Bronchiectasis is a common disabling and heterogeneous disease that has been neglected in terms of basic and clinical research. Recent controlled trials have failed to achieve their primary end-points, likely because the optimal patient population to benefit from antibiotic, mucoactive and anti-inflammatory drugs has not been identified. This study aims to explore the clinical, microbiological, inflammatory and functional heterogeneity of the disease with the aim of identifying patient endotypes for stratified medicine.
Study aims and objectives
- To determine the molecular endotypes of bronchiectasis during stable disease
- To determine the causes and inflammatory profiles of bronchiectasis exacerbations
- To validate candidate biomarkers of stable and exacerbation endotypes to use in stratified medicine
- To perform in-vivo and in-vitro proof of concept studies using phenotypic data to identify patient populations likely to benefit in future randomized controlled trials
Patients with bronchiectasis will be recruited into an observational study, the objectives of which will be to:
Aim 1 will define and validate endotypes of stable bronchiectasis by studying 1000 patients with bronchiectasis. Clinical data (described in the data collection section), sputum microbiome, sputum proteomics, and systemic and sputum inflammatory marker measurement will be incorporated for analysis. A sub-study (n=200) will be performed using air liquid interface culture of primary airway epithelial cells. Patients will have brushings of the inferior nasal turbinate with assessment of % ciliation, ciliary beat frequency and pattern by high speed video microscopy before and after culture.
Aim 2 will replicate the phenotyping approach to stable patients with 160 patients during exacerbation. This will identify changes from baseline in microbiota, proteomic and other markers associated with onset of exacerbation and allow classification of clusters of exacerbation.
Aim 3 we will externally validate candidate phenotype/endotypes in registered ethically approved external biobanks and aim to demonstrate that validated markers be linked to potential treatment responses for use in stratified medicine trials.
In total we will recruit 1000 patients for study. These patients will attend one of the participating study centres at least once and undergo sampling along with collecting of clinical data. Patients will be asked to consent for their samples to be linked to data held on an existing pan European bronchiectasis database (the EMBARC registry).