Adam Antczak

Publications of Adam Antczak

• The N363S and I559N single nucleotide polymorphisms of the h-GR/NR3C1 gene in patients with bronchial asthma.

  Authors: Michał Panek, Tadeusz Pietras, Adam Antczak, Artur Fabijan, Marcelina Przemęcka, Paweł Górski, Piotr Kuna, Janusz Szemraj

  International journal of molecular medicine. 04/2012;

  Bronchial asthma is a disease of multifactorial etiology. The natural variability of the DNA sequence within the h-GR/NR3C1 gene affects both the conformation and the activity of glucocorticoidBronchial asthma is a disease of multifactorial etiology. The natural variability of the DNA sequence within the h-GR/NR3C1 gene affects both the conformation and the activity of glucocorticoid receptors. There are 2 major types of resistance to glucocorticoids (GCS)-resistant asthma failing to respond to treatment with high doses of inhaled and oral glucocorticoids. Type I GCS-resistant asthma is cytokine-induced or acquired. Type II GCS resistance involves generalized primary cortisol resistance, which affects all tissues and is likely to be associated with a mutation in the glucocorticoid receptor (GCR) gene or in genes that modulate GCR function. There are clear examples of glucocorticoid gene h-GR/NR3C1 polymorphisms that can influence responses and sensitivity to glucocorticosteroids. Among the numerous polymorphisms observed within this gene, N363S and I559N single nucleotide polymorphisms (SNPs) may play an important role in the development of bronchial asthma and in the alteration of sensitivity to GCS in severe bronchial asthma. The aim of this research project was to study the correlation between the N363S and I559N polymorphisms of the h-GR/NR3C1 gene and the occurrence of asthma in a population of Polish asthmatics. Peripheral blood was obtained from 210 healthy volunteers and 234 asthma patients. Structuralized anamnesis, spirometry and allergy skin prick tests were performed in all participants. Genotyping was carried out using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and PCR-HRM methods. In the healthy, non-atopic population, the GG variant of the N363S polymorphism was found with a 5.7% frequency. In asthma patients, GG SNP of N363S occurred with the frequency of 6.4%. In the groups of patients with uncontrolled moderate asthma and uncontrolled severe disease, the genotype distribution for the investigated polymorphisms were as follows: N363S, AA, AG, GG occurring with 0.8750/0.0834/0.0416 frequency and I559N, TT, TA, AA occurring with 1.000/0.000/0.000 frequency. The analysis demonstrated a significantly higher frequency of the A and G variants of the N363S polymorphisms in uncontrolled moderate asthma and uncontrolled severe disease than in the healthy population. No variant-related differences in the frequency of the studied I559N polymorphism were demonstrated in healthy controls and asthma patients. In conclusion, the N363S polymorphism of the h-GR/NR3C1 gene is significantly associated with an increased sensitivity to glucococorticoids in vivo and susceptibility to the development of a moderate to severe form of uncontrolled bronchial asthma in the Polish population. This observation needs to be confirmed in a larger group of subjects.

• The role of functional single nucleotide polymorphisms of the human glucocorticoid receptor gene NR3C1 in Polish patients with bronchial asthma.

  Authors: Michał Panek, Tadeusz Pietras, Adam Antczak, Paweł Górski, Piotr Kuna, Janusz Szemraj

  Molecular biology reports. 04/2012; 39(4):4749-57.

  N363S and ER22/23EK polymorphisms observed within glucocorticoid receptor gene (NR3C1) may play an important role in the development of bronchial asthma. NR3C1 gene is associated with an alteredN363S and ER22/23EK polymorphisms observed within glucocorticoid receptor gene (NR3C1) may play an important role in the development of bronchial asthma. NR3C1 gene is associated with an altered sensitivity to GCs. The aim of the research project was to study the correlation between this NR3C1 gene polymorphisms and occurrence of asthma in the population of Polish asthmatics. Peripheral blood was obtained from 207 healthy volunteers and 221 asthma patients. Genotyping was carried out with PCR-RFLP method. In the groups of patients with uncontrolled moderate asthma and uncontrolled severe disease, the genotype distribution for the investigated polymorphisms was as follows: N363S-AA, AG, GG occurring with 0.881/0.073/0.046 frequency and ER22/23EK-GG, GA, AA occurring with 0.963/0.037/0.000 frequency. Chi-square analysis revealed a significantly different (P < 0.05) distribution between cases and controls for the N363S polymorphisms. The N363S polymorphism of NR3C1 gene is significantly associated with bronchial asthma, susceptibility to the development of moderate to severe form of uncontrolled bronchial asthma.

• Somatostatin receptor scintigraphy in sarcoidosis: relation to selected clinical and laboratory markers.

