口氣揭示的健康問題
這
是真正的非侵入性醫療檢測：越來越多的健康問題只要通過呼氣化驗就能診斷出來。這個理念的提出要追溯到希臘名醫希波克拉底(Hippocrates)﹐他在公元前400年左右曾就呼吸氣味和疾病寫過專著。隨後幾個世紀﹐醫生發現肝病和腎病患者會有特別的呼吸氣味。
相關報導
同時﹐除了肝病和腎病外﹐研究人員還在開發通過分析呼出氣體中所含生物標志物來診斷和監測其他疾病的檢測手段﹐如哮喘、糖尿病、肺結核、胃腸道感染等等﹐甚至還包括移植器官的排異。
克 利夫蘭診所勒納研究所(Cleveland Clinic's Lerner Research Institute)肺血管項目主任拉伊德•德維克(Raed A. Dweik)表示﹐“只要存在易揮發成分﹐任何可以進行血液測試的東西﹐都有希望通過呼吸測試檢測出來。”
與血液檢測相比﹐呼吸檢測不疼﹐輸出結果更快﹐檢測費用有望更低﹐而且便於重復檢測﹐甚至在患者沉睡或做運動時都可以進行檢測。
越來越多的健康問題可以通過分析病人呼出的氣被診斷出來。《華爾街日報》專欄作家Melinda Beck與克利夫蘭醫學中心(Cleveland Clinic)的Peter Mazzone博士對這一最新診斷手法進行了討論。
加州大學 (University of California)機械與航空航天工程學科的教授克里斯蒂娜•戴維斯(Cristina Davis)表示﹐“其靈感來自三錄儀(Star Trek Tricorder)﹐理想的效果是只要患者對著一個設備吹口氣﹐這個設備就會跳出一個信號﹐顯示患者存在哪些健康問題。”戴維斯博士在本月召開的一次呼 吸分析國際大會上擔任聯席主席。
戴維斯博士還在開發一種便攜式的小兒哮喘監控儀。這種監控儀像手機大小﹐帶有一根管子﹐便於兒童在一天中 的任意時間朝裡面吹氣。該儀器可分析患兒呼氣中的一氧化氮含量（炎症指標）﹐然後將數據傳送給醫生﹐以便醫生視情況調整用藥。（這種儀器跟一般的最大呼氣 流量計不同﹐後者主要幫助哮喘病患者測定其肺活量。）
很多呼吸檢測工具仍處在研究階段﹐尚有待標準化和大型臨床實驗的有效性檢驗﹐還不能被醫生用於臨床診斷。同時﹐科學家仍在對呼出氣體中所含有的數千種不同的分子進行整理歸類﹐以確定哪些分子集中情況是正常的﹐哪些則可作為診斷健康問題的指標。
就 像指紋一樣﹐每個人的呼吸特徵都是獨一無二的﹐其中不僅含有氧氣、氮氣和二氧化碳﹐還含有揮發性的有機化合物。這些來自體內外的化學物質在室溫下就會蒸發 ﹐大部分呼吸氣味都由它們決定。呼出的氣體還含有非揮發性的化合物﹐例如極微量的蛋白質、抗體、口、脫氧核糖核酸(DNA)等﹐它們也含有大量能夠透露健 康狀況的信息。
我們呼出的氣體還包含從週圍空氣中吸入的各種“雜質”﹐包括各種污染源、油漆、家具甚至地毯纖維所釋放的有害物質﹐這些都可能影響到呼氣的取樣檢測。事實上﹐我們的飲食、服用的藥物乃至刷牙的頻率等都會對我們的呼吸特徵產生影響。
患 者的心率、年齡和其他健康狀況同樣會對其呼出氣體的成分產生影響﹐因此研究人員很難在臨床試驗中獲取一致的結果。德維克博士稱﹐“要使醫生和美國食品藥品 監督管理局(FDA)信服這個理論﹐我們必須解釋清楚我們所吸入的化合物到底是什麼﹐以及這些化合物與人體疾病之間為什麼存在關聯﹐它們又是如何產生關聯 的。”
有些呼吸分析方法需要結合服用某種“引子”物質。例如﹐檢測患者體內是否存在幽門螺旋桿菌（可導致消化性潰瘍）時﹐會要求患者先服 用一粒用碳同位素做標記的尿素膠囊。如果患者體內存在幽門螺旋桿菌﹐尿素就會被其分解為二氧化碳﹐通過血液進入肺部。這時在患者呼出的氣體中﹐便可檢測到 碳同位素。
以色列特拉維夫大學的微生物學家Mel Rosenberg教授是全世界領先的口臭研究專家。他與《華爾街日報》專欄作家Melinda Beck在視頻中談論了口臭是如何形成的，以及養成怎樣的習慣能讓你告別口臭。
正 因如此﹐很多專家認為呼吸檢測的未來取決於“傳感器陣列”（又稱“電子鼻”）﹐這種方法可以識別特定的呼吸模式﹐就像人類和動物無需瞭解其中的化學組成也 可識別出熟悉的氣味一樣。傳感器陣列儀器的體積比質譜分析設備小﹐價格也較低﹐可以安放在患者的床頭﹐實時監控並顯示檢測結果。但與人類和動物一樣﹐這種 儀器也需要事先接受訓練或編程﹐以瞭解應該識別哪些呼吸模式。
在克利夫蘭診所呼吸系統疾病研究所(Cleveland Clinic's Respiratory Institute)﹐肺癌項目主任彼得•馬佐尼(Peter Mazzone)正在測試的一種傳感器陣列儀器由位於加州山景城(Mountain View)的診斷設備公司Metabolomx製造﹐當患者的呼吸吹過時﹐該儀器會變換顏色。據《胸腔腫瘤雜志》去年12月份發表的一項研究報告﹐這種儀 器在針對229名患者的測試中顯示出識別肺癌的效果﹐識別準確度為80%。一個範圍更大、敏感度更高的臨床試驗目前正在進行中。
