Understanding the allergy and asthma epidemic
This essay was written by Stephen Jolles and Jenny Hughes and was first published in the 2004 Mill Hill Essays.
Allergic disorders affect around thirty percent of the adult population and forty percent of children, making these amongst the commonest diseases in the United Kingdom. Allergy is rapidly escalating, especially in children, at a rate of approximately five percent per year, with major implications for the patients, their families and the Health Service. Allergies result from an exaggerated sensitivity to substances which are normally tolerated by humans. Such substances, known as allergens, include among many others peanuts, milk, horses, medicines and grass pollens. Allergic disorders include asthma, hay fever and eczema, which are characterised by inflammation and the production by the immune system of a harmful antibody called immunoglobulin E (IgE). In an allergic reaction, the interaction between IgE and the allergen causes the release of inflammatory chemicals, which in turn cause symptoms such as sneezing, itching, rashes, and falls in blood pressure. The release of these inflammatory agents may also cause airway narrowing which leads to shortness of breath and wheezing, and swelling which, if in the mouth throat or airway, causes severe difficulty in breathing.
Asthma is a narrowing of the airways that is reversible over short periods of time, either spontaneously or as a result of treatment. This clinical definition distinguishes it from other predominantly irreversible causes of airway narrowing such as smoking-related chronic obstructive airways disease. Another feature of asthma is that it may be brought on by non-specific factors such as exercise or cold air. These two characteristics of asthma – reversible airway narrowing and airway hyper-responsiveness – are signs of a particular pattern of airway inflammation. This causes movement of immune cells into the lungs, increased smooth muscle surrounding small airways and increased secretion of mucus into the airways, which may form obstructive plugs. Sufferers may experience coughing during the day and night, wheezing and feeling that the chest is tight, or difficulty breathing in and out. At its most extreme asthma may be fatal.
People suffering from hay fever show symptoms which may include itchy, runny or obstructed nose, loss of sense of smell, sneezing, itchy eyes, facial pain, disturbed sleep and worsening of coexisting asthma. Symptoms may appear trivial, but the effects on quality of life are marked. The incidence of hay fever has increased significantly since the 1950s so that it is now the commonest immunological disorder and the commonest chronic disease of man. As the disease-causing processes in hay fever and asthma are similar it is not surprising that it also affects the majority of asthmatics.
Eczema is a common skin condition affecting up to one in five children in developed countries. It is characterized by dry itchy scaling skin, particularly in the skin creases. The intense itch leads to scratching which may be involuntary at night resulting in skin damage and bleeding. Patients often report the sensation of chronic itch as worse than pain and those who suffer from both asthma and eczema often state they would rather have the eczema controlled than the asthma. The damaged skin is at risk both from viral infections leading to warts and herpes, and from bacterial infection. Eczema has profound effects on social function for both adults and children, some of whom feel unattractive and may have problems with self-image and self-confidence. An infant with severe eczema can have a major effect on the whole family through the necessary constant attention to apply creams, the inevitable sleep deprivation, and the pain and frustration of watching a child suffer. The incidence of eczema increased sharply during the twentieth century, from an incidence of one in fifty to one in about five of the population.
The tendency to respond to common allergens, known as atopy, occurs in over a quarter of the general population and is a factor in asthma, hay fever and eczema. When both parents are atopic, approximately half of their children also develop atopic disease; when one parent or sibling is atopic, this falls to less than a third and when neither parent is atopic just over one-tenth of children develop atopic disease. These observations suggest that there is genetic involvement in atopy. The genetics of allergic diseases are complex and reveal the involvement of different sets of genes that are disease-specific or specific for inflammation or other immune diseases. However, although genetic susceptibility to allergic disease is important it is unlikely the increase in allergic disease over the past few decades can be explained by genetic factors alone. Both age and sex are also believed to play a role. Asthma occurs more often in children than in adults. Children with mild disease are likely to become symptom-free as teenagers, whereas those with more severe disease will have symptoms that persist throughout adult life. More boys than girls have atopy asthma and hay fever although these differences between the sexes become less apparent later in life.
A wide range of environmental factors including diet, breast feeding, animal exposure, infections, pollution, cigarette smoking and ear infections have been studied for their effects on the development of allergic disease. In children, exposure often coincides with the child’s evolving interaction with the world.
