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Volatile diagnostic techniques for ventilator associated pneumonia

By Martyn Lee Humphreys

Abstract

Ventilator associated pneumonia (VAP) is a significant challenge for the Intensive Care doctors worldwide. It is both difficult to diagnose accurately and quickly and to treat effectively once the diagnosis has been established. Current diagnostic microbiological methods of diagnosis can take up to 48 hours to yield results. Early diagnosis and treatment remain the best way of improving outcome for patients with VAP. In this study we look at novel diagnostic techniques for VAP. Electronic nose (Enose) technology was used to identify to identify the presence of microorganisms in bronchoalveolar lavage (BAL) fluid samples taken from the respiratory tracts of ventilated patients. The results were compared with standard microbiological culture and sensitivities. The Enose was able to discriminate 83% of samples into growth or no growth groups on samples grown in the lab. When the technique was employed to samples taken directly from patients the accuracy fell to 68.2%. This suggests that patient related factors may be reducing the accuracy of the Enose classification. The use of antimicrobial drugs prior to patient sampling is likely to have played a major role. The second part of this study used Gas Chromatography-Mass Spectrometry (GC-MS) analysis of patient’s breath in an attempt to identify patients with VAP. Breath samples were taken at the same time as the bronchoalveolar lavage samples described above. The use of this technique did show differences between the breath samples of patients who did not have any microbiological growth from their BAL samples and those that did. Leave one out cross validation of a PC fed LDA model showed 84% correct classification between healthy volunteers, no growth and growth groups. Finally, we evaluated the Breathotron, which is a breath analysis device designed and built at Cranfield Health. It allows for analysis of breath samples using a single sensor system as opposed to a sensor array employed in traditional Enose devices. This allows it to be more portable and cheaper to build. The Breathotron also allows collection of breath onto sorbent cartridges for GC-MS analysis. Its single sensor did not allow for accurate discrimination between samples

Publisher: Cranfield University
Year: 2010
OAI identifier: oai:dspace.lib.cranfield.ac.uk:1826/5738
Provided by: Cranfield CERES

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Citations

  1. (1999). [Importance and perspectives of breath analysis]. Anasthesiol Intensivmed Notfallmed Schmerzther,
  2. (1998). 2nd, Measurement of lipid peroxidation. Free Radic Res, doi
  3. (2000). A comparative analysis of patients with early-onset vs lateonset nosocomial pneumonia in the ICU setting. Chest, doi
  4. (1988). A computerized classification technique for screening for the presence of breath biomarkers in lung cancer. Clin Chem,
  5. (1990). A device for sampling of human alveolar breath for the measurement of expired volatile organic compounds. J Anal Toxicol, doi
  6. (2003). A feature extraction method for chemical sensors in electronic noses. Sensors and Actuators B, doi
  7. (1997). A novel device for capturing breath samples for solvent analysis. Sci Total Environ, doi
  8. (2004). A time-dependent analysis of intensive care unit pneumonia in trauma patients. doi
  9. (2002). Alveolar and serum procalcitonin: diagnostic and prognostic value in ventilator-associated pneumonia. Anesthesiology, doi
  10. (1982). Analysis of discrimination mechanisms in the mammalian olfactory system using a model nose. Nature, doi
  11. (2002). Analysis of exhaled breath condensate for monitoring airway inflammation. Trends Pharmacol Sci, doi
  12. Analysis of lung air from patients with bronchogenic carcinoma and controls using gas chromatography-mass spectrometry. doi
  13. Analysis of volatile disease markers in blood.
  14. (2005). Antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and group A beta-haemolytic streptococci doi
  15. (2004). Antimicrobial susceptibility among communityacquired respiratory tract pathogens in the USA: data from PROTEKT US 2000-01. J Infect, doi
  16. Antioxidant vitamin supplementation in Crohn's disease decreases oxidative stress. a randomized controlled trial. doi
  17. (2003). Application of low-temperature glassy carboncoated macrofibers for solid-phase microextraction analysis of simulated breath volatiles. Anal Chem, doi
  18. (2004). Application of Machine Olfaction Principles for the Detection of High Voltage Transformer Oil Degredation.
