In humans, the normal glucose concentration of airway secretions is around 0.4mM; 12.5 times lower than plasma concentrations [1]. Airway glucose concentrations are increased by inflammation. We have found elevated luminal glucose concentrations in upper airways of people with viral rhinitis [2] and in lower airways of people with asthma, chronic obstructive pulmonary disease and cystic fibrosis [1]. Airway glucose concentrations are also increased by hyperglycaemia. The effect of inflammation and hyperglycaemia is synergistic, with further elevation of airway glucose in patients with cystic fibrosis who also have diabetes [1]. Airway luminal glucose concentrations are the net effect of transepithelial movement of glucose into the lumen and removal of glucose from the lumen. In polarised monolayers of human immortalised bronchiolar (H441) cells, L glucose (a non-transportable, non-metabolisable analogue) added to the basolateral compartment appeared in the apical compartment at concentrations inversely proportional to transepithelial electrical resistance [3]. Glucose thus moves across the epithelium down its concentration gradient to an extent determined by properties of intracellular junctions. In similar experiments, less D glucose (transportable and metabolisable) than L glucose appeared in the apical compartment, but apical D glucose concentrations increased in the presence of apical or basolateral phloretin. This indicates that apical and basolateral facilitated glucose transporters (GLUTs) restrict glucose appearance in the apical compartment. Phloretin also restricted apical appearance of lactate, indicating that airway epithelial cell glucose uptake through GLUTs is driven by a concentration gradient generated by intracellular glucose metabolism. A role for GLUTs in airway epithelial glucose homeostasis is supported by identification of GLUT2 protein in H441 cells and human bronchial epithelium on biopsy [4] and of GLUT10 in primary cultured human airway epithelial cells [5]. Inflammation disrupts epithelial glucose homeostasis. In H441 monolayers, pro-inflammatory cytokines reduce epithelial resistance, which is associated with increased transepithelial glucose flux [3]. By contrast, pro-inflammatory cytokines increased epithelial GLUT2 and GLUT10 protein expression and increased apical glucose uptake, possibly as a compensatory mechanism. Elevated glucose concentrations in inflamed airways therefore appear to be attributable to increased paracellular movement into airways secretions, overwhelming compensatory upregulation of glucose transport. Other investigators have shown structural abnormalities of tight junctions in inflamed airway epithelium, reproducible in vitro by exposure of cultured, airway epithelial cells to proinflammatory cytokines, which increase paracellular permeability to hydrophilic solutes. Elevated airway luminal glucose concentrations are associated with infection. In intubated patients on our intensive care unit, elevated airway glucose concentrations were associated with increased risk of acquiring respiratory methicillin resistant Staphylococcus aureus infection [6]. Glucose at concentrations found in lung secretions had a dose-dependent effect on growth of S. aureus and Pseudomonas aeruginosa in laboratory culture [7]. In a cultured airway epithelial cell model, increasing basolateral glucose concentrations increased apical glucose concentrations and caused a dose-dependent increase in growth of S. aureus at the epithelial cell surface. Other studies in this model have indicated that glucose increases adherence of S. aureus to the apical epithelial surface, possibly by enhancing integrin expression. In support of our findings, Pezzulo and colleagues found that increased glucose concentration in airway surface liquid augments growth of Ps. aeruginosa in vitro and in the lungs of hyperglycemic mice in vivo [5]. By contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a Ps. aeruginosa mutant that is unable to utilise glucose as a carbon source [5]. In summary, epithelial mechanisms normally maintain low glucose concentrations in airways secretions. This appears to be important for defence of the lung against infection. Inflammation and hyperglycaemia elevate glucose concentrations in lung secretions, promoting growth and pathogenicity of respiratory pathogens. Infection may lead to further inflammation with enhanced glucose leak fuelling the vicious cycle of infection and inflammation in chronic lung disease. Maintenance of low airway glucose concentrations represents a new therapeutic target in the field of lung infection.