Food allergy may be a trigger for eczema in some infants and young children. In toddlers, who are more mobile than babies, asthma is more likely to be triggered by airborne allergens such as pet dander, moulds and dust mites. As a child grows older, exposure to pollen may trigger asthma. It has nevertheless proved very difficult to demonstrate in a practical way any benefit from reduced exposure to environmental allergens, probably because it is so difficult to reduce the amount of, for example, house dust mite or pollen to a low level where benefit might be observed. What is clear however is that where an item of food is demonstrated to be a trigger then its elimination from the diet is effective.
Animal allergens are often an asthma trigger in susceptible individuals. Up to a quarter of biomedical research workers handling laboratory animals become sensitive to rats, mice and guinea pigs, particularly to allergens in the urine. One quarter to one third of people suffering with allergies in the USA are sensitive to dog and cat allergens. In one study almost three quarters of those who showed a reaction to cat allergens had asthma. Cats are the most common culprits. Their allergens are the minute scales from hair or skin, and salivary allergens deposited on the fur during grooming where they dry and then become airborne. These allergens are small and remain airborne for long periods of time.
The role of breastfeeding has been very controversial. It has been argued that prolonged breastfeeding in combination with avoidance by the mother of allergens such as cow’s milk, peanuts, eggs and fish, and later avoidance of allergens by the infant, can result in a reduced incidence of atopic disease. In one study the prevalence of asthma and hay fever was unaffected, while some other recent studies even showed an increase in eczema. So, although there are many good reasons to breastfeed, preventing asthma does not appear to be one of them.
It seems fairly certain that air pollution plays a role in increasing morbidity from asthma and possibly hay fever and eczema. These disorders have higher prevalence in urban settings than in rural areas and increases are particularly striking in areas of high pollution. The relative contribution of pollution in urban areas is difficult to assess because other factors such as poverty, overcrowding, differences in access to medical care, and ethnic diversity also play a role. Specific air pollutants such as cigarette smoke have been studied; the weight of evidence suggests that active or passive exposure to tobacco smoke, particularly in the early years of life, increases the risk of asthma. In order to understand how allergic disease develops we need to understand how the immune system generates different responses to different substances. The immune system is an organisation of cells and molecules with specialized roles in defending against infection. There are two fundamentally different types of responses to invaders, both of which involve an immune cell called a T helper cell. These are specialised cells that provide assistance to other cells in the immune system, firstly by recognizing foreign antigens and then secreting substances that activate these other immune response cells. The first type of response is called a T helper 1 (Th-1) type and it is essential in the protection against invading viruses and bacteria, which live and multiply inside cells. It also causes the type of inflammation seen in autoimmune disease. The second type of response is called a Th-2 response and is involved in allergic inflammation and the immune system’s struggle against parasites and worms. Th-2 responses result in the production of immunoglobulin E, IgE, and of molecules that control the inflammatory response. Every individual’s IgEs are different and each allergic substance stimulates production of its own specific IgE. This means that an IgE antibody that attaches to ragweed pollen will only attach to ragweed, and not to any other kind of pollen. When IgE antibodies attach to their specific allergen, e.g. ragweed, they are immediately contacted by special cells that release molecules into the surrounding tissue. It is these molecules – in particular histamine – that cause the familiar allergic symptoms.
An important conceptual theory, which attempts to explain the increasing prevalence of allergic disease is the ‘hygiene hypothesis’. This states that the post natal development of our immune systems is influenced by the antigens and infections which we encounter. Many infections require a Th-1 type response and when this response is stimulated it allows a balance to be established which prevents allergic Th-2 responses. In the developed world many of the infections requiring a Th-1 type response have been eradicated and we live in a much ‘cleaner’ environment without the burden of infectious disease but also without these necessary balancing signals to the immune system. Since the beginning of the twentieth century exposure of the population to once-common diseases has been enormously affected by improved sanitation and living conditions, declining family size, vaccinations and antibiotics. Changes in food production techniques, with a shift in food preservation from drying and natural fermentation to industrial pasteurization and sterilization, have also caused a reduction in microbial exposure associated with eating and drinking. On the other hand, exposure to allergens has either not altered or has increased. The question for researchers is how to identify ways in which the immune system can be guided back towards this balance, avoiding either excessive Th-1 or Th-2 responses, so that allergic disease can be prevented.
