Intranasal Corticosteroids in Management

of Acute Sinusitis: A Systematic Review and

Meta-Analysis
Gail Hayward, MBBChir, DPhil
Carl Heneghan, BM, BCH, MA,

ABSTRACT

MRCGP, DPhil

frequently treated with antibiotics, despite little evidence of their benefit. Intranasal corticosteroids might relieve symptoms; however, evidence for this benefit
is currently unclear. We performed a systematic review and meta-analysis of the
effects of intranasal corticosteroids on the symptoms of acute sinusitis.

Rafael Perera, MSc, DPhil

Matthew Thompson, MBChB,
MPH, DPhil, MRCGP
Department of Primary Care Health Sciences, Oxford University, Oxford, England

PURPOSE Acute sinusitis is a common condition in ambulatory care, where it is

METHODS We searched MEDLINE, EMBASE, the Cochrane Central register of

Controlled Trials (CENTRAL), and Centre for Reviews and Dissemination databases
until February 2011 for studies comparing intranasal corticosteroids with placebo
in children or adults having clinical symptoms and signs of acute sinusitis or rhinosinusitis in ambulatory settings. We excluded chronic/allergic sinusitis. Two authors
independently extracted data and assessed the studies methodologic quality.
RESULTS We included 6 studies having a total of 2,495 patients. In 5 studies,
antibiotics were prescribed in addition to corticosteroids or placebo. Intranasal
corticosteroids resulted in a significant, small increase in resolution of or improvement in symptoms at days 14 to 21 (risk difference [RD] = 0.08; 95% CI, 0.030.13). Analysis of individual symptom scores revealed most consistently significant
benefits for facial pain and congestion. Subgroup analysis by time of reported
outcomes showed a significant beneficial effect at 21 days (RD = 0.11; 95% CI,
0.06-0.17), but not at 14 to 15 days (RD = 0.05; 95% CI, 0.01 to 0.11). Metaregression analysis of trials using different doses of mometasone furoate showed
a significant dose-response relationship (P = .02).
CONCLUSIONS Intranasal corticosteroids offer a small therapeutic benefit in acute

sinusitis, which may be greater with high doses and with courses of 21 days
duration. Further trials are needed in antibiotic-nave patients.
Ann Fam Med 2012;10:241-249. doi:10.1370/afm.1338.

INTRODUCTION

A
Conicts of interest: authors report none.

CORRESPONDING AUTHOR

Gail Hayward, MBBChir, DPhil

Department of Primary Care Health
Sciences
2nd oor, 23-38 Hythe Bridge St
Oxford, OX1 2ET United Kingdom
gail.hayward@phc.ox.ac.uk

cute sinusitis is a common condition, affecting an estimated 31 million Americans annually.1 The majority of patients seen in primary
care for acute sinusitis are prescribed antibiotics,2,3 despite evidence
that they provide limited benet.4-6 The effectiveness of other treatments
such as decongestants and antihistamines is largely unknown.7,8 Corticosteroids are effective in reducing symptoms in other upper respiratory
tract infections such as croup, sore throat, and infectious mononucleosis,
and their anti-inammatory effects may be helpful for reducing sinus congestion and facilitating drainage in sinusitis.9-12
Currently, it is not clear whether corticosteroids offer signicant benets for patients with acute sinusitis. In particular, there have been no
good-quality double-blind randomized controlled trials (RCTs) examining
oral corticosteroids in acute sinusitis, even though the oral route is favored
for other upper respiratory tract infections. In terms of intranasal steroids,

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a Cochrane review of 4 RCTs showed a small benecial

effect on improvement of symptoms at 15 to 21 days;
however, interpretation was limited by both high heterogeneity and differing outcome measures used in the
primary studies.13 A recent large RCT found no difference between intranasal corticosteroids and placebo
for sinusitis.14 This trial was not included in the recent
Cochrane review.13
Given the conicting evidence, there is a pressing
clinical need to clarify whether intranasal corticosteroids should be prescribed for patients with acute
sinusitis. Accordingly, we undertook a systematic
review of the most recent evidence to attempt to
resolve this question.

