A pilot study of the noninvasive assessment of the lung microbiota as a potential tool for the early diagnosis of ventilator-associated pneumonia
Open accessAbstract
Background Ventilator-associated pneumonia (VAP) remains a common complication in critically ill surgical patients, and its diagnosis remains problematic. Exhaled breath contains aerosolized droplets that reflect the lung microbiota. We hypothesized that exhaled breath condensate fluid (EBCF) in hygroscopic condenser humidifier/heat and moisture exchanger (HCH/HME) filters would contain bacterial DNA that qualitatively and quantitatively correlate with pathogens isolated from quantitative BAL samples obtained for clinical suspicion of pneumonia.Methods Forty-eight adult patients who were mechanically ventilated and undergoing quantitative BAL (n = 51) for suspected pneumonia in the surgical ICU were enrolled. Per protocol, patients fulfilling VAP clinical criteria undergo quantitative BAL bacterial culture. Immediately prior to BAL, time-matched HCH/HME filters were collected for study of EBCF by real-time polymerase chain reaction. Additionally, convenience samples of serially collected filters in patients with BAL-diagnosed VAP were analyzed.Results Forty-nine of 51 time-matched EBCF/BAL fluid samples were fully concordant (concordance > 95% by κ statistic) relative to identified pathogens and strongly correlated with clinical cultures. Regression analysis of quantitative bacterial DNA in paired samples revealed a statistically significant positive correlation (r = 0.85). In a convenience sample, qualitative and quantitative polymerase chain reaction analysis of serial HCH/HME samples for bacterial DNA demonstrated an increase in load that preceded the suspicion of pneumonia.Conclusions Bacterial DNA within EBCF demonstrates a high correlation with BAL fluid and clinical cultures. Bacterial DNA within EBCF increases prior to the suspicion of pneumonia. Further study of this novel approach may allow development of a noninvasive tool for the early diagnosis of VAP.
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The predicted effect of ecological forces in the lungs of critically ill patients is a state of increased immigration, decreased elimination, and favourable growth conditions for potential pathogens.
“The predicted effect of these ecological forces in the lungs, therefore, is a state of increased immigration, decreased elimination, and favourable growth conditions for potential pathogens.”
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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
Oliveira, D. C., & de LENCASTRE, H. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.7.2155-2161.2002 · Cited by 1,344 · see citing works
Epidemiology and Outcomes of Ventilator-Associated Pneumonia in a Large US Database
Rello, J., Ollendorf, D. A., Oster, G., Vera‐Llonch, M., Bellm, L. A., Redman, R. L., & Kollef, M. H. (2002) · CHEST Journal · doi:10.1378/chest.122.6.2115 · Cited by 1,303 · see citing works
Clinical and economic consequences of ventilator-associated pneumonia: A systematic review
Safdar, N., Dezfulian, C., Collard, H. R., & Saint, S. K. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000181731.53912.d9 · Cited by 1,082 · see citing works
Impact of BAL Data on the Therapy and Outcome of Ventilator-Associated Pneumonia
Luna, C. M., Vujacich, P., Niederman, M. S., Vay, C. A., Gherardi, C. R., Matera, J., & Jolly, E. C. (1997) · CHEST Journal · doi:10.1378/chest.111.3.676 · Cited by 915 · see citing works
Ventilator-associated Pneumonia Caused by Potentially Drug-resistant Bacteria
Trouillet, J., Chastre, J. E., Vuagnat, A., Joly‐Guillou, M., Combaux, D., Dombret, M.-C., & Gibert, C. (1998) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.157.2.9705064 · Cited by 884 · see citing works
Invasive and Noninvasive Strategies for Management of Suspected Ventilator-Associated Pneumonia
Fagon, J.-Y., Chastre, J. E., Wolff, M., Gervais, C., Parer, S., Stéphan, F., Similowski, T., Mercat, A., Diehl, J., Sollet, J.-P., et al. (2000) · Annals of Internal Medicine · doi:10.7326/0003-4819-132-8-200004180-00004 · Cited by 844 · see citing works
Ventilator-associated pneumonia. A multivariate analysis
Kollef, M. H. (1993) · JAMA · doi:10.1001/jama.270.16.1965 · Cited by 745 · see citing works
Álvarez-Lerma, F., & ICU-Acquired Pneumonia Study Group (1996) · Intensive Care Medicine · doi:10.1007/bf01712153 · Cited by 649 · see citing works
Inadequate Antimicrobial Treatment: An Important Determinant of Outcome for Hospitalized Patients
