
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

39312354
MD-D-24-01744
00055
10.1097/MD.0000000000039711
3
6600
Research Article
Observational Study
Association between the systemic immune-inflammation index and hearing loss: A cross-sectional study of NHANES 2005 to 2018
Zhao Limei MS 1663028657@qq.com
a
Zhang Xi MS 2458739637@qq.com
b
https://orcid.org/0009-0005-4573-6286
Chen Lu MD a*
a Department of Otolaryngology Head and Neck Surgery, Jiangjin Hospital of Chongqing University, Chongqing University, Chongqing, China
b Department of Gastroenterology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
* Correspondence: Lu Chen, Department of Otolaryngology Head and Neck Surgery, Jiangjin Hospital of Chongqing University, Chongqing University, Chongqing 401331, China (e-mail: cl18166470599@163.com).
20 9 2024
20 9 2024
103 38 e3971119 2 2024
31 5 2024
23 8 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

The relationship between systemic inflammation and hearing loss (HL) remains unclear. To investigate the association between the systemic immune-inflammation index (SII) and objective HL, this study was performed. Participants from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2018 were analyzed. Two types of hearing loss were investigated: speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL). The SII score was constructed using the levels of peripheral neutrophil (N), lymphocyte (L), and platelet (P), and was defined as P multiplied by N/L (in units of 109/L). Weighted multivariable logistic regression and subgroup analysis were used to examine the relationship between HL and high-SII group (≥330 × 109/L). A total of 6428 participants were included in the study. This study found that the high-SII group was positively associated with a higher risk of HL (OR: 1.29, 95% CI: 1.05–1.57, P < .05) and HFHL (OR: 1.24, 95% CI: 1.05–1.46, P < .05), but not significant for SFHL (OR: 1.13, 95% CI: 0.94–1.37, P > .05). Subgroup analysis showed that this association was similar in different age groups. Finally, sensitivity analysis confirmed the robustness of the association. In the full model, increasing SII index per SD was associated with HL (OR: 1.17, 95% CI: 1.09–1.26, P < .001) and HFHL (OR: 1.13, 95% CI: 1.06–1.21, P < .001). The significance of SFHL was not detected with the increasing SII index (OR: 1.13, 95% CI: 0.94–1.37, P > .05). SII score was associated with HL and HFHL in the general adult population of the United States, but was not significantly correlated with SFHL.

hearing loss
inflammation
NHANES
systemic immune-inflammation index
OPEN-ACCESSTRUE
==== Body
pmc 1. Introduction

Hearing loss (HL) is a widespread global public health concern.[1] Its impact extends beyond the realms of physical and psychological well-being of individuals, exerting a considerable socioeconomic toll on both families and societies.[2] Hearing impairment affects learning, work, and quality of life, leading to reduced social communication, emotional instability, and cognitive dysfunction.[3] Factors contributing to HL include genetics, environmental risk factors, birth complications, infectious diseases, chronic ear infections, noise exposure, ototoxic drugs, and aging.[4–7] The search for novel risk factors or biomarkers to assess the risk of developing HL is gaining momentum and is anticipated to pave the way for new preventive measures.

The systemic immune-inflammation index (SII) is a novel and integrated inflammatory biomarker that reflects the local immune response and systemic inflammation throughout the human body.[8] SII is a quantitative indicator that combines information about the peripheral blood cell counts, particularly neutrophils, lymphocytes, and platelets. It is designed to provide insights into the balance between systemic immune responses and inflammatory processes in the body. The SII has gained attention in medical research due to its potential as a prognostic marker in various diseases, including cardiovascular diseases, and infectious diseases. It’s believed that a higher SII could indicate a more dysregulated balance between immune and inflammatory responses, which might contribute to disease progression or severity.[9]

Relevant studies have also confirmed that the SII exhibits strong prognostic value for tumors.[10–13] Additionally, SII has a high prognostic value for chronic diseases induced by chronic inflammation or immune dysfunction.[14,15] Regarding its potential association with HL, research is ongoing to explore the link between systemic inflammation and hearing impairment. Chronic inflammation has been implicated in various health conditions, including those affecting the auditory system. Inflammation may impact the blood vessels and nerves within the ear, further affecting hearing function.

Animal experiments have indicated an association between immune function and HL.[16] In addition, observational studies have shown an association between plasma inflammatory markers and HL.[17,18] Moreover, studies have also demonstrated that systemic inflammation may impact the function of hair cells.[19] However, evidence regarding the relationship between SII and HL is limited. Furthermore, the underlying mechanism of this association is still largely unknown.

