Statistical Analysis
Data analysis was performed using IBM SPSS Statistics software version
17.0 (IBM Corporation, Armonk, NY, USA). Whether the distributions of
continuous variables were normal was determined using the
Kolmogorov-Smirnov test. The assumption of the homogeneity of variances
was examined with the Levene test. Descriptive statistics for continuous
variables were expressed as mean ± standard deviation values or median
(25th – 75th percentiles), where
appropriate. Numbers and percentages were used for categorical data. The
mean differences between the groups were compared using Student’s t-test
when the parametrical test assumptions were met, and the Mann-Whitney U
test otherwise. Categorical data were analyzed using Pearson’s
χ2 test. The optimal cut-off points of laboratory
measurements to discriminate cases and controls were evaluated with the
ROC (Receiver Operating Characteristic) analysis by obtaining the
maximum sum of sensitivity and specificity for the significant test. The
sensitivity, specificity, positive and negative predictive values, and
accuracy levels for PMI were also calculated. A p value less than 0.05
was considered as statistically significant.
Results:
Table 1 presents a comparison of the demographic characteristics and
laboratory measurements of the control and tinnitus groups. There was no
statistically significant difference between the control and tinnitus
groups concerning the mean age, gender and RBC, neutrophil, lymphocyte,
PLR and NLR levels (p > 0.05). However, in the tinnitus
group, the hemoglobin and MPV levels were statistically significantly
higher (p < 0.001), and the PLT level was statistically
significantly lower (p = 0.033) compared to the control group. In
addition, the PMI of the tinnitus group was statistically significantly
higher than that of the control group (p < 0.001) (see Figure
1).
Table 2 shows the results of the ROC analysis conducted to determine
whether PMI, PLR and NLR were statistically significant markers in
distinguishing between the control and tinnitus groups. The area under
the curve (AUC) for the PMI measurements was found to be statistically
significant in this differentiation [AUC = 0.678, 95% CI: 0.623-0.732
and p < 0.001] (see Figure 2). The optimal cut-off value for
PMI was 1.6452, at which PMI had a sensitivity of 89.8%, specificity of
40.5%, and positive and negative predictive values of 58.3% and
81.1%, respectively, and the diagnostic accuracy rate of this parameter
was 64.2%.
The areas under the ROC curve for the PLR and NLR measurements in
differentiating between the control and tinnitus groups were not found
to be statistically significant (AUC = 0.539, 95% CI: 0.479-0.598 and p
= 0.201 and AUC = 0.521, 95% CI: 0.462-0.580 and p = 0.485,
respectively). In other words, neither PLR nor NLR has a statistically
significant effect on this differentiation.
Discussion:
Tinnitus is a disease in which the patient reports hearing sounds of
different character and intensity coming from the ear without any
external stimulus. This condition results in a large number of patients
presenting to otorhinolaryngology clinics. Although 10-15% prevalence
has been reported in different case series, this rate may exceed 30% in
the population over 60 years of age [9]. Tinnitus can affect one ear
or both ears. There are many studies on the role of platelets in this
condition. In our study, we tried to determine the rate of real vascular
causes by excluding factors leading to temporary tinnitus, such as
fatigue, insomnia, short-term drug use, and advanced age (presbycusis)
in order to reveal the independent effect of vascular and hematological
variables. It is known that MPV is directly related to inflammatory
processes and platelet function [8]. Increased MPV has been
identified as an independent risk factor for myocardial infarction and
stroke [10]. Therefore, the presence of various effects of mediators
secreted by platelets on tissues, especially neovascularization is a
fact that should not be overlooked. Considering only the volume of
platelets and evaluating them regardless of their number will lead to a
lack of interpretation concerning platelet function. However, it is also
important to recognize that the significant difference in MPV may be due
to pre-measurement factors, including blood collection tube selection,
processing and equipment used [11]. Increased MPV indicates an
increase in granulocytes in platelets, which is directly related to
their activity; i.e., larger platelets are more active than smaller
platelets [12].
In addition to the volumetric size of platelets, their number is also
important. Ischemia causes an inflammatory process to begin. In ischemic
tissues, many proinflammatory cytokines, mainly TNF-alpha, are released
in the affected tissue [13]. It is considered that an ischemic
situation in auditory pathways caused by vascular pathologies may
trigger a mechanism that results in an increase in MPV. This increase in
MPV or platelet count naturally leads to an increase in PMI. In our
study, NLR and PLR were found to be higher in the tinnitus patients than
in the control group, indicating the association of these parameters
with inflammatory and ischemic events, similar to many previous
publications. In a study by Kemal et al., MPV was observed to be
increased in tinnitus patients, and the authors suggested that tinnitus
might occur as a result of increased MPV causing microvascular
thrombosis in the vessels of the auditory tract and
hypoperfusion-ischemia [14]. However, we consider that it is not
appropriate to consider MPV alone to explain all these mechanisms. MPV
is a very practical and inexpensive parameter that can be measured as
part of a routine complete blood count analysis. However, various
factors, such as age, obesity, hyperlipidemia, diabetes, smoking, and
hypertension can affect platelet parameters [8]. Thus, the overall
platelet function can be more accurately reflected by platelet mass
compared to platelet count alone. This idea was first discussed by
Gerday et al., who demonstrated that with the use of PMI, the number of
platelet transfusions decreased [15].
