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* ENT Research Center, Children’s Hospital of Pittsburgh
Departments of Otolaryngology
Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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Methods. In a double-blind, randomized trial, children who were 1 to 9 years of age and had MEE of at least 2 months’ duration were assigned to 1 of 4 treatment arms: 1) steroid + amoxicillin for 14 days, then amoxicillin for 14 more days; 2) steroid + amoxicillin for 14 days, then placebo for amoxicillin for 14 more days; 3) placebo (for steroid) + amoxicillin for 14 days, then amoxicillin for 14 more days; or 4) placebo (for steroid) + amoxicillin for 14 days, then placebo for amoxicillin for 14 more days. Children were examined by otoscopy, tympanometry, and audiometry at entry and 2 and 4 weeks after entry; those without MEE at the 4-week visit returned monthly for up to 3 more visits or until recurrence of effusion. Serum immunoglobulin (Ig) G, IgM, IgA, and varicella titers were obtained at entry, and allergy skin testing was performed at the 4-week visit.
Results. A total of 144 children was entered; 135 children (94%) returned for the 2-week visit, and 132 (92%) were seen for the 4-week visit. At the 2-week visit, 33.3% of children in the steroid + amoxicillin group had no MEE compared with 16.7% in the placebo + amoxicillin group (95% confidence interval for the difference in proportions: 2.4%–31.0%). At the 4-week visit, the percentage of children with no MEE in the steroid-treated group was 32.8%, whereas that in the placebo group was 20.0% (95% confidence interval for the difference in proportions in the 2 groups: -2.0%–27.7%). Comparing change in middle ear status from the 2- to the 4-week visit, there were no significant differences in recurrence of MEE or additional clearance of MEE between those who were treated with amoxicillin for 2 weeks and those who were treated for 4 weeks. By the 4-month visit, 68.4% of children who were in the steroid group and had no MEE at the 4-week visit had recurrence of MEE as did 69.2% of such children in the placebo group. A total of 126 (87.5%) children underwent allergy skin testing. Of the 122 children who had a positive reaction to histamine, 51 (41.8%) had 1 or more positive reactions to the test allergens. There was no difference in response to treatment between those with positive allergy tests and those without.
Conclusions. There was a significant difference in the proportion of children who were effusion-free immediately after 14 days of treatment with steroid and amoxicillin compared with those who were treated only with amoxicillin for 14 days. Within 2 weeks of finishing treatment, there was no longer any significant difference between the 2 groups regardless of whether amoxicillin was continued or not. Therefore, we conclude that treatment with the dose and type of steroid used in this study should not be universally recommended for treatment of chronic otitis media with effusion, and treatment with amoxicillin, if used, should not continue beyond 14 days.
Key Words: otitis media • steroid • amoxicillin • middle ear effusion • allergy
Abbreviations: OME, otitis media with effusion • CHP, Children’s Hospital of Pittsburgh • MEE, middle ear effusion • AOM, acute otitis media • TW, tympanometric width • SRT, speech recognition threshold • Ig, immunoglobulin • PTA, pure tone average • CI, confidence interval
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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A short course of adrenocorticosteroids has often been proposed for the treatment of chronic OME and is used by some practitioners, although the question of the efficacy of this type of treatment has not been resolved. Many studies of steroids for this problem had been reported before the start of this study in 1994 (Table 1), but because of small sample size, differences in definitions of middle ear status, or other limitations in study design, none adequately answered the question of steroid efficacy. Of 3 studies with >100 subjects, 2 were nonrandomized and nonblinded12,13 and the third reported the outcome of 14 days of treatment only at 2 months after the start of treatment.23 The steroid used, as well as the dose and the length of time of treatment, varied widely. Outcome measures varied; some studies defined presence/absence of disease by tympanometry and/or audiometry only, others used otoscopy (some used validated observers,27 whereas others did not) or otomicroscopy, and others used combinations of these. Study populations were often not characterized for possible confounders such as laterality of effusion, history of middle ear disease, duration of effusion, or allergy status. The use of a concurrent antimicrobial agent was also not consistent in previous studies. In animal studies, concurrent use of an antimicrobial agent and a steroid was more effective than each alone in clearing middle ear effusion (MEE) and in lowering the levels of antiinflammatory mediators in MEE.28 Some of these previous studies tested steroid plus antibiotic against placebos, not clarifying whether the positive outcome in the treated group was attributable to the steroid or the antibiotic or the combination. A meta-analysis of the efficacy of systemic steroids for OME found evidence of steroid efficacy but with the presence of significant heterogeneity among the studies, making the answer to the question of the efficacy of this treatment unclear.29
