National Koranyi Institute of TB and Pulmonology

Budapest, Hungary

National Koranyi Institute of TB and Pulmonology

Budapest, Hungary
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Bikov A.,Semmelweis University | Galffy G.,Semmelweis University | Tamasi L.,Semmelweis University | Bartusek D.,Semmelweis University | And 3 more authors.
Respirology | Year: 2014

Background and objective Exercise-induced bronchoconstriction (EIB) is the temporary narrowing of the airways caused by physical exercise. Its exact pathophysiology is unclear; however, acute changes in airways pH may play a role. Exhaled breath condensate (EBC) pH was suggested as a surrogate indicator for airway acid-base status, but its value is also affected by volatile molecules and respiratory droplet dilution. The aim of the study was to assess changes in EBC pH during EIB. Methods Twenty-two asthmatics who reported breathlessness following exercise and 16 healthy individuals participated in the study. Lung function test was performed and exhaled breath samples were collected for pH, dilution factor and volatile compound pattern measurements (Cyranose 320) pre-exercise and at 0, 10, 20 and 30 min after physical exercise challenge. Fractional exhaled nitric oxide was measured before exercise. Results EIB developed in 13 asthmatic subjects. In these participants, but not in the EIB-negative asthmatics (P = 0.51), EBC pH reduced significantly during exercise (P = 0.01). In addition, changes in EBC pH were related to the degree of bronchospasm in the EIB-positive group (P = 0.01, r = 0.68). Exhaled volatile pattern became altered (P < 0.05) during exercise in all subjects (asthmatics and controls). EBC pH changes were not related to EBC dilution or volatile compound pattern alterations (P > 0.05). Conclusions The development of EIB was related to acute changes of EBC pH, which suggest the role of airway pH decrease in the pathophysiology of EIB. Exercise-induced changes in exhaled biomarkers suggest methodological precautions to avoid physical exercise before performing exhaled breath tests. © 2014 Asian Pacific Society of Respirology.


Antus B.,National Koranyi Institute of TB and Pulmonology | Barta I.,National Koranyi Institute of TB and Pulmonology | Kullmann T.,National Koranyi Institute of TB and Pulmonology | Lazar Z.,Semmelweis University | And 3 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010

Rationale: Exhaled breath condensate pH has been proposed as a noninvasive marker of airway inflammation. However, due to standardization difficulties in pH measurement techniques, different pH readings were obtained in previous studies. Objectives: In this longitudinal study we assessed condensate pH in patients with an exacerbation of asthma or chronic obstructive airway disease using the very precise carbon dioxide standardization method that negates the effect of this gas on condensate acidity. Methods: Condensate pH, fractional exhaled nitric oxide, lung function, andblood gases weremeasuredin 20nonsmoking patients with asthma and 21 smoking and 17 ex-smoking patients with chronic obstructive airway disease first at hospital admission due to an acute exacerbation of the disease and again at discharge after treatment. Condensate pH was also assessed in 18 smoking and 18 nonsmoking healthy control subjects. Measurements and Main Results: In patients with asthma, condensate pHwassignificantly decreasedat the time of exacerbationcompared with nonsmoking control subjects and increased with treatment. In patients with chronic obstructive airway disease, condensate pH remained unchanged during exacerbation, both in smokers and exsmokers. Nevertheless, condensates collected from smokers were more acidic than those of ex-smokers. A similar difference was observed between smoker and nonsmoker healthy control subjects. No correlations were found between condensate pH and fractional exhaled nitric oxide or lung function variables measured either at admission or discharge. Conclusions: Our data suggest that exacerbation of asthma, but not chronic obstructive airway disease, is associated with acidification of breath condensate.