To the best of our knowledge, this is the first study to explore the
relationship between PMI and tinnitus in the literature. We consider
that PMI, in which platelet counts are also evaluated, will be more
useful than MPV alone in explaining the mechanism of tinnitus. In animal
experiments, the antioxidant effects of platelets have been shown to
reduce oxidant-induced pulmonary edema by preventing increased membrane
permeability [16]. Platelets maintain normal endothelial
permeability in lungs exposed to ischemia-reperfusion injury by
releasing platelet glutathione-redox cycle antioxidants [17]. Lo et
al. also reported an increase in pulmonary vascular permeability in
animals with thrombocytopenia [18]. Some studies on platelet count
in neonatal lung tissues have revealed its effect on inflammatory
processes. PMI is associated with platelet functionality since larger
platelets are enzymatically more active than smaller platelets.
Recently, some studies aimed to reduce unnecessary transfusion by using
PMI rather than platelet count as an indicator of the need for this
procedure [15, 19]. For all these reasons, PMI is considered to be a
better marker than MPV in some cases. Okur et al. reported that
premature babies with bronchopulmonary dysplasia, intraventricular
hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, and
sepsis had lower PMI in the early period compared to those without these
neonatal morbidities. The authors noted that PMI was significantly lower
in these neonatal complications although the differences in MPV were not
significant [20]. This situation may also be valid for tinnitus
patients.
In our study, we found that PMI was statistically significantly higher
in the tinnitus group, but larger series are needed to prove the
superiority of PMI over MPV in tinnitus pathogenesis. Although there
were patients with lower MPV values in the tinnitus group than in the
control group, the fact that PMI was higher in the former suggests that
it is a more sensitive parameter. It was even the case that the MPV
value was very similar and almost equal for certain cases in the two
groups whereas PMI was consistently higher in the tinnitus group. When
these findings are analyzed one by one, they each indicate that PMI may
be a more accurate and sensitive parameter than MPV in the
etiopathogenesis of the disease and for use as a clinical marker in
tinnitus patients. In our evaluation, we did not take the severity of
tinnitus into account nor did we administer any questionnaire (e.g.,
Tinnitus Handicap Inventory) to the tinnitus patients for this purpose.
This is because we did not have enough evidence that vascular causes
affect the severity of tinnitus. The significant difference we detected
in PMI between the tinnitus and control groups can guide further studies
to investigate the relationship between tinnitus severity and PMI.
A high neutrophil and platelet count reflects inflammation while a low
lymphocyte count is indicative of general stress and impaired defense
mechanisms [21]. In otolaryngology practice, high NLR values have
been found to be associated with a variety of pathological conditions,
such as vestibular neuritis [22], Bell’s palsy [23], idiopathic
sudden sensorineural hearing loss [24], and squamous epithelial cell
carcinoma of the head and neck [25]. Recently, Özbay et al. [26]
reported significantly higher NLR values in patients with severe
tinnitus than controls and concluded that NLR should be considered as a
potential clinical marker of tinnitus. From this point of view, it is
seen that NLR has an important place in the evaluation of tinnitus. In
our study, we determined NLR values consistent with previous research
and confirmed that they were significantly different in tinnitus
patients compared to controls. We also observed a positive correlation
between PMI and NLR.
PLR, another marker of inflammatory processes, has been used together
with NLR in previous literature studies. In particular, higher PLR
values have been reported in vestibular neuritis and Bell’s palsy
compared to control groups, and in this respect, PLR has been accepted
as an important parameter [22, 23]. Some studies even argue that PLR
is a more significant inflammation marker than NLR and provides more
information concerning prognosis. For example, Türkmen et al. [27]
stated that it could predict inflammation better than NLR in patients
with end-stage renal disease. PLR was also found to be superior to NLR
in predicting clinical outcome in patients with soft tissue carcinoma
[28]. However, due to the lack of a detailed study on tinnitus, such
a comparison cannot yet be made for this condition. Although we do not
have data on the superiority of PLR or NLR over each other, when both
NLR and PLR are considered as inflammation markers, they are reported to
be correlated with each other in literature studies, as was the case in
our research.
Limitations:
The retrospective design was the greatest disadvantage of this study,
causing a serious limitation in the number of patients and the necessity
to keep the exclusion criteria very wide; thus, our patient sample group
was limited. In addition, the inclusion of tinnitus severity scoring in
a further study conducted in line with our results can provide data that
we were not able to present in the current study.
In conclusion, in this study, the NLR, PLR and MPV values were found
to be higher in the tinnitus group compared to the control group, as
expected. However, as additional data for tinnitus cases, PMI was also
observed to be significantly higher compared to the control group,
indicating that the study reached its objective. PMI has managed to
become a predictive value for tinnitus even in patients with lower MPV
levels than normal. Therefore, we consider that PMI is more sensitive
than other markers, especially MPV in inflammatory events. We believe
that PMI can be suitable and provide meaningful results in many areas in
otolaryngology and should be further investigated in cases with Bells’
palsy vestibular neuritis, nasal polyps and allergic rhinitis, and
sudden sensorineural hearing loss.
*The authors declare no conflict of interest.
**The authors declare that they did not receive any financial support
for the study.
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