Neonatal middle ear effusion predicts chronic otitis media with effusion.

HYPOTHESIS AND AIMS: The specific aims of the research are to determine whether newborn ears with persistent middle ear effusion at age 30 to 48 hours are more likely to develop chronic otitis media with effusion over the first year of life when compared with ears without persistent middle ear effusion. The hypothesis is that neonates with middle ear effusion persisting to 30 to 48 hours are more likely to develop chronic otitis media with effusion. STUDY DESIGN: Prospective, case-control design. Loupe-magnified pneumatic otoscopy performed at the time of newborn hearing screening determined presence or absence of effusion. Infants enrolled in the study returned for outpatient examinations. SETTING: University medical center well-baby nursery and out-patient audiology clinic. SUBJECTS: From 454 neonates, 14 experimental subjects with neonatal middle ear effusions and 15 control subjects free of neonatal effusion were recruited for the study and followed-up for 1 year. INTERVENTIONS: Outpatient study tests included transient-evoked otoacoustic emissions, tympanometry, pneumatic otoscopy, and visual reinforcement audiometry (starting at age 6 months), at 3, 6, 9, and 12 months of age. Experimental (neonatal effusion) infants were followed-up starting at age 1 month. Infants found at any follow-up examination to have effusion on otoscopy were followed-up and tested 1 month later. MAIN OUTCOME MEASURES: Chronic otitis media with effusion defined as hypomobile or immobile tympanic membrane on pneumatic otoscopy in one or both ears for three consecutive monthly examinations. Hearing loss defined as greater than 25-dB hearing loss visual reinforcement audiometry thresholds. RESULTS: Eight experimental infants (58%) and three control infants (20%) developed chronic otitis media with effusion (p < 0.04). The average number of effusions was 1.27 for control and 4.14 for experimental infants (average number of effusions for each group at 3-, 6-, 9-, and 12-month visits). Warbled tone and speech visual reinforcement audiometry thresholds averaged 3 dB worse in the experimental group, but these differences were not statistically significant. For the control group, mean visual reinforcement audiometry thresholds never exceeded 25 dB hearing loss. For the experimental group, mean visual reinforcement audiometry thresholds exceeded 25 dB hearing loss at 1,000, 2,000, and 4,000 Hz at 9 months. CONCLUSIONS: A majority of infants with persistent neonatal middle ear effusion found by pneumatic otoscopy at 30 to 48 hours will develop chronic otitis media with effusion during the first year of life. However, chronic otitis media with effusion is common in all infants (20% of controls), a time during which infants are examined and tested frequently.     

Experimental otitis media with effusion induced by middle ear effusion.

Experimental otitis media with effusion was induced in chinchillas by middle ear effusion, which was induced by an injection of immune complex into the tympanic cavity. To elucidate the pathogenesis of otitis media with effusion, cytologic and biochemical findings of the effusion and histopathology of the middle ear mucosa of effusion-induced chinchillas were compared with those of experimental otitis media with effusion induced by different procedures; eustachian tube obstruction, intratympanic inoculation of endotoxin, and immune reaction. No significant differences were seen in cytology, biochemistry, and histopathology among OMEs induced by these procedures. However, middle ear effusions, when compared with the corresponding sera, were proven to contain higher amounts of histamine and prostaglandin E2. These findings seem to demonstrate that middle ear effusion containing a large number of inflammatory mediators is essential for induction and prolongation of inflammatory reaction in the middle ear.     

Immunologic reactivity in the middle ear in otitis media with effusion

This article reviews the immunologic reactivity in the middle ear in both the human disease and in animal models of otitis media. It differentiates the role of immune complexes in otitis media in the animal model and in the human form of middle ear inflammation. The effect of immunization of the gut on the mucosal immune system in the middle ear is briefly explored, and the source of lymphocytes that make their way into the middle ear mucosa from other parts of the mucosal immune system and systemic immune system are briefly discussed. Finally, work from the author's laboratory on the immune response of children with recurrent otitis media due to nontypable Haemophilus influenzae is summarized.     

