David S. Hurst

Evidence of eosinophil, neutrophil, and mast‐cell mediators in the effusion of OME patients with and without atopy

Background: This study was designed to measure the involvement of eosinophils, neutrophils, and mast cells in the middle ear of patients with OME and to see whether that inflammatory response differed depending on whether or not the patient was atopic.

Increased expression of major basic protein (MBP) and interleukin-5(IL-5) in middle ear biopsy specimens from atopic patients with persistent otitis media with effusion.

BACKGROUND: Molecular biologic evidence to support an etiologic role for allergy in the pathogenesis of persistent otitis media with effusion (OME) is lacking. OBJECTIVE: The goal of this article was to document expression of allergy-associated Th-2-type cytokines and inflammatory cells in the middle ear mucosa of children with persistent OME. METHODS: With immunocytochemistry (CDS, major basic protein) and in situ hybridization (interleukin-5 mRNA), middle ear biopsy specimens from 7 children with persistent OME were stained. Nonatopic stapedectomy patients with no history of otitis media served as controls (n = 7). RESULTS: There was a statistically significant (P < 0.05) difference in expression of CDS, major basic protein, and interleukin-5 between experimental and control subjects. All 8 OME patients proved to be atopic by ELISA testing. CONCLUSIONS: Type I allergy involving a Th-2-type cytokine and cellular profile may be a contributing factor in the persistence of OME in atopic children. SIGNIFICANCE: The middle ear may serve as a target organ for allergic inflammation, suggesting that appropriate allergy management may be a useful adjunct to the management of OME.

Association of Otitis Media With Effusion and Allergy as Demonstrated by Intradermal Skin Testing and Eosinophil Cationic Protein Levels in Both Middle Ear Effusions and Mucosal Biopsies

This study was performed to ascertain the role of allergy, as defined by skin testing and histochemical markers, in the pathogenesis of otitis media with effusion (OME). A historical perspective of allergy as it relates to OME is presented. The study included 89 patients: 48 with persistent effusion but no recent acute infection, 25 with purulent OME complicated by a superimposed infection, and 16 control subjects. All 89 patients had persistent effusion for more than 2 months and subsequently required the placement of tympanostomy tubes.

Allergy management of refractory serous otitis media.

Twenty patients classified as having otitis media with effusion (OME) refractory to all previous medical and surgical therapy were entered Into a prospective study to see If classic allergy techniques could diagnose and treat otherwise unresolved effusion and persistent hearing loss in lieu of the re-Insertion of tympanostomy tubes. RAST testing, skin end point titration and food elimination diets identified a possible allergic etiology in all patients. Among those choosing allergy immunotherapy, 65% maintained normal hearing, normal tympanograms, and the elimination of recurrent infections for three years. The remaining 35% resolved on appropriate food elimination diets. None of the controls symptoms resolved. The history of chronic disease is defined. The pathophysiology of allergic mechanisms and studies attempting to prove or disprove an allergic effect on the middle ear and eustachian tube are reviewed.

Evidence of mast cell activity in the middle ears of children with otitis media with effusion

Objectives: This is the first study to report the presence of tryptase, a reflection of mast cell activity, in chronic middle ear effusion of patients whose atopic status was characterized. Design and Methods: Mediator activity of mast cells and eosinophils was measured prospectively from effusion of 33 randomly selected patients and 5 control subjects with chronic otitis media with effusion (OME). Atopy was determined by enzyme‐linked immunosorbent assay. Middle ear biopsies from a second group of 8 OME patients and 4 controls were fixed in plastic and stained immunohistochemically for mast cells. Results: Sixty‐one percent of patients had extensive activation of mast cells in their middle ears. Among those with elevated tryptase in their effusion, 95.6% were atopic and 94.7% also had elevated levels of effusion eosinophilic cationic protein (ECP). Tryptase levels were elevated only in the effusion of atopic patients, as compared with 5 controls (P < .01). Mast cells were present in 6 of 8 OME ears and absent in all 4 normal ears. Conclusion: Mast cells and its mediator tryptase, both indicators of a Th2‐driven immune response, are present in a majority of ears that have chronic effusion. These findings support the hypothesis that middle ear mucosa is capable of an allergic response and that the inflammation within the middle ear of most OME patients is allergic in nature.

Safety of home-based and office allergy immunotherapy: A multicenter prospective study ☆ ☆☆ ★

During a 1-year period, 27 otolaryngic allergy practices recorded all systemic reactions to immunotherapy resulting from 635,600 patient visits and 1,144,000 injections. Sixty percent of injections were given at home. Major systemic reactions were observed after 0.005% of injections. There were no hospitalizations or deaths. Eighty-seven percent of major reactions began within 20 minutes of injection. Frequently observed risk factors for major reactions were buildup phase of immunotherapy, active asthma, and first injection from a treatment vial. Home and office injections had similar rates of total systemic reactions, but home-based immunotherapy had far fewer major reactions. Home-based immunotherapy was found to be safe. The methods and precautions used to treat patients with this degree of safety are specified and discussed.

Allergic Rhinitis: Clinical Practice Guideline

This guideline was compiled by members of a standing committee of the American Academy of Otolaryngic Allergy. The intent of this guideline is to provide practitioners, referring physicians, patients, third-party payers, and cognizant government authorities with the fundamental principles involved in the diagnosis and treatment of the patient with allergic rhinitis. Although developed solely through the American Academy of Otolaryngic Allergy, the statements and recommendations are drawn from the entire spectrum of English-speaking literature from the United States and Europe. Articles were independently reviewed by members of the Committee, many of whom sit on editorial review boards for major professional publications. A grading system was used to categorize individual articles to demonstrate the format used to arrive at conclusions. The grade is recorded at the end of each article reference. The grading scale follows: Grade A: A study involving prospective or well-selected retrospective patient populations. The conclusions drawn are well supported by the scientific work. Little controversy relating to these conclusions would be expected. Grade B: A scientific study executed without major flaws. Limitations may exist such that the conclusions drawn remain subject to controversy. Grade C: An anecdotal or case report study.

