Introduction
Medically treating children with obstructive adenoids to relieve their symptoms has been practised for more than 15 years.Reference Demain and Goetz1 According to a review of randomised, controlled trials studying the use of topical intranasal steroids in children with obstructive adenoids, this treatment may significantly improve nasal obstruction symptoms.Reference Chadha, Zhang, Mendoza-Sassi and César2
The use of mometasone furoate monohydrate nasal spray in that context has been studied previously, with good outcomes.Reference Berlucchi, Salsi, Valetti, Parrinello and Nicolai3–Reference Bitar, Mahfoud, Nassar and Dana5 However, these studies had a relatively short-term follow up, and they reported symptom improvement while the patients were still on treatment. Cengel and AkyolReference Cengel and Akyol4 used a total treatment time of six weeks, which was beneficial in 67.2 per cent of patients. Berlucchi et al.Reference Berlucchi, Salsi, Valetti, Parrinello and Nicolai3 gave their patients 40 days (approximately 6 weeks) of treatment. They followed this with a maintenance therapy for responders (77.7 per cent of the subjects), for a period of three months, using either alternate days of therapy for the first two weeks of each month, or daily use of the medication for the first two weeks of each month.Reference Berlucchi, Salsi, Valetti, Parrinello and Nicolai3 They subsequently reported a 28-month follow up of their patients, but these patients were still on maintenance therapy.Reference Berlucchi, Valetti, Parrinello and Nicolai6 In our previously published pilot study, a three-month treatment duration was used, with a response rate of 89 per cent.Reference Bitar, Mahfoud, Nassar and Dana5
This study aimed to analyse the long-term effect of mometasone furoate monohydrate on obstructive adenoids in children, after the cessation of three months of treatment. We also performed a systematic review of the English literature regarding the short- and long-term effects of intranasal topical steroids on obstructive adenoids.
Materials and methods
Nineteen children, who were previously enrolled in a pilot study,Reference Bitar, Mahfoud, Nassar and Dana5 and who completed a three-month treatment period with mometasone furoate nasal spray, were included in this prospective cohort study. The study was approved by the institutional review board at the American University of Beirut, and written consent was obtained from the respective parents or guardians of enrolled patients.
The patients’ caregivers were contacted by telephone at 3 months, 6 months and 12 months after the cessation of treatment, to assess: any present allergic rhinitis symptoms, the severity of nasal obstruction and the degree of obstructive symptoms caused by the adenoids.
Allergic rhinitis symptoms included rhinorrhoea or post-nasal drip, nasal congestion, nasal itching, sneezing, and eye symptoms (e.g. redness, itching or hyperlacrimation). Symptom severity was recorded according to the following scale: 0 (none) = no symptom evident; 1 (mild) = symptom is present but with minimal awareness and is easily tolerated; 2 (moderate) = definite awareness of symptom which is bothersome but tolerable; and 3 (severe) = symptom is hard to tolerate and causes interference with activities of daily living and/or sleeping. Allergic rhinitis was classified as mild or moderate to severe, and intermittent or persistent, as per the Allergic Rhinitis and its Impact on Asthma guidelines.Reference Bachert, van Cauwenberge and Khaltaev7 Allergic rhinitis is considered moderate to severe if it affects sleep, daily activities or performance at school; otherwise, it is classified as mild. If the symptoms occur more frequently than 4 days per week, or if they have been present for more than 4 consecutive weeks, the allergic rhinitis will be considered persistent; otherwise, it will be classified as intermittent.Reference Bachert, van Cauwenberge and Khaltaev7
The severity of nasal obstruction in general was assessed using the above scale, while the clinical score included the following symptoms: mouth breathing, snoring, restless sleep, frequent waking up at night (at least three times per night because of respiratory discomfort or distress) and obstructive breathing during sleep. Each symptom received a score of 0 (if absent) or 1 (if the parents confirmed its presence during sleep) to generate a final clinical score out of 5. This score has been previously validated against lateral nasopharyngeal X-ray and intra-operative findings.Reference Bitar, Rahi, Khalife and Madanat8
The above variables were compared at each point of follow up with the baseline values (obtained at the end of the previous treatment) using the Wilcoxon signed-rank test for non-parametric samples. The mean value of each variable was also reported.
