Ear, Nose & Throat Journal2023, Vol. 102(3) 198–203© The Author(s) 2022Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/01455613221140281journals.sagepub.com/home/ear
Objectives: Eustachian tube dysfunction (ETD) is frequent in children with adenoid hypertrophy (AH). Although the most common treatment of AH is surgical removal of adenoid tissue, numerous studies have reported the efficacy of intranasal steroids. The effects of the intranasal steroid and azelastine combination on AH and ETD have not been reported before. In this study, we tried to determine the effects of 3-month intranasal Azelastine-Fluticasone dipropionate combination (Aze-Flu) treatment in children with ETD and AH. Materials and Methods: 100 children who had open mouth sleep, snoring, and sleep apnea and were diagnosed with AH and ETD participated in this study. The mean age was 7.73 ± 2.37 (4–14 years). The rates of adenoid tissue hypertrophy and choanal occlusion were evaluated using a rigid pediatric nasal endoscope and reassessed after 3 months of Aze-Flu nasal spray treatment. The function of the Eustachian tube (ET) was evaluated before and after medical treatment using the Eustachian tube score, the Eustachian dysfunction test-7 (ETS-7) and tubomanometry (TMM). Results: The results were evaluated in 100 patients with AH and ETD. The adenoid tissue to choana rate was 82% before treatment and decreased to 37% after treatment. The ETS-7 test score was 6.36 before treatment and increased to 9.72 at the end of 3 months. Both the regression of the adenoid tissue and the improvement in the Eustachian function scores were statistically significant (p < 0.05). Conclusions: AH significantly increases the frequency of ETD. In this study, it was observed that Aze-Flu treatment was significantly effective in both regression of the adenoid tissue and Eustachian tube dysfunction. We believe that it can be applied as an initial therapy in children with AH and associated ETD.
Keywordsazelastine, fluticasone, Eustachian tube dysfunction, tympanometry, Eustachian tube score, adenoid hypertrophy, otitis media with effusion
Adenoid is an enlargement of lymphoid tissue in the posterior aspect of the nasopharynx. Although it has a protective role against infections normally found in the upper respiratory tract, it can cause chronic and recurrent infections. AH is a prevalent childhood disease that presents symptoms related to airway blockage such as snoring, hyponasal speech, and mouth breathing. In more severe cases, it can cause otitis media leading to conductive hearing loss, obstructive sleep apnea, growth retardation, and cor pulmonale.
In effusion-mediated otitis media (OME), a fluid collection is seen in the middle ear (ME). It is a frequent and recurrent childhood disease. It has the potential to cause hearing loss. It also negatively affects speech development and behavior. ETD plays an important role in the etiopathology of OME.1 The ME pressure is equalized by the ET opening due to the pressure difference between the nasopharynx and the ME.
ETD may cause a failure in pressure balancing and gas interchange through the ME mucosa, causing an effusion. The passive opening function of the ET may be obstructed by the hypertrophied adjacent structure, infections of the upper respiratory tract, insufficiency of active muscle strength during deglutition, and/or anatomical constrictions in the nasopharynx.
Numerous research data from children have approved the presence of a connection between AH and OME, advocating that AH forms an occlusion in the ET opening at the level of the torus tubarius, which may cause persistent ET inflammation and also recurrent infections of the adenoids. Nasal endoscopy and tympanometry are considered the ideal diagnostic method to examine OME and adenoids.2
Due to the difficulties in investigating the situation, a cautious assessment of ETD is not always carried out in the daily routine. TMM is one of the tests that detect the presence of effusion in ME and provides only data on ET function. With the widespread use of the TMM test in recent periods, the diagnosis and treatment of ETD has improved. This comparatively basic assessment provides satisfactory data on the patency and dynamic capacity of the ET.
