Mometasone Furoate Use for Recurrent Adenoid Hypertrophy: Randomized Controlled Clinical Trial

Abstract

Background& Objective: Adenoid hypertrophy (AH) in children is one of the most causes of nasal obstruction and is associated with many nasal and respiratory symptoms. Till now, surgery is the main option for managing the associated symptom of AH. The intranasal steroid has an effective role in the control of allergic rhinitis and associated AH. This work aimed to assess the effects of local mometasone on recurrent AH in children. Patients& Methods: A randomized controlled trial enrolled 39 patients aged between 2 and 15 years with recurrent AH. Those patients were randomly subdivided into three groups; group (A) received topical mometasone furoate (MF), group (B) did not receive any medication, and group (C) received topical normal saline. All groups were followed up for 8 weeks. Results: Patients who received Mometasone furoate had temporary relief of adenoid hypertrophy-related symptoms (84.6%) in comparison to the control group and placebo group during the duration of treatment. After cessation of treatment with local steroids, all cases experienced symptoms caused by adenoid hypertrophy, and by the end of the third month of follow up all cases underwent adenoidectomy. Conclusion: Mometasone furoate can temporarily reduce the adenoid size, reducing symptoms related to adenoid hypertrophy.

Introduction

Adenoids are considered a member of waldeyer’s ring that has a basic role in immunologic development, its smallest size is found at birth and gradually growths and increases in size especially in allergic patients after exposure to respiratory air and therefore to various antigens; they produce antibodies against exposed antigens [1].

Adenoid hypertrophy (AH) is a common cause of bilateral nasal obstruction in children and commonly needs surgical removal in these patients because of its multiple morbidities [2]. Adenoids hypertrophy usually leads to nasopharyngeal fullness and an increase in the rate of upper respiratory tract infections, appetite reduction, growth retardation, facial growth abnormalities (adenoid face), nocturnal enuresis, alveolar hypoventilation, cor-pulmonale. Nasal obstruction results in open-mouth breathing, halitosis, snoring, nasal speech, obstructive sleep apnea (OSA), and some olfactory disorders [3–5].

Surgery is commonly recommended in symptomatic patients, but there are some limitations to surgery like cleft palate and coagulopathy disorders [6]. Also, there are two difficulties to do complete adenoidal removal. Firstly, lymphoid tissue located in the pharyngeal recess is difficult to remove [7], in addition to the bulge of adenoidal tissue in the choana [8].

Topical nasal steroids are reliable to be the most effective medication in controlling symptoms related to allergic rhinitis (AR) especially nasal obstruction [9–11]. Over the past years, good results were reported regarding the use of nasal steroids in children with chronic obstructive nasal symptoms due to hypertrophy of adenoid tissue [12–15]. Mometasone furoate is well-established to be safe in children aged 2 years or older [16–19]. Our study is aimed to evaluate the effect of local Mometasone Furoate on recurrent adenoids.

Patients and Methods

Study Design

This randomized controlled clinical trial was conducted at the ENT department, Assiut University Hospital year from July 2016 to July 2017.

Written consent was obtained from one parent of the participant children were obtained before joining the study which was approved by the ethical committee of the Faculty of Medicine, Assiut University. (IRB No 17,100,250)

Inclusion Criteria

Included in the study were children attending the clinic old with recurrent Adenoids aged 2–15 years after confirming diagnosis radiologically by x-ray lateral view of the nasopharynx and endoscopically before they enrolled in our study.

Exclusion Criteria

Patient with one or more of the following conditions was excluded; age less than 2 or more than 15 years old, nasal obstruction caused by other than AH (e.g., polyp and septal deviation), contraindication to steroids, and/or parent refuses to participate in the study.

Method

We estimated a 1.3% incidence of recurrent symptomatic adenoids that required surgical intervention [20, 21]. Therefore, 13 patients in each group will be required to provide a 90% confidence level for a three-sided with a marginal error of 5%.

