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Sampling and analyzing alveolar exhaled breath condensate in mechanically ventilated patients: a feasibility study
This content has been downloaded from IOPscience. Please scroll down to see the full text. 2015 J. Breath Res. 9 047106 (http://iopscience.iop.org/1752-7163/9/4/047106) View the table of contents for this issue, or go to the journal homepage for more
Download details: IP Address: 144.122.201.150 This content was downloaded on 18/02/2016 at 17:48
Please note that terms and conditions apply.
J. Breath Res. 9 (2015) 047106
doi:10.1088/1752-7155/9/4/047106
paper
received
8 June 2015
Sampling and analyzing alveolar exhaled breath condensate in mechanically ventilated patients: a feasibility study
re vised
29 July 2015
published
Rosanna Vaschetto1,*, Massimo Corradi2,*, Matteo Goldoni2, Laura Cancelliere1, Simone Pulvirenti1, Ugo Fazzini1, Fabio Capuzzi1, Federico Longhini3, Antonio Mutti2, Francesco Della Corte1,4 and Paolo Navalesi3,4,5
18 November 2015
1
accep ted for publication
21 August 2015
‘Maggiore della Carità’ Hospital, Department of Anesthesia and Intensive Care, Corso Mazzini 18, 28100, Novara, Italy Laboratory of Industrial Toxicology, Department of Clinical and Experimental Medicine, University of Parma, via Gramsci 14, I-43126 Parma, Italy 3 Sant’Andrea Hospital, Anesthesia and Intensive Care, Corso Abbiate 21, 13100, Vercelli, Italy 4 Università del Piemonte Orientale ‘Amedeo Avogadro’, Alessandria-Novara-Vercelli, Dipartimento di Medicina Traslazionale, via Solaroli 17, 28100, Novara, Italy 5 CRRF Mons. L. Novarese, Moncrivello, Vercelli, Italy 2
E-mail: [email protected], [email protected], [email protected], [email protected], simo. [email protected], [email protected], [email protected], [email protected], [email protected], [email protected] and [email protected] Keywords: exhaled breath condensate, mechanically ventilated patients, inflammation
Abstract Recent studies in spontaneously breathing subjects indicate the possibility of obtaining the alveolar fraction of exhaled breath condensate (aEBC). In critically ill mechanically ventilated patients, in whom microbial colonization of the upper airways is constant, collection of aEBC could considerably add to the ability of monitoring alveolar inflammation. We designed this study to test the feasibility of collecting aEBC in mechanically ventilated critically ill patients through a dedicated apparatus, i.e. a CO2 valve combined with a condenser placed in the expiratory limb of the ventilator circuit. We also aimed to assess the adequacy of the samples obtained by measuring different markers of oxidative stress and inflammation. We enrolled 40 mechanically ventilated patients, 20 with and 20 without acute respiratory distress syndrome (ARDS). Measurements of respiratory mechanics, gas exchange and hemodynamics were obtained with a standard ventilator circuit after 30 min of aEBC collection and after inserting the dedicated collecting apparatus. Data showed that intrinsic positive end-expiratory pressure, peak and plateau pressure, static compliance and airway resistance (Raw) were similar before and after adding the collecting apparatus in both ARDS and controls. Similarly, gas exchange and hemodynamic variables did not change and 30 min collection provided a median aEBC volume of 2.100 and 2.300 ml for ARDS and controls, respectively. aEBC pH showed a trend toward a slight reduction in the ARDS group of patients, as opposed to controls (7.83 (7.62–8.03) versus 7.98 (7.87– 8.12), respectively, p = 0.055)). H2O2 was higher in patients with ARDS, compared to controls (0.09 (0.06–0.12) μM versus 0.03 (0.01–0.09) μM, p = 0.043), while no difference was found in proteins content, 8-isoprostane, 4-hydroxy-2-nonhenal. In conclusion, we demonstrate, in patients receiving controlled mechanical ventilation, that aEBC collection is feasible without detrimental effects on ventilator functioning, respiratory mechanics and gas exchange. In addition, we show that the sample obtained is appropriate for compounds analysis.
