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ABSTRACT: BACKGROUND: Cigarette smoking (CS) is the most important risk factor for COPD, which is associated with neutrophilic airway inflammation. We hypothesize, that highly reactive aldehydes are critical for CS-induced neutrophilic airway inflammation. METHODS: BALB/c mice were exposed to CS, water filtered CS (WF-CS) or air for 5 days. Levels of total particulate matter (TPM) and aldehydes in CS and WF-CS were measured. Six hours after the last exposure, inflammatory cells and cytokine levels were measured in lung tissue and bronchoalveolar lavage fluid (BALF). Furthermore, Beas-2b bronchial epithelial cells were exposed to CS extract (CSE) or WF-CS extract (WF-CSE) in the absence or presence of the aldehyde acrolein and IL-8 production was measured after 24 hrs. RESULTS: Compared to CS, in WF-CS strongly decreased (CS; 271.1 +/- 41.5 muM, WF-CS; 58.5 +/- 8.2 muM) levels of aldehydes were present whereas levels of TPM were only slightly reduced (CS; 20.78 +/- 0.59 mg, WF-CS; 16.38 +/- 0.36 mg). The numbers of mononuclear cells in BALF (p<0.01) and lung tissue (p<0.01) were significantly increased in the CS- and WF-CS-exposed mice compared to air control mice. Interestingly, the numbers of neutrophils (p<0.001) in BALF and neutrophils and eosinophils (p<0.05) in lung tissue were significantly increased in the CS-exposed but not in WF-CS-exposed mice as compared to air control mice. Levels of the neutrophil and eosinophil chemoattractants KC, MCP-1, MIP-1alpha and IL-5 were all significantly increased in lung tissue from CS-exposed mice compared to both WF-CS-exposed and air control mice. Interestingly, depletion of aldehydes in WF-CS extract significantly reduced IL-8 production in Beas-2b as compared to CSE, which could be restored by the aldehyde acrolein. CONCLUSION: Aldehydes present in CS play a critical role in inflammatory cytokine production and neutrophilic- but not mononuclear airway inflammation.
Respiratory research 04/2013; 14(1):45. · 3.36 Impact Factor
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European Respiratory Journal 12/2012; 40(6):1566-7. · 5.89 Impact Factor
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ABSTRACT: Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) causes oxidative stress and severe damage to proteins in the lungs. One of the main systems to protect cells from the accumulation of damaged proteins is the ubiquitin-proteasome pathway. In the present study, we were interested whether CS exposure of alveolar epithelial cells induces endoplasmic reticulum (ER) stress response by accumulation of damaged proteins that are inefficiently degraded by the proteasomes. The hypothesis was tested in human alveolar epithelial cell line (A549) exposed to gas-phase CS. Exposure to gas-phase CS for 5 min caused an increase in the amount of ubiquitin-protein conjugates within 4 h. CS exposure also induced the ER stress response marker eIF2alpha, followed by a significant reduction of nascent protein synthesis and increase in the level of free intracellular amino acids. Moreover, CS exposure significantly reduced all three proteasomal activities (caspase-, trypsin- and chymotrypsin-like activity) within 4 h, which was still present after 24 h. It can be concluded that gas-phase CS induces ER stress in A549 alveolar epithelial cells leading to inadequate protein turnover caused by an accumulation of damaged proteins, reduction in nascent protein synthesis and inhibition of the proteasome. We suggest that prolonged ER stress may lead to an excessive cell death with disruption of the epithelial barrier, contributing to COPD development.
Experimental physiology 07/2012; · 3.17 Impact Factor
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American Journal of Respiratory and Critical Care Medicine 07/2012; 186(2):197. · 11.08 Impact Factor
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ABSTRACT: One-way endobronchial valves (EBV) have been shown to relieve symptoms of emphysema, particularly in patients without collateral ventilation (CV) between the target and adjacent lobes. In this study, we investigated the ability of the bronchoscopic Chartis Pulmonary Assessment System(TM) to predict treatment response by determining the presence of CV.EBV patients (n=80) underwent a pre-treatment Chartis assessment. Before and 30 days after implantation, high-resolution CT scans were taken to determine target lobe volume reduction (TLVR). A pre- to post-treatment reduction of ≥350 mL was defined as significant. In addition, clinical outcomes (FEV1, 6-minute walk test and SGRQ) were compared over the same time period.Of the 51 patients classified as having an absence of CV according to their Chartis reading, 36 showed a TLVR ≥350 mL. Twenty-nine patients were classified as having CV, and of these 24 did not meet this TLVR cut-off. Chartis showed an accuracy level of 75% in predicting whether or not the TLVR cut-off would be reached. Those predicted to respond showed significantly greater TLVR (p < 0.0001) and FEV1 improvement (p=0.0013) than those predicted not to respond.Chartis is a safe and effective method of predicting response to EBV treatment.
