Nasal and otologic effects of experimental respiratory syncytial virus infection in adults

PURPOSE: Upper respiratory tract viral infections continue to cause substantial patient morbidity and complications including sinusitis, otitis media, and pneumonia. This study was conducted to more clearly define the extent and frequency of nasal and otologic effects of respiratory syncytial virus infection in healthy adult volunteers. MATERIALS AND METHODS: Thirty-two healthy, susceptible adult volunteers were cloistered for a 9-day period. During this time, subjects underwent nasal inoculation with respiratory syncytial virus. Monitoring included daily self-assessment of general health, as well as nasal and otologic symptoms. Objective measurements of nasal and otologic function included expelled nasal secretion weight, saccharin-dye mucociliary clearance, sonotubometry, tympanometry, and physical examination. A nasal lavage was done each morning, and fluids were submitted for viral detection. Twenty-one days after viral inoculation, all subjects had convalescent blood samples drawn for assay of virus-specific antibody titres. RESULTS: Eighteen subjects (56%) became infected with the challenge as determined by either viral shedding (47%) or antigen detection (41%) from the nose or a 4-fold rise in virus-specific antibody titer (34%). Infected subjects more frequently reported adverse nasal (congestion, rhinorrhea) and general symptoms (fever, malaise, illness). By day 6, only 46% of infected subjects had normal middle ear pressure (> -100 mm H2O). Nasal secretion also increased substantially after infection. No patterned changes in mucociliary clearance or sonotubometry occurred, and no subjects developed otitis media. CONCLUSIONS: Nasal inoculation of healthy, susceptible adult volunteers with respiratory syncytial virus results in detectable infection in only about half of the subjects challenged. Infected subjects experience substantial symptoms and signs of a viral upper respiratory tract illness. As in our previous studies using rhinovirus and influenza A virus, respiratory syncytial virus disrupted the maintenance of normal middle ear pressures. These findings provide further support for the relationship between viral upper respiratory tract infections and otitis media.     

Alterations of the eustachian tube, middle ear, and nose in rhinovirus infection

This study measured the changes in 64 ears of 32 adult volunteers in eustachian tube function by the nine-step test, middle ear pressure by tympanometry, and nasal patency by active posterior rhinomanometry for 18 days following type 39 or Hanks rhinovirus infection. Abnormal measures were limited to the 75% of subjects (24) with clinical illness (colds) defined by symptom scores. Two days after infection, tubal function was present in only 50% of ears (48) and 20% of persons (5), middle ear underpressures of less than -50 mm H2O were measured in 50% of volunteers (12), and decreased nasal patency was observed in 54% of those with colds (13). These changes resolved 6 to 10 days after challenge. These results support a causal relationship between viral upper respiratory tract infection eustachian tube obstruction and abnormal middle ear pressure.     

The role of allergic rhinitis in the development of otitis media with effusion: effect on eustachian tube function

PURPOSE: The pathogenesis of otitis media with effusion (OME) is considered multifactorial, with viral upper respiratory tract infection and eustachian tube dysfunction. Allergy may be related to the pathogenesis of OME or to another etiological factor. We investigated the role of allergic rhinitis (AR) in children with OME and evaluated eustachian tube function in patients with AR. MATERIALS AND METHODS: We prospectively analyzed the prevalence of AR, serum eosinophil count, and serum total IgE concentrations in 123 children with OME and in 141 controls. IgE concentration in middle ear effusion was compared in children with OME with and without AR, and eustachian tube function after a nasal provocation test was compared between patients with AR and controls. RESULTS: The prevalence of AR in children with OME (28.4%) and control subjects (24.1%) did not differ significantly. These 2 groups also showed no differences in total eosinophil count and serum and middle ear effusion IgE concentration. Abnormalities in eustachian tube function were the same in patients with AR and controls. CONCLUSIONS: Allergic rhinitis may not be related to the development of OME in children.     

Hyperbaric oxygen therapy: effect on middle ear and eustachian tube function.

