Introduction

Sudden hearing loss (SHL) is a disease characterized by a loss of hearing greater than 30 dB in three contiguous frequen­cies that occurs in less than 3 days 1. The incidence of SHL ranges from 5-20 cases per 100,000 persons 2,3. Since the physiopathology of SHL is still unclear, there are many theories as to the origin of this disease, including bacterial, viral and protozoal infections, blood disorders, vascular occlusion, immune disorders, ototoxic drugs and metabolic conditions 3-7.

Cochlea is very susceptible for any alteration of bloodstream. Vascular diseases and platelet alterations may cause some cochlear injuries and be related to SHL 8.

Platelets secrete and express a large number of substances that are crucial mediators of coagulation, inflammation, thrombosis, and atherosclerosis 9. The size and functional activity of circulating platelets vary. Larger platelets are often younger, more reactive and produce more thrombogenic factors. Mean platelet volume (MPV), which is an indicator of platelet activation, is also used as a marker of atherothrombosis 10, and may be important as a prophylactic and diagnostic tool in thrombotic and prothrombotic cases.

White blood cell (WBC) count is a useful inflammatory biomarker in clinical practice. Even if the WBC is within a normal range, subtypes of WBC, such as neutrophil-to-lymphocyte ratio (NLR), may predict cardiovascular mortality 11,12. The NLR is an easily measurable laboratory marker that is used to evaluate systemic inflammation and it has also superiority compared to other WBC subtype counts (e.g., neutrophil, lymphocyte, and total leukocyte counts). This superiority may be due to the stability of NLR compared to the other WBC subtype counts that could be affected by various pathological and physiological conditions. As these factors can alter the individual WBC subtype counts, the NLR may remain more stable. Moreover, the NLR may represent the both inflammatory and immune pathways that exist together in the patients. NLR has been defined as a novel and potential marker to determine inflammation in cardiac and non-cardiac disorders 11,13-18.

Recently, the relationship between MPV and NLR with SHL were investigated individually 15,19-21. However, to our knowledge, ours is the first study evaluating MPV and NLR together, and in comparison with one other, in the diagnosis and prognosis of the SHL patients. Since NLR is an indicator of inflammation and MPV indicates atherothrombosis, this study aimed to contribute to the literature by investigating the role of inflammation and atherothrombosis in SHL patients by using NLR and MPV, respectively.

Methods

This cross-sectional historical cohort study included an SHL patient group and a healthy control group. The SHL group included 59 patients who were admitted to a tertiary referral hospital ENT Clinic and were diagnosed with SHL between May 2010 and December 2013. Patients with history or clinical findings of any inflammatory, autoimmune, acute or chronic infectious diseases, hypertension, conductive hearing loss, angina pectoris, myocardial infarction, diabetes mellitus, metabolic syndrome, chronic obstructive pulmonary disease, amyloidosis, chronic renal insufficiency obstructive sleep apnea, current smoking, or active otologic disease were excluded, as were those who did not have a type A audiometric tympanogram. The control group included 59 age–sex–matched healthy individuals who came to the ENT polyclinic for a required examination due to an employment application, and had no active symptoms and normal audiological findings.

The NLR was calculated as a simple ratio between the absolute neutrophil and the absolute lymphocyte counts. The Beckman Coulter LH 750 automated blood cell counter (Beckman Coulter analyzer, California, USA) was used for complete blood count (CBC) measurements (Neutrophil, lymphocyte, platelet, NLR, MPV and WBC), which based on technique of laser flow cytometry scattergramc, and were performed within 2 hours after blood sampling. Blood samples from the patient group were obtained before the patient was administered any treatment. All samples were run in duplicate, and the mean values were used for statistical analysis.

Audiometric examinations were performed in quiet rooms with an Interacoustics AC–40 clinical audiometer according to the standards of the Industrial Acoustics Company, and all of the tests were carried out by the same audiometrist. Audiologic data were reported in accordance with the recommended methods of the Hearing Committee of the American Academy of Otolaryngology, Head and Neck Surgery, which endorsed a new minimal standard for reporting hearing results in clinical trials 22. Audiometric examinations were performed initially and after 1 month of the treatment. The SHL patients had a minimum of 30 dB hearing loss at 3 consecutive frequencies that developed within 72 hours and was not associated with other known pathologies, including Meniere’s disease, autoimmune disease, ototoxicity, or neoplasm. The hearing loss was unilateral in all patients.