European Respiratory Journal 05/2012; · 5.89 Impact Factor
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ABSTRACT: AbstractBackgroundThe Lung Volume Reduction Coil (LVR-coil) is a new experimental device to achieve lung volume reduction by bronchoscopy in patients with severe emphysema, working in a manner unaffected by collateral airflow. We investigated the safety and efficacy of LVR-coil treatment in patients with heterogeneous emphysema.MethodsIn this prospective cohort pilot study patients were treated bronchoscopically with Nitinol LVR-coils under fluoroscopic guidance in either one, or two sequential procedures. Follow-up tests included SGRQ, pulmonary function testing and 6MWT.ResultsTwenty-eight LVR-coil procedures were performed in 16 patients (baseline FEV(1) 28% (±7.6%) predicted). Four patients were treated in one, and 12 patients were treated in both lungs. Median 10 (5-12) coils in 36.5 (20-60) minutes were placed per lung. Adverse events rated as possibly related to either the device or the procedure <30 days after treatment were pneumothorax (n=1), pneumonia (n=2), COPD exacerbation (n=6), chest pain (n=4), or mild (<5mL) hemoptysis (n=21). From 30 days to 6 months these were: pneumonia (n=3), and COPD exacerbation (n=14). All events resolved with standard care. Six months after LVR-coil treatment there were significant improvements in SGRQ: -14.9 points (±12.1 points, with 11 patients improving >4 points), in FEV1 (+14.9% ±17.0%), FVC (+13.4% ±12.9%), RV (-11.4% ±9.0%), and 6MWT (+84.4m ±73.4m), all p<0.005.ConclusionsLVR-coil treatment is a promising technique for the treatment of patients with severe heterogeneous emphysema. The treatment is technically feasible and results in significant improvements in pulmonary function, exercise capacity and quality of life with an acceptable safety profile.
Chest 11/2011; · 5.25 Impact Factor
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ABSTRACT: A 45-year-old woman underwent a bronchoscopy shortly after lung transplantation. The airway mucosal appearance significantly differed between both lungs, with a pale aspect of the left bronchial tree. Computed tomography (CT) and perfusion scan confirmed a left pulmonary artery stenosis, improving with conservative treatment.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 03/2011; 39(3):e27-8. · 2.40 Impact Factor
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Clinical neurology and neurosurgery 10/2010; 113(2):153-5. · 1.30 Impact Factor
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ABSTRACT: Lung volume reduction aims to improve symptoms by reducing hyperinflation. Endoscopic approaches so far have generally been hampered in their efficacy by collateral ventilation (CV). We sought to determine the safety and feasibility of a new endoscopic lung volume reduction approach independent of the effects of CV.
Patients with severe emphysema were eligible. Inclusion and exclusion criteria were modeled after the National Emphysema Treatment Trial (NETT) study. Homogenous and heterogeneous disease was allowed. Treatment consisted of the placement of coils into the parenchyma of the most diseased area with the intent of achieving parenchymal compression. Primary endpoints were safety and feasibility assessments. Secondary endpoints were efficacy outcomes.
Eleven patients underwent 21 procedures. Procedures were performed under general anesthesia and lasted 45+/-15 minutes and per procedure 4.9+/-0.6 coils were placed. All procedures were well tolerated. The total follow-up time was 7-11 months and in that time 33 adverse events were reported, none of them severe. No pneumothorax occurred. Efficacy seemed better in heterogeneous rather than homogenous disease.
Endoscopic lung volume reduction with coils is safe and feasible. Further studies of the efficacy are indicated.
Therapeutic Advances in Respiratory Disease 08/2010; 4(4):225-31.
