Monday, May 12, 2014 C7
HEALTH Dr Dan Martin uses an SDF camera to measure blood flow under his tongue at Everest Base Camp.
The air
up there
A series of medical studies conducted on Mount Everest aims to help people suffering from a variety of conditions, writes Kate Whitehead
T
he first thing most people who reach the summit of Mount Everest do is take a trophy photograph, but when Mike Grocott scaled the world’s highest mountain in 2007 he had other things on his mind. Grocott, professor of anaesthesia and critical care at the University of Southampton, was leading a team of “climbing doctors” to better understand the variation in terms of how people respond to oxygen, an important factor in determining why some people fare better than others in intensive care units. The scientists are still sifting through the vast amount of data obtained from that study – Caudwell Xtreme Everest – as well as a second trip to Everest last year, but already they have made some breakthrough findings. It is the research into type 2 diabetes that is getting a lot of attention, particularly as rising global obesity levels mean the condition is more prevalent.
Type-2 diabetes is when cells in the body fail to respond to insulin, a hormone that helps regulate blood sugar levels. Too much sugar can be toxic and lead to kidney and nerve damage if left untreated. Although it used to be associated with older people, younger people are now affected, too. In Hong Kong, about one in 10 people have diabetes mellitus, of which more than 90 per cent have type 2 diabetes.
Part of the Caudwell Xtreme Everest team en route to base camp.
The Caudwell Xtreme Everest study by the University of Southampton and University College London took 24 healthy volunteers to Everest Base Camp, which is at about 5,300 metres above sea level. “If you like, it’s the human equivalent of laboratory rats. The great advantage over animals or test tube-based science was studying the right species – humans – and the functions of all the different systems working together. You can’t really get that unless you study whole humans,” says Grocott. Half the group stayed at Everest Base Camp for two months while Grocott led the other half to the 8,848-metre high summit. At six and eight weeks, the volunteers’ blood sugar control and weight changes were monitored as well as “inflammation biomarkers” which indicate the presence of a disease. “The plan had been to take an arterial blood sample on the summit to find out what the level of oxygen is in a critically hypoxic environment, but in fact not terribly surprisingly it was a bit cold and a bit windy,” says Grocott, whose wife Dr Denny Levett was on the team. He led the team back down the mountain to a structure known as “the balcony” at 8,400 metres, and took the blood tests there. A Sherpa then ran the samples down to the Western Cwm, a broad valley on the mountain at 6,400 metres where there was a fully set up lab. “It was a very different experience to most people’s climbing trips. We left in the middle of March and didn’t
come back until the end of June, and were at Base Camp before any other climbing teams and left after the other teams had gone. The climbing was a relatively small component of what we were doing,” says Grocott, who has 30 years mountaineering experience and ascended Nepal’s Cho Oyu at 8,201 metres the year before his Everest summit. “We had this unique opportunity to study whole humans exposed for a long period of time to quite severe hypoxia and what you find is that you do develop this picture of glucose intolerance, which thankfully recovers when you return to sea level,” says Grocott. The findings, published in PLOS ONE last month, are a window into better understanding insulin resistance. Fat tissue in overweight and obese people is thought to exist in a state of mild hypoxia because the small blood vessels aren’t able to supply enough oxygen. What the researchers found was that some of the known biomarkers for insulin resistance were increased after the subjects had been in a low oxygen environment for several weeks.
It was a very different experience to most people’s climbing trips DR MIKE GROCOTT
Dr Sundeep Dhillon being tested at Everest Base Camp. It’s thought that this was due to increased amounts of tissue damage caused by oxidative stress, a situation whereby the cells aren’t able to repair themselves properly. “The results suggest possible interventions to reduce progression to full-blown diabetes, including measures to reduce oxidative stress and inflammation,” says Grocott. The ability to scale Everest was just one of the many challenges faced by the climbing doctors. They also had to think about how to look after their equipment at temperatures well below freezing. While most of the kit was fine as long it didn’t freeze rapidly, some items were more sensitive and needed to be kept in insulated boxes. That was easily done at Base Camp, but not above the Western Cwm and the researchers had to come up with a Plan B.
