Chronic Inflammation and Hearing Loss: Key Biomarkers and Subgroup Differences by Gender and BMI in a National Cohort

Abstract

Background: Hearing loss (HL) significantly impacts quality of life and economic status worldwide. Chronic inflammation is suggested to influence hearing, yet the connection with inflammation-related indexes in the general population is not well understood.

Methods: This cross-sectional study analyzed data from 7231 adults from six cycles (2005-2012 and 2015-2018) of the National Health and Nutrition Examination Survey (NHANES). It examined the correlation between systemic immune-inflammatory biomarkers (NLR, SII, PLR, and LMR) and auditory threshold shifts/HL using multivariable logistic regression models. Smooth curve fitting visualized the association, and log-likelihood ratio tests determined the existence of thresholds in biomarker effects, supplemented by subgroup analyses.

Results: After adjustments, significant associations were found for low-frequency HL with ln-transformed NLR (OR = 1.29, 95% CI: 1.06-1.56, p = 0.0116), ln-SII (OR = 1.31, 95% CI: 1.08-1.59, p = 0.0065), and ln-LMR (OR = 0.74, 95% CI: 0.60-0.91, p = 0.00043). For high-frequency HL, similar patterns were observed for ln-SII (OR = 1.25, 95% CI: 1.05-1.48, p = 0.0105) and ln-LMR (OR = 0.76, 95% CI: 0.64-0.90, p = 0.007); however, the association with ln-NLR did not reach statistical significance (OR = 1.18, 95% CI: 1.00-1.40, p = 0.0562). NLR and SII positively correlated with HL, while LMR showed a negative correlation. No significant association was noted with PLR. Dose-response relationships were observed, particularly between LMR and all categorized frequencies of HL and between SII and high-frequency HL. Subgroup analyses indicated that NLR and SII are risk factors for HL in healthy BMI males, with LMR being more protective in males, the elderly, and diabetics.

Conclusions: Systemic inflammation-related indexes, especially SII, are predictive of both high- and low-frequency HL, highlighting the role of inflammatory homeostasis in hearing health. LMR may offer protective effects, particularly in specific subgroups. These findings suggest potential targets for HL treatment by regulating inflammation, warranting further investigation into their clinical application.

Keywords: NHANES; hearing loss; inflammatory biomarkers; population‐based study; systemic immune‐inflammation index.

Figure 1

Flowchart of participant selection. From 60,015 NHANES participants (2005–2012, 2015–2018), 44,733 were excluded for missing NLR/SII/LMR/PLR and audiometric data, 5487 were under age 19, 1669 had abnormal tympanometry, otoscopic exam, or upper respiratory infections, and 895 had inadequate covariate data, resulting in a final sample of 7231 participants.

Figure 2

Visualization of the relationship between inflammatory index and HL. A, A1, and A2 show the relationship between NLR and low‐freq, speech‐freq, and high‐freq HL. B, B1, and B2 show the relationship between SII and low‐freq, speech‐freq, and high‐freq HL. C, C1, and C2 show the relationship between PLR and low‐freq, speech‐freq, and high‐freq HL. D, D1, and D2 show the relationship between LMR and low‐freq, speech‐freq, and high‐freq HL. The blue lines represent the fitted regression lines, and the red lines represent the 95%.

Figure 3

1. Interaction effects of various factors on the relationship between NLR and HL. A: Interaction effects between NLR and low‐freq HL. No interaction effects were detected among the subgroups. B: Interaction effects between NLR and high‐freq HL. Interaction effects were detected in the gender and BMI subgroups, with p for interaction < 0.05. 2. Interaction effects of various factors on the relationship between SII and HL. A: Interaction effects between SII and low‐freq HL. No interaction effects were detected among the subgroups. B: Interaction effects between SII and high‐freq HL. Interaction effects were detected in the gender and BMI subgroups, with p for interaction < 0.05. 3. Interaction effects of various factors on the relationship between LMR and HL. A: Interaction effects between LMR and low‐freq HL. No interaction effects were detected among the subgroups. B: Interaction effects were detected in the gender, age, and diabetes subgroups, with p for interaction < 0.05.

Figure 4

The role of cochlear macrophages in hearing loss: pathway and activation. Monocytes enter the spiral ligament through the microvascular network of the stria vascularis and differentiate into macrophages. Both transformed macrophages and resident cochlear macrophages become activated and contribute to hearing loss. The diagram shows key cochlear structures, including the stria vascularis, spiral ligament, scala vestibuli, scala tympani, spiral limbus, and basilar membrane. Macrophage activation may be a mechanism of immune‐related hearing loss.