Kollef, M. H. (2000) · Clinical Infectious Diseases · doi:10.1086/314079 · Cited by 641 · see citing works
Harbarth, S., Samore, M. H., Lichtenberg, D., & Carmeli, Y. (2000) · Circulation · doi:10.1161/01.cir.101.25.2916 · Cited by 589 · see citing works
Exhaled droplets due to talking and coughing
Xie, X., Li, Y., Sun, H., & Liu, L. (2009) · Journal of The Royal Society Interface · doi:10.1098/rsif.2009.0388.focus · Cited by 528 · see citing works
Aspiration in severe trauma: a prospective study
Lockey, D., Coats, T., & Parr, M. J. (1999) · Anaesthesia · doi:10.1046/j.1365-2044.1999.00754.x · Cited by 515 · see citing works
Influenza Virus in Human Exhaled Breath: An Observational Study
Fabian, P., McDevitt, J. J., DeHaan, W. H., Fung, R. O. P., Cowling, B. J., Chan, K. H., Leung, G. M., & Milton, D. K. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002691 · Cited by 496 · see citing works
The Value of Routine Microbial Investigation in Ventilator-Associated Pneumonia
Rello, J., Gallego, M., Mariscal, D., Sonora, R., & Vallés, J. (1997) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.156.1.9607030 · Cited by 467 · see citing works
Meduri, G. U., Mauldin, G. L., Wunderink, R. G., Leeper, K. V., Jones, C. B., Tolley, E. A., & Mayhall, G. (1994) · CHEST Journal · doi:10.1378/chest.106.1.221 · Cited by 338 · see citing works
Diagnosing Pneumonia during Mechanical Ventilation
Fartoukh, M. S., Maître, B., Honoré, S., et al. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200212-1449oc · Cited by 319 · see citing works
Diagnosis of ventilator-associated pneumonia: a systematic review of the literature
Réa-Neto, Á., Youssef, N. C. M., Tuche, F., et al. (2008) · Critical Care · doi:10.1186/cc6877 · Cited by 267 · see citing works
Schurink, C. A. M., van Nieuwenhoven, C. A., Jacobs, J. A., et al. (2004) · Intensive Care Medicine · doi:10.1007/s00134-003-2018-2 · Cited by 249 · see citing works
Airborne transmission of disease in hospitals
Eames, I., Tang, J. W.-T., Li, Y., & Wilson, P. (2009) · Journal of The Royal Society Interface · doi:10.1098/rsif.2009.0407.focus · Cited by 219 · see citing works
Exhaled Breath Condensate: An Overview
Hunt, J. (2007) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2007.09.001 · Cited by 202 · see citing works
Risk Factors for ICU-Acquired Pneumonia
Cook, D. J. (1998) · JAMA · doi:10.1001/jama.279.20.1605 · Cited by 191 · see citing works
Early Antibiotic Treatment for BAL-Confirmed Ventilator-Associated Pneumonia
Michel, F., Franceschini, B., Berger, P. A., et al. (2005) · CHEST Journal · doi:10.1378/chest.127.2.589 · Cited by 184 · see citing works
Bahrani-Mougeot, F. K., Paster, B. J., Coleman, S., Barbuto, S., Brennan, M. T., Noll, J., Kennedy, T., Fox, P. C., & Lockhart, P. B. (2007) · Journal of Clinical Microbiology · doi:10.1128/jcm.01963-06 · Cited by 176 · see citing works
Glycerophospholipid Identification and Quantitation by Electrospray Ionization Mass Spectrometry
Ivanova, P. T., Milne, S. B., Byrne, M. O., Xiang, Y., & Brown, H. A. (2007) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(07)32002-8 · Cited by 174 · see citing works
Luyt, C., Chastre, J. E., Fagon, J.-Y., et al. (2004) · Intensive Care Medicine · doi:10.1007/s00134-003-2125-0 · Cited by 167 · see citing works
Comparison of Biomarkers in Exhaled Breath Condensate and Bronchoalveolar Lavage
Jackson, A. S., Sandrini, A., Campbell, C., Chow, S., Thomas, P. S., & Yates, D. H. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200601-107oc · Cited by 158 · see citing works
Jünger, M., Vautz, W., Kuhns, M., Hofmann, L. K., Ulbricht, S., Baumbach, J., Quintel, M., & Perl, T. (2012) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-012-3924-4 · Cited by 156 · see citing works
Edmiston, C. E., Seabrook, G. R., Cambria, R. A., et al. (2005) · Surgery · doi:10.1016/j.surg.2005.06.045 · Cited by 154 · see citing works
The promise and perils of exhaled breath condensates
Effros, R. M., Dunning, M. B., Biller, J. A., & Shaker, R. (2004) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00069.2004 · Cited by 135 · see citing works
Horz, H., Vianna, M. E., Gomes, B. P. F. D. A., & Conrads, G. (2005) · Journal of Clinical Microbiology · doi:10.1128/jcm.43.10.5332-5337.2005 · Cited by 132 · see citing works
Barie, P. S., Hydo, L. J., Shou, J., Larone, D. H., & Eachempati, S. R. (2005) · Surgical Infections · doi:10.1089/sur.2005.6.41 · Cited by 119 · see citing works
Duration of antibiotic therapy for penetrating abdominal trauma: a prospective trial.