  Authors: Wojciech J Piotrowski, Małgorzata Bieńkiewicz, Izabella Frieske, Jerzy Marczak, Adam Antczak, Paweł Górski, Jacek Kuśmierek, Anna Płachcińska

  Polskie Archiwum Medycyny Wewnetrznej. 01/2012;

  INTRODUCTION: Differentiation between active and inactive sarcoidosis may be problematic. Several biochemical markers have been proposed for this purpose. Somatostatin receptor scintigraphy with theINTRODUCTION: Differentiation between active and inactive sarcoidosis may be problematic. Several biochemical markers have been proposed for this purpose. Somatostatin receptor scintigraphy with the use of 99mTc Tectreotide as a radiotracer may be used for estimation of disease activity. OBJECTIVES: To estimate the value of traditional biomarkers (serum angiotensin converting enzyme - SACE, C-reactive protein - CRP, markers of calcium metabolism, bronchoalveolar lavage fluid - BALF - lymphocytes) and a novel biomarker 8-isoprostane (8-IP) in exhaled breath condensate (EBC) for estimation of disease activity in relation to somatostatin receptor scintigraphy results. PATIENTS AND METHODS: 32 patients with sarcoidosis were included. 99mTc-HYNIC-TOC was used as a tracer, planar and SPECT/CT images were performed. Patients were divided into a subgroup with positive radiotracer uptake (n=20) and lack of visible uptake (n=12). 8-IP was measured in EBC by EIA method. RESULTS: We found a significant difference between the positive and negative uptake group in EBC 8-IP (19.119.8 vs 5.43.5 pg/ml, p=0.02). The concentration of SACE and % of BALF lymphocytes were also elevated, but did not reach the statistical significance. In the group of patients with positive scintigraphy results, a positive correlation was found between the uptake ratio and SACE (r=0.44, p=0.041). We show examples of practical application of somatostatin receptor scintigraphy for estimation of disease activity. CONCLUSIONS: The study shows low value of biochemical markers in clinical monitoring of sarcoidosis, but indicates the potential usefulness of somatostatin receptor scintigraphy in the monitoring of sarcoidosis.

• [Small airways in obstructive lung diseases].

  Authors: Andrzej M Fal, Ewa Niżankowska-Mogilnicka, Paweł Sliwiński, Andrzej Emeryk, Adam Antczak, Jerzy Kruszewski

  Pneumonologia i alergologia polska : organ Polskiego Towarzystwa Ftyzjopneumonologicznego, Polskiego Towarzystwa Alergologicznego, i Instytutu Gruźlicy i Chorób Płuc. 01/2012; 80(2):146-51.

  The term small airways (SA) applies to the bronchi below 7th generation with diameter smaller than 2 mm. This paper presents data showing that this part of the respiratory system is distinct in termsThe term small airways (SA) applies to the bronchi below 7th generation with diameter smaller than 2 mm. This paper presents data showing that this part of the respiratory system is distinct in terms of its architecture, physiology and pathophysiology. The most important role SA play in obstructive airway diseases. In healthy subjects SA resistance accounts for 10% of the total airway resistance while in patients with obstructive disease, due to the constriction of the airways together with airway inflammation, SA are responsible even for 60% of the total resistance. Changes in SA in asthma and COPD are responsible for air trapping especially prominent in the latter disease. There are no precise tools to diagnose SA. Depending availability and experience HRCT, body pletysmography (RV/TLS plus other parameters) are frequently used. Some hope for the future is placed in combined use of oscilometry, multiple (or single) breath nitrogen wash-out and eNO concentration measurement. Due to our increasing knowledge on the role of SA in airway obstruction ultra-fine particle aerosols have been developed that penetrate to this compartment of the respiratory system (deposition confirmed in cascade impactors as well as by ozone scans after aerosol inhalation). Authors present selected publications investigating whereas deep drug penetration influences its clinical efficacy. For LABAs deposition in SA doesn't seem to increase their bronchodilating effect. Using ultrafine CS aerosol allows to maintain clinical effects even with half the dose of the active steroid, however. In summary, SA seem to be crucial in obstructive diseases of the airways and therefore constitute an important target for therapy.

• Functional polymorphism of cyclooxygenase-2 gene (G-765C) in chronic obstructive pulmonary disease patients.

  Authors: Tadeusz Pietras, Janusz Szemraj, Michał Panek, Andrzej Witusik, Maciej Banasiak, Adam Antczak, Paweł Górski

  Molecular biology reports. 06/2011; 39(3):2163-7.