Hyperbaric oxygen therapy (HBO) involves intermittent inhalation of 100% oxygen under a pressure greater than 1 atm. It is an important mode of adjuvant therapy for disease processes such as decompression sickness, osteomyelitis, carbon monoxide poisoning, and poorly healing wounds. Patients undergoing this therapy often complain of ear pain and/or fullness which can be transient or long standing. This prospective study objectively measured the changes in eustachian tube function before and after HBO treatment in 33 adult patients by the 9-step inflation-deflation test described by Bluestone. The results show 15 of the 33 patients (45%) had evidence of eustachian tube dysfunction after treatment was initiated. Of these, 15 (100%) developed the sensation of fullness, 13 (87%) developed serous otitis media, and 7 (47%) required tympanostomy tubes. The overall incidence of middle ear problems was 27 patients (82%) experiencing a sensation of fullness, 17 (52%) developing serous otitis media, and 8 (24%) requiring tympanostomy tubes. The middle ear complications reported in this study are much higher than those in previous reports in the literature. Twelve of 33 patients presented with a subjective history of eustachian tube dysfunction, and all 12 (100%) developed fullness in their ears and serous otitis media during the course of the treatment. The findings reveal that patients manifesting eustachian tube dysfunction after their first HBO treatment were at significantly greater risk toward developing symptoms of fullness and serous otitis media, often requiring tympanostomy tube placement. In addition, a history of eustachian tube dysfunction accurately predicted the development of fullness and serous otitis media.     

Waldeyer's ring and otitis media: the nasopharyngeal tonsil and otitis media

This overview of the relationship between the nasopharyngeal tonsil and otitis media will review three important concepts: (1) Adenoid inflammation leads to inflammatory obstruction of the Eustachian tube; (2) early colonization of the adenoid with the three major bacterial pathogens of otitis media is the most important factor in the early pathogenesis of otitis media; (3) the local immune system in the adenoid particularly specific secretory IgA directed against both viruses and bacterial pathogens are probably genetically controlled and represent the immunological factor in protecting the host against invasion of these agents in the Eustachian tube and middle ear. This overview of the relationship between the adenoid and the development of otitis media emphasizes that nasopharyngeal colonization with the three major middle ear pathogens is among the most important risk factors in the pathogenesis of otitis media. Inasmuch as these pathogens normally reside in the nasopharynges of most healthy children, the factors which trigger development of otitis media need to be carefully evaluated. Among these two triggers are viral infections and upper respiratory tract allergy.     

Clinical characteristics of so called eosinophilic otitis media.

OBJECTIVE: Although "eosinophilic otitis media" is not as uncommon a condition as was previously believed, its cause and pathogenesis are not yet fully understood. The purpose of this study was to describe the clinical characteristics in patients with "eosinophilic otitis media" to clarify its pathogenesis. METHODS: Seven adult patients with persistent and intractable otitis media with viscous middle ear effusion containing many eosinophils, who were also under treatment for bronchial asthma, were studied. The following examinations were conducted: nasopharyngeal endoscopy, pure-tone audiometry, eustachian tube function test, temporal bone CT scan, blood analysis, bacterial and fungal culture of middle ear effusion, histological study of the middle ear and nasal specimens, and measurement of eosinophilic cationic protein (ECP) in middle ear effusion. RESULTS: Some patients had persistent perforation with papillomatous granulation tissue arising from the mesotympanic mucosa, and all the patients had nasal polyposis. The pure-tone audiometry showed the mixed-type of hearing loss in all the patients, and the hearing level deteriorated progressively during the course in some patients. The eustachian tube function was not always poor but was patulous in some cases. The most severely diseased areas were in the eustachian tube and mesotympanum by temporal bone CT images. All the seven patients had the high levels of total serum IgE, but the RAST scores were negative in three patients and low grade in three patients. The accumulation of eosinophils was observed in middle ear effusion, middle ear mucosa and nasal polyps, and the eosinophils were highly activated with degranulation. High level of ECP was also recovered from middle ear effusion. CONCLUSIONS: Active eosinophilic inflammation occurs in the entire respiratory tract, including the middle ear in these patients. From our present investigation, we propose the criteria and clinical characteristics of "eosinophilic otitis media".     

