Respiratory Allergy: prevention and treatment

The meeting of the Allergy Research Foundation - November 2007
Michelle Berriedale-Johnson reports

For anyone interested in either respiratory diseases or allergy this was a really fascinating meeting of the experts in the field.

The asthma-rhinitis connection

First to speak was Dr Glennis Scadding, from the Royal National Throat, Nose and Ear Hospital, who made the point, so often ignored by both asthma and rhinitis specialists, that the nose is part of the same respiratory system as the lungs, so the connection between rhinitis (a nasal condition) and asthma (a respiratory one) is very close.
For example, 80% of asthmatics also have rhinitis while those with allergic rhinitis are three times more likely to develop asthma. Moreover, 20-25% of asthmatics also have rhino-sinusitis, which involves the sinuses and causes facial pain as well as the blocked nose and mouth breathing of simple rhinitis. Both of the latter, which also increase the chances of contracting a virus, will have a deleterious effect on asthma.

Studies suggest that asthmatics who suffer from allergic rhinitis need fewer hospital visits if they are receiving treatment for the rhinitis.
The usual treatment is intra- nasal steroids although there is a concern about steroid load as these patients may also be on steroids for asthma and/or eczema - and 80% of what goes into the nose finds its way into the stomach and the liver.

Alternative treatments which show promise are allergen-
specific immunotherapy (see below) and anti-IgE drugs (see below).
Asked whether she had tried any nutritional interventions Dr Scadding said that she had not but that she was a great believer in warm salt water nasal douches.

Allergic sensitisation and asthma

Professor Adnan Custovic, professor of allergy at the University of Manchester, maintained that allergic sensitisation was crucial in asthma.

Although there are a huge number of people who are sensitised to allergens (house dust mite, pollen, cats, dogs etc) but who do not have asthma or any symptoms of asthma, there is a strong correlation between the level of allergic sensitisation and the presence of asthma.
The severity of the asthma may also depend on which allergen the patient is sensitised to. Sensitivity to moulds, for example, usually suggests more severe disease. And the severity of the disease will also be closely linked to the level of exposure to the allergen.
Viral infection will also be relevant so, while an asthmatic who is exposed to a high level of allergens will make an increased number of hospital visits, an asthmatic exposed to high levels of allergens and a virus will make even more.

Because lung function that is set very in early childhood persists into adult life it is very important to identify allergic sensitisation that could lead to asthma as young as possible. Three year olds who were atopic had poorer lung function than non-atopic children, even though they had no symptoms of asthma or wheeze.

Genetic predispositions are entirely dependent on environmental factors so, depending on the latter, genetics can either predispose or protect. Thus although allergy is really important for some patients, it is not for all. Treatments need to be individualised to patients - one size really does not fit all.

Proteins versus sugars

Dr Tom Platts-Mills is head of the Asthma and Allergic Disease Center at the University of Virginia.

He pointed out that asthmatic children taken to the Alps improve not only because of the reduction in their exposure to mites but because they take more exercise, eat different (better?) food etc. So although exposure to allergens is important it is not the only factor.

Other interesting points:
• Allergic asthma is becoming more common; intrinsic (non-
allergic) asthma is not.
• There are basically four cat allergens and over 20 dust mite allergens - yet it takes a far higher exposure to cat proteins to induce allergy than it does to mite allergens.
This could be explained by the fact that dog and cat proteins are, in evolutionary terms, far closer to human proteins than those of mites, cockroaches etc. So it may require a higher exposure to the relatively similar dog or cat proteins than to the less similar mite proteins to trigger a reaction.
• In New Zealand 50-55% of households have cats and asthma rates are three times higher than they are in Germany, for instance. Yet,
although New Zealanders have high levels of IgE antibodies to mites, they have none to cats. This suggests that high exposure may have induced tolerance to cat proteins.
• On the other hand, high exposure to a potential allergen (such as the Asian lady beetle which has recently invaded the US) can trigger an IgE mediated allergy at any point in life.
• IgE antibodies are not only created in response to a protein; they can also be created to a carbohydrate - specifically galactose, which is a non-human sugar. We all carry antibodies to it. Humans need an enzyme (galactose alpha 1-3 galactose transferase) to process this sugar, but it would appear that only certain blood groups carry it. Raised levels of IgE to galactose do not show up in skin or prick tests; they appear to be related to anaphylaxis, but not to allergy.

Asthma and food allergy

Graham Roberts is the director of the David Hide Asthma and Allergy Research Centre on the Isle of Wight, with a very specific interest in the relationship between asthma and food allergy. He opened his talk with some statistics:
• 20% of children in the UK have asthma
• 2% of children in the UK have food allergy
• 2-8% of asthmatic children have food allergy
• 30-60% of children with food allergy have asthma

But does this mean that there is a causal relationship between them?
There is no doubt that food often causes respiratory symptoms and that nearly all deaths from anaphylaxis to food (especially milk and nuts) occur in poorly controlled asthmatics.

The fact that food proteins can be aero-allergens (breathed in rather than eaten) may be relevant since 0.4 nanograms of allergen in the air has been shown to be enough to cause a reaction.