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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Children were excluded from entry when they had any of the following conditions: hypersensitivity or significant adverse reactions to penicillins; previous tonsillectomy and/or adenoidectomy; previous ear surgery other than tympanocentesis or myringotomy with or without tube insertion; history of seizure disorder, diabetes mellitus, asthma requiring daily medication, or any health condition that could make entry potentially dangerous; medical conditions with a predisposition for MEE, such as cleft palate, Down syndrome, congenital malformations of the ear, cholesteatoma, or chronic mastoiditis; severe retraction pockets; acute or chronic diffuse external otitis; perforation of the tympanic membrane; intracranial or intratemporal complications of MEE; upper respiratory obstruction attributable to tonsil or adenoid enlargement or both with cor pulmonale, sleep apnea, or severe dysphagia; conductive hearing loss attributable to destructive changes in the middle ear; sensorineural hearing loss; distance from CHP that would make follow-up difficult; history of varicella exposure within the previous 30 days (if never had clinical varicella or varicella vaccine) or clinical varicella in the previous 3 weeks; history of measles exposure in the previous 30 days; or immunization in the previous 30 days.
All available patients who fulfilled the entry criteria and whose parents gave informed consent were enrolled in the study. The children were stratified for age (12–23 months, 2–5 years, 6–9 years), laterality of effusion (unilateral or bilateral), and duration of effusion (2–3 months, 
4 months, unknown). The stratification scheme resulted in 18 subgroups. Within each subgroup, children were randomly assigned in a double-blind manner, in blocks of 4, to 1 of 4 treatment arms: 1) steroid + amoxicillin for 14 days, then amoxicillin for 14 more days; 2) steroid + amoxicillin for 14 days, then placebo for amoxicillin for 14 more days; 3) placebo (for steroid) + amoxicillin for 14 days, then amoxicillin for 14 more days; or 4) placebo (for steroid) + amoxicillin for 14 days, then placebo for amoxicillin for 14 more days.
Follow-up Observations and Subsequent Treatment
Children were examined routinely at 2 and 4 weeks after entry. An examination of the ears, nose, and throat (including pneumatic otoscopy); tympanometry; and audiometry were performed at each visit. When MEE was present in 1 or both ears at the 4-week visit, the children were discharged from the study and were returned to their referring physician for additional treatment. When no MEE was present at the 4-week visit, the children were monitored for recurrence of MEE up to 16 weeks after entry. They were examined with pneumatic otoscopy and tympanometry at 8, 12, and 16 weeks after entry, continuing in the study until MEE was noted at any time until 16 weeks. Parents were also instructed to return for examination any time symptoms of ear disease occurred.
Blood was drawn at entry for quantitative immunoglobulins and for varicella titers, the former to rule out immunoglobulin deficiency and the latter to better define susceptibility in case of varicella exposure. Allergy skin testing was performed, usually at the 4-week visit, to better characterize the study population.
Parents were instructed to contact the study physicians if their child had not previously had clinical varicella or the varicella vaccine and was exposed to varicella or developed varicella. Parents were also instructed to call if the child was involved in major trauma during the 6-week period after study entry.
Definition of Disease
The term MEE was used to designate middle ear disease diagnosed as either OME or acute otitis media (AOM). OME was defined as asymptomatic MEE, ie, without the symptoms of inflammation found in AOM. The determination of the presence or absence of effusion was based on a previously described decision tree algorithm32 that combined admittance testing and pneumatic otoscopy by a validated otoscopist.27 The following set of criteria using tympanometric width (TW) to categorize middle ear status was used: TW 
150 = no OME; TW 350 = OME; TW between 150 and 350 = diagnose by otoscopy. The finding of fluid levels or bubbles on otoscopic examination superseded the above rules and automatically led to the diagnosis of OME.