One year ago, in our study with a different group of pediatric patients with only AH, we determined that Aze- Flutreatmenthadsignificant curative effects on AH. As the results of this study encouraged us, we planned to observe the therapeutic effect of Aze-Flu in children with ETD and AH.3
The purpose of this trial was to interpret ETD in the pediatric age group with AH and to evaluate the clinical effectiveness of medical treatment on ETD in children. In this trial, the effect of Aze-Flu nasal spray on AH and ETD was examined for the first time and the possibility of obviating the need for surgical treatment was evaluated.4
One hundred children with adenoid hypertrophy, aged 4– 14 years, were examined between November 2021 and March 2022. The study was carried out in accordance with the Declaration of Helsinki. The treatment protocol was authorized by the ethics committee for a randomized prospective longitudinal study (Protocol number: 020-9041 22/ 10/2021).
Children with a history of ventilation tube application, current acute infection, tympanic membrane perforation, previous ME or mastoid bone surgery, and previous nose or sinus surgery, craniofacial abnormalities, genetic syndrome, neuromuscular disease were excluded from the study.
All patients were evaluated with ETS-7 before and after treatment. Written informed consent was obtained for treatment and participation in the study from the parents or legal guardians of all patients.
Children were administered AZE-FLU (137 mmcg AZE and 50 mcg FP per spray) as one spray per nostril twice a day, in the morning and evening. The daily total dose was 548 mcg for AZE-Flu and 200 mcg for FP. Treatment efficacy was evaluated pre-treatment and after an 18-week treatment period.
ENT examination and tympanometry were performed in all patients prior to treatment to investigate any ETD. Tympanometry findings were processed with respect to the Jerger system, and a type B output was accepted as the presence of fluid collection in ME. [3] AH was examined with nasal endoscopy (2.70 mm rigid endoscope) and children were classified into 4 groups according to the volume of adenoid.5
The TMM and ETS-7 scale were performed in all patients before treatment to investigate an ETD. TMM is an audiometric method that measures gas transport to the tympanic cavity from the nasopharynx.6 This process relies on simultaneous airflow to the nasopharynx via a nasal cannula placed in each nostril while a compression receptor catheter is inserted into the external ear canal during swallowing. Pressure alterations are conducted to the probe placed in the ear canal via fluctuations of the tympanic membrane. TMM may also be applied in the presence of a ventilation tube or a damaged tympanic membrane.7
The TMM device measures variable pressure curves, and various measurement data are determined. The opening delay index (R score) is a parameter of the Eustachian tube function and determines the time elapsed between the application of the pressure to the nasopharynx and the measurement of pressure changes in the external ear canal. If ET works correctly, the pressure applied to the nasopharynx during swallowing is transmitted to the ME. R value less than or equal to 1 indicates that the Eustachian tube is working properly and opens immediately. An R value greater than 1 indicates that the Eustachian tube is not functioning properly and is opening late. No opening (R is negative or unmeasurable) shows total occlusion.
After the TMM test, the ETS-7 score generated by Schroder et al.8 The ETS-7 score is determined over 4 parameters: (1) Measurement of the ET function at 3 different pressure levels with TMM (30, 40, and 50 millibars),2 (2) subjective relative estimates of the applicability of Valsalva symptoms,3 (3) clinical findings based on Toynbee’s predictions, and (4) results of the tympanometry test. The range of the ETS-7 scale is between 0 and 14. A diagnosis of ETD is made with scores of 7 or less based on ETS-7.
All pre-treatment tests were repeated in all patients three months after treatment to recalculate the ETS-7 score. (including rigid endoscopic evaluation, clinical evaluation of subjective findings, tympanometry, and TMM)
A total of 100 children participated in the study (58 girls and 42 boys) with a mean age 7.73 ± 2.39 (range: 4–14), examined between 2021 November and 2022 March (shown in Table 1).
Before treatment, adenoid volumes were 25–50% in 6, 50– 75% in 39, and 75–100% in 55 patients. After treatment, the adenoid volumes were 0–25% in 34, 25–50% in 57% and 50–75% in 9 patients. The reduction in adenoid volumes after treatment was statistically significant (P = .001; P < .01) (shown in Table 2 and Figure 1).
The mean ETS-7 score was 6.36 ± 1.09 and the median was 6.5 before treatment, and increased to a mean of 9.72 ± 1.62 and a median of 9.5. The increase in ETS-7 scores after treatment compared to pre-treatment was statistically significant (P = .001; P < .01) (shown in Table 3 and Figure 2).
