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  • 學位論文

職業性噪音性聽力損失:從職場暴露到動物實驗

Occupational Noise-induced Hearing Loss: From workplace exposure to animal experiment

指導教授 : 王榮德

摘要


職業性與環境性噪音所引起的聽力損失,長久以來,一直是後天性感覺神經性聽力損失的最重要一環;更是造成近年來全球性聽力損失疾病負擔的最主要原因之一。本論文結合環境與職業醫學和耳鼻喉科學的觀點,從職業場所的噪音危害評估、勞工的聽力保護、職業病鑑定;進而利用動物實驗基礎模型,以電生理學和分子生物學方法,研究噪音性聽力損失的機轉,以及噪音對於平衡系統的影響。 工作場所的噪音,一直是自工業革命以來,職業醫學中不容忽視的一環。不僅是噪音的來源無所不在,噪音性聽力損失的臨床診治,也一直困擾著耳鼻喉科醫師與職業病醫師。預防重於治療的公共衛生觀點,讓我們將聽力保護的觀念推廣到醫院以外的職場。藉由與某石油公司的合作,我們進行了一個橫斷面的研究,並根據此資料的分析得知,噪音性聽力損失在加油站男性勞工的高頻率區聽力圖表現,以6k Hz凹陷為最多,4k Hz凹陷其次;其危險因子主要為年齡及噪音暴露。並且,環境評估的個人噪音八小時累計音壓逼近一般所建議的85 dBA;頻譜分析顯示,主要的噪音源分布於500 Hz~4k Hz。 職業病鑑定是職業醫學訓練中的重要課題,如何準確而客觀的評估噪音對於勞工聽力的損害一直是聽力學上的挑戰之一。近年來,隨著醫療科技的精進,能夠客觀性評估聽覺功能的聽力檢查儀器推陳出新,譬如:耳聲傳射、聽性穩定狀態誘發電位聽力檢查等;除了讓我們可以更為客觀而準確的判斷勞工聽力損失的閾值之外;並且,更能提供臨床上職業醫學門診及耳鼻喉科醫師專業上,客觀而可信賴的鑑別診斷工具,特別是一些有爭議的職業病鑑定或是勞工殘廢補償判定時的詐聾案例。因此,藉由醫學中心職業病門診的噪音性聽力損失案例,結合耳鼻喉科與聽力學的專業知識,我們發現能夠提供臨床醫師客觀判斷勞工聽力閾值的新工具 “聽性穩定狀態誘發電位聽力檢查”。 噪音性聽力損失的基本分子機轉,一直是基礎耳科學研究中的熱門話題;因為,藉由基礎實驗的探討,不僅能讓臨床醫師更了解疾病的病理機制,更有機會能從這些基礎研究中,尋找治療噪音性聽力損失的契機。於是採用動物實驗模式,進行內耳耳蝸細胞的基礎實驗,發現耳蝸側壁細胞中,富含與先天性聽障基因有關的Connexin 26蛋白質;並且,經過噪音的急性刺激後,會有明顯的增加。可見Connexin 26蛋白基因,可能不只與先天性的遺傳性聽障有關,在後天性的噪音性聽力損失機轉中,仍有其重要地位。 噪音對於內耳系統的影響,除了表現出聽覺喪失外,還有不易察覺的平衡障礙。由於中樞系統的代償作用,往往使得這些平衡失調現象,潛藏在臨床症狀之下。近年來,藉由前庭誘發肌性電位的發展,提供了臨床醫師得以直接紀錄,並偵測內耳球囊頸肌反射的絕佳工具。所以,先採用動物實驗模式進行噪音刺激後天竺鼠前庭誘發肌性電位變化的研究;並進而在臨床上,驗證於急性音響外傷患者的變化。結果發現噪音對於天竺鼠及人類前庭功能的影響,有類似聽覺耳蝸系統的暫時性及永久性喪失之經時變化;而且,平衡系統的回復,早於聽覺系統的回復,可成為未來聽性外傷後,患者聽力是否可以回復的一項指標。 所以,本論文包括五部份: 第一部分以環境醫學觀點:研究男性加油站加油員高頻率凹陷型聽力圖的發生率及其危險因子 第二部分以職業醫學觀點:研究以聽性穩定狀態誘發電位聽力檢查作為客觀評估噪音性聽力損失者實際聽力閾值的工具 第三部分以分子生物學觀點:研究Connexin 26在天竺鼠耳蝸側壁經噪音聽性外傷刺激後的變化 第四部份以電生理學觀點:研究天竺鼠經急性音響外傷後前庭誘發肌性電位的永久性與暫時性變化 第五部份以臨床醫學觀點:研究急性音響外傷後患者之前庭誘發肌性電位的臨床表現

並列摘要


Hearing loss from occupational and environmental noise exposures remains the most significant causes of acquired sensorineural hearing loss in the world. The majority of global disease burden from hearing loss is attributed to occupational and environmental noise worldwide. As recent medico-technological advancements of audiological battery in the objectively hearing assessment, such as otoacoustic emission, auditory steady state evoked potential, we could identify more objectively the hearing threshold level of workers, who suffered from hearing impairment. On the other hand, occupational clinician and otolaryngologist could also take this advantage to differentiate those workers who intended to malinger for occupational compensation or medico-legal issues. Moreover, although the 4k Hz dip was well known as the clinical sign of audiometry for noise-induced hearing loss and 85 dBA was well accepted for recommended permission exposure level in modern industry, we further investigate the major determinants of risk factors on high frequency notch audiogram among male gasoline distribution workers in Taiwan. With new understanding of mechanistic insights in noise-induced hearing loss from animal laboratory, we can identify the safe and effective interventions that provide scientific rationale to eliminate this most important cause of acquired hearing loss. Such as the role of gap junction protein, connexin 26, in the lateral wall of cochlea, this has been proved to be related to congenital and hereditary deafness. Moreover, a new electrophysiological tool, vestibular evoked myogenic potential, was applied in animal model of noise-induced hearing loss to assess objectively the permanent and temporary damages of vestibular system in inner ear after acoustic trauma. Here we present an update review and propose new tools to identify noise-induced hearing loss in epidemiological aspects from human workplaces exposure of male gasoline distribution workers in a petrochemical company in Taiwan. Besides, the pathophysiology of acute acoustic injury to inner ear, both cochlear and vestibular systems, was investigated by electrophysiological instruments and molecular biological techniques in animal experimental models, then applied to human subjects with acute acoustic trauma. There were five domain parts included in this thesis: Part I: Environmental perspective - Prevalence and determinants of high frequency audiometric notch in male gasoline distribution workers. Part II: Occupational perspective - Objective assessment of auditory thresholds in noise-induced hearing loss using steady-state evoked potentials. Part III: Molecular biological perspective - Expression of connexin 26 in the lateral wall of rat cochlea after acoustic trauma. Part IV: Electrophysiological perspective - Temporary and permanent loss of vestibular evoked myogenic potentials after acute acoustic trauma in guinea pigs. Part V: Clinical perspective - Vestibular evoked myogenic potentials in acute acoustic trauma

參考文獻


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