Background:
Acute exacerbations of chronic obstructive pulmonary disease (COPD) play a pivotal role in the burden and natural course of the disease and contribute to a progressive decline in lung function, reduced health status, decreased physical activity and increased mortality risk. Although the risk of exacerbations is related to the severity of airflow limitation, the susceptibility of an individual patient to exacerbate remains largely unknown. Moreover, personalized predictors are lacking.

Objectives:
The Early diagnostic BioMARKers in Exacerbations of COPD (MARKED) study primarily aims to explore what (bio)markers (i.e. symptoms, vital signs, lung function and biosamples of sputum, nasal swabs, stools and blood) measured frequently (i.e. daily, 3x weekly or at acute exacerbation) predict a (preclinical) exacerbation and/or respiratory infection in patients with COPD.

Methods:
This exploratory, prospective, observational, longitudinal, single-center study will recruit 150 patients with COPD admitted to an 8-week inpatient pulmonary rehabilitation program at CIRO (Horn, the Netherlands). The study aims to include 50 unique individual patients with ≥1 exacerbation to provide accurate benchmark data for exploratory biomarkers. Furthermore, microbial composition and host-microbiome interactions will be extensively studied as these are increasingly recognized to affect exacerbation susceptibility.

Valorization:
The lack of prediction and early and accurate diagnosis of exacerbations forms a great unmet need in the management of COPD and a clear rationale for the MARKED study. This study aims to increase our knowledge of exacerbation (bio)markers to steer variable selection for future studies, in order to reduce the impact of exacerbations, avoid unnecessary treatments, reduce healthcare utilization and improve overall care for patients with COPD.