METHODS
Search Strategy and Selection
We included in our meta-analysis RCTs that compared
intranasal corticosteroids with placebo in children or
adults who had clinical symptoms and signs of acute
sinusitis or rhinosinusitis, in outpatient (ambulatory)
settings. We excluded studies examining patients
with chronic/allergic sinusitis and studies performed
exclusively in patient populations selected because of
chronic underlying health conditions (eg, immunocompromised patients).
We searched MEDLINE, EMBASE, the Cochrane
Library including the Cochrane Central register
of Controlled Trials (CENTRAL), the Database of
Reviews of Effectiveness (DARE), and the National
Health Service Health Economics Database from
the beginning of each database until February 2011
using a maximally sensitive strategy.15 Medical Subject
Heading (MeSH) terms used included rhinosinusitis,
sinusitis, and corticosteroids (including dexamethasone, betamethasone, prednisone, and all variations of these terms)
and viral and bacterial upper respiratory tract pathogens (full search strategy available from authors).
Two authors independently reviewed the titles and
abstracts of electronic searches, obtaining full-text
articles to assess for relevance where necessary. Disagreements were resolved by discussion with a third
author. We performed citation searches of all full-text
papers retrieved.
Data Extraction and Quality Assessment
Two authors independently assessed the methodologic quality of studies. Quality was assessed using
the criteria of allocation concealment, randomization,
comparability of groups at baseline, blinding, treatment
adherence, and percentage participation. Two authors
independently extracted data using an extraction template. In both data extraction and quality assessment,
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disagreements were documented and resolved by discussion with a third author.

Primary outcomes included the proportion of participants with improvement or complete resolution
of symptoms. Secondary outcomes included mean
change in symptom scores over 0 to 21 days, adverse
events, relapse rates, and days missed from school/
work. Where necessary, we used Grab It XP Microsoft
Excel software (http://www.datatrendsoftware.com) to
extract data from gures.
Data Synthesis and Analysis
For pooled analysis of dichotomous outcomes, we calculated the risk difference (RD), 95% CI, and number
needed to treat (NNT). For continuous variables, we
used weighted mean difference and 95% CIs. We tested
dose response by undertaking a post hoc subgroup
analysis according to intranasal corticosteroid dosage.
We used meta-regression in Stata (StataCorp, LP) to
test subgroup interactions on the outcomes and the I2
statistic to measure the proportion of statistical heterogeneity for each outcome.16 Where no heterogeneity
was present, we performed a xed-effect meta-analysis.
Where substantial heterogeneity was detected, we
looked for the direction of effect and considered the
reasons for this heterogeneity. Where applicable, we
used a random-effects analysis or considered not pooling the outcomes and reporting the reasons for this.

RESULTS
Study Characteristics
We identied 3,257 potentially relevant study records,
of which 21 were relevant to acute sinusitis/rhinosinusitis (Figure 1). We excluded 15 of these studies for the
following reasons: 5 were abstracts only with no full
paper published or available from the authors, 3 were
not limited to acute sinusitis, 3 examined oral steroids,
3 did not directly compare steroids and placebo, and 1
examined prevention of acute sinusitis.
The characteristics of included studies are presented in Table 1. The 6 included studies randomized
2,495 patients recruited from outpatient otorhinolaryngology, emergency medicine, and general practice
settings in 3 countries: the United States (4 studies),
Turkey (1), and United Kingdom (1). The age range
of participants varied: 12 years or older (3 studies); 16
years or older (1); 18 years or older (1); and 15 years or
younger (1). The corticosteroids used were budesonide
(2 studies), uticasone propionate (1), and mometasone
furoate (3). Two trials compared 2 different doses of
mometasone furoate.17,18
In addition to intranasal corticosteroids, 5 trials14,18-21 prescribed antibiotics (amoxicillin, co-amox-

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iclav, or cefuroxime) to patients in both groups. One

of these trials19 prescribed intranasal xylometazoline
hydrochloride to all participants before administration of the study spray for the rst 3 days. Two trials
reported outcomes based on computed tomography
scans of sinuses.18,21
All 6 included studies demonstrated adequate allocation concealment, blinding, percentage participation,
and comparability of groups both at baseline and in
provision of care apart from the intervention; however,
3 studies did not report the method of randomization
(Table 2). We therefore performed a sensitivity analysis
excluding these studies.
Resolution or Improvement of Symptoms at
Days 14 to 21
In 5 RCTs14,17,18,20,21 that assessed resolution or improvement of symptoms at days 14 to 21, intranasal steroids
had a modest clinical benecial effect, with an RD of

Figure 1. Flow diagram of search results.

