Introduction P4O2

About 1 in 7 people have a lung disease and lung diseases are the number one cause of death worldwide according to the World Health Organization. Lung diseases almost without exception lead to extremely debilitating symptoms and loss of quality of life and productivity. The fact that the number of patients with lung diseases is still increasing is a major concern.

The healthy lung has a complex defense mechanism towards the continuous exposure to the environment that is often harmful. A failing defense mechanism towards environmental insults leads to critical damage to the lung. During years or even decades, accumulation of damage will manifest in symptoms and respiratory disease such as asthma, COPD and lung cancer. Lung disease is often associated with damage to other organs, such as the heart, bone, and skeletal muscles.

At present, there are no adequate strategies to prevent toxic environmental exposure or progression from external insults to lung disease. Moreover, very few approaches are known to support repair of lung and extra-pulmonary tissue once disease has developed. A major impediment to the development of such strategies is the large heterogeneity in phenotypic presentation amongst individual patients with chronic lung diseases. In addition, the currently available diagnostic tools are insufficient to detect the damage in early, preclinical / asymptomatic stages. As a result, for many years lung disease have been relatively fatal and treatment has been largely symptomatic or palliative. Recent technological developments, however, have made it possible to make a radical impact. Today, unique opportunities enable the development of innovative strategies for prevention and reversal of lung diseases and their burden to patients.

Of crucial importance for a fundamental new approach towards lung disease, is the identification of novel biomarkers that reflect early damage rather than end stage disease and implementation of these biomarkers in diagnostics. These biomarkers can also be used to longitudinally monitor damage processes and develop personalized lifestyle interventions. In addition, more advanced ex vivo/in vitro models are needed to increase insight into 1) overarching mechanisms of lung damage and extra-pulmonary tissue dysfunction and their repair in various respiratory conditions, and 2) into personal determinants (e.g. [epi-]genetics) of the susceptibility to damage (for instance in utero) and abnormal repair.

The P4O2 program aims to identify treatable traits and innovative personalized therapeutic strategies to both prevent progression of early stage damage and to reverse established lung damage by stimulating repair.

P4O2 is a national multidisciplinary collaborative program to innovate, reinforce and display the current know-how and physical infrastructure for biomarker and data acquisition, storage and analysis. The program will develop and combine cutting edge imaging with analysis of different human materials (tissues, cells, blood samples, exhaled air) and participant reported outcomes, to develop tailored strategies for prevention and treatment of individual subjects. With our combined effort, we aim to integrate traditional phenotypic data (e.g. demographics and lung physiology) with analysis of innovative biomarkers (e.g. molecular/microscopic imaging, radiomics, [epi]genomics, proteomics, metabolomics).

 

 

Because of an exceptional research infrastructure and tradition, the Dutch respiratory field is uniquely positioned for a leading role in this transition. Various patient cohorts are already available, and Dutch lung research is rather unique in the fact that in many cases also tissue data (basic research) of these patients is available. Furthermore, the Netherlands is one of the main players in eHealth and big data and has experience in combining basic science with eHealth. 

The scale and ambition of the P4O2 program empowers fundamental improvements in quality of life, perspectives and societal participation of patients with chronic lung diseases by 2030. P4O2 will provide unique opportunities for universities and business enterprises in the Netherlands to remain in the driver seat of respiratory research.   

Goals

1. Give insight in areas of high exposure to harmful substances in the environment, e.g. by acquiring and analyzing Big Data sets, such as traffic patterns, meteorological conditions, use of smart inhalers, maternal health.

2. Early detection of lung and extra-pulmonary tissue damage, by optimizing protocols for imaging data acquisition and analysis, and development of innovative advanced imaging modalities, including radiological and molecular imaging.

3. Develop innovative tools for less invasive longitudinal sampling of patient material (tissue, cells, bodily fluids, exhaled air), combined with patient reported outcomes.

4. Identify and validate novel biomarkers for early, subclinical lung disease and related systemic damage (for example, but not exclusively cardiac and skeletal muscle), including those derived from advanced quantitative imaging techniques, nasal epithelium, exhaled air and blood (e.g. platelet transcriptome analysis).

5. Provide in vitro models (organoids, lung-on-a-chip) to study new (personalized) treatment modalities for specific diseases (asthma, COPD, lung cancer, pulmonary hypertension etc).

6. Provide novel insight into overarching mechanisms of damage and tissue repair in all lung diseases. For example, but not exclusively, study the role of the extracellular matrix and stem cells in lung repair, or mechanisms of skeletal and cardiac muscle dysfunction.

7. Develop and validate novel biomarkers (imaging, blood, epithelial cells, exhaled air, etc) for outcome measurements and assessment of treatment responses.

8. Develop tools for the introduction of precision medicine into the clinic: the right treatment for the right patient using a combination of imaging, biomarkers, and behavioral characteristics.

The program is built of 12 work packages which have their own specific focus, but also support each other. The knowledge that can be extracted from the research in these different packages is expected to make a major impact on early treatment of patients with lung damage. 

In the COVID-19 extension, that has been accepted by Health~Holland, 100 ex-COVID-19 patients will be added to the PRIL-cohort. CT scans, exposome measurements and different -omics measurements will be performed in these ex-patients.