Antus B.,National Koranyi Institute of TB and Pulmonology | Kardos Z.,National Koranyi Institute of TB and Pulmonology
Current Medicinal Chemistry | Year: 2015

Chronic obstructive pulmonary disease (COPD) is a major and rapidly increasing health problem associated with a chronic inflammatory response, predominantly in small airways and lung parenchyma. Oxidative stress induced by reactive oxygen and nitrogen species (ROS and RNS) plays a central role in the pathophysiology of COPD. There is evidence that several molecules formed during oxidative processes may have the potential to serve as biomarkers of oxidative stress in the airways of patients with COPD. Among these molecules carbon monoxide, ethane and pentane can be measured in the exhaled air, while 8-isoprostane, malondialdehyde, 4-hydroxyhexenal, 4-hyroxynonenal, acrolein, hydrogen peroxide, nitrogen oxides and 3-nitrotyrosine can be detected in exhaled breath condensate and/or sputum supernatant. In this review the molecular background of these processes including the formation of ROS and RNS, the biosynthesis of essential ω-3 and ω-6 polyunsaturated fatty acids as building blocks of lipids in the cellular membranes and their enzymatic and non-enzymatic metabolism to eicosanoids and related compounds have been summarized. Moreover, the formation of oxidative stress markers studied most commonly in the context of COPD has been briefly discussed. The associations between biomarkers and clinical variables have also been highlighted in an attempt to illustrate the potential clinical applicability of these biomarker measurements. © 2015 Bentham Science Publishers.


Antus B.,National Koranyi Institute of TB and Pulmonology | Harnasi G.,National Koranyi Institute of TB and Pulmonology | Drozdovszky O.,National Koranyi Institute of TB and Pulmonology | Barta I.,National Koranyi Institute of TB and Pulmonology
Respirology | Year: 2014

Background and objective Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this longitudinal study changes in the level of malondialdehyde (MDA), an end product of polyunsaturated fatty acid peroxidation, were investigated in the airways of patients with acute exacerbation of COPD (AECOPD). Methods Levels of MDA were measured in sputum and exhaled breath condensate (EBC) of 34 COPD patients at the time of hospital admission due to an acute exacerbation of the disease, and again following treatment at the time of hospital discharge. MDA was also assessed in 21 stable patients with COPD and 20 healthy controls. Measurements were performed using high-performance liquid chromatography. Results Sputum MDA levels were significantly increased in AECOPD (220.0 ± 17.5 nmol/L) compared with stable disease (144.6 ± 14.3 nmol/L, P < 0.01) and healthy controls (85.9 ± 11.3 nmol/L, P < 0.001). MDA levels decreased after treatment (190.7 ± 16.3 nmol/L, P < 0.05). In contrast to sputum, EBC MDA levels were comparable between controls, stable COPD patients and AECOPD patients (73.1 ± 5.1 nmol/L, 96.1 ± 11.6 nmol/L and 93.3 ± 7.6 nmol/L, P = NS). Measurement of MDA had good repeatability in both sputum and EBC, but the between-day variability was considerably higher in EBC. Sputum induction did not influence MDA levels. Conclusions MDA in sputum, but not in EBC, appears to be a useful marker for monitoring exacerbation-associated oxidative stress in AECOPD. Malondialdehyde, an established by-product of lipid peroxidation, can be precisely measured in the sputum and is a useful marker to monitor exacerbation-associated oxidative stress in patients with COPD. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.


Drozdovszky O.,National Koranyi Institute of TB and Pulmonology | Barta I.,National Koranyi Institute of TB and Pulmonology | Antus B.,National Koranyi Institute of TB and Pulmonology
Respiration | Year: 2014

