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Original Contribution

A double-blind randomised placebo-controlled trialof topical intranasal mometasone furoate nasalspray in children of adenoidal hypertrophy withotitis media with effusion

Rahul Bhargava, MBBS⁎, Arunabha Chakravarti, MS, DNB1

Department of Otorhinolaryngology – Head & Neck Surgery, Lady Hardinge Medical College, New Delhi-110001, India

A R T I C L E I N F O

⁎ Corresponding author at: Department of OtoIndia. Tel.: +91 9868047427 (Mobile).

E-mail addresses: dr.rahul.bhargava@gma1 Tel.: +91 9868093035 (Mobile).

http://dx.doi.org/10.1016/j.amjoto.2014.06.0060196-0709/© 2014 Elsevier Inc. All rights rese

Please cite this article as: Bhargava R, Chmometasone furoate..., Am J Otolaryngo

A B S T R A C T

Article history:Received 17 March 2014

Purpose: To study the effects of topical intranasal mometasone furoate nasal spray formanagement of otitis media with effusion in children aged 2–12 years with adenoidalhypertrophy and its impact on change in quality of life.Method: A prospective randomized double blind interventional placebo control study wasconducted. Hundred patients of endoscopic grade 3 or 4 adenoidal hypertrophy aged 2–12years were enrolled in this study. Among these sixty two patients had persistent bilateralotitis media with effusion more than three months. These were randomly divided into twogroups, group A and group B. Group A received mometasone nasal spray for six months andgroup B received saline nasal spray for the same period. Patients were evaluated withsymptom, pure tone audiometry wherever possible, pneumatic otoscopic examination andtympanogram at 0, 8 and 24 weeks.Results: Resolution of otitis media with effusion in study group (28 out of 30) wassignificantly higher as compared control group (16 out of 32) (p value 0.0004). A significantimprovement in hearing and symptoms was seen in the study group (p < 0.04). Statisticallysignificant change in quality of life was seen with mometasone nasal spray (37.11) ascompared to saline nasal spray (11.02) (p value 0.0001).Conclusion: Mometasone nasal spray appears to be effective for the treatment of otitismedia with effusion in patients of adenoidal hypertrophy.

© 2014 Elsevier Inc. All rights reserved.

1. Introduction

Otitismedia with effusion (OME) or glue ear is collection of fluidbehind the tympanic membrane without inflammatory signspresent for six weeks [1]. By the age of 4 years, approximately

rhinolaryngology- Head &

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80% of children will have had an episode of otitis media witheffusion,most ofwhich resolve andonly 10%of episodes last fora year or more [2].

The sterile fluid in the middle ear mechanically dampensthe transmission of sound and results in the significant

Neck Surgery, Lady Hardinge Medical College, New Delhi-110001,

chakravarti@yahoo.co.in (A. Chakravarti).

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conductive hearing loss. This hearing loss especially whenbilateral has an important impact on children’s lives anddevelopment [3].

The adenoids are pyramid-shaped aggregation of lymphoidtissue in the nasopharynx which are present at birth. Adenoidswhen enlarged obstruct the nasopharyngeal airway and causenasal obstruction, mouth-breathing, rhinorrhoea, snoring andhyponasal voice. Adenoid when enlarged can mechanicallyobstruct the eustachian tube opening and is a known causefor OME.

Traditionally adenoidectomy with grommet insertion isconsidered to be the treatment of choice. Various conservativeapproach to it’s management are under research. Recentlyrole of steroids in such context has been explored. Topicalsteroids nasal spraymay be beneficial, are under-research andmore robust evidence are needed [4–10].

Mometasone furoate when used as nasal spray has lowerbioavailability, extensive first pass metabolism and a rela-tively higher binding affinity for the glucocorticoid receptorthan the other intranasal corticosteroids [11]. Mometasonefuroate nasal spray does not suppresses the function of thehypothalamic-pituitary adrenal axis when administered atclinically relevant doses of 100–200 mcg/day [11].

The present study was undertaken to evaluate the role ofmometasone furoate nasal spray in children of persistent OMEwith adenoidal hypertrophy.

