Carnitine metabolizes in the gut based on diet to promote heart disease

The compound carnitine that is taken as a dietary supplement, added to energy drinks and is abundant in red meat was found by researchers to promote fatty plaque in the arteries, according to study results published in Nature Medicine – but only for meat eaters.

Stanley Hazen, M.D., Ph.D., Vice Chair of Translational Research for the Lerner Research Institute and section head of Preventive Cardiology & Rehabilitation in the Miller Family Heart and Vascular Institute at Cleveland Clinic, and Robert Koeth, a medical student at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University who conducted the study found live bacteria in the human gut turn carnitine into trimethylamine-N-oxide (TMAO).

For their study, they tested carnitine and TMAO levels of meat eaters, vegans and vegetarians and then analyzed data from 2,595 patients electively undergoing cardiac screening.

The researchers also compared normal mice given a carnitine rich diet to mice with low levels of gut bacteria given the same diet.

The finding revealed TMAO restricts cholesterol metabolism to explain how it promotes removal of cholesterol.

What else does carnitine do?

The compound is manufactured in the body and is important for converting fat into energy. Carnitine is stored in the skeletal muscles, brain, sperm and heart. It is produced in the liver and kidneys. Healthy people make enough carnitine for optimal health.

Supplements have been proposed to improve athletic performance.erectile dysfunction and heart conditions, but studies are not conclusive that they provide any benefit.

In addition to red med, the compound is mainly found in fish, asparagus, wheat, avocados and peanut butter.

Diet affects TMAO levels and thus heart risks

Patients with high carnitine and TMAO levels were more prone to heart attack, stroke and death. Vegans and vegetarians had much lower levels of TMAO.

Another interesting finding is the discovery that certain gut microbes seem to influence who might get heart disease – but so does diet.

In the study, carnitine boosted TMAO levels for meat eaters, but not for vegans and vegetarians.

Hazen says what we eat over a long period of time affects bacteria living in the gut. Meat eaters have a higher chance of heart disease because their gut bacteria produces higher levels of TMAO that promotes clogged arteries.

A vegetarian diet may lower the chances of heart disease because vegetarian guts can’t synthesize TMAO from carnitine that is not just in meat, supplements and drinks. It is occurs naturally in the body.

Hazen said the new research suggests a new and different connection between heart disease and red meat. It may not be the saturated fat, salt added to meat, the cooking process or even additives that have all been suggested to this point.

Carnitine metabolism could be the answer to how red meat promotes heart disease, the researcher suggests, that is different in everyone.

Hazen and his team have been studying the role of gut microbes and their role in atherosclerosis that goes beyond the role of genes. Hazen says the new study means a closer look should be taken at carnitine supplements that might be fostering heart disease for some individuals. The finding also supports the heart healthy benefits of a plant based diet. Have you considered making a dietary change for the sake of your own heart?

Source:
Cleveland Clinic
April 7, 2013

==================

심장병 부르는 고기의 그것

한겨레 등록 : 2013.04.08 19:39 수정 : 2013.04.08 20:47
http://www.hani.co.kr/arti/society/health/581838.html

포화지방 아닌 ‘카르니틴’이 주범

‘불안은 영혼을 잠식한다.’ 이는 상징도 아니고 비유도 아니다. 2011년 한국, 지금 여기에서 아포리즘을 넘어 현실을 정확히 반영하는 한 표현이 되었다.

2009년 4월부터 2011년 4월까지 2년 동안, 2646명의 특정 인구 집단에 소속된 이 중 6명이 자살했고, 5명이 뇌심혈관계 질환으로 사망했다. 2명의 가족 또한 자살을 선택했다. 2년 만에 노동자와 가족을 포함해 8명의 자살자와 5명의 뇌심혈관계 질환 사망자가 생겨 죽음의 이미지가 깊게 드리워진 이름이 바로 쌍용자동차다. 쌍용자동차 해고 노동자의 자살률은 비슷한 나이 또래의 일반 인구에 견줘 3.7배 높고, 심혈관계 질환 사망률은 18.3배 높다. 죽음의 집적이고 절망의 클러스터이다.

쌍용차 심혈관계 사망, 평균의 18배

기업의 구조조정이 노동자 건강에 악영향을 끼친다는 보고나 연구는 많다. 전 지구적으로 신자유주의적 구조조정이 판을 쳤던 지난 30여 년간, 한국뿐 아니라 많은 나라의 노동자들이 구조조정으로 해고되거나 직장을 옮겨야 했다. 그 결과 그들은 건강이 나빠지고 생명을 잃었다. 하지만 이런 일반론과 구별되는 쌍용자동차 사례의 특수성이 존재한다. 다른 나라 사례와 비교해도 쌍용자동차 해고 노동자들은 이례적으로 너무 많이 죽고 있다.

구조조정으로 인한 해고는 확실히 노동자를 죽음으로 몰고 간다. 상대적으로 사회 안전망이 잘 갖추어진 나라라고 평가받는 스웨덴·핀란드 등에서 이루어진 연구에서도 구조조정을 당한 노동자가 심혈관계 질환이나 자살로 생을 마감하는 비율이 높다고 밝혀졌다.

구조조정은 해고된 노동자뿐 아니라 이른바 ‘살아남은 자’들의 건강과 생명도 위협한다. 구조조정을 겪고 생존한 노동자들도 높은 사고율, 정신질환 등에 시달린다. 구조조정 자체는 해고된 노동자뿐 아니라 ‘생존자’에게도 트라우마를 남긴다. 이들은 해고 노동자에게 늘 미안한 감정을 가지게 되고, 자신도 언제 해고될지 모른다는 불안에 떤다. 이렇게 되면 회사에 대한 신뢰와 충성심이 떨어져 생산성이 떨어지고, 만성적인 스트레스와 과로에 시달려 개인의 건강도 해친다. 이를 가리켜 ‘생존자 질환 증후군’이라 표현한다.

해고로 인한 실직은 소득 감소를 동반한다. 해고로 인한 고통은 1차적으로 경제적인 것이다. 그나마 사회보장이 잘된 사회에서는 위험이 감소할 수 있다. 기존 가계 부채가 적거나 저축률이 높은 가정, 가족이나 친지 등 사회적 지지 네트워크가 발달된 가정 역시 위험이 줄어들 수 있다. 그럼에도 대부분의 가정에 주된 소득을 담당하던 가족 구성원의 해고는 경제적으로 큰 타격이 되고, 이는 해고 노동자 본인뿐 아니라 가족 모두에게 큰 스트레스가 된다.

정신적·육체적 파괴

심적 스트레스와 무력감은 우울과 불안 같은 정신병리적 증상을 낳음과 동시에 직접적으로 육체적 건강도 파괴한다. 스트레스가 많을 때 분비되는 호르몬은 인체의 면역 기능을 떨어뜨리고, 몸을 항상적인 긴장 상태로 만들어 심혈관계 기관에 많은 부담을 준다. 혈압을 높이고, 혈중 콜레스테롤이나 혈당 같은 성인병 위험 요소를 증가시킨다. 그 결과 인체의 신진대사에 장애가 생겨 대사증후군이라는 질병에 걸리거나 비만해지는데, 이 모든 것은 심장병이나 뇌혈관 질환의 발생 위험을 높인다.

이런 상황이 건강에 좋지 않은 습관에서 헤어나오지 못하게 만든다는 것 또한 큰 문제다. 해고 노동자들은 일반적으로 스트레스와 무력감을 떨치기 위해 술과 담배에 의존한다. 잠을 설치면서 수면제에 의존하는 이가 많아진다. 식사를 거르거나 제대로 먹지 않게 되고 활동량이 줄어들어, 이중 삼중의 건강 위험 상황에 빠진다.

관계의 악화… 건강 위험 악순환

경제적 상황이 나빠짐에 따라 가족 관계와 다른 친분 관계에 금이 가는 것도 문제다. 심한 스트레스와 무력감, 우울감과 불안감의 증가, 그로 인한 생활습관 변화 등은 본인의 건강뿐 아니라 관계의 건강도 해치기 쉽다. 무력감과 우울감에 젖어 불면과 수면 과다에 시달리며, 술과 담배를 많이 하고, 대화가 줄어들 뿐 아니라 신경질이 많아진 남편과 아버지를 언제까지나 참고 기다려줄 아내와 자녀는 많지 않다. 많은 가정에서 해고는 가족 관계의 파탄과 친구 관계의 단절로 이어진다. 이런 파탄과 단절은 상황을 더욱 나쁘게 만든다. 악순환의 고리에 들어서는 것이다.  낮은 자아존중감, 자기애 감소, 미래에 대한 불안, 자포자기 등을 낳고, 이런 모든 요인이 복합적으로 작용하면 최악의 상황이 연출된다.

특히 가족 및 친구 등 사회적 지지망의 손실과 단절은 치명적인 효과를 낸다. 관계가 손상된 이는 사회적으로 더욱 고립되고, 자아 정체성의 혼란을 낳는다. 자포자기 상태에 빠지게 되고 새로운 시작을 하는 것이 두려워진다. 이들에게 가해지는 사회적 ‘낙인’과 배제가 이들을 극한 상황으로 몰고 간다.

