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Work package 4

Building the PRIL (Persons at high RIsk for Lung disease )-cohort for detection of early lung damage

In WP1, risk areas and risk populations for lung diseases in the Netherlands will be identified. However, not everybody in these risk areas or that belong to these risk populations will eventually develop lung disease and early detection of disease remains a problem. A gradual decline in lung function caused by early damage usually happens without being noticed, as most young people have an enormous overcapacity in their respiratory system. Together with the decline in lung function, extra-pulmonary manifestations (e.g. muscle wasting, bone loss, decreased cardiovascular and cognitive function) might be present or can be developed without being noticed. Once a patient develops complaints the disease process usually has already proceeded beyond the point of no return. It is hardly possible to cure these patients and most of the treatments are only there to relieve complaints. We hypothesize that it would be important to identify easy to measure biomarkers that allow us to diagnose lung damage at a much earlier stage and that can optimize therapy to prevent the occurrence of lung disease.

This work package describes setting up the PRIL cohort for studying differences between people with high risk and normal/moderate risk of lung diseases with the goal to diagnose lung damage at an earlier stage.

The first aim is to inventorize the prevalence of a high risk profile in the Netherlands. The second aim is setting up the PRIL cohort of 5000 subjects. The third aim is follow-up of at least one year for all participants of the PRIL-cohort. A five-year follow-up is planned in the long-term.

A high risk profile for lung disease is defined by risk factors (for example exposure to air pollution, second hand smoking, family history of respiratory disease, professional exposure to detergents etc). To inventorize the prevalence of a high risk profile both in a high and in a low risk group, we will characterize the exposome and respiratory complaints of 5000 people between 40-50 years of age, with and without high risk on developing respiratory disease, using questionnaires. This is the PRIL-cohort. Half of this sample will be a random sample from this age group within the Netherlands, the other half will be selected from high risk groups identified in WP1. We expect that these high risk groups will for example include subjects that live in areas with a high exposure to air pollution, subjects that are current smokers, subjects with a family history of lung disease and subject that have a professional exposure to risk factors for lung disease. This PRIL cohort will be followed for multiple years on the long run.

Using the information from the 5000 questionnaires, 1000 people will be selected for further analysis. 650 of them will be followed up using non-invasive detection methods only, and 350 people with both high risk and with average risk will be followed up using non invasive and deep phenotyping methods. We will follow up these patients for 5 years in the long-term (and hopefully extend the funding thereafter so we can follow them until old age).

At their first visit, participants in the PRIL-cohort that receive the deep phenotyping (n=350) undergo a medical exam. This includes testing of physical function (cardiovascular function [blood pressure], exercise performance [maximal cycling test, accelerometry], muscle function [1RM test]), cognitive function (CANTAB), body composition (DEXA, BIA, CT-derived muscle and adipose tissue mass and distribution), lung function, and exhaled breath (electronic Nose [eNose] and GC-MS). Furthermore, a blood sample (biomarkers for inflammation, cell sorting, (epi-)genome, transcriptome), urine sample (metabolomics), feces samples (microbiome), and 2 nose swab samples (epigenome and microbiome) will be taken. In addition, the patient will be asked to answer questionnaires on life style characteristics (e.g. dietary questionnaires and smoking history), psychosocial function, and health status.

In year 2, 3, 4 and 5 the subjects will be invited for a yearly visit. General health will be assessed by testing cardiovascular function (blood pressure), physical activity levels (accelerometer),  muscle function (1RM test), cognitive function, and body composition (BIA). During these visits lung function and exhaled breath measurement will also be performed. Additionally, the patient will be asked to fill in the questionnaires on lifestyle characteristics and health status again. After 5 years (year 6 of the study) the patient will be invited for visit 6, and all measurements from visit 1 will be repeated.

The first deliverable of this work package is information on the prevalence of a high risk profile for lung disease in a random population, and in a high risk population in the Netherlands. The second deliverable is the PRIL cohort with patient information/study samples collected over 5 years of time. Participants of the PRIL cohort will be selected for measurement of exposome characteristics using wearable devices (WP5). The samples of the 5 year follow up will be used to define biomarkers of early lung damage that can help in early detection of patients that will develop lung damage (WP6). They will be participating in imaging studies (WP7). The yearly follow-up measurements will be used to assess the efficacy of the personalized lifestyle intervention (WP9).

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