This prospective twin study is designed to determine the genetic component in otitis media (OM) by using like-sex mono- and dizygotic (MZ and DZ) twins. The twin pairs enrolled as newborns are examined at monthly intervals. At each monthly visit an interval history is obtained and middle ear status and hearing sensitivity (every two months) are assessed. Zygosity testing is performed at age one year and consists of extensive red blood cell marker and enzyme determination which gives a probability of greater than 0.99 for monozygosity in completely concordant pairs. The advantages of this study design are two-fold. First, the use of twins allows for separation of genetic and environmental factors in predisposition to OM. Second, the prospective aspect allows for the accurate assessment of disease state and eliminates dependency on recalled information. In this unique cohort of children with documentation of middle ear status since birth, the heritability of immune status can also be assessed and information gained will enhance our understanding of the pathogenesis, complications and sequelae of the disease. Should a substantial genetic component be defined, this study would make a significant clinical contribution by influencing the primary care physician to identify the siblings and offspring of affected patients as """"""""high risk"""""""" cases. Closer surveillance of patients at risk for OM could result in earlier detection, treatment and avoidance of possible developmental problems. The study design will also provide the incidence, prevalence, and natural history of OM in this young population. In addition, blood samples for DNA extraction and B-cell immortalization will be collected from all children. The DNA and Epstein-Barr virus immortalized cell lines will be used to establish a specimen repository for future molecular genetic studies including quantitative trait loci mapping. The present proposal is only requesting funds to complete the follow-up of enrolled twin pairs and perform the data analysis.
| 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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