Otitis media: treatment with intranasal aerosolized surfactant

OBJECTIVES/HYPOTHESIS: The objective was to determine the effect of intranasal surfactant alone and with other medications administered by metered dose inhaler aerosol on the function of the eustachian tube and on the resolution of experimentally induced otitis media with effusion (OME) and acute otitis media (AOM). STUDY DESIGN: Randomized, experimental, controlled animal studies. METHODS: Previously unreported (experiment 4) as well as published (experiments 1-3) data were detailed so that the reader could understand the continuum of information leading to the conclusions. In experiment 1, after a live-animal technique of measuring eustachian tube passive opening pressure was developed and validated, eustachian tube passive opening pressure was determined in 61 adult gerbils and 34 mice at baseline and 5 and 10 minutes after delivery of aerosolized intranasal metered dose inhaler surfactant. In experiments 2 and 3 (Klebsiella pneumoniae), lipopolysaccharide-induced OME was developed in gerbils. Thirty-five animals were randomly assigned to control, placebo, surfactant, surfactant with betamethasone, and surfactant with phenylephrine groups. Seventy animals were randomly assigned to control, placebo once daily (QD) and twice daily (BID), surfactant QD and BID, surfactant with betamethasone QD and BID, and surfactant with phenylephrine QD and BID groups. Intranasal aerosolized MDI medications were administered from postinfection day 2 until the effusion resolved. Otomicroscopy and tympanometry were performed on alternate days for 30 days. In experiment 4, AOM was developed in 39 chinchillas via transbullar injection of nontypeable Haemophilus influenzae on day 1. Thirteen animals each received placebo BID or surfactant BID, beginning on day 1. Thirteen animals received surfactant BID beginning on day 3. All administrations were continued for 10 days. Examinations were performed on seven occasions until day 27. Appropriate statistical measurements were employed, including one- and two-way ANOVA, strength-of-association measure (omega) calculation, chi, and Newman-Keuls post hoc multiple comparison tests. Significance was set as P value of less than.05. RESULTS: In experiment 1, a significant reduction in passive opening pressure was seen in both 5- and 10-minute postsurfactant measurements. Propellant alone was not effective. In experiments 2 and 3, OME resolved after an average period of 16 to 16.5 days in control, placebo QD and BID, and surfactant with phenylephrine QD groups. A significant decrease in OME days was seen in the surfactant QD (10.57 d) and BID (8.57 d), and surfactant with betamethasone QD (8.57 d) and BID (6.3 d) groups. A significant increase was seen in the phenylephrine BID group (18.67 d). In experiment 4, tympanometry was normal or near-normal in 62% and 48% of treated ears and in only 24% of placebo ears on day 12. Sixty-seven percent of placebo ears were culture positive at day 27, compared with 10% and 16% in surfactant groups 1 and 2. Seventy-five percent of untreated animals developed severe labyrinthitis, compared with 15% in groups 1 and 2. On day 27, 58% of placebo group middle ears had fluid, whereas 61% and 62% of ears in groups 1 and 2, respectively, were dry. These findings were significant. CONCLUSION: Intranasal application of aerosolized metered dose inhaler surfactant alone or with steroid reduced eustachian tube passive opening pressure in normal animals and duration of effusion in animals with experimental OME. Intranasal surfactant reduced the severity and duration of middle ear infection in AOM in this animal model.     

Mucociliary function of the eustachian tube in the eustachian tube dysfunction

Background: Most of the tests to evaluate the eustachian tube (ET) function are focused on the ventilation function of the ET.

Aim: Here we evaluate mucociliary function of the ET in patients with ET dysfunction.

Materials and methods: Ten patients with ET dysfunction were enrolled into the study. Six patients had chronic tympanic membrane retraction and four patients had chronic middle ear effusion (MEE). All patients had intact tympanic membranes. Tympanometry and clinical examinations were done to all patients. Mucociliary function was evaluated with technetium labeled albumin and blue dye. Tympanometry and clinical examinations were done to six patients with chronic tympanic membrane retraction and four patients with chronic middle ear effusion (MEE). Mucociliary function of the ET was evaluated with technetium labeled albumin and blue dye placed into middle ear through an intact tympanic membrane and followed from nasopharynx ET orifice (blue dye) and with gamma camera (technetium).

Results: Blue dye was observed in tubal orifice in six (6 of 10) patients during 30?min observation. Five of those patients (5 of 6) had tympanic membrane retraction and one patient (1 of 6) had MEE. Tracer activity decreased from middle ear in six (6 of 10) patients. Four of those patients had tympanic membrane retraction and two had MEE.

