help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on October 9, 2003, doi:10.1164/rccm.200307-1005OC
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200307-1005OCv1
169/1/64    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moloney, E. D.
Right arrow Articles by Griffiths, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moloney, E. D.
Right arrow Articles by Griffiths, M. J.
American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 64-69, (2004)
© 2004 American Thoracic Society

Exhaled Breath Condensate Detects Markers of Pulmonary Inflammation after Cardiothoracic Surgery

Edward D. Moloney, Sharon E. Mumby, Reka Gajdocsi, Julius H. Cranshaw, Sergei A. Kharitonov, Gregory J. Quinlan and Mark J. Griffiths

Unit of Critical Care and Thoracic Medicine, Imperial College London at the National Heart and Lung Institute, Royal Brompton Hospital, London, United Kingdom

Correspondence and requests for reprints should be addressed to Dr. Mark Griffiths, Ph.D., M.R.C.P., Adult Intensive Care Unit, Royal Brompton Hospital, Sydney Street, London SW3 6NP UK. E-mail: m.griffiths{at}imperial.ac.uk


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Cardiac surgery using cardiopulmonary by-pass and, to a greater extent, lung resection, causes acute lung injury that is usually subclinical. Analysis of mediators in exhaled breath condensate is a promising means of monitoring inflammation in a variety of airway diseases but the contribution of the airway lining fluid from the lower respiratory tract is uncertain. We compared the analysis of markers of lung injury in exhaled breath condensate and bronchoalveolar lavage in endotracheally intubated patients before and after coronary artery bypass graft surgery with cardiopulmonary bypass and lobectomy. The neutrophil count and leukotriene B4 concentration in bronchoalveolar lavage fluid rose after coronary artery bypass graft surgery (p < 0.05), but there was no significant change in leukotriene B4, hydrogen peroxide, or hydrogen ion concentrations in exhaled breath condensate. By contrast, after lobectomy, the concentration in exhaled breath condensate of leukotriene B4, hydrogen peroxide and hydrogen ions rose significantly (p < 0.05). Exhaled breath condensate is a safe, noninvasive method of sampling the milieu of the distal lung and is sufficiently sensitive to detect markers of inflammation and oxidative stress in patients after lobectomy, but not after the milder insult associated with cardiac surgery.

Key Words: exhaled breath condensate • bronchoalveolar lavage • cardiothoracic surgery • acute lung injury

Patients undergoing cardiothoracic surgery rarely develop acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome (ARDS) (1), but this complication is associated with a high mortality. The incidence of ARDS after cardiac surgery involving cardiopulmonary bypass is 0.4–1.3%, with an associated mortality of 15–68.4% (2–5). By comparison, ALI or ARDS occurs after 2.2–5.2% of lobectomies (6–8), and was thought to have contributed to more than 70% of postoperative deaths (7). In the absence of clinically significant ALI, lung inflammation and dysfunction are detectable after uncomplicated cardiac surgery (9).

Inflammation associated with cardiac surgery is produced by complex humoral and cellular interactions (10). We have previously reported that the bronchoalveolar lavage (BAL) fluid of patients after cardiopulmonary bypass contains a significantly higher proportion of neutrophils than a sample taken preoperatively (11). Similarly, lung resection and one-lung ventilation are associated with ischemia reperfusion injury and neutrophil recruitment and activation (12). Leukotriene (LT) B4 promotes neutrophil recruitment and release of lysosomal enzymes and reactive oxygen species (13, 14). Neutrophilic inflammation affects the gas exchange surface of the lung in patients with ALI, producing superoxide and hydrogen peroxide that react with biological molecules including membrane lipids (15). For example, isoprostanes, formed by nonenzymatic oxidation of arachidonic acid residues, are detected in the exhaled breath condensate (EBC) of patients with ARDS (16). Similarly, neutrophilic airway inflammation is associated with acidification of EBC in patients with chronic obstructive pulmonary disease (COPD) (17), bronchiectasis (17), acute asthma (18), and cystic fibrosis exacerbations (19).

BAL is the gold standard means of sampling the milieu of the distal lung, despite its occasional complications (20–22). EBC collection is a noninvasive technique for sampling airway-lining fluid, containing both volatile and nonvolatile compounds, that evaporates or becomes aerosolized during turbulent airflow (23–25). Unlike BAL, EBC can be collected safely in the same patient repeatedly and in patients with critical respiratory failure.