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ABSTRACT: Reactive oxygen species (ROS) present in cigarette smoke (CS) are thought to contribute to the development of COPD. Although CS-ROS can hardly enter airway epithelial cells, and certainly not the circulation, systemic levels of ROS have been found to be elevated in COPD patients. We hypothesize that lipophilic components present in CS can enter airway epithelial cells and increase intracellular ROS production by disturbing mitochondrial function. Different airway epithelial cells were exposed to CS extract (CSE), hexane-treated CSE (CSE without lipophilic components), gaseous-phase CS, and water-filtered CS (gaseous-phase CS without ROS). Mitochondrial membrane potential (Deltapsi(m)) and ATP levels were assessed using the bronchial epithelial cell line Beas-2b. ROS generation measured directly by DCF fluorescence and indirectly by measuring free thiol groups (-SH) upon exposure to CS was assessed using lung alveolar epithelial cells devoid of functional mitochondria (A549-rho0), with normal A549 cells serving as controls. In Beas-2b cells, CSE (4 h) caused a dose-dependent decrease in Deltapsi(m) and ATP levels, whereas hexane-treated CSE did not. DCF fluorescence in A549 cells increased in response to CSE, whereas this was not the case in A549-rho0 cells. Exposure of A549 cells to CS resulted in a rapid decrease in free -SH, whereas exposure to ROS-depleted CS only resulted in a delayed decrease. This delayed decrease was less pronounced in A549-rho0 cells. Lipophilic components in CS disturb mitochondrial function, which contributes to increased intracellular generation of ROS. Our results are of importance in understanding the systemic effects of smoking observed in patients with COPD.
AJP Lung Cellular and Molecular Physiology 06/2009; 297(1):L109-14. · 3.66 Impact Factor
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ABSTRACT: Most chronic liver diseases are accompanied by oxidative stress, which may induce apoptosis in hepatocytes and liver injury. Oxidative stress induces heme oxygenase-1 (HO-1) expression. This stress-responsive cytoprotective protein is responsible for heme degradation into carbon monoxide (CO), free iron, and biliverdin. CO is an important intracellular messenger; however, the exact mechanisms responsible for its cytoprotective effect are not yet elucidated. Thus, we investigated whether HO-1 and CO protect primary hepatocytes against oxidative-stress-induced apoptosis. In vivo, bile duct ligation was used as model of chronic liver disease. In vitro, primary hepatocytes were exposed to the superoxide anion donor menadione in a normal and in a CO-- containing atmosphere. Apoptosis was determined by measuring caspase-9, -6, -3 activity and poly(ADP-ribose) polymerase cleavage, and necrosis was determined by Sytox green staining. The results showed that (1) HO-1 is induced in chronic cholestatic liver disease, (2) superoxide anions time- and dose-dependently induce HO-1 activity, (3) HO-1 overexpression inhibits superoxide-anions-induced apoptosis, and (4) CO blocks superoxide-anions-induced JNK phosphorylation and caspase-9, -6, -3 activation and abolishes apoptosis but does not increase necrosis. We conclude that HO-1 and CO protect primary hepatocytes against superoxide-anions-induced apoptosis partially via inhibition of JNK activity. CO could represent an important candidate for the treatment of liver diseases.
Free Radical Biology and Medicine 05/2008; 44(7):1323-33. · 5.42 Impact Factor
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ABSTRACT: Smoking is the most important cause for the development of COPD. Since not all smokers develop COPD, it is obvious that other factors must be involved in disease development. We hypothesize that heme oxygenase-1 (HO-1), a protective enzyme against oxidative stress and inflammation, is insufficiently upregulated in COPD. The effects of HO-1 modulation on cigarette smoke induced inflammation and emphysema were tested in a smoking mouse model.
Mice were either exposed or sham exposed to cigarette smoke exposure for 20 weeks. Cobalt protoporphyrin or tin protoporphyrin was injected during this period to induce or inhibit HO-1 activity, respectively. Afterwards, emphysema development, levels of inflammatory cells and cytokines, and the presence of B-cell infiltrates in lung tissue were analyzed.
Smoke exposure induced emphysema and increased the numbers of inflammatory cells and numbers of B-cell infiltrates, as well as the levels of inflammatory cytokines in lung tissue. HO-1 modulation had no effects on smoke induced emphysema development, or the increases in neutrophils and macrophages and inflammatory cytokines. Interestingly, HO-1 induction prevented the development of smoke induced B-cell infiltrates and increased the levels of CD4+CD25+ T cells and Foxp3 positive cells in the lungs. Additionally, the CD4+CD25+ T cells correlated positively with the number of Foxp3 positive cells in lung tissue, indicating that these cells were regulatory T cells.