Viscosity of effusion in the middle ear and eustachian tube in patients with otitis media with effusion

The viscosity of middle ear effusion (MEE) in the tympanic cavity and in the bony portion of the eustachian tube (ET) was compared in 11 specimens (10 patients) with otitis media with effusion (OME). Twenty microliters of effusion from the bony portion of the ET was sampled through myringotomy on the anterosuperior quadrant of the tympanic membrane with a micro-syringe with a curved needle. MEE in the hypotympanum was also sampled by separately puncturing the posteroinferior quadrant of the tympanic membrane. Using the microviscometer developed by one of the authors, the relative viscosity of these effusions were measured, and their natural logarithmic values were compared between the two sites mentioned above in each patient by obtaining their ratios (ET/ME). Effusion was found to have a significantly higher viscosity in the bony portion of the ET than in the hypotympanum (paired t-test: t = 3.859, p less than 0.01). In two patients with OME (serous mastoiditis) due to radiation to the temporal region, the ratios of the viscosity were comparatively small. On the other hand, excluding these two patients with serous mastoiditis mentioned above, the ratios were highest in two patients with a history of more than 60 days of hearing loss. These results were considered to be a clue to the possibility that viscous effusion aggravates ET function as a result of OME.     

Vascular permeability of the middle ear mucosa in otitis media with effusion

Summary Vascular permeability (VP) of the middle ear mucosa (MEM) in chronic otitis media with effusion (OME) was estimated in both pediatric and adult patients by calculating the middle ear effusion (MEE) to serum concentration ratios of albumin and of four protease inhibitors: 1-antitrypsin (1-AT), 1-antichymotrypsin (1-X), inter--trypsin inhibitor (I--I) and 2-macroglobulin (2-M). The levels of albumin and 1-AT in MEE were higher while those of I--I and 2-M were lower than their serum levels in both adult serous and pediatric mucoid groups. There was a negative correlation between molecular weight and the mean value of the ratio (MEE/serum) of the four inhibitors in both serous (r=–0.989) and mucoid (r=–0.924) groups. Vascular permeability of the MEM seems to be variable in both serous and mucoid groups during middle ear inflammation. Selective leakage of proteins by molecular weight appears to occur in MEM. Our findings further indicate that a high level of the high-molecular-weight inhibitor 2-M in MEE may be a significant index reflecting the remarkably enhanced VP of the MEM.     

Vascular permeability of the middle ear mucosa in otitis media with effusion

Vascular permeability (VP) of the middle ear mucosa (MEM) in chronic otitis media with effusion (OME) was estimated in both pediatric and adult patients by calculating the middle ear effusion (MEE) to serum concentration ratios of albumin and of four protease inhibitors: alpha 1-antitrypsin (alpha 1-AT), alpha 1-antichymotrypsin (alpha 1-X), inter-alpha-trypsin inhibitor (I-alpha-I) and alpha 2-macroglobulin (alpha 2-M). The levels of albumin and alpha 1-AT in MEE were higher while those of I-alpha-I and alpha 2-M were lower than their serum levels in both adult serous and pediatric mucoid groups. There was a negative correlation between molecular weight and the mean value of the ratio (MEE/serum) of the four inhibitors in both serous (r = -0.989) and mucoid (r = -0.924) groups. Vascular permeability of the MEM seems to be variable in both serous and mucoid groups during middle ear inflammation. Selective leakage of proteins by molecular weight appears to occur in MEM. Our findings further indicate that a high level of the high-molecular-weight inhibitor alpha 2-M in MEE may be a significant index reflecting the remarkably enhanced VP of the MEM.     

The middle ear mucosal immune system in otitis media with effusion

The mucous membrane of the middle ear cavity in otitis media with effusion has a number of immunobiological mechanisms capable of defending the organ. A humoral immune mechanism, with all the attributes of a local mucosal immune system, appears to be present and capable of preventing viral and bacterial access to middle ear tissue. Putative cells of a cell-mediated immune response also appear to be present, and the distribution of T cells and B cells and T-helper and T-suppressor cells is described. The exact role of these cells in either cell-mediated immunity or delayed hypersensitivity remains to be defined in otitis media. Lymphocyte--macrophage interaction is briefly described and may represent an important aspect of immune modulation in the middle ear in otitis media with effusion. Finally, the effect of middle ear supernatants on natural killer cell activity is discussed. Serous effusions appear to augment natural killer cell activity of peripheral blood lymphocytes.     

