Efficacy of Mometasone Furoate Nasal Spray with Oral Montelukast in the treatment of Otitis Media with Effusion with or without Adenoid Hypertrophy and Atopic diseases.

Bacground: Otitis media with effusion [OME] is a common chronic but silent disease of middle ear in children and is the commonest cause of hearing impairment, delayedlanguage development and altered quality of life.Though surgical management is the treatment of choice but now alternative medical treatment with steroid nasal spray is well accepted. Aim of this study: In this prospective, randomized placebo control study we want to observe the efficacy of Mometasone furoate nasal spray in conjunction with oral Leukotriene receptor blocker [Montelukast] in comparison to Mometasone furoate nasal spray only and normal saline spray as placebo for 3 months. Materials and Methods: Total sixty children aged 2-12 years old diagnosed with bilateral OME for at least 3 months with or without enlarged adenoid & atopic diseases, were randomly allocated into three equal groups. The first group A received Mometasonefouroate nasal spray plus Tab Montelukast for 12 weeks and second group B received only mometasonefouroate nasal spray &third group C received normal saline spray for the same duration. Result: Otoscopic clinical exam, Pure Tone audiometry & tympanometry were done at the end of treatment [3 months duration]. In otoscopic examination normal tympanic membrane finding show significant improvement in group A than group B & group C and tympanometric result in group A , show 80% improvement in middle ear status & had larger chi-square value then group B [60% improvement] and group C [10% improvement] and pure tone audiometry result show highest hearing threshold improved in group A and were more significant than group B and control group C. Conclusion: Mometasone furoate nasal spray is a much more effective medical treatment option in resulution of OME when it is combined with oral Leukotriene receptor blocker Montelukastas it helps to normalize the Eustachian tube function and middle ear status by decreasing enlarged adenoid size, atopic disorders and improving hearing power & quality of life.


Introduction
Otitis media with effusion (OME) is a common and important ear problem of childhood.It is a chronic disease where accumulation of mucus or serous sticky fluid accumulate in middle ear and mastoid air cells without features of an acute infection .1 The etiology of OME is multifactorial.Adenoid hypertrophy, allergy/atopy, repeated upper respiratory tract infection and gastro-oesophageal reflux disease including poor eustachian tube function, all have been identified as etiological factors .2,3 It is the leading cause of acquired hearing loss in children. This may affect language and mental development .4 Conventional medical therapy has been tried for OME, including antibiotics, nasal decongestants, antihistamines, but all fail to provide satisfactory relief of otogenicsymptoms and ultimatly they require surgery which are more cost effective and again some parents do not agree with it under General Anaesthesia because of hazards. 5,6 So, some authors have suggested the use of short term systemic as well as topical intra nasal corticosteroid spray in the treatment of OME for decades, .2,7,8,10,11 Topical intranasal steroid is relatively safe especially the glucocorticoid which is rapidly degraded in the nasal mucosa to less active metabolites and is absorbed & metabolized through the liver. The systemic adverse effects are therefore less likely while the desired anti-inflammatory effects are so good .19,20 In this experimental study , we choose mometasone furoate monohydrate topical nasal spray with leukotriene receptor blocker tab Montelukast in the treatment of OME compared with only mometasonefuroate monohydrate nasal spray and in control group normal saline spray in children aged between 2-12 years .The efficacy of the topical mometasonfuroate steroid spray with leukotreine receptors blocker Montelukast significantly improved[ p<0.001 with large chi-squre value] the clinical and audiological status of children with OME.

Materials and Methods:
This is an experimental, randomized prospective placebo control study, carried out from January'20 to December'20 on 66 children of the age group 2-12 years and were diagnosed as bilateral Otitis Media with effusion in the Department Otolaryngologyand Department of Pediatrics of a tertiary care hospital in Dhaka, Bangladesh. It was approved by the institutional ethical committee. Informed written consent was obtained from parents of children under study after explanation of the research purpose.
Following steps were implemented in reaching the diagnosis of OME in children.History was taken from the parents, giving importance on different aspects of the condition including nasal obstruction, nasal discharge, snorring, hypo-nasal voice, difficulties in hearing and school performance, H/O previous earache and previous operation in the field of ear, nose and throat. Clinical examination of ear, nose, throat, otoscopy& Pure tone audiometry with tympanometry weredone to see hearing impairment and middle ear compliance. X-ray nasopharynx L/V view was done for diagnosis of enlarged adenoid inevery child.In our study 50 children had enlarged adenoid (grade-2 & 3). Total circulating oesonophil and S.IgE level were done for evaluation of allergic diseases.
The exclusion criteria for the study were: Parents were instructed how to use intra nasal spray and given Mometason Furoate nasal spray with oral Montelukast in group A and only Mometasonfuroate nasal spray in Group-B, Nosomist spray (normal saline ) as placebo in group C with the instruction to take 1 spray mometasone furoate (100 mcg/day) into each nostril once daily for 12 weeks.Instructed dose of Montelucast was 4 mgtablet upto age 5 years & 5 mg for 6-12 years of age.
Otoscopy examination, with basic audiological evaluation including pure tone audiometry and tympanometrywere performed before treatment, 8 weeks treatment after and after stopping of treatment (after 12 weeks). Tympanometry and pure tone audiometry were done by an audiologist in a standardized room. A type 'B' flat tympanogram was considered to support diagnosis of OME and 'C' Curve indicate negative pressure in middle ear. Clinical examinations and otoscopywere done once per week for 3 weeks and at the end of treatment. OME resolution was defined as normal finding of tympanic membrane on otoscopy, type A tympanogram and improved hearing to normal threshold.The efficacy of nasal steroid Mometasone Furoate with Montelukast in the management of OME was compared with that of only MometasonFuroate nasal spray and normal saline spray as placebo.