이와 같이 구조조정은 해고 노동자들의 건강과 생명을 파괴한다. 일반적인 수준에서 진리이지만, 일반적인 진리가 쌍용자동차 해고 노동자의 경우를 다 설명해주지는 못한다. 앞에서 언급한 바와 같이 일반적인 사례에 비춰보더라도 쌍용자동차 노동자들의 죽음은 이례적이기 때문이다. 도대체 무엇이 상황을 이렇게 나쁘게 만들고 있는 것일까? 이에 대해 확실한 답을 얻으려면 면밀한 조사와 분석이 필요하다. 그 작업에 앞서 몇 가지 측면에서 가설적 설명을 시도해볼 수 있다.

회사를 너무 사랑했기에 더욱 취약

첫째, 급격히 변화된 경제적 상태가 영향을 주었다. 대부분의 쌍용자동차 해고 노동자들은 해고 이전에 도시가구 노동자 평균을 상회하는 소득을 올렸다. 그런데 이들이 하루아침에 소득 기준으로 빈곤계층으로 전락하면 그 충격이 더욱 크다. 이들은 해고 이전에도 자녀 사교육 부담, 주거 부담 등으로 이미 상당한 가계 부채가 있을 수 있다. 이들은 쌍용자동차에서 장기근속하며 이 부채를 해결할 계획이었을 것이다. 그 계획과 예상이 하루아침에 무너졌을 때, 낭패감과 상실감은 더욱 클 수 있다.

둘째, 미래의 고용에 대한 불안감이 상황을 더욱 나쁘게 만들었다. 많은 이들이 2001년 대우자동차 해고와 쌍용자동차 해고를 비교한다. 2001년 대우자동차 해고 때도 1750명이나 되는 노동자들이 대량 해고됐는데, 그때와 지금이 무엇이 다르냐는 것이다. 이에 대해서는 다각도로 분석해야 한다. 그런데 거시적 측면에서 보면, 2001년과 2009년은 확실히 다른 측면이 있다. 2001년은 1998년 국제통화기금(IMF) 사태의 구조조정을 겪은 뒤 경제가 회복 국면을 보이던 때다.  1998년 마이너스 성장을 기록한 한국 경제는 1999년 9.5%, 2000년 8.5%의 실질경제성장률을 기록하며 빠르게 IMF 위기의 파고를 넘고 있었다. 하지만 2009년은 달랐다. 2008년 미국발 경제위기로 한국 경제는 큰 타격을 입었고, 상황은 아직까지 나아지지 않고 있다. 이런 거시 경제지표가 해고자 개개인에게 미치는 영향을 무시할 수 없다. 전반적 경제 상황이 그리 나쁘지 않을 때와 최악의 상황일 때, 개인이 느끼는 장래 고용 전망의 불확실성은 확실히 차이가 나기 때문이다. 쌍용자동차 해고 노동자들은 세계적인 경제위기와 한국의 불안정한 고용시장을 복합적으로 고려하면서, 장래의 고용 가능성을 더욱 비관적으로 인식했을 수 있다. 이런 비관적 장래 인식이 영혼을 갉아먹은 것이다.

셋째, 회사에 대한 신뢰 상실과 배신감이 악영향을 주었다. 외국의 연구에 따르면, 회사와 직업에 대한 헌신성이 큰 이들일수록 구조조정에 따른 악영향이 큰 것으로 나타났다. 회사에 대한 충성심이 높은 이들일수록 그 배신감과 신뢰 상실의 여파가 커서 건강에 더 악영향을 받는 것이다. 쌍용자동차 노동자들은 그간 몇 번의 위기 속에서 나름대로 회사를 위해 희생하고 노력해왔다는 생각을 했을 것이다. 이런 상황에서 노동자의 희생에도 불구하고 위기의 책임을 노동자에게만 전가하는 회사 경영진에게 큰 배신감을 느꼈을 것이다. 배신감은 노동자 개개인의 마음속에 깊은 상처를 냈다.

넷째, 관계의 파국 정도가 극심했다. 쌍용차 해고 노동자 중 많은 이들이 가족 관계 파탄, 지역사회에서의 소외, 이전 친분 관계의 단절을 호소하고 있다. 이들의 관계 단절, 소외, 낙인, 배제의 문제는 광범위하다. 1차적으로는 경제적 어려움, 우울과 불안 등에 따른 정신적 자아존중감 감소로 인해 부부 관계와 부자 관계에 금이 간다. 공장 점거 농성 등으로 우리 사회를 떠들썩하게 한 여파로 지역사회의 눈길도 이전과 다르다. 지역에서 일상적인 소외가 발생하고, 이전에는 친하게 지내던 다른 쌍용차 노동자들과의 관계가 서먹서먹해진다. 점거 농성 와중에 적과 아로 나뉘어 욕을 하고 싸웠기 때문이다. 술자리에 가서도, 다른 직장을 구할 때도, 자신이 쌍용차 해고 노동자임을 드러내기 힘들어진다. 자꾸 자신을 감추고 사람들과의 소통을 멀리하게 된다. 몇몇 노동자에게 들은 상황과 증언을 종합해볼 때, 관계 단절과 소외, 배제, 낙인, 인간과 사회에 대한 신뢰 상실의 문제는 예상보다 크다.

구조조정 계획이 발표된 뒤 실제 구조조정이 행해지기까지 3명이 자살하고, 2명이 뇌심혈관계 질환으로 사망한 쌍용자동차 해고 노동자와 그 가족들. 구조조정 뒤 지금까지 5명이 추가로 자살을 선택했고, 3명이 심혈관계 질환으로 유명을 달리했다. 이런 죽음의 행렬을 멈추려면 특단의 대책이 필요하다.

먼저 상처의 원인을 진단하기 위해 노력해야 한다. 이들이 무엇 때문에 힘들어하고 아파하는지 실체적 진실이 아직 충분히 드러나지 않았다. 필자를 비롯한 몇몇 연구자와 작가들이 사례를 인터뷰하고 상담한 것으로는 치명적 죽음의 원인을 드러내는 데 한계가 있다. 이들이 겪고 있는 아픔과 어려움, 더불어 그 원인의 실체적 진실을 밝히기 위한 조사와 연구가 필요하다. 늦은 감이 있지만 경기도 평택시가 나서 이런 작업을 수행할 예정이라고 하니 그나마 다행이다. 조사 과정이 그들의 아픔을 오히려 헤집고 아픈 기억을 되살리는 것이 되지 않도록 세심한 주의가 필요하다.

회사가 ‘존재적 복권’에 나서라

지방자치단체, 회사 등은 이 조사 결과를 바탕으로 쌍용차 해고 노동자 마음의 상처와 육체적 질병을 보듬고 돌볼 수 있는 해결책을 제시해야 한다. 그 처음은 약속을 지키는 것부터 시작해야 한다. 쌍용차 노동자들의 신뢰 상실과 배신감은 그들의 생명을 갉아먹고 있다. 회사와 사회에 느끼는 배신감을 치유하기 위해 회사와 사회가 나서야 한다. 다음으로 지자체와 회사가 이들의 경제적 문제와 고용 문제를 해결하기 위해 앞장서야 한다. 결자해지라 하지 않았던가. 가족 관계, 동료 관계, 지역사회에서 일상적인 단절, 소외, 배제, 낙인 등에 시달리는 이들의 존재에 대한 ‘존재적 복권’ 역시 절실하다. 인간이 살기 위해서는 밥뿐 아니라 존재에 대한 인정과 존중이 필요하다. 범죄자, 낙오자, 관계 파괴자 등으로 낙인찍힌 이들 존재에 대한 긍정과 사회적 재호명이 필요하다.

이상윤(건강과대안 책임연구원/노동건강연대 정책국장) / 르몽드 디플로마티크 4월호

How genes influence obesity, senility – and the effects of olive oil

The genome has allowed scientists to shed new light on some of the most intractable medical conditions. Steve Connor reports

출처 : [Independent] Tuesday, 20 April 2010
http://www.independent.co.uk/news/science/how-genes-influence-obesity-senility-ndash-and-the-effects-of-olive-oil-1948818.html

In 2000 President Bill Clinton and Prime Minister Tony Blair announced in a joint satellite broadcast from the White House and Downing Street that scientists had completed the first draft of the human genome. Ten years on and medical researchers are now enjoying a ‘genome bonanza’ that has begun to elucidate the complex role of genes in human health.

Three such studies are published today. One describes how a gene linked to obesity is also associated with mental deterioration, a second shows how another gene affects memory and thinking in old age and the third study identifies the part of the human genome affected by a healthy Mediterranean diet – or more specifically virgin olive oil.

When the draft genome was published, President Clinton ruffled a few atheistic feathers when he suggested that the milestone represents the translation of a mysterious code designed by a higher being. “Today, we are learning the language in which God created life,” he said.