Simple randomization was performed through sequentially numbered opaque envelopes using a random numbers Table (1:1 ratio) by using http://www.randomizer.org where those patients were subdivided into three groups where each group had 13 patients:

Group (A) received topical mometasone furoate (MF) at a dose of 50 micrograms in one puff/ nostril/ day. This was done with the following instructions: testing of nasal spray bottle before using, remove of mucous from the nose before use, Making the child’s head bent forward and bringing the chin to the chest, using the parent’s opposite hand to the nostril in which the spray would be applied to place the end of the spray bottle just inside the nostril, aiming it away from the nasal septum, block the other nostril while activating the spray and avoidance sniffing while or after spraying of the drug.

Group (B) received no medications and was prepared for adenoidectomy. The patient’s waiting time was the same as the duration of the study.

Group (C) received topical 0.9% normal saline: by using emptied nasal spray bottle after purifying it and adding saline to the bottle to mimic the original spray bottle.

Parameters used to compare between groups and to judge the response and reduction in adenoids size are:

1-History.

• Age and sex.

• Nasal obstructive symptoms especially nasal obstruction, hypo nasal speech, snoring, and open mouth breathing.

• allergic symptoms especially itching and/or sneezing.

The intensity of each symptom was scored as score 0 (absent), score 1 (mild or sometimes), score 2 (moderate or > 50% of times), or score 3 (severe or constant).

2-Examination:

• To exclude other causes of nasal obstruction.

• The size of adenoids was assessed endoscopically using a flexible endoscope, it was graded according to Clemens et al. classification [22]:

• Grade I: Adenoid tissue filling one-third of the vertical portion of the choanae.

• Grade II: Adenoid tissue filling up to two-thirds of the choanae.

• Grade III: From up to two-thirds to nearly complete obstruction of the choanae.

• Grade IV: Complete choanal obstruction.

3-Radiological assessment.

X-ray lateral view of the nasopharynx was done and the size of adenoids was assessed and graded as follows.

• Grade I: adenoids occupy ≤ 25% of the nasopharynx.

• Grade II: adenoids occupy > 25% - ≤ 50% of the nasopharynx.

• Grade III: adenoids occupy > 50% - ≤ 75% of the nasopharynx.

• Grade IV: adenoids occupy > 75% of the nasopharynx.

Follow Up

Follow-up was done for the 8 weeks after the child enrolled in the study. At the end of the 8th week; patients were re-assessed by lateral view X-ray of the nasopharynx and nasopharyngeal endoscopic examination under local anesthesia.

Patients who were found to have no or mild nasal obstruction were followed up for three months, and adenoidectomy was done for patients with moderate and severe obstruction.

Statistical Analysis

Data was collected and analyzed by using SPSS (Statistical Package for the Social Science version 20, IBM, and Armonk, New York). Continuous data were expressed in the form of mean ± standard deviation or median range while nominal data were expressed in the form of frequency and percentage. The P-value was considered to be statistically significant if < 0.0.

Results

This study includes 39 children with recurrent adenoids. Patients’ age ranged between 2 and 15 years old with a mean age of 7 ± 3.74. the majority of patients were males (61.1%) with no statistically significant difference in the three groups regarding age and sex.

There were changes in symptoms related to Adenoids hypertrophy (nasal obstruction, open mouth breathing, snoring, and hyponasal speech) pretreatment and 8 weeks after enrolling in the study and shows statistically significant improvement of symptoms only in group A (P-value = 0.03, < 0.001, < 0.001, = 0.02 respectively). (Table 1)

Table 1.