Fig. 1 –Measuring the size of adenoid tissue and nasopharynxsize on nasopharyngoscopy.

2. Materials and methods

This prospective randomized double blind interventionalplacebo control study enrolled 100 patients with the symp-toms of adenoidal hypertrophy attending the Department ofOtorhinolaryngology and Head &Neck Surgery, Lady HardingeMedical College and associated Kalawati Saran Children’sHospital, New Delhi from October 2011 to march 2013. Thepatients of age 2–12 years of both sexes having grade 3 and 4adenoidal hypertrophy according to Cassano classification [12]with duration of symptoms for at least 3 months and notresponsive to previous medical treatment were enrolled. Theexclusion criteria were: 1) previous adenoidectomy, 2) use ofintranasal topical or systemic steroid in last 1 year, 3) associ-ated marked tonsillar hypertrophy, 4) anatomic deformity ofthe nose or sinonasal disease such as nasal polyposis orinferior turbinate hypertrophy, 5) craniofacial abnormalitiessuch as cleft lip/cleft palate, 6) genetic diseases such as DownSyndrome, 7) acute upper respiratory infectionwithin 2 weeksof enrolling in the study, and 8) patients with any clinicallysignificantmetabolic cardiovascular, neurologic, hematologic,gastrointestinal, cerebrovascular or respiratory disease.

Detailed history and ENT examination including pneumaticotoscopy were done at Vo. Clinical grading of symptom scorewas done ranging from 0 to 3 (0 = absent; 1 = occasional;2 = frequent; 3 = daytime and night-time symptoms) to assessthe degree of nasal obstruction, rhinorrhoea, cough, snoringand obstructive sleep apnoea [12] at baseline (V0), 8(V1) and24(V2) weeks visits. These patients were subjected totympanometry, pure tone audiometry (PTA) whereverpossible and nasopharyngoscopy under local anaesthetic

Please cite this article as: Bhargava R, Chakravarti A, A double-blmometasone furoate..., Am J Otolaryngol–Head and Neck Med a

spray (lignocaine spray 15%)/sedation with midazolam ifrequired using rigid 2.7 mm/4 mm diameter nasal telescope.The endoscopy was videotaped and stored by AIDA (AdvancedInterface Database Application) and still photographs weretaken from the video (Fig. 1). The grading of adenoidalhypertrophy was noted as described by Cassano et al. [12].

62 patients of adenoidal hypertrophy were diagnosed withbilateral otitis media with effusion on otoscopy & tympano-metry (modified Jeger’s type B or C2) and were included [13].The study was approved by institutional ethical committee.Written informed consent was taken from the parents/caregiver before enrollment.

The children included in this study were divided into 2groups randomly by chit selection into group A (study) and thegroup B (control). The group A received initial treatment of 2puffs ofmometasone furoate nasal spray (50mcg/puff) in eachnostril once a day, a total of 200 mcg/day for the first 8 weeks.This was followed by a maintenance dose of 2 puffs ofmometasone furoate nasal spray in each nostril on alternatedays for 16 weeks. The group B received initial treatment of 2puffs of saline nasal spray in each nostril once a day for8 weeks, followed by 2 puffs of saline nasal spray on alternatedays for 16 weeks.

Follow-up was done at every 2 weeks for the first 8 weeksand then monthly for the next 16 weeks. Patients bottle werechecked on the each visit for compliance to therapy and anylocal adverse effect were recorded.

After completion of therapy, patients were evaluated withsymptoms score, otoscopic picture, change in the adenoidsize, PTA and tympanometry. The quality of life was assessedby using Glasgow Children’s Benefit Inventory in each case atV2 visits [14].

2.1. Statistical Analysis

The observations were recorded on a pre-designed proformaand then transferred to MS Excel spreadsheet. After verifica-tion and cleansing, data analysis was done by using SPSS 19.0

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software. The observations were described in terms of mean,median, standard deviation, and 95% confidence interval forcontinuous data. The quantitative data of symptoms,nasopharyngoscopic grade, tympanometric analysis betweentwo groups were compared by using student’s ‘t’ test. Thequalitative data change in quality life between two groupswascompared by using chi-square test/Fisher exact test. Ap value < 0.05 was considered as cut off point for levelof significance.