In this study, we investigated the association between SII and HL in adults by utilizing a large sample of individuals from the National Health and Nutrition Examination Survey (NHANES), which may provide more evidence for early intervention for HL.

2. Methods

2.1. Study population

NHANES is a prominent initiative of the National Center for Health Statistics, comprising a continuous series of cross-sectional surveys. It aims at gauging the health and nutritional well-being of both children and adults in the United States. To secure a representative sample of the population, NHANES employs a multistage probability sampling design. The program gathers information via extensive home interviews. The face to face interview collected information including various health-related behaviors, environmental exposures, and lifestyles that could influence health risk factors. Additionally, specialized mobile examination centers (MECs) are utilized to carry out physical examinations and medical history interviews. For further details on NHANES, please visit the program’s website at https://www.cdc.gov/nchs/nhanes/index.htm.

Our study recruited participants from NHANES surveys conducted between 2005 and 2018, inclusive of the years 2005 to 2006, 2007 to 2008, 2009 to 2010, 2011 to 2012, 2013 to 2014, 2015 to 2016, and 2017 to 2018. We included individuals aged 20 years and older who provided blood samples for biomarker detection and underwent measurements of weight, height, and hearing. NHANES surveys were conducted with the approval of the National Health Statistics Research Ethics Review Board, and all participants provided informed consent before taking part in the study.

2.2. Audiometric measures and hearing loss

Our study utilized data from the Examination Database to evaluate HL. In NHANES, all age-eligible participants are required to undergo a hearing test. However, participants with hearing aids that could not be removed for testing, as well as those experiencing earaches that could not tolerate headphones, were excluded from the audiometric component. Furthermore, individuals who self-reported ear disease, had excessive cerumen, or displayed abnormal otoscopy findings were excluded. Before the audiometric testing, an ambient noise survey was conducted using a Quest 1800 sound level meter (Quest, Idaho, America). The examiners at the MEC administered all the audiometric examinations to the participants. Hearing threshold tests were performed on the participants’ left and right ears at frequencies of 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz. The modified Hughson Westlake procedure was utilized for the testing, and the automatic test mode of the audiometer was employed. The audiometric components employed included an Interacoustics Model AD226 audiometer (William Demant, Denmark) with standard TDH-39 headphones (GN Otometrics, Denmark) and Etymotic EarTone 3A insert earphones (Illinois). The examiners were trained by certified audiologists at the National Institute for Occupational Safety and Health.

In this study, HL was defined as pure-tone averages exceeding 25 dB in both ears. Participants were considered to have HL if their hearing thresholds were >25 dB in either ear at any frequency, including 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz.[20] Furthermore, 2 distinct types of HL were investigated, namely speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL), which are not mutually exclusive. The hearing thresholds for SFHL were assessed at 500, 1000, 2000, and 4000 Hz, while those for HFHL were evaluated at 3000, 4000, and 6000 Hz.[21]

2.3. Assessment of systemic immune-inflammation index

The term of SII was initially proposed by Hu et al[8] to assess the prognostic value of several diseases. The SII was constructed using the levels of peripheral neutrophil (N), lymphocyte (L), and platelet (P), and was defined as P multiplied by N/L (in units of 109/L). Based on earlier studies of the NHANES, we established a cutoff value of 330 × 109/L for all subsequent analyses.[22]

2.4. Covariates

Participants self-reported age, gender, race/ethnicity, education level, family income-to-poverty ratio, smoking history, and alcohol drinking history.[23] Race/ethnicity was divided into non-Hispanic Black, non-Hispanic White, Hispanic/Mexican, and other races. The family income-to-poverty ratio was classified into low (<1.5), median (1.5–3.5), and high (>3.5). Body mass index (BMI) was divided into 4 groups, including 0 to 19.9 km/m2, 20 to 24.9 kg/m2, 25 to 29.9 kg/m2, and more than 30 kg/m2. Smoking status and alcohol drinking were former, never, and current, respectively. Self-reported chronic diseases composed of cardiovascular disease, diabetes, hypertension, and stroke were obtained as yes or no.