Comparison between studied groups regarding obstructive symptoms

item	Time and P-value	Group A	Group B	Group C	Item	Time	Group A	Group B	Group C
Nasal obstruction	Before				Snoring	Before
	0 Absent	0(0.0%)	0(0.0%)	0(0.0%)		0 Absent	0	0	0
	1Mild/Sometimes	0(0.0%)	0(0.0%)	0(0.0%)		1Mild-Sometime	4(30.8%)	2(15.4%)	5(38.5%)
	2 Moderate	3(23.1%)	3(23.1%)	1(7.7%)		2 Moderate	6(46.2%)	9(69.2%)	7(53.8%)
	3Sever-Constant	10(76.9%)	10(76.9%)	12(92.3%)		3Sever-Constant	3(23.1%)	2(15.4%)	1(7.7%)
	After					After
	0 Absent	2(15.4%)	0(0.0%)	0(0.0%)		0 Absent	2(15.4%)	0	0
	1Mild-Sometimes	9(69.2%)	0(0.0%)	0(0.0%)		1Mild-Sometimes	9(69.2%)	2(15.4%)	5(38.5%)
	2 Moderate	1(7.7%)	3(23.1%)	1(7.7%)		2 Moderate	2(15.4%)	9(69.2%)	8(61.5%)
	3Sever-Constant	1(7.7%)	10(76.9%)	12(92.3%)		3Sever-Constant	0(0.0%)	2(15.4%)	0
	P-value	0.03*	1	0.38		P-value	< 0.001*	1	0.28
hypo-nasal speech	Before				Mouth breathing	Before
	0 Absent	1(7.7%)	0	0		0 Absent	0	0	0
	1Mild-Sometime	7(53.8%)	8(61.5%)	8(61.5%)		1Mild-Sometime	1(7.7%)	0	0
	2 Moderate	3(23.1%)	3(23.1%)	4(30.8%)		2 Moderate	8(61.5%)	11(84.6%)	12(92.3%)
	3Sever-Constant	2(15.4%)	2(15.4%)	1(7.7%)		3Sever-Constant	4(30.8%	2(15.4%)	1(7.7%)
	After					After
	0 Absent	1(7.7%)	0	0		0 Absent	3(23.1%)	0	0
	1Mild-Sometimea	11(84.6%)	8(61.5%)	9(69.2%)		1Mild-Sometimes	10(76.9%)	0	0
	2 Moderate	1(7.7%)	3(23.1%)	3(23.1%)		2 Moderate	0	11(84.6%)	12(92.3%)
	3Sever-Constant	0	2(15.4%)	1(7.7%)		3Sever-Constant	0	2(15.4%)	1(7.7%)
	P-value	0.02*	1	0.59		P-value	< 0.001*	1	0.64

There was a marked improvement in allergic symptoms like nasal itching and sneezing among patients of group A (p-value < 0.001) but in the other groups, no significant change was observed in both symptoms. (Table 2)

Table 2.

Comparison between studied groups regarding allergic symptoms

item	Time and P-value	Group A	Group B	Group C
Nasal itching	Before
	0 Absent	0	0	0
	1Mild/Sometimes	1(7.7%)	0	0
	2 Moderate	9(69.2%)	6(46.2%)	4(30.8%)
	3Sever-Constant	3(23.1%)	7(53.8%)	9(69.2%)
	After
	0 Absent	0	0	0
	1Mild-Sometimes	12(92.3%)	0	0
	2 Moderate	1(7.7%)	6(46.2%)	5(38.46%)
	3Sever-Constant	0	7(53.8%)	8(61.53%)
	P-value	< 0.001*	1	0.48
Sneezing	Before
	0 Absent	0	0	0
	1Mild-Sometime	0	0	0
	2 Moderate	3(23.1%)	2(15.4%)	2(15.4%)
	3Sever-Constant	10(76.9%)	11(84.6%)	11(84.6%)
	After
	0 Absent	1(7.7%)	0	0
	1Mild-Sometimes	10(76.9%)	0	0
	2 Moderate	0	2(15.4%)	2(15.4%)
	3Sever-Constant	2(15.4%)	11(84.6%)	11(84.6%)
	P-value	< 0.001*	1	0.48

Endoscopic examination of the nasopharynx revealed a reduction of adenoids size in group A during the eight weeks of treatment with local mometasone furoate (P-value < 0.001) with no improvement or reduction of adenoid size in groups B and C (P-value = 1, 0.48 respectively). Radiological assessment using lateral view x-ray of the nasopharynx clarifies the reduction of adenoid size immediately at the end of the eighth week of treatment in group A patients (P = 0.02) while no difference was experienced in patient groups B and C. (Table 3) (Fig. 1).

