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Neutrophil count in sputum is associated with increased sputum glucose and sputum L-lactate in cystic fibrosis.

ABSTRACT: BACKGROUND:Markers of lung inflammation measured directly in expectorated sputum have the potential of improving the timing of antibiotic treatment in cystic fibrosis (CF). L-Lactate might be a marker of inflammation, as it is produced from glucose by polymorphonuclear neutrophils (PMNs) in CF lungs. We aimed to investigate changes in and associations between PMNs, glucose and L-lactate in sputum during antibiotic treatment. In addition, the effect of hemoglobin A1c and plasma glucose on these biomarkers were investigated. METHODS:We sampled non-induced sputum at day 0, 7, 14 and 42 in 27 chronically infected CF patients electively treated with 14 days of intravenous antibiotic. To analyze sputum samples, we used flowcytometry to count PMNs and colorimetric assays to estimate lactate and glucose. RESULTS:No changes in levels of PMNs, glucose and lactate were detected in sputum during the antibiotic treatment. Sputum PMNs were positively associated with both glucose (log coefficient = 0.20, p = 0.01) and L-lactate (log coefficient = 0.34, p<0.001). In multivariate analyses, hemoglobin A1c was negatively associated with sputum PMNs (log coefficient = -1.68, p<0.001) and plasma glucose was negatively associated with sputum glucose (log coefficient = -0.09, p = 0.02). CONCLUSIONS:In CF sputum PMNs, glucose and lactate were unchanged during elective antibiotic treatment. However, sputum PMNs were associated with both sputum glucose and sputum lactate. Surprisingly, hyperglycemia seemed to be associated with less PMNs infiltration and less glucose in CF sputum.

SUBMITTER: Nielsen BU

PROVIDER: S-EPMC7485830 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Neutrophil count in sputum is associated with increased sputum glucose and sputum L-lactate in cystic fibrosis.

Nielsen Bibi Uhre BU Kolpen Mette M Jensen Peter Østrup PØ Katzenstein Terese T Pressler Tacjana T Ritz Christian C Mathiesen Inger Hee Mabuza IHM Faurholt-Jepsen Daniel D

PloS one 20200911 9

<h4>Background</h4>Markers of lung inflammation measured directly in expectorated sputum have the potential of improving the timing of antibiotic treatment in cystic fibrosis (CF). L-Lactate might be a marker of inflammation, as it is produced from glucose by polymorphonuclear neutrophils (PMNs) in CF lungs. We aimed to investigate changes in and associations between PMNs, glucose and L-lactate in sputum during antibiotic treatment. In addition, the effect of hemoglobin A1c and plasma glucose on ...[more]

PMID: 32915806

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Project description:Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen that can infect the lungs of people with cystic fibrosis (CF). The highly viscous mucus in the CF lung, expectorated as sputum, serves as the primary nutrient source for microbes colonizing this site and induces virulence-associated phenotypes and gene expression in several CF pathogens. Here, we characterized the transcriptional responses of three S. maltophilia strains during exposure to synthetic CF sputum medium (SCFM2) to gain insight into how this organism interacts with the host in the CF lung. These efforts led to the identification of 881 transcripts differentially expressed by all three strains, many of which reflect the metabolic pathways used by S. maltophilia in sputum, as well as altered stress responses. The latter correlated with increased resistance to peroxide exposure after pregrowth in SCFM2 for two of the strains. We also compared the SCFM2 transcriptomes of two S. maltophilia CF isolates to that of the acute infection strain, S. maltophilia K279a, allowing us to identify CF isolate-specific signatures in differential gene expression. The expression of genes from the accessory genomes was also differentially altered in response to SCFM2. Finally, a number of biofilm-associated genes were differentially induced in SCFM2, particularly in K279a, which corresponded to increased aggregation and biofilm formation in this strain relative to both CF strains. Collectively, this work details the response of S. maltophilia to an environment that mimics important aspects of the CF lung, identifying potential survival strategies and metabolic pathways used by S. maltophilia during infections.IMPORTANCEStenotrophomonas maltophilia is an important infecting bacterium in the airways of people with cystic fibrosis (CF). However, compared to the other CF pathogens, S. maltophilia has been relatively understudied. The significance of our research is to provide insight into the global transcriptomic changes of S. maltophilia in response to a medium that was designed to mimic important aspects of the CF lung. This study elucidates the overall metabolic changes that occur when S. maltophilia encounters the CF lung and generates a road map of candidate genes to test using in vitro and in vivo models of CF.

Dataset Information

Neutrophil count in sputum is associated with increased sputum glucose and sputum L-lactate in cystic fibrosis.

Publications

Neutrophil count in sputum is associated with increased sputum glucose and sputum L-lactate in cystic fibrosis.

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