2.5. Statistical analysis

To compare the SII subgroups, we employed the Chi-square test to analyze categorical variables (n and percent). Furthermore, we conducted multivariate logistic regression analyses to examine the relationship between SII and HL, SFHL, and HFHL. The NHANES MEC examination weights were used for data analysis. Model 1 was adjusted for no covariates, while Model 2 was a minimally-adjusted model accounting for age, sex, education, race, and family income-to-poverty ratio. Model 3 was adjusted for a broader range of covariates, including age, sex, education, race, family income-to-poverty ratio, BMI, alcohol consumption, cardiovascular disease, diabetes mellitus, hypertension, and stroke. We conducted age-stratified subgroup analysis to clarify the impact of SII. In addition, stratified logistic regression analyses were performed to identify variables that modify the association in participants aged 20 to 50. We also conducted sensitivity analyses using a linear regression model, wherein SII was taken as a continuous variable, and similar variable inclusion was adopted. Furthermore, we performed subgroup analyses of age between those under 50 years old and those aged 50 or above in the linear regression model.[24] All analyses were conducted utilizing R software version 4.2 (http://www.R-project.org; The R Foundation). We set P < .05 (2-sided) as the threshold for a significant difference.

3. Results

3.1. Characteristics of the study population

A total of 6428 participants were included in the study. Characteristics of included participants were shown in Table 1. Of these participants, 4106 (64.9%) exhibited hearing loss, with 2743 (42.7%) of them demonstrating SFHL, and 3525 (54.8%) showing HFHL. Among the participants, 3488 (54.3%) were aged 50 years and above, 3437 (53.5%) were male, 2662 (41.4%) were non-Hispanic White, 5018 (78.1%) had attained education beyond high school, and 1989 (30.9%) had an income-to-poverty ratio above 3.5.

Table 1 General characteristics of the participants in NHANES 2005 to 2018 (n = 6428).

Variables	SII (109/L)	Overall	P value	
<330	≥330	
(N = 1792)	(N = 4636)	(N = 6428)	
Age (yr)				.178	
 <50	795 (44.4%)	2145 (46.3%)	2940 (45.7%)		
 ≥50	997 (55.6%)	2491 (53.7%)	3488 (54.3%)		
Sex				<.001	
 Female	715 (39.9%)	2276 (49.1%)	2991 (46.5%)		
 Male	1077 (60.1%)	2360 (50.9%)	3437 (53.5%)		
Race/ethnicity				<.001	
 Mexican American	186 (10.4%)	609 (13.1%)	795 (12.4%)		
 Non-Hispanic Black	605 (33.8%)	826 (17.8%)	1431 (22.3%)		
 Non-Hispanic White	563 (31.4%)	2099 (45.3%)	2662 (41.4%)		
 Other Hispanic	160 (8.9%)	469 (10.1%)	629 (9.8%)		
 Other races	278 (15.5%)	633 (13.7%)	911 (14.2%)		
Education				.03	
 Less than high school	118 (6.6%)	333 (7.2%)	451 (7.0%)		
 High school	236 (13.2%)	721 (15.6%)	957 (14.9%)		
 Above high school	1437 (80.2%)	3581 (77.2%)	5018 (78.1%)		
 Missing	1 (0.1%)	1 (0.0%)	2 (0.0%)		
The ratio of income poverty				.42	
 0–1.5	563 (31.4%)	1441 (31.1%)	2004 (31.2%)		
 1.5–3.5	524 (29.2%)	1427 (30.8%)	1951 (30.4%)		
 3.5–	571 (31.9%)	1418 (30.6%)	1989 (30.9%)		
 Missing	134 (7.5%)	350 (7.5%)	484 (7.5%)		
BMI (kg/m2)				<.001	
 <20	87 (4.9%)	162 (3.5%)	249 (3.9%)		
 20–24.9	498 (27.8%)	1174 (25.3%)	1672 (26.0%)		
 25–29.9	623 (34.8%)	1485 (32.0%)	2108 (32.8%)		
 30–	584 (32.6%)	1815 (39.2%)	2399 (37.3%)		
Smoking				.018	
 Former	435 (24.3%)	1185 (25.6%)	1620 (25.2%)		
 Never	1037 (57.9%)	2564 (55.3%)	3601 (56.0%)		
 Now	320 (17.9%)	887 (19.1%)	1207 (18.8%)		
Alcohol drinking				.558	
 Current	1016 (56.7%)	2598 (56.0%)	3614 (56.2%)		
 Former	284 (15.8%)	669 (14.4%)	953 (14.8%)		
 Never	233 (13.0%)	602 (13.0%)	835 (13.0%)		
 Missing	259 (14.5%)	767 (16.5%)	1026 (16.0%)		
Cardiovascular disease				.796	
 No	1626 (90.7%)	4195 (90.5%)	5821 (90.6%)		
 Yes	166 (9.3%)	441 (9.5%)	607 (9.4%)		
Diabetes				.018	
 No	1367 (76.3%)	3401 (73.4%)	4768 (74.2%)		
 Yes	425 (23.7%)	1235 (26.6%)	1660 (25.8%)		
Hypertension				.045	
 No	1090 (60.8%)	2691 (58.0%)	3781 (58.8%)		
 Yes	702 (39.2%)	1945 (42.0%)	2647 (41.2%)		
Stroke				.200	
 No	1745 (97.4%)	4484 (96.7%)	6229 (96.9%)		
 Yes	47 (2.6%)	152 (3.3%)	199 (3.1%)		
HL				<.001	
 No	708 (39.5%)	1614 (34.8%)	2322 (36.1%)		
 Yes	1084 (60.5%)	3022 (65.2%)	4106 (63.9%)		
SFHL				<.001	
 No	1097 (61.2%)	2588 (55.8%)	3685 (57.3%)		
 Yes	695 (38.8%)	2048 (44.2%)	2743 (42.7%)		
HFHL				<.001	
 No	878 (49.0%)	2025 (43.7%)	2903 (45.2%)		
 Yes	914 (51.0%)	2611 (56.3%)	3525 (54.8%)		
Data were n (%).

