title: Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study.
abstract: BACKGROUND
  Pulmonary 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.
  
  
  OBJECTIVE
  To investigate systemic 2-alkyl-4-quinolones as potential biomarkers for pulmonary P. aeruginosa infection.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Cross-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).
  
  
  CONCLUSIONS
  AQs 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.
authors: Division of Respiratory Medicine, University of Nottingham, City Hospital Campus, Nottingham, UK. Electronic address: Helen.barr@nottingham.ac.uk.
authors: Helen L
authors: HL
authors: Barr
authors: School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.
authors: Nigel
authors: N
authors: Halliday
authors: Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, Nottingham, UK.
authors: David A
authors: DA
authors: Barrett
authors: School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.
authors: Paul
authors: P
authors: Williams
authors: Division of Respiratory Medicine, University of Nottingham, City Hospital Campus, Nottingham, UK.
authors: Douglas L
authors: DL
authors: Forrester
authors: Leeds Adult Cystic Fibrosis Centre, St James's University Hospital, Leeds, UK.
authors: Daniel
authors: D
authors: Peckham
authors: Leeds Adult Cystic Fibrosis Centre, St James's University Hospital, Leeds, UK.
authors: Kate
authors: K
authors: Williams
authors: Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, UK.
authors: Alan R
authors: AR
authors: Smyth
authors: West Midlands Adult CF Centre, Heart of England, NHS Foundation Trust, Birmingham, UK.
authors: David
authors: D
authors: Honeybourne
authors: West Midlands Adult CF Centre, Heart of England, NHS Foundation Trust, Birmingham, UK.
authors: Joanna
authors: J
authors: L Whitehouse
authors: West Midlands Adult CF Centre, Heart of England, NHS Foundation Trust, Birmingham, UK.
authors: Edward F
authors: EF
authors: Nash
authors: Wolfson Cystic Fibrosis Centre, Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors: Jane
authors: J
authors: Dewar
authors: Wolfson Cystic Fibrosis Centre, Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors: Andrew
authors: A
authors: Clayton
authors: Division of Respiratory Medicine, University of Nottingham, City Hospital Campus, Nottingham, UK.
authors: Alan J
authors: AJ
authors: Knox
authors: School of Life Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.
authors: Miguel
authors: M
authors: Cámara
authors: Division of Epidemiology and Public Health, University of Nottingham, Clinical Sciences Building, University of Nottingham, Nottingham, UK.
authors: Andrew W
authors: AW
authors: Fogarty
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002648:Child; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000000981:diagnostic imaging / Q000382:microbiology; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification / Q000502:physiology; D015363:Quinolones / Q000032:analysis / Q000378:metabolism; D015203:Reproducibility of Results; D012141:Respiratory Tract Infections / Q000175:diagnosis / Q000382:microbiology; D006113:United Kingdom
chemical_list: D015415:Biomarkers; D015363:Quinolones