There are many factors that can lead to the acute exacerbation of tinnitus and new factors are continuously being identified. At present, it is more well-recognized with diseases that can cause tinnitus such as migraine, OSAHS, allergic rhinitis, etc. Some newly discovered phenomena such as tinnitus patients suffer from nasal septum deviation and the tinnitus disappeared after surgery to correct the nasal septum deviation, and tinnitus patients also suffered from sinusitis and tinnitus disappeared after the cure of sinusitis. The intrinsic link between these comorbidities and tinnitus is still under research.
The relationship between hearing loss and tinnitus has always been a difficult problem for tinnitus researchers. Hearing loss is a risk factor for tinnitus and tinnitus is almost always accompanied by hearing loss, however, it is currently considered that tinnitus is not directly related to the degree of the hearing loss. Tinnitus may be the result of a combination of causes. In the past years, it has become evident that hearing impairments can indirectly influence the function of the central nervous system and promote expression of neural plasticity while hearing impairments may both be the result of a combination of deficits in the auditory periphery and the effect of changes in the central nervous system. In recent years, evidence has accumulated that plastic changes in the central auditory nervous system can cause tinnitus because symptoms such as tinnitus are likely to have components that originate in the central nervous system, causing deprivation and changed balance between inhibition and excitation11. Therefore, in addition to hearing loss, other factors that can affect neural plasticity may also cause tinnitus, and cochlear-related diseases that can cause hearing loss may indirectly cause tinnitus12. This study found that the aggravation of tinnitus is often accompanied by the aggravation of hearing loss, probably because the deterioration of hearing impairment breaks the rebalancing of nervous system inhibition and excitement and the aggravation of tinnitus. Therefore, factors that can cause deterioration of hearing impairment loss may also aggravate tinnitus, such as hypoperfusion of cochlea or a viral infection.
In general, people who present with tinnitus are more likely to have sleep disorders, depression, anxiety, stress, and suicidal ideation13. Concentration, emotional stability, alertness, and adequate sleep may all influence the ability of Service members to carry out their assigned tasks, especially military man. One might therefore speculate that bothersome tinnitus may complicate the efficiency of operational missions 14.
Fatigue and stress are the two most important factors aggravating tinnitus. However, in the clinic, patients often complain of insomnia, short sleep time, easy to wake up, etc., causing doctors to misjudge the role of sleep disorders in the acute exacerbation of chronic tinnitus, and ignore the effects of fatigue and stress, while the objective sleep quality score of patients shows no serious sleep disorders and fatigue-stress assessment shows patients with more severe fatigue stress. Stress events may cause a psychosocial stress response in patients, which may cause functional changes in the immune system, such as immune defense, immune homeostasis, and immune surveillance, and changes in the immune system may be related to the occurrence and aggravation of tinnitus15, 16. Current research suggests that psychosocial stress is related to biological factors such as genetics, neuroendocrine system, and intestinal flora changes, and inheritance is the key factor determining the physiological response of stress. 5-hydroxytryptamine transporter (5HTT) gene polymorphism is an important factor determining the individual’s difference in physiological stress response. IL-1β of testers carrying the SS gene without carrying the SL gene is significantly increased after the Trier Social Stress Test17; changes in the endocrine system are mainly associated with the activation of sympathetic-adrenal medulla (SAM) system and hypothalamic-pituitary-adrenal (HPA), which affects the balance of the autonomic nervous system, the secretion and synthesis of hormones, as well as related biological changes. The decline in the richness and diversity of intestinal microflora caused by stress response may be closely related to the brain-intestinal-microbial axis, with the fluctuation of adrenaline causing the deterioration of immune regulation18. In a word, fatigue stress may cause a physiological stress response in patients with tinnitus, resulting in changes in the neuroendocrine system and some biological factors like intestinal flora in susceptible populations. And then it will cause abnormal immune system responses such as the increased level of the pro-inflammatory cytokine IL-1β mRNA, central IL-6, and so on. The function of the immune system will change and the integrity of the blood-brain barrier will be altered and psychological abnormalities or diseases will be induced such as depression, anxiety, hypertension19–21, eventually aggravating tinnitus.