Change of middle ear transfer function in otitis media with effusion model of guinea pigs

Otitis media with effusion (OME) is an inflammatory disease of the middle ear that causes most cases of conductive hearing loss observed in the pediatric population. With the long term goal of evaluating middle ear function with OME, the aim of the current study was to create an animal model of OME in which middle ear transfer functions could be measured. In guinea pigs, OME was created by injecting lipopolysaccharide (LPS) into the middle ear. Evidence of OME was assessed by otoscopy, tympanometry, histology, and by measuring the volume of fluid in the middle ear. Vibrations of the umbo and round window membrane were measured with a laser Doppler vibrometer at frequency range of 200-40kHz in three groups of 3, 7, and 14 days after injection of LPS. Changes in displacement of the umbo and round window membrane in response to 80dB SPL sound in the ear canal were measured across the frequency range. Displacement of both the umbo and round window membrane was reduced at all time points following LPS injections. Further, the change of the displacement transmission ratio (DTR) from the tympanic membrane to the round window occurred mainly in chronic (e.g. 14 days post-LPS injection) OME ears. This study provides useful data for analyzing the change of middle ear transfer function in OME ears.     

分泌性中耳炎中耳积液嗜酸细胞阳离子蛋白与IgE测定

目的：通过测量分泌性中耳炎（OME）患者中耳积液中嗜酸细胞阳离子蛋白（MECP）、中耳积液IgE（MIgE）及血ECP（SECP）的含量,进一步探讨OME发病机制与变态反应的关系。方法：对31例OME患者,用Uni-CAP-100型变应原体外检测系统分别测量MECP、MIgE及SECP含量,得出结果并统计学处理。结果：31例OME患者检测到MECP均值为56．88μg／L,明显升高9例,占28．1％;MIgE均值为27．2ku／L,明显升高3例,占9．7％。MECP与MIgE呈正相关（P〈0．05）;SECP均值为5．6μg／L。结论：ECP存在于OME的鼓室积液中,部分OME是中耳的局限性变态反应炎性过程。OME发病过程中存在着复杂的变态反应机制。     

Soluble adhesion molecules in middle ear effusions from patients with chronic otitis media with effusion

Soluble forms of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been identified in the peripheral blood and other body fluids. These soluble adhesion molecules have been reported to reflect the upregulation of cell surface ICAM-1 and VCAM-1 expression in inflammatory diseases. The levels of soluble ICAM-1 and soluble VCAM-1 in 37 middle ear effusions from 37 patients with chronic otitis media with effusion (OME) were quantitatively determined with enzyme-linked immunosorbent assays. The levels of soluble ICAM-1 in mucoid effusions were significantly higher than those in serous effusions, but the levels of soluble VCAM-1 did not differ significantly between the two types of effusion. The levels of soluble VCAM-1 in effusions from atopic patients were significantly higher than those from non-atopic patients, whereas the levels of soluble ICAM-1 in samples from atopic patients were significantly lower than those from non-atopic patients. Therefore, our data suggest that an increase in soluble VCAM-1 plays a more important role in the pathogenesis of OME in atopic patients than in non-atopic patients. In addition, soluble ICAM-1 is likely to play a more important role in the pathogenesis of OME in nonatopic patients than soluble VCAM-1.     

Penetration of cefprozil to middle ear effusion in children with chronic otitis media with effusion

BACKGROUND: Because of chronic otitis media with effusion (COME) demonstrates pathogenic bacteria, treatment with appropriate antibiotic is reasonable. OBJECTIVE: We determined the penetration of cefprozil into the middle ear effusion (MEE) in children with COME. MATERIALS AND METHODS: 25 patients 2-13 years of age with COME were eligible for study. After the single dose of 15 mg/kg patients were assigned to have MEE, and serum samples were obtained during ventilation tube insertion at 0.5, 2, 3, 5, or 6 h after administration of the dose. The concentration of cefprozil was measured using validated high performance liquid chromatography method. RESULTS: The mean concentrations of cefprozil in the MEE ranged from 0.4 to 4.4 microg/ml. The penetration into MEE was rapid and effective. Cefprozil in the MEE was maintained at a greater level than MIC 90 in S. pneumoniae for at least 6 h after administration of 15 mg/kg. CONCLUSION: Cefprozil penetrated well into the MEE in children with COME.     