Fabian, T. C., Croce, M. A., PAYNE, L. W., Minard, G., Pritchard, F. E., & Kudsk, K. A. (1992) · PubMed · Cited by 105 · see citing works
Croce, M. A., Fabian, T. C., Schurr, M. J., et al. (1995) · doi:10.1097/00005373-199512000-00022 · Cited by 104 · see citing works
Risk and prognostic factors of ventilator-associated pneumonia in trauma patients
Cavalcanti, M. A. D. N., Ferrer, M., Ferrer, R., Morforte, R., Garnacho, A., & Torres, A. (2006) · Critical Care Medicine · doi:10.1097/01.ccm.0000206471.44161.a0 · Cited by 96 · see citing works
Carroll, K. C., Glanz, B. D., Borek, A. P., Burger, C., Bhally, H. S., Henciak, S., & Flayhart, D. C. (2006) · Journal of Clinical Microbiology · doi:10.1128/jcm.00994-06 · Cited by 88 · see citing works
Cost and morbidity associated with antibiotic prophylaxis in the ICU
Namias, N., Harvill, S., Ball, S., et al. (1999) · Journal of the American College of Surgeons · doi:10.1016/s1072-7515(98)00287-7 · Cited by 84 · see citing works
Schmidt, R., Steinhilber, W., Ruppert, C., et al. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.165.4.2102080 · Cited by 81 · see citing works
Minei, J. P., Nathens, A. B., West, M. A., Harbrecht, B. G., Moore, E. E., Shapiro, M. B., Bankey, P. E., Johnson, J. L., Freeman, B. D., McKinley, B. A., et al. (2006) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/01.ta.0000220424.34835.f1 · Cited by 78 · see citing works
Severe Trauma Is Not an Excuse for Prolonged Antibiotic Prophylaxis
Velmahos, G. C. (2002) · Archives of Surgery · doi:10.1001/archsurg.137.5.537 · Cited by 75 · see citing works
Bodini, A., D’Orazio, C., Peroni, D. G., Corradi, M., Folesani, G., Baraldi, E., Assael, B. M., Boner, A. L., & PIACENTINI, G. L. (2005) · Pediatric Pulmonology · doi:10.1002/ppul.20336 · Cited by 56 · see citing works
Croce, M. A., Tolley, E. A., & Fabian, T. C. (2003) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/01.ta.0000054643.54218.c5 · Cited by 56 · see citing works
Airborne Particulates in the OR Environment
Edmiston, C. E., Sinski, S., Seabrook, G. R., et al. (1999) · AORN Journal · doi:10.1016/s0001-2092(06)61884-x · Cited by 55 · see citing works
May, A. K., Fleming, S. B., Carpenter, R. O., et al. (2006) · Surgical Infections · doi:10.1089/sur.2006.7.409 · Cited by 53 · see citing works
Self-citationLauzier, F., Ruest, A., Cook, D., Dodek, P., Albert, M., Shorr, A. F., Day, A. G., Jiang, X., & Heyland, D. K. (2008) · Journal of Critical Care · doi:10.1016/j.jcrc.2008.01.006 · Cited by 51 · see citing works
Siala, M., Gdoura, R., Fourati, H., Rihl, M., Jaulhac, B., Younès, M., Sibilia, J., Baklouti, S., Bargaoui, N., Sellami, S., et al. (2009) · Arthritis Research & Therapy · doi:10.1186/ar2748 · Cited by 50 · see citing works
ELISA Technique for Quantification of Surfactant Protein B (SP-B) in Bronchoalveolar Lavage Fluid
Krämer, H.-R., Schmidt, R., Günther, A., et al. (1995) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.152.5.7582290 · Cited by 49 · see citing works
Detection of VirulentRhodococcus equiin Exhaled Air Samples from Naturally Infected Foals
Muscatello, G., Gilkerson, J. R., & Browning, G. F. (2009) · Journal of Clinical Microbiology · doi:10.1128/jcm.01395-08 · Cited by 47 · see citing works
Standard error of the kappa statistic.