“The oxygen sensors, the laptops and the other things we knew were temperature sensitive spent the night in our sleeping bags,” says Grocott. Of course, having a large team of doctors carrying out medical research meant safety was the number one priority, over and above any climbing feats – which is why they descended from the summit to the relative shelter of the balcony before taking the blood samples. The medical team was also able to step in and save the lives of two people who might otherwise not have survived. The first was Usha Bista, a Nepalese woman found unconscious in the region known as the “Death Zone” by American climber Dave Hahn. Grocott and his team helped her down the mountain and, aside from losing the end of her thumb, she was fine and surprised Grocott by e-mailing him a year later to say she’d just successfully summited Everest. The second was a Nepalese climber who the team found unconscious. They gave him oxygen and food and he recovered sufficiently to get off the mountain by himself. In spring last year Xtreme Everest 2 was launched to add further data to the study. Six years on and Grocott’s personal situation had changed, so he didn’t scale Everest. Instead he and his wife – with their three children aged under four in tow – ran the laboratory in Katmandu, analysing blood samples from the volunteers. “In a way it was almost as challenging as in 2007, but for very different reasons,” says
Grocott, referring to challenge of looking after the children as well as a lab. As well as looking at type-2 diabetes, they were also looking at nitrogen oxide biology. Unlike the first big study, half the subjects in the second one were Sherpas. They wanted to study the Nepalese guides to see how their bodies have adapted to function well at high altitude. “The Sherpas seem to have a very high level of nitrogen oxide. Potentially – although we won’t be able to confirm this until later in the year – the Sherpas have mitochondrial changes, which are particularly beneficial,” says Grocott. The findings on how Sherpas are adapted to a low-oxygen environment could help critically ill patients. If the researchers can identify what gives Sherpas an advantage in high altitude, doctors might be able to offer something similar to those in intensive care wards where oxygen shortage claims many lives. The key to helping people with sleep apnea might also lie at the top of the mountain. The condition, common in the obese, causes disrupted breathing during sleep – for 10 seconds or more at a time. Sleep apnea sufferers also tend to develop type-2 diabetes. “We are very interested if the same picture is seen, particularly those with obstructive sleep apnea and obesity where you have these periods of hypoxia – or shortage of oxygen – during sleep,” says Grocott, adding that it will be some time yet before their findings alter patient care. life@scmp.com
................................................ Jeanette Wang jeanette.wang@scmp.com By the time you’ve finished reading this sentence, you’ve likely taken two breaths and inhaled about two litres of air. In a day, the average person will breathe in about 20,000 litres. Consider the amount of pollution that air contains and it’s easy to imagine how ill you can become from just breathing. It’s no surprise, then, that air pollution is a major contributor to asthma, the most common chronic disorder in children. Almost half of all children have at least one episode of wheezing before six years of age, according to a report which was published in The Lancet to coincide with World Asthma Day last week. Forty-eight per cent of children under five years of age with asthma report an attack in the preceding year, a rate higher than any other age group. In Hong Kong, more than 330,000 people suffer from asthma, according to 2011 figures from the Hong Kong Thoracic Society. About 8 per cent of primary students aged six to seven years, and 10 per cent of secondary students aged 13 to 14
years, have asthma. Every year, about 70 to 90 people in the city die from asthma attacks; among them, 20 to 30 people are aged between 15 and 44. Evidence from studies during the past several decades makes it clear that air pollution can exacerbate pre-existing asthma. But recent research suggests that air pollution might cause newonset asthma as well, say the authors of The Lancet report, professors Michael Guarnieri and John Balmes, of the University of California, San Francisco. Reviewing studies from the past five years since 2009, the authors show that short-term exposure to ozone, nitrogen dioxide, sulphur dioxide, PM2.5 particulate matter and trafficrelated air pollution can increase the risk of exacerbations of asthma. They also found that long-term exposure to air pollution, especially from traffic, can lead to new cases of asthma in adults and children. A study of 10 European cities published last year in the European Respiratory Journal estimated that 14 per cent of chronic childhood asthma is due to exposure to traffic pollution near busy roads.