The diagnosis of AOM required the finding of MEE on otoscopy with at least 1 symptom and 1 sign. The symptoms of AOM included fever (a temperature >37.2°C [99.0°F] orally or >37.8°C [100.0°F] rectally, as taken by the parent or by measurement at the examination); earache or recent onset of ear tugging; and irritability, defined as a recent change in the child’s behavior pattern with fussiness. Otoscopic criteria for the diagnosis of AOM included erythema and/or white opacification (other than from scarring) of the tympanic membrane, fullness or bulging of the tympanic membrane, white fluid level, and otorrhea from a perforation of a previously intact tympanic membrane.
Drug Administration and Compliance
Amoxicillin suspension (supplied by SmithKline Beecham Pharmaceuticals, Collegeville, PA) was administered to all children from days 1 to 14 in a dose of 40 mg/kg/d in 3 divided doses. Prednisolone syrup or its placebo (both supplied by Muro Pharmaceutical, Inc, Tewksbury, MA) was administered concomitantly with amoxicillin in a dose of 0.5 mg/kg given twice a day on days 1 through 10 (total daily dose 1 mg/kg, maximum 30 mg/d), then given once a day on days 11 through 14 (total daily dose 0.5 mg/kg, maximum 15 mg/d). On days 15 through 28, amoxicillin or its placebo (also supplied by SmithKline Beecham Pharmaceuticals) was administered in a dose of 40 mg/kg/d in 3 divided doses. All study medication for the 4-week period was provided to the parents at entry. The amoxicillin or its placebo for days 15 to 28 was provided as unmixed powder with the premeasured water necessary for reconstitution in separate bottles.
Compliance with the assigned medication regimen was determined by 3 methods: 1) the child’s parents recorded administration of each dose of medication on diaries supplied at entry, 2) the volumes of dispensed and returned medication were compared, and 3) a urine specimen collected within 24 hours of finishing each of the 2 courses of medication was tested for the presence of riboflavin by fluorescence with a Wood’s (ultraviolet) light. Riboflavin (50 mg) was added to each bottle of amoxicillin and its placebo before being dispensed.
Acoustic Immittance and Audiometric Testing
Acoustic immittance testing was performed at all scheduled visits using a GSI-33 Middle Ear Analyzer (Grason-Stadler, Inc, Milford, NH). The test included an estimate of the acoustic equivalent volume of the external ear canal; a tympanogram from which estimates of peak compensated static acoustic admittance, tympanometric width, and tympanometric peak pressure were determined; and acoustic reflex tests.
Audiometry was performed at the entry, 2-week, and 4-week visits. Procedures varied as a function of the age of the child. For children 5 to 9 years of age, air-conduction pure-tone thresholds for each ear at 0.5, 1, 2, and 4 kHz and a speech recognition threshold (SRT) were obtained in each ear using conventional audiometric methods. Bone-conduction testing was done when air-conduction thresholds exceeded 15 dB HL. For children 30 to 59 months of age, play audiometry was used to obtain pure tone thresholds and an SRT in each ear. The threshold-estimating protocol and criterion for bone conduction were the same as that used for older children. For children 12 to 29 months of age, visual reinforcement audiometry with a unilateral head turn, as described by Wilson and Thompson,33 was used to obtain sound field minimum response levels. Stimuli used were speech and warble tones at audiometric test frequencies of 500 to 4000 Hz.
Allergy and Immunology Evaluation
Blood was drawn for immunoglobulin (Ig) isotypes IgG, IgA, and IgM at entry. Serum IgG, IgA, and IgM were measured by enzyme-linked immunosorbent assay with commercial reagents procured from ALerCHEK Inc (Portland, ME).
