Intervention Review

You have free access to this content

Intranasal steroids for acute sinusitis

  1. Anca Zalmanovici Trestioreanu1,*,
  2. John Yaphe2

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 2 DEC 2013

Assessed as up-to-date: 22 MAY 2013

DOI: 10.1002/14651858.CD005149.pub4


How to Cite

Zalmanovici Trestioreanu A, Yaphe J. Intranasal steroids for acute sinusitis. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD005149. DOI: 10.1002/14651858.CD005149.pub4.

Author Information

  1. 1

    Beilinson Campus, Rabin Medical Center, Department of Family Medicine, Petah Tikva, Israel

  2. 2

    University of Minho, School of Health Science, Braga, Portugal

*Anca Zalmanovici Trestioreanu, Department of Family Medicine, Beilinson Campus, Rabin Medical Center, 39 Jabotinski Street, Petah Tikva, 49100, Israel. anca_z@hotmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 2 DEC 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Barlan 1997

MethodsRandomised: method of randomisation not mentioned
Allocation concealment not mentioned
Double-blind: yes
Intention-to-treat not mentioned
Follow-up described
151 recruited; 89 (59%) completed study; 41% drop-out
Design: parallel


ParticipantsN = 89; 42 male, 47 female
Age 1 to 15 years
Inclusion criteria: 2 of 3 major criteria - purulent nasal discharge, cough, purulent pharyngeal drainage or 1 major and 2 minor criteria: facial pain, periorbital oedema, earache, tooth pain, sore throat, headache, increased wheeze, fever, foul breath for more than 7 days and Rx criteria
Water radiographs at the beginning of study positive if complete opacification or maxillary mucoperiosteal thickening more than 4 mm. 79 participants had positive Rx
Exclusion criteria: history of allergic rhinitis, asthma, recurrent/chronic sinusitis
Baseline characteristics: similar in both groups, no significant differences
Patients maintained daily symptom cards and were examined by the same physician each week. Symptom scores were evaluated by a scale from 0 to 3


InterventionsTx group: budesonide 50 µg bid nasal spray to each nostril, N = 43
C group: placebo nasal spray bid, N = 46
All participants in both groups received amoxicillin-clavulanate potassium 40 mg/kg/day tid
Duration: 3 weeks


OutcomesDifference in weekly symptom scores for cough and nasal discharge in the first, second and third week of the study in both groups, as difference between groups or change from baseline
Relapse: results were reported as medians of scores using non-parametric tests because a wide range of scores without normal distribution


NotesMarmara University Hospital Outpatient Clinic patients enrolled from November 1993 to October 1994
Informed consent signed by all parents. 151 patients enrolled, 89 completed study, 62 dropped out, no separate data for both groups
Reasons for drop-outs: non-compliance with weekly visits or not recording daily symptoms


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomised, method not mentioned

Allocation concealment (selection bias)Unclear riskNot mentioned

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo separate data for groups, ITT not mentioned

Selective reporting (reporting bias)Low riskNo evidence of reporting bias

Other biasUnclear risk-

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blind

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk-

Dolor 2001

MethodsMulticentre randomisation - permuted blocks scheme stratified by site with a block size of 4 generated using SAS version 6.12
Allocation concealment - study kits administered sequentially by blinding site personnel to block size
Blinding: yes
Intention-to-treat: yes
Follow-up described: yes
88 (93%) completed study
Design: parallel


ParticipantsN = 95; 30 men, 65 women
Age 30 to 50; median age 39 years
Inclusion criteria: older than 18 years, history of recurrent sinusitis or chronic rhinitis and clinical evidence of acute sinusitis confirmed Rx or by nasal endoscopy
Diagnosis of acute sinusitis: clinical criteria - participants with 2 of the 5 following symptoms present were enrolled: headache, facial pain, nasal congestion, thick coloured nasal discharge, olfactory disturbance
Rx criteria: air-fluid level, mucosal thickening or opacification of sinus
Exclusion criteria: previous sinus surgery, sinus lavage in the past 7 days, nasal polyposis, recurrent epistaxis, chronic bacterial sinusitis with failure of antibiotic therapy, INCS use within past 14 days, chronic use of corticosteroids or immunosuppressives, immunocompromised, allergy to penicillin/cephalosporins, participants without a telephone, pregnant, nursing women
Baseline characteristics - similar in both groups, no significant differences
Participants assessed at baseline, 10, 21, 56 days by diary records and telephone follow-up