Conclusion: Mucociliary function of the ET seems to be better in patients with tympanic membrane retraction than patients with middle ear effusion.

Significance: Mucociliary function of the ET is an important function for middle ear aeration, blue dye test is easily available to be used also in clinical practice.     

The evaluation of eustachian tube function in patients with chronic otitis media

In this study we evaluated eustachian tube function in patients with chronic otitis media and compared the results with normal subjects. Two different eustachian tube function tests were applied to 60 ears of the chronic otitis media group and 146 ears of the control group. While eustachian tube dysfunction was observed in 71.7% of the chronic suppurative otitis media group, it was only seen in 34.9% of the control group.     

Laser eustachian tuboplasty: two-year results

OBJECTIVE/HYPOTHESIS: Laser eustachian tuboplasty (LETP) combined with appropriate medical management will eliminate the chronic presence of middle ear effusions in selected patients. METHODS: The study population consisted of 13 adults with otitis media with effusion (OME). Patients underwent slow-motion video endoscopy to identify the location and extent of surgical resection. A diode or argon laser was used to vaporize areas of hypertrophic mucosa and submucosa along the cartilaginous eustachian tube. Patients were evaluated at 6, 12, and 24 months. Successful outcome was defined as absence of OME. Patients with evidence of reflux disease or allergic rhinitis were treated with medical therapy before surgery and throughout the follow-up period as indicated. RESULTS: LETP combined with medical management eliminated OME in 36% (4 of 11) of patients at 6 months, 40% (4 of 10) at 1 year, and 38% (3 of 8) at 2 years. Failure of LETP correlated with presence of laryngopharyngeal reflux (P = .01) or allergic disease (P = .05) for the results at 1 year but not at 2 years. CONCLUSIONS: LETP combined with appropriate medical management may be an effective treatment in select patients with chronic persistent eustachian tube dysfunction. A controlled trial with a larger number of subjects will be necessary to determine the efficacy of LETP and identify those factors predictive of successful outcome.     

Laser eustachian tuboplasty: a preliminary report

OBJECTIVES/HYPOTHESIS: Surgical correction of eustachian tube dysfunction remains an elusive challenge. Repeat ventilation tube placement is often inadequate to prevent tympanic membrane and middle ear complications. Endoscopic analyses of eustachian tube dynamics have localized the site of primary pathophysiology to within the cartilaginous tube. The study investigated the feasibility, safety, and efficacy of a new endoluminal eustachian tube operation for the treatment of eustachian tube dysfunction. STUDY DESIGN: Prospective, institutional review board-approved surgical trial in a tertiary-care medical center. METHODS: Ten patients with more than 5 consecutive years of intractable otitis media with effusion recurring after two or more tympanostomy tube placements were treated with unilateral laser eustachian tuboplasty. Surgery was performed on an outpatient basis with the use of general anesthesia and combined both transnasal and transoral approaches. A 980-nm diode or argon laser was used to vaporize an appropriate amount of mucosa and cartilage on the posterior wall of the tubal lumen. Preoperative and postoperative dynamic video eustachian tube function analyses were compared. Outcome measures were presence or absence of middle ear effusion and impedance tympanograms. RESULTS: Five patients had at least 12 months of follow-up, and three of them had absence of any effusion (60%). Two patients had recurrence of their otitis media with effusion and required tympanostomy tubes again. Five patients had at least 6 months of follow-up, and four of them had absence of any effusion. The remaining patient had recurrence of otitis media with effusion and received a tympanostomy tube again. Overall results for all 10 patients after 6 months were 7 free of effusion (70%). There were no intraoperative complications. Postoperative complications were limited to minimal peritubal adhesions and one intranasal synechia. CONCLUSIONS: Preliminary results suggest that laser eustachian tuboplasty is safe and efficacious in the treatment of intractable eustachian tube dysfunction. Further study will be necessary to determine whether laser eustachian tuboplasty is a suitable alternative to repeated tympanostomy tube placement in selected patients.     