Allergy skin testing was performed by a technician in the allergy department at CHP using the prick technique and allergen procured from Hollister-Stier Laboratories (Spokane, WA). The inhalant allergens and their concentrations that were applied were grass (1:20), ragweed (1:20), house dust mite (30 000 Au/ml), cockroach (1:10), Alternaria (1:10), Aspergillus (1:10), dog (1:10), and cat (10 000 Bau/mL), as well as histamine (6 mg/mL) and a diluent control. A test was considered positive when it was 3 mm above the reaction to the diluent control.
Varicella Titers
Serum antibodies to varicella-zoster virus were detected by immunofluorescence (Hemagen Diagnostics, Inc, Columbia, MD). Specimens were reported as positive or negative for varicella-zoster virus antibody.
Statistical Considerations
Sample size estimates were based on detecting an absolute difference of 0.20 in the proportions of children with no MEE in the 2 treatment groups (steroid/placebo) at the 2-week endpoint. Assumptions included an 
= 0.05 1-sided test, power of 0.90, a proportion with MEE in the no steroid group (placebo) of 0.25, and an 8% dropout rate. These assumptions resulted in a sample size estimate of 188 patients.
The comparisons between treatment groups of the proportions of children with MEE at the 2- and 4-week endpoints were conducted using a logistic regression model adjusting for the stratification variables. All analysis was done on the basis of the principle of "intent to treat." Adjustment for other covariates and tests for interactions were also conducted within the framework of a logistic regression model. The 
2 statistical test was used to test for a linear trend.34 Speech awareness threshold data were analyzed using analysis of covariance. SRT and pure tone average (PTA) data were analyzed by assuming a normal distribution and using the method of generalized estimating equations.35 This procedure takes into consideration the correlation resulting from measuring 2 ears from the same individual. Hearing levels at 2 and 4 weeks, respectively, were compared controlling for hearing level at entry. Compliance was compared using analysis of variance. The primary analysis compared children who were randomized to steroid + amoxicillin with children who were randomized to placebo + amoxicillin at the 2-week endpoint. These same 2 groups were compared at 4 weeks, and those with no MEE were evaluated at 8, 12, and 16 weeks. As a secondary hypothesis, we compared the proportion of children with no MEE at 4 weeks in the groups that were receiving amoxicillin during weeks 3 and 4 with those that were receiving placebo for amoxicillin during those weeks. Although the sample size estimates were based on a 1-sided primary hypothesis, all tests in this report used the more conservative and more conventional 2-sided significance levels. For a 2-sided = 0.05 test and given our actual number of assessable children at 2 weeks, the actual statistical power to detect a difference in the proportion of children with no MEE between the steroid and placebo groups was 0.74.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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Middle Ear Status at 2 Weeks
Middle ear status at 2 weeks is shown in Table 3. In the steroid + amoxicillin group, 33.3% of children had no MEE compared with 16.7% in the placebo + amoxicillin group (P = .03, adjusting for stratification variables; 95% confidence interval [CI] on the difference in proportions: 2.4%–31.0%). In the steroid + amoxicillin group, 73.9% had their 2-week visit on days 14 to 15 and 95.7% of children had their 2-week visit between 11 and 17 days after entry; corresponding numbers in the placebo + amoxicillin group are 60.6% and 87.9%. Restricting the analysis to children who were evaluated within the 11- to 17-day interval did not change outcome.
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Recurrence of MEE by Week 16
Of children who had no MEE at the 4-week endpoint and had additional follow-up, 13 (68.4%) of 19 children who received active steroid had recurrence of MEE (11 as OME and 2 as AOM) by the 16-week visit as did 9 (69.2%) of 13 children who received placebo (8 as OME and 1 as AOM; P = .94, adjusting for treatment during weeks 3–4). Because steroid treatment lasted only 14 days, recurrence of MEE after the 2-week visit was also examined: 20 (87.0%) of 23 children in the steroid group who were effusion-free at the 2-week visit compared with 9 (81.8%) of 11 children in the placebo group had recurrence of effusion (P = .98, adjusting for treatment during weeks 3–4). AOM was responsible for recurrence in 4 of the 20 steroid-treated children and 2 of the 9 placebo children.
