Association between occupational noise exposure level and pure-tone audiometry abnormalities among Metropolitan Manila Development Authority employees: A cross-sectional study.

Traffic enforcers are exposed to various occupational health and safety hazards, including noise pollution, which may lead to occupational hearing loss. This cross-sectional study aimed to estimate the prevalence of hearing loss and to assess the relationship between occupational noise exposure level (ONEL) and abnormalities in air conduction thresholds among Metropolitan Manila Development Authority (MMDA) employees along Epifanio delos Santos Avenue, Philippines. Eight-hour ONELs were measured among 108 participants working with greater than 5 years of service. Participants had hearing evaluations using pure tone audiometry (PTA) to calculate the prevalence of hearing loss. Generalized linear models with a Poisson distribution were fitted to estimate the association between ONEL and audiologic abnormalities, controlling for confounding factors. Approximately 16% of employees had hearing loss. The prevalence of hearing loss was higher with ONEL exposures greater than 85 A-weighted decibels (dBA), with traffic enforcers exposed to higher ONELs than office workers. ONELs greater than 85 dBA were related to audiologic abnormalities at different frequencies in PTA. The prevalence of audiologic abnormalities at 4000 Hz and 6000 Hz was 48% higher (adjusted prevalence ratio [aPR], 1.48; 95% CI, 1.12-1.96) and 25% higher (aPR, 1.25; 95% CI, 1.00-1.55), respectively, among participants with ONELs greater than 85 dBA than with ONELs less than or equal to 85 dBA. Participants exposed to ONELs greater than 85 dBA, more likely traffic enforcers, may have increased risk of audiologic abnormalities. Regular ONEL monitoring is warranted for occupational risk assessment of traffic enforcers. A hearing conservation program may need to be considered for this population. Additional studies are needed to determine trends in hearing deterioration among traffic enforcers.

Lack of Methylation Changes in GJB2 and RB1 Non-coding Regions of Cochlear Implant Patients with Sensorineural Hearing Loss.

Objective: Recent advances in epigenetic studies continue to reveal novel mechanisms of gene regulation and control, however little is known on the role of epigenetics in sensorineural hearing loss (SNHL) in humans. We aimed to investigate the methylation patterns of two regions, one in RB1 and another in GJB2 in Filipino patients with SNHL compared to hearing control individuals. Methods: We investigated an RB1 promoter region that was previously identified as differentially methylated in children with SNHL and lead exposure. Additionally, we investigated a sequence in an enhancer-like region within GJB2 that contains four CpGs in close proximity. Bisulfite conversion was performed on salivary DNA samples from 15 children with SNHL and 45 unrelated ethnically-matched individuals. We then performed methylation-specific real-time PCR analysis (qMSP) using TaqMan® probes to determine percentage methylation of the two regions. Results: Using qMSP, both our cases and controls had zero methylation at the targeted GJB2 and RB1 regions. Conclusion: Our study showed no changes in methylation at the selected CpG regions in RB1 and GJB2 in the two comparison groups with or without SNHL. This may be due to a lack of environmental exposures to these target regions. Other epigenetic marks may be present around these regions as well as those of other HL-associated genes.

Audiologic Measures in an Indigenous Community with A2ML1- and FUT2-Related Otitis Media.

Background: Many indigenous peoples are at elevated risk for otitis media, however there is limited information on hearing loss due to OM in these communities. An Indigenous Filipino community that has previously been described with an elevated prevalence of OM that is due to rare A2ML1 variants and a common FUT2 variant underwent additional phenological testing. In this study, we describe the audiologic profiles in A2ML1- and FUT2-related otitis media and the validity of otoscopy and genotyping for A2ML1 and FUT2 variants in screening for otitis media and hearing loss. Method: We analyzed A2ML1 and FUT2 genotypes together with demographic, otologic and audiologic data from tympanometry and hearing level assessments of 109 indigenous individuals. Results: We confirmed previous findings of a spectrum of nonsyndromic otitis media as associated with A2ML1 variants. A2ML1 and FUT2 variants were associated with high-frequency hearing loss at 4000 Hz. As expected, young age was associated with flat tympanograms, and eardrum perforations due to chronic otitis media were associated with severe-to-profound hearing loss across frequencies. Adding A2ML1 or FUT2 genotypes improved the validity of otoscopy as a screening test to rule out moderate-to-profound hearing loss. Conclusion: Continued multi-disciplinary management and audiologic follow-up using tympanometry and screening audiometry are needed to document and treat otitis media and prevent permanent hearing loss in the indigenous community.

Identification of Novel Candidate Genes and Variants for Hearing Loss and Temporal Bone Anomalies.

Background: Hearing loss remains an important global health problem that is potentially addressed through early identification of a genetic etiology, which helps to predict outcomes of hearing rehabilitation such as cochlear implantation and also to mitigate the long-term effects of comorbidities. The identification of variants for hearing loss and detailed descriptions of clinical phenotypes in patients from various populations are needed to improve the utility of clinical genetic screening for hearing loss. Methods: Clinical and exome data from 15 children with hearing loss were reviewed. Standard tools for annotating variants were used and rare, putatively deleterious variants were selected from the exome data. Results: In 15 children, 21 rare damaging variants in 17 genes were identified, including: 14 known hearing loss or neurodevelopmental genes, 11 of which had novel variants; and three candidate genes IST1, CBLN3 and GDPD5, two of which were identified in children with both hearing loss and enlarged vestibular aqueducts. Patients with variants within IST1 and MYO18B had poorer outcomes after cochlear implantation. Conclusion: Our findings highlight the importance of identifying novel variants and genes in ethnic groups that are understudied for hearing loss.

Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants.

BACKGROUND: Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility. METHODS: We performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues. RESULTS: A large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel SPINK5 variants were identified in 12 families and individuals with OM. A role for SPINK5 in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased SPINK5 expression in human cholesteatoma. CONCLUSION: SPINK5 variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.

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.

When do aided auditory thresholds reach the speech spectrum after cochlear implant switch on?

OBJECTIVES: This paper aims to determine the length of time before a cochlear implantee would reach aided hearing threshold of METHODS: From January 2009 to February 2011, the aided earing thresholds of 41 prelingually deaf children with cochlear implants after switch on were reviewed. RESULTS: There were 21 males and 20 females. Majority of children 7 years old reached it at CONCLUSION: Sixty-six percent of the children with cochlear nplants reached the target threshold within the first 3 months post fitting and 80% within the first 6 months post fitting. More of the older children reached target threshold earlier than the younger children. There was a trend that more females reached the target threshold earlier than the males but this was not statistically significant.

Auditory brainstem response latencies of infants and maternal eposure to environmental toxic product

OBJECTIVE: To explore the effects of pesticide exposure on the auditory system, specifically on hearing status based on auditory brainstem responses. METHODS: A cohort of pregnant women was identified in several communities in a rural area from April 2002 to February 2003 and followed up until delivery. Mother-infant dyads were assessed for exposure to pesticides. Maternal and fetal exposures to environmental toxic products were determined by measuring levels in maternal hair and blood, and infant cord blood, hair, and meconium, respectively. Hearing status was measured using otoacoustic emissions (OAE) and confirmed by diagnostic auditory brainstem responses (ABR) measured at 80, 60, and 40 decibels. Waves I, III, V were identified and absolute latencies measured, including inter-peak latencies from waves 11III, I-V, and III-V. Pesticide exposure was then correlated with latencies of Waves I, III, V, and interpeak latencies of waves I-III, IIV, and III-V. Hearing loss and pesticide exposures were correlated with Griffiths Mental Development Scores (GMDS). RESULTS: Significant delays in the ABR wave latencies were noted in the group with exposure to pesticides. Propoxur was the most common toxic product detected in infants and meconium the best substrate for its detection. There was a 1.4% risk of hearing loss with exposure to propoxur (RR=0.52 (0.12-2.30), p = 0.06), a 6.25% risk with cypermethrin exposure (RR= 4.53 (0.61133.64), P = 0.10) and 6.25% risk with pretilachlor exposure (3.13 (0.44-22.30), p = 0.07). Griffith's Mental Developmental Scale scores (GMDS- hearing and speech subscale and general quotient scores) were not significantly different between exposed and unexposed groups. However, three infants with positive exposures and hearing loss had below average, or low to average scores using this scale. CONCLUSION: Maternal exposure to environmental toxic products may affect the auditory pathway in infants at birth. Pregnant women should limit their exposure to such toxic products in order to avoid neurodevelopmental effects particularly on hearing because this is very important in the critical stage of language and speech development.

Neonatal hearing screening in a neonatal intensive care unit using distortion-product otoacoustic emissions.

OBJECTIVE: To determine pass and refer rates, and identify risk factors relating to refer responses, in neonates screened using distortion-product otoacoustic emissions (DPOAEs). MATERIAL AND METHODS: A total of 435 neonates admitted to the neonatal intensive care unit (NICU) of the Philippine General Hospital between May and October 2000 were screened using DPOAEs within 48 h of admission. RESULTS: The male:female ratio in the sample was 1.05. In total, 56% of neonates were born preterm, the mean birthweight was 2,428.39 +/- 710.39 g and 8.9% weighed < 1,500 g. In total, 47.9% were delivered by Caesarian section and 44.9% were delivered vaginally. Almost 14% of neonates had 1-min Apgar scores of < 6, and 4% had 5-min Apgar scores of < 7. Approximately 95% of neonates had a poor perinatal history. Using pediatric aging it was noted that 46% of these neonates were born preterm. and 30.4% were small for gestational age. At least one neonatal disease was found in 42% of neonates, whilst 95.7% had to be given medication. The bilateral refer rate was 29.1%. Two-by-two analysis of risk factors for hearing loss and DPOAE measurements showed that only male sex seemed to have a significant association with a refer response. Neonates weighing < 1,500 g at birth showed a marginally significant association with a refer response (p = 0.07). All other neonates showed no crude association with DPOAE measurements. CONCLUSION: These preliminary data show that a high proportion of NICU patients may have poor outer hair cell function, and thus poor hearing. In order to develop an effective neonatal hearing screening program, further studies of prevalence and risk factors should be pursued in the same setting.