  Cyclooxygenase two (COX-2) is an important enzyme metabolizing arachidonic acid. In contrast to constitutive cyclooxygenase one (COX-1), COX-2 is induced by proinflammatory factors. Polymorphism -765Cyclooxygenase two (COX-2) is an important enzyme metabolizing arachidonic acid. In contrast to constitutive cyclooxygenase one (COX-1), COX-2 is induced by proinflammatory factors. Polymorphism -765 G/C in COX-2-encoding gene promoter is associated with development of Alzheimer's disease, depression, carcinoma of the pancreas in smokers, breast cancer and rheumatoid arthritis. It is interesting whether the -765 G/C polymorphism in COX-2-encoding gene promoter can be associated with COPD, a disease which is inflammatory in character. It is highly probable as the breast and pancreas cancers, whose associations with the analyzed polymorphism have been studied, are smoking-dependent tumors. Additionally, tobacco smoke has been demonstrated to induce COX-2 in the lungs. The study group consisted of 122 COPD patients (48 females, 74 males). The control group consisted of 149 healthy nonsmoking subjects (83 females, 66 males). Polymerase chain reaction/restriction fragment length polymorphism was used for genotyping. A statistically significant difference in genotype distribution was observed as a result of the comparison between healthy subjects and patients with COPD. The distribution of alleles in both groups conformed with Hardy-Weinberg equilibrium. In the group of COPD patients, GG allele was found in 79 subjects, GC in 36, and CC in 7 subjects (F = 0.094, P = 0.296927); in the control group, 73 subjects had GG allele, 68--GC and 8--CC (F = 0.12728, P = 0.120265). The allele frequency revealed differences between those groups, attaining the level of statistical significance (χ(2) = 29.043, df = 2, P = 0.0000. The carriers of -765 G allele are at 1.53-fold higher risk of developing COPD. The presence of GG genotype does not increase significantly the risk of the disease. It is also noteworthy that the carriers of CC or GC genotypes are at significantly lower risk of developing COPD than the group of subjects with GG genotype.

• Inflammatory Markers: Exhaled Nitric Oxide and Carbon Monoxide During the Ovarian Cycle.

  Authors: Adam Antczak, Maciej Ciebiada, Sergei A Kharitonov, Pawel Gorski, Peter J Barnes

  Inflammation. 05/2011;

  Nitric oxide (NO) production and carbon monoxide (CO) production are increased in inflammatory lung diseases. Although there are some pieces of evidence for hormonal modulation by estrogen, little isNitric oxide (NO) production and carbon monoxide (CO) production are increased in inflammatory lung diseases. Although there are some pieces of evidence for hormonal modulation by estrogen, little is known about exhaled NO and CO during the ovarian cycle. In 23 subjects, we measured exhaled NO and CO by an online analyzer. Significantly higher levels of exhaled NO were found at the midcycle compared with those in the premenstrual period or during menstruation. Higher levels of CO were after ovulation and reached a peak in the premenstrual phase. The lowest levels of CO were observed in the first days of the estrogen phase. In males, there was no significant variation in exhaled NO and CO. Exhaled NO and CO levels vary during the ovarian cycle in women, and this fact should be taken into account during serial measurements of these markers in the female population.

• [Pathogens isolated from patients with community-acquired lower respiratory tract infections].

  Authors: Agnieszka Kiryszewska, Adam Antczak

  Medycyna doświadczalna i mikrobiologia. 01/2011; 63(4):333-9.

  The aim of the study was to assess the prevalence and antimicrobial susceptibility of pathogens in patients hospitalized in Clinic of Pneumology and Alergology University Clinical Hospital No 1 inThe aim of the study was to assess the prevalence and antimicrobial susceptibility of pathogens in patients hospitalized in Clinic of Pneumology and Alergology University Clinical Hospital No 1 in Łodź in 2006-2008 period, due to community-acquired lower respiratory tract infections. In this samples of sputum, bronchoaspirate and BAL's were evaluated. The most frequent pathogens isolated from all examinated patients were Gram-negative rods. This bacteria were susceptible in most to imipenem (91%), ceftazydym (71%), amikacin (67%), ciprofloxacin (63%) and to amoxicillin with clavulanic acid only in 18%. This study show high prevalence of Gram-negative rods in patients hospitalized due to community-acquired lower respiratory tract infections.

• Correlation between eicosanoids in bronchoalveolar lavage fluid and in exhaled breath condensate.

  Authors: Adam Antczak, Wojciech Piotrowski, Jerzy Marczak, Maciej Ciebiada, Pawel Gorski, Peter J Barnes

  Disease markers. 01/2011; 30(5):213-20.