We hypothesized that analyzing EBC would be as sensitive a method as analyzing BAL in detecting markers of lung inflammation. Therefore, we collected BAL and EBC in ventilated subjects before and after coronary artery bypass graft (CABG) surgery, and we examined EBC before and after the greater injury associated with lobectomy. By investigating patients ventilated through endotracheal tubes suffering mild ALI, we were able to exclude the upper airway as a source of EBC contamination and to test the sensitivity of analyzing EBC compared with that of analyzing BAL in detecting inflammatory markers from the lower respiratory tract. Some of the results of these studies have been reported as abstracts (26).


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
Twenty-six patients (21 males; median age [range], 64 [56–72] years) undergoing CABG surgery and 19 patients (9 males; median age [range] 62 [57–69] years) undergoing lobectomy for cancer participated in the study (characteristics of the study population are summarized in Table E1 in the online supplement). Prior to surgery, all patients gave informed consent for the investigation, the protocol for which was approved by the ethics committee of the Royal Brompton and Harefield Hospitals NHS Trust. Hydrogen peroxide, pH, LTB4, and myeloperoxidase were all measured in EBC collected from the same patients. 8-Isoprostane was measured in BAL and EBC samples taken from a different patient group.

CABG Surgery
All operations were performed through a median sternotomy on cardiopulmonary bypass using a membrane oxygenator (D903 Avant; Dideco, Gloucester, UK). After heparinization (300 units/kg), cardiopulmonary bypass commenced with a flow rate of 2.4 L/minute/m2 at 37°C, and patients were cooled to 32°C. The lungs remained at functional residual capacity during cardiopulmonary bypass. After rewarming, mechanical ventilation was recommenced and heparinization reversed with protamine (4.5 mg/kg).

Lobectomy
After induction of anesthesia, patients underwent rigid bronchoscopy and a double lumen endotracheal tube was sited. To facilitate resection, the lung was deflated and the contralateral lung ventilated. Postoperatively, the endotracheal tube was removed either in the operating room or after transfer to the recovery unit.

Exhaled Breath Condensate Collection
EBC was collected from intubated patients before and 30 minutes after surgery. The fraction of inspired oxygen was 0.4–0.5 and the tidal volume was standardized at 10 ml/kg during EBC collection. Humidification, in the form of a heat and moisture exchanger (Hydro-Therm HME; Intersurgical Ltd., Berkshire, UK) was disconnected from the ventilator tubing a minute before EBC collection was started. Exhaled breath flowed through a one-way valve into the polypropylene collection tube that was cooled by a surrounding aluminium sleeve at -20°C. (RTube; Respiratory Research Inc., Charlottesville, VA; Figure 1) . Preliminary experiments were performed collecting EBC from ventilated patients, the results of which suggested that the yield of EBC (1–2 ml) did not increase substantially and reliably after 15 minutes. The antioxidant, butylated hydroxytoluene (20 µM final concentration; BDH Chemicals Ltd., Poole, UK) was added and the aliquoted samples stored at -70°C.



View larger version (20K):
[in this window]
[in a new window]
  		Figure 1. Diagram representing the collection of exhaled breath condensate in a patient being mechanically ventilated through an endotracheal tube. Filled arrows demonstrate the direction of gas flow.

 
BAL Fluid Collection
BAL was performed, after EBC collection, using buffered normal saline (3 aliquots of 60 ml), in different segments of the right middle lobe before and after cardiac surgery. The fluid was centrifuged (300 g, for 10 min at 4°C), butylated hydroxytoluene (20 µM final concentration) was added, and aliquots stored at -70°C. Cytocentrifuge slide preparations were made (Shandon Cytospin 2; Thermo Electron Corp., Runcorn, UK), stained with May-Grunwald-Giemsa and differential cell counts performed on at least 300 cells in random fields.

pH Measurement
pH measurements (Jenway 350 pH meter; Spectronic Instruments, Leeds, UK) were performed immediately after collection of EBC (0.5 ml), after deaeration with argon (350 ml/minute for 10 minutes [18]).

Hydrogen Peroxide Analysis
Hydrogen peroxide was measured in EBC (0.5 ml) using a colorimetric method previously described (27). Values in EBC were calculated from a standard curve prepared from stock standardized hydrogen peroxide solution (Sigma, Poole, UK).