Introduction The analysis of the volatile and non-volatile constituents of exhaled breath condensate (EBC) is a *
Contributed equally.
© 2015 IOP Publishing Ltd
non-invasive method to study oxidant markers [1, 2] and inflammatory mediators [3, 4] in the airway surface liquid. In spontaneously breathing healthy subjects [5] and patients [1, 3, 6], EBC can be collected with no discomfort and without complications. In mechanically ventilated patients with [7–9] and without [10, 11]
J. Breath Res. 9 (2015) 047106
R Vaschetto et al
lung injury, EBC has been obtained by placing homemade [8] or commercially available [7, 9–11] collecting devices in-line with the expiratory limb of the ventilator circuit. Recent studies on spontaneously breathing healthy individuals [12, 13] and patients [14] indicate the possibility of obtaining the alveolar component of the overall EBC, namely alveolar EBC (aEBC). EBC fractionation was first obtained considering that after breathing out, 30% of the tidal volume (VT) of the exhaled air would come from the alveolar compartment (volume threshold) [14]. More recently, aEBC has been collected through a valve designed to fractionate the exhaled air according to the end-tidal carbon dioxide signal [12], identifying a 50% CO2 increase as a safe limit to consider the exhaled air completely alveolar. These studies also showed the concentration of biomarkers in the alveolar fraction to be quite different from the upper/ medium airway fraction [12–14]. So far, all the studies performed on mechanically ventilated patients analyzed the whole (unfractioned) EBC [7–11]. In critically ill mechanically ventilated patients, however, the microbial colonization of the upper airways is constant and tracheobronchitis is common, being definitely more frequent than ventilatorassociated pneumonia [15]. The possibility of separately collecting aEBC would considerably add to the ability of diagnosing and monitoring deep (alveolar) lung inflammation.We therefore modified the device previously utilized to obtain aEBC during spontaneous breathing [12] to sample during mechanical ventilation. Because collecting aEBC implies adding an external valve and circuitry to an expiratory limb, however, dynamic hyperinflation consequent to increased (expiratory) resistance might occur and affect ventilator functioning. In this pilot study we test the feasibility of collecting aEBC in mechanically ventilated critically ill patients through a dedicated apparatus, i.e. a CO2 valve combined with a condenser, sited in the expiratory limb of the circuit of patients with lung injury. We also aim to assess the adequacy of the samples obtained by measuring different markers of oxidative stress and inflammation.
Materials and methods Patients The study was performed at the intensive care unit (ICU) of the University Hospital ‘Maggiore della Carità’ in Novara (Italy), between January 2013 and December 2013, according to the principles outlined in the Declaration of Helsinki. The protocol was approved by the local Ethics Committee, and written informed consent was obtained for all patients according to the Italian regulations. We enrolled 20 consecutive patients with mild to moderate acute respiratory distress syndrome (ARDS) [16], and 20 control patients without ARDS and intubated for neurosurgery with planned postoperative 2
ICU admission. ARDS is characterized by bilateral pulmonary infiltrates and hypoxemia in the absence of evidence for cardiogenic pulmonary edema. Mild ARDS identifies patients with a ratio of partial pressure of oxygen and fraction of inspired oxygen (PaO2/FiO2) between 200 and 300 mmHg, evaluated with a positive end-expiratory pressure (PEEP) or a continuous positive airway pressure (CPAP) value of 5 cmH2O or higher [16]. If PaO2/FiO2 is between 100 and 200 mmHg with PEEP of 5 cmH2O or higher, ARDS is defined as moderate, but is severe with a PaO2/FiO2 below 100 mmHg [16]. Exclusion criteria were: (1) age 5 μg kg−1 min−1; (6) life-threatening arrhythmias or electro-cardiographic signs of ischemia. Predefined criteria for study interruption and resumption of ventilation with the standard circuit of the mechanical ventilator were: (1) hemodynamic instability, i.e. systolic arterial pressure 0.2 μg kg−1 min−1, and dopamine or dobutamine >5 μg kg−1 min−1; (3) life-threatening arrhythmias or electro-cardiographic signs of ischemia; (4) heart rate >120 per minute; (5) oxygen desaturation (SaO2
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Contact us
My IOPscience
Sampling and analyzing alveolar exhaled breath condensate in mechanically ventilated patients: a feasibility study
This content has been downloaded from IOPscience. Please scroll down to see the full text. 2015 J. Breath Res. 9 047106 (http://iopscience.iop.org/1752-7163/9/4/047106) View the table of contents for this issue, or go to the journal homepage for more
Download details: IP Address: 144.122.201.150 This content was downloaded on 18/02/2016 at 17:48
Please note that terms and conditions apply.