  Exhaled breath condensate (EBC) has been increasingly used as a new and non-invasive method to study airway inflammation. In this study we have compared the concentrations of lipid mediators in EBCExhaled breath condensate (EBC) has been increasingly used as a new and non-invasive method to study airway inflammation. In this study we have compared the concentrations of lipid mediators in EBC with concentrations in bronchoalveolar lavage fluid (BALF). We included 37 patients undergoing bronchoscopy (12 sarcoidosis, 12 COPD, 6 lung cancer, 5 chronic cough, 1 Wegener's granulomatosis, 1 sclerodermia). Patients were not allowed to have exacerbation or any change in concomitant medication for at least 4 weeks prior to the study. In all patients, EBC was collected immediately prior to the bronchoscopy. The levels of cys-LTs, LTB _{4} , 8-isoprostane were significantly higher in BALF compared to EBC (p < 0.0001, p< 0.001, p< 0.0001 for cys-LTs, LTB4, 8-isoprostane respectively). Moreover, there was a strong positive correlation between both leukotriene B _{4} and 8-isoprostane in BALF and EBC (r=0.53 and r=0.79, p< 0.01, respectively) in patients with sarcoidosis and COPD but there was no correlation between eicosanoids BALF and EBC in patients with chronic cough and lung cancer. This is the first study to compare EBC and BALF in different lung diseases which demonstrated significant correlations between the levels of eicosanoids in BALF and EBC in patients with COPD and sarcoidosis. EBC may be useful in measuring inflammation in several inflammatory lung diseases.

• Exhaled 8-isoprostane in sarcoidosis: relation to superoxide anion production by bronchoalveolar lavage cells.

  Authors: Wojciech J Piotrowski, Zofia Kurmanowska, Adam Antczak, Jerzy Marczak, Maciej Ciebiada, Paweł Górski

  Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 12/2010; 59(12):1027-32.

  This study was designed to examine the mutual relationship between 8-isoprostane in exhaled breath condensate (EBC) and superoxide anion generation by bronchoalveolar lavage fluid (BALF) cells inThis study was designed to examine the mutual relationship between 8-isoprostane in exhaled breath condensate (EBC) and superoxide anion generation by bronchoalveolar lavage fluid (BALF) cells in patients with sarcoidosis. About 29 patients with sarcoidosis, 34 healthy never smokers (control group for EBC) and 15 healthy never smokers (control group for BAL) were examined. EBC was collected directly before bronchoscopy. 8-Isoprostane was measured by ELISA, and superoxide anion by colorimetry. Exhaled breath condensate 8-isoprostane is increased in sarcoidosis (median, 25-75 percentile): 2.50; 2.50-3.90 versus 6.20; 2.50-16.95 pg/ml, p ≤ 0.05). Spontaneous superoxide anion release from BALF cells was significantly elevated only in patients with a high percentage of lymphocytes in BALF (6.42 ± 1.24 vs. 23.52 ± 4.30 nmol/10(6) cells, p ≤ 0.01). There were no correlations between 8-isoprostane and spontaneous or stimulated superoxide anion release. We confirmed higher concentrations of EBC 8-isoprostane in sarcoidosis and higher spontaneous release of superoxide anion from BALF cells in patients with sarcoidosis. The increase of EBC 8-isoprostane is not directly related to superoxide anion released from BALF cells.

• Rhinosinusitis in COPD: symptoms, mucosal changes, nasal lavage cells and eicosanoids.

  Authors: Violetta M Piotrowska, Wojciech J Piotrowski, Zofia Kurmanowska, Jerzy Marczak, Paweł Górski, Adam Antczak

  International journal of chronic obstructive pulmonary disease. 01/2010; 5:107-17.

  The coexistence of upper airways disease with chronic obstructive pulmonary disease (COPD) is not well documented. The aim of this research was to assess sino-nasal inflammation in COPD by variousThe coexistence of upper airways disease with chronic obstructive pulmonary disease (COPD) is not well documented. The aim of this research was to assess sino-nasal inflammation in COPD by various tools, and look for the impact on quality of life, relation to smoking, disease severity and systemic inflammation. Current and ex-smokers with COPD (n = 42) and healthy never-smokers (n = 21) were included in this study. COPD severity was assessed by GOLD criteria and BODE index. Markers of systemic inflammation were measured. Nasal symptoms and general quality of life were assessed using the questionnaires; sino-nasal questionnaire (SNAQ-11) and St. George's Respiratory Questionnaire (SGRQ). Nasal endoscopy and saccharine test were performed. Nasal lavages were collected for cytological examination and eicosanoids (cysteinyl leukotrienes, leukotriene B4, 8-isoprostane). Symptoms and endoscopic scores were higher in COPD (P < or = 0.0001). Only SGRQ symptoms subscore correlated with SNAQ-11 (r = 0.34, P = 0.035). Mucociliary clearance was impaired only in current smokers (9.91 +/- 0.49 versus 13.12 +/- 0.68 minutes, P < or = 0.001). 8-isoprostane was higher in COPD smokers compared to the controls (0.17 +/- 0.04 versus 0.34 +/- 0.09 pg/g protein, P < 0.05). Endoscopic score and mucociliary of impairment patients who currently smoked cigarettes correlated with concentrations of 8-isoprostane. None of the parameters correlated with disease severity and markers of systemic inflammation. We provide evidence of upper airways disease in COPD, which appears to be related more to patients who currently smoke than to disease severity.

