Clinical and experimental evidences show that disruption of the mechanism for middle ear (ME) pressure regulation is associated with pathophysiological changes including the development of significant under- pressures and mucosal inflammation that if prolonged results in otitis media with effusion (OME). Adequate regulation of ME pressure requires that the intermittent transient openings of the Eustachian tube (ET) provide a sufficient quantity of gas to balance the net glasses associated with the gradient driven exchange between the ME and blood. Poor ET function causes ME under-pressures and OME by the hydrops ex vacuo mechanism, the validity of which has been convincingly demonstrated in experiments conducted under this program. Indeed, treatments for OME that bypass the ET to supply the ME with gas were shown in clinical trials to promote disease resolution. ET function tests in children and adults with concurrent diseases that predispose them to OME show changes in intraluminal congestion that present as a decreased efficiency of the muscular assisted mechanism of tubal dilation. Other studies in children """"""""t risk"""""""" for OME and with concomitant OME, show a primary impairment of the active mechanism for tubal openings. However, the prognostic value of ET function tests with respect to disease course is limited, provoking controversy as to the role of ET dysfunction in the pathogenesis of OME. Recent studies conducted under this program show that the discordance between disease progression and test results may be explained by the failure of current test protocols to assess concurrently the functional demand placed upon the ET by the varying rates of transmucosal gas exchange. The overall objective of this project is to develop clinically applicable tests for ME pressure regulation that assess simultaneously these demand and supply functions. Also evaluated is the effect of measured test parameters associated with mucosal healing. Because histopathological studies cannot demonstrate an anatomic basis for poor ET function, new MRI imaging techniques will be used in an attempt to relate in vivo ET structure and function. The goals of this project are to develop a better understanding of ME pressure-dysregulation in the pathogenesis of OME, to evaluate the prognostic value of newly developed test protocols for assessing that function, to identify the underlying cause(s) of ET dysfunction, and to utilize this knowledge in suggesting new treatment strategies for OME..

Project Start
1999-07-01
Project End
2000-06-30
Budget Start
Budget End
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Children's Hosp Pittsburgh/Upmc Health Sys
Department
Type
DUNS #
044304145
City
Pittsburgh
State
PA
Country
United States
Zip Code
15224
Doyle, William J; Swarts, J Douglas (2010) Eustachian tube-Tensor veli palatini muscle-cranial base relationships in children and adults: an osteological study. Int J Pediatr Otorhinolaryngol 74:986-90
Doyle, William J; Yuksel, Sancak; Banks, Juliane et al. (2007) Directional asymmetry in the measured nitrous oxide time constant for middle ear transmucosal gas exchange. Ann Otol Rhinol Laryngol 116:69-75
Doyle, William J (2007) The mastoid as a functional rate-limiter of middle ear pressure change. Int J Pediatr Otorhinolaryngol 71:393-402
Li-Korotky, Ha-Sheng; Kelly, Lori A; Piltcher, Otavio et al. (2007) Evaluation of microbial RNA extractions from Streptococcus pneumoniae. J Microbiol Methods 68:342-8
Chad Kanick, S; Kasi, Sundeep; Douglas Swarts, J et al. (2006) Accuracy of CO2 conductance predicted using a morphometric model of the middle ear mucosa. Acta Otolaryngol 126:1252-9
Yuksel, Sancak; Doyle, William J; Banks, Juliane et al. (2005) Nasal prostaglandin challenge increases N2O exchange from blood to middle ear. Auris Nasus Larynx 32:29-32
Kanick, Stephen Chad; Doyle, William J; Ghadiali, Samir N et al. (2005) On morphometric measurement of oxygen diffusing capacity in middle ear gas exchange. J Appl Physiol 98:114-9
Chen, Anton; Li, Ha-Sheng; Hebda, Patricia A et al. (2005) Gene expression profiles of early pneumococcal otitis media in the rat. Int J Pediatr Otorhinolaryngol 69:1383-93
Casselbrant, Margaretha L; Mandel, Ellen M; Rockette, Howard E et al. (2004) The genetic component of middle ear disease in the first 5 years of life. Arch Otolaryngol Head Neck Surg 130:273-8
Li-Korotky, Ha-Sheng; Swarts, J Douglas; Hebda, Patricia A et al. (2004) Cathepsin gene expression profile in rat acute pneumococcal otitis media. Laryngoscope 114:1032-6

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