Hyperglycemia and cystic fibrosis alter respiratory fluid glucose concentrations estimated by breath condensate analysis

Abstract

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.

Glucose homeostasis across human airway epithelial cell monolayers: role of diffusion, transport and metabolism

“…Therefore, the in vitro data presented in this study support the notion that the human airway is relatively leaky to glucose. They also support our previous observations in vivo that glucose rapidly diffuses across the epithelium into ASL when blood glucose is raised in human subjects [3,40].…”

“…We have previously shown that glucose concentrations in normal ASL are approximately 12.5 times lower than blood glucose concentrations [3]. Our human observations are similar to those in sheep and rat lungs where glucose concentrations were three times to 20 times lower in ASL than in blood [5,33].…”

“…Both sides of the epithelial cells were bathed in a physiological salt solution (in millimolars): NaCl, 117; NaHCO 3 ]-L-glucose, respectively, or 5 mM D-glucose or 5 mM L-glucose alone to the basolateral side of the epithelial cells. After mixing, initial samples of 0.5 mL were removed immediately from the apical and basolateral baths.…”

“…In healthy humans, ASL glucose concentrations rise in response to an experimental increase in blood glucose [3,40]. This could be explained if glucose moves across the epithelium from interstitium into ASL down its concentration gradient by paracellular diffusion (Fig.…”

“…1). In healthy volunteers, when experimental hyper-glycaemia is reversed, ASL glucose concentrations fall, but against a transepithelial glucose concentration gradient as ASL glucose always remains lower than blood glucose concentrations [3,40]. This indicates that glucose is removed from ASL via glucose uptake by epithelial cells.…”