Hanley, J. A. (1987) · Psychological Bulletin · doi:10.1037/0033-2909.102.2.315 · Cited by 45 · see citing works
Cherkaoui, A., Emonet, S., Ceroni, D., et al. (2009) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2009.09.014 · Cited by 39 · see citing works
A simple breath sampling method in intubated and mechanically ventilated critically ill patients
Bos, L. D. J., Wang, Y., Weda, H., et al. (2013) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2013.11.001 · Cited by 35 · see citing works
Pre-Hospital Intubation Factors and Pneumonia in Trauma Patients
Evans, H. L., Warner, K. J., Bulger, E. M., et al. (2011) · Surgical Infections · doi:10.1089/sur.2010.074 · Cited by 33 · see citing works
Non-invasive detection of pulmonary pathogens in ventilator-circuit filters by PCR.
Isaacs, R. J., Debelak, K., Norris, P. R., Jenkins, J. M., Rooks, J. C., Young, T., May, A. K., & Boczko, E. M. (2012) · PubMed Central · Cited by 15 · see citing works
Self-citationEarly nonbronchoscopic bronchoalveolar lavage
Minshall, C. T., Eriksson, E. A., Hawkins, K. S., et al. (2013) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0b013e31827e212c · Cited by 14 · see citing works
An analysis of quantitative PCR reliability through replicates using the Ct method
Stowers, C. C., Haselton, F. R., & Boczko, E. M. (2010) · Journal of Biomedical Science and Engineering · doi:10.4236/jbise.2010.35064 · Cited by 13 · see citing works
Self-citationBacterial 16S rRNA/rDNA Profiling in the Liquid Phase of Human Saliva
Gu, F., Li, Y., Zhou, C., Wong, D. T., Ho, C. M., Qi, F., & Shi, W. K. (2009) · The Open Dentistry Journal · doi:10.2174/1874210600903010080 · Cited by 12 · see citing works
Rice, L. M., Reis, A. H., Mistry, R. A., et al. (2013) · Journal of Applied Microbiology · doi:10.1111/jam.12281 · Cited by 2 · see citing works
Detecting and describing heterogeneity in meta-analysis
Hardy, R. J., & Thompson, S. G. (1998) · Statistics in Medicine · doi:10.1002/(sici)1097-0258(19980430)17:8
Flagged first, then by citations
Research works printed but not linked: 3
- Ivanova PT , Milne SB , Byrne MO , Xiang Y , Brown HA . Glycerophospholipid identifi cation and quantitation by elec- trospray ionization mass spectrometry . Methods Enzymol . 2007 ; 432 : 21 -57 .
- Newcombe RG . Two-sided confi dence intervals for the single proportion: com- parison of seven methods . Stat Med . 1998 ; 17 ( 8 ): 857 -872 .
- Muscatello G , Gilkerson JR , Browning GF . Detection of virulent Rhodococcus equi in exhaled air samples from nat- urally infected foals . J Clin Microbiol . 2009 ; 47 ( 3 ): 734 -737 .
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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
- Authors
- May, A. K., Brady, J. S., Romano-Keeler, J., Drake, W. P., Norris, P. R., Jenkins, J. M., Isaacs, R. J., & Boczko, E. M.
- Affiliations
- Vanderbilt University (US)
- Ohio University (US)
- Corresponding author
- May, Addison K.
- Venue
- Chest
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 147
- Issue
- 6
- Pages
- 1494-1502
- ISSN
- 0012-3692 (ISSN-L)
- PMC
- PMC4451706
- OpenAlex
- W1989394087
- Cited by
- 40
- References
- 59
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 10 · 2016: 2 · 2015: 4
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- CHEST Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vanderbilt University (UL1 RR024975)
- Vanderbilt Institute for Clinical and Translational Research (RR024975, CTSA 1 UL1 RR024975, UL1 RR024975)
- Georgia Clinical and Translational Science Alliance (UL1 RR024975, RR024975)
- National Heart, Lung, and Blood Institute (U01HL112694)
- National Center for Research Resources (UL1RR024975)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD068256)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Nosocomial Infections in ICU
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Keywords
- ventilator-associated pneumonia, lung microbiome, bacterial DNA, bronchoalveolar lavage, early diagnosis, non-invasive diagnosis, mechanical ventilation, surgical intensive care unit, bacterial load
- MeSH terms
- Diagnostic Tests, Routine, DNA, Bacterial, Humans, Intensive Care Units, Lung, Microbiological Techniques, Pilot Projects, Regression Analysis, Sensitivity and Specificity, Critical Illness, Bronchoalveolar Lavage, Exhalation, Pneumonia, Ventilator-Associated, Real-Time Polymerase Chain Reaction, Microbiota
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