To ensure the absence of any emergent causes of nasal obstruction during the intervals between the telephone calls, the parents were asked about any current or recent upper respiratory tract infection, and any recent history of trauma to the nose or nasal surgery.
A systematic review of the English literature was performed using Medline and Embase databases and the Cochrane Library. The terms ‘intranasal’, ‘topical’, ‘steroid’, ‘corticosteroid’, ‘spray’, ‘drops’ and ‘adenoid’ were used in various combinations to identify relevant articles published between 1970 and 2014. The results of the included studies were analysed regarding the short- and long-term effects of such treatment, and our results were compared to theirs.
Results
Nineteen children (8 females and 11 males), with a mean age of 4.24 years (range, 2.25–8.50 years; median age of 4.00 years) completed the previous treatment. Their caregivers were subsequently contacted by telephone.
The patients had an initial mean clinical score of 3.89, mean symptom severity score of 2.37, mean obstruction on endoscopy of 85 per cent and mean allergic rhinitis score of 4.05.Reference Bitar, Mahfoud, Nassar and Dana5 At the end of treatment, these decreased to 1.26, 0.79, 61 per cent and 1.42, respectively. Overall, 89 per cent (17 out of 19) of the enrolled patients significantly improved.Reference Bitar, Mahfoud, Nassar and Dana5 Three months later, 94.12 per cent (16 of 17) had no worsening of their symptoms, while 1 patient needed adenoidectomy; 2 patients were lost to follow up (Table I). At 6 months’ follow up, 88.24 per cent (15 of 17) of patients had stable symptoms, and 1 more patient required adenoidectomy. By one year, three patients had been lost to follow up. Twenty-five per cent (4 of 16) of the patients required adenoidectomy, while the remaining patients (12 of 16) had no significant change in: clinical score (p = 0.464) nasal obstruction symptoms (p = 0.191) or allergic rhinitis (p = 0.284) (Figure 1). Two patients used mometasone furoate monohydrate when needed to relieve transiently reappearing obstructive symptoms.
Fig. 1 Graph showing a slight but non-significant rise in the severity of nasal obstruction and obstructive symptoms over time, with a non-significant decrease in allergic rhinitis symptoms.
Table I Obstructive and allergic symptom changes over follow-up period
*Baseline refers to the end of the previous three-month treatment period. †After the cessation of treatment. ‡Compared with values at baseline (using the Wilcoxon signed-rank test)
We identified 14 studies (comprising 856 children) reporting the use of intranasal topical steroids for obstructive adenoids (Table II).Reference Demain and Goetz1, Reference Berlucchi, Salsi, Valetti, Parrinello and Nicolai3–Reference Berlucchi, Valetti, Parrinello and Nicolai6, Reference Brouillette, Manoukian, Ducharme, Oudjhane, Earle and Ladan9–Reference Rezende, Silveira, Barbosa, Menezes, Ferriani and Rezende17 The most commonly used steroid was mometasone furoate monohydrate, used in 6 studies (comprising 311 children), followed by beclomethasone (3 studies) and flunisolide drops (2 studies). All but one study (Lepcha et al.Reference Lepcha, Kurien and Job10) showed a positive effect of intranasal steroids on the obstructive adenoid symptoms.
Table II Topical intranasal steroids used in treating obstructive adenoids
Pts = patients; AH = adenoid hypertrophy; wk = week; ATH = adenotonsillar hypertrophy; OSA = obstructive sleep apnoea; mth = month; OSA-18 = 18-item obstructive sleep apnoea quality-of-life survey
In addition to the variety of steroids used, the various studies employed different treatment regimens. There was variability in terms of the duration of treatment, which ranged from 4 to 112 weeks; the duration of continuous daily treatment ranged from 4 to 28 weeks.
Most studies relied on a symptom score (11 studies) and nasal endoscopy (10 studies) to evaluate the response to treatment. Others relied on X-rays (4 studies) and polysomnography (2 studies). The variability of the symptom scores, duration of treatment and type of steroid used precluded performing a meta-analysis.
