Objective. To describe the long-term outcome of a cohort of children with symptomatic adenotonsillar hypertrophy treated with aqueous nasal beclomethasone.
Methods. The children enrolled completed a 4-week single-blind, saline solution controlled crossover study of aqueous beclomethasone (total: 400 μg/d). In a 24-week open-label follow-on study, beclomethasone 200 μg/d was offered to all patients. During a 100-week follow-up, the degree of nasal obstruction and the frequency of adenotonsillectomy were assessed.
Results. Fifty-three children of the 60 enrolled completed the study. After the 4-week crossover trial, the severity of nasal obstruction of 24 children (45%) significantly decreased during the use of nasal steroids, but no child improved when saline solution was used. At 24, 52, and 100 weeks, the 24 children who had initially improved showed a significant decrease of the severity of nasal obstruction and of the frequency of adenotonsillectomy (54% vs 83%) compared with the 29 children who had not responded after the initial steroidal therapy.
Conclusions. Evidence from this study suggests that 45% of children with adenoidal hypertrophy improved after 2 weeks of steroidal therapy. Among these children, an additional 24-week treatment at a lower steroid dosage was associated with a significant 52- and 100-week clinical improvement and with reduction of adenotonsillectomy compared with children (55%) who had not responded after the initial 2-week steroidal therapy.
Adenotonsillar hypertrophy represents 1 of the most frequent indications for surgery in children1 and is associated with significant morbidity ranging from obstructive sleep apnea and cardiorespiratory syndrome to nasal airway obstruction, recurrent otitis media, and chronic sinusitis.2–4 It has been recently suggested that treatment with antibiotics5 or with topical steroids6 can decrease the severity of symptoms, but it has not been established whether medical treatment can also decrease the frequency of adenotonsillectomy. We report here the results of a controlled study that investigated the long-term effects of the use of nasal beclomethasone among children affected by adenotonsillar hypertrophy.
The study was approved by the Institutional Review Board of the Department of Pediatrics of Naples. Children recruited were all those who were observed in the outpatient department of Santobono Pediatric Hospital in Naples between November 1998 and April 1999 and whose primary diagnosis was adenotonsillar hypertrophy. Inclusion criteria for the study required that each patient 1) had symptoms of nasal obstruction for at least 6 months, 2) had adenoidal hypertrophy assessed on radiography as an adenoidal/nasopharyngeal ratio >0.5 or 2+ or 3+ tonsillar hypertrophy assessed on clinical evaluation7, and 3) was booked for adenotonsillectomy after the initial assessment. Children were excluded when they had used intranasal, topical, or systemic steroids within the last year; had a history of chronic epistaxis or immunodeficiency; and had an active upper respiratory infection within 2 weeks of entering the study.
The first part of this study was single-blind and crossover in design. After informed consent of the parents was obtained, eligible children were randomly allocated to receive either 2 weeks of intranasal aqueous beclomethasone (400 μg/d) followed by 2 weeks of intranasal saline or the same treatment in the reverse order. At the end of the first 4-week period, all subjects continued in a 24-week open assessment of intranasal beclomethasone (200 μg/d). During the 4-week and the 24-week periods, the patients dispensed respectively 2 sprays and 1 spray (50 μg) of the study drug in each nostril twice daily.
Initial assessment of each patient on entering the study included history and physical examination, parental questionnaire, lateral neck radiograph, prick skin testing to aeroallergens, fiberoptic rhinoscopy, tympanogram, and audiogram. Subsequent assessments were done at 2, 4, 24, 52, and 100 weeks. All examinations were done by 2 otolaryngology consultants (G.R., G.C.) who were unaware of the design of the study and of the treatment that the children received throughout the study. The degree of nasal obstruction was assessed by the Nasal Obstruction Index proposed by Paradise et al,8 which uses a 4-point scale (1 = absent, 2 = mild, 3 = moderate, 4 = marked). Compliance with medication was assessed by 2 physicians who were blinded to the design of the research by telephone interviews to the families and by biweekly measurements of drugs used. The occurrence of any illness and the prescription of any drug was also recorded every 2 weeks, and any use of systemic steroids resulted in removal of the patients from the study.
After the 4-week crossover trial, the primary outcome was the reduction of Nasal Obstruction Index by at least 50% compared with the baseline: the children who showed such reduction were considered as “responders” compared with those whose index did not change at all or decreased by <50% (nonresponders). During the 100-week follow-up, the outcomes that we measured were the Nasal Obstruction Index categories and the frequency of adenotonsillectomy.
Sample size was determined after a 12-month pilot study that assessed the short-term efficacy of beclomethasone and the frequency of operation. We assumed that a 50% reduction of Nasal Obstruction Index after 2 weeks of steroids use and a 30% reduction of adenotonsillectomy after 52 weeks would be clinically relevant. Statistical analyses were conducted for the intention-to-treat population; Wilcoxon signed-rank test and relative risk with 95% confidence intervals were respectively used for 4-week crossover and for the remaining part of the study. All comparisons between treatment groups were performed using 2-sided tests with a significance level of .05.