Whether God-given or not, it took another three years for scientists to finally complete the entire ‘book of life’, as the human genome came to be called. And it was soon clear that as a powerful research tool it would unleash untold insights into the workings of the human body, as well as our relationships to the wider living world.

The genome contains the entire digital recipe for making a human being. It consists of three billion individual letters of the genetic alphabet, arranged in a sequence that is unique to each person, which includes approximately 23,000 human genes that determine the production of the proteins, cells and tissues of the body.

For decades, biological science argued abut “nature versus nurture”. Is environment and upbringing the important influence that determines a person’s health and psychological makeup, or is it in the genes that they have inherited?

It turns out that both are important but more interestingly it is the influence of the environment on the genes that appears to play a decisive role in how people develop. The human genome has shown how a disparate variety of individual genes combine together, along with environmental influences, to affect a person’s physical and mental well-being.

Take the influence of diet on health. There is strong evidence to suggest that a Mediterranean diet lowers the risk of heart disease, stroke and even Alzheimer’s disease. This is the environment at work. But a study by Francisco Perez-Jimenez from the University of Cordoba in Spain, published in the journal BMC Genomics, shows how virgin olive oil can actually influence certain genes involved in triggering inflammatory processes of the immune system.

Professor Perez-Jimenez took 20 patients with metabolic syndrome, which is linked with heart disease and type-2 diabetes, and fed them for six weeks with two types of breakfast, one with virgin olive oil, which is rich in substances called phenols, and the other with low-phenol olive oil. As the experiment unfolded, the scientists tested the activity of the volunteers’ genes and found a clear association between virgin olive oil and the suppression of the inflammatory genes.

“We identified 98 differentially expressed genes when comparing the intake of phenol-rick olive oil with low-phenol oil. Several of the repressed genes are known to be involved in pro-inflammatory processes, suggesting that the diet can switch the activity of the immune system to a less deleterious inflammatory profile, as seen in metabolic syndrome,” Professor Perez-Jimenez said. “These findings strengthen the relationship between inflammation, obesity and diet and provide evidence at the most basic level of healthy effects derived from virgin olive oil consumption in humans.”

But it is not just physical health that is benefiting from understanding the human genome. A number of studies into the genes involved in brain development and function are helping to revolutionise our understanding of human cognition and mental health.

Alexandra Fiocco at the University of California, San Francisco, led a study of nearly 3,000 people aged between 70 and 79 who were regularly tested for mental performance, specifically memory and concentration. Their DNA had also been tested to see which of two genetic variants of a gene called COMT the volunteers were carrying.

The COMT gene, which was already known to influence thinking and mental performance, comes in two forms, or alleles, called Val and Met. The study, published in the journal Neurology, demonstrated that elderly people with the Val version of the gene seemed to be better protected against mental decline as they got older compared to people carrying the Met version of the COMT gene.

“This is the first study to identify a protective relationship between this gene variant and cognitive function. This finding is interesting because in younger people, the Val genotype has been shown to have a detrimental effect,” Dr Fiocco said. “But in our study of older people, the reverse was true. Finding connections between this gene, its variants and cognitive function may help scientists find new treatments for the prevention of cognitive decline.”

The third genome-related study, published in the Proceedings of the National Academy of Sciences, investigated 200 healthy, elderly people whose brains were scanned as part of research into Alzheimer’s disease. In addition to measuring their brains, scientists also analysed their DNA, specifically a gene known to be involved in obesity, called fat mass and obesity associated (FTO) gene.

What emerged was a clear association between diminished brain volume – or atrophy – and a certain version of the FTO gene. It was already known that obesity is a risk factor for cognitive decline in older age, and it has been previously associated with detectable differences in the brain volume of overweight people.

The researchers, led by Paul Thompson of the University of California, Los Angeles, could not identify the mechanism causing the brain atrophy, or how the FTO might influence this process. However, they believe there is enough evidence to suggest that the particular variant of the FTO contributes to brain deterioration beyond the simple influence of a person’s body weight.

The FTO gene, sometimes called the “fatso” gene, has emerged from the genome project as a leading genetic influence in obesity. It seems to account for a substantial proportion of obesity cases.

In 2007, for instance, scientists found a genetic variation of the FTO gene that gives a child a 70 per cent higher risk of developing obesity compared to a child with another version of the gene. It was the first real insight into why some people are born with a predisposition to putting on weight, while others stay slim even in a high-calorie environment.

“Even though we have yet to fully understand the role played by the FTO gene in obesity, our findings are as source of great excitement,” said Professor Mark McCarthy of Oxford University. “By identifying this genetic link, it should be possible to improve our understanding of why some people are more obese, with all the associated implications such as increased risk of diabetes and heart disease.”

Shortly before that study was published, another research team analysed the genetic factors that may play a role in determining whether someone is likely to be able to give up smoking or not. It found that people who tried to give up and failed were much more likely to have inherited a series of genetic traits compared to successful quitters. Scientists screened more than 520,000 genes from hundreds of smokers who had tried to quit. The screening eventually led to 221 genes that distinguished successful from unsuccessful quitters. Many of these genes were already associated with addiction and drug dependence.

Nora Volkow, director of the US National Institute on Drug Abuse in Washington, said the study marked the first time that scientists had been able to identify the genes involved in the ability to stop smoking. She said: “These findings lend further support to the idea that nicotine dependence shares some common genetic vulnerabilities with addictions to other legal and illegal substances.”

================================================

인간 유전자, 비만ㆍ노화에 영향

출처 : 연합뉴스 2010/04/20 11:37 송고 
http://www.yonhapnews.co.kr/international/2010/04/20/0606000000AKR20100420105600009.HTML?template=2088

(서울=연합뉴스) 인간 게놈지도 초안이 완성된지 10년이 지난 현재 인간 건강에 대한 유전자의 복잡한 역할을 규명해주는 연구가 본격적으로 시작됐다고 영국 일간 인디펜던트 인터넷판이 20일 보도했다.

   이날 세편의 관련 연구가 발표됐는데 한 연구는 비만과 연관된 유전자가 뇌기능 쇠퇴와도 관련이 있다는 내용, 또 한 연구는 특정 유전자가 노인들의 기억과 사고에 영향을 준다는 내용, 마지막 연구는 건강식인 지중해식 식사, 특히 천연 올리브유가 인간 게놈에 영향을 준다는 내용으로 되어있다.

   지난 수십년 동안 과학자들은 인간의 건강과 심리적 기제에 영향을 주는 것이 환경과 교육인지, 유전인지에 대해 논쟁을 벌여왔다.

   두 가지 모두 중요한 것으로 판명됐으나 유전자에 대한 환경의 영향이 인간 발전에 결정적인 역할을 하는 것으로 보인다. 인간 게놈은 어떻게 서로 다른 각각의 유전자들이 환경의 영향을 받아 서로 합쳐져 인간의 육체적, 정신적 건강에 작용을 하는지를 설명했다.

   건강에 대한 다이어트의 예를 들면 지중해식 식사가 심장병, 뇌졸중, 심지어 치매의 위험을 낮춘다는 강력한 증거가 있다. 이때 중요한 것은 환경이다.

   그러나 스페인 코르도바대학의 프란시스코 페레스-지메네스 교수는 천연 올리브 오일이 실제로 면역체계의 염증을 유발하는데 관련된 특정 유전자들에 영향을 줄 수 있다는 사실을 발견했다.

   그는 대사 증후군 환자 20명을 상대로 6주에 걸쳐 한 그룹에는 페놀이 풍부한 천연 올리브유, 다른 그룹에는 저 페놀 올리브유를 아침식사에 제공했다. 과학자들은 이들의 유전자의 행동을 측정하고 천연 올리브유와 염증 유전자 억제 사이에 명백한 관련이 있다는 사실을 확인했다.

   이 연구는 ‘BMC 게노믹스’에 실렸다.

   한편 샌프란시스코의 캘리포니아대학 알렉산드라 피오코 교수는 70세에서 79세 사이의 노인 약 3천명을 상대로 주기적으로 기억력과 집중력 등 정신적 활동을 관찰하고 이들이 COMT 유전자의 두가지 유전적 변형 중 어떤 것을 갖고 있는지 알아보기 위해 DNA 검사를 실시했다.

   이미 사고와 정신적 활동에 영향을 주는 것으로 알려진 COMT 유전자는 Val과 Met 두 형태로 구분되는데 연구 결과 Val 형태의 COMT 유전자를 가진 노인들은 Met 형태를 가진 노인들보다 노화에 따른 정신적 쇠퇴로부터 더 잘 보호되고 있었다.

   이 연구는 ‘뉴롤로지’ 최근호에 게재됐다.

   마지막 게놈관련 연구는 ‘전국과학아카데미회보’에 발표된 것으로, 로스앤젤레스 캘리포니아대학의 폴 톰슨 교수가 이끄는 연구팀은 치매 연구의 일환으로 200명의 건강한 노인의 뇌의 크기를 측정하고 DNA를 분석했으며 특히 FTO로 알려진 비만관련 유전자를 관찰했다.

