Background: Hyperglycaemia is associated with poor outcomes from pneumonia, myocardial infarction and stroke, but the effect of blood glucose on outcomes from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has not been established. Recent UK guidelines do not comment on measurement or control of blood glucose in AECOPD. A study was therefore undertaken to determine the relationship between blood glucose concentrations, length of stay in hospital, and mortality in patients admitted with AECOPD. Methods: Data were retrieved from electronic records for patients admitted with AECOPD with lower respiratory tract infection in 2001-2. The patients were grouped according to blood glucose quartile (group 1, ,6 mmol/l (n = 69); group 2, 6.0-6.9 mmol/l (n = 69); group 3, 7.0-8.9 mmol/l (n = 75); and group 4, .9.0 mmol/l (n = 71)). Results: The relative risk (RR) of death or long inpatient stay was significantly increased in group 3 (RR 1.46, 95% CI 1.05 to 2.02, p = 0.02) and group 4 (RR 1.97, 95% CI 1.33 to 2.92, p,0.0001) compared with group 1. For each 1 mmol/l increase in blood glucose the absolute risk of adverse outcomes increased by 15% (95% CI 4 to 27), p = 0.006. The risk of adverse outcomes increased with increasing hyperglycaemia independent of age, sex, a previous diagnosis of diabetes, and COPD severity. Isolation of multiple pathogens and Staphylococcus aureus from sputum also increased with increasing blood glucose. Conclusion: Increasing blood glucose concentrations are associated with adverse clinical outcomes in patients with AECOPD. Tight control of blood glucose reduces mortality in patients in intensive care or following myocardial infarction. A prospective study is now required to determine whether control of blood glucose can also improve outcomes from AECOPD.

Glucose is not normally present in airways secretions, but appears where hyperglycaemia or epithelial inflammation occur. The detection of glucose cannot reliably be used to detect enteral feed aspiration.

In animals, glucose concentrations are 3-20 times lower in lung lining fluid than in plasma. In humans, glucose concentrations are normally low (<1 mmol/l) in nasal and bronchial fluid, but they are elevated by inflammation or hyperglycemia. Furthermore, elevated bronchial glucose is associated with increased respiratory infection in intensive care patients. Our aims were to estimate normal glucose concentrations in fluid from distal human lung sampled noninvasively and to determine effects of hyperglycemia and lung disease on lung glucose concentrations. Respiratory fluid was sampled as exhaled breath condensate, and glucose was measured by chromatography with pulsed amperometric detection. Dilution corrections, based on conductivity, were applied to estimate respiratory fluid glucose concentrations (breath glucose). We found that breath glucose in healthy volunteers was 0.40 mmol/l (SD 0.24), reproducible, and unaffected by changes in salivary glucose. Breath-to-blood glucose ratio (BBGR) was 0.08 (SD 0.05). Breath glucose increased during experimental hyperglycemia (P < 0.05) and was elevated in diabetic patients without lung disease [1.20 mmol/l (SD 0.69)] in proportion to hyperglycemia [BBGR 0.09 (SD 0.06)]. Breath glucose was elevated more than expected for blood glucose in cystic fibrosis patients [breath 2.04 mmol/l (SD 1.14), BBGR 0.29 (SD 0.17)] and in cystic fibrosis-related diabetes [breath 4.00 mmol/l (SD 2.07), BBGR 0.54 (0.28); P < 0.0001]. These data indicate that 1) this method makes a biologically plausible estimate of respiratory fluid glucose concentration, 2) respiratory fluid glucose concentrations are elevated by hyperglycemia and lung disease, and 3) effects of hyperglycemia and lung disease can be distinguished using the BBGR. This method will support future in vivo investigation of the cause and effect of elevated respiratory fluid glucose in human lung disease.

BG> or =8 mmol L(-1) predicted elevated AG concentrations in CF, at least in nasal secretions. CFRD patients spent approximately 50% day with BG>airway threshold, implying persistently elevated AG concentrations. Further studies are required to determine whether elevated airway glucose concentrations contribute to accelerated pulmonary decline in CFRD.

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Radiographic bronchiectasis in COPD patients is associated with increased respiratory infection and hospitalisation, independent of coexisting emphysema and BWT. COPD-related bronchiectasis is therefore an important diagnosis with potential implications for treatment.

For over 50 years, glucose has been recognised to cross the lung epithelial barrier and be transported by lung epithelial cells. However, until recently, research into these processes focused on their effects on lung liquid volume. Here, we consider a newly identified role for pulmonary glucose transport in maintaining low airway surface liquid (ASL) glucose concentrations and propose that this contributes to lung defence against infection.Glucose diffuses into ASL via paracellular pathways at a rate determined by paracellular permeability and the transepithelial glucose gradient. Glucose is removed from ASL in proximal airways via facilitative glucose transporters, down a concentration gradient generated by intracellular glucose metabolism. In the distal lung, glucose transport via sodium-coupled glucose transporters predominates. These processes vary between species but universally maintain ASL glucose at 3-20-fold lower concentrations than plasma.ASL glucose concentrations are increased in respiratory disease and by hyperglycaemia. Elevated ASL glucose in intensive care patients was associated with increased Staphylococcus aureus infection. Diabetic patients with and without chronic lung disease are at increased risk of respiratory infection. Understanding of mechanisms underlying lung glucose homeostasis could identify new therapeutic targets for control of ASL glucose and prevention and treatment of lung infection.

BackgroundDiabetes is a risk factor for respiratory infection, and hyperglycaemia is associated with increased glucose in airway surface liquid and risk of Staphylococcus aureus infection.ObjectivesTo investigate whether elevation of basolateral/blood glucose concentration promotes airway Staphylococcus aureus growth and whether pretreatment with the antidiabetic drug metformin affects this relationship.MethodsHuman airway epithelial cells grown at air–liquid interface (±18 h pre-treatment, 30 μM–1 mM metformin) were inoculated with 5×105 colony-forming units (CFU)/cm2 S aureus 8325-4 or JE2 or Pseudomonas aeruginosa PA01 on the apical surface and incubated for 7 h. Wild-type C57BL/6 or db/db (leptin receptor-deficient) mice, 6–10 weeks old, were treated with intraperitoneal phosphate-buffered saline or 40 mg/kg metformin for 2 days before intranasal inoculation with 1×107 CFU S aureus. Mice were culled 24 h after infection and bronchoalveolar lavage fluid collected.ResultsApical S aureus growth increased with basolateral glucose concentration in an in vitro airway epithelia–bacteria co-culture model. S aureus reduced transepithelial electrical resistance (RT) and increased paracellular glucose flux. Metformin inhibited the glucose-induced growth of S aureus, increased RT and decreased glucose flux. Diabetic (db/db) mice infected with S aureus exhibited a higher bacterial load in their airways than control mice after 2 days and metformin treatment reversed this effect. Metformin did not decrease blood glucose but reduced paracellular flux across ex vivo murine tracheas.ConclusionsHyperglycaemia promotes respiratory S aureus infection, and metformin modifies glucose flux across the airway epithelium to limit hyperglycaemia-induced bacterial growth. Metformin might, therefore, be of additional benefit in the prevention and treatment of respiratory infection.