3,257 Potentially relevant records
for corticosteroids and upper respiratory tract infection identified and
screened by 2 reviewers

2,817 Records excluded

as not relevant

419 Records on other

upper respiratory tract
infection

21 Articles examining sinusitis

15 Articles excluded:
5 Abstracts with insufficient
information
3 Not limited to acute
sinusitis
3 Examined oral steroids
3 Had no direct comparison
of steroid and placebo
combinations

Individual Symptom Scores

Three RCTs reported individual symptom scores in
5 groups of patients who received different doses of
mometasone furoate compared with placebo17,18,21 For
each group, the symptoms of facial pain, nasal congestion, headache, rhinorrhea, postnasal drip, and cough

1 Studied prevention of
acute sinusitis

6 Articles meeting all

inclusion criteria

Outcome Timing
Combining the 3 studies reporting this outcome at 14
to 15 days14,17,20 showed no signicant effect of intranasal corticosteroids, with an RD of 0.05 (95% CI,
0.01 to 0.11; P = .13; I2 = 22%) (Figure 2A). In contrast,
combining the 3 studies that reported resolution or
improvement at 21 days18,20,21 showed that intranasal
corticosteroids had a signicant benecial effect with
no heterogeneity, with an RD of 0.11 (95% CI, 0.060.17; P <.001; I2 = 0) and an NNT of 9 (95% CI, 6-17)
(Figure 2B).
In the 2 trials14,20 that reported the proportion of
participants with persistent symptoms at 10 days after
onset of treatment, there was no benet of intranasal
corticosteroids, with an RD of 0.06 (95% CI, 0.09
to 0.22; P = .41; I2 = 47%). Two trials reported a small
but signicant 7% absolute improvement in physician
evaluation scores at 21 days in patients receiving intranasal steroids vs placebo (Nayak et al18: 61% vs 53%,
P = .006; Meltzer et al21: 68% vs 61%, P <.01).
Dose-Dependent Benefit
Three trials using mometasone furoate nasal spray17,18,21
showed a signicant effect on symptom resolution
or improvement at 15 to 21 days, with an RD of 0.08
(95% CI, 0.01-0.14; P = .02; I2 = 62%) and an NNT of
13 (95% CI, 7-100). The daily dose of mometasone
furoate ranged in these 3 trials from 200 g to 800
g. We therefore investigated the high heterogeneity
by performing subgroup analysis by dose. As depicted
in Figure 3, meta-regression analysis of mometasone
furoate dose and symptom resolution showed a signicant dose-response relationship (P = .02), with the
effect size increasing with dose. For patients receiving
800 g of mometasone furoate nasal spray daily, the
RD was 0.12 (95% CI, 0.06-0.18; P = .0002) and the
NNT was 8 (95% CI, 6-17); for those receiving 400 g
daily, the RD was 0.07 (95% CI, 0.03-0.11; P = .001)
and the NNT was 14 (95% CI, 9-33).

440 Potentially relevant records

screened by 2 reviewers

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0.08 (95% CI, 0.03-0.13; P = .004; I2 = 47%) and an

NNT of 13 (95% CI, 8-33). This overall result was
similar even with the removal of the 2 trials of lower
quality,18,21 with an RD of 0.07 (95% CI, 0.01-0.12;
P = .02; I2 = 43%). Given that both analyses showed heterogeneity, however, we performed subgroup analyses
on outcome timing and on dosage.

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Table 1. Characteristics of Trials Included in the Meta-Analysis

No. Analyzed

Study (Year and

Location)

Age Range
(Mean), y

Intervention

Control

Williamson et al14
(2007; United
Kingdom, general
practice)

16 (42.5)

102a

105b

Meltzer et al17 (2005;

14 countries, medical centers)

12 (35.3)

Nayak et al18 (2002;

United States, 61
treatment centers)

12 (39.1)

Criteria for Sinusitis; Duration of Symptoms at Entry

2 of following: predominantly unilateral purulent nasal discharge and
local pain, bilateral purulent nasal discharge, pus on inspection
Median duration of symptoms 7 days (IQR 10)