Table 3.

compares nasopharyngoscopic examination and X-ray lateral view of the nasopharynx in the studied groups

item	Time and P-value	Group A	Group B	Group C
Nasopharyngeal endoscopic ex.	Before
	Grade 1	0	0	0
	Grade 2	0	0	0
	Grade 3	3(23.1%)	3(23.1%)	1(7.7%)
	Grade 4	10(76.9%)	10(76.9%)	12(92.3%)
	After
	Grade 1	2(15.4%)	0	0
	Grade 2	9(69.2%)	0	0
	Grade 3	1(7.7%)	3(23.1%)	2(15.38%)
	Grade 4	1(7.7%)	10(76.9%)	11(84.61%)
	P-value	< 0.001*	1	0.48
X-ray lateral view of nasopharynx	Before
	Grade 1	0	0	0
	Grade 2	2(15.4%)	2(15.4%)	1(7.7%)
	Grade 3	6(46.2%)	8(61.5%)	10(76.9%)
	Grade 4	5(38.5%)	3(23.1%)	2(15.4%)
	After
	Grade 1	2(15.4%)	0	0
	Grade 2	9(69.2%)	2(15.4%)	1(7.7%)
	Grade 3	2(15.4%)	8(61.5%)	11(84.61%)
	Grade 4	0	3(23.1%)	1(7.7%)
	P-value	0.02*	1	0.67

Fig. 1.

Follow up of 8 years male patient in the MF group

X-ray lateral view of nasopharynx shows adenoids reduction (pretreatment 1a and posttreatment 1a).

Endoscopic evaluation of adenoids size (pretreatment 2a and post-treatment 2b).

All patients in groups B& C underwent adenoidectomy at the end of the eighth week. Two patients in group A did not respond to steroid treatment and adenoidectomy was performed at the end of the eighth week. Eleven patients in group A experienced marked improvement during the duration of treatment and after stopping the treatment recurrence of symptoms was noted, then all eleven patients underwent adenoidectomy: 4 patients (36.36%) by the end of the first month, 5 patients (45.45%) during the second month, 2 patients by the end of the third month. (Fig. 2).

Fig. 2.

Flow chart of the current study summarizing pathways of all children enrolled in our study and showing temporary improvement of symptoms related to adenoid hypertrophy in patients in group A with no improvement in both groups B and C

Discussion

Usually, the proper treatment of adenoid hypertrophy is surgical removal, however, there were some contraindications and limitations of surgery.

In our study, we compared the efficacy of using MF nasal spray (group A or MF group) to using normal saline spray (group C) or just follow-up without any medication (group B) in children who have adenoid hypertrophy.

Our study included children of both sexes from age 3–12 years as regression of adenoid is seen with age. The mean age of presentation in our study was 7.56 years. The male to female ratio was 1.6:1. This data was nearly similar to Lesinskas & Drigotas’s study which was conducted on 105 children with adenoids and published in 2009 and found that The mean age of the children was 6.53 ± 3.13 years with a range from 3 to 15 years, of whom (60.6%) were male and (39.4%) female [23] and similar to Bhargava & Chakravarti study which reported that the maximum incidence of adenoidal hypertrophy was found at a mean age of 7.4 years [23,24]. Mohebbi et al. found that (60.7%) were males and (39.3%) were females [25]. But this data was different from Demirhan et al. study that females were more than males and the mean age was more than 9 years [26] and Hassan who reported that the age was ranged from 5 to 14 years and females were more than males [27].