  19. (1991). Automatic end-expiratory air sampling device for breath hydrogen test in infants. Lancet, doi
  20. (2002). Bacteria classification using Cyranose 320 electronic nose. Biomed Eng Online, doi
  21. (1995). Bacteria produce the volatile hydrocarbon isoprene. Curr Microbiol, doi
  22. (1998). Bacterial or crystal-associated arthritis? Discriminating ability of serum inflammatory markers. doi
  23. (2002). Biomarkers of some pulmonary diseases in exhaled breath. Biomarkers, doi
  24. (1999). Blood cultures have limited value in predicting severity of illness and as a diagnostic tool in ventilator-associated pneumonia. Chest, doi
  25. (1996). Breath isoprene: temporal changes in respiratory output after exposure to ozone.
  26. (1994). Breath pentane is a marker of acute cardiac allograft rejection.
  27. (1992). Breath tests in medicine. Sci Am, doi
  28. (2000). Bronchoscopic BAL in the diagnosis of ventilatorassociated pneumonia.
  29. (1999). Clinical application of breath biomarkers of oxidative stress status. Free Radic Biol Med, doi
  30. (2002). Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest, doi
  31. (2001). CO(2)-controlled sampling of alveolar gas in mechanically ventilated patients.
  32. (2003). Community-acquired Staphylococcus aureus infections: Increasing virulence and emerging methicillin resistance in the new millennium. Curr Opin Infect Dis, doi
  33. (2003). Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA, doi
  34. (2008). Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: prevention. J Crit Care, doi
  35. (1997). Computational parallels between the biological olfactory pathway and its analogue 'the electronic nose': Part II. Sensor-based machine olfaction. Biosystems, doi
  36. (1996). Concentrating breath samples using liquid nitrogen: a reliable method for the simultaneous determination of ethane and pentane. Anal Biochem, doi
  37. (1998). Cytokine kinetics and other host factors in response to pneumococcal pulmonary infection in mice. Infect Immun,
  38. (1980). Deaths from nosocomial infections: experience in a university hospital and a community hospital. doi
  39. (2005). Detection of lung cancer by sensor array analyses of exhaled breath. doi
  40. (2004). Detection of Mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in combination with a neural network system. Biosens Bioelectron, doi
  41. Determination of ethane, pentane and isoprene in exhaled air using a multi-bed adsorbent and end-cut gas-solid chromatography. doi
  42. (2003). Diagnosing pneumonia during mechanical ventilation: the clinical pulmonary infection score revisited. doi
  43. (1995). Diagnosis and differential diagnosis of ventilator-associated pneumonia. Clin Chest Med, doi
  44. (1993). Diagnosis of nosocomial pneumonia in mechanically ventilated patients by the blind protected telescoping catheter. Intensive Care Med, doi
  45. (2004). Diagnosis of pneumonia with an electronic nose: correlation of vapor signature with chest computed tomography scan findings. Laryngoscope, doi
  46. (2004). Diagnostic potential of breath analysis--focus on volatile organic compounds. Clin Chim Acta, doi
  47. (1994). Diet and oxidative stress in breast, colon and prostate cancer patients: a case-control study.
