Air pollution and Paediatric Bronchiectasis Airway Macrophage Function
Research type
Research Study
Full title
Airway macrophage function against microorganisms in children with CF and non-CF bronchiectasis, in face of air pollution
IRAS ID
327730
Contact name
Norrice Liu
Contact email
Sponsor organisation
Queen Mary University of London
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
3 years, 11 months, 30 days
Research summary
Bronchiectasis is a condition where the breathing tubes (airway) in the lungs are irreversibly enlarged – caused by conditions such as cystic fibrosis (CF; which is due to a genetic mutation) and non-CF bronchiectasis (an umbrella term encompassing genetic and non-genetic conditions). CF is the commonest inherited life-limiting lung condition; non-CF bronchiectasis result from frequent chest infections and rare conditions including immune deficiency and inborn structural airway/lung abnormalities. Children with bronchiectasis suffer from recurrent infections, lung function decline, and eventually the need for lung transplantation.
Although new CF treatments have revolutionised the disease course; there remain children who are ineligible for, or unresponsive to, these treatments. Non-CF bronchiectasis is rare and under-researched, with no curative therapies to date. It is therefore important to understand the mechanisms underlying these children’s vulnerability and protect them from lung damage.
Macrophages are immune cells that engulf and destroy foreign insults (bacteria, pollutants). Remarkably, some bacteria can manipulate the body’s immune killing mechanism, allowing for unexpected bacterial survival within cells.
We previously reported that children with CF had defective immune function against air pollutants, due to increased production of a substance (prostaglandin-E2, PEG2) when the body is fighting infections– a frequent occurrence in CF. We observed bacteria residing in, rather than destroyed by, immune cells in children with CF. We developed a method to isolate these immune cells; and identified the bacteria within. This impaired immune cells killing may be worsened by air pollutants, which can change the bacteria’s structure and stickiness, improving their survival in immune cells.
We hypothesise there is impaired immune cells handling of microorganism in bronchiectasis, which is worsened by air pollution exposure. We hypothesise these children have; i) increased PGE2 (substance produced during infection and in CF, there are recurrent chest infections) which impairs immune killing of bacteria, leading to ii) bacterial survival within immune cells, which is iii) exacerbated by exposure to air pollution; vi) that PGE2 suppression (using medications like Ibuprofen, a safe, over-the-counter anti-inflammatory drug) will improve immune cells function.
REC name
London - Camden & Kings Cross Research Ethics Committee
REC reference
24/LO/0326
Date of REC Opinion
29 Apr 2024
REC opinion
Unfavourable Opinion