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ENFUMOSA (courriel: Chanez (at) montp.inserm.fr ) The European Network For Understanding Mechanisms of Severe Asthma BIOMED 2 Program - European Commission 4th quaterly meeting, with the support of INSERM and Merck Sharp & Dohme Laboratory February 13-14th 1998 in Montpellier- France (see programm, abstracts and experts comments ) Report by Alison Campbell on the following session : Vendredi 13 Février 1988 Présentateurs/Speakers Modérateurs Experts 11h30-12h30 Pollution domestique et atmosphérique Indoor and atmospheric pollution F. de Blay (Strasbourg) M. Aubier (Paris) Discussion 15' 15' 30' D. Charpin (Marseille) G. Pauli (Strasbourg) J. Anto (Barcelone, E) N. Papageorgiou (Athenes, G) Dr de Blay showed that patients with cat allergy responded to low levels of Fel d1 in the home whilst 200 fold greater amounts were required to cause a 20 % drop in FEV1 under laboratory conditions. In patients with mild asthma and cat allergy but no cat at home adminsitration of low levels of Fel d1 resulted in bronhial hyperresponsiveness and an increase in both serum and BAL ECP. Dr de Blay concluded that exposure to low doses of Fel d1 in sensitized patients, whilst not causing clinical symptoms caused eosinophil activation and increased bronchial hyperreactivity. He suggested that serum ECP could be a good marker in non-symptomatic asthmatic patients. Professor Aubier's presentation began with the comment that pollution has cytotoxic effects on the epithelium, results in increased bronchial hyperrreactivity and intereacts with the immune system. Exposure of an epithelial cell line to diesel particles (DP) increased GM-CSF production. Exposure of nasal poyp cells also increased GM-CSF but did not affect levels of other cytokines. Two recent studies had shown that concomittant exposure of allergic patients to antigen and DP caused increase in IgE levels with a maximum occuring 4 days after exposure. Epidemiologic studies take 2 forms: Ecologic - indices of hospitalization or mortality with pollution levels Panel studies - comparing symptoms in individuals against pollution levels. In the short term it is clear that asthma is worsened by pollution and increases of 50 µg/m3 of pollutant increases the risk of symptoms by 1,3-2,8 fold. Long term effects are more difficult to assess, SO2 levels have decreased whilst asthma has increased over the last 2 decades. In 1994, it was shown that asthma i higher in West Germany, whilst East Germany has higher pollution levels and the incidence of asthma is not hgher in urban areas.

Discussion:

Prof Anto congratulated Dr de Blay on his work and asked if there was data from other studies suggesting that low antigen exposure leads to chronic inflammation without symptoms ?

Dr de Blay replied that 2 similar studies had beeen performed but both included symptomatic patients. The next step should be to repeat the study with increased numbers of patients and to look for other markers of inflammation.

Anto asked if exposure to cat allergen in non-sensitized patients could have an effect ?

De Blay agreed it would be an interesting study.

Anto asked if passive exposure to cat antigens could be involved eg sitting next to a cat owner

De Blay replied that allergen levels were measured in the home and in these patients allergen eviction does not work.

Prof Bousquet cautioned that exposure of non cat atopic patients could lead to later sensitization.

Prof. Siafakas suggested that since ECP levels were raised when FEV1 levels did not change by 20% that smaller changes in FEV1 should be considered positive.

Prof Holgate said that this was an excellent model which touched on the real world. In animals, exposure over time leads to decreased sensitization and induction of tolerance whereas teh reverse phenomena was demonstrated by de Blay in man. What are the cells infitrating the airways causing increased sensitization. Are they FceRI bearing dendritic cells ?

Prof Charpin remarked that de Blay had shown that cat allergic patients were highly sensitive and could passive exposure lead to an attack ?

De Blay agreed saying that some attacks occur in aeroplanes. He stressed that we need to know the significance of these patients in the asthmatic population.

Dr Papageorgiou showed an overhead demonstrating that the incidence of asthma is 2,9 % in Athens and 5.1% in Paris but polution levels were almost twice as high in Athens. Short term effects of pollution is to increase asthma but places with very low pollution such as the Scottish Highland or Australia have a high incidence of asthma.

J Bousquet said that asthma is a very complex disease with many factors. There is no link between asthma and sensitization yet many patients develop symptoms during the pollen season. Outdoor pollution may play a minor role as 70-80 % of our time is spent indoors. Finally he added that polyaromatic hydrocarbons have an immunologic effect and since 1972 these have increase in the Western World due to changes in cracking.

Aubier agreed, inert carbon particles do not cause GM-CSF release.

Dr Siafakas said that the exposure time was interesting, with a maximum effect at 4 days and perhaps signs could be looked for earlier.

Aubier replied that that the changes in peak flow were very small and the major effect was seen after 3 days but changes could be detected at 1 or 2 days.

Dr Chanez asked if there was a link between Prof Aubier's work and that of Dr de Blay in that low levels of pollution could increase sensitivity and bronchial hyperreactivity (BHR).

Aubier replied that yes, in a paper published in 1996 or 1997, pre-exposure to ozone for 3 hours resulted in an increase in an increase in BHR after allergen challenge.

Chanez: Yes but in real life ?

Aubier: there is no data but I imagine this is the case.

Prof Fabbri: there was some data several years ago involving a study in Germany with nasal lavage after exposure to NO2 and increased neutrophils. Even minute concentrations of pollutants lead to significant inflammatory effects in the airways.

Aubier: Yes, there were similar findings with macrophages.

Anto: Long term effects are difficult to measure and changes in peak flow are not very sensitive. We need more studies to appraise the clinical relevance.

Aubier: This is important. Changes in peak flow of 4.5% can be detected but may not mean anything. Changes are only seen in mild asthmatics as severe asthmatics are treated and the changes are too small. Interactions between allergens and pollution are important.

Prof. Pauli: Is there data concerning allergen load in athens.

Aubier: I don't know.

Prof Papergeorgiou: We have good genes for low asthma prevelance in Athens ! Asthma seems less severe there.

Prof Holgate: This is very complex, with genetic susceptibility to pollution. In Nature 2 weeks ago thre was a paper on ozone sensitivity in mice. Ozone and NO2 are oxidizing agents. One can protect oneself with vitamin C or vitamin E. There is strong evidence that severity is linked with oxidant status of the population. A selenium deficiency leads to increased risk of oxidant related disease. We need to find out the interactions.

Prof Fan Chung: Steve said everything I had to say. What was the spread of the response?

M Aubier: We only observed changes in mild asthmatics and they were always very small. We never saw changes of 25 -30 % in peak flow.

Holgate: In the laboratory there are high and low responders to ozone.

. Enfumosa Congrès   Conçue et réalisée par: Michel Godard (at) Top
Date de création: 12 Février 1998 -Dernière mise à jour: 23/07/98
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