Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study

Helen L. Barr; Nigel Halliday; David A. Barrett; Paul Williams; Douglas L. Forrester; Daniel Peckham; Kate Williams; Alan R. Smyth; David Honeybourne; Joanna L. Whitehouse; Edward F. Nash; Jane Dewar; Andrew Clayton; Alan J. Knox; Miguel Cámara; Andrew W. Fogarty

doi:10.1016/j.jcf.2016.10.005

Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study

Helen L. Barr^*
, Nigel Halliday
, David A. Barrett
, Paul Williams
, Douglas L. Forrester
, Daniel Peckham
, Kate Williams
, Alan R. Smyth
, David Honeybourne
, Joanna L. Whitehouse
, Edward F. Nash
, Jane Dewar
, Andrew Clayton
, Alan J. Knox
, Miguel Cámara
, Andrew W. Fogarty

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

35 Citations (Scopus)

19 Downloads (Pure)

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.

Aim

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.

Original language	English
Pages (from-to)	230-238
Number of pages	9
Journal	Journal of Cystic Fibrosis
Volume	16
Issue number	2
DOIs	https://doi.org/10.1016/j.jcf.2016.10.005
Publication status	Published - 01 Mar 2017
Externally published	Yes

Bibliographical note

Funding Information:
Medical Research Council (G0801558); Doug Forrester is funded by the Wellcome Trust, fellow number: WT088614.

Publisher Copyright:
© 2016 The Authors

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Pulmonary and Respiratory Medicine

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10.1016/j.jcf.2016.10.005Licence: CC BY

Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study
Copyright 2016 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 318 KBLicence: CC BY

35 Citations
1 Letter

Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study; response to comments
Barr, H. L., Halliday, N., Barrett, D. A., Williams, P., Forrester, D. L., Peckham, D., Williams, K., Smyth, A. R., Honeybourne, D., Whitehouse, J. L., Nash, E. F., Dewar, J., Clayton, A., Knox, A. J., Cámara, M. & Fogarty, A. W., 14 Nov 2017, In: Journal of Cystic Fibrosis. 16, 6, p. e21
Research output: Contribution to journal › Letter › peer-review

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Cite this

Barr, H. L., Halliday, N., Barrett, D. A., Williams, P., Forrester, D. L., Peckham, D., Williams, K., Smyth, A. R., Honeybourne, D., L. Whitehouse, J., Nash, E. F., Dewar, J., Clayton, A., Knox, A. J., Cámara, M., & Fogarty, A. W. (2017). Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study. Journal of Cystic Fibrosis, 16(2), 230-238. https://doi.org/10.1016/j.jcf.2016.10.005

@article{675964352bde4d41ba5673a92b743759,

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. Aim 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.",

author = "Barr, \{Helen L.\} and Nigel Halliday and Barrett, \{David A.\} and Paul Williams and Forrester, \{Douglas L.\} and Daniel Peckham and Kate Williams and Smyth, \{Alan R.\} and David Honeybourne and \{L. Whitehouse\}, Joanna and Nash, \{Edward F.\} and Jane Dewar and Andrew Clayton and Knox, \{Alan J.\} and Miguel C{\'a}mara and Fogarty, \{Andrew W.\}",

note = "Funding Information: Medical Research Council (G0801558); Doug Forrester is funded by the Wellcome Trust, fellow number: WT088614. Publisher Copyright: {\textcopyright} 2016 The Authors",

year = "2017",

month = mar,

day = "1",

doi = "10.1016/j.jcf.2016.10.005",

language = "English",

volume = "16",

pages = "230--238",

journal = "Journal of Cystic Fibrosis",

issn = "1569-1993",

publisher = "Elsevier B.V.",

number = "2",

}

Barr, HL, Halliday, N, Barrett, DA, Williams, P, Forrester, DL, Peckham, D, Williams, K, Smyth, AR, Honeybourne, D, L. Whitehouse, J, Nash, EF, Dewar, J, Clayton, A, Knox, AJ, Cámara, M & Fogarty, AW 2017, 'Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study', Journal of Cystic Fibrosis, vol. 16, no. 2, pp. 230-238. https://doi.org/10.1016/j.jcf.2016.10.005

TY - JOUR

T1 - Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study

AU - Barr, Helen L.

AU - Halliday, Nigel

AU - Barrett, David A.

AU - Williams, Paul

AU - Forrester, Douglas L.

AU - Peckham, Daniel

AU - Williams, Kate

AU - Smyth, Alan R.

AU - Honeybourne, David

AU - L. Whitehouse, Joanna

AU - Nash, Edward F.

AU - Dewar, Jane

AU - Clayton, Andrew

AU - Knox, Alan J.

AU - Cámara, Miguel

AU - Fogarty, Andrew W.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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. Aim 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.

AB - 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. Aim 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.

U2 - 10.1016/j.jcf.2016.10.005

DO - 10.1016/j.jcf.2016.10.005

M3 - Article

C2 - 27773591

AN - SCOPUS:85008931797

SN - 1569-1993

VL - 16

SP - 230

EP - 238

JO - Journal of Cystic Fibrosis

JF - Journal of Cystic Fibrosis

IS - 2

ER -

Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study

Abstract

Bibliographical note

ASJC Scopus subject areas

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Research output

Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study; response to comments

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