Leukotriene B4 and Myeloperoxidase Assays
Specific enzyme immunoassays for LTB4 (Cayman Chemical, Ann Arbor, MI) and myeloperoxidase (Calbiochem-Novabiochem Co., San Diego, CA) were performed on EBC (0.1 ml). The intraassay and interassay variabilities were less than 10%. The detection limit of the assays was 7.8 pg/ml for LTB4 and 1.5 ng/ml for myeloperoxidase.

8-Isoprostane Measurement by Mass Spectrometry
8-Isoprostane was measured in EBC and BAL (1 ml aliquots) by gas chromatography negative ion chemical ionization mass spectrometry, as previously described (28). 8-Isoprostane was purified using affinity columns containing anti–8-isoprostane antibodies (Cayman Chemical Co.). Samples were dried in a centrifuge under vacuum at room temperature for 8–12 hours (Speed Vac Concentrator; ThermoSavant, Holbrook, NY) and derivatized in a two-stage process to pentafluorobenzyl ester trimethysilyl ethers. Analysis was performed on a Hewlett-Packard 5890 Series II gas chromatograph (Hewlett-Packard, Bracknell, UK) linked to a Trio 1000 (DSR, Warrington, UK) mass spectrometer with chemical ionisation capability. Quantification of the characteristic m/z -569 ion was performed with reference to a standard curve of authentic 8-isoprostane over the range of 0–200 pg/ml. Authenticity was confirmed by retention time and by spiking samples with the authentic compound.

Statistical Analysis
Data were analyzed using GraphPad Prism version 3.00 (GraphPad Software, San Diego, CA). Data were not normally distributed (as assessed by the Kolmogorov-Smirnov test) and groups were compared using the Mann-Whitney test. Correlation coefficients were determined using Spearman's rank correlation test. All data are expressed as median and interquartile range. Significance was defined as a p value less than 0.05.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
None of the patients in this study satisfied the criteria for ALI/ARDS (1) or required mechanical ventilation for more than 24 hours after surgery. Neither BAL nor EBC collection was associated with adverse effects.

Markers of Lung Inflammation after CABG Surgery are Detectable in BAL Fluid but not in Exhaled Breath Condensate
The neutrophil differential count in BAL fluid rose significantly from 6 (4–10)% preoperatively to 24 (14–31)% (n = 26; p < 0.0001; Figure 2A) after cardiac surgery. The median bypass and cross-clamp times were 92 (78–115) and 52 (40–57) minutes, respectively. There was no correlation between the change in neutrophil count and either the bypass time or cross-clamp time (data not shown). The LTB4 concentration in BAL rose significantly from 25 (15–37) pg/ml pre- to 41 (25–80) pg/ml postoperatively (n = 26; p = 0.003; Figure 2C). After correcting for the protein concentration, the LTB4 concentration in BAL still rose significantly, from 0.17 (0.09–0.33) pg/µg protein pre- to 0.45 (0.17–0.58) pg/µg protein postoperatively (p = 0.03). A positive correlation was observed between the change in BAL neutrophil differential count and the change in LTB4 concentration in BAL after surgery (n = 26; r = 0.54, p = 0.005; Figure 2B), consistent with a role for LTB4 in neutrophil recruitment (13). However, analyzing EBC samples pre- and postoperatively revealed no significant change in LTB4 (Figure 2D), hydrogen peroxide (Figure 3A) , or pH (Figure 3B). The 8-isoprostane concentrations in BAL and EBC (Figures 3C and 3D) did not change after cardiac surgery.



View larger version (19K):
[in this window]
[in a new window]
  		Figure 2. (A) Change in the percent neutrophil count in bronchoalveolar lavage (BAL) fluid after coronary artery bypass graft (CABG) surgery (n = 26, ***p < 0.0001); data show the individual values and median (bar). (B) Relationship between the change in the neutrophil count and change in leukotriene (LT) B4 concentration in BAL. Each point represents the data from individual samples. Correlations were conducted with the Spearman's rank correlation test (n = 26, r = 0.54, p = 0.005). (C) Change in BAL LTB4 concentration after CABG surgery (n = 26, **p = 0.003); data show the individual values and median (bar). (D) Change in exhaled breath condensate (EBC) LTB4 concentration after CABG surgery (n = 26, p = 0.9); data show the individual values and median (bar).