與此同時 ﹐馬佐尼博士及其同事正在盡可能多地收集患者呼吸樣本﹐收集工作不僅限於癌症患者﹐以便研究出更多更具體的呼吸模式﹐應用在未來的呼吸檢測中。他舉例說道 ﹐“我希望達到的效果是﹐當面對一位有長達30年吸煙史、患有肺氣腫的60歲老人﹐我們的傳感器陣列儀能夠判斷出這個人罹患癌症的幾率有多大。但首先﹐我 們必須讓這個儀器知道﹐如果此人患有癌症﹐其呼吸模式應該是怎樣的。”
馬佐尼博士和其他一些專家希望﹐呼吸檢測能夠和CT掃描結合起來使用﹐以減少不必要的活體檢查的次數。他說﹐“如果肺部CT掃描發現了一個疑似結節﹐但呼吸檢測結果呈陰性﹐那麼醫生就可以決定﹐現在還不需要做活體檢查﹐等六個月後再復查一次。”
克利夫蘭診所及其他機構的研究人員還在研究針對乳腺癌和結腸癌的呼吸檢測﹐這兩種癌症也會導致患者血液內產生具有警示性的化合物並通過呼吸排出體外。
雖然要使這些檢測標準化並通過有效性檢驗﹐還有很多障礙需要克服﹐但研究工作正在迅速推進。正如戴維斯博士所說﹐“從這個領域目前的情況來看﹐未來1-4年內我們就會看到一些令人興奮的進展。”
What Your Breath Reveals
Melinda Beck
It's the ultimate
noninvasive medical test: A growing number of health problems can be diagnosed by analyzing a patient's breath alone.
The concept goes back to Hippocrates, who wrote a treatise on breath aroma and disease around 400 B.C. For centuries afterward, doctors noticed that patients with liver and kidney disorders had distinctive smells to their breath.
Now, scientists are identifying thousands of chemical compounds that create those telltale odors. Tools called mass spectrometers can detect them in quantities as minute as parts per trillion, the equivalent of finding a single ping-pong ball in a thousand baseball fields filled with ping-pong balls.
And researchers are developing tests that can diagnose and monitor not just liver and kidney disorders, but also asthma, diabetes, tuberculosis, gastrointestinal infections─even the rejection of transplanted organs─by analyzing biomarkers in exhaled breath.
'Anything you can have a blood test for, there is potentially a breath test for, as long as there is a volatile component,' says Raed A. Dweik, director of the pulmonary vascular program at the Cleveland Clinic's Lerner Research Institute.
Breath tests are also painless, faster to return results and potentially less expensive than blood tests─and easy to repeat as often as needed, even while patients are sleeping or exercising.
