Abstract
This study aimed to investigate the neutrophil-to-lymphocyte ratio (NLR) and severity of the chronic otitis media according to middle ear risk index (MERI) scores. The NLR and middle ear risk index were calculated for 210 chronic otitis media (COM) patients retrospectively. NLR compared between COM patients and 159 participants in control group. Pearson correlation analysis was performed for NLR and MERI. In addition, The cut-off value, sensitivity, and specificity for NLR were determined in COM according to the severity of the disease with ROC analysis. The average of NLR in all patients was 1.94 ± 0.89. NLR was calculated as 2.05 ± 1.03 in the patients with COM and 1.79 ± 0.64 in the control group (p = 0.006, 95% CI 0.07–0.44, t test). According to the ROC analysis, the cut-off point was determined as 1.95 for moderate and severe disease in MERI. For the cut of a NLR = 1.95, sensitivity was calculated as 48.5% and the specificity 57.1% for moderate and severe COM. MERI score was found significantly higher in patients with postoperative graft perforation (p < 0.001, 95% CI 0.7–1.8). NLR has not related significantly with the MERI score according to linear regression analysis (p = 0.927). NLR was found to be significantly higher in chronic otitis media patients compared to the control group. But NLR was not related to the severity of the disease classified with MERI. The cut-off value, sensitivity and sensitivity rates of NLR obtained was not available for clinically use.
Keywords: Neutrophil-to-lymphocyte ratio, Middle ear risk index, Chronic otitis media, Tympanoplasty
Introduction
Chronic otitis media (COM) is a multifactorial disease arising from the complex interactions among otopathogens with inflammatory responses in the middle ear, either alone or in combination [1]. The innate immune system activates against invading microbial pathogens at the first line of defense and lack of this system promotes easy colonization of pathogen at the upper airway mucosa [1]. The inflammation with innate immunity involves both neutrophils, macrophages, eosinophils, mast cells, natural killer cells, innate lymphoid cells [2]. Also, neutrophils are an absolutely essential part of the innate immune system and predominant of the leukocyte population in human blood and among the first cells recruited to an inflammatory site [3]. The neutrophil-to-lymphocyte ratio (NLR) is a basic parameter to assess the inflammatory status of humans with complete blood count and normally distributes between 0.78 and 3.58 [4]. NLR has been detected as an available marker for otitis media with mucoid effusion [5], facial palsy with viral infections [6] and favorable prognostic factor for idiopathic sudden sensorineural hearing loss [7]. Studies investigating NLR in chronic otitis media and related diseases are few and limited In the literature. Kartush developed middle ear risk index (MERI) which combines the known preoperative and intraoperative risk factors for tympanoplasty prognosis by a scale [8].
Material and Methods
The study designed retrospectively. The patients underwent ear surgery at the tertiary ear-nose-throat clinic, scanned by the institutional electronic archive. Control group was formed from patients who underwent simple septoplasty surgery in the same clinic without obstructive sleep apnea. It has been shown that NLR was not affected by septal deviation previously [9]. Peripheral blood was collected from all included subjects just before the surgery as a routine part of the preoperative examination for operations with general anesthesia. NLR was calculated according to the peripheral blood for both COM patients and the control group. MERI score calculated with the patient's history, preoperative examination and intraoperative findings for COM patients. MERI was scored between 0 to 12 points according to middle ear status, and then classified as MERI 0; Normal, MERI 1–3; Mild disease, MERI 4–6; Moderate disease, MERI 7–12: Severe disease. Also age, gender and side of the chronic otitis media and the preoperative and postoperative pure-tone average (PTA; 0.5, 1, 2, 4 kHz) of the patients recorded.
Patients with COM and between 18 and 60 years old who underwent COM surgery were only included in the study. Also, COM patients who were followed up with medical treatment were not included in the study. Complicated COM patients such as facial paralysis or meningitis and patients undergoing radical mastoidectomy or complication surgery were excluded. In addition, data of patients with erythrocyte and platelet counts in the reference range according to the complete blood count have included analysis. Patients with any history of acute or chronic inflammation, hypertension, diabetes mellitus, metabolic syndrome, heart failure, myocardial infarction, cerebral embolism, cancer, hepatitis, nephritis, an autoimmune disease, chronic obstructive pulmonary disease and/or, lymphoproliferative disease were excluded. The presence of C-reactive protein (CRP) value was not determined as a selection criterion, but the patients whose CRP was measured in the blood sample at the same time and found to be high were excluded from the study.