All of the patients were treated with the standard SHL protocol, which included prednisone in the dose of 1 mg/kg per day, with a progressive dose reduction, maintained for at least 2 weeks. The mean interval of the blood tests following the onset of SHL was 1.98 ± 1.26 days (range 1-6 days)

Patients were classified as follows (according to the recovery that was seen in a month in the follow-up period). 1) Complete: Pure tone average (PTA) within 10 dB hearing levels (HL) of initial HL or within 10 dB HL of the HL of the unaffected ear; 2) Partial: PTA dB HL within 50% of initial HL or greater than 10 dB HL improvement of the HL; and 3) No recovery: less than 10 dB HL improvement in HL relative to the initial HL 1. Then, the patients were divided into 2 groups as recovered (Complete + Partial) and unrecovered (No recovery). The patients were also divided into three subgroups according to severity of hearing loss as mild (< 40 dB loss for any frequency), moderate (up to 80 dB), and severe ( > 80 dB).

Age, gender, MPV, NLR and other laboratory data of the patients were recorded for all groups. The correlations between the MPV and NLR were evaluated in the SHL group and the control group, and SHL patients were compared according to the recovery and severity of hearing loss. Also, correlation between the MPV and NLR was determined in the SHL patient group.

Our study was approved by the local ethics committee and conducted in accordance with the ethical principles described by the Declaration of Helsinki. Informed consent form was obtained from all participants before the study.

The statistical package for the social sciences (SPSS for Windows, version 15.0) software was used for all data analyses. Data distributions were analyzed with the Shapiro–Wilk test. The independent sample T test was used to analyze age and MPV values, and platelet count. In cases of normal distribution, the Mann–Whitney U test was used to compare the groups (gender). The correlations between the variable pairs were analyzed with a Pearson’s correlation test. A level of p < 0.05 was considered significant.

Results

There was no significant difference between the age or gender of the SHL and control groups. The mean ages of the patients and the control group were 46.10 ± 11.91 and 42.84± 11.85 years, respectively. The male-to-female ratio of the SHL patients was 38:21, and was 31:28 for the control group (Table 1).

The laboratory data of the patients and the control group were given in Table 1. The mean MPV value was 9.83 ± 1.50 femtoliters (fl) in the patients and 9.98 ± 0.07 fl in the control group, and the difference was not statistically significant (p = 0.470). The mean NLR value was 3.24 ± 2.26 in the SHL patients and 1.53 ± 0.47 in the control group, and the difference was statistically significant (p=0.001) (Table 1).

The laboratory data of the SHL patients according to response to the treatment as recovered and unrecovered groups, were given in Table 2. The mean MPV value was 9.91 ± 1.49 fl in the unrecovered group and 9.75 ± 1.52 fl in the recovered group, and the difference was not statistically significant (p = 0.785). The mean NLR value was 4.45 ± 2.63 in the unrecovered group and 2.15 ± 1.04 in the recovered group, and the difference was statistically significant (p = 0.001) (Table 2).

The mean NLR and MPV values according to severity of hearing loss were given in Table 3. There was statistically significant correlation between NLR values and severity of hearing loss (p = 0.015). The mean NLR values in the patients with severe SHL were significantly higher than in the mild SHL group (p = 0.004). However, there was no correlation between MPV values and severity of hearing loss (p = 0.701).

There was no correlation between MPV and NLR in the SHL patient group (r = 0.190, p = 0.149)

Discussion

The key to successful treatment of diseases lies in the understanding of their etiopathogenesis. Since SHL physiopathology is still unclear, there are conflicting theories regarding its true cause 8,23,24. There are many theories as to the origin of this disease, including viral infections, inflammation, blood disorders, vascular causes, immune disorders and rupture of the labyrinthine membrane 12,25,26. Since the cochlea is mainly supplied by a single, terminal artery (the labyrinthine artery), the inner ear is very much prone to circulatory alterations 27. In vascular cases, the problems may be present on the blood vessel wall, as is the case in arteritis and spasms, or they may be located intravascularly. A history of vascular disease or platelet alterations is the only clinical finding that could lead one to infer a vascular cause of SHL. Although the most widely accused factor in the etiology is viral inflammation of the neural fibers and ganglia 28, this has not been proven yet.

The NLR is an easily measured biomarker that correlates with clinical status. It is calculated from the CBC, and is an inexpensive, easy to obtain, widely available marker of inflammation that can aid in the risk stratification of patients with various diseases 1,13,29,30. It is as valuable as some high-cost inflammatory markers including IL-6, IL-1β, IL-8, and TNF-α 31. On the other hand, MPV can be used as marker for high platelet activity which takes an active role in the pathophysiology of thrombosis, coagulation and atherosclerosis 32.