478

252

Symptoms score 5/15 (scores of 0 = none to 3 = severe for facial pain,

nasal congestion, headache, rhinorrhea, and postnasal drip)
Clinical signs/symptoms for >7 days but <28 days

642

325

Coronal CT evidence of sinusitis

Total symptom score of 6/18 (scores of 0 = none to 3 = severe for facial
pain, nasal congestion, headache, rhinorrhea, cough, and postnasal
drip)
No information on duration given

Dolor et al20 (2001;

United States,
12primary care and
10otorhinolaryngology clinics)

18

Meltzer et al21
(2000; United
States, 29 medical
centers, outpatient)

12 (40.4)

47

48

History of recurrent sinusitis

Clinical criteria: 2/5 of headache; facial pain and pressure; nasal congestion; purulent nasal discharge; and olfactory disturbance; and Water
radiographic or endoscopic evidence of sinusitis
No information on duration given

200

207

History of sinusitis episodes separated by symptom-free periods

Symptom score >6/18 (scores of 0 = none to 3 = severe on facial pain,
nasal congestion, headache, rhinorrhea, cough, and postnasal drip)
and coronal CT evidence of sinusitis
Mean duration of symptoms 13.5 days

Barlan et al19 (1997;

Turkey, pediatric
outpatient clinic)

15 (6.95)

43

46

Clinical criteria: 2/3 of purulent nasal discharge, purulent pharyngeal

drainage, and cough, or 1/3 of the above plus 2 of facial or tooth pain,
edema, earache, sore throat, wheeze, headache, fever, and foul breath
No information on duration given

CT = computed tomography; IQR = interquartile range; MFNS = mometasone furoate nasal spray; MSS = mean symptom score; SNOT-20 = 20-item Sino-Nasal Outcome Test.24
Total dose both nostrils.
Factorial design means that each group included patients receiving both active and placebo antibiotics.
c
Results of the 2 arms were combined for the overall analysis.
d
A third arm evaluated amoxicillin 500 mg 3 times a day; therefore, these patients also received placebo capsules as a control for amoxicillin.
a

were reported on a scale of 0 (none) to 3 (severe)

at baseline and averaged across the rst 15 days of
therapy (see the Supplemental Appendix at http://
www.annfammed.org/content/10/3/241/suppl/DC1
for full data). Compared with their counterparts
who received placebo, patients who received intranasal
corticosteroids in these 3 trials reported signicantly
greater improvement in facial pain (3 of the trials), conANNALS O F FAMILY MED ICINE

gestion (3), rhinorrhea (2), headache (1), and postnasal

drip (1) (all P <.05).
Adverse Events
One trial reported that no adverse events occurred
with steroid therapy19; 2 trials reported no serious
adverse events in either group14,20; and the remaining
trials reported that adverse events were mainly mild or

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Treatment
Interventiona

Control

400 g budesonide
once daily for 10
days

Placebo spray

2 arms:c,d

Placebo spray

MFNS 200 g twice

daily or

Other Medications
Used

Outcomes and Definition of Symptom

Resolution

Analgesia

Amoxicillin 500 mg 3
times a day for 7 days
or placebo, factorial
design used

Not restricted,
not reported

Separate study arm

received amoxicillin

Resolution = patient reporting 0 or 1 on 7-point

scale for 11 individual symptom scores
Major symptom score = sum of individual symptom scores over days 2-15 of treatment

Prohibited

Time to onset of MSS being statistically different

from placebo
Global response to treatment at day 15
Adverse events
Recurrence

Each given for 15 days

Placebo spray

MFNS 200 g twice

daily or

Amoxicillinclavulanate
potassium 875 mg twice
daily for 21 days

Not specifically
commented on;
not recorded

MFNS 400 g twice

daily

Resolution = absence of failure of treatment

Change from baseline in total symptom score
CT appearance of sinuses at 21 days
Percent of patients with resolution of symptoms
Adverse events

Each given for 21 days

400 g fluticasone
propionate once
daily for 21 days

Time to resolution of symptoms

Percent with complete resolution of symptoms up
to day 14

MFNS 200 g once

in the morning
with placebo spray
in the evening

2 arms:c

Symptom scores assessed on 7-point scales

Placebo spray

Cefuroxime axetil 250 mg

twice daily for 10 days

Allowed,
unregulated

2 puffs of xylometazoline
hydrochloride in each
nostril 10 min before
the study nasal spray for
the first 3 days