分泌性中耳炎患者血清,中耳积液补体和免疫复合物含量测定

２０例（２０耳）分泌性中耳炎患者血清与对照组血清比较，Ｃ５、Ｃ１－ＩＮＨ含量明显增高，Ｃ９、Ｂ因子（Ｂｆ）含量明显降低，免疫复合物（ＩＣ）含量明显升高。患者的中耳积液与血清比较，Ｃ３、Ｃ４、Ｃ５含量明显降低，Ｂｆ含量明显增高，ＩＣ含量明显增高，提示补体对ＩＣ清除等功能降低，有可能引起ＩＣ沉积在中耳粘膜，从而导致毛细血管通透性增加，出现中耳积液。     

Conservative treatment of otitis media with effusion by autoinflation of the middle ear

A total of 85 children on the waiting list for grommet insertion aged between 3 and 10 years with bilateral chronic otitis media with effusion (OME) were assigned at random to an observation or treatment group. Those in the treatment group were given the Otovent® device to use three times a day for the duration of the study and both groups were then seen at monthly intervals for 3 months for pneumatic otoscopy and tympanometry. Statistically significant improvement was seen in those using the treatment with a compliance of more than 70%. This was detected on the outcome measures of tympanometry and pneumatic otoscopy after 1, 2 and 3 months. No side effects were demonstrated. We conclude that autoinflation is an effective short-term treatment for children with OME when used regularly under supervision.     

Lymphangioma of the middle ear and mastoid simulating chronic otitis media with effusion

Lymphangiomas are benign congenital malformations of the lymphatic system. Middle ear lymphangioma is extremely rare entity. A 14-year-old male patient with otitis media with effusion, which was previously diagnosed to be middle ear and mastoid lymphangioma, was treated. There were no cerebrospinal fluid fistula, solitary mass, and meningitis findings. All properties of chronic otitis media with effusion were present in that case. This case is unique with these clinical properties. Middle ear and/or mastoid lymphangioma should be remembered in the differential diagnosis of chronic middle ear effusions.     

Lysozyme levels in middle ear effusion and serum in otitis media

Lysozyme concentrations in middle ear effusion and serum were determined in patients with otitis media with effusion. Lysozyme concentrations in middle ear effusion were significantly higher than in serum. Children with mucoid otitis media showed significantly higher levels of lysozyme in middle ear effusion than children with serous otitis media and adults with otitis media with effusion. Higher levels of lysozyme were observed in the group of children younger than 5 years old compared with the age group of 6- to 10-year-olds. Lysozyme concentrations of middle ear effusion in adults were significantly lower than those of mucoid otitis media in children. These results indicate that lysozyme plays an important role in the disease process of otitis media.     

Relationship between severity of middle ear mucosal lesion and middle ear pneumatic space volume in patients with otitis media with effusion.

If we assume that the state of suppression of pneumatic cells is the result of suppression of pneumatic cell growth by inflammatory stimulation in the middle ear pneumatic space, it is possible to improve the state of suppression by performing sufficient treatment during the growth period of the pneumatic cells. We indwelt a tympanic membrane ventilation tube (hereinafter referred to as tube) for treatment of otitis media with effusion (OME) in child patients aged 3-13 years and investigated the following points: i) relationship between the severity of inflammation of the lamina propria of middle ear mucosal specimens (hereinafter referred to as lamina propria) collected at the time of tube indwelling and the degree of growth of the pneumatic space; and ii) changes in the pneumatic space associated with treatment by tube indwelling, which was studied by comparing the above-described mucosal severity with the pneumatic space area of 2 years after tube indwelling, and with increase in the pneumatic space volume measured periodically after tube indwelling. The results indicated that mastoid cell growth suppression is higher in patients with a higher degree of inflammatory changes in the lamina propria. In association with treatment by tube indwelling, effusion accumulated in the pneumatic space and mucosal swelling disappeared early after the treatment, or 2 months of tube indwelling. After that, in patients with severe mucosal lesion, a long time, 1.5-2 years, was found to be required for repneumatization accompanying regrowth of the temporal bone. We confirmed that the severity of inflammation of the lamina propria is deeply involved in the growth and repneumatization of the pneumatic cells.     

Magnesium levels in middle ear fluids and sera in otitis media with effusion

Summary Middle ear fluids (MEE) and matched sera (S) were obtained from 50 patients with serous otitis media and magnesium levels were measured to determine if magnesium concentration was distinctly varied in otitis media with effusion (OME). The MEE/S ratio was considerably raised along with transient sensory hearing loss in chronic OME when compared with acute OME. The higher magnesium level found in the MEE implies that it is probably produced locally by the middle ear mucosa and may contribute to the hearing loss found. We also regard the MEE/S ratio as a prognostic factor in OME. Correspondence to: W. L. Yue