In recent studies, NLR was determined to be a reliable marker for the diagnosis of and predicting the prognosis of SHL and Bell’s palsy 14,15,33. Ulu et al. reported that when the patients with SHL were compared according to the recovery, NLR levels were higher in patients without recovery, and this may be explained with the higher inflammatory situation in unrecovered patients, and this result may help clinicians for SHL patients with higher NLR levels in terms of the treatment and the prognosis 15. In the previous study by Masuda et al., neutrophil and levels of inflammatory markers were higher in SHL patients 34. Most recently, Ozler classified the SHL patients according to severity of hearing loss as mild (< 40 dB loss for any frequency), moderate (up to 80 dB), and severe (profound, > 80 dB) and found that the mean NLR values in the patients with SHL were significantly higher than in the control group, and also the mean NLR values in the patients with severe sensorineural hearing loss were significantly higher than in the other groups 35. In our study, NLR values were significantly higher in patients with SHL compared to the control group. Similarly, the mean NLR was higher in the unrecovered patients compared with the recovered ones, and also there was significant correlation between NLR values and severity of hearing loss, indicating the presence of inflammation.

Platelets play an active role in the pathophysiology of thrombosis, coagulation, inflammation and atherosclerosis 9,36. Upon activation, platelets release vasoactive and thrombogenic agents, which are important factors in the formation of thrombosis in the vessel. Several investigators have used a series of platelet indices that are measured by hematology analyzers since platelet activation causes them to have morphologic changes 37. Large platelets are more active metabolically and enzymatically and have more thrombotic potential 38. Higher MPV values are beneficial markers of higher platelet activity and have been found to be associated with atherothrombosis. In addition, MPV is one of the most extensively studied platelet activation markers 32,39.

MPV values were studied in patients with SHL yielding controversial results. In the recent studies by Ulu et al. (with 40 patients and controls) and Sagit et al (with 31 patients and controls), the mean MPV values in SHL patients were 10.5 ± 0.9 fl and 9.01 ± 1.24 fl, respectively, which were significantly higher than the values of the control groups (9.6 ± 0.5 fl and 8.21 ± 0.76 fl, respectively) 20,21. In another study by Karli et al. (with 46 patients and controls), the mean MPV value was 8.25 ± 0.86 fl in SHL patients and 7.98 ± 0.87 fl in the control group, which was not significantly different, and they concluded that, there is no microvascular response theory in the etiology of SHL 19. In our study (with 59 patients and controls), the mean MPV value was 9.83 ± 1.50 fl in SHL patients and 9.98 ± 0.07 fl in the control group, and similarly, the mean MPV value was 9.91 ± 1.49 fl in the unrecovered group, and 9.75 ± 1.52 fl in the recovered group, and there was no significantly difference between the groups. Absence any correlation of MPV with any of the studied parameters may suggest that microvascular response is a suspicious theory in etiopatogenesis of SHL.

In a large epidemiologic study with 326 patients by Demirin et al., the mean MPV value in normal Turkish adults was 8.9 ± 1.4 fl, and 95% of the individuals had an MPV between 7.2 and 11.7 fl 40. If the MPV values ​​of the control group in our study were equivalent to those of the study by Demirin et al., our results would have been considered significant.

Conclusion

The results of our study indicated that when the SHL patients were compared according to the recovery, NLR levels were higher in patients without recovery. However there was no such a correlation between the MPV levels and the patients’ recovery. This may indicate that inflammation plays a larger role in the pathogenesis of SHL than does the microvascular response. In the evaluation of SHL, NLR is a quick and reliable marker of predicting the diagnosis and prognosis, while MPV may be a less important marker. Although our sample size is larger than that used in previous studies, this issue should be investigated in a larger patient group. Because this area of research is a novel field, prospective, multicenter, and controlled studies need to be done.

Acknowledgments: None.

Conflict of interest : The authors declare that they have no conflict of interest.

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Tables

Table 1. Intergroup comparison of age, gender, mean platelet volume (MPV), Neutrophil-to-lymphocyte ratio (NLR) values and platelet counts of the patients and the control group.

*p < 0.05

SD: Standard deviation, WBC: White blood cell.

Table 2. Comparison of laboratory data between the recovered and unrecovered patients.

*p < 0.05

SD: Standard deviation, MPV: Mean platelet volume, NLR: Neutrophil-to-lymphocyte ratio, WBC: White blood cell.

Table 3. Mean analysis for NLR and MPV according to severity of hearing loss as mild (< 40 dB), moderate (up to 80 dB), and severe (profound, > 80 dB).

*p < 0.05

SD: Standard deviation, MPV: Mean platelet volume, NLR: Neutrophil-to-lymphocyte ratio.