PAFR in Health and Disease
Research type
Research Study
Full title
PAFR Expression and Streptococcus pneumoniae adhesion to nasal epithelial cells in Health and Disease; a cross-sectional study
IRAS ID
227903
Contact name
Jonathan Grigg
Contact email
Sponsor organisation
Queen Mary University of London
Duration of Study in the UK
2 years, 11 months, 28 days
Research summary
Streptococcus pneumoniae is a common bacteria that causes pneumonia, sepsis and meningitis in childhood, leading to significant morbidity and mortality worldwide. Compared to healthy individuals, children with chronic underlying disease are at a higher risk of developing pneumococcal infections. Sickle cell disease and asthma are two common chronic medical conditions of childhood that confer an increased risk of streptococcal infection.
Streptococcus pneumoniae colonizes the nose and throat of up to 40% of the population, without causing any symptoms or problems. In order to cause invasive disease, the bacteria must also successfully enter into human host cells. To achieve this, Streptococcus pneumoniae binds to the platelet activating factor (PAF) receptor (PAFR) on human cells. In previous experimental studies, when PAFR is genetically deleted from model animals or when PAFR is blocked by targeted drugs, we have seen that that Streptococcus pneumoniae has much more difficulty binding to human cells.
We speculate whether individuals with asthma and sickle cell disease may have higher expression of PAFR, given their increased vulnerability to pneumococcal infections. Furthermore, we know that PAFR levels fluctuate with exposure to air pollution.
The aim of this study therefore is to compare PAFR levels in children with increased risk of streptococcal disease (those with asthma and sickle cell disease), compared to their healthy peers. We will gain samples of the cells lining the inside of the nostrils of all participants and measure the levels of PAFR and S. pneumoniae adeherence to see if there is any difference between the groups.
We will also measure air pollution exposure in all children in the study. This will allow us to assess the relationship between air pollution and PAFR levels within the different groups of children and control for any effects of air pollution on PAFR levels.Lay summary of study results: In a laboratory setting, traffic-related air pollution caused cells that line the airway to produce more of a protein called platelet-activating factor receptor (PAFR) when exposed to particulate matter pollutants at concentration of 10 ug/ml (p < 0.05). This increase made it easier for bacteria to stick to these lining cells.
In children with sickle cell disease, there were much higher levels of PAFR compared to all other groups studied (children with asthma, children with allergies, and healthy children). Children with asthma did not show a meaningful difference compared to healthy children.
The study also found that 24% of the participating children were exposed to air pollution levels higher than the daily safety limit recommended by the World Health Organization.
Conclusion
Exposure to traffic-related air pollution appears to increase PAFR levels, which may help bacteria attach more easily to the cells which line the airways. Children with sickle cell disease already have naturally higher PAFR levels, which could help explain why they are at greater risk of serious infections such as invasive pneumococcal disease. Despite efforts to improve air quality, pollution levels in London are still often above safe limits.
REC name
London - Bloomsbury Research Ethics Committee
REC reference
17/LO/1752
Date of REC Opinion
16 Oct 2017
REC opinion
Favourable Opinion