BMI = body mass index, HFHL = high-frequency hearing loss, HL = hearing loss, NHANES = National Health and Nutrition Examination Survey, SFHL = speech-frequency hearing loss, SII = systemic immune-inflammatory index.

3.2. Comparison between the SII group

Comparing the differences between low-SII group and high-SII group, the results showed that these 2 subgroups were significant in sex (P < .001), race/ethnicity (P < .001), educational attainment (P = .03), BMI (P < .001), smoking status (P = .018), diabetes (P = .018), HL (P < .001), SFHL (P < .001) and HFHL (P < .001; Table 1).

3.3. Association of SII with HL, SFHL, and HFHL

The weighted multivariable logistic regression was presented in Table 2. Compared with the low-SII group, the high-SII group had a higher risk of HL (OR: 1.30, 95% CI: 1.12–1.52, P < .01), SFHL (OR: 1.29, 95% CI: 1.11–1.49, P < .05), and HFHL (OR: 1.21, 95% CI: 1.04–1.40, P < .05) in the crude model. After adjusting age, sex, education, races and family income-to-poverty ratio, high-SII group was positively associated with HL (OR: 1.34, 95% CI: 1.10–1.63, P < .01) and HFHL (OR: 1.31, 95% CI: 1.10–1.54, P < .01), and associated with higher SFHL (OR: 1.15, 95% CI: 0.95–1.40, P = .15), though insignificant. Similar results were found when further adjusted for BMI, alcohol drinking, cardiovascular disease, diabetes mellitus, hypertension, and stroke, with increasingly pronounced effects on HL (OR: 1.29, 95% CI: 1.05–1.57, P < .05) and HFHL (OR: 1.24, 95% CI: 1.05–1.46, P < .05), respectively.

Table 2 The association of systemic immune-inflammatory index (SII) with hearing loss.

Outcomes	Model 1	Model 2	Model 3	
OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P	
HL	
 <330	Ref	–	Ref	–	Ref	–	
 ≥330	1.30 (1.12, 1.52)	.001	1.34 (1.10, 1.63)	.005	1.29 (1.05, 1.57)	.014	
HFHL	
 <330	Ref	–	Ref	–	Ref	–	
 ≥330	1.29 (1.11, 1.49)	<.001	1.31 (1.10, 1.54)	.002	1.24 (1.05, 1.46)	.012	
SFHL	
 <330	Ref	–	Ref	–	Ref	–	
 ≥330	1.21 (1.04, 1.40)	.013	1.15 (0.95, 1.40)	.152	1.13 (0.94, 1.37)	.201	
HFHL = high-frequency hearing loss, HL = hearing loss, SFHL = speech-frequency hearing loss, SII = systemic immune-inflammatory index.

3.4. The subgroup analysis stratified by age

Table 3 presented the results of the subgroup analysis stratified by age. The high-SII group exerted consistent effects on HL impairment in ages below 50 (OR: 1.34, 95% CI: 1.05–1.69, P < .05) and above 50 years (OR: 1.31, 95% CI: 1.10–1.56, P < .01), respectively. Similar results were identified in HFHL, with 1.37-folds ORs in age below 50 years (95% CI: 1.07–1.76, P < .05) and 1.22-folds ORs in age above 50 years (95% CI: 1.04–1.44, P < .05). There was no sign of significance in either age group of SFHL (P > .05).