Statistical Analysis:
Distribution of the characteristics of the sampled patients were presented using graphical representation (Horizontal Bar Plot). Then, efficacy of the treatments on Group A and B compared to controlled group was assessed using Pearson's Chi-Squared test (2) and visualization of the efficacy using vertical bar plot. Hearing improvement within each group was assessed using paired t-test (3) and finally effect of treatment was measured using ANOVA (4) and Duncan Multiple Range Test (5). Level of significance considered 5% for all tests. All statistical analyses have been conducted using Microsoft Excel and RStudio (R version 3.6.2).

Ethical clarity:
Ethical clearance of this research was received from the Ethical committee of Green Life Medical College, Dhaka.

Result:
Distribution of the analytic sample (n=60) presented in Figure 1. Two treatments groups and one control group contain 20 patients each and the sample is dominated by male patients. On the other hand, least patients are from 9-12 age groups and highest number of patients allocated in age group 3-4.          To assess the magnitude of the hearing thresholds improvement we conducted ANOVA followed by Duncun's Multiple range test on hearing thresholds improvement (Pre treatment dB -Post treatment dB) ( Table 4). Significant p-value in ANOVA explains the significant effect of treatments on patients. Duncun's multiple range test clearly showed that average hearing improvement is significantly highest among Group A (23.25dB) followed by Group B (18.70dB) and lowest hearing improvement found in control group. Otitis media with effusion is a very common but silent disease of ear in childhood. It is a non-inflammatory condition of middle ear with accumulation of fluid which causes hearing impairment, delayed language development and affects quality of life. 1, OME is mostly diagnosed at the age of 1-4 years of age because in this paediatric age group eustachian tube remain shorter, wider and morehorizontal in position so liquid food or upper respiratory secretions easily reach middle ear and act as cofactor in developing otitis media with effusion. 2,3 Hearing impairment in otitis media with effusion is conductive in type and often mild to moderate in severity (26-40 DB).We performed pure tone audiogramand tympanometry to all patients of our study to asses' middle ear status and hearing loss.
Surgical procedures like insertion of tympanostomy tube, myringotomy with or without adenoidectomy are universally accepted modality in the treatment of persistent middle ear effusion.However, these procedure are always done under general anesthesia and thus may have complications and incurs cost. 5,6 Medical treatment with systemic corticosteroid or topical intranasal corticosteroid especially glucocorticoid has anti-inflammatory, anti-allergic effect locally as well as systemic without significant side effect. They act by preventing the synthesis of inflammatory mediators, increase insurfactant in Eustachian tube, decrease adenoid size and shrink peritubal lymphatic swelling which allow bettereustachian tubal functions. In addition, they decrease the viscosity of middle ear fluids,allergy and upregulate transepithelial sodium transport in middle ear epithelium and promote removal of middle fluid. Mode of action of intra nasal steroid is very complex but significantly beneficial. 7,8,9 Lots of study have been done previously with different type of steroid in the treatment of persistant otitis media with effusion with or without enlarged adenoid and show statistically significant outcome 10,11,12,17,20 mostly using the steroid mometasonefuroate.
In our study with mometasonefuroate nasal spray we added new drug Leucotrine receptor blocker Montelukast which binds with high affinity the Leukotrine receptors LTC4, LTD4, LTE4 and reduceinflamations, mucus secretions and relax smooth muscle in upper respiratory tract, nasopharynx, eustacian tube, middle ear & lungs and give good result in the treatment of enlarged adenoid, and atopic diseases which are the contributing factors of developing otitis media with effusion. 13,14.15.21 Our study is comparable to W Liu et al.2017. 18 and AboubakrElshafeyRas et al study 2020 19 . InAboubakrElshafeyRas et al study which included 100 children with adenoid hypertrophy with or without otitis media effusion and they were randomly devided into two equal groups. Group-1, received combined therapy using oral Montelukast and Mometasonfouroat naasal spray. Group-2, received only Mometasonefuroatenasal spray for 12 weeks.
Result was significantly reduced enlarged adenoid size in group -1 than Group -2 [p<0.001] and also reduced enlarged adenoid related sign & symptoms especially otitis media with effusion.
In our experimental, prospective, randomized, controlled study [(n-60) we used Mometasonfuroate nasal spray in combination with oral Montelukast in Group -A. only Mometasonfouroate nasal spray in Group-B, and normal saline spray as placebo in Group -C. for 3 months. Both treatment in Group -A & Group-B, founds significantly effective but chisquare test values depicts that Mometasonefuroate nasal spray with oral Montelukast statistically significant improvement in the treatment of OME with or without adenoid hypertrophy and atopic diseases.
Limitation of study: Short -term follow up and small sample size are the limitation of our study