These results support the concept that HO-1 expression influences regulatory T cells and indicates that this mechanism is involved in the suppression of smoke induced B-cell infiltrates. The translation of this interaction to human COPD should now be pursued.
Respiratory research 02/2008; 9:17. · 3.36 Impact Factor
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ABSTRACT: Abstract
Background
Smoking is the most important cause for the development of COPD. Since not all smokers develop COPD, it is obvious that other factors must be involved in disease development. We hypothesize that heme oxygenase-1 (HO-1), a protective enzyme against oxidative stress and inflammation, is insufficiently upregulated in COPD.
The effects of HO-1 modulation on cigarette smoke induced inflammation and emphysema were tested in a smoking mouse model.
Methods
Mice were either exposed or sham exposed to cigarette smoke exposure for 20 weeks. Cobalt protoporphyrin or tin protoporphyrin was injected during this period to induce or inhibit HO-1 activity, respectively. Afterwards, emphysema development, levels of inflammatory cells and cytokines, and the presence of B-cell infiltrates in lung tissue were analyzed.
Results
Smoke exposure induced emphysema and increased the numbers of inflammatory cells and numbers of B-cell infiltrates, as well as the levels of inflammatory cytokines in lung tissue. HO-1 modulation had no effects on smoke induced emphysema development, or the increases in neutrophils and macrophages and inflammatory cytokines. Interestingly, HO-1 induction prevented the development of smoke induced B-cell infiltrates and increased the levels of CD4<sup>+</sup>CD25<sup>+ </sup>T cells and Foxp3 positive cells in the lungs. Additionally, the CD4<sup>+</sup>CD25<sup>+ </sup>T cells correlated positively with the number of Foxp3 positive cells in lung tissue, indicating that these cells were regulatory T cells.
Conclusion
These results support the concept that HO-1 expression influences regulatory T cells and indicates that this mechanism is involved in the suppression of smoke induced B-cell infiltrates. The translation of this interaction to human COPD should now be pursued.
Respiratory Research. 01/2008;
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ABSTRACT: In patients with chronic obstructive pulmonary disease (COPD), an imbalance between oxidants and antioxidants is acknowledged to result in disease development and progression. Cigarette smoke (CS) is known to deplete total glutathione (GSH + GSSG) in the airways. We hypothesized that components in the gaseous phase of CS may irreversibly react with GSH to form GSH derivatives that cannot be reduced (GSX), thereby causing this depletion. To understand this phenomenon, we investigated the effect of CS on GSH metabolism and identified the actual GSX compounds. CS and H(2)O(2) (control) deplete reduced GSH in solution [Delta = -54.1 +/- 1.7 microM (P < 0.01) and -39.8 +/- 0.9 microM (P < 0.01), respectively]. However, a significant decrease of GSH + GSSG was observed after CS (Delta = -75.1 +/- 7.6 microM, P < 0.01), but not after H(2)O(2). Exposure of A549 cells and primary bronchial epithelial cells to CS decreased free sulfhydryl (-SH) groups (Delta = -64.2 +/- 14.6 microM/mg protein, P < 0.05) and irreversibly modified GSH + GSSG (Delta = -17.7 +/- 1.9 microM, P < 0.01) compared with nonexposed cells or H(2)O(2) control. Mass spectrometry (MS) showed that GSH was modified to glutathione-aldehyde derivatives. Further MS identification showed that GSH was bound to acrolein and crotonaldehyde and another, yet to be identified, structure. Our data show that CS does not oxidize GSH to GSSG but, rather, reacts to nonreducible glutathione-aldehyde derivatives, thereby depleting the total available GSH pool.