Normality distribution of the obtained numerical data was measured by the Kolmogorov–Smirnov test. According to the normality hypothesis, the analysis of the scaled data between the groups was done by t test or Mann Whitney U test. Correlation between age, NLR, PTA and MERI score was investigated by Pearson’s correlation analysis. For the measurements, p significance value and r correlation coefficients were determined. SPSS 22.0 program (IBM Corp., Armonk, NY, USA) was used for statistics. The study was carried out in accordance with the 1964 Helsinki Declaration and subsequent amendments.
Results
The records of 216 COM patients were reviewed and 3 patients were excluded from the study because of COM with complications, 2 patients with radical mastoidectomy, and 1 patient due to preoperative CRP elevation. Finally, 210 patients included in the COM group and 159 participants included in the control group. 89 of the patients were female (42.4%) and 121 were male (57.6%) in COM patients. Control group included 79 (49.3%) female and 80 (50.7%) male. The mean age was determined as 32.3 ± 14.6 in all patients, and 31.3 ± 14.8 in the COM patients, 33.4 ± 14.4 was in the control group. The average of NLR in all patients was 1.94 ± 0.89. NLR was calculated as 2.05 ± 1.03 in the patients with COM and 1.79 ± 0.64 in the control group (p = 0.006, 95% CI 0.07–0.44, t-test). The mean of NLR was not affected by gender, bilateral COM and graft success (p = 0.358, 0.327, 0.144, respectively) (Table 1). In addition, NLR has not related significantly with the MERI score and the age according to linear regression analysis (p = 0.927, 0.703, respectively). According to the ROC analysis, the cut-off point was determined as 1.95 for NLR (AUC: 0.488, Likelihood ratio: 1.12) for moderate and severe disease. According to this cut-off point, the sensitivity was calculated as 48.5% and the specificity 57.1% for moderate and severe COM.
Table 1.
Summary of the study groups
| Gender | p | Age | p | NLR | p | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Male | Female | Mean | SD | Mean | SD | ||||||
| n | % | n | % | ||||||||
| Study groups | |||||||||||
| Control | 80 | 21.7 | 79 | 21.4 | 0.130 | 33,4 | 14.4 | 0.172 | 1,79 | 0.64 | 0,006 |
| COM | 89 | 24.1 | 121 | 32.8 | 31,3 | 14.8 | 2,05 | 1.03 | |||
| Total | 169 | 45.8 | 200 | 54.2 | 32,3 | 14.6 | 1,94 | 0.89 | |||
NLR neutrophil-to-lymphocyte ratio, COM chronic otitis media
MERI score was found to be 2.3 ± 1.1 in all patients. MERI was scored as 1–3 (mild disease) in 177 (84.3%) patients and 33 (15.7%) (moderate and severe disease) in 33 patients. MERI score was found significantly higher in patients with postoperative graft perforation (p < 0.001, 95%CI 0.7–1.8). But MERI score was not affected by gender and the presence of bilateral COM (p = 0.169, 0.355, respectively) (Table 2). MERI has shown a significant positive correlation with age, preoperative PTA, and Postoperative PTA (p = 0.003, p < 0.001, p < 0.000, respectively). According to Pearson correlation analysis, no significant correlation was found between NRL with MERI and age (p = 0.861, 0.682, respectively) (Table 3).
Table 2.