Sleep is a major concern for military personnel and can directly impact safety and performance22. Nearly half of the soldiers had a sleep disorder or sleep-related medical diagnosis in 201823. Simultaneously, sleep is an essential physiological process. Sleep disorders affect performance in multiple domains of functioning including but not restricted to cognitive, emotional, metabolic, and immunologic. Sleep disorder is a major problem associated with tinnitus, especially in acute exacerbation. The more serious sleep-disturbed, the worse their tinnitus is. The prevalence of disturbed sleep in tinnitus persons varies from 25 to 60%24, 25. Tinnitus patients with disturbed sleep often have a headache and appear memory deficits26, simultaneously migraine is currently thought to be closely related to the occurrence of tinnitus to aggravate sleep disorders27. Sleep disorders may cause central sensitization, reduced adaptability, and then the central nervous system is more sensitive to tinnitus stimulation, resulting in increased tinnitus. We detected coexistence and mutual interactions of fatigue, stress, sleep disorders, and negative emotions. As Fig. 1 shows the one key finding of this study, the coexistence of fatigue stress and negative emotions is the main model leading to worse tinnitus. Jastreboff28 presented a tinnitus neurophysiological model based on the relationship between the auditory system and the limbic system and autonomic nervous system after tinnitus occurrence. Their relationship has also been verified clinically. Fatigue stress increased the negative emotions of patients, then negative emotions caused disturbed sleep by excessive autonomic nervous system excitement. If the limbic system and cerebral cortex are not adjusted in time, sleep disorders can cause negative emotions to further aggravate. Finally, tinnitus worsens. Insomnia and tinnitus in sleep-disturbed tinnitus patients can be treated with hypnotics or with insomnia-specific psychotherapy or cognitive behavior therapy.
Most patients with tinnitus have no serious emotional problems, and a part of them have negative emotions such as irritability, anxiety, and depression. Among them, anxiety (47%) is the main performance29. Anxiety patients are often characterized by some accentuated personality traits such as introversion, dysfunctional cognition. Many aspects of such dysfunctional cognitions are also frequently found in tinnitus patients. This cognition can come from the patient itself or outsiders or even doctors. For example, getting to realize that tinnitus beyond their control and fear that the tinnitus will get worse. According to De Ridder30, it is believed that the relationship between tinnitus and emotion is mainly manifested in the central and autonomic nervous system. When tinnitus occurs, tinnitus and negative emotions jointly activate the marginal neuronal reflex to form a negative feedback pathway with tinnitus-negative emotions-aggravation of tinnitus that strengthens negative emotions, making tinnitus worse or decompensated. When the negative factors caused by tinnitus continue to affect the physiological and psychological changes in the body, these changes will adversely affect the tinnitus, thus forming a vicious feedback loop, causing serious consequences. However, due to the presence of the limbic system, it can suppress the tinnitus signal from reaching the auditory cortex to a certain extent to prevent the brain from consciously perceiving the tinnitus signal31. Thus it relieves the negative emotions of patients. For anxious or depressed tinnitus patients, treatment of concurrent anxiety or depression symptoms in tinnitus patients is essential. Treatment options include pharmacological, for example, antidepressants, and psychotherapeutic approaches.
Usually, we believe that peripheral damage caused by noise in the cochlea leads to abnormal neural activity in the brain and the false perception of tinnitus. Prolonged exposure to noisy environments causes neural degeneration in the central nervous system or changes in the balance of excitation and inhibition in auditory pathways. Tinnitus appeared afterward32, 33. For such reason, Gilles, A34 emphasizes the prevention of noise or loud sounds, reducing the probability of tinnitus from the source, as well as the maintenance of tinnitus prognosis. Besides, Shiming Yang proposed a brand new hypothesis named “bionic active noise reduction” by presenting the innate structures in the auditory system that may contribute to noise suppression. If this hypothesis can be verified, it may have significant implications for noise protection in social medical services, especially to prevent the occurrence and aggravation of tinnitus35. The study also found that abrupt changes in barometric pressure such as diving in water or during a flight are also the cause of acute exacerbation of chronic tinnitus. Barotrauma may have caused aggravated tinnitus because of the cochlear fluids has been further affected for an abrupt change in barometric pressure. Aggravated tinnitus may either be temporary or persistent.
Patients with tinnitus frequently have headaches but the relation between these two disorders is not always casual. More and more researcher believes that headaches and tinnitus may be symptoms of the same disease. they cause a high degree of disability, and both are often accompanied by psychiatric disorders36. Additionally, these two symptoms share some common mechanisms in their tendency to become chronic. However, in this study, it was regrettable that headaches were not included in the study to prove that the onset of headache can induce acute exacerbation of chronic tinnitus. In the face of exacerbation of chronic subjective tinnitus, we not only need to think about the problem from the perspective of hearing loss-tinnitus, but also understand the possible causes of the disease aggravation from the factors of social support, patient's work, and life, and social psychological stress,and analyze the intrinsic relationship between incentives and diseases, help patients rebuild good living habits, social interpersonal relationships, improve their ability to cope with stressors, and prevent tinnitus aggravation and prognosis maintenance.