3.4 Correlation between outcomes of patients with SSNHL and Clinical characteristics
Based on the final PTA, patients were dichotomized into treatment responders and treatment non-responders. A chi-squared test was performed to disclose the potential correlation between clinical characteristics and outcomes of patients. As indicated in Table. III, patients with increased concentration of MMP-9 following treatment were more frequently accompanied by favorable outcomes (P=0.007, χ2=7.436). However, the incidence of tinnitus or vertigo had no significant difference between the two groups (tinnitus vs vertigo, P=0.332 vs P=0.239, χ2=0.724 vs χ2=1.213). Moreover, treatment responders had similar trends in gender or side of hearing loss as compared with treatment non-responders (gender vs side, P=0.353 vs P=0.474, χ2=0.439 vs χ2=0.123). Whereas, patients with favorable outcome was younger than those suffered from treatment resistance (P=0.03, χ2=4.623).
Though the Chi-squared test did not reveal the incidence of tinnitus or vertigo was related with the outcomes, we still put them into binary multiple logistic regression analysis, given several pieces of literature reported the opposite results. Interestingly, the result disclosed changes in MMP-9 concentration was the only factor closely associated with favorable outcomes (P=0.008, OR=5.13, 95% CI: 1.53-17.28, Table. III).
Discussion
To the best of our knowledge, this is the first study about the correlation between changes of MMP-9 concentration and outcomes of patients with SSNHL. In our previous study, we found the concentration of MMP-9 was decreased in patients with SSNHL, as compared with in healthy controls, and the difference had no correlation with the types of SSNHL [12]. The same conclusion is formulated in this further study. Though in these 4 types of SSNHL, the mean concentration of MMP-9 seemed to be elevated following treatment, the increment did not have a significant difference. Besides, this increment seemed more due to the variational therapy responses in different types of SSNHL. Patients with a profound type of SSNHL are known to accompany with the worse outcomes, while patients with ascending type, the prognoses are in contrast. Hence, the post-treatment concentrations of MMP-9 in patients with profound type were almost the same as the pre-treatment concentrations, whereas patients with an ascending type of SSNHL gained significant increment in MMP-9 concentrations following treatment.
The correlations between age, vertigo, or tinnitus with the favorable outcomes of patients with SSNHL are in debate [14-16]. In our study, we displayed that age and the increment of MMP-9 concentration following treatment were correlated to the hearing gain by the Chi-squared test. However, age failed to show the association with outcome in the binary multiple logistic regression test and the increment of MMP-9 was the only factor closely related to favorable outcomes. MMP-9 is recognized as a metalloproteinase to degrade the extracellular matrix and to induce the infiltration of inflammatory cells [17]. Recently, several studies have shown that hyperhomocysteinemia was associated with SSNHL and can induce an increase in the cochlear expression of MMP-2 and MMP-9 in mice models [18-19]. In consideration of these studies, we speculated that MMP-9 might deposit in different sites of the inner ear and induce inflammation by degrading the extracellular matrix. When the damage occurred at the top inner hair cells of the cochlea, patients suffered from ascending type of SSNHL, whereas the damage occurred at the bottom inner hair cells of the cochlea, patients developed descending type of SSNHL. Following treatment, especially with the glucocorticoid, the deposition of MMP-9 in the inner ear decreased and then induced the relief of the inflammatory reaction in the inner ear. Due to this nonspecific deposit, the outcome of patients had no significant difference with the types of SSNHL but with the changes in the concentration of MMP-9 following therapy.
The etiology of SSNHL is still unknown. The immune disorder is considered as one of the major causes of SSNHL, but there is no direct evidence to prove it. Several studies have revealed the correlations between MMP-9 and other diseases. Robaka, et al found serum MMP-9 level was decreased in patients with active SLE, and the level was elevated when SLE turned to an inactive state [20]. Vira H, et al obtained the same conclusion with detecting the polymorphisms of MMP-9 in patients with SLE [21]. In contrast, studies in cardiovascular diseases or tumors indicated that serum conc-entration of MMP-9 was positively associated with the activity of the diseases [22,23]. In our study, the altering level of MMP-9 was accordant with the changes in patients with autoimmune disease [24], thus provided further evidence that autoimmune disorder was one of the major causes of SSNHL.
Altogether, we identified that elevated serum concentrations of MMP-9 was not associated with different types of SSNHL, stratified by the different shapes of the audiogram, but closely correlated to favorable outcomes in patients with SSNHL, therefore it might serve as a prognosis prediction factors of patients with SSNHL. Given the increment of MMP-9 concentration following treatment was accordant with patients with the auto-immune diseases rather than patients with cardiovascular diseases or tumors, it proved another indirect evidence that immune disorder was one of the major pathogenesis in SSNHL.
Limitations in our study are mainly the small case number of patients with SSNHL. We ascribed this limitation to several patients admitted to our hospital with treatment in outpatient department or other hospitals. Whereas, there were still several patients refused to take audiometry test following treatment, which leaves the clinical characteristics uncompleted. Furthermore, we only performed an ELISA test to provide the indirectly evidence, the mechanism of the altering MMP-9 concentration in patients with SSNHL needed to be further proved.
Conclusions
Our study revealed that elevated serum concentration of MMP-9 following treatment in patients with SSNHL was closely correlated with favorable outcomes. The result is accordant with patients with auto-immune diseases, therefore to provide an indirectly evidence that immune disorder was one of the main pathogenesis in SSNHL. Further study was in need to investigate the underlying mechanism in the increment of MMP-9 concentration following treatment with patients benefited from hearing gained.