The BRIDGE study - Bronchiectasis Research Involving Databases, Genomics and Endotyping to match the right treatment to the right patient.

Bronchiectasis has been described as one of the most neglected diseases in
respiratory medicine.(1,2) There are no licensed treatments, and the burden of
disease is high and increasing. In the UK, bronchiectasis affects 485 per
100,000 men and 566 per 100,000 women and the prevalence has increased by
approximately 40% in the past decade.(3) Traditional bronchiectasis guideline
approaches to treatment are focussed on airway infection (long term
oral/inhaled antibiotic treatments), mucus clearance (physiotherapy, devices,
mucoactive drugs) and airway inflammation (inhaled corticosteroids,
macrolides).(1) Clinical trials have failed to demonstrate clear benefit of
inhaled antibiotics across multiple compounds.(4-6) Macrolides reduced the
frequency of exacerbations in 3 randomized trials, but up to 40% of patients do
not respond to treatment in practice.(7-10) Mucoactive drugs are not widely
used and clinical trials of mannitol have failed to meet their primary
end-points, DNAse was found to be harmful in bronchiectasis despite benefits in
cystic fibrosis, while hypertonic saline has not shown clear benefits over 0.9%
saline.(11-14) A Cochrane review concluded that there is insufficient evidence
to support the use of inhaled corticosteroids.(15) The failure of therapies to
translate from cystic fibrosis to bronchiectasis is thought to be due to the
greater inflammatory, microbiological, radiological and aetiological
heterogeneity in bronchiectasis.(16)
Achieving success in developing new therapies for this disease requires
detailed translational research to define patient phenotypes and endotypes.
Personalised, stratified or precision medicine is increasing advocated across a
range of conditions to improve targeting of therapies.(17-20).

This study aims to phenotype and endotype bronchiectasis during stable disease
and exacerbations, to develop strategies for personalised medicine.

3.1 Primary Objective
To determine molecular endotypes of bronchiectasis which can guide response to
treatment.

3.2 Secondary Objectives
1. To determine molecular endotypes of stable bronchiectasis
2. To determine the causes and inflammatory profiles of bronchiectasis
exacerbations
3. To validate candidate biomarkers of stable and exacerbation endotypes to use
in stratified medicine
4. To perform in-vivo or in-vitro proof of concept studies using phenotypic
data to identify patient populations likely to benefit in future randomized
controlled trials

This is an observational, multi-centre study performed through the EMBARC
consortium. Data and samples will be collected from approximately 8 European
centres. Ethical approval of this protocol will be sought at country level.

The Dutch study site will aim to recruit 80 patients over the course of the
study with 1000 recruited Europe-wide. These numbers are indicative and we
reserve the right to recruit more or less patients in the Netherlands and
elsewhere according to study need. Patients will be recruited whilst clinically
stable and asked to attend an annual visit at a clinical research facility for
the research procedures outlined below.

This study is observational and no interventional product or device will be
adminstered. The majority of study procedures are part of the routine follow up
of bronchiectasis patients in our hospital and thus will not provide additional
risks and/ or burden for participants.

Therefore, the participant's burden consists of the extra time needed for:

- quality of life questionnaires
- blood/ urine sampling
- naso-pharyngeal swabs

The risks for participants are limited to the risks knowing to be involved in
venapunction (hematoma, mild pijn, infection of puncture site).