary practice guidelines recommend
(C-I grade of evidence and recommendation) consideration of endoscopic sinus surgery for select patients with chronic sinusitis who have
persistentsymptomsdespitetrialsofappropriatemedicaltherapy.1,2,95
ARTICLE INFORMATION
Author Contributions: Drs Rudmik and Soler had
full access to all of the data in the study and take
responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: All authors.
Acquisition, analysis, or interpretation of data: All
authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important
intellectual content: All authors.
Administrative, technical, or material support: All
authors.
Study supervision: Rudmik.
Conflict of Interest Disclosures: Both authors
have completed and submitted the ICMJE Form for
jama.com
Evidence-Based Approach: Medical Therapy for Chronic

Sinusitis Without Nasal Polyps
The initial approach to managing chronic sinusitis without nasal polyps is similar to that of nasal polyposis with several notable differences (Figure 2). First, patients without polyps benefit to a greater degree from prolonged courses of macrolide therapy compared with
patients with nasal polyps. Evidence-based long-term macrolide protocols may require 3 months of clarithromycin 250 to 500 mg once
daily, roxithromycin 150 mg daily, or azithromycin 500 mg once per
week.63,97 Potential adverse effects of prolonged macrolide therapy
should be considered, including rhabdomyolysis98 and prolonged QT
interval with cardiovascular death,99 along with prolonged bleeding
risk and sedation with co-administration with warfarin and benzodiazepines, respectively (Table 3).100,101 The estimated risk of death attributable to macrolide is 1 event per every 4100 prescriptions among
patients with high cardiovascular risk and 1 event per 100 000 among
patients with low cardiovascular risk.99 Second, there is a lack of consistent evidence supporting the routine use of short-course systemic corticosteroids (C-II grade of evidence with recommendation)
in patients without polyps, whereas evidence is stronger in patients
with polyps. Lastly, there is no research evaluating the use of leukotriene antagonists for patients without nasal polyps.
Future Directions
Given the high prevalence and large economic burden of chronic
sinusitis,15 future research should improve the quality of evidence
for individual therapies and validate treatment pathways to optimize the quality of care. Furthermore, the studies included in this
review considered chronic sinusitis as a single clinical entity with subgroups defined only by polyp status. Future research should develop personalized therapies that target precise features of the patients abnormal immune-environment interaction to maximally
improve outcomes.
Conclusion
Evidence supports daily high-volume saline irrigation with topical corticosteroid therapy as a first-line therapy for chronic sinusitis. A short
course of systemic corticosteroids (1-3 weeks), short course of doxycycline (3 weeks), or a leukotriene antagonist may be considered in
patients with nasal polyps. A prolonged course (3 months) of macrolide antibiotic may be considered for patients without polyps.
Disclosure of Potential Conflicts of Interest. Dr Soler

reports receiving consulting fees from Brainlab and
Olympus and receiving grant support from the
National Institutes of Health and the National
Institute on Deafness and Other Communication
Disorders. No other disclosures were reported.
Additional Contributions: We thank Timothy L.
Smith, MD, MPH (Oregon Health and Science
University), and Rodney J. Schlosser, MD (Medical
University of South Carolina), for their academic
mentorship and support of this project. No one
received compensation for their contribution.
Submissions:We encourage authors to
submit papers for consideration as a Review.
Please contact Edward Livingston, MD,
at Edward.livingston@jamanetwork.org
or Mary McGrae McDermott, MD, at

mdm608@northwestern.edu.
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Clinical Review & Education

Medical Therapies for Adult Chronic Sinusitis

IMPORTANCE Chronic sinusitis is a common inflammatory condition defined by persistent

Author Audio Interview at

Author Affiliations: Department of

JAMA. 2015;314(9):926-939. doi:10.1001/jama.2015.7544

Section Editors: Edward Livingston,

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Medical Therapies for Adult Chronic Sinusitis

Review Clinical Review & Education

Maintenance Medical Therapies for Chronic Sinusitis

Corticosteroids reduce sinonasal mucosal inflammation, decrease

Copyright 2015 American Medical Association. All rights reserved.

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Clinical Review & Education Review

Medical Therapies for Adult Chronic Sinusitis

Box 1. Consensus-Based Diagnostic Criteria for Chronic Sinusitis

Reduced sense of smell

Nasal polyps on anterior rhinoscopy or nasal endoscopy

CT indicates computed tomography.

One of the 2 symptoms must be either obstruction or discharge.

Source: US, European, and Canadian guidelines on chronic sinusitis1-3

Leukotriene Pathway Antagonists

Table 1. Presenting Symptoms of Chronic Sinusitis

Data sources: Bhattacharyya,4,5 Soler et al,6 and Dietz de Loos et al.7

In summary, an A-II grade and recommendation supports using

Antihistamines and Allergy Immunotherapy

Intermittent or Rescue Medical Therapies

JAMA September 1, 2015 Volume 314, Number 9 (Reprinted)

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Medical Therapies for Adult Chronic Sinusitis

Review Clinical Review & Education

Figure 1. Proposed Mechanisms of Action for Chronic Sinusitis Medical Therapies

Treat bacterial infection

Fibroblast activation and

Binds free IL-5

(Reprinted) JAMA September 1, 2015 Volume 314, Number 9

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Clinical Review & Education Review

Medical Therapies for Adult Chronic Sinusitis

Box 2. American Heart Association Grade of Evidence and

polyps comes from prospective case series without control groups

Short-term Oral Antibiotics (Nonmacrolide)

analysis. One RCT evaluated 200 mg of doxycycline once, followed

Long-term Macrolide Therapy

JAMA September 1, 2015 Volume 314, Number 9 (Reprinted)

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Medical Therapies for Adult Chronic Sinusitis

Review Clinical Review & Education

Evidence-Based Medical Therapy Approach: Chronic

Evidence-Based Approach: Medical Therapy for Chronic

Disclosure of Potential Conflicts of Interest. Dr Soler

or Mary McGrae McDermott, MD, at

(Reprinted) JAMA September 1, 2015 Volume 314, Number 9

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Clinical Review & Education Review

Medical Therapies for Adult Chronic Sinusitis

4. Bhattacharyya N. The economic burden and

23. Adappa ND, Howland TJ, Palmer JN, et al.