• Exhaled 8-isoprostane as a prognostic marker in sarcoidosis. A short term follow-up.

  Authors: Wojciech J Piotrowski, Zofia Kurmanowska, Adam Antczak, Jerzy Marczak, Paweł Górski

  BMC pulmonary medicine. 01/2010; 10:23.

  8-Isoprostane (8-IP) is a marker of lipid peroxidation. Elevated concentrations have been reported in BAL fluid and exhaled breath condensate (EBC) in sarcoidosis (S). To validate the prognostic8-Isoprostane (8-IP) is a marker of lipid peroxidation. Elevated concentrations have been reported in BAL fluid and exhaled breath condensate (EBC) in sarcoidosis (S). To validate the prognostic value of this marker we tested whether: 1. high initial EBC 8-IP predispose to more severe disease; 2. low initial concentrations increase a chance of early remission; 3. remissions are connected with the decrease of EBC 8-IP. 40 patients (S) have been examined initially (V1) and after 8.5 +/- 0.5 months (V2). EBC 8-IP concentrations were measured by ELISA. Chest X-ray, lung function test, serum ACE and Ca2+ concentrations, 24 hrs Ca2+loss, abdominal ultrasonography, symptoms evaluation were performed. We confirmed higher concentrations of 8-IP in EBC of patients with sarcoidosis (p = 0.001). Relative risk (RR) of persistence of disease at V2 when initial 8-IP was above 20 pg/mL was 1.04, and the frequency distributions estimated by chi2 test were not significantly different. A chance (RR) of early complete remission when V1 8-IP was below DL, was 3.33 (p = 0.04 by chi2 test). A significant decrease of 8-IP at V2 was observed only in patients who received treatment (p = 0.03), but not in those with spontaneous remission. We come to the conclusion, that low initial 8-IP may be a positive prognostic factor. A decrease of 8-IP in treated patients reflects a non-specific effect of treatment and is not related to mere regression of disease.

• Hepatocyte growth factor in exhaled breath and BAL fluid in sarcoidosis.

  Authors: Wojciech J Piotrowski, Zofia Kurmanowska, Adam Antczak, Jerzy Marczak, Paweł Górski

  Pneumonologia i alergologia polska : organ Polskiego Towarzystwa Ftyzjopneumonologicznego, Polskiego Towarzystwa Alergologicznego, i Instytutu Gruźlicy i Chorób Płuc. 01/2010; 78(3):187-91.

  Hepatocyte growth factor (HGF) is a strong mitogen stimulating lung epithelial cell growth. Elevated levels of HGF have been reported in various biological materials of patients with acuteHepatocyte growth factor (HGF) is a strong mitogen stimulating lung epithelial cell growth. Elevated levels of HGF have been reported in various biological materials of patients with acute respiratory distress syndrome and in patients recovering from pneumonia or pneumonectomy. Sarcoidosis may be complicated by lung fibrosis. Consequently, HGF could be considered a new biomarker identifying patients with a higher risk of lung fibrosis. The aim of the study was to verify whether: 1. HGF is measurable in bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC); 2. HGF in BALF or EBC is impaired in sarcoidosis; and 3. HGF correlates with chosen activity and prognostic markers. Sixty-four EBC and 30 BALF of sarcoid patients, and 15 and 9 of healthy controls, respectively, were collected for the measurement of HGF using an ELISA test. HGF was detectable in 62% of EBC samples (56% sarcoidosis and 87% of controls) and in all the BALF samples. EBC and BALF concentrations were not different in comparison to the controls. Moreover, no correlation was found between EBC/BALF concentrations and radiological stage, lung function tests, duration of disease, number of relapses, BALF lymphocytes, serum ACE, or serum and urine calcium concentrations. HGF is detectable in BAL and EBC. However, it does not distinguish sarcoidosis patients from healthy subjects. The above, as well as the lack of correlations with various parameters of disease activity and severity rule out EBC/ /BALF HGF as a biomarker for sarcoidosis monitoring.

• Superoxide anion production by bronchoalveolar lavage cells in relation to cellular composition and lung function in sarcoidosis and chronic bronchitis.

