(Prof J. Just)

Thematic developed in the context of Trousseau Asthma Program (TAP)

Specific objectives and research axis

a) Describe the origins of allergic and respiratory diseases by identifying their main phenotypes/endotypes using appropriate methodological tools. The pole's main research themes focus on the clinical and genetic determinants of Asthma and Allergies in relation to environmental factors. Searches are made using multiple databases. First a database constituted of clinical and laboratory records of more than 25,000 asthma patients investigated in a standardized way (TAP). This registry is fed longitudinally and prospectively with data from all patients investigated and treated at the day hospital. Besides clinical and laboratory data there are also a serum bank and, for more specific studies, a DNA-library. Using this database, many studies approaching issues as key determinants of persistence of asthma during childhood and / or asthma phenotypes have been performed. Data on environmental exposures are available through questionnaires.

Between 2014-8, the main projects within ORALL include:

i) The ORLAC cohort (Risk Observatory of skin atopy) is a two-center study of the Center of Asthma and Allergy and Department of Dermatology of Prof. Bagot at Hospital Saint Louis. An estimated 40% of infants with atopic dermatitis (AD) will develop asthma between the ages of 3 and 4 years. The association between asthma and DA (or dermo-respiratory syndrome) is another phenotype of early-onset severe asthma. The aim of our prospective longitudinal study is to identify genes involved in the onset of asthma in a cohort of 250 infants with AD before age 1 year and followed prospectively during the first 6 years of life. This study will better understand the pathophysiology of this disease and diagnose infants at risk of developing asthma in this population to establish prevention strategies. At Centre of Asthma and Allergies, this cohort is explored annually by questionnaires administered by a doctor, skin prick tests, looking for specific IgE, the total serum IgE, the eosinophil count in the blood. From the age of 6, the resistance of airway obstruction and NO levels in exhaled air were also measured. These clinical and laboratory data will be correlated with polymorphisms of candidate genes in collaboration with Professor Alain Hovnanian’s team, INSERM U781, and Dr. Rémy Couderc’s Service of Biology. ORLAC cohort will also study the evolution of allergen sensitization in childhood and their roles in the developmentof allergies. Polysensitization allergen is a risk factor for allergic diseases more severe. Preliminary data indicate that the amount of sensitization to food allergens predicts severe AD, the amounts of sensitization to food allergens at age 18 months predicted sensitization to aeroallergens at the age of 5 years. Currently a new molecular biology technique (ImmunoCAP ISAC biochip: Immuno Solid-phase Allergen Chip) allows searching for 103 specific IgE vis-à-vis f allergenic components from 47 different sources. One of our ongoing researches with the immunology laboratory of Prof. Rudolf Valenta Austrian is to test the hypothesis that allergen polysensitization vis-à-vis of recombinant allergens and species belonging to different molecular families could be associated with a risk of progression of passage of atopic dermatitis to asthma ii) The SAMP cohort (Severe Asthma Molecular Phenotype) has just begun. Starting from the two phenotypes of severe asthma (as we previously described using the cluster analyses), this study aims to: (1) to investigate inflammatory markers attached to these two phenotypes of severe asthma in both the liquid bronchoalveolar lavage and peripheral blood (2); to advance the understanding of the pathophysiology of these phenotypes and approach targeted therapies. This study will be conducted in collaboration with the Laboratory of Biochemistry and Molecular Biology Dr. Rémy Couderc at the Trousseau Hospital, INSERM U 1013 Dr Lucienne Chatenou at the Necker Hospital for the Exploration of the innate and adaptive immunity and finally with Dr. Philippe Saint-Pierre and Dr. Isabella Annesi-Maesano.