   연구결과 뇌의 크기 위축과 특정 형태의 FTO 유전자 사이에 명확한 관계가 나타났다.

   나이가 들면서 비만이 인지기능 저하를 일으키는 위험 요소라는 것은 이미 알려진 사실이다.

   연구팀은 뇌 위축 메커니즘이나 FTO 유전자가 이 과정에 어떤 작용을 하는지는 규명해내지 못했으나 FTO의 특정 형태가 몸무게의 단순한 영향에서 벗어나 뇌기능 저하에 하나의 원인이 된다는 것을 시사하는 충분한 증거가 있다고 밝혔다.

   kej@yna.co.kr

<고속도로변 살면 동맥경화 위험 높다>

출처 : 연합뉴스 2010/02/15 09:53  
http://www.yonhapnews.co.kr/international/2010/02/15/0601110100AKR20100215017500075.HTML?template=3398

(로스앤젤레스=연합뉴스) 최재석 특파원 = 고속도로 주변에 사는 사람은 심장병이나 뇌졸중을 일으킬 수 있는 동맥경화 위험이 일반 주민보다 두 배가량 높다는 연구결과가 나왔다.

   14일 로스앤젤레스타임스(LAT)에 따르면 미국 서던캘리포니아대(USC)와 UC버클리 연구팀이 LA 지역의 고속도로 100ｍ 내에 사는 주민 1천483명의 경동맥 혈관벽 두께를 초음파를 이용해 3년간 6개월 단위로 측정했다,

그 결과 이 연구에 참여한 주민들의 혈관벽 두께가 매년 일반인의 2배인 5.5마이크로미터(㎛)씩 두꺼워지는 것으로 나타났다.

   연구팀은 이 같은 결과가 고속도로 주변 집에서 검출된 외부 분진(자동차 배기관에서 뿜어나오는 독성먼지)의 양과 관련 있다고 밝혔다.

   USC의 하워드 호디스 박사는 이번 연구 결과 “환경적인 요소가 심장 혈관질환 위험에 이전의 생각보다 더 큰 영향을 미칠 수 있다는 점을 알 수 있다”고 설명했다.

   이번 연구결과는 이번 주 학술지인 플로스원(PloS ONE)에 실릴 예정이다.

   bondong@yna.co.kr

Obesity and overweight

What are overweight and obesity?

Related links :: WHO Global Infobase :: WHO Global Database on Body Mass Index (BMI) :: WHO Global Strategy on Diet, Physical Activity and Health :: WHO Child Growth Standards :: WHO Department of Chronic Diseases and Health Promotion :: WHO Department of Nutrition for Health and Development

Overweight and obesity are defined as abnormal or excessive fat accumulation that may impair health.

Body mass index (BMI) is a simple index of weight-for-height that is commonly used in classifying overweight and obesity in adult populations and individuals. It is defined as the weight in kilograms divided by the square of the height in meters (kg/m2).

BMI provides the most useful population-level measure of overweight and obesity as it is the same for both sexes and for all ages of adults. However, it should be considered as a rough guide because it may not correspond to the same degree of fatness in different individuals.

The World Health Organization (WHO) defines “overweight” as a BMI equal to or more than 25, and “obesity” as a BMI equal to or more than 30. These cut-off points provide a benchmark for individual assessment, but there is evidence that risk of chronic disease in populations increases progressively from a BMI of 21.

The new WHO Child Growth Standards, launched in April 2006, include BMI charts for infants and young children up to age 5. However, measuring overweight and obesity in children aged 5 to 14 years is challenging because there is not a standard definition of childhood obesity applied worldwide. WHO is currently developing an international growth reference for school-age children and adolescents.

Facts about overweight and obesity

WHO’s latest projections indicate that globally in 2005:

• approximately 1.6 billion adults (age 15+) were overweight;
  
• at least 400 million adults were obese.

WHO further projects that by 2015, approximately 2.3 billion adults will be overweight and more than 700 million will be obese.

At least 20 million children under the age of 5 years are overweight globally in 2005.

Once considered a problem only in high-income countries, overweight and obesity are now dramatically on the rise in low- and middle-income countries, particularly in urban settings.

What causes obesity and overweight?

The fundamental cause of obesity and overweight is an energy imbalance between calories consumed on one hand, and calories expended on the other hand. Global increases in overweight and obesity are attributable to a number of factors including:

• a global shift in diet towards increased intake of energy-dense foods that are high in fat and sugars but low in vitamins, minerals and other micronutrients; and
  
• a trend towards decreased physical activity due to the increasingly sedentary nature of many forms of work, changing modes of transportation, and increasing urbanization.

What are common health consequences of overweight and obesity?

Overweight and obesity lead to serious health consequences. Risk increases progressively as BMI increases. Raised body mass index is a major risk factor for chronic diseases such as:

• Cardiovascular disease (mainly heart disease and stroke) – already the world’s number one cause of death, killing 17 million people each year.
  
• Diabetes – which has rapidly become a global epidemic. WHO projects that diabetes deaths will increase by more than 50% worldwide in the next 10 years.
  
• Musculoskeletal disorders – especially osteoarthritis.
  
• Some cancers (endometrial, breast, and colon).

Childhood obesity is associated with a higher chance of premature death and disability in adulthood.

Many low- and middle-income countries are now facing a “double burden” of disease:

• While they continue to deal with the problems of infectious disease and under-nutrition, at the same time they are experiencing a rapid upsurge in chronic disease risk factors such as obesity and overweight, particularly in urban settings.
  
• It is not uncommon to find under-nutrition and obesity existing side-by-side within the same country, the same community and even within the same household.
  
• This double burden is caused by inadequate pre-natal, infant and young child nutrition followed by exposure to high-fat, energy-dense, micronutrient-poor foods and lack of physical activity.

How can the burden of overweight and obesity be reduced?

Overweight and obesity, as well as their related chronic diseases, are largely preventable.

At the individual level, people can:

• achieve energy balance and a healthy weight;
  
• limit energy intake from total fats and shift fat consumption away from saturated fats to unsaturated fats;
  
• increase consumption of fruit and vegetables, as well as legumes, whole grains and nuts;
  
• limit the intake of sugars; and
  
• increase physical activity – at least 30 minutes of regular, moderate-intensity activity on most days. More activity may be required for weight control.

The implementation of these recommendations requires sustained political commitment and the collaboration of many stakeholders, public and private. Governments, international partners, civil society and nongovernmental organizations and the private sector have vital roles to play in shaping healthy environments and making healthier diet options affordable and easily accessible. This is especially important for the most vulnerable in society – the poor and children – who have limited choices about the food they eat and the environments in which they live.

Initiatives by the food industry to reduce the fat, sugar and salt content of processed foods and portion sizes, to increase introduction of innovative, healthy, and nutritious choices, and to review current marketing practices could accelerate health gains worldwide.

WHO’s strategy for preventing overweight and obesity

Adopted by the World Health Assembly in 2004, the WHO Global Strategy on Diet, Physical Activity and Health describes the actions needed to support the adoption of healthy diets and regular physical activity. The Strategy calls upon all stakeholders to take action at global, regional and local levels and aims to lead to a significant reduction in the prevalence of chronic diseases and their common risk factors, primarily unhealthy diet and physical inactivity.

WHO’s work on diet and physical activity is part of the overall WHO chronic disease prevention and control framework of the Department of Chronic Diseases and Health Promotion. The strategic objectives of the department are to: advocate for health promotion and chronic disease prevention and control; promote health, especially for poor and disadvantaged populations; slow and reverse the adverse trends in the common chronic disease risk factors; and prevent premature deaths and avoidable disability due to major chronic diseases.

This work is complemented by that of the Department of Nutrition for Health and Development. The strategic objectives of the department are to promote healthy diets and improve the nutritional status of the population throughout the life course, particularly among the vulnerable. This is achieved by providing support to countries in developing and implementing national intersectoral Food and Nutrition Policies and Programmes to address double-burden of nutrition-related ill-health, and to contribute to the achievement of the Millennium Development Goals (MDGs).

For more information contact:

WHO Media centre
Telephone: +41 22 791 2222
E-mail: mediainquiries@who.int

2009년 4월~6월, 미국의 신종플루 입원환자 분석

신종플루 증상으로 24시간 이상 입원한 272명 환자의 의료기록 분석.

272명의 환자 중에서 25%는 중환자실(intensive care unit)에 입원. 7% 사망. 18세 이하 청소년 및 영유아는 45%, 65세 이상 노령자는 5%. 87% 환자가 1개 이상의 기저질환(천식, 당뇨, 심장병, 신경질환, 임신)

방사선 촬영을 실시한 249명의 환자 중에서 100명(40%)에서 폐렴 소견 확인. 항바이러스제 투약 실시한 268명의 환자 중에서 200명(75%)는 발병 후 3일 이내에 항바이러스제 투약 시작.
의료기록은 입원환자들에게 초기에 항바이러스제를 투여하는 것은 아주 유용하고 효과적이었음을 암시하고 있음.