Allergy and Immunologic Testing
Serum Ig levels were obtained on 103 children (71.5%). No children in either treatment group had an immunologic deficiency, as defined by levels >2 standard deviations below normal values for age.
Allergy skin testing was performed on 126 (87.5%) of 144 entered children. Four children (3%) tested negative to the histamine control. Of the 122 children who had a positive reaction to histamine, 51 (41.8%) had 1 or more positive reactions to the test allergens (48.4% of children in the active steroid group and 35.0% in the steroid placebo group; P = .19). The percentage of children with positive skin tests increased with increasing age: 22.7% in the 12- to 23-month-old age group, 39.3% in the 2- to 5-year-old group, and 54.5% in the 6- to 9-year-old group (test for trend, P = .01). The percentages of children who tested positive to the various allergens were 22.1% to dust mite dF/dP, 13.9% to dog/cat pelt, 13.1% to Alternaria/Aspergillus mix, 10.7% to grass, 9.8% to cockroach, and 9.0% to ragweed.
MEE status at 2 weeks by allergy test status is shown in Table 6. There was no difference in MEE outcome after 14 days of steroid and amoxicillin treatment compared with treatment with placebo (for steroid) and amoxicillin in children who were positive for 1 or more of applied allergens: of skin-test-positive children, 8 (26.7%) of 30 steroid-treated children had no MEE compared with 5 (23.8%) of 21 who received placebo (P > .99). For children who did not have any positive skin tests, 13 (41.9%) of 31 children had no MEE at 2 weeks after steroid treatment compared with 6 (15.8%) of 38 children who received placebo (P = .03). The test for interaction that formally tests whether efficacy of steroid differs for skin-test-positive and skin-test-negative children results in a significance level of P = .08.
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Hearing
A comparison of hearing measures between the steroid-treated and non-steroid-treated groups is shown in Table 7. There were no significant differences between the groups at entry, but at the 2-week visit, mean hearing measures except for speech awareness threshold were significantly better in the steroid group than in the placebo group. At the 4-week visit, the results remained statistically significant for PTA (P = .048) but were no longer statistically significant for SRT (P = .09). There were no significant differences in hearing at the 4-week visit in children who received amoxicillin for 2 weeks compared with children who received amoxicillin for 4 weeks.
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Compliance
Of the 138 children who returned for follow-up, compliance data for the steroid regimen were available for 122 children (88.4%) using the contents remaining in the bottle as the criterion and for 132 children (95.7%) using the diary as the criterion. There were no significant differences between treatment groups in the percentages of children who took 90% to 100% of the prescribed "steroid" (88.7% steroid vs 86.7% placebo by the bottle method, 95.4% vs 86.4%, respectively, by the diary method). There were also no differences in the mean percentages of "steroid" taken (94.5% in both the active steroid group and the placebo group by the bottle method, 95.9% in the active steroid group vs 95.3% in the placebo group by the diary method).
Compliance data for amoxicillin during days 1 to 14 were available for 112 children (81.2% of children with follow-up) by the bottle criterion and 130 children (94.2%) by the diary criterion. There were no significant differences between groups in the percentages of children who took 90% to 100% of the prescribed amoxicillin by the bottle method (89.2% of the steroid group vs 87.5% of the placebo group) or by the diary method (92.3% and 90.7%, respectively), and there were no differences in mean percentages taken (97.1% in the steroid group and 93.7% in the placebo group by the bottle method; 97.3% vs 94.2%, respectively, by the diary method).
Compliance information on the amount of amoxicillin or placebo taken during days 15 to 28 was available for 111 children (80.4%) by the bottle method and 133 children (96.4%) using the diaries. Again, there were no significant differences between the groups in the percentages who took 90% to 100% of prescribed amoxicillin (68.3% in the active amoxicillin group vs 76.5% in the placebo group according to amount returned in bottles; 82.6% vs 75.0%, respectively, according to diaries) or in mean percentages of "amoxicillin" taken (88.9% in the amoxicillin group and 90.5% in the placebo group as determined by the bottle method; 89.5% and 88.8%, respectively, by diaries).