Most studies investigated the effects of the steroid while the patients were taking the medication and the short-term effects (one to six months) post-treatment. The long-term effect was investigated in only 3 previous studies; these had a follow-up period of 12 to 28 months.Reference Berlucchi, Valetti, Parrinello and Nicolai6, Reference Criscuoli, D'Amora, Ripa, Cinquegrana, Mansi and Impagliazzo11, Reference Varricchio, Tortoriello, Capasso, De Lucia, Marchisio and Varricchio14 The current study, with a follow-up period of 12 months, may add information to the scarce literature regarding the long-term effects.
Discussion
In 1995, Demain and GoetzReference Demain and Goetz1 described the first successful use of intranasal steroid therapy (beclomethasone) for obstructive adenoids in paediatric patients. Since then, other authors have reported encouraging results utilising different steroids (Table II). All but one study (Lepcha et al.Reference Lepcha, Kurien and Job10) showed improvement in the treated patients. Lepcha et al.Reference Lepcha, Kurien and Job10 attributed the lack of improvement in their group to the absence of a history of atopy among their studied patients. However, they did not perform any objective testing to rule out the presence of allergy in their patients, and the presence of allergic rhinitis or atopy was not among their exclusion criteria.
The short-term effect of intranasal steroids on obstructive adenoids is encouraging, especially given that this effect was observed using a variety of steroids. The optimal treatment duration is not known. A positive effect has been reported with a treatment duration as short as four weeks, but others have given a treatment time as long as seven months. In our previous published study, we observed that no additional effect was gained after six weeks of treatment with mometasone furoate spray.Reference Bitar, Mahfoud, Nassar and Dana5 The optimal duration is yet to be determined.
Another issue for future consideration is the methodology of evaluating responses to treatment in children with obstructive adenoids. There should be standardisation of symptom scores, in addition to the endoscopy and radiological studies performed. This will allow a meta-analysis to be performed on this subject.
Among the steroids used in the various reviewed trials, mometasone is the most studied. However, none of the previous studies investigated the long-term effect of this treatment. In the present study, we demonstrated a persistence of the improvement in 75 per cent of the patients who continued to attend follow up, one year after the cessation of treatment. To our knowledge, this is the first long-term follow-up study on patients previously treated with mometasone furoate monohydrate. Although Berlucchi et al.Reference Berlucchi, Valetti, Parrinello and Nicolai6 reported a long-term follow up for patients previously treated with mometasone furoate, their patients were kept on maintenance therapy using mometasone furoate nasal spray (100 mcg/day) for the first 2 weeks of every month, for up to 28 months.
Regarding those studies that used other steroids, we could identify two studies with long-term follow-up periods. Criscuoli et al.Reference Criscuoli, D'Amora, Ripa, Cinquegrana, Mansi and Impagliazzo11 reported the use of beclomethasone (400 mcg/day) in 53 children with adenotonsillar hypertrophy in a randomised, single-blind, placebo-controlled, cross-over study, and then followed them up in an ‘open-label’ study for 24 weeks. One hundred weeks later, it was found that the initial responders (45 per cent of the patients) had clinical improvement and a reduction of adenotonsillectomy compared to the non-responders. The only drawback of using this study for comparison was the inclusion of patients with adenotonsillar obstruction and not with isolated obstructive adenoids. In the other study, Varricchio et al.Reference Varricchio, Tortoriello, Capasso, De Lucia, Marchisio and Varricchio14 reported a 12-month follow up of 139 children who received flunisolide drops for 8 weeks. They found that the long-term effect was maintained mainly in the allergic patients, while almost all the non-allergic patients relapsed.
This long-term improvement only in allergic patients raises the question of whether the true effect of the intranasal steroids is through suppression of a present allergic condition or a real decrease in the volume of the adenoid tissue. Our observed short-term improvement, and the persistence of this improvement in most patients, was not found to be influenced by the presence or absence of allergic rhinitis or atopy. However, our patients initially had mild intermittent allergic rhinitis symptoms, and thus did not have nasal obstruction related to inferior turbinate hypertrophy or congested nasal mucosa in general.