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SYMPTOM SCORE ADENOID SIZE OME PTA

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ig. 2 – Comparison of mean of symptoms score, adenoidize, OME, PTA before and after treatment with Mometasoneasal spray.

3. Results

62 children (62%) between ages 2–12 years had bilateral OMEon tympanometric analysis. The maximum incidence wasseen in the age group 6–9 years (53%) with a mean age of7.4 years (Table 1). PTA could be done in 48 patients (26 groupA and 22 group B) and 20.4 dB of average hearing losswas seenbefore the initiation of therapy. The average loss post therapyin group A was 5.2 dB while in group B was 11.6 dB. Thischange in hearing with therapy between two groups wasstatistically significant (Table 1).

In group A 28(93%) out of 30 children OME resolved over aperiod of 24 weeks after initiation of therapy as compared to 16out of 32(50%) in the control group. After 24 weeks of treatmentin group A statistically significant reduction in symptom scorewas observed [8.57–0.87(p value 0.0001)] (Table 1) (Fig. 2). Aftersame duration in group B statistically significant reduction insymptom score was seen in symptom score [8.01–1.61 (p value0.0001)] (Table 1) (Fig. 3). On comparing study group (Group A)with control group (group B) statistically significant change innasal obstruction score (p value 0.004), snoring score (p value

Table 1 – Comparison of response of mometasone nasalspray with saline nasal spray.

Parameters Mometasone nasalspray (N = 30)

Saline nasalspray (N = 32)

Age (years) 7.28 ± 3.17 7.61 ± 2.48Sex 18 M, 12 F 20 M, 12 FSymptom scoreBefore 8.57 ± 1.74 8.01 ± 1.71After 0.83 ± 1.02 1.33 ± 1.32p value 0.0001* 0.0001*Change in symptomscore

7.73 ± 1.96 6.63 ± 2.04p value = 0.04*

Adenoid sizeBefore 86 ± 11.62 78.36 ± 19.19After 71.67 ± 12.34 71.33 ± 14.56p value 0.0001* 0.11

OMEBefore 30 32After 2 16P value <0.0001* <0.002*Change in OME 30 16p value 0.0004*

PTABefore 20.5 20.4After 5.2 11.6p value

Please cite this article as: Bhargava R, Chakravarti A, A double-bmometasone furoate..., Am J Otolaryngol–Head and Neck Med a

Fsn

<0.0001), OSA score (p value 0.04) and total score (p value 0.04)was seen. While change in rhinorrhoea score (p value 0.87) andcoughscore (p value 0.81) between the twogroupsafter 24 weeksof treatment was statistically not significant (Table 1).

Nasopharyngoscopy was tolerated well by 60 children with15% lignocaine spray. Oral midazolam 0.5 mg/kg of bodyweight for sedation was used in 2 patients. Nasopharyngo-scopywas done using rigid 4 mm0° endoscope in 59 cases andin only 3 cases required rigid 2.7 mm endoscope. In our studyin only 6% of nasopharyngoscopies decongestion of nose wasdonewhile in 94% of nasopharyngoscopies no decongestion ofnose was required.

The reduction in size of adenoid was seen with bothmometasone furoate and saline nasal spray but statisticallysignificant reduction was seen only in group A (p value 0.0001)and not in group B (p value 0.11) (Table 1) (Fig. 4).

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ig. 3 –Comparisonofmeanof symptomsscore, adenoidsize,ME, PTA before and after treatmentwith Saline nasal spray.

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Fig. 4 – Comparison of change in symptoms score, OME andquality of life before and after each treatment.

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Statistically significant change in quality of life was seenbetween the group A (37.11 ± 25.5) as compared to group B(11.02 ± 19.8) (p value of 0.0001) (Table 1) (Fig. 4).