A urine sample obtained between days 11 and 15 was submitted by 90 children (66.6% of those with 2-week visits). Approximately 90% in each treatment group were positive for the presence of riboflavin, 2% were negative, and 8% were considered "unknown." Eighty-two children (62.1% of children with 4-week visits) submitted a urine specimen obtained between days 21 and 28. Approximately 90% were positive in each group; 3% of those who received active amoxicillin and 6% of those who received placebo for amoxicillin were negative.
The lack of a significant difference in compliance in the 2 groups suggests that blinding was effective. The relatively high rate of compliance in the steroid + amoxicillin group is consistent with the observation of a treatment effect.
Adverse Events and Side Effects of Medication
During weeks 1 and 2, 1 or more possible side effects of medication were reported by 22 (31.9%) of 69 children in the steroid group for whom information is available and by 17 (25.8%) of 66 children in the placebo group (P = .55). Possible side effects reported included hyperactivity (10 children in the steroid group, 6 in the placebo group), increased appetite (8 steroid, 4 placebo), vomiting (3 steroid, 2 placebo), diarrhea (4 steroid, 1 placebo), irritability (1 steroid, 2 placebo), abdominal discomfort (1 steroid, 2 placebo), hives (0 steroid, 1 placebo), and other rash (4 steroid, 2 placebo). For weeks 3 and 4 of medication, 16 children reported 1 or more possible side effects of medication: 7 (10.4%) of 67 children in the groups that received amoxicillin and 9 (13.8%) of 65 children in the placebo groups (P = .74). Possible side effects included vomiting (3 amoxicillin, 3 placebo), diarrhea (3 amoxicillin, 1 placebo), increased appetite (1 amoxicillin, 1 placebo), hyperactivity (1 placebo), and rash other than hives (2 amoxicillin, 2 placebo); no hives were reported.
Steroid or its placebo was discontinued by 7 children: 2 in the active steroid group (1 possible varicella exposure, 1 refusal to take medication) and 5 in the placebo group (1 varicella, 1 AOM, 1 irritability, 1 vomiting and diarrhea, 1 parents decided against giving "steroid"). During weeks 1 to 2, amoxicillin was discontinued by 3 children in the steroid placebo group (1 rash and possible penicillin allergy, 1 AOM, and 1 vomiting and diarrhea). During weeks 3 to 4, amoxicillin or its placebo was discontinued by 5 children, 3 in the amoxicillin group (2 AOM, 1 rash and possible penicillin allergy) and 2 in the placebo group (1 antibiotic change because of other illness and 1 tonsillitis).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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Several studies on the efficacy of systemic steroids for MEE have been published since we began this study. Rosenfeld25 reported the results of his experience of treatment of chronic OME with prednisolone (1 mg/kg for 10 days) given with various antimicrobial agents (all ß-lactamase resistant) versus no treatment in a nonrandomized, nonblinded study design in 122 children. At the first follow-up visit, 3 to 4 weeks after the start of treatment, 32% of children whose parents chose treatment with steroid and antibiotic were effusion-free compared with 2% in the group that remained untreated. Children who were in the treated group and whose effusion had resolved were given sulfisoxazole prophylaxis for a minimum of 6 weeks or "until the end of the viral season (October through to May)." At a second visit 6 months after entry, resolution of OME was noted in 25% of children who received steroid treatment; relapse between the first and second follow-up visits occurred in 12 (43%) of 28 children. No comparative data were available for the children in the control group because most had undergone myringotomy and tube insertion. Hemlin et al26 published their randomized, double-blind trial of cefixime for 10 days with and without 1 dose of betamethasone versus placebo for children with OME for at least 3 months. Of 140 assessable children at the first follow-up visit 2 to 11 days after completing treatment, 26 (44.1%) of 59 children who were receiving both active medications were considered to be "cured" as were 12 (19.7%) of 61 who were receiving only cefixime and 1 (5.0%) of 20 in the placebo group. However, children were considered to be cured at follow-up when they had at least 1 "normal" ear if they had bilateral MEE at entry or, if unilateral MEE at entry, both ears were clear. Children who were considered to be cured at the first follow-up visit were seen at 6 weeks and 6 months. Recurrence was common in all groups, and no statistically significant difference in middle ear status was noted at either follow-up visit.
