Does bacterial density in cystic fibrosis sputum increase prior to pulmonary exacerbation?
Open accessAbstract
Background Cystic Fibrosis (CF) lung disease is characterised by an inexorable decline in lung function, punctuated by periods of symptomatic worsening known as pulmonary exacerbations (referred to here as CFPE). Despite their clinical significance, the cause of CFPE remains undetermined. It has been suggested that an increase in bacterial density may be a trigger, although this has not been shown empirically.Methods Here, a previously validated quantitative PCR-based approach was used to assess numbers of Pseudomonas aeruginosa and of total bacteria in respiratory secretions from patients during the period leading up to CFPE. Sputum samples collected from 12 adult CF patients were selected retrospectively to fall approximately 21, 14, 7 and 0 days prior to CFPE diagnosis. In addition, the relationships between clinical parameters (FEV(1), temperature and patient reported outcome measures) and microbiological data were investigated.Results No significant changes either in total bacterial or P. aeruginosa numbers were identified prior to CFPE. Of all the correlations tested, only temperature showed a significant correlation with total bacterial numbers in the period leading to CFPE.Conclusions These findings strongly suggest that CFPE do not generally result from increased bacterial density within the airways. Instead, data presented here are consistent with alternative models of pulmonary exacerbation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Culture-independent studies comparing bacterial communities at baseline and during exacerbations in the airways of patients with COPD, cystic fibrosis, or bronchiectasis consistently report no increase in bacterial burden and no decrease in community diversity during exacerbations.
“With remarkable consistency, all studies report no increase in bacterial burden and no decrease in community diversity during exacerbations.”
From The microbiome and critical illness (2016) · cites this paper as [134]
Cites
Ratjen, A. K. W. F. A. (2006) · Cited by 4,406 · see citing works
Nadkarni, M. A., Martin, F. E., Jacques, N. A., & Hunter, N. (2002) · Microbiology · doi:10.1099/00221287-148-1-257 · Cited by 1,931 · see citing works
Pathophysiology and Management of Pulmonary Infections in Cystic Fibrosis
Gibson, R. L., Burns, J. L., & Ramsey, B. W. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200304-505so · Cited by 1,629 · see citing works
Fuchs, H. J., Borowitz, D., Christiansen, D. H., Morris, E. M., Nash, M. L., Ramsey, B. W., Rosenstein, B. J., Smith, A. L., & Wohl, M. E. B. (1994) · New England Journal of Medicine · doi:10.1056/nejm199409083311003 · Cited by 1,532 · see citing works
Real-Time PCR in Clinical Microbiology: Applications for Routine Laboratory Testing
Espy, M. J., Uhl, J. R., Sloan, L. M., Buckwalter, S. P., Jones, M. F., Vetter, E. A., Yao, J. D. C., Wengenack, N. L., Rosenblatt, J. E., Cockerill, F. R., et al. (2006) · Clinical Microbiology Reviews · doi:10.1128/cmr.19.1.165-256.2006 · Cited by 1,318 · see citing works
Intermittent Administration of Inhaled Tobramycin in Patients with Cystic Fibrosis
Ramsey, B. W., PEPE, M. S., Quan, J. M., Otto, K., Montgomery, A. B., Williams‐Warren, J., Vasiljev-K, M., Borowitz, D., Bowman, C. M., Marshall, B. C., et al. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901073400104 · Cited by 1,296 · see citing works
Saiman, L., Marshall, B. C., Mayer-Hamblett, N., Burns, J. L., Quittner, A. L., Cibene, D. A., Coquillette, S., Fieberg, A. Y., Accurso, F. J., Campbell III, P. W., et al. (2003) · JAMA · doi:10.1001/jama.290.13.1749 · Cited by 958 · see citing works
Predictive 5-year survivorship model of cystic fibrosis