The allergic march is usually presumed to be eczema to food allergy to rhino-conjunctivitis to asthma, but should it actually be eczema to rhinoconjunctivitis /asthma to food allergy?
• 50% of egg-allergic children go on to develop asthma
• 80% of eczematous and egg- allergic children go onto
develop asthma
• Occupational asthma often is triggered by exposure to a food to which an allergy is developed.

Maybe the route could be:
1. Atopic child develops food allergy
2. It breathes in food allergens which sensitise the airways
3. It develops allergic asthma

All asthmatic children should be screened (a case history and oral food challenge) for food allergy. Ideally they should also undergo an inhaled food challenge. This is not being done at the moment which may explain why some children who do not react to an oral challenge do react later - maybe to an aero-allergen.

SCIT versus SLIT

Dr Moises Calderon is head of the clinical trials unit at the Royal Brompton Hospital where he has been carrying out a meta-analysis of the recent trials of sub-cutaneous and sub-lingual immunotherapy - SCIT and SLIT.

Immunotherapy is the process by which the allergic patient is given, over a period, increasing doses of their allergen to attempt to ‘induce tolerance’ to the allergen (educate the immune system to treat it as harmless).

Subcutaneous immunotherapy (SCIT) involves introducing a tiny amount of the allergen beneath the skin and has been widely used in central Europe, Germany and Spain since the early 1900s. As a result of a number of fatalities which occurred here in the 1970s it has been little used in the UK.

Sub-lingual immunotherapy (SLIT) involves introducing the allergen beneath the tongue and has been used in France and Italy (especially amongst children) since the 1970s.

Dr Calderon’s analyses of the literature suggests that SCIT achieved better both immediate and long term outcomes, but that there could be questions over its safety, especially amongst poorly controlled asthmatics.

On the other hand SLIT has an excellent safety record and does achieve very positive results, if not quite as good as SCIT. One trial found that patients still remained symptom free after seven years (there is no longer term data) and that children treated with SLIT
developed fewer other allergies and less asthma. There is also the possibility that SLIT, unlike SCIT, could be administered at home rather than in a clinic.

Anti IgE

Professor Ulrich Wahn is professor of paediatrics, allergology and pneumology at Humbolt University in Berlin and has been working with anti-IgE therapy.

IgE antibodies are what the body creates in response to ‘an ?invasion’ by an allergen. They bind, or stick, to what are called ‘mast cells’ thereby triggering a release of histamine, the chemical responsible for the allergic reaction - the inflammation (itching and swelling of face, lips etc) and the contraction of the smooth muscles around the airways.
Anti IgE drugs prevent the IgE antibodies binding to the mast cells, thereby preventing the release of the histamine.

Although they have been developed to be used against any
allergen so far, for political/economic reasons, they have only been used in allergic asthma where the response has been very positive. Patients, especially young people with poor lung function, have found their daily lives transformed.

Although still in their infancy anti-IgE drugs seem to be safe and to be particularly promising for multiple allergies. Early trials also suggest that they combine very well with specific immunotherapy. There is no data as yet as to their longevity - whether the response wears off or not - although so far there does not seem to be any ‘rebound’ when the treatment is stopped. Nor is it known whether they could be used in early infancy to prevent the onset of the allergic march.

Reversal of roles and barrier genes

Professor Stephen Holgate, Medical Research Council professor of immunopharmacology and consultant physician at Southampton University Hospital Trust, posed some interesting questions:
• 40% of western populations are atopic but what deter- mines which organ will be affected?
• Why is it that one third of allergic asthmatics respond well to treatment, one third do OK but one third do not respond at all?
• How is it that in the 1950s when air pollution was very high, the incidence of asthma was very low?

It has always been assumed that it was the inflammatory
aspect of asthma that caused structural damage to the lungs - the epithelium (the lining of the lungs) the mucus secretions etc. Yet reduction of the inflammation seems to have little effect on the structural changes.

Inflammation is normally a response to injury so, could the inflammatory response inasthma be a response to a
damaged or wounded lung, rather than the cause of it?
The recent discovery of a group of 100 odd genes involved in the barrier function of the skin has been seen as relevant mainly to eczema and atopic dermatitis - allowing allergens, bacteria and viruses to penetrate the skin and sensitise the system. (See research reports: Are people with eczema just too thin skinned? and Eczema gene secrets in the research section.)

However, in asthma, the tight protein web which should seal the cells in the epithelium or lining of the airways is often damaged and ‘leaky’ so is unable to repel an environmental assault by allergens, tobacco smoke, viruses, bacteria, air pollution etc. Damaged epitheliums appear in children as young as three.

In asthmatic patients the epithelium seems unable to repair itself unless aided by growth factors (naturally occurring proteins which are able to stimulate cell growth). But once it does repair, the inflammation subsides. So maybe asthmatic treatment should concentrate not on reducing inflammation but on repairing the structural damage to the lung?

More information from the
Allergy Research Foundation
Box 18 Aylesbury HP22 4XJ
(44) 1296 655818

Click here for more general articles on asthma

First Published in November 2007

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