InterventionsTx group: nasal spray fluticasone propionate 2 puffs (total dose 200 µg) once daily in each nostril; N = 47
C group: nasal spray placebo 2 puffs once daily in each nostril; N = 48
All participants in both groups received 2 puffs xylometazoline hydrochloride in each nostril twice daily 10 minutes before the study nasal spray and 250 mg cefuroxime axetil twice daily for 10 days
Duration of study: 21 days
Follow-up: 8 weeks
Allowed to continue: NSAIDs, analgesics, immunotherapy for allergies, orally inhaled corticosteroids
Not permitted during study: oral decongestants, mucolytics, corticosteroids oral or parenteral, antihistamines, immunosuppressives
Sinus lavage or sinus surgery was discouraged during the first 3 weeks of the trial, antibiotic use in the past 7 days or 21 days if longer half-life was not permitted
Compliance with Tx: assessed by a standardised form given to patients for recording daily symptoms, Tx, adverse events, work attendance. 94% completed study Tx without difference between groups


OutcomesProportion of patients with clinical success (cured or much improved) at 10, 21, 56 days on telephone follow-up
Time to clinical success differences over time in sinusitis and quality of life scores
Level of work performance
Total number of hours lost from work
Recurrences


NotesStudy conducted between October 1998 to April 2000 at 22 sites (12 primary care and 10 otolaryngology)
Equal proportions of participants from primary care and otolaryngology practices in both treatment arms
All study sites received standardised instructions for conducting the study
Study progress monitored by a research associate
Patients assessed symptoms on numeric scales and received booklets with specific instructions for use of nasal spray
High agreement between patient-recorded and interviewer-obtained symptoms
Drop-outs:
Tx group: 1 - rash, 1 - unknown, 1 - lost to follow-up
44 completed 21-day Tx and telephone follow-up, 36 completed diary, 46 included in primary analysis
C group: 1 - withdrew, 2 - switched to different antibiotics
45 completed 21-day Tx, 44 completed telephone follow-up, 32 completed diary, 46 included in primary analysis


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskSee methods

Allocation concealment (selection bias)Low riskSee methods

Incomplete outcome data (attrition bias)
All outcomes
Low riskSee methods

Selective reporting (reporting bias)Low riskNo evidence of selective reporting

Other biasLow risk-

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee methods

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk-

Meltzer 2005

MethodsMulticentre randomisation
1:1:1:1 ratio to 1 of 4 arms by computer-generated code
Allocation concealment: not mentioned
Double-blind: yes
Intention-to-treat: yes
Follow-up described
10% drop-out in Tx phase, 95% completed follow-up phase
Design: parallel


ParticipantsN = 981; 338 men, 643 women
Age 12 to 76 years
Inclusion criteria: age more than 12 years with clinical criteria for acute sinusitis; MSS more than 5 but less than 12 at baseline, assessed by participant and investigator and no more than 3/5 symptoms rated severe (rhinorrhoea, PND nasal congestion, stuffiness, sinus headache and facial pain on pressure) adding cough to the TSS
Exclusion criteria: fulminant bacterial rhinosinusitis, chronic rhinosinusitis, nasal/sinus surgery within the last 6 months for this condition, otitis, atrophic rhinitis, nasal polyps, symptomatic seasonal allergic rhinitis, allergy to corticosteroids
Asthmatic participants needed to be stable last 30 days and FEV1 more than 65% last 3 months before screening
Rhinoscopic examination was performed at all visits
Participants were assessed at baseline days 8, 15, 29 and monitored by telephone on days 3 to 4. Response to Tx evaluated by participant and investigator as scores for symptoms on a scale from 0 to 3
Baseline characteristics similar for all the arms


Interventions4 groups
Tx groups:
1. MFNS 200 µg once daily nasal spray + placebo nasal spray once daily + placebo capsules tid; N = 243
2. MFNS 200 µg nasal spray bid + placebo capsules tid; N = 235
3. amoxicillin 500 mg tid for 10 days + placebo nasal spray bid; N = 251
C group: placebo nasal spray bid + placebo capsules tid; N = 252
Duration of study: 15 days
Capsules given for 10 days
Follow-up: 14 days
Not allowed during study: nasal saline, nasal cromolyn sodium, ipratropium bromide, corticosteroids (excluding oral inhaled corticosteroids for mild/moderate asthma), antihistamines, decongestants, leukotriene pathway modificants, analgesics, NSAID
Compliance assessed at days 8 and 15 by questioning whether drug had been taken
Each participant received at least 1 dose of study drug


