Centre de recherche Inserm UMR1152 – Physiopathology and Epidemiology of Respiratory Diseases

Director: Marina Pretolani, DR1 Inserm

–     Team 1: Epidemiology of respiratory diseases: from the etiology of asthma and COPD to the prognosis of lung transplantation (Leader: G. Thabut, PUPH2).

–     Team 2: Airway inflammation and remodeling in obstructive lung diseases (Leaders: M. Pretolani, DR1 Inserm and M. Aubier, PREM).

–     Team 3: Lung inflammation and fibrogenesis (Leader: B. Crestani, PUPH1).

–     Team 4: Innate immunity and anti-infective pulmonary defense (Leader: J.M. Sallenave, PUEX).

Présentation :

The research projects of Inserm U1152 focus on the identification of risk factors and of genetic, cellular, and molecular mechanisms underlying the development and progression of chronic lung diseases, such as severe asthma, chronic obstructive pulmonary disease (COPD)/emphysema and idiopathic pulmonary fibrosis (IPF). The laboratory also concentrates its interest on innate immunity against pulmonary infections during COPD and cystic fibrosis, as well as and on different aspects and complications of lung transplantation.

Thématiques de recherche clinique :

The UMR1152 investigates novel mechanisms, biomarkers, prognostic indices and genetic factors implicated in the onset and evolution of severe therapy-refractory asthma, chronic dysfunctions in lung transplantation, α1 antitrypsin deficiency-related emphysema and IPF. Thes projects are developed using on-site and longitudinal multicenter patient cohorts managed, by a large part, by the Teams.

Faits marquants :

–     identification of airway cell and structures involved in the clinical benefit of bronchial thermoplasty in severe therapy-refractory asthmatics;

–     involvement of the RTEL1 gene, that contributes to telomere homeostasis, in the onset of familial pulmonary fibrosis;

–     evidence that overexpression of the tolerogenic molecule, human leukocyte antigen (HLA)-G, in lung transplant recipients is a predictor of graft survival;

–     demonstration of the survival benefit of lung transplant in patients with cystic fibrosis and of the pros and cons of an high-emergency, based organ allocation.

Selected publications :

1) Thabut G, Christie JD, Mal H, Fournier M, Brugiere O, Leseche G, Castier Y, Rizopoulos D. Survival benefit of lung transplant for cystic fibrosis since lung allocation score implementation. Am J Respir Crit Care Med 2013; Jun 15 187:1335-40.

2) Pretolani M, Dombret MC, Thabut G, Knap D, Hamidi F, Debray MP, Taille C, Chanez P, Aubier M. Reduction of airway smooth muscle mass by bronchial thermoplasty in patients with severe asthma. Am J Respir Crit Care Med 2014; Dec 15 190:1452-4.

3) Brugière O, Thabut G, Krawice-Radanne I, Rizzo R, Dauriat G, Danel C, Suberbielle C, Mal H, Stern M, Schilte C, Pretolani M, Carosella ED, Rouas-Freiss N. Role of HLA-G as a predictive marker of low risk of chronic rejection in lung transplant recipients: a clinical prospective study. Am J Transplant. 2015;15:461-71.

4) Kannengiesser C, Borie R, Ménard C, Réocreux M, Nitschké P, Gazal S, Mal H, Taillé C, Cadranel J, Nunes H, Valeyre D, Cordier JF, Callebaut I, Boileau C, Cottin V, Grandchamp B, Revy P, Crestani B. Heterozygous RTEL1 mutations are associated with familial pulmonary fibrosis. Eur Respir J. 2015;46:474-85.

5) Pretolani M, Bergqvist A, Thabut G, Dombret MC, Knapp D, Hamidi F, Alavoine L, Taillé C, Chanez P, Erjefält JS, Aubier M. Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: clinical and histopathological correlations. J Allergy Clin Immunol. 2017;139:1176-85 (with editorial).

Contacts:

Marina Pretolani : marina.pretolani@inserm.fr

Michel Aubier: michel.aubier@inserm.fr

Bruno Crestani: bruno.crestani@aphp.fr

Gabriel Thabut: gabriel.thabut@aphp.fr

Jean-Michel Sallenave: jean-michel.sallenave@inserm.fr