Currently the treatment of allergies involves three elements: a careful search to identify triggers which should be avoided; desensitization for some allergens, and where these measures fail, symptom control. The avoidance of allergens is sometimes but not always possible. It might seem easy to eliminate a foodstuff such as peanuts from the diet but in fact sufferers from peanut allergy will be all too aware of the many hidden sources. An innocent kiss from someone who has just eaten peanut-containing food may be enough to cause a serious reaction. Others, which are particularly difficult to control, arise from situations such as eating in a restaurant. Manufacturers now tend to label foodstuffs but the frequent label of ‘may contain traces of nut’ leaves the sufferer in a difficult position. It is even more difficult to avoid allergens such as house dust mite, which are everywhere in our enclosed centrally heated homes and work places. It has been estimated that we now spend at least ninety-five percent of our time indoors. The house dust mite particularly enjoys warm moist environments and feeds on dead skin cells, which we shed into our clothes, sofas and beds. The main allergens are in fact digestive enzymes contained in the mite’s faeces. It has been estimated that a pillow which has not been laundered for more than five years may contain fifteen percent of mite faeces by weight. It is possible to reduce but not eliminate our exposure to the mite. Special bed covers help, as does replacing carpets with wooden or laminate flooring, and replacing soft furnishings with leather or equivalent coverings. Mites are made to feel especially unwelcome in a minimalist environment with wooden floors, leather sofas and venetian blinds.
In some circumstances patients may be desensitized to particular allergens. This involves controlled exposure to gradually increasing amounts of the allergen to which the patient is sensitive, usually over a prolonged treatment course. Desensitization is remarkably effective particularly for bee and wasp venom, which may cause severe allergic reactions, with success rates of over ninety-five percent. This is especially important as the fear of being stung and suffering a life threatening reaction can cause severe social disruption, indeed fear of leaving the house. The success rates for other allergens are not as good as for bee and wasp venom but desensitization may be appropriate where a particular allergen is known to be the major trigger for the allergic disease. The disadvantage of this type of treatment is the small risk of a reaction and the duration of therapy, which may be three years or more. However, there is evidence that once a patient has been fully desensitized the duration of protection from severe reactions can last a long time.
When avoidance measures are not possible, or symptoms persist, various medications are used. In the most severe form of allergic reaction, known as anaphylaxis, the patient may require emergency medication. In the case of asthma, first line treatment involves the use of inhalers. Hay fever is generally treated with antihistamines and nasal sprays. Eczema, depending on severity, is usually managed with moisturisers and steroid creams as well as antihistamines for itch. Complementary therapies are popular, especially as a means to avoid steroid treatment, but there have been few properly designed and conducted studies of efficacy. In a recent study eight out of eleven Chinese ‘herbal’ eczema creams were found to contain manufactured steroids. It is important however to keep an open mind regarding complementary therapies so that potentially useful treatments can be rigorously assessed. In severe disease, drugs which were first developed to prevent transplant rejection can be used. Recently, formulations allowing these immunosuppressive agents to be applied directly to the affected skin have advanced the treatment of eczema. Improvements in the treatment of hay fever include newer more effective antihistamines and an increasing use of pollen desensitization. There are also now a range of allergy treatments in development based on manipulation of the Th-1/Th-2 balance and its regulation as well as other strategies involving attempts to reduce harmful IgE antibody levels.
Rapid progress in emerging treatments make this an exciting time. The success of these new approaches depends on a very detailed understanding of the immune system and how Th-2 allergic responses and Th-1 side effects can be avoided. More research in this area may also guide approaches in primary prevention of allergies as our understanding of this area is currently far from complete. These efforts will require not only support for ongoing research but funds for the development of Allergy as a clinical specialty in the United Kingdom. It is a sobering thought that there are less than ten full-time Paediatric Allergists in the United Kingdom for a population of sixty million. Compare this with Sweden where, for a population of only eight million, there are ninety. There has now however been recognition by the House of Commons Health Committee paper entitled ‘The Provision of Allergy Services’ of the urgent need to develop a coordinated approach tackling both prevention and treatment in terms of the numbers of allergists and allergy centers in the face of the rapidly increasing prevalence of allergic diseases.