Table 3 The association of systemic immune-inflammatory index (SII) with hearing loss stratified by age group.

Outcomes	Model 1	Model 2	Model 3	
OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P	
HL	
 <50 yr	
  <330	Ref	–	Ref	–	Ref	–	
  ≥330	1.25 (1.00, 1.56)	.052	1.34 (1.06, 1.69)	.016	1.34 (1.05, 1.69)	.019	
 ≥50 yr	
  <330	Ref	–	Ref	–	Ref	–	
  ≥330	1.30 (1.12, 1.52)	.001	1.28 (1.08, 1.53)	.005	1.31 (1.10, 1.56)	.003	
SFHL	
 <50 yr	
  <330	Ref	–	Ref	–	Ref	–	
  ≥330	1.10 (0.86, 1.40)	.416	1.24 (0.98, 1.58)	.073	1.29 (0.99, 1.69)	.059	
 ≥50 yr	
  <330	Ref	–	Ref	–	Ref	–	
  ≥330	1.21 (1.04, 1.40)	.013	1.18 (1.00, 1.40)	.053	1.16 (0.97, 1.39)	.103	
HFHL	
 <50 yr	
  <330	Ref	–	Ref	–	Ref	–	
  ≥330	1.29 (1.02, 1.62)	.032	1.43 (1.14, 1.79)	.003	1.37 (1.07, 1.76)	.017	
 ≥50 yr	
  <330	Ref	–	Ref	–	Ref	–	
  ≥330	1.29 (1.11, 1.49)	<.001	1.28 (1.09, 1.49)	.002	1.22 (1.04, 1.44)	.017	
Model 1: adjusted for none. Model 2: adjusted for sex, education, races, and family income-to-poverty ratio. Model 3: adjusted for sex, education, races, and family income-to-poverty ratio, BMI, alcohol drinking, cardiovascular disease, diabetes mellitus, hypertension and stroke.

BMI = body mass index, HFHL = high-frequency hearing loss, HL = hearing loss, SFHL = speech-frequency hearing loss, SII = systemic immune-inflammatory index.

3.5. Sensitively analysis

Across the sensitivity analysis using multivariable linear regression models, robust results were found for HL, HFHL, and SFHL (Table 4). For example, increasing SII index per SD was associated with HL (OR: 1.17, 95% CI: 1.09–1.26, P < .001) and HFHL (OR: 1.13, 95% CI: 1.06–1.21, P < .001) in the full model. The significance of SFHL was not detected with the increasing SII index (P > .05). In addition, the results were examined after subgroup analysis stratified by age (Table 5). For example, the SII index with per SD increase was associated with an increment of ORs of HL in the young (OR: 1.15, 95% CI: 1.05–1.26, P < .01) and old group (OR: 1.12, 95% CI: 1.03–1.22, P < .01).

Table 4 Sensitivity analysis of the association of systemic immune-inflammatory index (SII) with hearing loss using linear regression model.

Outcomes	Model 1	Model 2	Model 3	
OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P	
HL	1.16 (1.08, 1.25)	<.001	1.18 (1.09, 1.28)	<.001	1.17 (1.09, 1.26)	<.001	
HFHL	1.15 (1.08, 1.23)	<.001	1.17 (1.09, 1.25)	<.001	1.13 (1.06, 1.21)	<.001	
SFHL	1.10 (1.03, 1.18)	.005	1.07 (1.00, 1.14)	.056	1.04 (0.96, 1.12)	.365	
Model 1: adjusted for none. Model 2: adjusted for age, sex, education, races, and family income-to-poverty ratio. Model 3: adjusted for age, sex, education, races, and family income-to-poverty ratio, BMI, alcohol drinking, cardiovascular disease, diabetes mellitus, hypertension and stroke.

BMI = body mass index, HFHL = high-frequency hearing loss, HL = hearing loss, SFHL = speech-frequency hearing loss.

Table 5 Sensitivity analysis of the association of systemic immune-inflammatory index (SII) with hearing loss using linear regression model stratified by age group.