  Authors: Wojciech J Piotrowski, Zofia Kurmanowska, Adam Antczak, Jerzy Marczak, Sebastian Majewski, Paweł Górski

  Polskie archiwum medycyny wewnȩtrznej. 12/2009; 119(12):777-84.

  INTRODUCTION: Increased generation of superoxide anion (O2 -.) by bronchoalveolar lavage (BAL) cells has been reported in various inflammatory disorders. However, the clinical relevance of thisINTRODUCTION: Increased generation of superoxide anion (O2 -.) by bronchoalveolar lavage (BAL) cells has been reported in various inflammatory disorders. However, the clinical relevance of this phenomenon is unclear. OBJECTIVES: The aim of the study was to investigate whether production of O2-. is enhanced in smoking-related chronic bronchitis and sarcoidosis, and to assess a relationship between O2-. generation and lung function impairment and changes in BAL cellular pattern. PATIENTS AND METHODS: Forty-two patients with sarcoidosis, 24 smokers with chronic bronchitis, and 17 controls were examined. A number/percentage of BAL cells was calculated. Spontaneous and phorbol myristate acetate (PMA)-stimulated O2-. production was measured in BAL cells. Spirometry was performed. RESULTS: Patients with smoking-related chronic bronchitis produced more O2 -. spontaneously (6.42 -/+1.24 vs. 15.39 -/+2.47 nmol/106 cells, P = 0.003) and after stimulation (3.73 -/+1.32 vs. 14.76 -/+2.79 nmol/106 cells; P = 0.001). PMA-stimulated excess production correlated with the percentage of neutrophils (r = 0.66, P = 0.0005). In sarcoidosis, only spontaneous production of O2 -. was higher (vs. 18.07 -/+2.49 nmol/106 cells, P = 0.004) and correlated with the percentage of BAL lymphocytes. There was no correlation between O2-. production and lung function parameters. CONCLUSIONS: Patients with smoking-related chronic bronchitis produce more O2-., and this phenomenon is related to BAL neutrophils. In sarcoidosis, spontaneous release of O2-. from BAL cells is related to the extent of lymphocytic alveolitis. Higher O2-. generation did not impair lung function.

• Metalloproteinases MMP-9, MMP-2 and their tissue inhibitors TIMP-1, TIMP-2 in peripheral transbronchial lung biopsies of patients with sarcoidosis.

  Authors: Wojciech J Piotrowski, Agnieszka Nawrocka-Kunecka, Adam Antczak, Jerzy Marczak, Romuald Biernacki, Piotr Kordek, Zofia Kurmanowska, Paweł Górski

  Polskie archiwum medycyny wewnȩtrznej. 10/2009; 119(10):628-35.

  INTRODUCTION: The imbalance between metalloproteinases (MMPs) and their tissue inhibitors TIMPs) may be involved in the pathogenesis of lung sarcoidosis, a granulomatous inflammatory disease whichINTRODUCTION: The imbalance between metalloproteinases (MMPs) and their tissue inhibitors TIMPs) may be involved in the pathogenesis of lung sarcoidosis, a granulomatous inflammatory disease which may lead to lung fibrosis. OBJECTIVES: The aim of the study was to verify whether the expression of MMP-9, MMP-2, TIMP-1, and TIMP-2 in peripheral lung biopsies of patients with sarcoidosis correlate with lung function tests, radiological pattern, and bronchoalveolar lavage (BAL) cells. We compared the expression of MMPs and TIMPs between patients with sarcoid-positive vs. - negative biopsy and fibrosing vs. non-fibrosing high-resolution computed tomography (HRCT)pattern. PATIENTS AND METHODS: We examined patients with histologically proven stage II and III sarcoidosis (n = 17). Immunohistochemistry with antibodies against the studied molecules was performed in the lung and bronchial tissue specimens obtained from transbronchial lung biopsies. The radiological pattern was evaluated based on HRCT. The total cell number and percentage of cells were calculated in the BAL samples. RESULTS: MMPs and TIMPs were present in the cells of sarcoid granuloma, and were more prevalent in the parenchyma than in the bronchi. We found no correlation between MMP-9, MMP-2, TIMP-1, TIMP-2 and HRCT pattern or BAL cells. There were inverse associations between MMP-9 and FEV1 (% predicted), and also between MMP-2 and maximal expiratory flow 25-75% (L and % predicted) in patients with sarcoidosis diagnosed by transbronchial lung biopsy. There were no differences in the measured parameters between patients with and without fibrotic changes and between those with negative vs. positive lung biopsy results. CONCLUSIONS: Our study provides an indirect evidence for a potential involvement of MMPs/TIMPs in the sarcoid inflammation of the distal airways.

