Rapid breath analysis for acute respiratory distress syndrome diagnostics using a portable two-dimensional gas chromatography device

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Abstract

Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung injury, responsible for high mortality and long-term morbidity. As a dynamic syndrome with multiple etiologies its timely diagnosis is difficult as is tracking the course of the syndrome. Therefore, there is a significant need for early, rapid detection and diagnosis as well as clinical trajectory monitoring of ARDS. Here we report our work on using human breath to differentiate ARDS and non-ARDS causes of respiratory failure. A fully automated portable 2-dimensional gas chromatography device with high peak capacity (>200 at the resolution of 1), high sensitivity (sub-ppb), and rapid analysis capability (~30 minutes) was designed and made in-house for on-site analysis of patients’ breath. A total of 85 breath samples from 48 ARDS patients and controls were collected. Ninety-seven elution peaks were separated and detected in 13 minutes. An algorithm based on machine learning, principal component analysis (PCA), and linear discriminant analysis (LDA) was developed. As compared to the adjudications done by physicians based on the Berlin criteria, our device and algorithm achieved an overall accuracy of 87.1% with 94.1% positive predictive value and 82.4% negative predictive value. The high overall accuracy and high positive predicative value suggest that the breath analysis method can accurately diagnose ARDS. The ability to continuously and non-invasively monitor exhaled breath for early diagnosis, disease trajectory tracking, and outcome prediction monitoring of ARDS may have a significant impact on changing practice and improving patient outcomes.

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Diagnostic potential of breath analysis--focus on volatile organic compounds.

Wolfram Miekisch, Jochen K. Schubert, Gabriele Noeldge-Schomburg (2004)

Breath analysis has attracted a considerable amount of scientific and clinical interest during the last decade. In contrast to NO, which is predominantly generated in the bronchial system, volatile organic compounds (VOCs) are mainly blood borne and therefore enable monitoring of different processes in the body. Exhaled ethane and pentane concentrations were elevated in inflammatory diseases. Acetone was linked to dextrose metabolism and lipolysis. Exhaled isoprene concentrations showed correlations with cholesterol biosynthesis. Exhaled levels of sulphur-containing compounds were elevated in liver failure and allograft rejection. Looking at a set of volatile markers may enable recognition and diagnosis of complex diseases such as lung or breast cancer. Due to technical problems of sampling and analysis and a lack of normalization and standardization, huge variations exist between results of different studies. This is among the main reasons why breath analysis could not yet been introduced into clinical practice. This review addresses the basic principles of breath analysis and the diagnostic potential of different volatile breath markers. Analytical procedures, issues concerning biochemistry and exhalation mechanisms of volatile substances, and future developments will be discussed.

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Daily cost of an intensive care unit day: the contribution of mechanical ventilation.

Joseph Dasta, Trent McLaughlin, Samir Mody … (2005)

To quantify the mean daily cost of intensive care, identify key factors associated with increased cost, and determine the incremental cost of mechanical ventilation during a day in the intensive care unit. Retrospective cohort analysis using data from NDCHealth's Hospital Patient Level Database. A total of 253 geographically diverse U.S. hospitals. The study included 51,009 patients >/=18 yrs of age admitted to an intensive care unit between October 1, 2002, and December 31, 2002. None. Days of intensive care and mechanical ventilation were identified using billing data, and daily costs were calculated as the sum of daily charges multiplied by hospital-specific cost-to-charge ratios. Cost data are presented as mean (+/-sd). Incremental daily cost of mechanical ventilation was calculated using log-linear regression, adjusting for patient and hospital characteristics. Approximately 36% of identified patients were mechanically ventilated at some point during their intensive care unit stay. Mechanically ventilated patients were older (63.5 yrs vs. 61.7 yrs, p < .0001) and more likely to be male (56.1% vs. 51.8%, p < 0.0001), compared with patients who were not mechanically ventilated, and required mechanical ventilation for a mean duration of 5.6 days +/- 9.6. Mean intensive care unit cost and length of stay were 31,574 +/- 42,570 dollars and 14.4 days +/- 15.8 for patients requiring mechanical ventilation and 12,931 +/- 20,569 dollars and 8.5 days +/- 10.5 for those not requiring mechanical ventilation. Daily costs were greatest on intensive care unit day 1 (mechanical ventilation, 10,794 dollars; no mechanical ventilation, 6,667 dollars), decreased on day 2 (mechanical ventilation:, 4,796 dollars; no mechanical ventilation, 3,496 dollars), and became stable after day 3 (mechanical ventilation, 3,968 dollars; no mechanical ventilation, 3,184 dollars). Adjusting for patient and hospital characteristics, the mean incremental cost of mechanical ventilation in intensive care unit patients was 1,522 dollars per day (p < .001). Intensive care unit costs are highest during the first 2 days of admission, stabilizing at a lower level thereafter. Mechanical ventilation is associated with significantly higher daily costs for patients receiving treatment in the intensive care unit throughout their entire intensive care unit stay. Interventions that result in reduced intensive care unit length of stay and/or duration of mechanical ventilation could lead to substantial reductions in total inpatient cost.

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Clinical risks for development of the acute respiratory distress syndrome.

L D Hudson, J Milberg, D Anardi … (1995)

To further understanding of the epidemiology of acute respiratory distress syndrome (ARDS), we prospectively identified 695 patients admitted to our intensive care units from 1983 through 1985 meeting criteria for seven clinical risks, and followed them for development of ARDS and eventual outcome. ARDS occurred in 179 of the 695 patients (26%). The highest incidence of ARDS occurred in patients with sepsis syndrome (75 of 176; 43%) and those with multiple emergency transfusions (> or = 15 units in 24 h) (46 of 115; 40%). Of patients with multiple trauma, 69 of 271 (25%) developed ARDS. If any two clinical risks for trauma were present, the incidence of ARDS was 23 of 57, or 40%. During the study period, we identified 48 patients with ARDS who did not have one of the defined clinical risks, yielding a sensitivity of 79% (179 of 227). Secondary factors associated with increased risk for ARDS in clinical risk subgroups include an elevated Acute Physiologic and Chronic Health Evaluation II (APACHE II) score in patients with sepsis and increased APACHE II and Injury Severity Scores (ISS) in trauma victims. Mortality was threefold higher when ARDS was present (62%) than among patients with clinical risks who did not develop ARDS (19%; p < 0.05). The difference in mortality if ARDS developed was particularly striking in patients with trauma (56% versus 13%), but less in those with sepsis (69% versus 49%). The mortality data should be interpreted with caution, since the fatality rate in ARDS patients appears to have decreased in our institution from the time that these data were collected.(ABSTRACT TRUNCATED AT 250 WORDS)