OutcomesMean MSS
Mean TSS
Individual scores
Time to onset of action
Global response to Tx
Adverse events
Disease recurrence
Tx failure (worsening or not improvement in symptoms during the Tx phase)


NotesStudy conducted at 71 medical centres in 14 countries from January to September 2003
Drop-outs: during the Tx phase in the 200 µg, 400 µg MFNS, amoxicillin, placebo were 9%, 9%, 8%, 13%
Reasons for discontinuation: adverse events, Tx failure, loss to follow-up, did not wish to continue, non-compliance with protocol, did not meet protocol criteria for entry


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskSee methods

Allocation concealment (selection bias)Unclear riskSee methods

Incomplete outcome data (attrition bias)
All outcomes
Low riskSee methods

Selective reporting (reporting bias)Low risk-

Other biasUnclear risk-

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskSee methods

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk-

Nayak 2002

MethodsMulticentre, randomised; method of randomisation not mentioned
Allocation concealment not mentioned
Double-blind: yes
Follow-up described: yes
864 (89%) participants included in the primary efficacy analysis
Design: parallel


ParticipantsN = 967; 402 men, 565 women
Age 8 to 78 years
Inclusion criteria: acute episode of rhinosinusitis, at least 1 moderate/severe nasal symptom (these may include purulent rhinorrhoea, stuffiness/congestion, post-nasal drip, sinus headache, facial pain, cough), purulent rhinorrhoea present, sinusitis confirmed by a CT scan, which is read by a radiologist at each study site at baseline, a total symptom score more than 6
Exclusion criteria: nasal polyps, cystic fibrosis, Kartagener syndrome, expected immediate sinus or nasal surgery, glaucoma, history of subcapsular cataracts, clinical significant diseases
Symptoms evaluated at baseline (day 1) and day 21 by patient and investigator by scales. Patients evaluated at baseline, 15, 21 days
CT scans of paranasal sinuses at baseline and 21 days evaluated by an independent blinded radiologist
Similar baseline characteristics and baseline symptoms scores in all 3 groups
Patients recorded symptom scores, adverse events and use of medication twice daily


Interventions3 groups
Tx groups:
1 MFNS 400 µg nasal spray twice daily; N = 324
2 MFNS 200 µg nasal spray twice daily; N = 318
C group:
Matching placebo nasal spray twice daily; N = 325
All participants in all groups received amoxicillin-clavulanate potassium 875 mg twice daily for 21 days
Not allowed during study: any form of corticosteroid, nasal decongestants, antihistamines
Washout period before the baseline visit for previous use of antibiotics, intranasal or systemic corticosteroids, decongestants
Adherence to therapy assessed by weighing the nasal spray dosing containers without patients' knowledge


OutcomesImprovement in total symptoms score
Improvement in individual symptom score
Overall response to treatment: proportion of participants with complete or marked relief
Onset of relief
Evaluation of changes in CT scans of sinuses
Adverse events


NotesOutpatients from 61 Tx centres in the US
967 participants randomised, 103 participants (11%) not included in analysis because CT did not confirm sinusitis and excluded post-randomisation, diary data not available, less than 80% compliance with Tx, less than 7 days Tx (32, 36, 35 in the MFNS 400, 200 µg and placebo groups)
Reasons for exclusion or discontinuation were evenly distributed among the groups
Physician evaluation of symptoms at day 21 was consistent with patient-recorded evaluation


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskSee methods

Allocation concealment (selection bias)Unclear riskSee methods

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSee notes

Selective reporting (reporting bias)Unclear risk-

Other biasUnclear risk-

Blinding of participants and personnel (performance bias)
All outcomes
Low riskSee methods

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk-

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Bachert 2007Study on quality of life. Outcome for a subset of patients from one of the included studies (Meltzer 2005)

Gehanno 2000Allocation: randomised, parallel
Participants: N = 433 adults with confirmed acute sinusitis
Intervention: amoxicillin-clavulanate and methylprednisolone or placebo per oral administration
No intranasal steroids used

Jurkiewicz 2004Abstract and full paper not available

Meltzer 1993Allocation: randomised, parallel
Participants: N = 175 participants 14 years or older with confirmed acute or chronic sinusitis
Intervention: amoxicillin-clavulanate potassium combined with nasal spray of either flunisolide or placebo
No separate arms for acute and chronic sinusitis reported