Middle ear pressures in eustachian tube malfunction: manometric studies

We made direct measurements of the difference in pressure between the middle ear and the ambient atmosphere in 300 ears affected with chronic adhesive otitis media (CAOM), serous otitis media (SOM), and similar disorders of the ear caused by eustachian tube malfunction. We utilized a narrow bore, open U-tube manometer made of No. 205 polyethylene tubing which was connected to a 20 or 22 gauge spinal needle. The needle was passed through the intact tympanic membrane and the displacement of the column of 95 percent alcohol in the manometer was noted and recorded. Our results showed that in 101 ears with CAOM, the average negative pressure difference between the middle ear and the ambient atmosphere was 9 mm 95 percent alcohol, equivalent to 7 mm of H₂O. In 136 ears with SOM, the average negative middle ear pressure was 8 mm 95 percent alcohol, equivalent to 6.5 mm H₂O. In 80 of the 300 diseased ears we tested, the middle and ambient atmospheric pressures were equal. Direct readings of the middle ear pressure tell us the status of the middle ear ventilation at the moment of the measurement.     

Presence of human herpesviruses in young children with acute otitis media

Some herpesviruses have been detected in middle ear fluid (MEF) of patients with acute otitis media (AOM), but their role in middle ear disease is unknown. We examined 73 middle ear fluid samples from 73 children with acute otitis media for the presence of four major herpesviral DNA, respiratory viral genomes, and bacterial DNA by multiplex polymerase chain reaction (PCR). Herpesviruses were detected in 16 specimens (22%), with 18 viral infections were identified overall. Respiratory viruses were detected in 35 specimens (48%), 39 viral infections overall. Bacterial DNA was detected in 51 specimens (70%), 60 bacterial infections overall. Clinical outcome was compared in patients with and without herpesvirus DNA, respiratory viral genomes, or bacterial DNA. Progression to otitis media with effusion (OME) was more common when herpesviral DNA was present. Presence of herpesvirus DNA may reflect an immunocompromised state that may make it difficult to eliminate bacteria from the middle ear after infection.     

The significance of experimental animal studies in otitis media

Animal models have been instrumental in investigating otitis media. Experimental models have allowed for focused research on how such factors as eustachian tube dysfunction and microbial infection contribute to the pathogenesis of otitis media. Antibacterial therapy and immunologic prophylaxis have been developed using these models. Current research is aimed at generating an objective index of middle ear inflammation for guiding patient management.     

Patulous eustachian tube following otitis media

Loss of weight, dehydration, pregnancy, fatigue, and otitis media are among the factors proposed as causes of a patulous eustachian tube, but true details remain obscure. We studied patients who developed a patulous eustachian tube following otitis media and discuss the relationship between these 2 conditions. Subjects were 12 patients diagnosed with otitis media at our department who later developed a patulous eustachian tube. The initial middle ear disease progressed from acute otitis media to otitis media with effusion in 2, acute otitis media in or acute mastoiditis in 1 each, and otitis media with effusion in the remaining 8 patients. Seven patients evidenced a low body mass index (BMI), weight loss, and underlying disease, but 5 with a patulous eustachian tube following otitis media did not. We retrospectively analyzed 119 patients diagnosed with a patulous eustachian tube in our department for whether they had been diagnosed by an ENT physician as having otitis media, i.e., acute otitis media or otitis media with effusion. Some 42 (35.3%) had a history of otitis media. At acute otitis media or otitis media with effusion, the tympanic cavity becomes inflamed, accompanied by inflammation of the eustachian tube mucosa and a stenotic tendency. Healing from otitis media is accompanied by decreased eustachian tube mucosa inflammation. We surmise that, depending on how inflammation disappears, fibrosis of the eustachian tube mucosa occurs, leading to a pathologically patulous eustachian tube. Many aspects of the causation of this condition remain unclear, but we surmised that in patients with earlier otitis media, a pathological patulous eustachian tube develops during resolution of inflammation. Our findings indicate the involvement of otitis media as a causative factors in a patulous eustacian tube.     

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.     

Pediatric middle ear infections and gastroesophageal reflux

OBJECTIVES: The pathogenesis of middle ear infections in children is multifactorial and includes infection, anatomical factors, impaired immunologic status, allergy, familial predisposition, male sex, method of feeding and environmental factors. Glue ear remains the commonest cause of deafness in childhood. Gastroesophageal reflux (GOR) is a common problem in the newborn and preschool periods. Recent research suggests that it may be related to eustachian tube dysfunction and otitis media. METHODS: We review the literature and discuss the possible relationship between Gastroesophageal reflux and otitis media in children. CONCLUSIONS: The current data are not enough to support antireflux treatment in children with refractory middle ear infections. More prospective randomised placebo-controlled studies are needed.     