AJP Lung Cellular and Molecular Physiology 11/2007; 293(5):L1156-62. · 3.66 Impact Factor
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ABSTRACT: Cyclosporin A induces closure of the mitochondrial permeability transition pore. We aimed to investigate whether this closure results in concomitant increases in mitochondrial membrane potential (DeltaPsim) and the production of reactive oxygen species. Fluorescent probes were used to assess DeltaPsim (JC-1, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl-carbocyanine iodide), reactive oxygen species [DCF, 5- (and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester] and [Ca2+][Fluo-3, glycine N-[4-[6-[(acetyloxy)methoxy]-2,7-dichloro-3-oxo-3H-xanthen-9-yl]-2-[2-[2-[bis[2-[(acetyloxy)methoxy]-2-oxyethyl]amino]-5-methylphenoxy]ethoxy]phenyl]-N-[2-[(acetyloxy)methoxy]-2-oxyethyl]-(acetyloxy)methyl ester] in human kidney cells (HK-2 cells) and in a line of human small cell carcinoma cells (GLC4 cells), because these do not express cyclosporin A-sensitive P-glycoprotein. We used transfected GLC4 cells expressing P-glycoprotein as control for GLC4 cells. NIM811 (N-methyl-4-isoleucine-cyclosporin) and PSC833 (SDZ-PSC833) were applied as selective mitochondrial permeability transition pore and P-glycoprotein blockers, respectively. To study the effect of cyclosporin A on mitochondrial function, we isolated mitochondria from fresh pig livers. Cyclosporin A and PSC833 induced a more than two-fold increase in JC-1 fluorescence in HK-2 cells, whereas NIM811 had no effect. None of the three substances induced a significant increase in JC-1 fluorescence in GLC4 cells. Despite this, cyclosporin A, NIM811 and PSC833 induced a 1.5-fold increase in DCF fluorescence (P<0.05) and a two-fold increase in Fluo-3 fluorescence (P<0.05). Studies in isolated mitochondria showed that blockage of mitochondrial permeability transition pores by cyclosporin A affected neither DeltaPsim, ATP synthesis, nor respiration rate. The mitochondrial permeability transition pore blockers cyclosporin A and NIM811, but also the non-mitochondrial permeability transition pore blocker PSC833, induced comparable degrees of reactive oxygen species production and cytosolic [Ca2+]. Neither mitochondria, effects on P-glycoprotein nor inhibition of calcineurin therefore play a role in cyclosporin A-induced oxidative stress and disturbed Ca2+ homeostasis.
FEBS Journal 06/2007; 274(12):3003-12. · 3.79 Impact Factor
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ABSTRACT: Increased lung cell apoptosis and necrosis occur in patients with chronic obstructive pulmonary disease (COPD). Mitochondria are crucially involved in the regulation of these cell death processes. Cigarette smoke is the main risk factor for development of COPD. We hypothesized that cigarette smoke disturbs mitochondrial function, thereby decreasing the capacity of mitochondria for ATP synthesis, leading to cellular necrosis. This hypothesis was tested in both human bronchial epithelial cells and isolated mitochondria. Cigarette smoke extract exposure resulted in a dose-dependent inhibition of complex I and II activities. This inhibition was accompanied by decreases in mitochondrial membrane potential, mitochondrial oxygen consumption, and production of ATP. Cigarette smoke extract abolished the staurosporin-induced caspase-3 and -7 activities and induced a switch from epithelial cell apoptosis into necrosis. Cigarette smoke induced mitochondrial dysfunction, with compounds of cigarette smoke acting as blocking agents of the mitochondrial respiratory chain; loss of ATP generation leading to cellular necrosis instead of apoptosis is a new pathophysiological concept of COPD development.
AJP Lung Cellular and Molecular Physiology 06/2007; 292(5):L1211-8. · 3.66 Impact Factor
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Dirk-Jan Slebos,
Stefan W Ryter,
Marco van der Toorn,
Fang Liu,
Fengli Guo,
Catherine J Baty,
Jenny M Karlsson,
Simon C Watkins,
Hong Pyo Kim,
Xue Wang,
Janet S Lee,
Dirkje S Postma,
Henk F Kauffman,
Augustine M K Choi
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ABSTRACT: Cigarette smoke-induced apoptosis and necrosis contribute to the pathogenesis of chronic obstructive pulmonary disease. The induction of heme oxygenase-1 provides cytoprotection against oxidative stress, and may protect in smoking-related disease. Since mitochondria regulate cellular death, we examined the functional expression and mitochondrial localization of heme oxygenase-1 in pulmonary epithelial cells exposed to cigarette smoke extract (CSE), and its role in modulating cell death. Heme oxygenase-1 expression increased dramatically in cytosolic and mitochondrial fractions of human alveolar (A549), or bronchial epithelial cells (Beas-2b) exposed to either hemin, lipopolysaccharide, or CSE. Mitochondrial localization of heme oxygenase-1 was also observed in a primary culture of human small airway epithelial cells. Furthermore, heme oxygenase activity increased dramatically in mitochondrial fractions, and in whole cell extracts of Beas-2b after exposure to hemin and CSE. The mitochondrial localization of heme oxygenase-1 in Beas-2b was confirmed using immunogold-electron microscopy and immunofluorescence labeling on confocal laser microscopy. CSE caused loss of cellular ATP and rapid depolarization of mitochondrial membrane potential. Apoptosis occurred in Beas-2b at low concentrations of cigarette smoke extract, whereas necrosis occurred at high concentrations. Overexpression of heme oxygenase-1 inhibited CSE-induced Beas-2b cell death and preserved cellular ATP levels. Finally, heme oxygenase-1 mRNA expression was elevated in the lungs of mice chronically exposed to cigarette smoke. We demonstrate the functional compartmentalization of heme oxygenase-1 in the mitochondria of lung epithelial cells, and its potential role in defense against mitochondria-mediated cell death during CSE exposure.