Liou, T. G., Adler, F. R., FitzSimmons, S. C., Cahill, B. C., Hibbs, J. R., & Marshall, B. C. (2001) · American Journal of Epidemiology · doi:10.1093/aje/153.4.345 · Cited by 749 · see citing works
Detection of Anaerobic Bacteria in High Numbers in Sputum from Patients with Cystic Fibrosis
Tunney, M. M., Field, T. R., Moriarty, T. F., Patrick, S., Doering, G., Muhlebach, M. S., Wolfgang, M. C., Boucher, R. C., Gilpin, D. F., McDowell, A., et al. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200708-1151oc · Cited by 466 · see citing works
Exacerbations in cystic fibrosis {middle dot} 1: Epidemiology and pathogenesis
Goss, C. H., & Burns, J. L. (2007) · Thorax · doi:10.1136/thx.2006.060889 · Cited by 445 · see citing works
Konstan, M. W., Morgan, W. J., Butler, S. M., Pasta, D. J., Craib, M. L., Silva, S. J., Stokes, D. C., Wohl, M. E. B., Wagener, J. S., Regelmann, W. E., et al. (2007) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2007.03.006 · Cited by 436 · see citing works
Moskowitz, S. M., Foster, J. M., Emerson, J., & Burns, J. L. (2004) · Journal of Clinical Microbiology · doi:10.1128/jcm.42.5.1915-1922.2004 · Cited by 398 · see citing works
Impact of Recent Pulmonary Exacerbations on Quality of Life in Patients With Cystic Fibrosis
Britto, M. T., Kotagal, U. R., Hornung, R., Atherton, H. D., Tsevat, J., & Wilmott, R. W. (2002) · CHEST Journal · doi:10.1378/chest.121.1.64 · Cited by 347 · see citing works
Significant Microbiological Effect of Inhaled Tobramycin in Young Children with Cystic Fibrosis
Gibson, R. L., Emerson, J., McNamara, S., et al. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200208-855oc · Cited by 318 · see citing works
Nocker, A., Sossa, K. E., & Camper, A. K. (2007) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2007.04.014 · Cited by 311 · see citing works
Defining a pulmonary exacerbation in cystic fibrosis
Rosenfeld, M., Emerson, J., Williams‐Warren, J., PEPE, M. S., Smith, A. L., Montgomery, A., & Ramsey, B. W. (2001) · The Journal of Pediatrics · doi:10.1067/mpd.2001.117288 · Cited by 301 · see citing works
Shannon, K., Lee, D., Trevors, J., & Beaudette, L. (2007) · Science of the Total Environment · doi:10.1016/j.scitotenv.2007.02.039 · Cited by 288 · see citing works
Effect of Ambient Air Pollution on Pulmonary Exacerbations and Lung Function in Cystic Fibrosis
Goss, C. H., Newsom, S. A., Schildcrout, J. S., Sheppard, L. A., & Kaufman, J. D. (2004) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200306-779oc · Cited by 272 · see citing works
Regelmann, W. E., Elliott, G. R., Warwick, W. J., & Clawson, C. C. (1990) · American Review of Respiratory Disease · doi:10.1164/ajrccm/141.4_pt_1.914 · Cited by 261 · see citing works
Viable but nonculturable bacteria: a survival strategy
Colwell, R. R. (2000) · Journal of Infection and Chemotherapy · doi:10.1007/pl00012151 · Cited by 224 · see citing works
Effects of Viral Lower Respiratory Tract Infection on Lung Function in Infants With Cystic Fibrosis
Hiatt, P., Grace, S. C., Kozinetz, C. A., RABOUDI, S. H., Treece, D. G., Taber, L. H., & Piedra, P. A. (1999) · PEDIATRICS · doi:10.1542/peds.103.3.619 · Cited by 215 · see citing works
Molecular diagnosis of bloodstream infections caused by non-cultivable bacteria
Fenollar, F., & Raoult, D. (2007) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2007.06.024 · Cited by 215 · see citing works
Mucociliary clearance in cystic fibrosis
Robinson, M., & Bye, P. T. P. (2002) · Pediatric Pulmonology · doi:10.1002/ppul.10079 · Cited by 159 · see citing works
Sputum changes associated with therapy for endobronchial exacerbation in cystic fibrosis
Smith, A. L., Redding, G. J., Doershuk, C. F., et al. (1988) · The Journal of Pediatrics · doi:10.1016/s0022-3476(88)80165-3 · Cited by 146 · see citing works