We examined the potential influence of allergic rhinitis and/or atopy as reported in the studies reviewed (Table III). All but four studiesReference Berlucchi, Salsi, Valetti, Parrinello and Nicolai3, Reference Berlucchi, Valetti, Parrinello and Nicolai6, Reference Lepcha, Kurien and Job10, Reference Demirhan, Aksoy, Ozturan, Yildirim and Veyseller15 included patients with atopy or allergic rhinitis. In the short-term, only Cengel and AkyolReference Cengel and Akyol4 reported an influence of atopy on their results. The atopic patients in their study group showed significant improvements (while on treatment) in terms of the degree of obstruction (p < 0.05), as compared to atopic patients in the control group who did not show any difference (p = 0.221). In that study, the incidence of atopy was the same in both the study group (8.9 per cent) and the control group (9 per cent).
Table III Studies that did not exclude patients with atopy or allergic rhinitis
AR = allergic rhinitis; NR = not reported
In contrast, Demain and Goetz,Reference Demain and Goetz1 Bitar et al.,Reference Bitar, Mahfoud, Nassar and Dana5 Ciprandi et al.,Reference Ciprandi, Varricchio, Capasso, Varricchio, De Lucia and Ascione12 Kheirandish-Gozal and Gozal,Reference Kheirandish-Gozal and Gozal13 and Jung et al.Reference Jung, Kim, Min, Dhong and Chung16 did not find any effect of allergy on the obtained results. In some studies, although allergy was present in the patients, its effect was not studied or commented on (Brouillette et al.Reference Brouillette, Manoukian, Ducharme, Oudjhane, Earle and Ladan9), nor its effect eliminated by environmental control of the causative allergens (Rezende et al.Reference Rezende, Silveira, Barbosa, Menezes, Ferriani and Rezende17).
In the long-term follow-up studies, one investigation excluded the atopic patients (Berlucchi et al.Reference Berlucchi, Valetti, Parrinello and Nicolai6), another had the incidence of atopy equally distributed between subjects and controls (Criscuoli et al.Reference Criscuoli, D'Amora, Ripa, Cinquegrana, Mansi and Impagliazzo11), while in the third study, atopy had a positive effect on maintaining the initial response (Varricchio et al.Reference Varricchio, Tortoriello, Capasso, De Lucia, Marchisio and Varricchio14). Although most previous studies showed no significant effect on the observed results, the heterogeneity of the studied population makes one careful in drawing a definite conclusion regarding the suspected influence. In principle, patients with moderate-to-severe or persistent allergic rhinitis symptoms should not be included in such studies, as the resultant allergic inflammation will be a significant confounding variable affecting the results. Therefore, it would be necessary to exclude patients with atopy or allergic rhinitis, or to include only patients with mild and intermittent allergic rhinitis, to avoid the presence of nasal obstruction caused by allergic nasal congestion.
• Children with obstructive adenoids have been medically treated to relieve symptoms for more than 15 years
• Most previous studies have focused on benefits of topical intranasal steroids during treatment
• There are no studies on the long-term effect of mometasone spray after cessation of treatment
• Intranasal steroids are an effective treatment for children with obstructive adenoids, in the short- and long-term
• The short-term effect appears to persist in a number of patients after cessation of treatment
• The evaluation process of treated children needs standardising to obtain more coherent results
One important factor to keep in mind when observing the long-term effect of topical intranasal steroids used in children with obstructive adenoids is the fact that, as the children grow, their nasopharyngeal space enlarges and their obstructive nasal symptoms improve. This may be an important confounding variable if an extended period of follow up is contemplated (e.g. more than 12 months). It may be useful in future investigations to obtain cephalometric studies during the follow-up period to assess the degree of nasopharyngeal growth; however, a concern will be raised against exposing children to unnecessary radiation. Other future studies might focus on endoscopic assessment of adenoidal impact on the posterior choanae, or the use of magnetic resonance imaging in calculating the adenoidal size and its impact on the posterior nasal choana.
Conclusion
Intranasal steroids are an effective treatment for children with obstructive adenoids, in both the short-term and the long-term. Various steroids have been shown to be effective. There is a need to standardise the evaluation process of the treated children in order to obtain more coherent results. This will help in deciding on the optimal treatment regimen. Further studies are needed to contemplate the observed long-term effect of such treatment.