 


View larger version (17K):
[in this window]
[in a new window]
  		Figure 3. (A) Change in exhaled breath condensate (EBC) hydrogen peroxide (H2O2) concentration after CABG surgery (n = 26, p = 0.3). (B) Change in EBC pH measurement after CABG surgery (n = 26, p = 0.1). (C) Change in bronchoalveolar lavage (BAL) 8-isoprostane concentration after CABG surgery (n = 8, p = 0.8). (D) Change in EBC 8-isoprostane concentration after CABG surgery (n = 8, p = 0.82); data show the individual values and median (bar).

 
Markers of Lung Inflammation after Lobectomy are Detectable in Exhaled Breath Condensate
The duration of one-lung ventilation was 146 (121–188) minutes, but this did not correlate with the change in markers of lung inflammation in EBC. The LTB4 concentration in EBC rose after lobectomy from 4 (2–11) pg/ml pre- to 23 (5–64) pg/ml postoperatively (n = 19; p = 0.003; Figure 4A) . Similarly, the hydrogen peroxide concentration in EBC rose from 0.2 (0.03–0.5) µM pre- to 0.8 (0.15–1.9) µM postoperatively (n = 19; p = 0.03; Figure 4B). The EBC pH fell significantly from 6 (5.7–6.4) pre- to 5.5 (5.3–6) postoperatively (n = 19; p = 0.02; Figure 4C). However, there was no difference in EBC 8-isoprostane measured as 11 (7–25) pg/ml pre- and 10 (7–13) pg/ml postoperatively (n = 19; p = 0.45; Figure 4D). Myeloperoxidase was undetectable in EBC preoperatively, and was only detected in 5 of 19 patients postoperatively (1.7 [0.7–5.3] ng/ml.



View larger version (16K):
[in this window]
[in a new window]
  		Figure 4. (A) Change in exhaled breath condensate (EBC) LTB4 concentration after lobectomy (n = 19, **p = 0.003). (B) Change in EBC H2O2 concentration after lobectomy (n = 19, *p = 0.03). (C) Change in EBC pH measurement after lobectomy (n = 15, *p = 0.02). (D) Change in EBC 8-isoprostane concentration after lobectomy (n = 8, p = 0.46); data show the individual values and median (bar).

 
Comparing Markers of Lung Inflammation in the Exhaled Breath Condensate from Patients Undergoing Lobectomy and CABG Surgery
Comparing lobectomy and cardiac surgery groups, there was no difference in preoperative EBC hydrogen peroxide concentration (p = 0.32) and pH (p = 0.92), but lower preoperative EBC LTB4 concentrations were measured in patients undergoing lobectomy (p = 0.04). There was no difference between the groups in postoperative EBC LTB4 concentration (p = 0.14) or pH (p = 0.19). However, greater postoperative EBC hydrogen peroxide concentrations were measured in patients undergoing lobectomy than in those undergoing cardiac surgery (p = 0.008). 8-Isoprostane levels were similar in both groups pre- and postoperatively.


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
This study demonstrates that EBC may be safely collected from patients who are mechanically ventilated through an endotracheal tube, and that analysis of EBC permits detection of inflammatory markers, even when the lung inflammation has no clinical effect. Neutrophilic inflammation after CABG surgery was confirmed by a significant elevation of neutrophil count and LTB4 in BAL fluid, and by the close correlation between changes in these parameters in individual subjects. This was not reflected in significant changes in indices of inflammation (LTB4 and pH) or oxidative stress (hydrogen peroxide and 8-isoprostane) in EBC that was collected simultaneously. However, after lobectomy, inflammatory markers were elevated in EBC using the same indices and time points. The most obvious explanation for this discrepancy is that the insult associated with cardiac surgery is less than that associated with lobectomy, as supported by the higher incidence of ALI after the latter (2–8). Conceivably, the nature of inflammation after cardiac surgery may differ from that associated with lobectomy. However, neutrophil activation and oxidative damage have been implicated in the pathogenesis of lung and other organ injury after both cardiopulmonary bypass (29, 30) and lobectomy (31). Finally, the time course of lung inflammation after cardiac surgery and lobectomy may differ, leading to a false negative result. We attempted to control for this result by measuring LTB4 in BAL and EBC simultaneously before and after CABG. Our data demonstrate similar levels of LTB4 in EBC postoperatively in CABG and lobectomy groups, but the level measured preoperatively was significantly and surprisingly higher in the patients undergoing CABG, despite a greater number of lobectomy patients being current smokers (see Table E1). LTB4 levels measured in EBC from normal subjects in five studies have reported levels of approximately 6–63 pg/ml (32–36). One relevant difference between the groups is that all of the patients who a CABG took aspirin, which was stopped between a week and 48 hours preoperatively.