We noticed a significant improvement in eleven patients (84.6%) who received MF (Group A) -before and after the 8week duration of MF nasal administration- in form of decreased symptoms (nasal obstruction, hyponasal speech, snoring, mouth breathing, nasal itching, and sneezing) and reduction of adenoid size endoscopically and radiologically.

In group A, Nasal obstruction was significantly improved (P < 0.03) in 84.6% of our patients. Cengel and Akyol compared the nasal obstruction before and after 100 µgm MF administration for 6 weeks and declared significantly decreased nasal obstruction (p < 0.001) which was absent in 55.5% of their patients [15]. Bhargava & Chakravarti noticed a great improvement in nasal obstruction after 8 weeks of treatment with 200 µgm MF/day followed by 16 weeks with 200 µgm MF/other day (p = 0.0001) and reported a statistically significant difference between the study and placebo group (p = 0.004) [24]. Mohebbi et al. found significant improvement in nasal obstruction (p = 0.001) after receiving 200 µgm MF/day for 3 months [25]. Berlucchi et al. stated that there was a great improvement in nasal obstruction in 77.7% of patients (p = 0.00005) on 100 µgm MF/day for 40 days [11]. Hassan reported a good response after 100 µgm MF/day for 12 weeks (P = 0.004) [27]. Yildirim et al. used 80 µgm MF/day for 6 months and described good improvement in nasal obstruction (p = 0.019) [28]. Rezende et al. found a significant reduction in nasal obstruction (p < 0.0001) after 100 µgm MF/day for 40 days [29].

Hyponasal speech is one of the adenoid symptoms. We observed a markedly positive response in group A during the evaluation of nasality before and after the treatment. Most of our patients (92.3%) showed significant improvement. Yildirim et al. found that there were statistically significant differences between the study and saline groups in terms of improvement in hyponasal speech (p = 0.001) [28]. Mohebbi et al. noticed a great improvement in hyponasal speech after using MF (p < 0.001) [25]. Demirhan et al. who used fluticasone propionate in their study reported good improvement of hypo nasal speech [26].

Snoring is one of the main symptoms of AH, we found a statistically significant difference before and after treatment (P < 0.001). Improvement in snoring is secondary to the reduction of adenoid size. Our findings are comparable to those of the most relevant studies [11, 15, 23, 24, 26–28,24, 25, 27–29].

Only in children who received MF nasal spray, Open mouth breathing was markedly improved after treatment (P < 0.001). Cengel and Akyol noticed normal nasal breathing after treatment (p < 0.001) with a curative rate of 34.3% [15]. Hassan found a great response after MF administration (P = 0.004) [26,27]. Yildirim et al. also reported significant improvement in mouth breathing in patients who received MF (p = 0.02) [28]. Mohebbi et al. observed nasal patency after using MF (p < 0.008) [25].

Nasal itching and sneezing were markedly reduced in response to MF administration (P < 0.000). Rezende et al. noticed a marked reduction of itching and sneezing as well (p < 0.0001) [29].

Endoscopic evaluation of the patients after MF administration showed a significant reduction of adenoid size (P < 0.001). Eleven patients (84.6%) had adenoids less than 50% of the rhinopharyngeal cavity. Shrinkage of adenoids after administration of nasal steroids is attributed to their lymphocytolytic effect as they arrest growth and induce apoptosis in lymphoid tissue [30]. Cengel and Akyol reported marked adenoid shrinkage after treatment (P < 0.001) with 58.2% of patients showing adenoid size less than 50% nasopharyngeal cavity[15]. Yildirim et al. noticed a great improvement in adenoid size after 6 months of treatment (p = 0.001) [28]. Hassan observed a reduction of adenoid size by 35.72% [27]. Bhargava & Chakravarti found that the adenoid size was greatly reduced after receiving MF (p = 0.0001). [24] nearly similar data was reported by Berlucchi et al [11], Rezende et al [29] as they stated significant shrinkage of adenoids (P = 0.0007), (p < 0.0001) respectively.

