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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 Isabelle Vachier on the following session : Vendredi 13 Février 1988 Présentateurs/Speakers Modérateurs Experts 15h00-16h00 Epithelium A. Campbell (Montpellier) D. Dusser (Paris) Discussion 15' 15' 30' M. Murris (Toulouse) N. Roche (Paris) A.M. Vignola (Palerme) W. Coers (Groningen, NL) Dr A.M. CAMPBELL focused on the role of epithelial cells as inflammatory cells which were able to participate to the inflammatory process by release mediators, its ability to be stimulated and activated. She demonstrated that in a subpopulation of allergic asthmatic patients, bronchial epithelial cells (BEC) from brushing were positive to the Low Affinity Receptor of IgE (CD23 or FceRII) using alkaline phosphatase and immunofluorescence reveletion. Cells were stimulated with anti-IgE and release endothelin. In 50% asthmatic patients, BEC were also positive to the Hight Affinity Receptor for IgE (FceRI). On bronchial biopsies, basal and ciliated cells were positive to the a chain, the incubation with the soluble receptor was negative. Biopsies from control subjects and patients with chronic bronchitis were negative. However the expression of mRNA was positive for a and g chain in control and asthmatic subjects. When cells from asthmatic patient were incubated with an antibody against FceRI the release of 15-HETE was higher than for control subjects. When BEC were incubated in presence of NO2 the release of TNFa and IL-8 increase, showing the activation of cells with polluants. Moreover mediators such as histamine were able to activate BEC and increased levels of 15-HETE, HLA-DR and ICAM-1.

Discussion : Dr Coers highlight the fact that Dr Campbell used human fresh cells which is relevant. He wanted to have some information about the phenotype changing in culture epithelial cells. Prof Bousquet explained that few days cultures did not dediferenciated cells.

Dr Campbell indicate that they have been able to assay the enzyme activity with 15-HETE measurements and the use of the brushing methods were close related to cells in the bronchial tree.

Dr Roche asked to have some details about the correlation between the special characteristic of patients (allergy, symptoms...) and results concerning the expression of CD23 in 4 out 15 patients. Dr Campbell answered that there was no correlation, and they asked the question if BEC could be Antigen Presenting Cells?

Prof Dahlen was impress about the possibility to assess 15-HETE measurements without any stimulation with Calcium Ionophore.

Prof D. DUSSER  focused on the role of infiltrating cells in the epithelium, and the particularily of these cells found in severe asthma. The kinetic of increase number of eosinophils was slow as compared to PMN which was sudden, and PMN more than eosinophils were found to be increased in BAL fluid and in bronchial biopsie in severe asthma.

Then he highlight the problem of the poor perception of bronchoconstriction by patients which was very important in fatal asthma. A study was performed evaluating VAS/FEV1 slope in inhaled steroid treated and untreated asthmatic patients after metacholine or bradikinine challenge. The sensitivity of the perception was decreased using bradikinine as compared to metacholine for untreated but was identical for steroid-treated asthmatics. Bronchial biopsies were performed after the challenge and show that the bad perception of asthma was related to increase epithelium shedding and number of eosinophils in epithelium and lamina propia. The presence of eosiniphils was related to the epithelium shedding, to an increase hyperreactivity and to a poor perception of asthma.

Neutrophils are chemotactic cells and released large amount of proteases (elastase). A study performed in allergic asthmatic patients compared to chronic bronchitis showed that the level of elastase was lower in asthma as compared to CB in cells, but was higher in secretions. High elastase levels was correlated to the high number of PMN in secretions and low levels of FEV1. The presence of neutrophils found in severe asthma was related to the remodelling, alteration of host defense, increase inflammation and elastase secretion.

Discussion : Dr Vignola asked if epithelial damage was the consequence of eosinophils or neutrophils? Prof Dusser indicates that eosinophils are involved in the poor perception and the release of toxic products which acted on nerves and epithelium shedding. Neutrophils have effect on epithelial shedding.

Dr Fabbri indicated that in 4 cases of asthma sudden death, neutrophils were found instead of eosinophils. Dr Dusser aswered that PMN came quick and went quick. In induced sputum, elastase was found in supernatants but not in cells in asthma. However in COPD elastase levels were very high in cells.

Then a discussion debated with Dr Bel, Prof Chung and Dr Coers about the effect of treatment with inhaled steroids on neutrophil number and elastase activity.

Dr Chanez focused on new methods which gave us today the possibility to assess neutrophils in asthma. This topic is new and we have to increase the number of study to better understand the clinical relevance of the presence of these neutrophils.

. 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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