=======================================

Volume 361:1935-1944  November 12, 2009  Number 20 

Hospitalized Patients with 2009 H1N1 Influenza in the United States, April–June 2009

Seema Jain, M.D., Laurie Kamimoto, M.D., M.P.H., Anna M. Bramley, M.P.H., Ann M. Schmitz, D.V.M., Stephen R. Benoit, M.D., M.P.H., Janice Louie, M.D., M.P.H., David E. Sugerman, M.D., M.P.H., Jean K. Druckenmiller, B.S., S.M.(N.R.M.), Kathleen A. Ritger, M.D., M.P.H., Rashmi Chugh, M.D., M.P.H., Supriya Jasuja, M.D., M.P.H., Meredith Deutscher, M.D., Sanny Chen, Ph.D., M.H.S., John D. Walker, M.D., Jeffrey S. Duchin, M.D., Susan Lett, M.D., M.P.H., Susan Soliva, M.P.H., Eden V. Wells, M.D., M.P.H., David Swerdlow, M.D., Timothy M. Uyeki, M.D., M.P.H., Anthony E. Fiore, M.D., M.P.H., Sonja J. Olsen, Ph.D., Alicia M. Fry, M.D., M.P.H., Carolyn B. Bridges, M.D., Lyn Finelli, Dr.P.H., for the 2009 Pandemic Influenza A (H1N1) Virus Hospitalizations Investigation Team

출처 : http://content.nejm.org/cgi/content/full/361/20/1935

ABSTRACT

Background During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. We describe the clinical characteristics of patients who were hospitalized with 2009 H1N1 influenza in the United States from April 2009 to mid-June 2009.

Methods Using medical charts, we collected data on 272 patients who were hospitalized for at least 24 hours for influenza-like illness and who tested positive for the 2009 H1N1 virus with the use of a real-time reverse-transcriptase–polymerase-chain-reaction assay.

Results Of the 272 patients we studied, 25% were admitted to an intensive care unit and 7% died. Forty-five percent of the patients were children under the age of 18 years, and 5% were 65 years of age or older. Seventy-three percent of the patients had at least one underlying medical condition; these conditions included asthma; diabetes; heart, lung, and neurologic diseases; and pregnancy. Of the 249 patients who underwent chest radiography on admission, 100 (40%) had findings consistent with pneumonia. Of the 268 patients for whom data were available regarding the use of antiviral drugs, such therapy was initiated in 200 patients (75%) at a median of 3 days after the onset of illness. Data suggest that the use of antiviral drugs was beneficial in hospitalized patients, especially when such therapy was initiated early.

Conclusions During the evaluation period, 2009 H1N1 influenza caused severe illness requiring hospitalization, including pneumonia and death. Nearly three quarters of the patients had one or more underlying medical conditions. Few severe illnesses were reported among persons 65 years of age or older. Patients seemed to benefit from antiviral therapy.

——————————————————————————–
On April 15, 2009, and April 17, 2009, the Centers for Disease Control and Prevention (CDC) confirmed the first two cases of human infection with a pandemic influenza A (H1N1) virus in the United States.1 The 2009 H1N1 virus contained a unique combination of gene segments that had not previously been identified in humans or animals.2,3 As of September 20, 2009, human infection with 2009 H1N1 virus had been identified in 191 countries and territories.4
Information on the clinical spectrum of illness and risk factors for severity among persons who are hospitalized for the treatment of 2009 H1N1 influenza is still emerging.5 During peak periods of seasonal influenza, most hospitalizations occur among persons less than 2 years of age or 65 years of age or older and among patients with certain medical conditions.6,7 More than 90% of influenza-related deaths occur in patients in the older age group.8 Underlying medical conditions that have been reported in patients who were hospitalized with seasonal influenza have included diabetes and cardiovascular, neurologic, and pulmonary diseases, including asthma.7,9,10 Frequently reported complications have included pneumonia, bacterial coinfection, and exacerbation of underlying medical conditions, such as congestive heart failure.7,9,10 This report summarizes the clinical findings regarding patients who were hospitalized for the treatment of 2009 H1N1 influenza early in the U.S. epidemic.

Methods

Patients

We describe patients who were hospitalized for at least 24 hours with an influenza-like illness (temperature of 37.8°C [100°F] or higher and cough or sore throat) and who had 2009 H1N1 virus infection, as confirmed by a real-time reverse-transcriptase–polymerase-chain-reaction assay at either the CDC or state health departments. All testing was based on standard CDC-based primers. We identified patients through daily reports regarding case-level information (including hospitalization status) from state health departments to the CDC. State and local public health officials were asked to collect clinical information for each hospitalized patient as part of the public health response to assess the severity of the pandemic; such participation was voluntary.

Study Design

From May 1, 2009, to June 9, 2009, data regarding the first hospitalized patients in each participating state were sequentially reviewed and medical-chart abstractions were performed by infection-control practitioners, physicians, nurses, and epidemiologists at local and state public health departments. The reviewers used a standardized form that included demographic data, influenza-vaccination history for the previous year, underlying medical conditions, clinical signs and symptoms, selected laboratory tests, radiographic findings, and treatment course. All diagnostic testing was clinically driven. For some patients, specimens were sent to the CDC for testing for bacterial infections. The protocol and standardized clinical form were approved by the CDC’s institutional review board.

For time calculations, the day of admission was considered to be hospital day 0. The body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) was calculated, for patients for whom height and weight were available, to determine whether the patient was obese (with obesity defined as a BMI of 30 to 39.9 in adults 18 years of age or older or a BMI percentile of 95 to 100 in children between the ages of 2 and 18 years) or morbidly obese (BMI 40 in adults only); the BMI was not calculated in pregnant women. We performed bivariate analysis to compare the outcomes for patients who were not admitted to an intensive care unit (ICU) and who survived with those for patients who either died or were admitted to an ICU. We used multivariate logistic-regression models to further investigate associations with the severity of illness.

Results

Clinical Characteristics

From May 1, 2009, to June 9, 2009, a total of 13,217 human cases of infection with 2009 H1N1 influenza and 1082 hospitalizations in the United States were reported to the CDC. This report describes the first 272 completed chart abstractions for hospitalized patients with 2009 H1N1 virus infection that were reported to the CDC from 24 states (Figure 1).5 The patients represented 25% of those who were hospitalized with 2009 H1N1 influenza and whose cases were reported to the CDC during the surveillance period that ended on June 9, 2009. Dates of the onset of illness ranged from April 1, 2009, to June 5, 2009. The median age of the patients was 21 years (range, 21 days to 86 years). A majority of the patients were either Hispanic (30%) or non-Hispanic white (27%) (Table 1).

View larger version (38K): [in this window] [in a new window]

Figure 1. Distribution of the 272 Patients in the Study, as Compared with the Total Number of Patients Hospitalized for 2009 H1N1 Influenza, as Reported by the States to the CDC as of June 9, 2009. States that had any reported hospitalizations of patients with 2009 H1N1 influenza during the study period are indicated in blue (states in orange had no reported hospitalizations). The number shown for each state is the proportion of patients from that state who were included in the study, as compared with the total number of hospitalized patients with confirmed 2009 H1N1 influenza that was reported by the state. Thus, the number 1 indicates that all hospitalized patients in that state were included in the study, and 0 indicates that none of the hospitalized patients were included in the study. States with 0 had no more than 5 hospitalized patients, except for Florida, which had 20; New Jersey, which had 36; and Virginia, which had 10. The study focused on approximately 25% of patients who were hospitalized, because of the availability of complete data concerning the patients’ clinical characteristics.

View this table: [in this window] [in a new window]   Table 1. Characteristics of 272 Hospitalized Patients Who Were Infected with the 2009 H1N1 Virus in the United States (April–June 2009).

Symptoms at presentation included fever and cough (Table 1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). Diarrhea or vomiting was reported in 39% of patients, including 42% of children (i.e., patients under the age of 18 years) and 37% of adults (those 18 years). The median time from the onset of illness to hospital admission was 3 days (range, 0 to 18). Of the 272 patients, 198 (73%) had an underlying medical condition, including 60% of children and 83% of adults; 32% had at least two such conditions (Table 2, and Table 1 in the Supplementary Appendix). Among patients 65 years of age or older, 100% had an underlying medical condition. Asthma was the most common condition seen in both children (29%) and adults (27%). Neurocognitive, neuromuscular, or seizure disorders were seen in both groups (14%) but were more common among children (20%) than among adults (9%). A total of 18 patients (7%) were pregnant, of whom 6 (33%) had another underlying medical condition (asthma in 4 patients and diabetes in 2 patients). Of the 18 pregnant patients, 2 (11%) were in the first trimester, 3 (17%) were in the second trimester, and 12 (67%) were in the third trimester; the gestational duration of 1 patient was not known.

View this table: [in this window] [in a new window]

Table 2. Underlying Medical Conditions among the Patients, According to Age Group.