J. Breath Res. 9 (2015) 047106
doi:10.1088/1752-7155/9/4/047106
paper
received
8 June 2015
Sampling and analyzing alveolar exhaled breath condensate in mechanically ventilated patients: a feasibility study
re vised
29 July 2015
published
Rosanna Vaschetto1,*, Massimo Corradi2,*, Matteo Goldoni2, Laura Cancelliere1, Simone Pulvirenti1, Ugo Fazzini1, Fabio Capuzzi1, Federico Longhini3, Antonio Mutti2, Francesco Della Corte1,4 and Paolo Navalesi3,4,5
18 November 2015
1
accep ted for publication
21 August 2015
‘Maggiore della Carità’ Hospital, Department of Anesthesia and Intensive Care, Corso Mazzini 18, 28100, Novara, Italy Laboratory of Industrial Toxicology, Department of Clinical and Experimental Medicine, University of Parma, via Gramsci 14, I-43126 Parma, Italy 3 Sant’Andrea Hospital, Anesthesia and Intensive Care, Corso Abbiate 21, 13100, Vercelli, Italy 4 Università del Piemonte Orientale ‘Amedeo Avogadro’, Alessandria-Novara-Vercelli, Dipartimento di Medicina Traslazionale, via Solaroli 17, 28100, Novara, Italy 5 CRRF Mons. L. Novarese, Moncrivello, Vercelli, Italy 2
E-mail: [email protected], [email protected], [email protected], [email protected], simo. [email protected], [email protected], [email protected], [email protected], [email protected], [email protected] and [email protected] Keywords: exhaled breath condensate, mechanically ventilated patients, inflammation
Abstract Recent studies in spontaneously breathing subjects indicate the possibility of obtaining the alveolar fraction of exhaled breath condensate (aEBC). In critically ill mechanically ventilated patients, in whom microbial colonization of the upper airways is constant, collection of aEBC could considerably add to the ability of monitoring alveolar inflammation. We designed this study to test the feasibility of collecting aEBC in mechanically ventilated critically ill patients through a dedicated apparatus, i.e. a CO2 valve combined with a condenser placed in the expiratory limb of the ventilator circuit. We also aimed to assess the adequacy of the samples obtained by measuring different markers of oxidative stress and inflammation. We enrolled 40 mechanically ventilated patients, 20 with and 20 without acute respiratory distress syndrome (ARDS). Measurements of respiratory mechanics, gas exchange and hemodynamics were obtained with a standard ventilator circuit after 30 min of aEBC collection and after inserting the dedicated collecting apparatus. Data showed that intrinsic positive end-expiratory pressure, peak and plateau pressure, static compliance and airway resistance (Raw) were similar before and after adding the collecting apparatus in both ARDS and controls. Similarly, gas exchange and hemodynamic variables did not change and 30 min collection provided a median aEBC volume of 2.100 and 2.300 ml for ARDS and controls, respectively. aEBC pH showed a trend toward a slight reduction in the ARDS group of patients, as opposed to controls (7.83 (7.62–8.03) versus 7.98 (7.87– 8.12), respectively, p = 0.055)). H2O2 was higher in patients with ARDS, compared to controls (0.09 (0.06–0.12) μM versus 0.03 (0.01–0.09) μM, p = 0.043), while no difference was found in proteins content, 8-isoprostane, 4-hydroxy-2-nonhenal. In conclusion, we demonstrate, in patients receiving controlled mechanical ventilation, that aEBC collection is feasible without detrimental effects on ventilator functioning, respiratory mechanics and gas exchange. In addition, we show that the sample obtained is appropriate for compounds analysis.