Illustration: Co rbis
Traffic pollution seen as major contributor to new asthma cases
“Because many urban centres in the developing world are undergoing rapid population growth accompanied by increased outdoor air pollution, the global burden of asthma is likely to increase,” write Guarnieri and Balmes. “In view of the burden of asthma attributed to outdoor air pollution, better understanding of why asthmatic individuals are
susceptible to this exposure should enable the design of effective preventive strategies.” Britain’s Committee on the Medical Effects of Air Pollutants proposes four main mechanisms of how pollutants affect asthma: oxidative stress and damage, inflamed pathways, airway remodelling, and enhancement of respiratory sensitisation to aeroallergens. In a genetically predisposed person, this could result in newonset asthma or exacerbations of existing asthma. Some evidence shows that particulate matter causes new cases of asthma, though findings have not been consistent. There is substantial evidence that ambient levels of particular matter exacerbate existing asthma, particularly by contributing to oxidative stress and allergic inflammation. Particulate matter is characterised according to size: coarse (a diameter of 2.5 to 10 micrometres) deposits mainly in the head and large conducting airways. Fine particular matter (PM2.5) deposits throughout the respiratory tract, particularly in small airways and alveoli. Ultrafine PM (smaller than 0.1 micrometres) deposits in the alveoli.
Oxidising gases, such as nitrogen dioxide, ozone and sulphur dioxide, are another component of air pollution. There have been extensive studies on the short-term controlled exposure to ozone and sulphur dioxide at relevant concentrations. Ozone exposure results in airway inflammation, airway hyper-responsiveness, and reductions in lung function in healthy and asthmatic adults, whereas sulphur dioxide causes more prominent bronchoconstriction, especially in asthmatics. Experimental data on nitrogen dioxide has been inconsistent. But studies of asthmatic children and adults in the past five years have found
Patients should ideally live at least 300 metres from major roadways PROFESSORS GUARNIERI AND BALMES
links between nitrogen dioxide and symptoms of asthma, reduced response to bronchodilators, decrements in lung function, and exacerbation of asthma. Several studies have identified an increase in asthma incidence or prevalence associated with exposure to nitrogen dioxide. A third component of air pollution comes from traffic, which is made up of a complex mixture of particulate matter from combustion and noncombustion sources, as well as primary gaseous emissions, including nitrogen oxides. These primary emissions lead to the generation of secondary pollutants such as ozone, nitrates, and organic aerosol. There’s much data that suggests exposure to trafficrelated air pollution, especially in urban areas, has a tremendous effect on disease morbidity in individuals with asthma. A growing body of evidence, including several recent prospective studies of children with no asthma at enrolment, also shows it’s responsible for cases of incident asthma. These findings from the
reviewed studies have a few clinical implications, the authors note. First, local governments should publicise air quality monitoring data widely and on a daily basis, and issue smog alerts on days when ozone or PM2.5 levels are forecast to be high. People with asthma or other pre-existing cardiopulmonary disorders should be urged to stay indoors on such days. Second, asthmatic patients should ideally live at least 300 metres from major roadways. Third, patients should maintain inhaled corticosteroid therapy, which decreases adverse responses to pollutant exposures. Finally, policy initiatives can incentivise the development of alternatively powered vehicles and renewable electricity production, to help reduce overall pollution and mitigate climate change. Smart urban growth plans are needed. “Government investment in efficient public transportation systems and support of high-density, energyefficient housing along transit system corridors will reap longterm ... public health benefits,” the authors say.