Hyperglycaemia and Mortality in Community-Acquired Pneumonia

Matt P Wise and Andrew P Walden

Lepper and colleagues reported that even mild (6-10.99 mmol/L) hyperglycaemia on admission to hospital was predictive of mortality in a large prospective observational cohort of community-acquired pneumonia (CAP) in the absence of pre-existing diabetes1. This effect was apparent in those with low to moderate (0-2) but not high (3-4) CRB-65 scores. In a national audit in the United Kingdom mortality for patients admitted to hospital with CAP was 18.3% despite the majority of patients having low to moderate CURB-65 scores2. Incorporating glucose on admission into those patients with low CURB-65 scores may therefore improve the utility of this tool by identifying individuals at greatest risk of adverse outcome in what is generally considered a low mortality group.

The CAPNETZ investigators found no causal relationship between glucose on admission and mortality, and highlight that a common factor may be related to hyperglycaemia and death. However, the observation that this effect is not present in those with severe pneumonia and results in largely early deaths (<28 days) raises the possibility that mild hypergylcaemia is important in the initial pathophysiology of CAP. Glucose within the airway surface fluid of the lung is tightly regulated through polarized epithelial glucose transporters and intracellular glucose phosphorylation3, with a threshold effect when plasma glucose exceeds 6.7-9.7 mmol/L leading to its appearance in airway surface fluid4. Glucose competitively inhibits surfactant proteins A and D which are important in host defence and pulmonary immunoregulation5. Glucose in the airway surface fluid also promotes bacterial growth by providing a direct carbon source3 6. Mild hyperglycaemia can therefore facilitate bacterial growth and impair innate immunity in the early phases of pneumonia. This mechanism would elegantly explain why hyperglycaemia on admission has little effect on mortality for patients with higher CRB-65 scores that reflect increasing physiological instability as a consequence of the host response to infection.

References

1. Lepper PM, Ott S, Nüesch E, von Eynatten M, Schumann C, Pletz MW, et al; on behalf of the German Community Acquired Pneumonia Competence Network (CAPNETZ). Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ 2012; 344:e3397
2. Lim WS, Woodhead M; British Thoracic Society. British Thoracic Society adult community acquired pneumonia audit 2009/10. Thorax 2011; 66:548-9
3. Pezzulo AA, Gutiérrez J, Duschner KS, McConnell KS, Taft PJ, Ernst SE, et al. Glucose depletion in the airway surface liquid is essential for sterility of the airways. PLoS One 2011; 6:e16166
4. Baker EH, Wood DM, Brennan AL, Clark N, Baines DL, Philips BJ. Hyperglycaemia and pulmonary infection. Proc Nutr Soc 2006; 65:227-35
5. Reading PC, Allison J, Crouch EC, Anders EM. Increased susceptibility of diabetic mice to influenza virus infection: compromise of collectin-mediated host defense of the lung by glucose? J Virol 1998; 72:6884-7
6. Brennan AL, Gyi KM, Wood DM, Johnson J, Holliman R, Baines DL, et al. Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis. J Cyst Fibros 2007; 6:101-9

Competing interests: None declared