Airway microbiome driven mechanisms of disease after optimised self management: Colour-COPD trial

Research question: Do alterations in the airway microbiome and downstream inflammation occur if patients optimise self-management of exacerbations of chronic obstructive pulmonary disease (COPD)?

Background: Our hypothesis is that reduced antibiotic consumption due to better self-management (SM) may change airway bacterial profile, and that this will benefit health of COPD patients. To test this we plan to use sputum samples already being collected from Colour COPD trial patients for mechanistic work. The main trial will test whether a sputum colour chart is non-inferior to usual self-management, and has a primary outcome of COPD specific hospital admission.

Secondary outcomes include antibiotic consumption and quality of life (QOL). Since only half of exacerbations of COPD (AECOPD) are bacterial, and sputum colour has a good positive predictive value for bacterial presence, it is likely that our intervention will reduce antibiotic consumption. There are two main routes by which our intervention could improve patient outcomes (i) it could alter the airway microbiome, and subsequent pathological processes (ii) enhancing SM technique might result in more prompt treatment of AECOPD, thereby reducing loss of physical health in each event.

The parent trial will assess the latter; this add on study would assess the first, likely more important, route. Aims and objectives 1. Describe the airway microbiome in a primary care COPD population 2. Describe the relationship between antibiotic consumption and changes in airway microbiome 3. Explore the relationship between microbiome profile, inflammation and prognosis

Methods: We will store all sputum samples submitted by Colour COPD patients, and add microbiome and cytokine analyses to stable state samples. At the end of the parent trial stable state baseline samples will be measured to assess objectives 1 and 3. Sputum plugs will be split with one half being diluted in PBS, dispersed using glass beads and stored for qPCR/16S analysis of both virus and bacteria.

The second portion will be dispersed using sequential PBS and DTT treatment generating supernatants and cytospins for analysis of inflammatory markers and cells. Analysis of the microbial patterns seen will be compared to antibiotic consumption for AECOPD (days/year) steroid load (days/year and mg/year), AECOPD rate, FEV1 and longitudinally within individuals to determine the impact of frequent courses of antibiotics at group and individual level.

We will also assess viral patterns and determine if baseline colonisation impacts efficacy of the intervention, and conduct a between trial arm analysis for the microbiome. Finally we will measure inflammatory markers linked to neutrophilic and eosinophilic inflammation to determine if altering the microbiome has potential to reduce factors which drive disease progression.

Timelines: Colour COPD patients are recruited over 2-years and followed up for 1-year, thus samples will be received over 3-years. Post-trial processing and analysis will take 1-year

Anticipated impact and dissemination: Dissemination will occur through conferences, publications, the parent trial PPI group and newsletter. Impact is anticipated through changes in antibiotic prescribing in primary care.