Background: Eicosanoids are small lipid molecules with diverse biological functions in the airways. Objectives: The aim of this study was to investigate changes in leukotriene B4 (LTB4), 8-isoprostane, prostaglandin E2 (PGE2) and cysteinyl-leukotriene (cys-LT) levels in the sputum of patients with chronic obstructive pulmonary disease (COPD) at the onset of a severe exacerbation and during the course of recovery. Methods: Thirty-seven ex-smoker COPD patients suffering an episode of acute exacerbation were enrolled. Samples were taken (i) on hospital admission and (ii) after regular treatment. Twenty-five stable ex-smoker COPD patients served as controls. Eicosanoids were determined by enzyme immunoassay. Results: Sputum PGE2 [39.8 (13.3-103.3) vs. 5.05 (2.3-12.1) pg/ml, p < 0.001], 8-isoprostane [89.5 (36.9-184.7) vs. 29.7 (13.8-68.8) pg/ml, p < 0.01] and LTB4 [587.7 (252.9-774.8) vs. 276.1 (105.4-594.7) pg/ml, p < 0.05] levels were increased in patients with exacerbation compared to stable subjects. After treatment only PGE2 levels decreased significantly [at discharge: 19.6 (4.6-52.5) pg/ml, p < 0.01], the levels of other eicosanoids remained elevated (p = NS). Sputum cys-LT levels were similar in stable patients and in those with exacerbation and treatment did not influence cys-LTs either. There was a significant correlation between PGE2 and sputum neutrophil and lymphocyte cell counts in patients with exacerbation. Conclusions: Our results suggest that 8-isoprostane, LTB4 and PGE2 but not cys-LTs may be involved in exacerbation-associated inflammatory processes in the airways of patients with COPD. Validation of PGE2 for use as a biomarker of recovery from an exacerbation requires further studies. © 2014 S. Karger AG, Basel.


Antus B.,National Koranyi Institute of TB and Pulmonology
Oxidative Medicine and Cellular Longevity | Year: 2016

Although oxidative stress is thought to play a pivotal role in the pathogenesis of inflammatory airway diseases, its assessment in clinical practice remains elusive. In recent years, it has been conceptualized that oxidative stress markers in sputum should be employed to monitor oxidative processes in patients with asthma, chronic obstructive pulmonary disease (COPD), or cystic fibrosis (CF). In this review, the use of sputum-based oxidative markers was explored and potential clinical applications were considered. Among lipid peroxidation-derived products, 8-isoprostane and malondialdehyde have been the most frequently investigated, while nitrosothiols and nitrotyrosine may serve as markers of nitrosative stress. Several studies have showed higher levels of these products in patients with asthma, COPD, or CF compared to healthy subjects. Marker concentrations could be further increased during exacerbations and decreased along with recovery of these diseases. Measurement of oxidized guanine species and antioxidant enzymes in the sputum could be other approaches for assessing oxidative stress in pulmonary patients. Collectively, even though there are promising findings in this field, further clinical studies using more established detection techniques are needed to clearly show the benefit of these measurements in the follow-up of patients with inflammatory airway diseases. © 2016 Balazs Antus.


Antus B.,National Koranyi Institute of TB and Pulmonology | Barta I.,National Koranyi Institute of TB and Pulmonology
Lung Cancer | Year: 2012

Assessment of exhaled breath condensate (EBC) pH is a promising method for investigating and monitoring airway pathology in a number of lung diseases. In this cross-sectional study we tested whether development of lung cancer is associated with acidification of EBC. EBC was collected in 43 smoking patients with lung cancer (squamous cell carcinoma: 17 patients, adenocarcinoma: 16 patients, and small cell lung cancer: 10 patients) before receiving any anticancer treatment and in 20 healthy smokers without any clinical and radiological evidence of pulmonary tumor. EBC pH was measured by CO 2 gas standardization, the most reliable and accurate method at present. EBC pH in patients with pulmonary tumor (6.68±0.02) and in controls (6.63±0.05) was similar (p>0.05). Results were affected neither by the histological subtype nor the stage of the tumors. Our data suggest that assessment of EBC pH is of limited value for the diagnosis and/or screening of lung cancer. © 2011 Elsevier Ireland Ltd.


