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作者：Jacquelyn K. Beals, PhD  
出處：WebMD醫學新聞

　　December 15, 2009 (阿根廷布宜諾斯艾利斯) —一篇新研究的結果顯示，因為維他命B12缺乏引起的感覺神經病變，可能是長期無法解釋的咳嗽與咽喉功能不佳原因之一，維他命B12補充品改善組織胺閾值且顯著提升維他命缺乏患者的咳嗽閾值，但是對於控制組並無效果。
　　
　　在世界過敏組織第21屆世界過敏研討會中，由義大利Turin大學與Mauriziano醫院過敏與臨床免疫科的Giuseppe Guida醫師發表該研究，檢視組織胺對於無法解釋之咳嗽患者的咳嗽閾值和上下呼吸道反應的影響。
　　
　　Guida醫師在發表時表示，長期咳嗽的原因很多，他們診所的302名長期咳嗽患者中，原因包括藥物副作用、咳嗽反射敏感、胃食道逆流疾病、過敏性鼻炎；約有15%病患屬於原因不明的長期咳嗽。
　　
　　研究團隊問道，長期咳嗽和胸腔外呼吸道失能是否為神經病變的表徵。Guida醫師表示，維他命B12缺乏在以前曾被認為會引起許多年長病患的週邊感覺神經病變，因此，這種缺乏情況可能是無法解釋的長期咳嗽的一個可能原因。
　　
　　目前的研究探討長期不明原因咳嗽的40名患者，其中，25人被發現有維他命B12缺乏(血清濃度<300 pg/mL)；控制組的15名長期咳嗽患者並未發現營養不足。
　　
　　Guida醫師向Medscape Allergy and Immunology表示，維他命B12缺乏在年長者比較常見。一般而言，你可以發現年長者的維他命值較低，因為他們的營養上有一些問題。
　　
　　以肺功能量計評估維他命不足者和對照組，測量他們的呼氣一氧化氮。使用組織胺吸入以評估支氣管、胸腔外呼吸道、與咳嗽閾值。組織胺激發測試可以刺激呼吸道而足以引起劇咳。這項檢測引起氣道收縮，高反應性呼吸道的病患對較低劑量的組織胺會有反應。本研究之高反應性定義為閾值低於8 mg/mL。
　　
　　維他命B12缺乏的病患被發現，胸腔外呼吸道與咳嗽閾值顯著較低，不過支氣管閾值和對照組無差異。
　　
　　已知維他命B12缺乏會伴隨有較高的神經生長因子(NGF)值，可能會導致呼吸道的神經發炎。分析6名維他命B12缺乏病患與3名對照組的口咽切片，發現維他命B12缺乏病患上皮細胞的NGF值顯著高於對照組(P< .02)。資料圖顯示，NGF值和維他命B12血清濃度(pg/mL)對數之間有反向關係。
　　
　　維他命B12補充品改善維他命B12缺乏病患的組織胺閾值(降低高過敏性)，對照組則無顯著改變。支氣管(P< .01)、胸腔外呼吸道(P< .001)、咳嗽(P< .01)等閾值都有改善。
　　
　　Guida醫師向Medscape Allergy and Immunology表示，藉由肌肉注射可以簡單地給予補充品，所以，理論上，有一個好方法用來治療此疾病。
　　
　　會議共同主持人、巴西de Santa Catarina聯邦大學、氣喘與呼吸道發炎中心主任、呼吸內科教授、Emilio Pizzichini博士有所懷疑。他向Medscape Allergy and Immunology表示，這是我第一次聽到維他命B12和呼吸道發炎的關係，它並不被視為相關原因，我也不那麼認為，我瞭解甲狀腺疾病和其他狀況，但是我未曾聽過這和維他命B12的關聯。
　　
　　Guida醫師承認，當然，我們需要更多資料來確認這個事實：維他命B12缺乏和長期咳嗽之間有強烈關聯，不過，若真如此，將可以很簡單的就對這些病患有所幫助，特別是因為他們較年長，這也是很容易給予的藥物。
　　
　　Guida醫師和 Pizzichini博士皆宣告沒有相關財務關係。
　　
　　世界過敏組織第21屆世界過敏研討會(WAC)：摘要290。發表於2009年12月8日。


Vitamin B12 Deficiency Implicated in Chronic Unexplained Cough

By Jacquelyn K. Beals, PhD
Medscape Medical News

December 15, 2009 (Buenos Aires, Argentina) — Results of a new study show that sensory neuropathy due to deficiency of vitamin?B12 might be a factor in unexplained chronic cough and dysfunction of the pharynx and larynx. Vitamin?B12 supplements improved histamine thresholds and significantly raised the cough threshold in patients with vitamin deficiency, but had no effect on control subjects.

