Department of Respiratory Medicine Academic, Medical Center University of Amsterdam.
Unbiased BIOmarkers for the PREDiction of respiratory disease outcome
Department of Respiratory Medicine Academic, Medical Center University of Amsterdam. The Netherlands.
The most prevalent respiratory diseases exhibit far from simple pathophysiology. The complex biology of asthma and COPD is currently fueling the discovery of various disease phenotypes. Nevertheless, current guidelines for diagnosis and treatment are almost exclusively based on clinical and functional characteristics. Even though single biomarkers (e.g. sputum eosinophils) are gradually introduced in the management of these diseases (based on evidence provided by ‘algorithm studies’), it can be postulated that composite biomarker fingerpints will provide more comprehensive patho-biological information of these diseases and their underlying phenotypes1.
High-throughput “omics” technologies based on unbiased systems biology approaches, including transcriptomics, proteomics, lipidomics, and metabolomics are increasingly used for biomarker discovery in asthma2. This has led to unravelling and validation of e.g. transcriptomic phenotypes of asthma based on epithelial, sputum or bronchial biopsy analysis. The leading principle here is to strictly obey the recent guidelines on omics analysis in clinical medicine, thereby purposely limiting false discovery with proper (external validation)3.
There are two challenges when bringing this to clinical practice. First, the measurements should be feasible at point of care with real-time availability of results. Metabolomics of exhaled air (breathomics) qualifies for this purpose and is currently applied in longitudinal, monitoring studies. Second, the ‘omics’ fingerprints have to be integrated with clinical data, requiring a quantitative multi-scale systems approach. The latter is key of the U-BIOPRED project that, after recently completing its longitudinal follow-up of (severe) asthma patients, is delivering its first unbiased, bio-clinical phenotypic fingerprints (www.ubiopred.eu). It is envisaged that this will lead to effective integration of molecular fingerprints in patient phenotyping and clinical management.
Peter J. Sterk, MD, PhD, is head of research of the Dept. Respiratory Medicine, Academic Medical Centre, University of Amsterdam. He was trained as clinical physiologist and currently focuses on bioclinical phenotyping of patients with airways diseases. Current research focuses on translational studies in the diagnosis, monitoring and therapy of asthma and COPD, in collaboration with (inter)national networks. It includes human proof of concept models, such as experimental human in vivo exacerbations by rhinovirus infection, together with long-term cohort studies in child- and adulthood. An integrative approach prevails, in which the dynamics of airway function is coupled to molecular profiles within the airways, such as transcriptomics and breathomics. This is now following an unbiased, integrative ‘systems medicine’ strategy, aiming to introduce precision medicine for patients with various phenotypes of chronic airway diseases. He is currently coordinator of the U-BIOPRED project, funded by the Innovative Medicines Initiative (IMI) from the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA). He is Associate Dean of Graduate Studies of Academic Medical Centre, which provides teaching programs for 1200 PhD-fellows