Our investigation was inevitably constrained by clinical priorities. For example, we were unable to perform BAL in patients undergoing lobectomy, as the double-lumen endotracheal tube was too small to accommodate the "adult" bronchoscope, so that changing endotracheal tubes both pre- and postoperatively would have been required. Similarly, the timing of the postoperative collection of BAL and EBC was determined by the duration of the operation and the need to wake and wean the patient. Measurement of markers in BAL and EBC is potentially subject to a dilution artifact. However, we found that the change in LTB4 concentrations in BAL postoperatively remained significant after correcting for BAL protein concentration. Presently, the absence of an accepted dilution marker in EBC and the relatively low volume that is collected make attempts to adjust for a dilution factor impractical.

Markers of inflammation have been detected in EBC collected from patients with a variety of airway diseases, including: 8-isoprostane (36), cysteinyl leukotrienes (37) and hydrogen peroxide (38) in asthma; LTB4 and 8-isoprostane in COPD (34); LTB4, interleukin 6 (39), and 8-isoprostane (40) in cystic fibrosis; and hydrogen peroxide in bronchiectasis (41). Acidification of EBC is associated with exacerbations of asthma (18), COPD (17), bronchiectasis (17), and cystic fibrosis (19), and the pH returned to control values with treatment, suggesting that it may be a useful marker of airway inflammation. Salivary contamination may affect the reliability of EBC pH readings, but our findings in patients with endotracheal tubes suggest that acidification of EBC is a genuine marker of inflammation that may have relevance to the distal lung as well as the airways. This contention is supported by the detection in EBC, of markers of oxidative stress from ventilated patients with ARDS (15, 16), and of proteins specifically produced by alveolar epithelial cells in healthy volunteers (42).

Oxidative stress associated with cardiothoracic surgery is contributed to by ischemia–reperfusion injury (43) and the respiratory burst of activated neutrophils (44). Although we demonstrated neutrophil recruitment by BAL after cardiac surgery, the protein marker of leukocyte activation, myeloperoxidase, was detected postoperatively in only 5 of 19 subjects. It is likely that the moderate inflammatory stimulus associated with lobectomy and the low levels of protein in EBC (42) are at the limits of detection for this assay. However, measurement of myeloperoxidase activity in EBC of patients with severe pulmonary inflammation, such as ARDS, may be a useful means of monitoring neutrophil activation and the response to treatment (45). We found no change in 8-isoprostane, a specific marker of oxidative stress (46), after cardiac surgery or lobectomy, but the measured levels were in a similar range. This result may reflect the time of sample collection (30 minutes postoperatively). Isoprostanes are formed in situ by free radical–initiated peroxidation of arachidonic acid within a lipid membrane, and subsequently released by phospholipases (46). Only free isoprostanes are detected by the method used in these studies; by contrast, hydrogen peroxide is simultaneously formed and released, and is thus accessible for immediate measurement.

We conclude that EBC is a safe, noninvasive method of sampling the milieu of the distal lung and is sufficiently sensitive to detect markers of inflammation and oxidative stress after an insult that did not cause clinical lung injury. EBC has the potential to compliment BAL in investigation of the lower respiratory tract.


   Acknowledgments
 
E.D.M. has no declared conflict of interest; S.E.M. has no declared conflict of interest; R.G. received a grant of £700 from Jaeger (makers of equipment to collect exhaled breath condensate not used in the study); J.H.C. has no declared conflict of interest; S.A.K. has no declared conflict of interest; G.J.Q. has no declared conflict of interest; M.J.G. has no declared conflict of interest.


   FOOTNOTES
 
Supported by the European Respiratory Society, Intensive Care Society, Hospital Infection Society, Mason's Medical Research Foundation, and Peel Medical Research Trust.