Distribution of findings by groups and p significance values
| n | % | Age | Preop. PTA | NLR | Postop. PTA | MERI | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| m | SD | p | m | SD | p | m | SD | p | m | SD | p | m | SD | p | |||
| Gender | |||||||||||||||||
| Male | 89 | 42.4 | 31.2 | 16.4 | 0.898 | 35.4 | 15.4 | 0.192 | 1.97 | 0.89 | 0.358 | 27.6 | 18.5 | 0.503 | 2.44 | 1.40 | 0.169 |
| Famale | 121 | 57.6 | 31.5 | 13.5 | 32.1 | 19.0 | 2.10 | 1.12 | 25.6 | 20.4 | 2.20 | 1.00 | |||||
| Total | 210 | 100.0 | 31.3 | 14.8 | 33.5 | 17.6 | 2.05 | 1.03 | 26.4 | 19.6 | 2.30 | 1.19 | |||||
| Other Ear Status | |||||||||||||||||
| Unilateral COM | 147 | 70.0 | 31.3 | 14.1 | 0.959 | 33.0 | 17.6 | 0.475 | 2.00 | 0.99 | 0.327 | 25.6 | 19.2 | 0.381 | 2.24 | 1.08 | 0.355 |
| Bilateral COM | 63 | 30.0 | 31.4 | 16.4 | 34.9 | 17.6 | 2.15 | 1.12 | 28.4 | 20.5 | 2.43 | 1.40 | |||||
| Total | 210 | 100.0 | 31.3 | 14.8 | 33.5 | 17.6 | 2.05 | 1.03 | 26.4 | 19.6 | 2.30 | 1.19 | |||||
| Graft Take | |||||||||||||||||
| Perforated | 18 | 8.6 | 23.7 | 10.9 | 0.013 | 33.4 | 2.2 | 0.055 | 1.80 | 0.93 | 0.144 | 30.1 | 4.2 | 0 < 0.001 | 3.44 | 0.86 | < 0.001 |
| Graft Intact | 192 | 91.4 | 32.1 | 14.9 | 33.6 | 18.4 | 2.07 | 1,04 | 26.0 | 20.5 | 2.19 | 1.16 | |||||
| Total | 210 | 100.0 | 31.3 | 14.8 | 33.5 | 17.6 | 2.05 | 1.03 | 26.4 | 19.6 | 2.30 | 1.19 | |||||
NLR neutrophil-to-lymphocyte ratio, MERI middle ear risk index, PTA pure-tone average, COM chronic otitis media
Table 3.
Pearson correlation test statistics of variable in COM group
| NLR | MERI | Age | |
|---|---|---|---|
| NLRL | |||
| r | 1 | − 0.012 | − 0.028 |
| p | 0.861 | 0.682 | |
| MERI | |||
| r | − 0.012 | 1 | 0.208** |
| p | 0.861 | 0.003 | |
| Age | |||
| r | − 0.028 | 0.208** | 1 |
| p | 0.682 | 0.003 | |
| Preop. PTA | |||
| r | 0.072 | 0.346** | 0.420** |
| p | 0.317 | < 0.001 | < 0.001 |
| Postop. PTA | |||
| r | 0.064 | 0.408** | 0.406** |
| p | 0.386 | < 0.001 | < 0.001 |
Significant p values with correlation coefficients (r) are shown in bold
NLR neutrophil-to-lymphocyte ratio, MERI middle ear risk index, PTA pure-tone average
**Correlation is significant at the 0.01 level (2-tailed)
Discussion
The neutrophil-to-lymphocyte ratio (NLR) has been discussed as a basic parameter for ear-nose-throat practice like otitis media, facial palsy, idiopathic sudden sensorineural hearing loss and head and neck cancers [5–7, 10]. Studies investigating NLR in patients with COM in the literature are limited. Kılıçkaya et al. [11]. They examined the systemic inflammatory effects of the presence of cholesteatoma in COM patients [11]. They examined the systemic inflammatory effects of the presence of cholesteatoma in COM patients. They calculated the mean NLR as 1.94 ± 0.91 in the patients with cholesteatoma and 1.94 ± 0.85 in the control group and determined no statistically significant difference between the groups in respect of NLR (p = 0.983). Also, they reported that there was no increase in NLR in patients with bone erosions, ossicle erosion, or facial canal dehiscence. Tansuker et al. [12]. calculated NLR in 513 COM patients and divided patients into two groups as active and inactive. They found NLR a mean of 1.83 ± 0.89 for the active COM and 1.78 ± 0.85 for the inactive COM group, and groups did not reveal any significant difference (p = 0.511). Also, they reported that significantly higher percentages both of neutrophil and lymphocyte levels in active COM patients (p = 0.015, 0.004, respectively). This study does not include a control group. We find a significantly higher average of NLR in the patients with COM (2.05 ± 1.03) according to the control group (1.79 ± 0.64), (p = 0.006). The results are quite different with the reference study. This difference was thought to be due to the sample size. So post-hoc power analysis was done. According to the study reported by Kılıçkaya et al. [11], the effect size (d) for NLR calculated as 0.01. Power is calculated as 50% for α = 0.05 according to effect size (d) = 0.01. Also, power was calculated as 71% for the study presented by Tansuker et al. [12] according to an effect size (d) = 0.05 and a = 0.05. The power was calculated as 99% for this study with effect size (d) = 0.27 and α = 0.5. The effect size and power difference between studies can explain the discrepancy between results.