A comparison of an x-ray before and after using MF showed a significant reduction of adenoid size (P < 0.02). Eleven patients (84.6%) had adenoids less than 50% of the nasopharyngeal cavity. Tuhanioglu et al. [31] and Mohebbi et al. [25] reported nearly similar results (P < 0.05), (p < 0.001) respectively.

We didn’t experience any adverse effects after using MF for 8 weeks unlike Berlucchi et al. noticed only 1 patient episodic epistaxis, which resolved spontaneously without treatment. No other adverse effects were reported [11]. Bhargava & Chakravarti found two patients with minor nasal bleeding and they attributed this complication to the faulty use of the nasal spray by patients. The symptoms subsequently subsided, with no recurrence of nasal bleeding [24]. Yildirim et al. excluded one patient during the study because of epistaxis [28].

During the follow-up of the improved eleven patients which extend to 3months, we noticed the recurrence of adenoid symptoms and enlarged adenoids endoscopically and radiologically. This means that the MF doesn’t have long action to cure AH but is still a temporary solution.

Bhargava & Chakravarti used MF at a dose of 200 µgm MF/day for 8 weeks followed by 16 weeks of 200 µgm MF/other day as an alternative to surgical management [24].

Zhang et al. concluded that intranasal steroids are significantly reducing obstructive symptoms in children with moderate to severe AH, and this improvement was due to a reduction of adenoid size. The long-term effect of intranasal CS in these patients is still unclear [10].

Regarding the control group (Group B) and the other group (Group C), we found that all clinical data -including symptoms, signs, and investigations- before and after the study duration were statistically insignificant and all patients underwent adenoidectomy after eight weeks of close follow-up. Berlucchi et al. stated that there was no significant improvement in all clinical data in placebo group patients [11]. Hassan found that all patients who received saline hadn’t any significant difference in all parameters and all patients underwent adenoidectomy [27]. In Tuhanioglu et al. study, the control group was statistically insignificant [31]. Cengel and Akyol reported that the control group did not show any improvement [15]. Yildirim et al. noticed that most of the symptoms in the placebo group were improved after 6 months of nasal saline administration [28]. Bhargava & Chakravarti evaluated the adenoid size after 24 weeks of saline irrigation and they found that there was no significant reduction of adenoid size, however, most of the symptoms were improved [24]. Rezende et al. reported improvement in symptoms such as nasal obstruction, snoring, rhinorrhea, sneezing, and itching after 40 days of saline douching without significant change in adenoid size [29].

Our study was limited by a small sample size, a short course of steroid nasal spray, and we used only a daily dose of 50 micrograms in each nostril. We didn’t use adjuvants to MF nasal spray in treating adenoids. We didn’t compare the use of other available formulas of nasal steroids. The small sample size is due to the low incidence of symptomatic recurrence of adenoid regrowth which is 1.3% [20, 21].

Conclusion

Adenoid hypertrophy could be managed temporarily by using intranasal MF safely in children as MF reduce nasal obstructive symptoms related to adenoids and allergic symptoms.

Authors’ Contributions

Mohamed Mahmoud Roushdy: conception and design, critical revision of the submitted manuscript and supervision.

Ahmed Aboulwafa Abdel Jalil: critical revision of the submitted manuscript and supervision.

Ahmed Mahmoud Saeed: collection and analysis of data, writing and submitting the manuscript.

All authors have read and approved the manuscript.

Funding

None.

Data Availability

The datasets generated during and/or analyzed during the current study are available.

Declarations

Ethics Approval and Consent to Participate

Ethical committee of Assiut University (IRB No 17100250), Consent was obtained from the study participants before research; informed written consent is available.

Consent for Publication

No.

Competing Interests

The authors have no conflict of interest to declare.