  48. (2002). Dilution of respiratory solutes in exhaled condensates. doi
  49. (2005). Effect from multiple episodes of inadequate empiric antibiotic therapy for ventilator-associated pneumonia on morbidity and mortality among critically ill trauma patients. doi
  50. (2000). Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress. doi
  51. (2004). Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet, doi
  52. (1993). Effect of regulating cholesterol biosynthesis on breath isoprene excretion in men. Lipids, doi
  53. (2004). Effects of ventilation on the collection of exhaled breath in humans. doi
  54. (2004). Electronic noses and disease diagnostics. Nat Rev Microbiol, doi
  55. (1999). Electronic Noses:Principles and Applications. doi
  56. (2006). Empiric antimicrobial therapy for suspected ICU-acquired infection: the AATIC pilot study. Intensive Care Medicine,
  57. (1984). Endogenous isopropanol: forensic and biochemical implications. doi
  58. (1992). Endothelial modulation of pulmonary vascular tone. Eur Respir J, doi
  59. (1986). Enteral nutrition in patients receiving mechanical ventilation. Multiple sources of tracheal colonization include the stomach. Am J Med, doi
  60. (2002). Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. doi
  61. (1998). Epidemiology of ventilator-acquired pneumonia based on protected bronchoscopic sampling. doi
  62. (2004). Excessive antimicrobial usage causes measurable harm to patients with suspected ventilator-associated pneumonia. Intensive Care Med, doi
  63. (2001). Exhaled and nasal nitric oxide as a marker of pneumonia in ventilated patients. doi
  64. Exhaled human breath measurement method for assessing exposure to halogenated volatile organic compounds. Clin Chem,
  65. (1998). Exhaled isoprene and acetone in newborn infants and in children with diabetes mellitus. Pediatr Res, doi
  66. (2000). Exhaled nitric oxide production by nitric oxide synthasedeficient mice. doi
  67. (1997). Exhaled pentane levels in acute asthma. Chest, doi
  68. Experimental use of a new surface acoustic wave sensor for the rapid identification of bacteria and yeasts. doi
  69. (1995). Expired hydrocarbons in patients with acute myocardial infarction. Free Radic Res, doi
  70. (2003). GC analysis of human breath with a seriescoupled column ensemble and a multibed sorption trap. Anal Chem, doi
  71. Guidelines for the management of adults with hospital-acquired, ventilatorassociated, and healthcare-associated pneumonia. doi
  72. (2003). Haponik E, Bronchoscpoically guided management of ventilator-associated pneumonia in trauma patients. doi
  73. (1996). Histology and microbiology of ventilator-associated pneumonias. Semin Respir Infect,
  74. (1998). Hospital-acquired pneumonia: epidemiology, etiology, and treatment. Infect Dis Clin North Am, doi
  75. (2002). ICU-acquired nosocomial infection: impact of delay of adequate antibiotic treatment. doi
  76. (1997). Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. doi
  77. (1993). Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. doi
  78. (1997). Implementation of bronchoscopic techniques in the diagnosis of ventilator-associated pneumonia to reduce antibiotic use. Am J Respir Crit Care Med, doi
  79. (1999). Implications of endotracheal tube biofilm for ventilatorassociated pneumonia. Intensive Care Med, doi
  80. (2002). Incidence and outcome of polymicrobial ventilatorassociated pneumonia. Chest, doi
  81. (1993). Incidence and risk factors of pneumonia acquired in intensive care units. Results from a multicenter prospective study on 996 patients. doi
  82. (1998). Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients. Ann Intern Med, doi
  83. (1993). Increased amount of nitric oxide in exhaled air of asthmatics. doi
  84. (2000). Increased exhaled nitric oxide in chronic bronchitis: comparison with asthma doi
  85. (2000). Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis. Gastroenterology, doi
  86. (1992). Infections caused by Streptococcus pneumoniae: clinical spectrum, pathogenesis, immunity, and treatment. Clin Infect Dis, doi
  87. (2004). Introduction to Chemosensors, doi
  88. (2000). Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia. A randomized trial. Ann Intern Med, doi
  89. (1992). Ion-trap detection of volatile organic compounds in alveolar breath. Clin Chem,
  90. (2000). Is endogenous isoprene the only coeluting compound in the measurement of breath pentane? Clin Chim Acta, doi
  91. (1993). Is n-pentane really an index of lipid peroxidation in humans and animals? A methodological reevaluation. Anal Biochem, doi
  92. (1993). Lipid peroxidation: its mechanism, measurement, and significance.
