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iABC Programme (IABC PROGRAMME)
Date du début: 1 août 2015, Date de fin: 31 juil. 2020 PROJET  TERMINÉ 

Cystic Fibrosis (CF) is a common fatal inherited disease with a frequency of 1 in 2500 live births, affecting approximately 36,000 (0.737/10,000) people in the EU. Chronic bacterial pulmonary infection leading to an irreversible decline in lung structure and function is the main cause of mortality and morbidity in patients with CF, with more than 95% of deaths due to respiratory failure. Pseudomonas aeruginosa (Pa) is the most frequently isolated pathogen, chronically infecting up to 80% of adult patients. When this occurs patients require lifelong inhaled antibiotic therapy, which although onerous to take, has been fundamental in increasing life expectancy by suppressing infection, reducing exacerbations and preserving lung function in CF patients chronically infected with Pa. Studies employing enhanced culture techniques and culture-independent molecular approaches have recently shown that the lungs of CF patients harbour diverse polymicrobial communities, the “microbiome”. Other Gram-negative non-fermenting bacteria (GNnF), including Stenotrophomonas maltophilia and bacteria from the genera Burkholderia, Achromobacter, Acinetobacter, Ralstonia and Pandoraea may be present and contribute to disease. Moreover, Burkholderia cenocepacia is associated with rapid deterioration of lung function and poor clinical outcome. Estimates for the prevalence of non-CF bronchiectasis (BE) range from 4 per 100 000 in young adults to nearly 300 per 100,000 in persons 75 years and older in developed countries. The number of adults is increasing significantly and the forecast is that the number of adults with CF will increase by 100% between 2010 and 2025. These individuals will mostly have chronic infection with Pa. Individuals with BE have chronic cough and sputum production and frequent respiratory infections which lead to impaired lung function and health-related quality of life. Chronic infection with Pa affects 12–27% of adults with BE and is associated with an increased exacerbation frequency, an accelerated decline in lung function, hospital admissions and increased mortality. There is a direct relationship between bacterial load, airway inflammation and risk of exacerbation supporting the use of long-term administration of inhaled antibiotics in BE. Currently, a limited number of inhaled antimicrobials are available for use in CF with no antibiotics approved to treat lung infection in patients with BE. As median predicted survival of CF birth cohorts is now greater than 40 years, adherence to consensus treatment guidelines requires that chronically infected patients are treated for decades with inhaled antimicrobials. Furthermore, bacteria causing respiratory infection are becoming progressively more resistant to conventional antibiotics with up to 45% of CF patients colonised with multidrug resistant (MDR) pathogens. New antibiotics with activity against such respiratory pathogens are urgently needed. The iABC-consortium (inhaled Antibiotics in Bronchiectasis and Cystic fibrosis) brings together world leading collaborative researchers to develop new antibiotic treatment options for people with CF and BE by sharing expertise and resources. It involves about 20 public partners and 2 pharmaceutical companies in 6 countries and 4 pan-European networks: ECFS-CTN, CLIN-Net, LAB-Net and EMBARC. These networks inclide almost all European countries and will be used to recruit centres for the clinical trials. These groups combine experience and proven expertise and success in microbiology, antibiotic development, clinical trials, endpoints and patient registries. Their existing infrastructure provides an excellent basis for the successful achievement of the objectives of ND4BB Topic 7. The iABC consortium will build on and add to existing research networks and infrastructures within the IMI ND4BB-program, thereby strengthening these networks for future research programs. Considerable overlap already exists between ECFS-CTN

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