Height and weight were available for 161 of 231 patients (70%) over the age of 2 years (with the exclusion of pregnant women). Of 100 adults, 29 (29%) were obese, and 26 (26%) were morbidly obese; 26 of the obese patients (90%) and 21 of the morbidly obese patients (81%) had an underlying medical condition. Of 61 children, 18 were obese (30%); of the obese children, 12 (67%) had an underlying medical condition (Table 1 in the Supplementary Appendix).

Diagnostic Findings

On admission, 50 of 246 patients who were tested (20%) had leukopenia, 87 of 238 (37%) had anemia, and 33 of 234 (14%) had thrombocytopenia (Table 3).11 Three of 182 patients had positive blood cultures: a 78-year-old man with Escherichia coli urosepsis, a 55-year-old woman with Streptococcus pneumoniae and group A streptococcus infection and a lung-tissue specimen that was positive for S. pneumoniae (as identified by immunohistochemical and molecular assays performed at the CDC), and a 17-year-old boy with pneumonia who had blood and endotracheal-aspirate cultures that were positive for methicillin-resistant Staphylococcus aureus. Bacterial infections that were identified from sources aside from blood samples included group A streptococcus, which was identified by means of immunohistochemical and molecular assays performed at the CDC, in a pleural-biopsy specimen from a 23-month-old boy with pleural empyema, and S. pneumoniae in two patients: a 57-year-old woman with pneumonia who had a positive urinary antigen test and a 58-year-old woman with pneumonia who had a positive culture obtained from bronchoalveolar-lavage fluid.

View this table: [in this window] [in a new window]

Table 3. Selected Laboratory Abnormalities in the Patients.

Of the 249 patients who underwent chest radiography on admission, 100 (40%) had findings that were consistent with pneumonia; the median age of these patients was 27 years (range, 1 month to 86 years), and 66% had an underlying medical condition. Radiographic findings included bilateral infiltrates (in 66 patients), an infiltrate limited to one lobe (in 26), and multilobar infiltrates limited to one lung (in 6); data were not available for 2 patients.

Treatment

Of the 268 patients for whom data were available regarding the use of antiviral drugs, 200 (75%) received such drugs (Table 1 in the Supplementary Appendix). Of these patients, 188 received oseltamivir, and 19 received zanamivir; 13 patients received combination therapy with amantadine plus oseltamivir, and 14 received combination therapy with rimantadine plus oseltamivir. The median time from the onset of illness to the initiation of antiviral therapy was 3 days (range, 0 to 29); 39% of patients received antiviral therapy within 48 hours after the onset of symptoms. Among 195 patients for whom the date of the initiation of antiviral therapy was available, such therapy was started before admission in 18 patients (9%), on admission in 86 patients (44%), within 48 hours after admission in 61 patients (31%), and more than 48 hours after admission in 30 patients (15%).

Of 260 patients for whom data were available regarding antibiotic therapy, 206 (79%) received antibiotics. Of 198 patients for whom the date of initiation of antibiotics was available, such therapy was started before admission in 30 patients (15%), on admission in 117 patients (59%), within 48 hours after admission in 44 patients (22%), and more than 48 hours after admission in 7 patients (4%). Patients received a median of two antibiotics (range, one to seven); 70% of the patients received more than one antibiotic. Commonly used antibiotics included ceftriaxone (in 94 patients), azithromycin (in 84 patients), vancomycin (in 56 patients), and levofloxacin (in 47 patients). Seventy-three percent of patients who had radiographic findings that were consistent with pneumonia were treated with antiviral drugs, and 97% were treated with antibiotics.

Of 239 patients for whom data were available regarding the use of corticosteroids, 86 (36%) received such drugs, with oral administration in 44 patients, intravenous administration in 24 patients, and both oral and intravenous administration in 15 patients; data were not available for 3 patients. Of the patients who received corticosteroids, 76% had an underlying medical condition; the most common conditions were asthma or chronic obstructive pulmonary disease (COPD) (in 48%), immunosuppression (in 19%), and cardiovascular disease (in 15%).

ICU Admissions

Of the 272 patients we evaluated, 67 (25%) were admitted to an ICU; 19 died. The median age of those who were admitted to an ICU was 29 years (range, 1 to 86). Of the 67 patients who were admitted to an ICU, 45 (67%) had an underlying medical condition, including asthma or COPD (in 28%), immunosuppression (in 18%), and neurologic diseases (in 18%); 6 patients (9%) were pregnant. Of the 67 patients who were admitted to an ICU, 42 required mechanical ventilation, 24 had the acute respiratory distress syndrome (ARDS), and 21 had a clinical diagnosis of sepsis; 56 of 65 patients (86%) received antiviral drugs, and 62 of 65 patients (95%) received antibiotics. Among these patients, the median time from the onset of illness to the initiation of antiviral therapy was 6 days (range, 0 to 24); 23% of patients received antiviral drugs within 48 hours after the onset of illness.

Outcomes

Of the 272 hospitalized patients, 253 (93%) were discharged. Nineteen patients (7%) died; all 19 had been admitted to an ICU and required mechanical ventilation. The median age of patients who died was 26 years (range, 1.3 to 57); the median time from the onset of illness to death was 15 days (range, 4 to 52). Thirteen patients who died (68%) had an underlying medical condition, including neurologic disease (in 21%), asthma or COPD (in 16%), and pregnancy (in 16%). Of the 19 patients who died, 90% received antiviral drugs, and all received antibiotics. The median time from the onset of illness to the initiation of antiviral therapy was 8 days (range, 3 to 20); none of the patients who died received antiviral therapy within 48 hours after the onset of symptoms.

Patients who were admitted to an ICU and those who died were more likely than patients who were not admitted to an ICU to have shortness of breath, a neurologic disorder, radiographically confirmed pneumonia, ARDS, or sepsis; they were also more likely to have received antimicrobial agents or corticosteroids (Table 4, and Table 2 in the Supplementary Appendix). In addition, patients who were admitted to an ICU and those who died were older, were less likely to have been vaccinated for influenza during the 2008–2009 season, and had a longer time between the onset of illness and the initiation of antiviral therapy, as compared with patients who were not admitted to an ICU. In a multivariable model that included age, admission within 2 days or more than 2 days after the onset of illness, initiation of antiviral therapy within 2 days or more than 2 days after the onset of illness, and influenza-vaccination status, the only variable that was significantly associated with a positive outcome was the receipt of antiviral drugs within 2 days after the onset of illness.

View this table: [in this window] [in a new window]   Table 4. Characteristics of Hospitalized Patients Who Were Not Admitted to an Intensive Care Unit (ICU) and Survived and Patients Who Were Admitted to an ICU or Died.

Discussion

We report on a large U.S. case series of hospitalized patients with 2009 H1N1 virus infection during the first 2 months of the pandemic. The pandemic strain of H1N1 virus caused severe illness, including pneumonia and ARDS, and resulted in ICU admissions in 25% of patients and death in 7%. Although underlying medical conditions were common in the 272 patients we evaluated, we also identified severe illness from H1N1 virus infection among young, healthy persons. Antiviral drugs were administered to most patients, but such therapy was started more than 48 hours after the onset of illness in a majority of the patients. Delayed initiation of antiviral therapy may have contributed to an increased severity of illness.

In contrast to peak periods of seasonal influenza, when influenza hospitalizations are more common among persons 65 years of age or older and those under the age of 5 years,7 during the period of our study, almost half the hospitalizations involved persons under the age of 18 years; more than one third of the patients were between the ages of 18 and 49 years, and only 5% were 65 years of age or older. Possible explanations for this phenomenon include the fact that children are more likely to be exposed in schools, the young have a greater susceptibility to the virus (as compared with persons >60 years of age, on the basis of serologic studies12,13,14), and young, febrile patients are more likely to be tested, since older adults with influenza often do not have fever.15

The clinical features of patients who were hospitalized with 2009 H1N1 influenza were generally similar to those reported during peak periods of seasonal influenza and past pandemics with an acute onset of respiratory illness.15,16,17,18 Whereas diarrhea or vomiting have occasionally been reported in children and in less than 5% of adults during peak periods of seasonal influenza,15 these symptoms were reported in 39% of patients in our study, with no significant difference between children and adults. Studies are ongoing to determine whether the transmission of the 2009 H1N1 virus can occur from exposure to virus shed in stool.

In a pattern that was similar to that in patients with seasonal influenza, the patients in our study had a high prevalence of underlying medical conditions (73%). Eighty-two percent of the patients would be considered at increased risk for influenza-related complications on the basis of age (<5 years or 65 years) or the presence of an underlying medical condition. The proportion of children who had an underlying condition (60%) was higher than proportions that have been reported for children who were hospitalized with seasonal influenza (31 to 43%).9,19,20 In published studies and unpublished CDC data, 44 to 84% of adults who were hospitalized with seasonal influenza had an underlying condition.21,22,23 The upper end of this range is similar to the proportion of hospitalized adults in our study who had an underlying condition (83%).