Among the 60 children enrolled in the study, 53 completed the 4-week crossover trial (27 and 26 in the 2 arms) and were then followed for 100 weeks. Their background characteristics are shown in Table 1. The use of intranasal beclomethasone was associated with a significant (P < .001) Nasal Obstruction Index reduction compared with baseline and with postsaline solution index; on the contrary, saline solution was not associated with any improvement compared with baseline. Moreover, children who had initially improved after steroid use returned to a Nasal Obstruction Index not different from baseline after they had used saline solution during the subsequent 2 weeks.
Considering the response of each patient to beclomethasone, 24 (45%) children were classified as “responders” and 29 (55%) were classified as “nonresponder.” The background characteristics of these 2 groups at the beginning of the study were similar, and the only variable differently distributed between responders and nonresponders was the parental report of obstructive sleep apnea (respectively, 12% and 48% [P = .01]; Table 2); however, no diagnostic evaluation with polysomnography was performed. The compliance with therapy during the 24-week open part of the study was 71% among the responders and 41% among the nonresponders (P < .05). Nasal Obstruction Index among the responders significantly decreased compared with nonresponders at 24, 52, and 100 weeks; the overall frequency of adenotonsillectomy also was significantly reduced (54% vs 83%; relative risk: 0.65; 95% confidence interval: 0.44–0.98; Table 2). During the 24-week trial, 2 children assuming nasal steroids presented epistaxis, which disappeared 2 days after reducing drug dose by 50%. Among the 7 children who did not complete the 4-week crossover trial, 4 were operated on.
This represents the first study on long-term outcome of children with adenotonsillar hypertrophy treated with nasal steroids. The other published reports restricted the follow-up to a few months and did not provide information on the frequency of adenotonsillectomy among the children investigated.6,9 In this study, 45% of children showed a relevant clinical improvement after 2 weeks of steroidal therapy; among these same children, an additional 24-week treatment at a lower dosage of steroids was associated with a significant 52- and 100-week clinical improvement and reduction of adenotonsillectomy compared with children (55%) who had not responded after the initial 2-week steroidal therapy. In the study design, we decided to offer intranasal steroids for 24 weeks also to the children considered “nonresponders” after the first 4-week trial, because we did not know whether some children could need a treatment longer than 2 weeks to improve eventually. Unfortunately, we could not conduct a double-blind, placebo-controlled study because a previous pilot investigation suggested to us that most parents would not accept to be blinded to the treatment that their children would receive. At the moment, we are not able to provide information useful for the clinician on which children will and will not respond to steroidal treatment. The clinical characteristics of responders and of nonresponders at the beginning of the study did not enable us to predict the response to the therapy, and also the different sleep apnea frequency between responders and nonresponders cannot be considered a useful predictor as polysomnography was not performed and clinical history has been reported not to enable a clinician to distinguish primary snoring from obstructive sleep apnea.10 However, recent data suggest that steroids may be helpful in ameliorating obstructive sleep apnea, even if the frequency of surgery among the patients of this study was not assessed.9
Few data are available on the natural history of symptomatic adenotonsillar hypertrophy, and it has not been well established how many children improve and how many are operated on; 1 report5 and our unpublished pilot study show that approximately 90% of patients undergo surgery by 24 months after the initial diagnosis. Should our data be confirmed, the treatment with nasal steroids could represent for some children an effective means for avoiding adenotonsillectomy. Finally, as some data have reported a growth suppression during treatment with intranasal beclomethasone also at the low dosage of this study,11 other topical steroids not associated with such suppression could be used12 to explore whether a more prolonged treatment can provide additional benefits.
- ↵Sclafani AP, Ginsburg J, Shah MK, Dolitsky JN. Treatment of symptomatic chronic adenotonsillar hypertrophy with amoxicillin/clavulanate potassium: short- and long-term results. Pediatrics.1998;101 :675– 681
- ↵Demain JG, Goetz DW. Pediatric adenoidal hypertrophy and nasal airway obstruction: reduction with aqueous nasal beclomethasone. Pediatrics.1995;95 :355– 364
- ↵Paradise JL, Bernard BS, Colborn DK, Janosky JE. Assessment of adenoidal obstruction in children: clinical signs versus roentgenographic findings. Pediatrics.1998;101 :979– 986
- ↵Skoner DP, Rachelefsky GS, Meltzer EO, et al. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. Pediatrics.2000;105(2) . Available at: www.pediatrics.org/cgi/content/full/105/2/e23
- ↵Schenkel EJ, Skoner DP, Bronsky EA, et al. Absence of growth retardation in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray. Pediatrics.2000;105(2) . Available at: www.pediatrics.org/cgi/content/full/105/2/e22
- Copyright © 2003 by the American Academy of Pediatrics