FUT2 Variants Confer Susceptibility to Familial Otitis Media.

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202∗) variant co-segregates with otitis media in a Filipino pedigree (LOD = 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p = 1.2 × 10-5) and US trios (TDT p = 0.01). The c.461G>A (p.Trp154∗) variant was also over-transmitted in US trios (TDT p = 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p < 10-7) and increased biodiversity. When all missense and nonsense variants identified in multi-ethnic US trios with CADD > 20 were combined, FUT2 variants were over-transmitted in trios (TDT p = 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants-namely p.Ala104Val, p.Arg138Cys, p.Trp154∗, and p.Arg202∗-reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait.

A2ML1 and otitis media: novel variants, differential expression, and relevant pathways.

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media.

Obstructive Sleep Apnea and Sleep Position: Does It Matter for Infants With a Cleft Palate?

OBJECTIVE: To determine whether nonsupine sleep improves obstructive sleep apnea (OSA) in infants with cleft palate undergoing polysomnography (PSG). DESIGN: Retrospective chart review. SETTING: Tertiary care pediatric hospital. PATIENTS: Twenty-seven infants (1 month to 1 year) with cleft palate with or without cleft lip (CP ± L) undergoing PSG testing for suspected OSA were included. MAIN OUTCOME MEASURES: Polysomnography measures included obstructive apnea-hypopnea index (OAHI), central apnea-hypopnea index (CAHI), oxygen saturation (SpO2) nadir, SpO2, and end-tidal carbon dioxide (ETCO2). RESULTS: Twenty-three PSGs with at least 20 minutes of sleep in both the supine and the nonsupine positions were analyzed. The supine OAHI (mean: 16.8 events/hour; standard deviation [SD]: 18.5) and nonsupine OAHI (mean: 12.6 events/hour; SD: 12.6) did not differ significantly (P = .10). The supine CAHI (mean: 1.9 events/hour; SD: 2.7) and nonsupine CAHI (mean: 3.1 events/hour; SD: 3.7; P = .15), the supine SpO2 nadir (mean: 81.2%; SD: 6.3) and nonsupine SpO2 nadir (mean: 81.8%; SD: 5.3; P = .70), the supine mean SpO2 (mean: 95.5%; SD: 1.9) and nonsupine mean SpO2 saturation (mean: 95.3%; SD: 2.4; P = .34), and the supine ETCO2 (mean: 45.4 mm Hg; SD: 5.3) and nonsupine ETCO2 (mean: 42.5 mm Hg; SD: 10.1; P = .24) were also similar. CONCLUSIONS: There were no significant improvements in OSA metrics during nonsupine sleep in infants with CP ± L. Prior to recommending nonsupine positioning which increases infant's exposure to sudden infant death syndrome risk, we advocate obtaining a PSG to verify an objective improvement in OSA.

Patterns of facial trauma before and after legalization of marijuana in Denver, Colorado: A joint study between two Denver hospitals.

INTRODUCTION: The effect of marijuana on human health has been studied extensively. Marijuana intoxication has been shown to affect performance, attention span, and reaction time. The public health relationship between trauma and cannabis use has also been studied, with mixed conclusions. In this report, the effect of marijuana legalization on many aspects of facial trauma at two hospitals in Denver, Colorado is examined. METHODS: A retrospective review of the electronic medical records was undertaken. Mann-Whitney U tests were used to compare age of patients before and after legalization, and chi squared analyses were used to compare mechanism of injury, and fracture types before and after recreational marijuana legalization in Denver, Colorado. Geographical location of patients was also considered. RESULTS: No significant increase was found in race before and after marijuana legalization (p=0.19). A significant increase in age was found before (M=39.54,SD=16.37), and after (M=41.38,SD=16.66) legalization (p<0.01). Maxillary and skull base fracture proportions significantly increased following legalization (p<0.001 and p<0.001respectively). No significant differences were seen in the proportion of patients who lived in urban and rural counties before and after legalization (p>0.05). CONCLUSION: Public health efforts should be directed towards educating residents and visitors of Colorado on the effects and toxicology of marijuana. More epidemiologic studies are needed for further assessment of the long-term effects of the legalization of marijuana on the population.

A Review of Traditional Vaccine-Preventable Diseases and the Potential Impact on the Otolaryngologist.

Introduction A majority of otolaryngologists have not had direct experience with many vaccine-preventable diseases since the creation of national vaccination programs. Despite the elimination of endemic transmission of some of these diseases in the United States, outbreaks can occur anywhere and still pose a threat to public health around the world. Recent outbreaks and changing trends in exemption rates indicate that it is important for physicians to maintain a working knowledge of how these diseases present and of the recommended treatment guidelines. Objectives This review will evaluate the current state of vaccination rates, vaccine exemption rates and disease incidence in the United States and in the world. It will also examine the clinical presentation and treatment recommendations of these diseases. Data Synthesis United States estimated vaccination rates, vaccine exemption rates and vaccine-preventable disease incidences were obtained from data compiled by the Centers for Disease Control and Prevention. World vaccination rates and disease incidences were obtained from the World Health Organization databases, which compile official figures reported by member states. A PubMed literature review provided information on the current state of vaccination exemptions and outbreaks in the United States. Conclusion Vaccination and vaccine exemption rates continue to put the United States and many areas of the world at risk for outbreaks of vaccine-preventable diseases. Clinical guidelines should be reviewed in the event of a local outbreak.

A Review of Traditional Vaccine-Preventable Diseases and the Potential Impact on the Otolaryngologist

Abstract Introduction A majority of otolaryngologists have not had direct experience with many vaccine-preventable diseases since the creation of national vaccination programs. Despite the elimination of endemic transmission of some of these diseases in the United States, outbreaks can occur anywhere and still pose a threat to public health around the world. Recent outbreaks and changing trends in exemption rates indicate that it is important for physicians to maintain a working knowledge of how these diseases present and of the recommended treatment guidelines. Objectives This review will evaluate the current state of vaccination rates, vaccine exemption rates and disease incidence in the United States and in the world. It will also examine the clinical presentation and treatment recommendations of these diseases. Data Synthesis United States estimated vaccination rates, vaccine exemption rates and vaccine-preventable disease incidences were obtained from data compiled by the Centers for Disease Control and Prevention. World vaccination rates and disease incidences were obtained from the World Health Organization databases, which compile official figures reported by member states. A PubMed literature review provided information on the current state of vaccination exemptions and outbreaks in the United States. Conclusion Vaccination and vaccine exemption rates continue to put the United States and many areas of the world at risk for outbreaks of vaccine-preventable diseases. Clinical guidelines should be reviewed in the event of a local outbreak.