• A Randomized, Double-blind, Placebo-controlled Study of TNF-{alpha} Blockade in Severe Persistent Asthma.

  Authors: Sally E Wenzel, Peter J Barnes, Eugene R Bleecker, Jean Bousquet, William Busse, Sven Erik Dahlen, Stephen T Holgate, Deborah A Meyers, Klaus F Rabe, Adam Antczak, James Baker, Ildiko Horvath, Zsuzsanna Mark, David Bernstein, Edward Kerwin, Rozsa Schlenker-Herceg, Kim Hung Lo, Rosemary Watt, Elliot S Barnathan, Pascal Chanez

  American journal of respiratory and critical care medicine. 02/2009;

  RATIONALE: The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor-alpha, in severe persistent asthma is unknown. OBJECTIVES: To assess the safety and efficacy ofRATIONALE: The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor-alpha, in severe persistent asthma is unknown. OBJECTIVES: To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma. METHODS: From 2004 to 2006, 309 patients with severe asthma, uncontrolled despite high-dose inhaled corticosteroids and long-acting beta2 agonists, were randomized 1:1:1:1 to monthly subcutaneous injections of placebo or golimumab (50, 100, or 200mg) through week 52. Co-primary endpoints were change from baseline through week 24 in prebronchodilator percent-predicted FEV1 and number of severe asthma exacerbations through week 24. MEASUREMENTS AND MAIN RESULTS: No significant differences were observed for change in percent-predicted FEV1 (LS mean: placebo 2.44 [95% CI -0.574-5.461], combined 100 and 200mg 2.91 [0.696-5.116]) or severe exacerbations (mean+/-SD: placebo 0.5+/-1.07 versus combined 100 and 200 mg 0.5+/-0.97) through week 24. Through week 24, 2.6% of placebo- versus 19.5% of golimumab-treated patients discontinued study agent, and 1.3% and 7.8%, respectively, discontinued study participation. An unfavorable risk-benefit profile led to early discontinuation of study-agent administration after the week-24 database lock. Through week 76, 20.5% placebo- and 30.3% golimumab-treated patients experienced SAEs, with serious infections occurring more frequently in golimumab-treated patients. One death and all 8 malignancies occurred in the active groups. CONCLUSIONS: Overall, treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients with severe persistent asthma. Clinical Trial Registration: NCT00207740 registered at www.clinicaltrials.gov.

• Life threatening pneumonia in a lupus patient: a case report.

  Authors: Maciej Kupczyk, Adam Antczak, Piotr Kuna, Paweł Górski

  Cases journal. 02/2008; 1(1):70.

  ABSTRACT: We report a case of systemic lupus erythematosus (SLE) in a 44-year old Caucasian woman complicated with pneumonia and severe respiratory failure requiring ICU treatment and mechanicalABSTRACT: We report a case of systemic lupus erythematosus (SLE) in a 44-year old Caucasian woman complicated with pneumonia and severe respiratory failure requiring ICU treatment and mechanical ventilation. Symptoms developed in a generally well controlled SLE course after sudden stop in immunosupresant therapy (methotrexate, cyclosporin and methylprednisolone). A fulminant course of the disease, an interstitial pattern in a high resolution computed tomography (HRCT) and negative repeated sputum, blood and bronchoaspirate cultures enabled diagnosis of fulminant lupus pneumonitis. The response to pulses of cyclophosphamide and methylprednisolone was good but complicated with a significant leukopenia. HRCT confirmed significant remission of pulmonary changes. Fulminant lupus pneumonitis is a rare but potentially life threatening complication of SLE. Differential diagnosis requires exclusion of pneumonia induced by pathogens such as Pneumocystis jirovevecii (carinii) and Mycobacterium sp. Intensive immunosuppressive therapy and close cooperation between ICU, pulmonology and rheumatology departments is necessary in such a case to minimalize the risk of fatal outcome.

• Eicosanoids in exhaled breath condensate and BAL fluid of patients with sarcoidosis.

  Authors: Wojciech J Piotrowski, Adam Antczak, Jerzy Marczak, Agnieszka Nawrocka, Zofia Kurmanowska, Pawel Górski

  Chest. 09/2007; 132(2):589-96.