Resolution = patient reporting complete or marked

relief of symptoms
Overall symptom score
Percent of patients with resolution of symptoms
Work attendance
Work performance
Quality of life (SNOT-20 score)
Adverse events
Recurrences
Additional attendances

MFNS 400 g twice

daily for 21 days

Placebo spray

Co-amoxiclav 875 mg
twice daily for 21 days

Paracetamol only;
unregulated,
unrecorded

Resolution = patient report of symptoms much

improved or resolved
Symptom scores assessed on 6-point scale (individual symptoms and total scores)
Percent with complete resolution of symptoms at
21 days
CT scoring of sinusitis (10-point scale)
Adverse events

100 g budesonide
twice daily for 21
days

Propellantonly spray

Amoxicillinclavulanate
potassium 40 mg/kg
daily for 21 days

Not reported

Resolution = patient reporting complete or marked

relief of symptoms
Symptoms scores: median score of cough and
nasal discharge for first, second, and third weeks
Relapse
Resolution (no overall measure reported)

moderate in severity.17,18,21 Meta-analysis demonstrated

no signicant differences in the rate of overall adverse
events between patients taking intranasal corticosteroids (299 of 1,299, or 23%) and placebo (181 of 797,
also 23%) (P = .83). Common adverse events were
headache (noted in 2%-8% of patients, 4 studies),
epistaxis (3%-7%, 4 studies), nasal irritation (1%-2%,
3 studies), and pharyngitis (2%-4%, 3 studies). MetaANNALS O F FAMILY MED ICINE

analysis of the rate of occurrence of these outcomes

revealed no signicant differences between steroid
and placebo groups.
Relapse and Recurrence
Three trials17,19,20 reported the rate of relapse or recurrence of acute sinusitis up to 2 months after initiation
of treatment. Recurrence occurred in 5% to 15% of

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Table 2. Methodologic Quality of Included Studies

Study (Year)
Williamson
et al14 (2007)
Meltzer et al17
(2005)

Allocation
Concealment

Randomization

Adequate

Random number table,

block randomization
Computer-generated randomization stratified
by duration of symptoms at presentation
Randomized, method
not reported
Permuted block randomization scheme stratified by site
Randomized, method
not reported
Randomized, method
not reported

Adequate

Nayak et al18
(2002)
Dolor et al20
(2001)

Adequate: matching
placebo used
Adequate

Meltzer et al21
(2000)
Barlan et al19
(1997)

Adequate: matching
placebo used
Adequate

Blindinga

Provision of
Care Apart
From the
Intervention

Percentage
Participation

Comparable

Double blind

Equal

86

Comparable

Double blind

Equal

90

Comparable

Double blind

Equal

89

Comparable

Double blind

Equal

94

Comparable

Double blind

Equal

100

Comparable

Double blind

Equal

59

Comparability
of Groups at
Baseline

Williamson et al was the only study to specifically describe the method of double blinding.

Figure 2. Effect of intranasal steroids on resolution of symptoms of acute sinusitis at (A) 14 to 15 days
and (B) 21 days.
INCS
Events
Dolor et al

20

Meltzer et al17
Williamson
et al14

Total

Placebo
Events

Weight

36

47

28

48

9.7%

442

478

225

252

69.2%

0.03 (0.01 to 0.08)

78

102

77

105

21.1%

0.03 (0.09 to 0.15)

405

100.0%

627
Heterogeneity:

Total

Risk Difference
(Random Effects)
95% CI

Risk Difference
(Random)
95% CI

0.18 (0.00 to 0.37)

0.05 (0.01 to 0.11)

= 22%

Test for overall effect: Z = 1.51 (P = .13)

0.2

0.1

0.1

Favors placebo

INCS
Events
Dolor et al

Total

Placebo
Events

Total

Weight

Risk Difference
(Random Effects)
95% CI

41

47

33

48

10.7%

0.18 (0.02 to 0.35)

Meltzer et al

124

200

102

207

30.7%

0.13 (0.03 to 0.22)

Nayak et al18

370

574

160

290

58.6%

0.09 (0.02 to 0.16)

545

100.0%

20

21

821
Heterogeneity:

0.2

Favors steroid

Risk Difference
(Random)
95% CI

0.11 (0.06 to 0.17)

= 0%

Test for overall effect: Z = 4.18 (P <.0001)

0.2

0.1

Favors placebo

0.1

INCS = intranasal steroid.