On patients each visit irritation of nose and throat,crusting, transient dryness and epistaxis was enquired,examined and noted. In our study 2 patients in group Areported minor nasal bleeding while 3 patients reported nasalbleeding in group B. In these patients correct method ofspraying was reinforced (spray away from the septum),symptoms subsided on its own with no recurrence in nasalbleeding was observed.

4. Discussion

Otitis media with effusion in children is a global healthproblem due to its negative impact on quality of life. It is oneof the most common causes of treatable conductive hearingloss. Many patients remain undiagnosed especially in devel-oping countries which can lead to poor performance in schooland affect the overall development of the child.

In recent year’s concept of medical treatment havedeveloped. Many studies have been conduced however theusefulness of steroid spray in patients of otitis media witheffusion is debatable.

The mechanism of action of steroids in this context is stillunclear. Mometasone furoate has been shown to help in therecovery of transport function of ciliary epithelium helpingin appreciable clinical effect [5]. A high level of expression ofthe human glucocorticoid receptor-alpha (vs. beta) in theadenoids and tonsils of patients who have obstructive sleepapnea versus recurrent throat infections suggested a possiblechance for these patients to respond to topical steroid therapy[15]. We chosemometasone furoate nasal spray because of it’sfavorable benefit-risk ratio.

Our study included childrenof both sexes fromage2–12yearsas regression of adenoid in seen with age. The mean age ofpresentation in our study was 7.4 years. No sexual predilectionwas noted.

Steroid nasal spray for short duration is known to decreasethe OME [7]. We used mometasone nasal spray for six monthsand noted that with six months of mometasone nasal spray

Please cite this article as: Bhargava R, Chakravarti A, A double-blmometasone furoate..., Am J Otolaryngol–Head and Neck Med a

statistically significant improvement in the OME with mome-tasone nasal spray as compared to the placebo group. Similarfindings have been reported recently by other authors [4,16].The nonresponsive patients in this study were treated withventilation tube insertion.

In our study statistically significant improvement insymptom score with mometasone nasal spray was seen.Nasal obstruction (p value 0.004), snoring (p value <0.0001),OSA score (p value 0.04) and total symptom score (p value 0.04)showed statistically significant change over placebo group.These findings were comparable to the other authors [17–19].This change in symptom score was statistically significant ascompared with placebo group.

Hearing loss associated with OME is typically conductivehearing loss and usually of mild or moderate grade. PTA couldbe done in 48 patients and topical mometasone spray broughtstatistically improvement in hearing as compared to thecontrol group (p value <0.05).

Statistically significant reduction in size of adenoid onnasopharyngoscopy (p value 0.0001) was seen onlywith mometasone nasal spray while with saline nasal spray(p value 0.11) this reduction was not statistically significant.Similar observation of objective reduction in size of adenoidpre and post-treatment was noted by other authors [17–19].

Mometasone nasal spray brought statistically significantchange in quality of life (37.11) as compared to control group(11.025) (p value of 0.0001). This positive change in quality oflife is attributed to marked improvement symptoms, im-provement in hearing and OME. To the best of our knowledgeno other study has assessed the change in quality of life of thepatients post treatment.

There is no consensus over the optimal dose and durationof treatment. We prescribed mometasone in the dose of 200mcg/day for the period of 2 months followed by a mainte-nance dose of 200 mcg/2 days for 4 months resulting insignificant improvement in the symptoms score and reduc-tion of size of adenoid, resolution of OME and improvement inquality of life. Authors have used themometasone nasal sprayin the dose 100 mcg/day for a variable period ranging from40 days to 4 months 10 days [17–19].

Our series is among the largest series which usedmometasone nasal spray for the treatment of OME withadenoidal hypertrophy and studied the change in quality oflife. None of the previous studies have reported on the changein quality of life in these groups of patients. Confounding biasof adenoidal hypertrophy was removed in our study whichwas present in previous study which could have affected theresults. Only one other author have removed the same andfound similar results [4].

On the basis of this study we advocate the use ofmometasone furoate nasal spray in the management of otitismedia with effusion with adenoidal hypertrophy.

R E F E R E N C E S

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