Meltzer 2000Missing data - number randomised, numbers included in analyses, drop-outs and reasons for drop-out. The numbers reported do not add up to 100%. An email was sent to the author but there was no reply

Quarnberg 1992Allocation: randomised, parallel
Participants: N = 40 participants 16 years or older with confirmed recurrent or chronic sinusitis
Intervention: erythromycin and either budesonide or placebo aerosol
Separate arms for acute recurrent and chronic sinusitis were not reported

Tutkun 1996Missing data - not mentioned acute/chronic sinusitis, diagnostic criteria not reported, drop-outs not reported. Email was sent to the author but there was no reply

Williamson 2007Inclusion criteria for the review were not met

Yilmaz 2000Allocation: randomised, parallel
Participants: 52 children with confirmed acute sinusitis
Intervention: cefaclor and either oral pseudoephedrine or intranasal budesonide
No placebo used in the control group

 
Comparison 1. Intranasal corticosteroids versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Proportion of participants with resolution of symptoms or improved (MFNS 400 µg daily)21130Risk Ratio (M-H, Fixed, 95% CI)1.10 [1.02, 1.18]

 2 Proportion of participants with resolution of symptoms or improved (MFNS 200 µg daily)2590Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.98, 1.11]

 3 Proportion of participants with resolution of symptoms or improved (combined MFNS 200, 400 and 800 µg daily)31792Risk Ratio (M-H, Fixed, 95% CI)1.11 [1.04, 1.18]

 4 Number of participants that dropped out from the study (MFNS 400 µg daily)21130Risk Ratio (M-H, Fixed, 95% CI)0.86 [0.61, 1.20]

 5 Number of participants that dropped out from the study (MFNS 200 µg daily)2590Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.46, 1.21]

 6 Number of participants that dropped out from the study (combined MFNS 200, 400 and 800 µg daily)31792Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.64, 1.12]

 7 Relapse (combined 200 and 400 µg daily)2825Risk Ratio (M-H, Fixed, 95% CI)0.71 [0.44, 1.15]

 
Table 1. Adverse events

StudyInterventionSide effectsComments

Dolor 2001Fluticasone propionate 2 puffs - total dose 200 µg or placebo nasal spray once daily in addition to 250 mg cefuroxime axetil orally twice daily and 2 puffs of xylometazoline hydrochloride twice dailyHeadache, bloody nose, vaginal itching, yeast infection, nausea, stomach irritation, diarrhoea, increased congestion, hay fever, light-headed, sore throat, thirsty, itching, rash, cough, fatigue, metallic taste, felt dried out, nasal tissue felt inflamedNo serious unexpected adverse events reported

Any adverse event - 37% in the fluticasone group versus 20% in the placebo group (P value = 0.7) no statistical significant difference

Adverse events could be attributed also to the co-treatment

Nayak 2002Amoxicillin-clavulanate potassium 875 mg
twice daily orally and MFNS 200, 400 µg or placebo nasal spray twice daily
Epistaxis was the most frequently reported adverse event
Nasal burning, irritation and headache occurred in less than 2% of any treatment group
Treatment well-tolerated, adverse events similar for all 3 arms of mild/moderate intensity: 12%, 15%, 15% in the MFNS 400, 800 µg and placebo arms

50 patients discontinued treatment because of adverse events, most commonly diarrhoea and nausea due to the antibiotic and were equally distributed among groups. Epistaxis, nasal burning, irritation or infection were not a cause for discontinuation of treatment

Barlan 1997Budesonide 50 µg or placebo nasal spray to each nostril bid in addition to amoxicillin clavulanate potassium 40 mg/kg/day tidRash after 1 week attributed to the antibiotic in 1 subject that was switched to cefaclorNo specific adverse events related to the INCS use were reported

Meltzer 2005MFNS 200 µg once daily or twice daily nasal spray
Amoxicillin 500 mg tid
Placebo nasal spray and capsules
Headache and epistaxis were most common reportedMost adverse events were mild or moderate with a similar incidence among treatment groups: 36.2%,
35.4%, 33.5% and 38.1% with MFNS 200 µg, 400 µg,
amoxicillin and placebo
1%, 3%, 2% and 2% of participants discontinued treatment because of adverse events in the 200 µg, 400 µg INCS, antibiotic and placebo arms

 bid: twice daily
INCS: intranasal corticosteroid
MFNS: mometasone furoate
tid: three times daily