Levels of Eosinophil Cationic Protein and Myeloperoxidase from Chronic Middle Ear Effusion in Patients with Allergy and/or Acute Infection.

BACKGROUND AND OBJECTIVE Allergy may play a role in the middle ear inflammation that leads to otitis media with effusion. The purpose of this study was to determine whether an elevated mediator correlated with the patients disease and thus could be used to differentiate allergy vs. infection as the cause of the middle ear inflammation. METHODS WE evaluated 57 individuals with otitis media with effusion, 32 with persistent effusion but no recent acute infection, 14 with recent infection and purulent otitis media with effusion, and II healthy subjects. The mediator activity of eosinophils and neutrophils in effusion was studied in patients characterized as having allergy by positive intradermal skin test results and positive radioallergosorbent test results. Eosinophils were characterized by measurement of eosinophil cationic protein in the effusion. Neutrophils were characterized by measurement of myeloperoxidase in the effusion. The levels of eosinophil cationic protein and myeloperoxidase in patients with and without allergy were correlated to patient history. RESULTS Significantly elevated levels of both eosinophil cationic protein and myeloperoxidase indicated that inflammation in the ear of patients with otitis media with effusion was characterized by a pronounced involvement of both eosinophils and neutrophils. Eighty-nine percent of all patients with disease had allergy. A higher ratio of myeloperoxidase to eosinophil cationic protein in patients with purulent otitis media with effusion indicated that in patients with a superimposed acute infection, neutrophil activity was increased even further. The level of eosinophil cationic protein was elevated only during the effusion of patients with allergies as compared with controls (p < 0.01). Among 29 cases of nonpurulent otitis media with effusion, 96.5% had allergic immune-mediated disease proved by skin testing, which was related clinically to their ear disease. Eighty-nine percent (89.6%) of these patients had eosinophil cationic protein levels greater than 10 microgram/L. CONCLUSION Middle ear eosinophil cationic protein may be used as a marker of related allergy.

The Presence of Eosinophil Cationic Protein in Middle Ear Effusion

Eosinophil cationic protein (ECP) is probably responsible for the underlying Inflammatory mechanisms seen in asthma. It can be modulated in vivo by immunotherapy or steroids, with an appropriate reduction in symptoms of respiratory tract diseases. ECP is an identifiable mediator in additional target organs involved in allergic reactions, making it of potential interest in the study of otitis media with effusion. A qualitative prospective study was designed to discover the relationship of ECP and serum IgE in patients with middle ear effusion and allergy, as demonstrated by RAST and skin testing. The concentrations of ECP in the middle ear fluid from 23 consecutive patients with otitis media with effusion undergoing the placement of tympanostomy tubes ranged from 2 to 1248 μg (normal serum ECP, 5 to 15 μg), with 87% being abnormally elevated. There was no correlation between an individuals ear and serum levels of ECP (r = 0.1672; p = 0.6232), suggesting a more localized process. There was no relation between effusion ECP and serum IgE (p = 0.0040). ECP from middle ear effusion did correlate with a patients having allergy, as confirmed by RAST and skin testing (p = 0.0095). Mechanisms involving Immune mediated disease in the middle ear, of which the eosinophil may be one participant, are presented.

Efficacy of allergy immunotherapy as a treatment for patients with chronic otitis media with effusion

OBJECTIVE Controversy persists over the significance of allergy as it might relate to chronic middle-ear disease as no controlled study of the efficacy of allergy immunotherapy has been published. The aim of this study was (1) to evaluate the atopic status of patients with intractable chronic otitis media with effusion or drainage from their middle ear and (2) to determine in this select population the efficacy of specific allergy immunotherapy in preventing or limiting the duration of their chronic middle-ear disease. METHODS This was a prospective, cohort study of patients cared for in a private community practice. History, examination, audiogram, tympanometry and recurrence of effusion/infection were recorded on 89 patients (52 children <15 years old, 37 adults) referred with (1) effusion found to warrant myringotomy and ventilation tubes, or (2) chronic drainage from a perforation or tube. All were evaluated for allergy by intradermal skin testing according to criteria of the American Academy of Otolaryngic Allergy. A control cohort of 21 patients who refused therapy was included. Intervention consisted of immunotherapy for dust, pollen, and molds. Recurrence or persistence of fluid or drainage following 2-8 years of therapy was compared to the patients pretreatment status. RESULTS All 89 OME patients proved to be atopic. Most were allergic to dust (94%), animals (44%) and molds (88%) while 9% were allergic only to seasonal pollens. Associated allergic diseases included asthma (21%) and allergic rhinitis/sinusitis (63%). Otitis was the sole symptom among 37%. Immunotherapy provided complete resolution of effusion or drainage in 85% of 127 ears. CONCLUSION Intradermal testing proved all 89 patients with intractable middle-ear disease in this study who presented with chronic effusion or chronic draining perforations or tubes to be atopic. Specific allergy immunotherapy significantly improved 5.5% and completely resolved 85% of chronic otitis media with effusion in these ears. None of the controls resolved spontaneously (p<0.001). This supports the hypothesis that in many, otitis media with effusion is an immune mediated allergic disease and suggests that these patients deserve consideration for aggressive evaluation and allergy treatment, as most respond to immunotherapy.