This article has an online supplement, which is accessible from this issue's table of contents online at www.atsjournals.org

Received in original form July 22, 2003; accepted in final form October 8, 2003


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149:818–824.
  2. Messent M, Sullivan K, Keogh BF, Morgan CJ, Evans TW. Adult respiratory distress syndrome following cardiopulmonary bypass: incidence and prediction. Anaesthesia 1992;47:267–268.[Medline]
  3. Christenson JT, Aeberhard JM, Badel P, Pepcak F, Maurice J, Simonet F, Velebit V, Schmuziger M. Adult respiratory distress syndrome after cardiac surgery. Cardiovasc Surg 1996;4:15–21.[CrossRef][Medline]
  4. Asimakopoulos G, Taylor KM, Smith PL, Ratnatunga CP. Prevalence of acute respiratory distress syndrome after cardiac surgery. J Thorac Cardiovasc Surg 1999;117:620–621.[Free Full Text]
  5. Milot J, Perron J, Lacasse Y, Letourneau L, Cartier PC, Maltais F. Incidence and predictors of ARDS after cardiac surgery. Chest 2001;119:884–888.[Abstract/Free Full Text]
  6. Hayes JP, Williams EA, Goldstraw P, Evans TW. Lung injury in patients following thoracotomy. Thorax 1995;50:990–991.[Abstract]
  7. Kutlu CA, Williams EA, Evans TW, Pastorino U, Goldstraw P. Acute lung injury and acute respiratory distress syndrome after pulmonary resection. Ann Thorac Surg 2000;69:376–380.[Abstract/Free Full Text]
  8. Ruffini E, Parola A, Papalia E, Filosso PL, Mancuso M, Oliaro A, Actis-Dato G, Maggi G. Frequency and mortality of acute lung injury and acute respiratory distress syndrome after pulmonary resection for bronchogenic carcinoma. Eur J Cardiothorac Surg 2001;20:30–36.[Abstract/Free Full Text]
  9. Macnaughton PD, Braude S, Hunter DN, Denison DM, Evans TW. Changes in lung function and pulmonary capillary permeability after cardiopulmonary bypass. Crit Care Med 1992;20:1289–1294.[Medline]
  10. Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 2003;75:S715–S720.[Abstract/Free Full Text]
  11. Sinclair DG, Haslam PL, Quinlan GJ, Pepper JR, Evans TW. The effect of cardiopulmonary bypass on intestinal and pulmonary endothelial permeability. Chest 1995;108:718–724.[Abstract/Free Full Text]
  12. Jordan S, Mitchell JA, Quinlan GJ, Goldstraw P, Evans TW. The pathogenesis of lung injury following pulmonary resection. Eur Respir J 2000;15:790–799.[Abstract]
  13. Martin TR, Pistorese BP, Chi EY, Goodman RB, Matthay MA. Effects of leukotriene B4 in the human lung: recruitment of neutrophils into the alveolar spaces without a change in protein permeability. J Clin Invest 1989;84:1609–1619.
  14. Busse WW. Leukotrienes and inflammation. Am J Respir Crit Care Med 1998;157:S210–S213.[Medline]
  15. Baldwin SR, Simon RH, Grum CM, Ketai LH, Boxer LA, Devall LJ. Oxidant activity in expired breath of patients with adult respiratory distress syndrome. Lancet 1986;1:11–14.[Medline]
  16. Carpenter CT, Price PV, Christman BW. Exhaled breath condensate isoprostanes are elevated in patients with acute lung injury or ARDS. Chest 1998;114:1653–1659.[Abstract/Free Full Text]
  17. Kostikas K, Papatheodorou G, Ganas K. pH in expired breath condensate of patients with inflammatory airway diseases. Am J Respir Crit Care Med 2002;165:1364–1370.[Abstract/Free Full Text]
  18. Hunt JF, Fang K, Malik R, Snyder A, Malhotra N, Platts-Mills TA, Gaston B. Endogenous airway acidification: implications for asthma pathophysiology. Am J Respir Crit Care Med 2000;161:694–699.[Abstract/Free Full Text]
  19. Tate S, MacGregor G, Davis M, Innes JA, Greening AP. Airways in cystic fibrosis are acidified: detection by exhaled breath condensate. Thorax 2002;57:926–929.[Abstract/Free Full Text]
  20. Credle WF Jr, Smiddy JF, Elliott RC. Complications of fiberoptic bronchoscopy. Am Rev Respir Dis 1974;109:67–72.[Medline]
  21. Suratt PM, Smiddy JF, Gruber B. Deaths and complications associated with fiberoptic bronchoscopy. Chest 1976;69:747–751.[Abstract/Free Full Text]
  22. Simpson FG, Arnold AG, Purvis A, Belfield PW, Muers MF, Cooke NJ. Postal survey of bronchoscopic practice by physicians in the UK. Thorax 1986;41:311–317.[Abstract]
  23. Scheideler L, Manke HG, Schwulera U, Inacker O, Hammerle H. Detection of nonvolatile macromolecules in breath: a possible diagnostic tool? Am Rev Respir Dis 1993;148:778–784.[Medline]
  24. Kharitonov SA, Barnes PJ. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med 2001;163:1693–1722.[Free Full Text]
  25. Mutlu GM, Garey KW, Robbins RA, Danziger LH, Rubinstein I. Collection and analysis of exhaled breath condensate in humans. Am J Respir Crit Care Med 2001;164:731–737.[Free Full Text]
  26. Moloney ED, Gajdocsi R, Kharitonov S, Cranshaw J, Quinlan GJ, Griffiths MJD. Cardiopulmonary bypass (CPB) induced lung inflammation is detectable in bronchoalveolar lavage fluid but not by exhaled breath condensate (EBC). Am J Respir Crit Care Med 2003;167:A911.
  27. Pick E, Keisari Y. A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture. J Immunol Methods 1980;38:161–170.[CrossRef][Medline]
  28. Roberts LJ, Moore KP, Zackert WE, Oates JA, Morrow JD. Identification of the major urinary metabolite of the F2-isoprostane 8-iso-prostaglandin F2alpha in humans. J Biol Chem 1996;271:20617–20620.[Abstract/Free Full Text]