Rhinovirus RNA in children with longstanding otitis media with effusion

BACKGROUND: Earlier studies indicate that respiratory viruses may play a role in the pathogenesis of otitis media with effusion (OME). OBJECTIVES: To study the presence of rhinovirus RNA in middle ear mucosa in children with OME without signs of present acute infection. METHODS: Eighteen children scheduled for tympanostomy tube placement due to longstanding OME were recruited and a biopsy of the promontory mucosa was obtained. In addition, adenoidectomy was performed for eight of these children and a biopsy of adenoid tissue was taken as well. The samples were collected from December to May. Rhinovirus RNA was studied by in situ hybridization (ISH). RESULTS: Seven out of eight adenoid biopsies were positive for rhinovirus by ISH. However, rhinovirus RNA was not found in any of the 18 middle ear biopsies. CONCLUSIONS: These results show that children with longstanding OME do not have a rhinovirus infection in the middle ear mucosa, although the same children frequently harbor large amounts of rhinovirus RNA in their adenoid tissue.     

Effects of nasal obstruction on Eustachian tube function and middle ear pressure.

To evaluate the relationship between nasal obstruction and otitis media, 10 ferrets were studied before and after either unilateral (E = 5) or bilateral (n = 5) nasal obstruction. Observations included otomicroscopic assessments of middle ear status, tympanometric recordings of middle ear pressure and forced-response, inflation-deflation and continuous monitoring tests of Eustachian tube function. During the 6 8 week post-obstruction follow-up period no animal developed evidence of otitis media. Abnormal positive middle ear pressures lasting for the period of follow-up occurred only in the animals with bilateral nasal obstruction. Eustachian tube function test results showed these pressures to be generated during swallowing. No changes in the passive function of the tube were documented in either group, but changes in active function consistent with alterations in the pressure gradient between the middle ear and the nasopharynx were observed in both groups.     

Histo-morphological changes of eustachian tube of guinea pigs with effusion after being treated by pulmonary surfactant]

OBJECTIVE: To study the effect of pulmonary surfactant on otitis media with effusion in guinea pigs to find a new way to manage otitis media with effusion. METHODS: Nonviable heat-killed pneumococci (HKP) solution was inoculated into the middle ear cavity in guinea pigs via a transeardrum approach to set up a model of otitis media with effusion in guinea pigs. Seven days after being injected with pulmonary surfactant (PS) by transeardrum approach, ABR threshold and histomorphological changes of eustachian tube mucosa of guinea pigs were examined by light microscopy and scanning microscopy. RESULTS: Five days following inoculation of HKB serous effusion were present in the middle ear cavity of guinea pigs, but disappearance of light cone. Response (mean +/- s) threshold raised from (14.0 +/- 3.1) dB to (45.0 +/- 5.7) dB. The eustachian tube mucosa was thickened and lined eosin-stained structureless matter over mucosa, while cilia of eustachian tube mucosa irregularly arranged. Seven days after being treated by PS, serous effusion of tympanum was reduced or disappeared, and response threshold decreased from (45.0 +/- 5.7) dB to (23.5 +/- 6.3) dB. There was significantly difference between them (P < 0.001). Eustachian tube mucosa was thinned, Cilia of eustachian tube mucosa regularly arranged to the nasopharynx. CONCLUSION: Pulmonary surfactant plays a important role in otitis media with effusion of guinea pigs.     

Measurement of mucociliary function of the eustachian tube

Mucociliary function of the eustachian tube was measured with a radioisotopic method; 0.01 mL of a human serum albumin labeled with technetium 99m was instilled into the anterior part of the middle ear cavity either through a perforation or by puncturing the tympanic membrane, and its course was followed by a gamma-camera. In the normal eustachian tube, the velocity of the mucociliary transport was 0.7 to 1.1 mm/min. The mucociliary function was totally absent in chronic otitis media, in untreated secretory otitis media, and in the ear with a moist perforation of the tympanic membrane. The mucociliary transport returned to normal when the ear was clinically healed. It is assumed that the impairment of the mucociliary function of the eustachian tube and middle ear plays an important role in the pathogenesis of secretory otitis media and chronic ear discharge.     