The program used for statistical analysis was NCSS (Number Cruncher Statistical System) 2007 (Kaysville, Utah, USA). Descriptive statistical methods used in evaluating research data (mean, standard deviation, median, frequency, ratio, minimum, maximum). The compliance of quantitative data with the normal distribution was checked by Kolmogorov– Smirnov, Shapiro–Wilk, and graphical evaluations. Pairedsamples test was used for intragroup comparisons of normally distributed quantitative variables. The Wilcoxon Signed Ranks Test was used for in-group comparisons of nonnormally distributed parameters. The level of significance was established at P < .05
The potential occlusion of the Eustachian tube by enlarged adenoid tissue is the most important reason for the formation of ETD and OME in children.9 This occlusion precludes passive gas exchange through ET in ME. Many authors have tried to find the clues of the connection betweenOMEandAHinETocclusion.10 Wright et al. found a direct relationship between ET orifice occlusion of lateral adenoid tissue and OME development.11 Skoloudik et al. also reported indirect evidence of ET obstruction by AD. It has been observed that adenoidectomy is also effective in the resolution of OME at a rate of 89% in children with adenoids that obstruct the torus tubarious. However, the same operation was only 68% effective in terms of OME resolution in children with small adenoids that did not obstruct ET opening.12
Demain and Goetz were the first to identify the effective use of intranasal steroid therapy in children with AH.13 Although the mechanism that explains how steroids improve nasal airway obstruction is unknown, there are some assumptions. The size of adenoids is decreased by the direct lympholytic effect; the anti-inflammatory effect of steroids reduces inflammation in the adenoids and nasopharynx or reduces the possibility of the adenoids creating a reservoir for infection. Studies that demonstrate the presence of glucocorticoid receptors and messenger RNA in adenoid tissues reinforce this possible mechanism.14
In some studies a substantial correlation has been observed between the nasal symptoms score and the A/C ratio.13 The results of these studies showed that the reduction in nasal airway obstruction findings was due to the effect of intranasal steroids on the volumes of adenoid tissue. However, it is known to increase the passage of nasal airways with fluticasone proiponate and provide healing by reducing the soft tissue volume of the inferior turbinates.15 It is still a matter of debate what dosage and position should be used for the use of intranasal steroids. In a study that examined the distribution of topical nasal steroids in the nasal cavity, sprays were found to be not sufficiently dispersed in the cavity.16
Corticosteroids have low side effects in children. Studies report only one case of episodic nosebleed.17 The effects of intranasal steroids on growth were studied in a randomized, double-blind, placebo-controlled study. The growth rate in prepubescent children who used fluticasone nasal spray for 1 year has been reported to be equal to the control group.18 When the study was completed, the authors recommended that a maximum dose of 200 mg/day per nostril was used. In our study, a maximum dose of 200 mg/day for each nostril and a total dose of 400 mg/day for each patient for 12 weeks. No side effects were observed in the patients.