Allergy has been proposed as a risk factor for OME because of the suggestion that OM occurs more frequently in allergic children.36 This has been confirmed in several studies, including this report. Bernstein et al37 documented allergic rhinitis confirmed by positive allergy tests in 35% of 100 children who underwent tympanostomy tube insertion for OM. Tracy et al,38 in a study of 61 children with OM, showed that 25% had positive allergy skin tests. In the present report, 41.8% of the study patients had 1 or more positive allergy skin tests. The percentage of children with positive skin tests increased with increasing age: 22.7% in 1- to 2-year-olds, 39.3% in the 2- to 5-year-olds, and 54.5% in 6- to 9-year-olds. This observed frequency of positive allergy skin tests in children with OM is greater than that reported in a general pediatric population in the United Kingdom at 4 years of age of 20%39 but similar to the 39% reported in a population of healthy children followed to 6 years of age in Tucson, AZ.40 However, there was no significant difference in the resolution of MEE according to allergic status in children who were treated with steroids as compared with placebo at either 2 or 4 weeks of study within the parameters of this study design. The possibility exists that a higher dose of steroid is needed to promote greater resolution of MEE in children whose skin tests were positive. Tracy et al38 also did not show any difference in outcome in their study of intranasal beclomethasone therapy for OM when analyzed by allergy skin test status.
There are many hypotheses as to why OME should respond to treatment with steroid: direct anti-inflammatory action in the middle ear and the Eustachian tube by preventing the formation of arachidonic acid and its metabolites, thus preventing the synthesis of inflammatory mediators22,28,41,42; increase in surfactant in the Eustachian tube13 and shrinkage of peritubal lymphoid tissue,14,43 allowing for better tubal function; decrease in the viscosity of middle ear fluid by its action on mucoproteins14; amelioration of allergic diatheses that are thought to be responsible for MEE44; and upregulation of the transepithelial sodium transport in the middle ear epithelium promoting the removal of fluid from the middle ear space.45 The findings that there was a 2-fold difference in the proportion of children who were clear of effusion immediately after treatment with steroid and that hearing was improved even in children who continued to have MEE speak to an effect of steroid on the pathology involved in this disease. The mechanism or mechanisms of steroid’s action responsible for even the temporary improvement in MEE status and hearing found in our clinical trial should be investigated, as it may lead us in the direction of even more effective treatment.
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ACKNOWLEDGMENTS |
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We thank the following colleagues who contributed expertise to this project: Betty Angelini, RN; Gilbert J. Burckhart, PharmD; Patricia Fall, RN, CNP; Delores Fuller; Peter A. Lee, MD, PhD; Diane L. Sabo, PhD; Susan Strelinski; and Ellen R. Wald, MD. We also thank the Allegheny County Coroners Office Public Health Laboratory for performing the varicella-zoster assays.
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FOOTNOTES |
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Reprint requests to (E.M.M.) Department of Pediatric Otolaryngology, Children’s Hospital of Pittsburgh, 3705 Fifth Ave at DeSoto St, Pittsburgh, PA 15213. E-mail: mandele{at}pitt.edu
This study was presented in part at the Seventh International Symposium on Recent Advances in Otitis Media; Ft Lauderdale, FL; June 1–5, 1999.
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This article has been cited by other articles:
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  American Academy of Family Physicians, American Academy of Otolaryngology-Head and Neck S, and American Academy of Pediatrics Subcommittee on Oti Otitis Media With Effusion Pediatrics, May 1, 2004; 113(5): 1412 - 1429. [Abstract] [Full Text] [PDF]
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 OTHER ARTICLES NOTED (24 Jan 03 to 18 Apr 03) Evid. Based Nurs., July 1, 2003; 6(3): e1 - 12. [Full Text] [PDF]
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 Does Steroid Treatment Benefit Kids with Middle-Ear Effusions? Journal Watch Infectious Diseases, January 10, 2003; 2003(110): 7 - 7. [Full Text]
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