Antus B.,National Koranyi Institute of TB and Pulmonology | Drozdovszky O.,National Koranyi Institute of TB and Pulmonology | Barta I.,National Koranyi Institute of TB and Pulmonology | Kelemen K.,National Koranyi Institute of TB and Pulmonology
Lung | Year: 2015

Introduction: Oxidative stress plays a pivotal role in the pathogenesis of cystic fibrosis (CF). In this study, airway and systemic oxidative stress was investigated in CF using malondialdehyde (MDA), an established by-product of polyunsaturated fatty acid peroxidation. Methods: Exhaled breath condensate (EBC), sputum, and plasma were collected from 40 stable CF patients during routine clinical visits and from 25 healthy controls. MDA was measured by high-performance liquid chromatography. Results: MDA levels in sputum (279.8 ± 14.7 vs. 92.7 ± 9.2 nmol/L, p < 0.0001), EBC (139.9 ± 6.7 vs. 71.5 ± 4.3 nmol/L, p < 0.0001), and plasma (176.1 ± 15.9 vs. 129.6 ± 12.9 nmol/L, p < 0.05) were increased in patients with CF compared to healthy controls. MDA measurement in sputum [area under receiver operating characteristic curve (AUC): 0.977, p < 0.0001] or EBC (AUC: 0.94, p < 0.0001) discriminated between patients and controls with greater accuracy than in plasma (AUC: 0.677, p < 0.05). Sputum and EBC MDA levels were elevated in patients with severe pulmonary dysfunction [forced expiratory volume in 1 s (FEV1) <50 % predicted] compared to those with mild-to-moderate functional impairment (FEV1 ≥50 % predicted) (p < 0.05). MDA concentrations in CF patients colonized either with Pseudomonas aeruginosa or with other bacteria were similar (p = NS). The intra- and inter-assay repeatabilities of MDA measurements was similar in all the three types of samples, while the between-visit variability was higher in plasma. Conclusions: MDA is a potential new airway marker of oxidative stress in patients with CF. Sputum MDA differentiates best between patients and healthy subjects. © 2015, Springer Science+Business Media New York.


Soter S.,National Koranyi Institute of TB and Pulmonology | Barta I.,National Koranyi Institute of TB and Pulmonology | Antus B.,National Koranyi Institute of TB and Pulmonology
Inflammation | Year: 2013

Fractional exhaled nitric oxide (FENO) may be a pulmonary biomarker in chronic obstructive pulmonary disease (COPD). In this prospective study, the relationship between FENO and airway inflammation was assessed in COPD exacerbations. FENO and lung function were measured, and sputum was collected from 49 ex-smoking COPD patients, first at the time of hospital admission and again at discharge following treatment. There was a significant positive correlation between the percentage of sputum eosinophils and FENO concentrations, both at exacerbation (r = 0.593, p < 0.001) and discharge (r = 0.337, p = 0.044). The increase in forced expiratory volume in one second (FEV1) after treatment was greater in patients with sputum eosinophilia (ΔFEV1 0.35 ± 0.12 vs. 0.13 ± 0.04 L, p = 0.046), and FENO was a strong predictor of sputum eosinophilia (area under the receiver operating characteristic curve, 0.89). The optimum cut point was 19 parts per billion (sensitivity: 90 %; specificity: 74 %). Our data suggest that FENO is a good surrogate marker of eosinophilic inflammation in COPD patients with exacerbations. © 2013 Springer Science+Business Media New York.


Antus B.,National Koranyi Institute of TB and Pulmonology | Barta I.,National Koranyi Institute of TB and Pulmonology
Acta Physiologica Hungarica | Year: 2013

In a recent trial we have assessed fractional exhaled nitric oxide (FENO) in a cohort of patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD). In the current study we have retrospectively investigated the frequency of severe hospitalization-associated exacerbations in the same cohort over 3 years after the initial FENO measurement. A total of 58 COPD patients were enrolled and allocated either into the low (< 27 ppb) or the high (≥ 27 ppb) FENO group depending on their FENO level at exacerbation. Beside the annual rate of exacerbations, sputum culture results and the frequency of antibiotic treatments were also analyzed during the follow-up. Both the number of exacerbations per patient-year and the hospitalization days due to exacerbations were significantly increased in patients from the low FENO group compared to those from the high FENO group. Sputum samples derived from patients in the low FENO group were more frequently indicative of a bacterial infection compared to those obtained from the other subgroup. Also, the frequency of antibiotic treatments was significantly increased in subjects from the low FENO group. Results of this pilot study suggest that COPD patients have diverse risks for future exacerbations depending on their FENO levels at exacerbation.

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