Kılıçkaya et al. [11] reported that the mean of the neutrophil-to-lymphocyte ratio (NLR) was not revealed a significant difference according to presence of cholesteatoma in COM patients (p = 0.983). However, in this study, only three circumstances of MERI were investigated. But MERI reveals COM status with more characteristics MERI scores have been classified as; 0; normal, 1–3; mild diseases; 4–6; moderate disease; 7–12; severe disease [13]. Therefore, it is methodologically more accurate to reveal the cause-effect relationship between NLR and MERI score. In our study, we detected MERI was 1–3 (mild disease) in 177 (84%) patients and 4 and above (moderate and severe disease) in 33 (16%)patients. NRL was calculated as 2.05 ± 1.03 in the mild disease group and 2.02 ± 1.05 in the moderate and severe disease group, and there was no significant difference between the groups (p = 0.883). Also, no significant correlation was found between MERI and NLR (p = 0.861, r = − 0.012). However, MERI was again shown to be an excellent prognostic factor for COM. Thus, in patients with postoperative graft perforation, MERI was found to be 3.44 ± 0.86 and 1.19 ± 1.16 in patients with graft intact, and the difference is significant (p = < 0.001).
NLR is a simple and quick marker to perform and varies with age or body mass index of the patients, but there is not a cut-off value for normal or disease-specific [14]. Boztepe et al. [5]. found that NLR significantly higher in patients with serous otitis media (mean 1.81) than patients with mucoid effusion (mean 1.59) and control group (mean 1.29) (p = 0.036, p = 0.001, respectively). In this study, they found the cut-off value of NLR as 1.38 for serous otitis media. Also, in this study, the sensitivity of NLR for serous otitis media was 44.1% and the specificity was 85.1%. Any similar study investigating NLR in chronic otitis media and related conditions was not found in the literature. In this study, according to the ROC analysis, the cut off value of NLR found to be 1.95 (AUC: 0.488, Likelihood ratio: 1.12) for moderate and severe disease. For this cut-off value, the sensitivity of NLR for the moderate and severe disease with COM patients was 48.5% and the specificity was 57.1%.
Conclusion
The neutrophil-to-lymphocyte ratio (NLR) can be easily calculated with a complete blood count. However, it varies in acute and chronic inflammatory conditions. In this study, NLR was found to be significantly higher in chronic otitis media patients compared to the control group. However, the effect size is small for the validity of these statistical findings. This result indicates that the study must be repeated for larger sample sizes for NLR. In addition, although NLR is found high in patients with COM, it is not related to the severity of the disease decided with MERI. The cut-off value, sensitivity and sensitivity rates of NLR obtained are not available for clinically use. It was aimed to investigate in this study whether the NLR value could be used as a marker like MERI sub-items. However, it does not provide any useful information about the status of the COM or the middle ear status. Also, it is not recommended to be used as a criterion for deciding about COM. The status of the disease in a COM patient can be easily understood by otoscopy, and it can be easily decided to consult an ENT specialist in the same way by physicians.
Acknowledgements
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Authors' contributions
All authors contributed equally to the design of study, data collection, writing, review of the references, critical review, and final approved version of the manuscript.