As in patients with seasonal influenza, asthma and COPD were the most common underlying conditions in the patients we studied.9,19,20,21,22,23 Although few patients had neurocognitive or neuromuscular disorders, children in our study were disproportionately affected by these conditions and were at increased risk for severe influenza. The 7% prevalence of pregnancy in our study was higher than the expected prevalence in the general population (1%).24 During periods of seasonal influenza and past pandemics, pregnant women have been at higher risk for influenza-associated morbidity and mortality.24,25,26,27,28

Although data regarding height and weight were available for only 70% of patients in our study, 45% of these patients (including 18 children) were either obese or morbidly obese. A majority of these patients (81%) had an underlying condition associated with an increased risk of influenza-related complications. The prevalence of obesity among the adults in our study (29%) was similar to that in the adult U.S. population (27%).29 However, the prevalence of morbid obesity (26%) was higher than the estimated 5% in the adult U.S. population.29 Although obesity has not been linked to an increased risk of influenza-related complications, further investigation is warranted.

Few bacterial coinfections were detected, but bacterial diagnostic tests were not performed in all patients; most patients received antibiotics near the time of culture collection, which could have reduced the diagnostic sensitivity. Data on pediatric mortality associated with influenza in the United States have shown an increase in the rate of bacterial coinfection, from 6 to 24% between 2004–2005 and 2006–2007; the majority of these infections were caused by methicillin-resistant S. aureus.30 The implications of such trends for 2009 H1N1 influenza are not yet clear.

In our study, a significant proportion of hospitalized patients had findings on chest radiography that were consistent with pneumonia, and the majority had bilateral infiltrates. Although it is difficult to precisely determine the cause of pneumonia from radiographs, during the 1957–1958 influenza pandemic, Louria et al.18 reported findings of diffuse bilateral infiltrates in patients with primary influenza viral pneumonia, whereas lobar infiltrates were seen in patients with secondary bacterial infections. Better studies are needed to correlate radiographic findings with the cause of pneumonia during influenza outbreaks. In our study, only 73% of patients with radiographic evidence of pneumonia received antiviral drugs, whereas 97% received antibiotics. In the absence of accurate diagnostic methods, patients who are hospitalized with suspected influenza and lung infiltrates on chest radiography should be considered for treatment with both antibiotics and antiviral drugs.10

The majority of 2009 H1N1 viruses that have been tested at the CDC to date have been susceptible to two neuraminidase inhibitors, oseltamivir and zanamivir, and resistant to two adamantanes, amantadine and rimantadine.2,3,31 Recent guidelines from the Infectious Diseases Society of America recommended the use of antiviral drugs in adults and children who are hospitalized with seasonal influenza, regardless of the underlying illness or influenza-vaccination status.10 Current interim CDC guidelines for pandemic and seasonal influenza recommend the use of either oseltamivir or zanamivir for hospitalized patients with suspected or confirmed influenza and for outpatients who are at high risk for complications.32 Although the evidence of a benefit of antiviral therapy is strongest when treatment is initiated within 48 hours after the onset of illness, a prospective cohort study of oseltamivir therapy in hospitalized patients with influenza indicated a reduction in mortality, even when such therapy was initiated more than 48 hours after illness onset.23 Recent data from Thailand also showed that oseltamivir therapy was associated with survival in hospitalized patients with influenza pneumonia.33 Under an Emergency Use Authorization, the FDA recently approved oseltamivir therapy for 2009 H1N1 infection even if it is initiated more than 48 hours after the onset of illness and also approved its use in children under the age of 1 year.32

Data from our study suggest that the use of antiviral drugs is beneficial, especially when initiated early, since patients who were admitted to an ICU or died were less likely to have received such therapy within 48 hours after the onset of symptoms. Despite the absence of definitive data regarding clinical effectiveness, treatment with antiviral drugs should be initiated in hospitalized patients with suspected 2009 H1N1 infection, even if such therapy is initiated more than 48 hours after the onset of symptoms, especially in patients with pneumonia and outpatients who are at increased risk for complications, including pregnant women.

Our study has several limitations. The patients we evaluated represented 25% of total hospitalizations for 2009 H1N1 infection that were reported to the CDC during the surveillance period that ended on June 9, 2009, and they represented most of the states with substantial influenza outbreaks during that period. Participation in the study was voluntary and was therefore subject to reporting bias. We evaluated only patients with confirmed 2009 H1N1 infection, so the group may not be representative of hospitalized patients who may not have been tested. All diagnostic testing was clinically driven, and tests were not obtained in a standardized fashion. Finally, despite the use of a standardized data-collection form, not all information was collected for all patients.

Clinicians should consider influenza, including 2009 H1N1 infection, in the differential diagnosis for patients presenting with fever and respiratory illness or pneumonia. Empirical antiviral treatment for hospitalized patients with suspected influenza or pneumonia and for outpatients who have underlying medical conditions or who are pregnant should be considered. The benefits of treatment are probably greatest when such therapy is started early, but antiviral drugs should not be withheld if patients present more than 48 hours after the onset of symptoms. As the 2009 H1N1 pandemic evolves, continued investigation is needed to better define the clinical spectrum of disease and risk factors for an increased severity of illness, which will allow for improvements in treatment guidance.

Supported by the Influenza Division and Office of Workforce and Career Development at the CDC.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the CDC.

No potential conflict of interest relevant to this article was reported.

* Members of the 2009 Pandemic Influenza A (H1N1) Virus Hospitalizations Investigation Team are listed in the Appendix.

Source Information

The authors’ affiliations are listed in the Appendix.

This article (10.1056/NEJMoa0906695) was published on October 8, 2009, at NEJM.org.

Address reprint requests to Dr. Jain at the Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, MS A-32, Atlanta, GA 30333, or at bwc8@cdc.gov.

1. Swine influenza A (H1N1) infection in two children — Southern California, March-April 2009. MMWR Morb Mortal Wkly Rep 2009;58:400-402. [Medline]
   
2. Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009;360:2605-2615. [Erratum, N Engl J Med 2009;361:102.] [Free Full Text]
   
3. Garten RJ, Davis CT, Russell CA, et al. Antigenic and genetic characteristics of swine-origin 2009 A (H1N1) influenza viruses circulating in humans. Science 2009;325:197-201. [Free Full Text]
   
4. Pandemic (H1N1) 2009 — update 67. Geneva: World Health Organization. (Accessed October 19, 2009, at http://www.who.int/csr/don/2009_09_25/en/index.html.)
   
5. Hospitalized patients with novel influenza A (H1N1) virus infection — California, April-May 2009. MMWR Morb Mortal Wkly Rep 2009;58:536-541. [Medline]
   
6. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep 2008;57:1-60. [Medline]
   
7. Thompson WW, Shay DK, Weintraub E, et al. Influenza-associated hospitalizations in the United States. JAMA 2004;292:1333-1340. [Free Full Text]
   
8. Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003;289:179-186. [Free Full Text]
   
9. Schrag SJ, Shay DK, Gershman K, et al. Multistate surveillance for laboratory-confirmed, influenza-associated hospitalizations in children: 2003-2004. Pediatr Infect Dis J 2006;25:395-400. [CrossRef][Web of Science][Medline]
   
10. Harper SA, Bradley JS, Englund JA, et al. Seasonal influenza in adults and children — diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009;48:1003-1032. [CrossRef][Web of Science][Medline]
    
11. Custer JW, Rau RE, eds. The Harriet Lane handbook. 18th ed. Philadelphia: Elsevier Mosby, 2009.
    
12. Hancock K, Veguilla V, Lu X, et al. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med 2009;361:1945-1952. [Free Full Text]
    
13. Cate TR, Kasel JA, Couch RB, Six HR, Knight V. Clinical trials of bivalent influenza A/New Jersey/76-A/Victoria/75 vaccines in the elderly. J Infect Dis 1977;136:Suppl:S518-S525. [Web of Science][Medline]
    
14. Dolin R, Wise TG, Mazur MH, Tuazon CU, Ennis FA. Immunogenicity and reactogenicity of influenza A/New Jersey/76 virus vaccines in normal adults. J Infect Dis 1977;136:Suppl:S435-S442. [Web of Science][Medline]
    
15. Nicholson KG. Clinical features of influenza. Semin Respir Infect 1992;7:26-37. [Medline]
    
16. Cox NJ, Subbarao K. Influenza. Lancet 1999;354:1277-1282. [CrossRef][Web of Science][Medline]
    
17. Moore DL, Vaudry W, Scheifele DW, et al. Surveillance for influenza admissions among children hospitalized in Canadian immunization monitoring program active centers, 2003-2004. Pediatrics 2006;118:e610-e619. [Free Full Text]
    
18. Louria DB, Blumenfield HL, Ellis JT, Kilbourne ED, Rogers DE. Studies on influenza in the pandemic of 1957-1958. II. Pulmonary complications of influenza. J Clin Invest 1959;38:213-265. [Web of Science][Medline]
    
19. Keren R, Zaoutis TE, Bridges CB, et al. Neurological and neuromuscular disease as a risk factor for respiratory failure in children hospitalized with influenza infection. JAMA 2005;294:2188-2194. [Free Full Text]
    
