How the world around you affects the severity of sickle cell disease

We all know that sickle cell is a highly variable disorder; some people seem to be hardly affected by the condition, whereas others have multiple, serious problems. Trying to understand the cause of this variability has preoccupied sickle cell doctors for many years. Some of it is undoubtedly down to our genetic makeup, who we are and how our other genes affect the activity of the sickle cell mutation, but a large part of the variability is down to things outside of us, our environment. This was made clear in a wide-ranging presentation at the 9th Sickle Cell & Thalassaemia Conference in London, by Professor David Rees from Kings College Hospital. This is both important and topical; important because we can manipulate our environment potentially giving some control over the effects of sickle cell, and topical because air pollution, one of the key environmental factors, is very much in the news at the moment.

Firstly what about the weather, that perennial topic of conversation in the English speaking world. This is probably a major determinant of pain frequency.

Cold temperatures, snow and ice, high wind speed and high humidity are implicated in provoking more episodes of vaso-occlusion and sickle cell pain.

Low temperatures, snow and ice, high wind speeds and high humidity are all implicated in provoking episodes of vaso-occlusion and sickle cell pain.

Cold temperatures lead to vasoconstriction, or closing down of the blood vessels, as the body attempts to conserve heat. Blood flow slows down, the red cells lose more and more oxygen and eventually sickle provoking a painful crisis. But it is probably more complex than this. People with sickle cell appear to be hypersensitive to temperature changes with an excessive vasoconstriction response to cold, which can also affect parts of the body remote from the area which is chilled. There is also evidence for a “vascular steal syndrome” with cold exposure causing blood flow to be shunted away from the bone marrow to other areas causing sickling in the bone marrow. Whatever the reason, temperature is key and the explanation for why your doctor will repeatedly remind you to keep warm at all times. High wind speed probably works in similar ways by causing cooling of exposed skin. How a high humidity works is not clear and rainfall, although not correlated with pain frequency in Europe or the USA, is important in tropical countries where more admissions with pain occur in the rainy season.

Air pollution is very much in the news at the moment with the Volkswagon “defeat devices” scandal rumbling on, but may also be very relevant to both short and long term complications in sickle cell disease. We each breathe in about 20 cubic meters of air a day making us all very vulnerable to any toxic chemicals in the atmosphere.

Air pollution in the City of London. The main pollutants are nitrogen oxides (nitrogen dioxide giving the smog a brown colour and nitric oxide), sulphur dioxide, ozone and most importantly particulate matter.

Air pollution in the City of London. The main pollutants are nitrogen oxides (nitrogen dioxide, giving the smog a brown colour, and nitric oxide), sulphur dioxide, ozone, carbon monoxide and most importantly particulate matter. Although these may all be produced by industrial processes in cities vehicle emissions are the main culprit.

The WHO estimated that in 2014 air pollution was responsible for 7 million premature deaths worldwide, mainly due to heart and circulation disorders (heart attacks and strokes) and lung disease (asthma and lung cancer). But there is a growing body of evidence that air pollution, especially particulates, also affects the brain, causing cognitive, or thinking, disorders in children with reduced memory and processing speeds and poor attention span, as well as accelerating cognitive decline in older people.

Vehicle pollution in Glasgow. Particulate pollution is a feature of diesel engine exhaust.

Vehicle pollution in Glasgow. Particulate pollution is a feature of diesel engine exhaust and consists of minuscule particles and a mixture of complex organic compounds and heavy metals.

High ground level ozone levels and nitrogen dioxide have both been associated with an increased rate of sickle cell admissions for pain, and stroke and asthma are both serious complications of sickle cell disease which may be provoked by air pollutants. Of course, most people with sickle cell live in inner city areas where air pollution is at it’s highest levels. The European Union has legislated for permissible levels of the main air pollutants; but last year only 2 out of the 32 London boroughs passed these pollution limits and Oxford Street was found to have the highest levels of nitrogen dioxide in the world. If you live in London you can find out how exposed you are to air pollution at “How Polluted is My Road?” http://www.howpollutedismyroad.org.uk/

High altitude has long been recognised as a potential cause of problems, because the higher up you go the “thinner” the air becomes and the less oxygen there is. Low oxygen levels promote sickling and therefore increase the risk of a painful crisis.