Return of FEV1 after pulmonary exacerbation in children with cystic fibrosis
Sanders, D. B., Hoffman, L. R., Emerson, J., Gibson, R. L., Rosenfeld, M., Redding, G. J., & Goss, C. H. (2010) · Pediatric Pulmonology · doi:10.1002/ppul.21117 · Cited by 137 · see citing works
Self-citationMcLaughlin, F. J., Matthews, W. J., Strieder, D. J., et al. (1983) · The Journal of Infectious Diseases · doi:10.1093/infdis/147.3.559 · Cited by 126 · see citing works
Jaffar‐Bandjee, M., Lazdunski, A., Bally, M., et al. (1995) · Journal of Clinical Microbiology · doi:10.1128/jcm.33.4.924-929.1995 · Cited by 123 · see citing works
Remschmidt, H., & Schmidt, M. H. (2001) · Springer eBooks · doi:10.1007/978-3-642-59519-6_47 · Cited by 109 · see citing works
Viral respiratory infections in cystic fibrosis
van Ewijk, B. E., van der Zalm, M. M., Wolfs, T. F. W., & van der Ent, C. K. (2005) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2005.05.011 · Cited by 98 · see citing works
Defining an exacerbation of pulmonary disease in cystic fibrosis*
Dakin, C., Henry, R. L., Field, P., & Morton, J. (2001) · Pediatric Pulmonology · doi:10.1002/ppul.1072 · Cited by 96 · see citing works
Evaluating the “Leeds criteria” forPseudomonas aeruginosainfection in a cystic fibrosis centre
Proesmans, M., Balińska-Miśkiewicz, W., Dupont, L., et al. (2006) · European Respiratory Journal · doi:10.1183/09031936.06.00100805 · Cited by 91 · see citing works
Chattoraj, S. S., Ganesan, S., Jones, A. M., Helm, J. M., Comstock, A. T., Bright-Thomas, R. J., LiPuma, J. J., Hershenson, M. B., & Sajjan, U. S. (2011) · Thorax · doi:10.1136/thx.2010.151431 · Cited by 90 · see citing works
Rogers, G. B., Marsh, P., Stressmann, F. A., Allen, C. E., Daniels, T. V., Carroll, M. P., & Bruce, K. D. (2010) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2010.03189.x · Cited by 88 · see citing works
Self-citationJubin, V., Ranque, S., le Bel, N. S., Sarles, J., & Dubus, J. ‐. (2010) · Pediatric Pulmonology · doi:10.1002/ppul.21240 · Cited by 88 · see citing works
Zemanick, E. T., Wagner, B. D., Sagel, S. D., Stevens, M. J., Accurso, F. J., & Harris, J. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015101 · Cited by 87 · see citing works
Schneider, M., Mühlemann, K., Droz, S., Couzinet, S., Casaulta, C., & Zimmerli, S. (2008) · Journal of Clinical Microbiology · doi:10.1128/jcm.00361-08 · Cited by 85 · see citing works
Objective measurement of cough during pulmonary exacerbations in adults with cystic fibrosis
Smith, J. A. (2006) · Thorax · doi:10.1136/thx.2005.050963 · Cited by 84 · see citing works
Assessing the diagnostic importance of nonviable bacterial cells in respiratory infections
Rogers, G. B., Stressmann, F. A., Koller, G., Daniels, T. W. V., Carroll, M. P., & Bruce, K. D. (2008) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2008.06.011 · Cited by 79 · see citing works
Self-citationGold, R., OVERMEYER, A., KNIE, B., et al. (1985) · The Pediatric Infectious Disease Journal · doi:10.1097/00006454-198503000-00012 · Cited by 73 · see citing works
Deschaght, P., Baere, T. D., Simaey, L. V., et al. (2009) · BMC Microbiology · doi:10.1186/1471-2180-9-244 · Cited by 68 · see citing works
Simple method for quantifying viable bacterial numbers in sputum.
Pye, A., STOCKLEY, R. A., & Hill, S. L. (1995) · Journal of Clinical Pathology · doi:10.1136/jcp.48.8.719 · Cited by 66 · see citing works
Rogers, G. B., Daniels, T. W. V., Tuck, A. C., Carroll, M. P., Connett, G. J., David, G. J. P., & Bruce, K. D. (2009) · BMC Pulmonary Medicine · doi:10.1186/1471-2466-9-14 · Cited by 63 · see citing works
Self-citationInfections with Pseudomonas aeruginosa in patients with cystic fibrosis.
