A randomized, placebo-controlled trial of the effect of antihistamine or corticosteroid treatment in acute otitis media

doi:10.1067/S0022-3476(03)00293-2

The Journal of Pediatrics

Volume 143, Issue 3, September 2003, Pages 377-385

https://doi.org/10.1067/S0022-3476(03)00293-2 Get rights and content

Abstract

Objectives To determine whether the adjunctive drugs antihistamine and corticosteroid improve immediate and long-term outcomes of acute otitis media (AOM).

Study design Children with AOM (3 mos-6 y) were enrolled in a randomized, double-blind, placebo-controlled trial. All 179 children received one dose of intramuscular ceftriaxone and were assigned to receive either chlorpheniramine maleate (0.35 mg/kg/d) and/or prednisolone (2 mg/kg/day) or placebo for 5 days. Main outcome measures were rate of treatment failure during the first 2 weeks, duration of middle ear effusion, and rate of recurrences of AOM to 6 months.

Results Clinical outcomes and recurrence rates did not differ significantly with treatment. Children who received antihistamine alone had significantly longer duration of middle ear effusion (median, 73 days) than subjects in other treatment groups (median, 23 to 36 days, P = .04). Temporary normalization of tympanometric findings on day 5 occurred more frequently in the corticosteroid-treated group (P = .04).

Conclusions Five-day treatment with antihistamine or corticosteroid, in addition to antibiotic, did not improve AOM outcomes. Antihistamine use during an acute episode of OM should be avoided, since the drug may prolong the duration of middle ear effusion. The efficacy of 7- to 10-day treatment of AOM with corticosteroid, in addition to antibiotic, deserves further investigation.

Section snippets

Study design

This study was a randomized, double-blind, placebo-controlled trial, designed to evaluate approximately 180 children with AOM (3 months to 6 years of age) who were at risk for recurrent AOM episodes. The study took place at the pediatric outpatient clinics of the University of Texas Medical Branch at Galveston. We chose only children who were at high risk to receive adjunctive treatment because of the potential risk, the cost, and the inconvenience to patients. The inclusion criteria included

Results

Between July 1995 and June 2000, 198 subjects were enrolled and randomly assigned to 1 of the 4 treatment groups. Analyses included 179 subjects who were adherent to the protocol and whose outcome data on visit 2 and after were available. The subjects ranged in age from 3 months to 6 years (median age, 12.5 months). Forty-five percent of the cases were younger than 1 year of age (<6 months, 15%; 6–8 months, 22%; 9–11 months, 8%); 35% were 1 to 2 years old, 8% were 2 to 3 years old, and 11% were

Discussion

In this study, we have shown no statistically significant immediate or long-term benefit of antihistamine and/or corticosteroid used for 5 days as adjunctive therapy during an AOM episode. Unexpectedly, we also found that treatment with antihistamine lengthened the duration of MEE.

Previous studies of antihistamine, with or without decongestant, in treatment AOM in children have shown conflicting results.20., 21., 22., 23., 24., 25., 26. In a recently published Cochrane Library meta-analysis,

Acknowledgements

We thank Mary Owen, MD, and Monica Thint, MD, for their invaluable input and assistance with patient evaluation; Avelina Dimaandal, MD, Ralph W. Noble, MD, Patricia Rogers, MD, and the UTMB general pediatrics faculty and pediatric residents for patient referral; Ronald Deskin, MD, for otolaryngology consultation; Sarah Warnken, Theresa Bette, and Connie Ballon-Almanza for clinical care coordination; and Wen Yang for technical assistance.