  93. (1989). Long-term respiratory support and risk of pneumonia in critically ill patients. Intensive Care Unit Group of Infection Control. Am Rev Respir Dis, doi
  94. (2003). Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors. Biosens Bioelectron, doi
  95. (1974). Measurement of continuous distributions of ventilation-perfusion ratios: theory. doi
  96. (1998). Measuring exhaled nitric oxide: not only a matter of how--but also why--should we do it? Eur Respir J, doi
  97. (1970). Mercaptans and dimethyl sulfide in the breath of patients with cirrhosis of the liver. Effect of feeding methionine.
  98. (1998). Method for analysis of exhaled air by microwave energy desorption coupled with gas chromatography-flame ionization detection-mass spectrometry. doi
  99. (1997). Method for the collection and assay of volatile organic compounds in breath. Anal Biochem, doi
  100. (2008). Microbial and non Microbial Volatile Fngerprints: Potential Clinical Applications of Electronic Nose for Early Diagnoses and Detection of Disease, in Cranfield Health.
  101. (1993). Microbiological lung surveillance in mechanically ventilated patients, using non-directed bronchial lavage and quantitative culture. doi
  102. (1996). Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit. ICU-Acquired Pneumonia Study Group. Intensive Care Med, doi
  103. (2004). Multidrug-resistant Acinetobacter infections: an emerging challenge to clinicians. Ann Pharmacother, doi
  104. (1985). New methods for the release of volatile sulfur compounds from human serum: its determination by Tenax trapping and gas chromatography and its application in liver diseases. doi
  105. Nitric oxide and the lung. doi
  106. (2003). Nonbronchoscopic evaluation of ventilator-associated pneumonia. Semin Respir Infect, doi
  107. (2000). Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect Control Hosp Epidemiol, doi
  108. (1999). Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med, doi
  109. (1989). Nosocomial pneumonia in patients receiving continuous mechanical ventilation. Prospective analysis of 52 episodes with use of a protected specimen brush and quantitative culture techniques. Am Rev Respir Dis, doi
  110. (2000). Nosocomial pneumonia in patients undergoing heart surgery. Crit Care Med, doi
  111. (1982). Origin of breath acetaldehyde during ethanol oxidation. Effect of long-term cigarette smoking.
  112. Pneumonia due to Haemophilus influenzae among mechanically ventilated patients. Incidence, outcome, and risk factors. doi
  113. (1998). Pneumonia in acute respiratory distress syndrome. A prospective evaluation of bilateral bronchoscopic sampling. Am J Respir Crit Care Med, doi
  114. (1996). Pneumonia in intubated patients: role of respiratory airway care. doi
  115. Pneumonia in the intensive care unit. Crit Care Med, doi
  116. (1996). Pneumonitis-associated hyperprocalcitoninemia. doi
  117. (1998). Postoperative plasma concentrations of procalcitonin after different types of surgery. Intensive Care Med, doi
  118. (1998). Procalcitonin in the early phase after renal transplantation--will it add to diagnostic accuracy? Clin Transplant,
  119. (2005). Procalcitonin kinetics as a prognostic marker of ventilatorassociated pneumonia. doi
  120. (2006). Procalcitonin kinetics in the prognosis of severe community-acquired pneumonia. Intensive Care Med, doi
  121. (2003). Procalcitonin: what should be its role in the clinical management of febrile patients admitted to the hospital? Clin Infect Dis, doi
  122. (1997). Quantitative analysis of ammonia on the breath of patients in end-stage renal failure. Kidney Int, doi
  123. (1971). Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. doi
  124. (1992). Rapid diagnosis of gram negative pneumonia by assay of endotoxin in bronchoalveolar lavage fluid. Thorax, doi
  125. Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in doi
  126. (2001). Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia. doi
  127. (1999). Risk factors for developing pneumonia within 48 hours of intubation. doi
  128. (1992). Risk factors for nosocomial pneumonia in the elderly. doi
  129. (1997). Role of colonization of the upper intestinal tract in the pathogenesis of ventilator-associated pneumonia. Clin Infect Dis, doi