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Only 1 included trial assessed the

potential benet of intranasal corticosteroids for work and quality of life
outcomes in acute sinusitis.20 In this
18
17
21
Nayak et al
Meltzer et al
Meltzer et al
trial, the corticosteroid group had a
1.4
signicantly higher subjective level
of work performance (median, 100%
1.3
vs 90% for placebo); however, there
were no differences in work attendance or changes in quality of life as
1.2
measured by the 20-item Sino-Nasal
Outcome Test (SNOT-20)24 and the
12-Item Short Form Health Survey.25
1.1
An individual patient with acute
sinusitis may therefore experience
1
negligible adverse effects of intranasal corticosteroids in return for a
small increase in likelihood of earlier
0.9
resolution. This may be an accept0
200
400
600
800
1,000
able trade-off for some patients. The
Daily Dosage of Mometasone Furoate g
therapeutic benet at the population
level is currently unclear.
Our
subgroup
analysis suggests the benet of
patients taking intranasal corticosteroids and 4% to
intranasal
corticosteroids
is most marked at 21 days,
37% taking placebo.
with an additional 11 patients experiencing symptom
resolution for every 100 treated. In contrast, this effect
DISCUSSION
was not signicant at 15 days. Our subgroup analysis
had only a small number of trials, however, and further
Key Findings
research is needed to clarify the clinical benet at 15
This systematic review demonstrates that intranasal
days or less (as discussed below). Clearly, patients are
corticosteroids offer a small but signicant symplikely to experience pronounced symptoms in the rst
tomatic benet in acute sinusitis. This effect is most
7 to 14 days of their illness and may be less willing to
marked when patients are given longer durations of
consider a therapy that does not offer an increased
treatment (21 days) and higher doses of the medicalikelihood of improvement in this earlier time period.
tion. Our analysis of individual symptom scores sugWe found evidence of a dose-response relationgests that facial pain and nasal congestion may be most
ship
for mometasone furoate nasal spray: larger doses
responsive to intranasal corticosteroids. In our main
were
associated with a greater likelihood of symptom
analysis, we found that whereas 66% of patients would
resolution.
We had insufcient data to assess whether
experience improvement or resolution of symptoms
other
types
of intranasal corticosteroids showed a
at 14 to 21 days using placebo, an additional 7% of
similar
effect,
or whether this higher dose was associpatients would achieve this outcome with corticosteated
with
an
increase
in adverse events. On the basis
roids, equating to an NNT of 13.
of
our
review,
when
intranasal
corticosteroids are
This 7% gain is a relatively small increase in the conused,
we
recommend
doses
of
800
g of mometasone
text of a self-limiting condition, and this clinical benet
furoate
daily.
must be set against potential harms and economic implications. Our included trials reported no serious adverse
Comparison With Existing Literature
events associated with intranasal corticosteroid use and
The small benet of intranasal corticosteroids for the
no increase in frequency of nonserious adverse events
broad measure of symptom resolution or improvecompared with placebo. Other potential harms might
ment at 14 to 21 days was similar in direction and size
include effects from systemic absorption; however, the
to that found in a recent Cochrane review.13 In both
single included trial addressing this outcome found
no clinically relevant changes in the hypothalamiccases, however, marked heterogeneity was present.
pituitary-adrenal axis,20 and 2 recent reviews found no
We have demonstrated that this heterogeneity arises
evidence of suppression of this axis or of growth supfrom both the variation in the timing of the outcome
pression with intranasal corticosteroids.22,23
measure and the dose of intranasal corticosteroids
Relative Risk of Symptom Resolution

Figure 3. Dose-response relationship of mometasone furoate and

likelihood of symptom resolution.