And some go well beyond what blood tests can do. In a study in the Journal of Thoracic Oncology this month, researchers from Israel and Colorado reported that breath analysis could distinguish between benign and malignant pulmonary nodules in a group of 72 patients with 88% accuracy; the test could also assess the specific type and stage of the lung cancers.
'The Holy Grail is the Star Trek Tricorder concept, where you would breathe into a device and a sign would pop up saying what health problems you have,' says Cristina Davis, a professor of mechanical and aerospace engineering at the University of California, Davis, who is co-chairing an international conference on breath analysis later this month.
Dr. Davis is also developing a portable pediatric asthma monitor. The cellphone-like device would have a tube that children could breathe into during the day; it would analyze the level of nitric oxide in their breath, an indicator of inflammation, and transmit the data to their doctors to aid in fine tuning their medication. (This is different than the simple peak-flow meters that most asthmatics use to measure how quickly air can be blown from their lungs.)
Many of these breath tests are still in the research stage and need to be standardized and validated in large clinical trials before they will be ready for use in doctors' offices. Meanwhile, scientists are still cataloging the thousands of different molecules in exhaled breath and determining what concentrations are normal and what indicate health problems.
Every individual has a unique breath signature─like a fingerprint─that contains not only oxygen, nitrogen and carbon dioxide but also volatile organic compounds. Those are chemicals from inside and outside the body that evaporate at room temperature and are the source of most breath odors. Exhaled breath also contains nonvolatile compounds─microscopic droplets of proteins, antibodies, peptides and DNA that contain a wealth of additional health information.
Exhaled breath also contains a host of 'confounders' inhaled from the ambient air─including molecules of pollution, paint, furniture, even carpet fibers─that can interfere with breath sampling. In fact, what people eat, what medications they take and how often they brush their teeth can all affect their breath signature.
So can patients' heart rates, ages and other health conditions, making it difficult for researchers to get consistent results in clinical trials. 'For doctors and the FDA to buy into this concept,' says Dr. Dweik, 'we have to tell them what we are smelling and why and how that compound is related to the disease process.'
Some forms of breath analysis require a tagging material. Patients tested for Helicobacter pylori, the gut bacteria behind peptic ulcers, swallow a capsule containing urea, made from a carbon isotope. If H. pylori is present, it breaks up the urea into carbon dioxide, which travels through the blood to the lungs. The isotope can then be detected in the patient's exhaled breath.
Other breath tests use various forms of mass spectrometry, that can identify and measure specific volatile organic compounds. Scientists say mass spectrometry is a billion times more sensitive than the breath analyzers used by police to detect blood-alcohol levels, but it is also expensive and cumbersome.
That is why many experts believe that the future of breath testing lies in the use of sensor arrays (or 'electronic noses') that can recognize patterns in exhaled breath the way people and animals can identify familiar smells without knowing the chemical compounds that create them. Sensor arrays are smaller and less expensive than mass spectrometers and portable enough to be administered at a patient's bedside with the results given in real time. But like humans and animals, they need to be trained, or programmed, to know what patterns to look for.
At the Cleveland Clinic's Respiratory Institute, Peter Mazzone, director of the lung cancer program, is testing a sensor array that changes color when a patient's breath passes over it, made by Metabolomx, a Mountain View, Calif.-based diagnostic company. In a study of 229 patients reported in the Journal of Thoracic Oncology in December, the test was able to distinguish those with lung cancer with 80% accuracy. A larger trial with a far more sensitive version of the test is under way.
At the same time, Dr. Mazzone and his colleagues are collecting breath samples from as many patients as possible, with and without lung cancer, in order to develop still more specific patterns for breath tests to look for in the future. 'My vision is being able to say, 'This is a 60-year old with emphysema who smoked for 30 years─what's the chance of there being cancer there?' But we have to teach the device what it looks like first.'
He and other experts hope that breath tests can be used in conjunction with CT scans to cut down on the number of unnecessary biopsies. 'If you do a CT scan of the lungs and find a nodule, but the breath test was negative, you could say, 'I don't need a biopsy now. I'll follow it up in six months',' Dr. Mazzone says.
Researchers at the Cleveland Clinic and elsewhere are also studying breath tests for breast and colon cancer, which send similar telltale compounds through the blood stream and out in exhaled breath.
Many hurdles remain in getting such tests standardized and validated, but research is moving rapidly. Says Dr. Davis: 'The field is at the point where we'll start to see some exciting developments in the next one to four years.'
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