An Airbus over the Pyrennes. Most aircraft are presurissed so that the concentration of oxygen in the cabin is the same as if you were at 2000m. This compares with the Rockies, maximum height 4400m and the Alps 4800m.

An Airbus over the Pyrenees. Most aircraft are pressurised so that the concentration of oxygen in the cabin is the same as if you were at 2,000m. This compares with the highest peak in the Rockies at 4,400m and the Alps 4,800m.

Most people with sickle cell appear to tolerate flying very well but it is always sensible to tell your doctor before you travel and, if there is any concern, they can arrange a pre-flight assessment to make sure you can cope with the lower oxygen levels on the plane. It is usually only patients with pre-existing lung or heart problems who require additional oxygen during a flight.

It is however a matter of common experience that patients often do get a painful crisis when they travel. This seems to have more to do with a change in climate, dehydration and infections rather than the oxygen levels per se. It is important to drink plenty of fluids on the journey and whilst on holiday, use bottled water if there is any concern about the local drinking water and give yourself plenty of time to acclimatise. Needless to say it is always important to take all of your regular medicines with you as well as enough pain killers, just in case.

The last topic to consider is the home environment, something that many patients think has a very significant impact on their illness. Poverty, or a low socio-economic status, is a feature of many patient’s lives and is likely to worsen their disease, although there is very little scientific evidence to support this. It may be part of the explanation of why the severity of the illness is much worse in the developing world than in the USA or Europe. The Co-operative Study in the USA did find, in 1985, that sickle cell patients more often lived in single parent families, but on the other hand high school graduation rates and salaries were similar to an equivalent group of black Americans without sickle cell. There is clearly a need for more contemporary research to look at this more closely.

The quality of housing may also be important, particularly in northern climates, where central heating, double glazing and insulation may all mitigate the effects of the climate.

Dampness with the risk of dust and fungal spores triggering wheezing or asthma may be another factor.

Dampness with the risk of dust and fungal spores triggering wheezing or asthma may be another factor.

But yet again, there is no published evidence to support or refute this. Where we are on stronger grounds is the effect of active or passive smoking. Here there is considerable evidence that both forms are harmful to people with sickle cell disease. Studies from Jamaica showed that smoking is strongly associated with an increased risk of early death and in the USA it is linked to frequent attacks of the acute chest syndrome. Passive smoking, where you inhale other people’s smoke, results in an increased frequency of pain and hospital admissions in young people.

Finally, access to good medical care is clearly an important factor determining disease severity. The main aspects of medical care which are important for good disease control, on a global scale, are; newborn screening, so that babies with sickle cell are identified as soon after birth as possible, penicillin prophylaxis, or daily penicillin to prevent early infections, childhood vaccinations, rapid treatment of infections with antibiotics and access to safe blood for transfusion. The gradual implementation of these strategies through out the developed world over the last 40-50 years has seen childhood mortality in sickle cell fall to very low levels with an increase in average life expectancy to the mid forties. This compares to the terrible situation in the developing world where the majority of children with sickle cell still die before their fifth birthday because these simple measures are not in place.

Environmental determinants of severity in sickle cell disease. Sanjay Tewari, Valentine Brousse, Frederic Piel, Stephan Menzel and David Rees. Haematologica September 2015, volume 100, pages 1108-1116

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About rogerjamos

I am a consultant haematologist who has worked in Hackney, London, UK with patients who have sickle cell disease for many years. Knowledge is power; the hope is that this blog will empower patients by putting them in touch with contemporary research into sickle cell disease and facilitating informed discussion on the issues raised. Dr Roger Amos MA, MD, FRCPath
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