Dataset Information

Biomarkers of Systemic Inflammation and Risk of Incident Hearing Loss.

ABSTRACT: BACKGROUND:Chronic inflammation may lead to cochlear damage, and the only longitudinal study that examined biomarkers of systemic inflammation and risk of hearing loss found an association with a single biomarker in individuals <60 years of age. The purpose of our study was to determine whether plasma inflammatory markers are associated with incident hearing loss in two large prospective cohorts, Nurses' Health Studies (NHS) I and II. METHODS:We examined the independent associations between plasma levels of markers of systemic inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and soluble tumor necrosis factor receptor 2 [TNFR-2]) and self-reported hearing loss. The participants in NHS I (n = 6194 women) were 42 to 69 years of age at the start of the analysis in 1990, while the participants in NHS II (n = 2885 women) were 32 to 53 years in 1995. After excluding women with self-reported hearing loss before the time of blood-draw, incident cases of hearing loss were defined as those women who reported hearing loss on questionnaires administered in 2012 in NHS I and 2009 or 2013 in NHS II. The primary outcome was hearing loss that was reported as moderate or worse in severity, pooled across the NHS I and NHS II cohorts. We also examined the pooled multivariable-adjusted hazard ratios for mild or worse hearing loss. Cox proportional hazards regression was used to adjust for potential confounders. RESULTS:At baseline, women ranged from 42 to 69 years of age in NHS I and 32 to 53 years of age in NHS II. Among the NHS I and II women with measured plasma CRP, there were 628 incident cases of moderate or worse hearing loss during 100,277 person-years of follow-up. There was no significant association between the plasma levels of any of the three inflammatory markers and incident moderate or worse hearing loss (multivariable-adjusted pooled p trend for CRP = 0.33; p trend IL-6 = 0.54; p trend TNFR-2 = 0.70). There was also no significant relation between inflammatory marker levels and mild or worse hearing loss. While there was no significant effect modification by age for CRP or IL-6 in NHS I, there was a statistically significant higher risk of moderate or worse hearing loss (p interaction = 0.02) as well as mild or worse hearing loss (p interaction = 0.004) in women ?60 years of age who had higher plasma TNFR-2 levels. CONCLUSIONS:Overall, there was no significant association between plasma markers of inflammation and risk of hearing loss.

SUBMITTER: Gupta S

PROVIDER: S-EPMC6500774 | biostudies-literature | 2019 Jul/Aug

REPOSITORIES: biostudies-literature

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Biomarkers of Systemic Inflammation and Risk of Incident Hearing Loss.

Gupta Shruti S Curhan Sharon G SG Curhan Gary C GC

Ear and hearing 20190701 4

<h4>Background</h4>Chronic inflammation may lead to cochlear damage, and the only longitudinal study that examined biomarkers of systemic inflammation and risk of hearing loss found an association with a single biomarker in individuals <60 years of age. The purpose of our study was to determine whether plasma inflammatory markers are associated with incident hearing loss in two large prospective cohorts, Nurses' Health Studies (NHS) I and II.<h4>Methods</h4>We examined the independent associatio ...[more]

PMID: 30399011

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Project description:ImportanceBecause hearing loss is highly prevalent and treatable, determining its association with morbidity has major public health implications for disease prevention and the maintenance of health in adults with hearing loss.ObjectiveTo investigate the association between the diagnosis of incident hearing loss and medical comorbidities in adults 50 years or older.Design, setting, and participantsRetrospective, propensity-matched cohort study using administrative claims data from commercially insured and Medicare Advantage members in a geographically diverse US health plan. Adults 50 years or older with claims for services rendered from January 1, 2000, to December 31, 2016, were observed for 2 (n = 154 414), 5 (n = 44 852), and 10 (n = 4728) years. This research was conceptualized and data were analyzed between September 2016 and November 2017.ExposuresA claim for incident hearing loss is defined as 2 claims for hearing loss within 2 consecutive years without evidence of hearing device use, excluding claims for sudden hearing loss or hearing loss secondary to medical conditions.Main outcomes and measuresIncident claims for dementia, depression, accidental falls, nonvertebral fractures, acute myocardial infarction, and stroke.ResultsAfter cohort matching, 48% of participants were women (n = 74 464), 61% were white (n = 93 442), and 31% (n = 48 056) were Medicare Advantage insured, with a mean (SD) age of 64 (10) years. In a multivariate-adjusted modified Poisson regression with robust standard errors, relative associations were strongest for dementia (relative risk at 5 years, 1.50; 95% CI, 1.38-1.64) and depression (relative risk at 5 years, 1.41; 95% CI, 1.26-1.58). The absolute risk of all outcomes was greater in persons with hearing loss than in those without hearing loss at all times, with the greatest risk difference observed at 10 years for all outcomes. The 10-year risk attributable to hearing loss was 3.20 per 100 persons (95% CI, 1.76-4.63) for dementia, 3.57 per 100 persons (95% CI, 1.67-5.47) for falls, and 6.88 per 100 persons (95% CI, 4.62-9.14) for depression.Conclusions and relevanceIn this large observational study using administrative claims data, incident untreated hearing loss was associated with greater incident morbidity than no hearing loss across a range of health conditions. Future studies are needed to elucidate the mechanisms underlying these associations and to determine if treatment for hearing loss could reduce the risk of comorbidity.

Project description:BackgroundCryopyrin-associated periodic syndrome (CAPS) is an inherited autoinflammatory disease caused by a gain-of-function mutation in NLRP3. Although CAPS patients frequently suffer from sensorineural hearing loss, it remains unclear whether CAPS-associated mutation in NLRP3 is associated with the progression of hearing loss.MethodsWe generated a mice with conditional expression of CAPS-associated NLRP3 mutant (D301N) in cochlea-resident CX3CR1 macrophages and examined the susceptibility of CAPS mice to inflammation-mediated hearing loss in a local and systemic inflammation context.FindingsUpon lipopolysaccharide (LPS) injection into middle ear cavity, NLRP3 mutant mice exhibited severe cochlear inflammation, inflammasome activation and hearing loss. However, this middle ear injection model induced a considerable hearing loss in control mice and inevitably caused an inflammation-independent hearing loss possibly due to ear tissue damages by injection procedure. Subsequently, we optimized a systemic LPS injection model, which induced a significant hearing loss in NLRP3 mutant mice but not in control mice. Peripheral inflammation induced by a repetitive low dose of LPS injection caused a blood-labyrinth barrier disruption, macrophage infiltration into cochlea and cochlear inflammasome activation in an NLRP3-dependent manner. Interestingly, both cochlea-infiltrating and -resident macrophages contribute to peripheral inflammation-mediated hearing loss of CAPS mice. Furthermore, NLRP3-specific inhibitor, MCC950, as well as an interleukin-1 receptor antagonist significantly alleviated systemic LPS-induced hearing loss and inflammatory phenotypes in NLRP3 mutant mice.InterpretationOur findings reveal that CAPS-associated NLRP3 mutation is critical for peripheral inflammation-induced hearing loss in our CAPS mice model, and an NLRP3-specific inhibitor can be used to treat inflammation-mediated sensorineural hearing loss.FundingNational Research Foundation of Korea Grant funded by the Korean Government and the Team Science Award of Yonsei University College of Medicine.

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Biomarkers of Systemic Inflammation and Risk of Incident Hearing Loss.

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Biomarkers of Systemic Inflammation and Risk of Incident Hearing Loss.

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