Impact of evolution on the eustachian tube

I posit that humans appear to be the only species that develops otitis media. If animals in the wild had developed middle‐ear disease to any significant degree, they would have been selected out during evolution because they would not have survived their predators given the associated hearing loss. Why do humans have otitis media? Evolution has had a significant impact. It is well known that humans are born 12 months too early, which is the result of adaptations to bipedalism and our big brain that, over time, resulted in a relatively small female pelvic outlet compared with nonhuman primates. As a consequence of too early a birth, not only is our immune system immature, but the eustachian tube is too short and floppy in the first year of life. But why is otitis media still common in older individuals? What other adaptation is uniquely human? We developed speech that was associated with descent of the larynx and hyoid bone, which, along with a decrease in prognathism (i.e., facial flattening), resulted in a change in palatal morphology as compared with other primates. Comparative anatomic and physiologic studies have demonstrated significant differences between humans and monkeys, especially in the muscles of the eustachian tube. Paradoxic constriction, as apposed to dilation, on swallowing is a common tubal dysfunction in humans and certain monkey models with chronic middle‐ear effusion. My hypothesis is that chronic otitis media with effusion in patients with tubal constriction is a consequence of adaptation for speech and that, most likely, the levator veli palatini muscle is the cause.     

Gastroesophageal reflux and eustachian tube dysfunction in an animal model

OBJECTIVE: To explore the possible relationship between gastroesophageal reflux and eustachian tube dysfunction in an animal model. STUDY DESIGN: Randomized trial. METHODS: Twenty Sprague-Dawley rats were randomly assigned into two groups, the control (phosphate-buffered saline, n = 10) and experimental (hydrochloric acid [HCl]/pepsin, n = 10) groups. All rats underwent an operation to implant a polyethylene tube into the posterior nasopharynx, through which phosphate-buffered solution or simulated gastric juice (0.5 mg/mL pepsin in 0.01 HCl) was infused at a rate of 0.1 mL/h for 2 0 minutes three times a day for 7 days. Passive opening pressure (POP), passive closing pressure (PCP), active clearance of positive pressure (ACPP) and active clearance of negative pressure (ACNP) were measured before catheter implantation, on postoperative day 5, and after days 1, 3, 5, and 7 of infusion. Mucociliary clearance time (MCCT) was measured after day 7 of infusion. Statistical analysis used a two-way analysis of variance (POP, PCP, ACPP, and ACNP) and Mann-Whitney rank sum test (MCCT). RESULTS: Significant increases in POP (P = .004), PCP (P <.001), ACPP (P <.001), ACNP (P <.001), and MCCT (P <.001) were demonstrated in the HCl/pepsin group compared with the control group. No significant difference was seen between preoperative and postoperative values. CONCLUSIONS: Nasopharyngeal exposure to simulated gastric juice causes eustachian tube dysfunction in rats. Specifically, middle ear pressure regulation and mucociliary clearance of middle ear contents were disabled. These results support recent reports in the literature linking nasopharyngeal reflux to eustachian tube dysfunction and secondary development of otitis media.     

Effects of ciprofloxacin-dexamethasone on myringotomy wound healing

OBJECTIVE: To evaluate the effects of the ciprofloxacin-dexamethasone (CDX) combination ototopical treatment after myringotomy on tympanic membrane (TM) healing in ears with eustachian tube obstruction (ETO) and unobstructed ears. STUDY DESIGN: Prospective, randomized, masked, controlled. METHODS: ETO was created in the left ear of 30 rats to induce a model of otitis media with effusion (OME). After 3 weeks, bilateral myringotomy was performed (day 0). Animals were randomized into three groups to receive no treatment or bilateral once daily ototopical treatment with balanced salt solution (BSS, vehicle) or CDX for 13 days. Bilateral otomicroscopy was performed on days 7, 14, and 28. On day 14, five randomly selected animals per group were humanely euthanized and the TM harvested for histology. Three additional rats provided normal negative control ears for histologic comparisons. RESULTS: On day 14, TM perforation healing rates were 100% in all ears of untreated and BSS-treated animals, 89% (8/9) in CDX-treated obstructed ears, and 30% (3/10) in CDX-treated unobstructed ears (P < .05 vs. BSS). On day 28, 100% (5/5) of the CDX-treated unobstructed ears and 80% (4/5) of the CDX-treated obstructed ears were healed. Histology showed initial TM thickening postmyringotomy in all ears but no significant qualitative differences between groups on day 28. CONCLUSION: Myringotomy healing was transiently modulated by treatment with CDX but proceeded normally after CDX discontinuation. This early modulation might enhance middle ear drainage and middle ear concentrations of CDX when tympanostomy tube surgery is performed in patients with active OME and ETO, thus potentially reducing otorrhea and preventing or treating infection. It would not be expected to increase the risk of premature tube extrusion or adversely affect normal healing of the TM after usual spontaneous extrusion.     