Tümmler, B., Boßhammer, J., Breitenstein, S., et al. (1997) · PubMed · Cited by 61 · see citing works
VanDevanter, D. R., & Dalfsen, J. M. V. (2005) · Pediatric Pulmonology · doi:10.1002/ppul.20220 · Cited by 50 · see citing works
Aitken, M. L., Greene, K. E., Tonelli, M. R., et al. (2003) · CHEST Journal · doi:10.1378/chest.123.3.792 · Cited by 32 · see citing works
Rogers, G. B., Hoffman, L. R., Johnson, M. W., Mayer-Hamblett, N., Schwarze, J., Carroll, M. P., & Bruce, K. D. (2011) · Expert Review of Molecular Diagnostics · doi:10.1586/erm.10.117 · Cited by 19 · see citing works
Self-citationRoudière, L., Lorto, S., Tallagrand, E., et al. (2007) · Pathologie Biologie · doi:10.1016/j.patbio.2007.07.014 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Microbiome and the Respiratory Tract
Dickson, R. P., Erb-Downward, J. R., Martinez, F. J., & Huffnagle, G. B. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105238 · Cited by 953 · see citing works
Decade-long bacterial community dynamics in cystic fibrosis airways
Zhao, J., Schloss, P. D., Kalikin, L. M., Carmody, L. A., Foster, B. K., Petrosino, J. F., Cavalcoli, J. D., VanDevanter, D. R., Murray, S., Li, J. Z., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120577109 · Cited by 599 · see citing works
The role of the microbiome in exacerbations of chronic lung diseases
Dickson, R. P., Martinez, F. J., & Huffnagle, G. B. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61136-3 · Cited by 495 · see citing works
The microbiome and critical illness
Dickson, R. P. (2016) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(15)00427-0 · Cited by 460 · see citing works
The Lung Microbiome, Immunity, and the Pathogenesis of Chronic Lung Disease
O’Dwyer, D. N., Dickson, R. P., & Moore, B. B. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600279 · Cited by 362 · see citing works
Tunney, M. M., Einarsson, G. G., Wei, L., Drain, M., Klem, E. R., Cardwell, C., Ennis, M., Boucher, R. C., Wolfgang, M. C., & Elborn, J. S. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201210-1937oc · Cited by 316 · see citing works
Changes in cystic fibrosis airway microbiota at pulmonary exacerbation
Carmody, L. A., Zhao, J., Schloss, P. D., Petrosino, J. F., Murray, S., Young, V. B., Li, J. Z., & LiPuma, J. J. (2013) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201211-107oc · Cited by 239 · see citing works
Carmody, L. A., Zhao, J., Kalikin, L. M., LeBar, W., Simon, R. H., Venkataraman, A., Schmidt, T. M., Abdo, Z., Schloss, P. D., & LiPuma, J. J. (2015) · Microbiome · doi:10.1186/s40168-015-0074-9 · Cited by 135 · see citing works
Price, K. E., Hampton, T. H., Gifford, A. H., Dolben, E. L., Hogan, D. A., Morrison, H. G., Sogin, M. L., & O’Toole, G. A. (2013) · Microbiome · doi:10.1186/2049-2618-1-27 · Cited by 135 · see citing works
- Authors
- Stressmann, F. A., Rogers, G. B., Marsh, P., Lilley, A. K., Daniels, T. W. V., Carroll, M. P., Hoffman, L. R., Jones, G., Allen, C. E., Patel, N., Forbes, B., Tuck, A., & Bruce, K. D.
- Affiliations
- King's College London (GB)
- Southampton General Hospital (GB)
- University Hospital Southampton NHS Foundation Trust (GB)
- University of Washington (US)
- Corresponding author
- Rogers, Geraint B.
- ORCID
- Venue
- Journal of Cystic Fibrosis
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 10
- Issue
- 5
- Pages
- 357-365
- ISSN
- 1569-1993 (ISSN-L)
- OpenAlex
- W2009245754
- Cited by
- 130
- References
- 47
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 7 · 2022: 7 · 2021: 7 · 2020: 17 · 2019: 9 · 2018: 10 · 2017: 9 · 2016: 7 · 2015: 16 · 2014: 10 · 2013: 15 · 2012: 7
- FWCI
- 9.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Cystic Fibrosis (publishedVersion)
- PubMed (publishedVersion)
- Research Repository (Kingston University London) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Anna Trust
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- pulmonary exacerbations, sputum bacterial density, Pseudomonas aeruginosa, real-time PCR, respiratory secretions, airway microbiology, fever, disease triggers, lung function decline
- MeSH terms
- Adolescent, Adult, Anti-Bacterial Agents, Cystic Fibrosis, Female, Humans, Male, Middle Aged, Pseudomonas aeruginosa, Pseudomonas Infections, Respiratory Function Tests, Severity of Illness Index, Sputum, Pneumonia, Bacterial, Young Adult, Bacterial Load, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review