Abstract
Objectives
A number of etiologies of idiopathic sudden sensorineural hearing loss (ISSNHL) have been proposed. Vascular disturbance is one cause of ISSNHL and has been reported to be associated with fibrinogen. We aimed to determine whether hyperfibrinogenemia is associated with poor outcome and whether a serial change in fibrinogen level is associated with outcome.
Methods
Twenty-two patients with ISSNHL were enrolled. We compared the levels of fibrinogen in ISSNHL groups classified as improved and non-improved according to improvement of hearing. Blood samples were also collected from patients who visited the emergency room with coronary heart disease (CHD) as the control group.
Results
Initial fibrinogen level was significantly different between the non-improved and improved ISSNHL group (350.63 ± 87.20 vs. 310.71 ± 81.06. The improved ISSNHL group showed a “surge phenomenon”, in which fibrinogen started to decrease at day 5 and increased at day 26. In the non-improved group, fibrinogen remained elevated throughout the course of therapy.
Conclusion
It is important to measure not only the initial fibrinogen level but also to monitor its change throughout the course of therapy in order to predict the outcome of ISSNHL.
1
Introduction
Idiopathic sudden sensorineural hearing loss (ISSNHL) is an audiologic emergency disease characterized by sudden hearing loss that affects 5–20 per 100,000 individuals annually . A number of etiologies of ISSNHL have been proposed, including viral infection, vascular disturbance, and immune-mediated mechanisms. However, there is no conclusive evidence supporting any particular hypothesis .
A previous study showed that elevated fibrinogen levels lead to decreased blood flow in the cochlea of guinea pigs in vivo . Because elevated plasma fibrinogen plays a major role in cardiovascular diseases, it is possible that this plasma protein is also involved in the pathogenesis of sudden hearing loss of vascular origin . There have been reports of elevated fibrinogen in ISSNHL patients compared to controls, which could act as a risk factor and prognostic factor . However, the role of fibrinogen as a prognostic factor is controversial and little research has been performed on the relationship between serial changes of fibrinogen level and hearing outcome .
In this study, we aimed to determine whether hyperfibrinogenemia at the beginning of the disease is associated with poor outcome and whether a serial change in fibrinogen level is associated with outcome.
2
Methods
2.1
Patients
We assessed 53 patients with ISSNHL who visited the clinic in 2015. We defined ISSNHL as acute unilateral deafness with an abrupt onset (generally within 3 days) and with > 30 dB hearing loss at three consecutive frequencies. Inclusion criteria for this study were as follows: clinic visit within 1 week from onset, no previous steroid treatment, no previous hyperfibrinogenemia disease (e.g., cardiovascular disease, arrhythmia, cerebrovascular disease, atherosclerosis) and no previous history of taking any antiplatelet drugs. Patients were excluded from the study if they had any otologic disease such as chronic otitis media, otosclerosis, acoustic trauma history, and Meniere’s disease. They were usually discharged 5–7 days after admission and underwent clinical follow-up for 2 months. All patients were treated with prednisone at an initial dose of 1 mg/kg per day with a progressive dose reduction. After exclusion of patients with follow-up loss (13 patients) and those missing laboratory tests at regular follow-up days (18 patients), we finally included 22 patients in this study. To compare the level of fibrinogen with that in a control group, we included 39 patients who visited the emergency department for acute coronary heart disease (CHD). These patients were admitted for acute symptoms of CHD with no previous cardiovascular disease and had been diagnosed with CHD in the emergency room. All patients interested in participating in this prospective trial who met the inclusion criteria signed an informed consent approved by the Yonsei Wonju University of Medicine Review Board (IRB#CR315008).
2.2
Hematologic examinations
Blood samples for all patients were tested at the first visit by CBC and routine chemistry. An automated blood cell counter was used for CBC measurements using Sysmex XE-2100 (Sysmex, Kobe, Japan). NLR and PLR were calculated as the simple ratio between the absolute neutrophil and the absolute lymphocyte counts and the absolute platelet and absolute lymphocyte counts, respectively. Hemostasis determinations were made for prothrombin time (PT, international normalized ratio, [INR]), activated partial thromboplastin time (aPTT ratio), and plasma fibrinogen. The PT is the value of PT (test)/PT (normal). The aPTT (ratio) is the value of aPTT (test)/aPTT (normal). According to the study protocol, ISSNHL patients were monitored at five defined time points. Time point 0 was the first visit to the outpatient clinic and all patients were subsequently monitored on days 1, 5, 12, and 26. All samples were run in duplicate and the mean values were used for statistical analysis.