The effects of mastoid aeration on autophony in patients with patulous eustachian tube

The effect of the mastoid pneumatization on sound transmission from the nasopharyngeal cavity to the inner ear, which is one of the important factors to indicate the severity of the patulous eustachian tube (ET), are investigated in patients with patulous ET. Twenty ears of 13 subjects with patulous ET were retrospectively analyzed. Sound transmission from the nasopharyngeal cavity to the inner ear was evaluated by observing the masking effects of noise presented in the nasopharyngeal cavity on the auditory threshold (nasal noise masking audiometry). The relationship between this masking effect and mastoid pneumatization were examined among the patients with similar conditions of ET patency. The masking effect of nasally presented noise was greater with less developed mastoid pneumatization. The present results indicate that the symptoms associated with patulous ET may be more distressful in patients with poorly developed mastoid cavity than in those with well-aerated mastoid under similar conditions of ET patency.     

Histologic changes in eustachian tube mucosa of rats after exposure to gastric reflux

OBJECTIVE: Reflux is thought to be a risk factor for middle ear disease, but the mechanism underlying this relationship is unclear. In this study, we evaluated the effects of reflux on the eustachian tube (ET) mucosa. MATERIALS AND METHODS: Twenty-two healthy 150 to 220 g Wistar rats with normal middle ears were used. The animals were divided into three groups according to exposure time: 1-, 3-, and 12-week exposures. Four rats were used as a control group. An experimental model of gastroesophageal reflux was induced under general anesthesia. After exposure, the animals were sacrificed, and cross sections of the ETs were prepared. The histologic changes in the ET mucosa were observed under a light microscope. RESULTS: The density of goblet cells, numbers of lymphocytes, polymorphonuclear leukocytes, and eosinophils, subepithelial edema, subepithelial vasodilatation, subepithelial gland formation, and intraepithelial gland formation were compared among the groups. The goblet cell density and numbers of lymphocytes and polymorphonuclear leukocytes were significantly higher in the three exposure groups compared with the control group. CONCLUSION: Nasopharyngeal exposure to experimental reflux alters the ET mucosa histopathology, which suggests that gastroesophageal reflux has a role in ET dysfunction.     

咽鼓管-鼓室气流动态法对咽鼓管异常开放症的诊断价值

目的 :探讨咽鼓管异常开放症的检测方法。方法 :比较鼓室导抗图法、Morim itsu法和咽鼓管 -鼓室气流动态法 (TTAG法 )检测 2 0耳咽鼓管异常开放症患者的阳性率。结果 :鼓室导抗图法阳性者 5耳 ,阳性率 2 5 % ,Morim itsu法阳性者 12耳 ,阳性率 6 0 % ,TTAG法阳性者 2 0耳 ,阳性率 10 0 %。结论 :TTAG法是诊断和随访咽鼓管异常开放症最有价值的手段。     

Measurement of middle ear pressure changes during balloon eustachian tuboplasty: a pilot study

Conclusion: The middle ear pressure changes detected during BET can be directly attributed to the balloon inflation and may represent a second, immediate, mechanism of action of BET. BET seems to be safe with respect to the risk of a barotrauma. Further human studies are now necessary to confirm the results and gain more insight into the mechanism of action of BET.

Objective: Since the introduction of Balloon Eustachian Tuboplasty (BET) as a treatment of chronic Eustachian tube dysfunction, the precise mechanism of action is unknown. Long-term effects of BET may be related to observed microfractures of the Eustachian tube cartilage. However, clinical observations indicate a second, immediate mode of action. Therefore, this study investigated and characterized middle ear pressure changes occurring directly during BET procedure.

Methods: Using a micro-optical pressure sensor, pressure changes during BET were monitored transtympanically in a cadaveric animal study using heathland sheep.

Results: Middle ear pressure amplitudes during BET are dependent on the speed of balloon inflation as well as the maximum inflation pressure. A 10-bar inflation pressure yielded a mean middle ear pressure of 5.34?mmHg (71.0 daPA). Negative pressure amplitudes occurring on withdrawal of the balloon catheter are influenced by the speed of withdrawal. No pressure amplitudes capable of causing barotrauma to membranous ear structures could be detected.     

Allergic airway disease and otitis media in children

The occurrence of allergic rhinitis, asthma and otitis media was examined in 395 Indian children living on two separate reservations in Arizona. The children were followed from birth to age 5 years in a study of otitis media. On retrospective review of medical records, 45% of the children at Parker had a clinical diagnosis of allergic airway disease, in contrast to only 6% at San Carlos. At each site, about 55% had recurring otitis media in infancy; of these otitis-prone infants, 40% at Parker and 36% at San Carlos persisted to have 3 or more episodes of otitis media after age 2 years. The only allergic airway disease correlate with otitis media was allergic rhinitis in children age 2-4 years.