Due to the difficulty of methods for evaluating the function of ET, the number of published studies directly evaluating tubal dysfunction in children with AH is low. Traditional methods to assess the ET function are not effective. Specifically, the tympanogram shows only whether there is an effusion in the ME and provides indirect data on the function of ET. Furthermore, endoscopic examination with Valsava and Toynbee maneuvers causes significant difficulties in terms of quantification.19 However, the discovery of the TMM method has made great progress in the diagnosis and treatment of ETD. This relatively easy method provides precise information on ET patency and airflow dynamics from the nasopharynx to the ME cavity.20
Liu et al. conducted a study using TMM to measure ET patency in adults with OME. Their findings demonstrated that the rates of limited opening or blocked ET under 30, 40, and 50 mbar pressure using the TMM test were 10%, 5%, and 0%, respectively (control group) and 76.19%, 66.7%, and 57.97%, respectively (OME group) (P < .05 for all pressure groups). TMM is more valuable as a test than tympanometry to confirm the diagnosis of ETD.21
Schroder et al. recommended the scoring of ETS-7 together with TMM to increase the precision of the diagnosis of ETD.22 The ETS-7 scoring system, with an estimated specificity of 60% and a sensitivity of 73%, has been preferred in various studies to diagnose ETD in adults. It contains an easily applicable scoring system based on TMM results in children.7
Manno et al found out children with AH have a high incidence of ETD measured with TMM and ETS-7. In these patients, the ETS-7 could be considered a tool for assessment in the preoperative and postoperative evaluation of the ETD.23
In our study, we used the TMM and ETS-7 scores to assess ETD in children with AH. To our knowledge, no previous studies investigated these effects, using TMM and ETS-7, of Aze-Flu therapy on ET function in childhood with AH. As reported in various publications, adenoidectomy restores ET function by improving ME ventilation and drainage.24,25
In our study one year ago, we observed that Aze-Flu treatment has curative effects in children with AD. The results of this study led us to investigate the therapeutic effect of Aze-Flu in children with ETD and AD, and we found that this treatment is also effective in children with ETD.3
In our study, Aze-Flu treatment was found to improve ET functions. 66% of children with ETD whose ETS-7 values returned to normal after treatment were in the fourth group of the AD classification. After an average 3 months of Aze-Flu spray treatment, the mean ETS-7 score increased from 6.36 before treatment to 9.72, which was statistically significant (P = .001).
In addition, no new OME attacks were observed in children whose ETS-7 score improved during the 3 month follow-up after medical treatment. This showed that the quality of life of the patients also improved. The small number of patients is one of the major limitations of this study (100 children) and the comparison of the structures of patients between the ages of 4 and 14 years at quite different levels of anatomical development in this study. It is common opinion that the incidence of OME in children under 6 years of age is markedly higher due to the underdevelopment of ET and has a lower level of anatomical improvement compared to later ages.
Nasal steroids are generally accepted to be safe for the pediatric age group. Although the exact mechanism of action has not been established, it is critical to discover the effect of intranasal corticosteroids in the treatment of children with AH and ETD.26
Intranasal corticosteroids are well tolerated by children; however, there are ongoing prospective and randomized studies that aim to find the optimal drug, its dose, and duration of treatment. To validate the results and findings of our research, a multicenter study involving more patients is required.
A high frequency of ETD, detected by the TMM and ETS-7 tests, is observed in children with AH. In these patients, ETS-7 can be used as an assessment tool in the preand post-treatment evaluation of ETD. The Aze-Flu treatment was found to be efficient in increasing the ventilation of AH and ME.
There is a high incidence of ETD in children with AD, as measured by TMM and ETS-7. In these patients, ETS-7 can be used as an assessment tool in the pre-and post-treatment evaluation of ETD. The Aze-Flu treatment was found to be effective in improving the ventilation of ME.
The safety of nasal steroids for the pediatric population is widely accepted. Although the mechanism has not yet been clearly and fully elucidated, it is important to establish the role of intranasal corticosteroids in the treatment of children with adenoid hypertrophy and ETD.
Intranasal corticosteroids are well tolerated by children; however, there are ongoing prospective and randomized studies that aim to find the optimal drug, its dose, and duration of treatment.
All authors have substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data.
This study was conducted in accordance with the tenets of the Declaration of Helsinki.
Ethics approval was obtained from the local Research Ethics Committee prior to the study.
Every participant patient was informed comprehensively about the study and informed consent was obtained from each of them.
All data generated or analyzed during this study are included in this article [and/or] its supplementary material files.
Ahmet Mert Bilgili https://orcid.org/0000-0003-2326-4511
Supplemental material for this article is available online.
1 School of Health Sciences, Cyprus International University, Lefkoşe, Cyprus
2 Department of Odiology, Biruni University, İstanbul, Turkey
3 Private Practice, İstanbul, Turkey
Corresponding Author:Ahmet Mert Bilgili, School of Health Sciences, Cyprus International University, Lefkoşa Haspolat, UKÜ kampüsü, Lefkoşe 99258, Cyprus.Email: amertbilgili@gmail.com