  29. Hachida M, Hanayama N, Okamura T, Akasawa T, Maeda T, Bonkohara Y, Endo M, Hashimoto A, Koyanagi H. The role of leukocyte depletion in reducing injury to myocardium and lung during cardiopulmonary bypass. ASAIO J 1995;41:M291–M294.[Medline]
  30. Royston D, Fleming JS, Desai B, Westaby S, Taylor KM. Increased production of peroxidation products associated with cardiac operations. Evidence for free radical generation. J Thorac Cardiovasc Surg 1986(May);91:759–766.
  31. Williams EA, Quinlan GJ, Goldstraw P, Gothard JW, Evans TW. Postoperative lung injury and oxidative damage in patients undergoing pulmonary resection. Eur Respir J 1998;11:1028–1034.[Abstract]
  32. Hanazawa T, Kharitonov SA, Barnes PJ. Increased nitrotyrosine in exhaled breath condensate of patients with asthma. Am J Respir Crit Care Med 2000;162:1273–1276.[Abstract/Free Full Text]
  33. Csoma Z, Kharitonov SA, Balint B, Bush A, Wilson NM, Barnes PJ. Increased leukotrienes in exhaled breath condensate in childhood asthma. Am J Respir Crit Care Med 2002;166:1345–1349.[Abstract/Free Full Text]
  34. Biernacki WA, Kharitonov SA, Barnes PJ. Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD. Thorax 2003;58:294–298.[Abstract/Free Full Text]
  35. Carpagnano GE, Kharitonov SA, Foschino-Barbaro MP, Resta O, Gramiccioni E, Barnes PJ. Increased inflammatory markers in the exhaled breath condensate of cigarette smokers. Eur Respir J 2003;21:589–593.[Abstract/Free Full Text]
  36. Montuschi P, Kharitonov SA, Ciabattoni G, Barnes PJ. Exhaled leukotrienes and prostaglandins in COPD. Thorax 2003;58:585–588.[Abstract/Free Full Text]
  37. Baraldi E, Carraro S, Alinovi R, Pesci A, Ghiro L, Bodini A, Piacentini G, Zacchello F, Zanconato S. Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations. Thorax 2003;58:505–509.[Abstract/Free Full Text]
  38. Emelyanov A, Fedoseev G, Abulimity A, Rudinski K, Fedoulov A, Karabanov A, Barnes PJ. Elevated concentrations of exhaled hydrogen peroxide in asthmatic patients. Chest 2001;120:1136–1139.[Abstract/Free Full Text]
  39. Carpagnano GE, Barnes PJ, Geddes DM, Hodson ME, Kharitonov SA. Increased leukotriene b4 and interleukin-6 in exhaled breath condensate in cystic fibrosis. Am J Respir Crit Care Med 2003;167:1109–1112.[Abstract/Free Full Text]
  40. Montuschi P, Kharitonov SA, Ciabattoni G, Corradi M, van Rensen L, Geddes DM, Hodson ME, Barnes PJ. Exhaled 8-isoprostane as a new non-invasive biomarker of oxidative stress in cystic fibrosis. Thorax 2000;55:205–209.[Abstract/Free Full Text]
  41. Loukides S, Horvath I, Wodehouse T, Cole PJ, Barnes PJ. Elevated levels of expired breath hydrogen peroxide in bronchiectasis. Am J Respir Crit Care Med 1998;158:991–994.[Abstract/Free Full Text]
  42. Machado RF, Janocha AJ, Laskowski D. Analysis of the exhaled breath condensate protein profile. Am J Respir Crit Care Med 2003;167:A446.
  43. Lu YT, Hellewell PG, Evans TW. Ischemia–reperfusion lung injury: contribution of ischemia, neutrophils, and hydrostatic pressure. Am J Physiol 1997;273:L46–L54.
  44. Asimakopoulos G, Smith PL, Ratnatunga CP, Taylor KM. Lung injury and acute respiratory distress syndrome after cardiopulmonary bypass. Ann Thorac Surg 1999;68:1107–1115.[Abstract/Free Full Text]
  45. Baughman RP, Gunther KL, Rashkin MC, Keeton DA, Pattishall EN. Changes in the inflammatory response of the lung during acute respiratory distress syndrome: prognostic indicators. Am J Respir Crit Care Med 1996;154:76–81.[Abstract]
  46. Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ. A series of prostaglandin F2–like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA 1990;87:9383–9387.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Br J AnaesthHome page
T. Schilling, A. Kozian, M. Kretzschmar, C. Huth, T. Welte, F. Buhling, G. Hedenstierna, and T. Hachenberg
Effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to one-lung ventilation
Br. J. Anaesth., September 1, 2007; 99(3): 368 - 375.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
W. G. Muller, F. Morini, S. Eaton, M. Peters, and A. Jaffe
Safety and feasibility of exhaled breath condensate collection in ventilated infants and children
Eur. Respir. J., September 1, 2006; 28(3): 479 - 485.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. Hunt
Exhaled Breath Condensate pH: Reflecting Acidification of the Airway at All Levels
Am. J. Respir. Crit. Care Med., February 15, 2006; 173(4): 366 - 367.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. M. Effros, R. Casaburi, J. Su, M. Dunning, J. Torday, J. Biller, and R. Shaker
The Effects of Volatile Salivary Acids and Bases on Exhaled Breath Condensate pH
Am. J. Respir. Crit. Care Med., February 15, 2006; 173(4): 386 - 392.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
A. O. Paget-Brown, L. Ngamtrakulpanit, A. Smith, D. Bunyan, S. Hom, A. Nguyen, and J. F. Hunt
Normative Data for pH of Exhaled Breath Condensate.
Chest, February 1, 2006; 129(2): 426 - 430.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
R M Effros and R Casaburi
Cyclo-oxygenase-2 inhibitors and COPD: a bright spot?
Thorax, October 1, 2005; 60(10): 796 - 796.
[Full Text] [PDF]

