Airway infection in bronchiectasis patients
Research type
Research Study
Full title
Airway infection in bronchiectasis patients: A feasibility study
IRAS ID
235786
Contact name
Maria Koufali
Contact email
Sponsor organisation
Research & Innovation, Nottingham University Hospitals NHS Trust
Duration of Study in the UK
3 years, months, days
Research summary
Research Summary:
Bronchiectasis is a disease that results in scarring of the lungs and is associated with long-term chronic and recurrent infections. We propose to recruit patients with bronchiectasis who are acute exacerbating from an infection who are admitted to hospital or had a referral to OPAT (outpatient antimicrobial therapy) for intravenous antibiotic treatment. A blood sample and a sputum sample will be collected at the beginning of treatment and also at the end of treatment. A blowing test (spirometry) at this time will measure lung health. The sputum sample will be split, one sample will be stored and analysed later to look for markers of infection and another will be stored for genetic sequencing of the sputum microbiological community. The sputum will also be sent for routine microbiology at the NHS hospital laboratory to allow comparison. Furthermore, we will conduct our own quantitative microbiology on the sample, along with cell counts. The blood will be centrifuged and stored for later biomarker analysis. Patients will be reviewed at the beginning of their acute exacerbation, at the end of their exacerbation and at clinical stability. Samples as well as spirometry will be taken in all visits to allow later comparison. A Quality of life questionnaire will also be given to the patients at each visit. This longitudinal analysis will allow many patient factors in this cohort to be explored. Furthermore, after the patient visits and subsequent sampling analysis, the patients will continue to be followed up by the research fellow, this will include reviewing the medical electronic records.Lay summary of study results:
There is an ongoing need for more research in bronchiectasis and to understand the many factors involved in pulmonary exacerbations, disease severity and mortality. Fifty participants experiencing a pulmonary exacerbation and requiring IV antibiotics were recruited into an observational cohort study. The baseline demographics of participants were comparable to other large cohort studies; however, our study cohort had a higher exacerbation frequency and disease severity.
We found the levels of systemic inflammatory markers such as CRP, blood neutrophil count and sputum neutrophil count reduced after treatment for a pulmonary exacerbation and correlated with clinical improvement. In addition, after treatment for a pulmonary exacerbation, the sputum and blood neutrophil count correlated negatively with lung function. It is important to note that the levels of CRP and blood neutrophils at the start of treatment were not markedly raised and it was in fact the relative reduction of serum CRP and blood neutrophils after treatment that correlated with lung function improvement. For example, in our cohort, the median CRP reduced from 13 at the beginning of exacerbation to 5 after treatment. This has been noted in previous studies whereby higher levels of systemic inflammation correlate with severity of an exacerbation but a normal CRP does not exclude a pulmonary exacerbation warranting treatment with lung function improvement. Our data is consistent with previous studies whereby spirometric measures of lung function cannot reliably determine an exacerbation or treatment response. In fact, the most consistent clinical measurement that correlated with clinical status was the quality of life score, which has been previously described. We found the P. aeruginosa quantitative load measured by culture did not reduce between the beginning of an exacerbation and after treatment, but when measured by molecular methods, the quantitative load reduced. The amount of P. aeruginosa (culture and molecular methods) quantified after treatment for an exacerbation negatively correlated with lung function. Interestingly, those participants colonised with P. aeruginosa had a greater decline in lung function (measured as peak flow) after IV antibiotics compared to those who were not. Finally, we describe older age, lower lung function and current smokers were all associated with a higher exacerbation risk and mortality. In our cohort, male gender was associated with exacerbation risk. In addition, a higher blood neutrophil count at the end of treatment was associated with a 12% increased risk of exacerbation. A novel finding in our cohort showed chronic colonisation with non-mucoid strains of P. aeruginosa was associated with a higher exacerbation risk, which is contrary to data in CF. Similarly, a shorter time colonised with P. aeruginosa was associated with increased mortality. These factors may be explained by a reduction in virulence factor production due to long-term colonisation, however, this has not been previously recognised in bronchiectasis.REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
18/WM/0125
Date of REC Opinion
3 May 2018
REC opinion
Favourable Opinion