2.3
Auditory evaluation
Pure-tone thresholds were obtained for air conduction at 250 Hz, 500 Hz, 1 kHz, 2 kHz, 4 kHz, and 8 kHz and for bone conduction at 250 Hz, 500 Hz, 1 kHz, 2 kHz, and 4 kHz at each time point. Audiologic data were reported by the recommended methods of the Hearing Committee of the American Academy of Otolaryngology Head and Neck Surgery. Patients were evaluated according to the recovery observed during a maximum of 2 months during the follow-up period. Pure tone audiometry (PTA) was performed and responses of the patients to the treatment were classified according to Siegel’s criteria ( Table 1 ) . The patients were divided into two groups: improved ISSNHL (complete + partial + slight improvement) and non-improved ISSNHL (no improvement). The first recovery time indicates the time when the patient’s hearing first recovered according to Siegel’s criteria. Final recovery time indicates the last follow-up time.
| Type | Hearing recovery | |
|---|---|---|
| I | Complete recovery | Patients whose final hearing level is better than 25 dB regardless of the size of the gain |
| II | Partial recovery | Patients who show > 15 dB of gain and whose final hearing level is between 25 and 45 dB |
| III | Slight recovery | Patients who show > 15 dB of gain and whose final hearing level is poorer than 45 dB |
| IV | No improvement | Patients who show < 15 dB of gain |
2.4
Statistical analyses
A power analysis was performed to determine the extent to which the proposed sample size would be adequate (effect size = 0.082, α-risk = 0.05, sample size = 21). Continuous variables were summarized as mean ± standard deviation (SD) and comparisons between continuous variables were performed using the Student’s t -test for comparison of two variables and ANOVA for comparison among three variables. Categorical variables were summarized as percentages of the group total and comparisons between groups were analyzed using either the Fisher exact test or Chi-square test as appropriate. A simple linear analysis was performed between the recovery of hearing and hematologic results. All tests used a p -value of 0.05 as the threshold for significance. All statistical analyses were performed using SPSS Software (PASW for Windows, Rel. 18.0.0. 2009; SPSS Inc., Chicago, IL, USA).
2
Methods
2.1
Patients
We assessed 53 patients with ISSNHL who visited the clinic in 2015. We defined ISSNHL as acute unilateral deafness with an abrupt onset (generally within 3 days) and with > 30 dB hearing loss at three consecutive frequencies. Inclusion criteria for this study were as follows: clinic visit within 1 week from onset, no previous steroid treatment, no previous hyperfibrinogenemia disease (e.g., cardiovascular disease, arrhythmia, cerebrovascular disease, atherosclerosis) and no previous history of taking any antiplatelet drugs. Patients were excluded from the study if they had any otologic disease such as chronic otitis media, otosclerosis, acoustic trauma history, and Meniere’s disease. They were usually discharged 5–7 days after admission and underwent clinical follow-up for 2 months. All patients were treated with prednisone at an initial dose of 1 mg/kg per day with a progressive dose reduction. After exclusion of patients with follow-up loss (13 patients) and those missing laboratory tests at regular follow-up days (18 patients), we finally included 22 patients in this study. To compare the level of fibrinogen with that in a control group, we included 39 patients who visited the emergency department for acute coronary heart disease (CHD). These patients were admitted for acute symptoms of CHD with no previous cardiovascular disease and had been diagnosed with CHD in the emergency room. All patients interested in participating in this prospective trial who met the inclusion criteria signed an informed consent approved by the Yonsei Wonju University of Medicine Review Board (IRB#CR315008).
2.2
Hematologic examinations
Blood samples for all patients were tested at the first visit by CBC and routine chemistry. An automated blood cell counter was used for CBC measurements using Sysmex XE-2100 (Sysmex, Kobe, Japan). NLR and PLR were calculated as the simple ratio between the absolute neutrophil and the absolute lymphocyte counts and the absolute platelet and absolute lymphocyte counts, respectively. Hemostasis determinations were made for prothrombin time (PT, international normalized ratio, [INR]), activated partial thromboplastin time (aPTT ratio), and plasma fibrinogen. The PT is the value of PT (test)/PT (normal). The aPTT (ratio) is the value of aPTT (test)/aPTT (normal). According to the study protocol, ISSNHL patients were monitored at five defined time points. Time point 0 was the first visit to the outpatient clinic and all patients were subsequently monitored on days 1, 5, 12, and 26. All samples were run in duplicate and the mean values were used for statistical analysis.
2.3
Auditory evaluation
Pure-tone thresholds were obtained for air conduction at 250 Hz, 500 Hz, 1 kHz, 2 kHz, 4 kHz, and 8 kHz and for bone conduction at 250 Hz, 500 Hz, 1 kHz, 2 kHz, and 4 kHz at each time point. Audiologic data were reported by the recommended methods of the Hearing Committee of the American Academy of Otolaryngology Head and Neck Surgery. Patients were evaluated according to the recovery observed during a maximum of 2 months during the follow-up period. Pure tone audiometry (PTA) was performed and responses of the patients to the treatment were classified according to Siegel’s criteria ( Table 1 ) . The patients were divided into two groups: improved ISSNHL (complete + partial + slight improvement) and non-improved ISSNHL (no improvement). The first recovery time indicates the time when the patient’s hearing first recovered according to Siegel’s criteria. Final recovery time indicates the last follow-up time.