Outcomes	Model 1	Model 2	Model 3	
OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P	
HL	
 <50 yr	1.11 (1.01, 1.22)	.039	1.18 (1.07, 1.30)	.002	1.15 (1.05, 1.26)	.005	
 ≥50 yr	1.16 (1.08, 1.25)	<.001	1.17 (1.08, 1.27)	<.001	1.12 (1.03, 1.22)	.007	
SFHL	
 <50 yr	0.96 (0.85, 1.08)	.472	1.06 (0.95, 1.18)	.276	1.02 (0.93, 1.13)	.622	
 ≥50 yr	1.10 (1.03, 1.18)	.005	1.11 (1.04, 1.19)	.001	1.04 (0.97, 1.12)	.286	
HFHL	
 <50 yr	1.11 (1.01, 1.22)	.039	1.20 (1.08, 1.33)	.001	1.17 (1.06, 1.28)	.002	
 ≥50 yr	1.15 (1.08, 1.23)	<.001	1.17 (1.09, 1.26)	<.001	1.11 (1.03, 1.19)	.006	
Model 1: adjusted for none. Model 2: adjusted for sex, education, races, and family income-to-poverty ratio. Model 3: adjusted for sex, education, races, and family income-to-poverty ratio, BMI, alcohol drinking, cardiovascular disease, diabetes mellitus, hypertension and stroke.

BMI = body mass index, HFHL = high-frequency hearing loss, HL = hearing loss, SFHL = speech-frequency hearing loss.

4. Discussion

To the best of our knowledge, this is the first study that implicated the association between SII and hearing loss. We found positive associations between HL, HFHL, and high-SII (≥330 × 109/L) in US adults. And, the positive associations were further confirmed in sensitivity analysis using the linear regression model. However, no association was found between SII and SFHL in these patients. Subgroup analysis revealed that this association was consistent across different age groups.

As far as we know, this is the initial study that evaluates the correlation between SII and HL. Compared to traditional inflammatory markers, the SII has been shown to more accurately reflect the inflammatory state and has demonstrated superior prognostic value in several studies.[8,25,26] Currently, numerous studies have demonstrated that inflammation is associated with HL. The English Longitudinal Study of Ageing revealed that white blood cell count was positively associated with HL in older adults.[27] In addition, glycoprotein A (GlycA), a novel biomarker of chronic inflammation, was found to be associated with poor hearing in middle childhood.[28] Furthermore, Sahin found that the neutrophil-lymphocyte ratio may be considered as a predictive and prognostic marker of HL in patients diagnosed with diabetes mellitus.[29] However, the mechanisms underlying the association between inflammation and the progression of HL remain unclear. One theory is that chronic inflammation may alter neurotropism in the brain, subsequently affecting the function of the auditory cortex. This, in turn, may promote HL.[30] Experimental studies of inner ear inflammation have indicated that there is production of TNF-α, IL-1β, and IL-6 in the cochlea, along with synergistic leukocyte infiltration.[31] Animal model investigations have shown that the blockade of interleukin-6 signaling suppresses the cochlear inflammatory response and improves hearing impairment in noise-damaged mice cochlea.[32]

It is worth mentioning that this study did not observe any correlation between SII and SFHL. While the detailed mechanism remains uncertain, there are several interesting phenomena. At the time when acute auditory trauma occurred, HFHL (above 2 kHz) is observed in over 75% of cases, while the remaining 25% also exhibit impairment in the sub-2 kHz speech frequency range.[33] Acute otitis media can result in persistent sensorineural HL even after treatment and resolution of the effusion. Typically, damage is minimal or absent in the speech frequency ranges, but it can be detected through high-frequency audiometry.[34] Presbycusis is typically characterized by HFHL.[35] Similarly, noise tends to affect the high-frequency regions of the cochlea first.[35] These studies have shown that high-frequency hearing is naturally more impaired than low-frequency hearing for anatomical and physiological reasons.

The possible explanations for the SII and HL association were due to vascular effects, neuroinflammation, hair cell damage, and autoimmune response.[36] Measuring SII could serve as a potential biomarker for identifying individuals at higher risk of developing HL. Clinicians could incorporate SII measurements along with other relevant factors to assess an individual’s susceptibility to hearing impairment. Furthermore, If inflammation indeed plays a role in HL, targeting inflammation could become a therapeutic avenue. Anti-inflammatory interventions or medications might be explored as adjunct treatments to manage or prevent HL, especially in individuals with elevated SII levels. Moreover, Incorporating SII measurements into patient assessments could enable more personalized treatment plans. This could lead to tailored interventions based on an individual’s inflammation status, potentially improving treatment outcomes.

Our study has several strengths. Firstly, HL is measured using audiometry assessments, which are considered the gold standard. Secondly, the sample selection is representative, and the sample size is sufficiently large. Several limitations of this analysis should be considered. First, although we adjusted for some potential covariates, we could not completely eliminate the influence of other possible confounding factors, including genetics, dietary intake, and living condition. Second, due to the inherent limitations of NHANES’ design, platelet, neutrophil, and lymphocyte count were measured at a single time point at baseline, and may have changed over time during the follow-up. Thirdly, due to the cross-sectional nature of our analyses, it is impossible to deduce causal relationships between SII and HL. Therefore, future research that includes larger sample size and more precise measurements is necessary to establish a causal relationship.

