Respiratory infections are a leading cause of death globally. Although many factors increase the risk of lung infections, Professors Deborah Baines and Emma Baker have focused on the impact of raised glucose levels in fluids coating the airway epithelium. The fluid lining the lungs is normally sugar-free, which is important for preventing bacterial growth.
Professor Baines has untangled the mechanisms responsible for controlling lung glucose concentrations and discovered that both lung disease and a rise in blood glucose, such as seen in diabetes mellitus, increase glucose concentrations in lung fluid. In patients with chronic lung disease, such as cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD), elevated glucose concentrations can drive lung infections, which worsen lung function and shorten survival.
Professor Baines’ work indicates that if glucose levels in the lung rise, the additional nutrients promote the growth of pathogenic bacteria, particularly Staphylococcus aureus and Pseudomonas aeruginosa. She also discovered that glucose can suppress the defensive properties of other factors present in the fluid, revealing new therapeutic targets.
Metformin, a drug used to lower blood glucose in type 2 diabetes, was shown to limitmovement of glucose into the lung across the epithelial barrier in vivo. Through a collaboration with AstraZeneca, the use of a new generation anti-diabetic drug reduced respiratory infection in vivo. These discoveries have led to clinical trials aiming to reduce glucose accumulation in lung fluids to prevent or augment treatment and reduce the incidence of respiratory infection in patients with COPD andCF.
Publications
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Philips BJ, Redman J, Brennan A, et al. Glucose in bronchial aspirates increases the risk of respiratory MRSA in intubated patients. Thorax 2005;60:761-4.
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Baker EH, Clark N, Brennan AL, et al. Hyperglycemia and cystic fibrosis alter respiratory fluid glucose concentrations estimated by breath condensate analysis. J Appl Physiol 2007;102:1969-75.
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Garnett JP, Gray MA, Tarran R, et al. Elevated paracellular glucose flux across cystic fibrosis airway epithelial monolayers is an important factor for Pseudomonas aeruginosa growth. PLoS One 2013;8:e76283.
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Garnett JP, Kalsi KK, Sobotta M, et al. Hyperglycaemia and Pseudomonas aeruginosa acidify cystic fibrosis airway surface liquid by elevating epithelial monocarboxylate transporter 2 dependent lactate-H+ secretion. Sci Rep 2016;6:37955.
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Garnett JP, Baker EH, Naik S, et al. Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose. Thorax 2013;68:835-45.
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Astrand A, Wingren C, Benjamin A, et al. Dapagliflozin-lowered blood glucose reduces respiratory Pseudomonas aeruginosa infection in diabetic mice. Br J Pharmacol 2017;174:836-47.