Home page
 ThoraxHome page
C Ward, I A Forrest, I A Brownlee, G E Johnson, D M Murphy, J P Pearson, J H Dark, and P A Corris
Pepsin like activity in bronchoalveolar lavage fluid is suggestive of gastric aspiration in lung allografts
Thorax, October 1, 2005; 60(10): 872 - 874.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
I. Horvath, J. Hunt, P. J. Barnes, and On behalf of the ATS/ERS Task Force on Exhaled Bre
Exhaled breath condensate: methodological recommendations and unresolved questions
Eur. Respir. J., September 1, 2005; 26(3): 523 - 548.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. Angus, A. Ishizaka, M. Matthay, F. Lemaire, W. MacNee, and E. Abraham
Critical Care in AJRCCM 2004
Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 537 - 544.
[Full Text] [PDF]

Home page
 ThoraxHome page
K Wells, J Vaughan, T N Pajewski, S Hom, L Ngamtrakulpanit, A Smith, A Nguyen, R Turner, and J Hunt
Exhaled breath condensate pH assays are not influenced by oral ammonia
Thorax, January 1, 2005; 60(1): 27 - 31.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
J. Hunt
From the Authors
Eur. Respir. J., June 1, 2004; 23(6): 962 - 962.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200307-1005OCv1
169/1/64    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moloney, E. D.
Right arrow Articles by Griffiths, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moloney, E. D.
Right arrow Articles by Griffiths, M. J.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2004 American Thoracic Society