5. Conclusion

In summary, the SII score was associated with HL and HFHL in the general adult population of the United States, but was not significantly correlated with SFHL. To validate our findings, further large-scale prospective studies are still required.

Acknowledgments

We thank the NHANES team collecting and sharing this dataset. This work was not supported by any funding.

Author contributions

Conceptualization: Limei Zhao, Xi Zhang, Lu Chen.

Data curation: Lu Chen.

Formal analysis: Limei Zhao.

Investigation: Limei Zhao.

Methodology: Limei Zhao, Xi Zhang.

Software: Limei Zhao, Xi Zhang.

Supervision: Lu Chen.

Visualization: Lu Chen.

Writing – original draft: Limei Zhao, Xi Zhang.

Writing – review & editing: Lu Chen.

Abbreviations:

HFHL high-frequency hearing loss

HL hearing loss

L lymphocyte

N neutrophil

NHANES National Health and Nutrition Examination Survey

P platelet

SFHL speech-frequency hearing loss

SII systemic immune-inflammation index

This study was exempt from ethical review and approval. Informed consent was obtained from all subjects prior to their participation of this study.

The authors have no funding and conflicts of interest to disclose.

The datasets generated during and/or analyzed during the current study are publicly available.

How to cite this article: Zhao L, Zhang X, Chen L. Association between the systemic immune-inflammation index and hearing loss: A cross-sectional study of NHANES 2005 to 2018. Medicine 2024;103:38(e39711).