  130. (1981). Role of respiratory assistance devices in endemic nosocomial pneumonia. doi
  131. (2005). Selected ion flow tube mass spectrometry (SIFT-MS) for on-line trace gas analysis. Mass Spectrom Rev, doi
  132. (2005). Serial changes in soluble triggering receptor expressed on myeloid cells in the lung during development of ventilator-associated pneumonia. Intensive Care Med, doi
  133. (2003). Sevoflurane in exhaled air of operating room personnel. Anesth Analg, doi
  134. (1976). Should fiberoptic bronchoscopy aspirates be cultured? Am Rev Respir Dis,
  135. (1997). Solid-phase microextraction for the analysis of human breath. Anal Chem, doi
  136. (2004). Soluble form of the triggering receptor expressed on myeloid cells-1 as a marker of microbial infection. Clin Med Res, doi
  137. (2004). Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. doi
  138. (2001). Staphylococcus aureus in lower respiratory infections: clinical relevance of antimicrobial resistance. Semin Respir Infect, doi
  139. (1996). The accuracy of elevated concentrations of endotoxin in bronchoalveolar lavage fluid for the rapid diagnosis of gram-negative pneumonia. doi
  140. The effect of cephalosporin resistance on mortality in adult patients with nonmeningeal systemic pneumococcal infections. doi
  141. (1986). The extent of metabolism of inhaled anesthetics in humans. Anesthesiology, doi
  142. (1998). The influence of mini-BAL cultures on patient outcomes: implications for the antibiotic management of ventilator-associated pneumonia. doi
  143. (2005). The invasive (quantitative) diagnosis of ventilator-associated pneumonia. Respir Care, doi
  144. The microbiology of ventilator-associated pneumonia. Respir Care, doi
  145. (1987). The pharmacokinetics of pentane, a by-product of lipid peroxidation. Drug Metab Dispos,
  146. (1994). The potential of the hydrocarbon breath test as a measure of lipid peroxidation. Free Radic Biol Med, doi
  147. (1994). The regulation of transaminative flux of methionine in rat liver mitochondria. Arch Biochem Biophys, doi
  148. (1976). The Selected Ion Flow Tube (SIFT) ; A Technique for Studyiny Ion-Neutral reactions. doi
  149. (1992). The standardization of bronchoscopic techniques for ventilator-associated pneumonia. Chest, doi
  150. (2008). The value of pretest probability and modified clinical pulmonary infection score to diagnose ventilator-associated pneumonia. J Crit Care, doi
  151. (2001). TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature, doi
  152. (2002). Use of an electronic nose system for diagnoses of urinary tract infections. Biosens Bioelectron, doi
  153. (2005). Use of an electronic nose to diagnose Mycobacterium bovis infection in badgers and cattle. doi
  154. (1998). Utility of Gram's stain and efficacy of quantitative cultures for posttraumatic pneumonia: a prospective study. Ann Surg, doi
  155. (1999). Variation in volatile organic compounds in the breath of normal humans. doi
  156. (1999). Variations in etiology of ventilator-associated pneumonia across four treatment sites: implications for antimicrobial prescribing practices. Am J Respir Crit Care Med, doi
  157. (2006). Ventilator associated pneumonia and infection control. Ann Clin Microbiol Antimicrob,
  158. (1994). Ventilator-associated pneumonia by Staphylococcus aureus. Comparison of methicillin-resistant and methicillin-sensitive episodes. doi
  159. (1998). Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. doi
  160. (2006). Ventilator-associated pneumonia: diagnosis, treatment, and prevention. Clin Microbiol Rev, doi
  161. (2002). Ventilator-associated pneumonia. doi
  162. (2001). Ventilator-associated pneumonia. European Task Force on ventilator-associated pneumonia. Eur Respir J, doi
  163. Volatile markers of breast cancer in the breath. doi
  164. (2002). Volatile organic compounds as markers in normal and diseased states.,
  165. (1999). Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet, doi
  166. (1985). Volatile organic compounds in exhaled air from patients with lung cancer. Clin Chem,

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