Introduction The analysis of the volatile and non-volatile constituents of exhaled breath condensate (EBC) is a *
Contributed equally.
© 2015 IOP Publishing Ltd
non-invasive method to study oxidant markers [1, 2] and inflammatory mediators [3, 4] in the airway surface liquid. In spontaneously breathing healthy subjects [5] and patients [1, 3, 6], EBC can be collected with no discomfort and without complications. In mechanically ventilated patients with [7–9] and without [10, 11]
J. Breath Res. 9 (2015) 047106
R Vaschetto et al
lung injury, EBC has been obtained by placing homemade [8] or commercially available [7, 9–11] collecting devices in-line with the expiratory limb of the ventilator circuit. Recent studies on spontaneously breathing healthy individuals [12, 13] and patients [14] indicate the possibility of obtaining the alveolar component of the overall EBC, namely alveolar EBC (aEBC). EBC fractionation was first obtained considering that after breathing out, 30% of the tidal volume (VT) of the exhaled air would come from the alveolar compartment (volume threshold) [14]. More recently, aEBC has been collected through a valve designed to fractionate the exhaled air according to the end-tidal carbon dioxide signal [12], identifying a 50% CO2 increase as a safe limit to consider the exhaled air completely alveolar. These studies also showed the concentration of biomarkers in the alveolar fraction to be quite different from the upper/ medium airway fraction [12–14]. So far, all the studies performed on mechanically ventilated patients analyzed the whole (unfractioned) EBC [7–11]. In critically ill mechanically ventilated patients, however, the microbial colonization of the upper airways is constant and tracheobronchitis is common, being definitely more frequent than ventilatorassociated pneumonia [15]. The possibility of separately collecting aEBC would considerably add to the ability of diagnosing and monitoring deep (alveolar) lung inflammation.We therefore modified the device previously utilized to obtain aEBC during spontaneous breathing [12] to sample during mechanical ventilation. Because collecting aEBC implies adding an external valve and circuitry to an expiratory limb, however, dynamic hyperinflation consequent to increased (expiratory) resistance might occur and affect ventilator functioning. In this pilot study we test the feasibility of collecting aEBC in mechanically ventilated critically ill patients through a dedicated apparatus, i.e. a CO2 valve combined with a condenser, sited in the expiratory limb of the circuit of patients with lung injury. We also aim to assess the adequacy of the samples obtained by measuring different markers of oxidative stress and inflammation.
Materials and methods Patients The study was performed at the intensive care unit (ICU) of the University Hospital ‘Maggiore della Carità’ in Novara (Italy), between January 2013 and December 2013, according to the principles outlined in the Declaration of Helsinki. The protocol was approved by the local Ethics Committee, and written informed consent was obtained for all patients according to the Italian regulations. We enrolled 20 consecutive patients with mild to moderate acute respiratory distress syndrome (ARDS) [16], and 20 control patients without ARDS and intubated for neurosurgery with planned postoperative 2
ICU admission. ARDS is characterized by bilateral pulmonary infiltrates and hypoxemia in the absence of evidence for cardiogenic pulmonary edema. Mild ARDS identifies patients with a ratio of partial pressure of oxygen and fraction of inspired oxygen (PaO2/FiO2) between 200 and 300 mmHg, evaluated with a positive end-expiratory pressure (PEEP) or a continuous positive airway pressure (CPAP) value of 5 cmH2O or higher [16]. If PaO2/FiO2 is between 100 and 200 mmHg with PEEP of 5 cmH2O or higher, ARDS is defined as moderate, but is severe with a PaO2/FiO2 below 100 mmHg [16]. Exclusion criteria were: (1) age 5 μg kg−1 min−1; (6) life-threatening arrhythmias or electro-cardiographic signs of ischemia. Predefined criteria for study interruption and resumption of ventilation with the standard circuit of the mechanical ventilator were: (1) hemodynamic instability, i.e. systolic arterial pressure 0.2 μg kg−1 min−1, and dopamine or dobutamine >5 μg kg−1 min−1; (3) life-threatening arrhythmias or electro-cardiographic signs of ischemia; (4) heart rate >120 per minute; (5) oxygen desaturation (SaO2