American Journal of Respiratory Cell and Molecular Biology 05/2007; 36(4):409-17. · 5.13 Impact Factor
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ABSTRACT: A number of new immunosuppressive drugs have become available in transplant medicine. We investigated the effects of two different immunosuppressive protocols on bronchoalveolar lavage fluid cellular characteristics in 34 lung transplant recipients who were treated with anti-thymocyte globulin induction therapy, cyclosporine, azathioprine (AZA), and prednisolone (regimen I), compared with 17 recipients receiving basiliximab induction, tacrolimus, AZA, and prednisolone (regimen II). We performed bronchoalveolar lavages between 15 and 40 d post-transplantation, in stable clinical condition and no acute rejection, cytomegalovirus, and/or respiratory tract infection. The regimen II treatment was associated with a significantly lower percentage lavage fluid lymphocytes than with regimen I. The CD4/CD8 ratio was significantly higher with regimen II than with regimen I: 1.56 (range 0.41-2.16) and 0.33 (0.04-0.95) respectively; p < 0.001, mainly because of a lower percentage CD8(+) cells with regimen II: 25% (12-51) vs. regimen I: 60% (34-77); p < 0.001. The percentage CD4(+) CD25(+) cells appeared lower with regimen II: 21% (10-88) vs. regimen I: 50% (0-87); p = 0.04. Overall survival was similar between the groups, whereas a beneficial trend in freedom of bronchiolitis obliterans syndrome was observed with regimen II. Airway lymphocyte subtypes are affected by the immunosuppressive protocol used. This observation should be taken into account when studying transplant recipients, and may contribute to our understanding of alloreactive airway disease.
Clinical Transplantation 05/2005; 19(2):243-9. · 1.67 Impact Factor
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The Journal of Heart and Lung Transplantation 11/2004; 23(10):1213-4. · 4.33 Impact Factor
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ABSTRACT: Sputum induction (SI) is nowadays being applied as a non-invasive and safe method to investigate airway inflammation in pulmonary diseases. We investigated the feasibility of SI after lung transplantation (LTX), and compared sputum and bronchoalveolar lavage (BAL) cellular characteristics and interleukin-8 (IL-8) levels. Results were also compared with 11 healthy subjects. SI as performed between 26 and 1947 d after LTX in 19 recipients, was successful in 16 of 22 attempts (73%). Six patients failed to produce sputum after induction, mostly just post-LTX and with having a lower forced expiratory volume in 1 s (FEV1). The success rate in clinically stable patients after the first month post-LTX was 93%. Side-effects were absent. Sputum recovery, viability and squamous cell contamination were comparable between LTX patients and healthy subjects. In the LTX group, total cell counts, neutrophil percentages and IL-8 levels were much higher in SI than BAL (1.6 x 10(6)/mL, 65.5% and 54.2 ng/mL vs. 0.1 x 10(6)/mL, 3.0% and 0.01 ng/mL; p < 0.001). Although LTX-neutrophil percentages in SI and BAL correlated properly (rho=0.72, p=0.04), both techniques are not interchangeable. We conclude that sputum induction is feasible, well tolerated, and without major side-effects in stable patients after the first month post-LTX. Induced sputum may be a useful tool to study inflammatory changes of the airways after LTX, and because of the large quantity of neutrophils sampled, especially for further studies on the pathogenesis of bronchiolitis obliterans.
Clinical Transplantation 10/2004; 18(5):605-12. · 1.67 Impact Factor