咽鼓管功能障碍的慢性化脓性中耳炎治疗分析

目的 探讨合并咽鼓管功能障碍的慢性化脓性中耳炎病例的适宜手术方案。 方法 收集咽鼓管功能障碍的慢性化脓性中耳炎病例68耳,分为观察组(28耳),同期行中耳乳突手术及咽鼓管球囊扩张术,对照组(40耳),仅行中耳乳突手术。术前,术后3个月、6个月、12个月分别以ETDQ-7评分、听阈、气骨导差进行对比。 结果 观察组术后6~12个月随访气导平均听力改善率为89%(25/28),干耳率93%(26/28)。对照组听力改善率为75%(30/40),干耳率95%(38/40)。观察组术后3~6个月EDDQ-7评分及听阈达到较明显缓解,但术后6~12个月上述指标有加重趋势。观察组及对照组术后听力均比术前听力提高,有统计学差异,两组的术后听力相对比,观察组优于对照组,有统计学意义。 结论 在咽鼓管功能障碍的慢性化脓性中耳炎患者中,中耳手术同期咽鼓管球囊扩张术较单纯中耳手术的听力改善率高,改善程度高,重新内陷率低,重新粘连率低,干耳率无明显差别。术后3~6个月患者咽鼓管相应症状达到较明显缓解,6~12个月症状有反复。     

Update on eustachian tube dysfunction and the patulous eustachian tube

PURPOSE OF REVIEW: The purpose of this review is to summarize the recent knowledge on eustachian tube dysfunction and the patulous eustachian tube. RECENT FINDINGS: A clinically useful test for eustachian tube function is still lacking. Narrowing of the isthmus alone was demonstrated to be an insufficient cause of otitis media. Inflammatory mediators identified within the eustachian tube and middle ear cells were causally linked with otitis media with effusion. Increasing evidence was found that allergic disease and reflux may be two of the most important contributors of tubal inflammation causing otitis media with effusion. The adenoid size and proximity to the torus tubaris may also be important in considering which patients with persistent otitis media with effusion may benefit from adenoidectomy. Computed tomography scan has documented loss of soft tissue within the cartilaginous eustachian tube in patients with patulous eustachian tubes. An endoscopic approach to seal the tubal lumen has been found to be effective in relieving patulous symptoms. SUMMARY: These studies suggest that allergic rhinitis and gastroesophageal reflux should be investigated in patients with eustachian tube dysfunction. Adenoidectomy should also be considered in patients who have adenoids that obstruct the torus tubaris. Patients with a patulous eustachian tube may benefit from an endoscopic closure. Further research is needed to identify a clinically useful test for eustachian tube dysfunction.     

Illness and Otological Changes During Upper Respiratory Virus Infection

Objectives: Upper respiratory virus infection is associated with the expression of symptoms and signs of illness, and with the development of complications in anatomically contiguous structures. In most epidemiological studies, the frequency of the various complications is expressed as a fraction of the total population judged to be ill by report, signs, or symptoms. Because not all infected subjects become ill and because infected non-ill subjects may develop complications, such risk estimates could be inaccurate. The objective of this study was to estimate the magnitude of the presentation bias during controlled, experimental infections. Study Design: This was a prospective, experimental study of the relationship between illness and otological complications during experimental upper respiratory virus infection in 316 adult volunteers. Methods: The data for illness and for abnormal middle ear underpressure in adult (18–54 y) volunteers experimentally infected with one of three viruses (rhinovirus type 39, rhinovirus strain hanks, influenza A virus) were analyzed and expressed as the relative frequencies of infected subjects reporting illness, developing abnormal middle ear pressure, and developing abnormal middle ear pressure in the absence of illness. Results: For all three viruses, illness was documented in approximately 50% of the infected subjects. While the frequency of persons developing abnormal middle ear underpressure was greater in the infected-ill subjects, approximately one third of all infected subjects developing that complication did not report illness. Conclusions: These results support a large presentation bias in epidemiological surveys of viral upper respiratory infections, and infer that those surveys underestimate the true frequency of complications resulting from such infections.