Multi-pronged approach for early diagnosis and prognosis of Chronic Obstructive Pulmonary Disease

Background:

Chronic obstructive pulmonary disease (COPD) is a disease with large patient burden, high societal costs and the third cause of mortality worldwide. Spirometry is needed to establish diagnosis. However, spirometry requires patient cooperation and reflects primarily the central airways.

Forced oscillation technique (FOT) is a lung function test that reflects peripheral airways function and we have established reference values within the Swedish CardioPulmonary biolmage Study (SCAPIS). Recently, a non-radiological assessment of emphysema using nanoparticles, Airspace Dimension Assessment (AiDA), has been proposed. The ratio between blood neutrophils and lymphocytes, as well as composition of exhaled particles are promising biomarkers for COPD at an early stage.

Novel strategies of broadly assessing inflammation by means of proteomics are now avaialble. Mast cell involvement has been related to bronchial hyperresponsiveness and poorer lung function in COPD.

We lack simple tools to identify which individuals are at risk of developing COPD or which patients with COPD are at risk for exacerbation. Objective:

We will use a multi-pronged approach for two aims: early identification of individuals at risk of developing COPD and identification of subjects with an established COPD diagnosis that are at risk of exacerbation. Workplan:

The project consists of new studies and follow-up of clinical cohorts by means of registries and clinical visits. Several new techniques will be used: non-radiological assessment of emphysema, collection of particles in exhaled air, and novel physiological tests, as assessment of closing volume by forced oscillation technique (FOT) and changes in exhaled nitric oxide after bronchodilation.

We will also analyses of biomarkers in blood and exhaled air, tests of mast cell involvement by assessment of mast cell progenitors in blood and human tissue studies. Furthermore, the clinical value of candidate peptides and broader proteomics assays will also be tested. Significance:

This is the first project investigating the prognostic value of these methods. If successful, this novel approach of early identification of individuals at risk for developing / worsening of COPD could be used in larger scale, as most techniques can be implemented in primary care. Moreover, the novel, explorative analyses regarding the role of mast cells and search for candidate biomarkers through proteomics/peptidomics may offer new drug targets in COPD.