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used. We found larger effect sizes in subgroup analyses

by dose and timing of outcome measure. The recent
Cochrane review may therefore have underestimated
the benet of intranasal corticosteroids. Williamson et
al14 acknowledged that their RCT was underpowered
to detect clinically useful effects, and the study may
have used an inappropriately low dose of budesonide.26
Limitations
Important limitations of this systematic review include
rst, that 5 of the studies prescribed antibiotics to both
steroid and placebo groups. Williamson et al14 found
no interaction between antibiotic therapy and steroid
therapy using a factorial design, which argues against a
synergistic effect of these drug classes.
Second, included studies varied in the types and
doses of steroids, duration of therapy, and outcome
measures reported. Particularly, the denition of resolution of symptoms varied among the studies, and all
measures of resolution involved subjective assessment.
These factors prevented pooling of all outcomes and
are likely to have contributed to the heterogeneity of
the data.
Third, included studies were underpowered to
detect rare adverse effects of corticosteroid, as well
as relapse rates and days missed from work or school.
Fourth, the limited number of trials meant we were
unable to assess publication bias using funnel plots or
place undue weight on the ndings from small subgroup analyses. Finally, in 4 of the 6 included trials,
radiologic or endoscopic evidence of acute sinusitis
was an inclusion criterion. In ambulatory care, it is
impractical and inappropriate to perform radiologic
investigations on patients with symptoms of sinusitis.
Recommendations for Research
This review highlights the need for adequately powered RCTs comparing intranasal corticosteroids with
placebo in the absence of antibiotics for symptom relief
in acute sinusitis. We recommend that trials should use
at least 21 days of therapy with high-dose mometasone
furoate nasal spray. Inclusion criteria should be based
on a clinical scoring system rather than radiologic evidence. Self-report and telephone follow-up should be
used to assess the time to complete resolution of symptoms and also the time to onset of symptom resolution, which will be particularly important in clarifying
whether there is benet at time points earlier than 21
days. Recording the duration of symptoms at baseline
will also improve our understanding of patterns of
symptom resolution.
As acute sinusitis is diagnosed in an estimated
31 million Americans annually,1 a full assessment of
economic implications is important. Such assessment
ANNALS O F FAMILY MED ICINE

should look at the cost of 21 days of therapy with

high-dose mometasone furoate (equivalent to 3 bottles
containing 140 50-g doses) and the indirect cost
savings in terms of attendance and performance at
work or school and quality of life measures (eg, with
the SNOT-20 score).24 These data will improve our
understanding of whether the small benet of this
therapy for the individual has larger benets at the
population level. Antibiotics are widely prescribed for
acute sinusitis despite limited evidence of benecial
effect; thus, measuring the extent to which intranasal corticosteroids reduce antibiotic prescribing will
be highly relevant to clinical practice and policy. A
systematic review using individual patient data may
improve our ability to combine the data from existing
research. Finally, a double-blind, placebo-controlled
trial of the benet of oral steroids in acute sinusitis has
not yet been performed. Since delivery of intranasal
corticosteroids to the nasal mucosa may be reduced
by nasal congestion, and this may be a factor responsible for our nding of a nonsignicant benet at 15
days, oral drug delivery might offer earlier and greater
symptomatic relief.
In summary, on the basis of the current evidence,
we believe that intranasal corticosteroids offer a small
therapeutic benet in acute sinusitis and may be most
helpful for symptoms of facial pain and nasal congestion. This benet may be greater with courses of 21
days in duration and with high-dose mometasone
furoate. Future trials in antibiotic-nave patients that
clarify the time-course of clinical benet and the
impact on work and quality of life will be important to
guide management of this common condition in family practice.
To read or post commentaries in response to this article, see it
online at http://www.annfammed.org/content/10/3/241.
Key words: corticosteroids; sinusitis; meta-analysis; intranasal administration; inhaled; facial pain; congestion
Submitted April 20, 2011; submitted, revised, August 17, 2011; accepted
September 6, 2011.
Funding support: Funding for this work was provided in part by a
grant from the British Society for Antimicrobial Chemotherapy Systematic Review Grant (GA722SRG). The Department of Primary Health care
is part of the National Institute of Health Research (NIHR) School of
Primary Care Research.
Disclaimer: Neither the British Society for Antimicrobial Chemotherapy
nor the National Institute of Health Research had any role in the design
and conduct of the study; collection, management, analysis, and
interpretation of the data; and preparation, review, or approval of the
manuscript.
Acknowledgments: We would like to acknowledge the input of Professors Paul Glasziou and Chris Del Mar into the initial stages of this project.

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