Funding
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References
- 1.Li JD, Hermansson A, Ryan AF, Bakaletz LO, Brown SD, Cheeseman MT, Juhn SK, Jung TT, Lim DJ, Lim JH, Lin J, Moon SK, Post JC. Panel 4: recent advances in otitis media in molecular biology, biochemistry, genetics, and animal models. Otolaryngol Head Neck Surg. 2013;148(4 Suppl):E52–63. doi: 10.1177/0194599813479772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016;138(1):16–27. doi: 10.1016/j.jaci.2016.05.011. [DOI] [PubMed] [Google Scholar]
- 3.Castanheira FVS, Kubes P. Neutrophils and NETs in modulating acute and chronic inflammation. Blood. 2019;133(20):2178–2185. doi: 10.1182/blood-2018-11-844530. [DOI] [PubMed] [Google Scholar]
- 4.Forget P, Khalifa C, Defour JP, Latinne D, Van Pel MC, De Kock M. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Res Notes. 2017;10(1):12. doi: 10.1186/s13104-016-2335-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Boztepe OF, Demir M, Gün T, Bilal N, Ensari NA, Doğru H. A novel predictive marker for the viscosity of otitis media with effusion. Int J Pediatr Otorhinolaryngol. 2015;79(12):2355–2358. doi: 10.1016/j.ijporl.2015.10.043. [DOI] [PubMed] [Google Scholar]
- 6.Wasano K, Kawasaki T, Yamamoto S, Tomisato S, Shinden S, Ishikawa T, Minami S, Wakabayashi T, Ogawa K. Pretreatment hematologic findings as novel predictive markers for facial palsy prognosis. Otolaryngol Head Neck Surg. 2016;155(4):581–587. doi: 10.1177/0194599816646552. [DOI] [PubMed] [Google Scholar]
- 7.Ha R, Lim BW, Kim DH, Park JW, Cho CH, Lee JH. Predictive values of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and other prognostic factors in pediatric idiopathic sudden sensorineural hearing loss. Int J Pediatr Otorhinolaryngol. 2019;120:134–139. doi: 10.1016/j.ijporl.2019.02.023. [DOI] [PubMed] [Google Scholar]
- 8.Kartush JM. Ossicular chain reconstruction. Capitulum to malleus. Otolaryngol Clin N Am. 1994;27(4):689–715. doi: 10.1016/S0030-6665(20)30641-1. [DOI] [PubMed] [Google Scholar]
- 9.Kökoğlu K, Şahin MI. Use of neutrophil, eosinophil, basophil, and platelet to lymphocyte ratio to predict patient satisfaction after septoplasty plus ınferior turbinate reduction. J Craniofac Surg. 2019;30(4):1022–1026. doi: 10.1097/SCS.0000000000005527. [DOI] [PubMed] [Google Scholar]
- 10.Szilasi Z, Jósa V, Zrubka Z, Mezei T, Vass T, Merkel K, Helfferich F, Baranyai Z. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as prognostic markers of survival in patients with head and neck tumours-results of a retrospective multicentric study. Int J Environ Res Public Health. 2020;17(5):1742. doi: 10.3390/ijerph17051742. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Kılıçkaya MM, Aynali G, Tuz M, Bagcı Ö. Is there a systemıc ınflammatory effect of cholesteatoma? Int Arch Otorhinolaryngol. 2017;21(1):42–45. doi: 10.1055/s-0036-1584363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Tansuker HD, Eroğlu S, Yenigün A, Taşkin Ü, Oktay MF. Can serum neutrophil-to-lymphocyte ratio be a predictive biomarker to help differentiate active chronic otitis media from ınactive chronic otitis media? J Craniofac Surg. 2017;28(3):e260–e263. doi: 10.1097/SCS.0000000000003484. [DOI] [PubMed] [Google Scholar]
- 13.Kumar N, Madkikar NN, Kishve S, Chilke D, Shinde KJ. Using middle ear risk index and et function as parameters for predicting the outcome of tympanoplasty. Indian J Otolaryngol Head Neck Surg. 2012;64(1):13–16. doi: 10.1007/s12070-010-0115-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Kontorinis G, Crowther JA, Iliodromiti S, Taylor WA, Locke R. Neutrophil to lymphocyte ratio as a predictive marker of vestibular schwannoma growth. Otol Neurotol. 2016;37(5):580–585. doi: 10.1097/MAO.0000000000001026. [DOI] [PubMed] [Google Scholar]
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