Abstract
BackgroundPulmonary P. aeruginosa infection is associated with poor outcomes in cystic fibrosis (CF) and early diagnosis is challenging, particularly in those who are unable to expectorate sputum. Specific P. aeruginosa 2-alkyl-4-quinolones are detectable in the sputum, plasma and urine of adults with CF, suggesting that they have potential as biomarkers for P. aeruginosa infection. AimTo investigate systemic 2-alkyl-4-quinolones as potential biomarkers for pulmonary P. aeruginosa infection. MethodsA multicentre observational study of 176 adults and 68 children with CF. Cross-sectionally, comparisons were made between current P. aeruginosa infection using six 2-alkyl-4-quinolones detected in sputum, plasma and urine against hospital microbiological culture results. All participants without P. aeruginosa infection at baseline were followed up for one year to determine if 2-alkyl-4-quinolones were early biomarkers of pulmonary P. aeruginosa infection. ResultsCross-sectional analysis: the most promising biomarker with the greatest diagnostic accuracy was 2-heptyl-4-hydroxyquinoline (HHQ). In adults, areas under the ROC curves (95% confidence intervals) for HHQ analyses were 0.82 (0.75–0.89) in sputum, 0.76 (0.69–0.82) in plasma and 0.82 (0.77–0.88) in urine. In children, the corresponding values for HHQ analyses were 0.88 (0.77–0.99) in plasma and 0.83 (0.68–0.97) in urine.Longitudinal analysis: Ten adults and six children had a new positive respiratory culture for P. aeruginosa in follow-up. A positive plasma HHQ test at baseline was significantly associated with a new positive culture for P. aeruginosa in both adults and children in follow-up (odds ratio (OR)=6.67;-95% CI:-1.48–30.1;-p=0.01 and OR=70; 95% CI: 5–956;-p<0.001 respectively). ConclusionsAQs measured in sputum, plasma and urine may be used to diagnose current infection with P. aeruginosa in adults and children with CF. These preliminary data show that plasma HHQ may have potential as an early biomarker of pulmonary P. aeruginosa. Further studies are necessary to evaluate if HHQ could be used in clinical practice to aid early diagnosis of P. aeruginosa infection in the future.
Highlights
Chronic pulmonary infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is an important risk factor contributing to recurrent hospital admissions [1] and increased mortality [1]
AQ concentrations were positively correlated between sputum, plasma and urine with the strongest correlations between sputum and plasma concentrations of HQNO
The hospital culture results were obtained from 136 spontaneous sputum samples and 40 cough swabs
Summary
Chronic pulmonary infection with Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is an important risk factor contributing to recurrent hospital admissions [1] and increased mortality [1]. Early diagnosis of pulmonary P. aeruginosa infection is more challenging in those who are unable to expectorate sputum, such as young children and adults with well maintained lung function. In these circumstances, diagnostic options include sampling from the upper airways using cough swabs, which have a low sensitivity and may miss lower airways infection [8], or the use of more invasive techniques such as induced sputum [9] or bronchoalveolar lavage [9]. Cross-sectionally, comparisons were made between current P. aeruginosa infection using six 2-alkyl-4-quinolones detected in sputum, plasma and urine against hospital microbiological culture results. The corresponding values for HHQ analyses were 0.88 (0.77–0.99) in plasma and 0.83 (0.68–0.97) in urine
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