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Both viruses and bacteria have additive effects on the production of histamines in pediatric AOM [173]. Chonmeitree et al. conducted a double-blind RCT of 179 children with AOM, aged 3 months to 6 years, and compared the clinical outcomes of treatment with placebo, steroids, antihistamines, or a combination of steroids and antihistamines [174]. The study demonstrated that clinical outcomes and recurrence rates did not differ significantly among treatments, and that the children who received only antihistamines had a significantly longer duration of MEE.
“Clinical Practice Guidelines for the Diagnosis and Management of Acute Otitis Media in Children—2018 update (2018 Guidelines)” aim to provide appropriate recommendations about the diagnosis and management of children with acute otitis media (AOM), including recurrent acute otitis media (recurrent AOM), in children under 15 years of age. These evidence-based recommendations were created with the consensus of the subcommittee members, taking into consideration unique characteristics of bacteriology and antimicrobial susceptibilities of AOM pathogens in Japan, as well as global advances in vaccines.
The subcommittee re-evaluated key clinical issues based on SCOPE (a master plan of the guidelines) and created clinical questions (CQ) about the diagnosis and management of AOM patients. A literature search of the publications from 2013 to 2016 were added to the Guidelines 2013, not only to assess the evidence on the effectiveness of vaccines, but also to provide up to date information of the bacteriology and antimicrobial susceptibilities of AOM causative pathogens in Japan.
We have proposed guidelines for disease severity-based management of AOM patients, after classifying AOM severity into mild, moderate, and severe, based on age, clinical manifestations, and otoscopic findings.
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Among them, only steroids [9], leukotriene antagonists [4,5], and a PAF-inhibitor [4] successfully reduced ear effusion in animal models. The efficacy of a steroid and a leukotriene antagonist has also been verified in humans, although only three studies have been conducted for these drugs [10–12]. A treatment for AOM using steroids and antibiotics significantly shortens the duration of middle ear effusion compared with administration of antibiotic alone [10].
Conventional treatment for acute otitis media mainly targets bacteria with antibiotics, neglecting to control for mediators of inflammation. Mediators of inflammation, such as leukotrienes, have been identified in patients with acute otitis media (AOM) or subsequent secretory otitis media (SOM). They can cause functional eustachian tube dysfunction or increase mucous in the middle ear, causing persistent SOM following AOM. The objective of the present study was to evaluate whether or not administration of pranlukast, a widely used leukotriene C4, D4, and E4 antagonist, together with antibiotics could inhibit the progression to SOM.
Children with AOM, who were from two to 12 years old, were randomly divided into two groups as follows: a control group in which 50 patients received antibiotic-based conventional treatment according to guidelines for treating AOM proposed by the Japan Otological Society (version 2006); and a pranlukast group, in which 52 patients were administered pranlukast for up to 28 days as well as given conventional treatment. Cases were regarded as persistent SOM when a tympanogram was type B or C2 four weeks after treatment was initiated.
Two patients in the pranlukast group and 3 patients in the control group were excluded because they relapsed AOM within 28 days after initial treatment. Therefore, the analysis included 50 and 47 subjects in the pranlukast and control groups, respectively. The percentage of patients diagnosed with persistent SOM (22.0%) was significantly smaller in the pranlukast group compared with the control group (44.7%) (p = 0.018, chi-squared test).
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^☆: Supported by NIH grant R01 DC 2620. The study was conducted on the General Clinical Research Center at the University of Texas Medical Branch at Galveston, funded by grant M01 RR 00073 from the National Center for Research Resources, NIH, USPHS.

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A randomized, placebo-controlled trial of the effect of antihistamine or corticosteroid treatment in acute otitis media☆

Abstract

Section snippets

Study design

Results

Discussion

Acknowledgements

J Pediatr

J Pediatr

J Pediatr

J Pediatr

J Allergy Clin Immunol

J Pediatr

Ann Emerg Med

Am J Otolaryngol

J Pediatr

Int J Pediatr Otorhinolaryngol

Int J Pharmacol

Am J Otolaryngol

J Pediatr

Infect Dis Clin North Am

Trends in antimicrobial drug prescribing among office-based physicians in the United States

JAMA

Early eradication of pathogens from middle ear fluid during antibiotic treatment of acute otitis media is associated with improved clinical outcome

Pediatr Infect Dis J

Persistence of middle ear effusion after acute otitis media in children

N Engl J Med

Burden and practice of pediatrics: middle ear disease during the first five years of life

JAMA

Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study

J Infect Dis

Respiratory viruses interfere with bacteriologic response to antibiotic in children with acute otitis media

J Infect Dis

Virus and bacteria enhance histamine production in middle ear fluids of children with acute otitis media

J Infect Dis

Role of leukotriene B4 and interleukin-8 in acute bacterial and viral otitis media

Ann Otol Rhinol Laryngol

Action of inflammatory mediators on middle ear mucosa: a method for measuring permeability and swelling

Arch Otolaryngol

Studies on permeability of the middle ear mucosa. The feasibility of blocking inflammatory mediators

Arch Otolaryngol

Effect of prostaglandin, leukotriene, and arachidonic acid on experimental otitis media with effusion in chinchillas

Ann Otol Rhinol Laryngol Suppl