LZ and XZ contributed to this article equally.
==== Refs
References

[1] Zou M Huang M Zhang J Chen R . Exploring the effects and mechanisms of organophosphorus pesticide exposure and hearing loss. Front Public Health. 2022;10 :1001760.36438228
[2] Fu Y Chen W Guo L Liu Y . The inverted-U relationship between dietary inflammatory potential and hearing loss among adults aged 20 years and over in the United States: a cross-sectional study. J Inflamm Res. 2021;14 :6671–83.34916819
[3] Lin FR Yaffe K Xia J . Health ABC Study Group. Hearing loss and cognitive decline in older adults. JAMA Intern Med. 2013;173 :293–9.23337978
[4] Davis A McMahon CM Pichora-Fuller KM . Aging and hearing health: the life-course approach. Gerontologist. 2016;56 :S256–67.26994265
[5] Korver AM Smith RJ Van Camp G . Congenital hearing loss. Nat Rev Dis Primers. 2017;3 :16094.28079113
[6] Kohrman DC Wan G Cassinotti L Corfas G . Hidden hearing loss: a disorder with multiple etiologies and mechanisms. Cold Spring Harb Perspect Med. 2020;10 :a035493.30617057
[7] Kociszewska D Vlajkovic S . Age-related hearing loss: the link between inflammaging, immunosenescence, and gut dysbiosis. Int J Mol Sci. 2022;23 :7348.35806352
[8] Hu B Yang XR Xu Y . Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20 :6212–22.25271081
[9] Li H Wu X Bai Y . Physical activity attenuates the associations of systemic immune-inflammation index with total and cause-specific mortality among middle-aged and older populations. Sci Rep. 2021;11 :12532.34131164
[10] Liu YY Ruan GT Ge YZ . Systemic inflammation with sarcopenia predicts survival in patients with gastric cancer. J Cancer Res Clin Oncol. 2023;149 :1249–59.35435489
[11] Yilmaz M Baran A Yilmaz MK . Predictive significance of inflammatory indexes in metastatic nonsmall cell lung cancer patients treated with platinum-doublet chemotherapy. J Cancer Res Ther. 2022;18 :220–3.35381787
[12] Han R Tian Z Jiang Y . Prognostic significance of systemic immune-inflammation index and platelet-albumin-bilirubin grade in patients with pancreatic cancer undergoing radical surgery. Gland Surg. 2022;11 :576–87.35402206
[13] Huang Z Zheng Q Yu Y . Prognostic significance of platelet-to-albumin ratio in patients with esophageal squamous cell carcinoma receiving definitive radiotherapy. Sci Rep. 2022;12 :3535.35241740
[14] Liu Y Ye T Chen L . Systemic immune-inflammation index predicts the severity of coronary stenosis in patients with coronary heart disease. Coron Artery Dis. 2021;32 :715–20.33826540
[15] Trifan G Testai FD . Systemic Immune-Inflammation (SII) index predicts poor outcome after spontaneous supratentorial intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2020;29 :105057.32807462
[16] Shi X . Pathophysiology of the cochlear intrastrial fluid-blood barrier (review). Hear Res. 2016;338 :52–63.26802581
[17] Gupta S Curhan SG Curhan GC . Biomarkers of systemic inflammation and risk of incident hearing loss. Ear Hear. 2019;40 :981–9.30399011
[18] Nash SD Cruickshanks KJ Zhan W . Long-term assessment of systemic inflammation and the cumulative incidence of age-related hearing impairment in the epidemiology of hearing loss study. J Gerontol A Biol Sci Med Sci. 2014;69 :207–14.23739996
[19] Hueng DY Liu MY . Molecular mechanism of hearing loss. J Neurosurg. 2013;119 :1655–6.24116726
[20] Ikeda N Murray CJ Salomon JA . Tracking population health based on self-reported impairments: trends in the prevalence of hearing loss in US adults, 1976-2006. Am J Epidemiol. 2009;170 :80–7.19451176
[21] Choi YH Hu H Mukherjee B Miller J Park SK . Environmental cadmium and lead exposures and hearing loss in U.S. adults: the National Health and Nutrition Examination Survey, 1999 to 2004. Environ Health Perspect. 2012;120 :1544–50.22851306
[22] Di X Liu S Xiang L Jin X . Association between the systemic immune-inflammation index and kidney stone: a cross-sectional study of NHANES 2007-2018. Front Immunol. 2023;14 :1116224.36895572
[23] Zhang Y Liu W Zhang W . Association between blood lead levels and hyperlipidemiais: results from the NHANES (1999-2018). Front Public Health. 2022;10 :981749.36159291
[24] Tang Y Peng B Liu J Liu Z Xia Y Geng B . Systemic immune-inflammation index and bone mineral density in postmenopausal women: a cross-sectional study of the national health and nutrition examination survey (NHANES) 2007-2018. Front Immunol. 2022;13 :975400.36159805
[25] Chen JH Zhai ET Yuan YJ . Systemic immune-inflammation index for predicting prognosis of colorectal cancer. World J Gastroenterol. 2017;23 :6261–72.28974892
[26] Lu L Feng Y Liu YH . The systemic immune-inflammation index may be a novel and strong marker for the accurate early prediction of acute kidney injury in severe acute pancreatitis patients. J Invest Surg. 2022;35 :962–6.34468253
[27] Lassale C Vullo P Cadar D Batty GD Steptoe A Zaninotto P . Association of inflammatory markers with hearing impairment: the English Longitudinal Study of Ageing. Brain Behav Immun. 2020;83 :112–9.31562886
[28] Wang J Sung V Carew P Liu RS Burgner D Wake M . Inflammation and hearing status in mid-childhood and mid-life: a population-based cross-sectional study. Int J Epidemiol. 2019;48 :1556–66.30815675
[29] Ulu S Bucak A Ulu MS . Neutrophil-lymphocyte ratio as a new predictive and prognostic factor at the hearing loss of diabetic patients. Eur Arch Otorhinolaryngol. 2014;271 :2681–6.24121821
[30] Calsolaro V Edison P . Neuroinflammation in Alzheimer’s disease. Current evidence and future directions. Alzheimers Dement. 2016;12 :719–32.27179961
[31] Hashimoto S Billings P Harris JP Firestein GS Keithley EM . Innate immunity contributes to cochlear adaptive immune responses. Audiol Neurootol. 2005;10 :35–43.15567913
[32] Wakabayashi K Fujioka M Kanzaki S . Blockade of interleukin-6 signaling suppressed cochlear inflammatory response and improved hearing impairment in noise-damaged mice cochlea. Neurosci Res. 2010;66 :345–52.20026135
[33] Temmel AF Kierner AC Steurer M Riedl S Innitzer J . Hearing loss and tinnitus in acute acoustic trauma. Wien Klin Wochenschr. 1999;111 :891–3.10599152
[34] Tarlow M . Otitis media. pathogenesis and medical sequelae. Ear Nose Throat J. 1998;77 :3–6.9674327
[35] Gates GA Mills JH . Presbycusis. Lancet. 2005;366 :1111–20.16182900
[36] Trune DR Nguyen-Huynh A . Vascular pathophysiology in hearing disorders. Semin Hear. 2012;33 :242–50.25346568