The study, presented here at the World Allergy Organization XXI World Allergy Congress by Giuseppe Guida, MD, from Allergy and Clinical Immunology, University of Turin and Mauriziano Hospital in Italy, examined the effect of histamine on the cough threshold and the upper and lower airway responsiveness in patients with unexplained cough.

There are different causes of the chronic cough, said Dr. Guida in his presentation. Among 302 patients with chronic cough seen at their clinic, causes included adverse drug events, cough reflex sensitivity, gastroesophageal reflux disease, and allergic rhinitis; chronic cough of unknown origin comprised about 15% of the patients.

The team of investigators asked whether chronic cough and extrathoracic airway dysfunction might be manifestations of neuropathy. Vitamin?B12 deficiency had been previously found to cause peripheral sensory neuropathy in many older patients, said Dr. Guida. Thus, this deficiency was pursued as a possible cause of unexplained chronic cough.

The current study looked at 40 patients with chronic unexplained cough. Of these, 25 were found to have vitamin?B12 deficiency (serum levels <300?pg/mL); the control group consisted of 15 chronic-cough patients with no detected nutritional deficiency.

Vitamin?B12 deficiency is more common in older individuals, Dr. Guida told Medscape Allergy and Immunology. "Generally, you can find these lower levels of vitamins in older people because they can have some problem with their nutrition."

Vitamin-deficient and control subjects were evaluated with spirometry, and their exhaled nitric oxide was measured. Histamine inhalation was used to assess the bronchial, extrathoracic airway, and cough thresholds. The histamine challenge test can stimulate the airway enough to cause violent coughing. The test causes bronchoconstriction, and patients with hyperresponsive airways react to lower doses of histamine. For this study, hyperresponsiveness was defined as threshold values below 8?mg/mL.

Patients deficient in vitamin?B12 were found to have significantly lower threshold values for extrathoracic airway and cough, but bronchial thresholds did not differ from those of control subjects.

B12 deficiency is also known to be accompanied by higher levels of nerve growth factor (NGF), possibly leading to neurogenic inflammation of the airway. Analyses of oropharyngeal biopsies obtained from 6 B12-deficient patients and 3 control subjects revealed significantly higher NGF levels in the epithelial cells of vitamin-deficient patients than in control subjects (P?< .02). A graph of the data showed an inverse relation between NGF values and the log of the serum concentration of vitamin?B12 (pg/mL).

Vitamin?B12 supplementation improved histamine thresholds (reduced hyperresponsiveness) in vitamin-deficient patients without significantly changing them in control subjects. This improvement was found in bronchial (P?< .01), extrathoracic airway (P?< .001), and cough (P?< .01) thresholds.

"Supplementation is certainly very easy to perform?.?.?. by intramuscular injection," Dr. Guida told Medscape Allergy and Immunology. "So, theoretically, there is a good way to treat this disease."

Session comoderator Emilio Pizzichini, MD, PhD, professor of respiratory medicine, director of the Asthma and Airway Inflammation Center, Universidade Federal de Santa Catarina, in Florianopolis, Brazil, seemed skeptical. "That was the first time that I heard anything about vitamin?B12 and airway inflammation," he told Medscape Allergy and Immunology. "It's not related as a cause, not that I am aware of. I know about disease of the thyroid and other conditions, but I have never heard about this [effect of] vitamin?B12."

"Of course, we need more data to confirm the fact that there is a strong association between these 2 cofactors [chronic cough and the B12 deficiency]," acknowledged Dr. Guida. However, "if this is the case, [this] could be a very easy way to help these people," he said, "especially because they are older and it's a very easy medication to [administer]."

Dr. Guida and Dr. Pizzichini have disclosed no relevant financial relationships.

World Allergy Organization XXI World Allergy Congress (WAC): Abstract?290. Presented December?8, 2009.