20. Ampofo K, Gesteland PH, Bender J, et al. Epidemiology, complications, and cost of hospitalization in children with laboratory-confirmed influenza infection. Pediatrics 2006;118:2409-2417. [Free Full Text]
    
21. Walsh EE, Cox C, Falsey AR. Clinical features of influenza A infection in older hospitalized persons. J Am Geriatr Soc 2002;50:1498-1503. [CrossRef][Web of Science][Medline]
    
22. Neuzil KM, Maynard C, Griffin MR, Heagerty P. Winter respiratory viruses and health care use: a population-based study in the northwest United States. Clin Infect Dis 2003;37:201-207. [CrossRef][Web of Science][Medline]
    
23. McGeer A, Green KA, Plevneshi A, et al. Antiviral therapy and outcomes of influenza requiring hospitalization in Ontario, Canada. Clin Infect Dis 2007;45:1568-1575. [CrossRef][Web of Science][Medline]
    
24. Jamieson DJ, Honein MA, Rasmussen SA, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009;374:451-458. [CrossRef][Web of Science][Medline]
    
25. Dodds L, McNeil SA, Fell DB, et al. Impact of influenza exposure on rates of hospital admissions and physician visits because of respiratory illness among pregnant women. CMAJ 2007;176:463-468. [Free Full Text]
    
26. Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998;148:1094-1102. [Free Full Text]
    
27. Freeman DW, Barno A. Deaths from Asian influenza associated with pregnancy. Am J Obstet Gynecol 1959;78:1172-1175. [Web of Science][Medline]
    
28. Harris JW. Influenza occurring in pregnant women. JAMA 1919;72:978-980. [Free Full Text]
    
29. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 2006;295:1549-1555. [Free Full Text]
    
30. Finelli L, Fiore A, Dhara R, et al. Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection. Pediatrics 2008;122:805-811. [Free Full Text]
    
31. FluView: a weekly influenza surveillance report prepared by the Influenza Division. Atlanta: Centers for Disease Control and Prevention. (Accessed October 19, 2009, at http://www.cdc.gov/flu/weekly/.)
    
32. Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009-2010 season. Atlanta: Centers for Disease Control and Prevention. (Accessed October 19, 2009, at http://www.cdc.gov/h1n1flu/recommendations.htm.)
    
33. Hanshaoworakul W, Simmerman JM, Narueponjirakul U, et al. Severe human influenza infections in Thailand: oseltamivir treatment and risk factors for fatal outcome. PLoS One 2009;4(6):e6051.

Appendix
The authors’ affiliations are as follows: the Influenza Division, National Center for Immunization and Respiratory Diseases (S.J., L.K., A.M.B., D.E.S., T.M.U., A.E.F., S.J.O., A.M.F., C.B.B., L.F.), the Infectious Diseases Pathology Branch, National Center for Zoonotic, Vector-Borne, and Enteric Diseases (A.M.S.), the Division of Emergency Preparedness and Response, National Center for Public Health Informatics (S.R.B.), the Epidemic Intelligence Service, Office of Workforce and Career Development (D.S., M.D., S.C.), and the Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases (M.D.) — all at the Centers for Disease Control and Prevention, Atlanta; the California Department of Public Health, Richmond (J.L.); San Diego County Health and Human Services, San Diego, CA (D.S.); the Wisconsin Division of Public Health, Madison (J.K.D.); the Chicago Department of Public Health, Chicago (K.A.R.), DuPage County Health Department, Wheaton (R.C.), and Cook County Department of Public Health, Oak Park (S.J.) — all in Illinois; the Arizona Department of Public Health, Phoenix (S.C.); the Texas Department of State Health Services, Austin (J.D.W.); Public Health–Seattle and King County, Seattle (J.S.D.); the Massachusetts Department of Health, Jamaica Plain (S.L., S.S.); and the Michigan Department of Community Health, Lansing (E.V.W.).

The members of the 2009 Pandemic Influenza A (H1N1) Hospitalizations Investigation Team are as follows: Centers for Disease Control and Prevention (asterisks indicate members of the Epidemic Intelligence Service, Office of Workforce and Career Development, Centers for Disease Control and Prevention, Atlanta): E. Barzilay, M. Biggerstaff, D.M. Blau,* L. Brammer, J. Bresee, Y. Brown, A. Cohn, N. Cox, K. Date,* F. Dawood,* N. Dharan,* S. Doshi,* J. Finks,* G. Fischer, M. Fischer, A. Fowlkes, G. Grant, D. Gross, G. Han,* L. Hicks, F. Husain,* C. Kent, J. Jaeger,* D. Jernigan, E. Lutterloh,* T. Mallick,* E. Meites,* M. Menon, M. Moore, C. Nielsen, R. Novak, M. Nowell, E. Piercefield,* C. Reed,* C. O’Reilly, M. Patel,* P. Peters, E. Staples, C. VanBeneden, S. Zaki; Adventist Glen Oaks Hospital (IL): S. Gorman; Advocate Good Samaritan Hospital (IL): O. Jegede, S. Pur; Adventist Hinsdale Hospital (IL): B. Kratochvil; Alexian Brothers Medical Center (IL): J. Daniel; Arizona Department of Public Health: R. Sunenshine; Banner Desert Medical Center (AZ): M. Reich; Barren River District Health Department (KY): S. Ray, S. Seshadri; California Department of Public Health: M. Acosta, S. Gilliam, K. Winter; Cameron County Department of Health and Human Services (TX): O. Fritzler; Cape Girardeau County Public Health Center (MO): V. Landers; Carolinas Medical Center (NC): G. Butler; Central DuPage Hospital (IL): B. Kruse, S.J. Rivera; Chicago Department of Public Health: S. Gerber; Children’s Hospital of Wisconsin: M. Rotar; City of El Paso Department of Health (TX): Y. Vasquez; City of St. Louis Department of Health: S. Alexander; Colorado Department of Public Health and Environment: T. Gosh, K. Gershman; Cook County Department of Public Health (IL): P. Linchangco, S. Nelson, M.T. Patel, M. Vernon; Corpus Christi–Nueces County Public Health District (TX): L. Simmons; Delaware Division of Public Health: P. Eggers; Denton County Health Department (TX): D. O’Brien; DuPage County Health Department (IL): M. Lally, C. Petit, J. Vercillo; Edward Hospital and Human Services (IL): M. Anderson; Elmhurst Memorial Healthcare (IL): J. Allen, A. Schmocker, J. Lahvic; Georgia Department of Public Health: K. Arnold, C.L. Drenzek; Illinois Department of Public Health: C. Conover; Imperial County Public Health Department (CA): P. Kriner; Indian Health Services (AZ): M. Bell; Ingalls Memorial Hospital (IL): J. Gomez, R. Jain; Kansas Department of Public Health: I. Garrison, D.C. Hunt, D. Neises; Kentucky Department of Public Health: D. Thoroughman; Louisiana Department of Public Health: E. Stanley; Maricopa County Correctional Health Services (AZ): E. Shopteese, C. Wilson; Massachusetts Department of Health: N. Cocoros, M. Crockett, L. Madoff; Michigan Department of Community Health: S. Bohm, J. Collins, R. Sharangpani; Minnesota Department of Public Health: K. Como-Sabetti, S. Lowther, R. Lynfield, C. Morin, L. Triden; Missouri Department of Health and Senior Services: K.S. Oo, S. Patrick, G. Turabelidze; Nevada Department of Public Health: I. Azzam; New York City Department of Health and Mental Hygiene: Swine Flu Investigation Team; New York State Department of Health: N. Spina; North Carolina Department of Health and Human Services: D. Bergmire-Sweat, Z. Moore; Northwest Community Hospital (IL): M. Moore; Oklahoma State Department of Health: K.K. Bradley; Oregon Department of Health: M. Vandermeer; Palos Community Hospital (IL): M. Giglio; Pennsylvania Department of Health: T. Berezansky; Philadelphia Department of Public Health: C. Burke; San Diego County Health and Human Services (CA): M. Ginsberg; St. Alexius Medical Center (IL): A. Lucey; St. Catherine Hospital (IN): J. Seabrook; St. Luke’s South Hospital (KS): K. Hall-Meyer; St. Louis County Health: K. Howell; Public Health–Seattle and King County, Seattle: T. Kwan-Gett, S. McKiernan, L. Serafin, R.L. Smith; Snohomish Health District (WA): S. Patton; Tacoma–Pierce County Health Department (WA): S. Reinsvold; Tennessee Department of Health: A. Craig, T.F. Jones, M. Kainer; Texas Department of State Health Services: S. Damon, M. Davis, V.P. Fonseca, A. Martinez, J. Mireles, J.L. Smit; United States Air Force School of Aerospace Medicine (TX): K.W. Ma; Utah Department of Health: J. Coombs, R. Rolfs; Vanderbilt University School of Medicine (TN): W. Schaffner; Washington State Department of Health: C. DeBolt, A Marfin.