  BACKGROUND: Measurement of inflammatory mediators in exhaled breath condensate (EBC) is an easy and noninvasive diagnostic method, which has gained popularity in the past few years. However, theBACKGROUND: Measurement of inflammatory mediators in exhaled breath condensate (EBC) is an easy and noninvasive diagnostic method, which has gained popularity in the past few years. However, the source of these mediators is not precisely defined. It has been only presumed that inflammatory cells present in the airway lumen are the main source. Therefore, the aim of this study was to verify the relationship between EBC and BAL fluid (BALF) eicosanoids, and the percentage, number, and activity of cells in BALF. METHODS: In 28 sarcoidosis patients and 17 healthy subjects, 8-isoprostane, cysteinyl leukotrienes (CysLTs), and leukotriene B4 (LTB4) were measured in EBC by enzyme immunoassay. Eicosanoids were also examined in BALF in the study group. Cell count, percentage, and superoxide production by BALF cells were estimated. RESULTS: The mean (+/- SEM) CysLT and 8-isoprostane concentrations were higher in the sarcoidosis group (6.5 +/- 0 vs 27.82 +/- 6.65 pg/mL, respectively; and 2.67 +/- 0.16 vs 13.95 +/- 2.59 pg/mL, respectively). There were positive correlations between EBC and BALF 8-isoprostane concentration (r = 0.68, p < 0.0001) and LTB4 concentration (r = 0.43; p = 0.026). EBC LTB4 levels correlated with the number of lymphocytes per milliliter of BALF. The percentage and number of eosinophils in BALF correlated with EBC 8-isoprostane and BALF CysLT concentrations. No positive correlation was found between concentrations of EBC eicosanoids and percentages BALF lymphocytes, BALF macrophages, or superoxide production. CONCLUSIONS: The levels of 8-isoprostane and CysLT are elevated in EBC in sarcoidosis patients; however, a lack of correlation with BALF lymphocyte percentage does not encourage us to recommend the measurement of eicosanoids as activity markers. The positive correlation of EBC 8-isoprostane and BALF CysLT concentrations with the percentage of eosinophils in BALF, and the higher percentage of eosinophils in BALF from patients with grade 3 sarcoidosis, may suggest the possible prognostic value.

• Increased exhaled cysteinyl-leukotrienes and 8-isoprostane in aspirin-induced asthma.

  Authors: Adam Antczak, Paolo Montuschi, Sergei Kharitonov, Pawel Gorski, Peter J Barnes

  American journal of respiratory and critical care medicine. 08/2002; 166(3):301-6.

  The pathogenesis of aspirin-induced asthma (AIA) has not yet been clearly elucidated, although eicosanoid metabolites appear to play an important role. We hypothesized that levels of eicosanoids inThe pathogenesis of aspirin-induced asthma (AIA) has not yet been clearly elucidated, although eicosanoid metabolites appear to play an important role. We hypothesized that levels of eicosanoids in exhaled air condensate are abnormal in patients with AIA and that they change in patients receiving steroid therapy. We measured cysteinyl-leukotrienes (cys-LTs), prostaglandin E(2) (PGE(2)), and leukotriene B(4) (LTB(4)), and also 8-isoprostane as a marker of oxidative stress, by enzyme immunoassay in exhaled breath condensate from patients with AIA (17 steroid naive; mean age, 41 +/- 23 years; FEV(1), 63%pred), 26 patients with aspirin-tolerant asthma (ATA) (11 steroid naive; mean age, 47 +/- 18 years; FEV(1), 69%pred), and 16 healthy subjects (mean age, 45 +/- 17 years; FEV(1), 93%pred). Cys-LTs were significantly higher in steroid-naive patients with AIA compared with steroid-naive patients with ATA and healthy subjects (152.3 +/- 30.4 and 36.6 +/- 7.1 versus 19.4 +/- 2.8 pg/ml; p < 0.05 and p < 0.05, respectively). Steroid-naive patients with AIA also had higher levels of 8-isoprostane than normal subjects (131.8 +/- 31.0 versus 21.9 +/- 4.5 pg/ml; p < 0.05). There were significantly lower levels of both cys-LTs and 8-isoprostanes in steroid-treated patients with AIA. There was no difference in either the PGE(2) or LTB(4) level between the patient groups. This is the first study to show that cys-LTs and 8-isoprostanes are elevated in expired breath condensate of steroid-naive patients with AIA, and that cys-LTs are decreased in steroid-treated patients. Exhaled PGE(2) levels are not reduced, so that it is unlikely that a deficiency of PGE(2) is an important mechanism, whereas exhaled LTB(4) levels are unchanged, indicating an abnormality beyond 5-lipoxygenase.

• Markers of pulmonary diseases in exhaled breath condensate.

  Authors: Adam Antczak, Pawel Górski

  International journal of occupational medicine and environmental health. 02/2002; 15(4):317-23.

  Exhaled breath condensate has been more and more extensively used as a novel and non-invasive method to study airway inflammation. It is simple to perform, very well tolerated by patients and noExhaled breath condensate has been more and more extensively used as a novel and non-invasive method to study airway inflammation. It is simple to perform, very well tolerated by patients and no adverse events have been reported so far. Serial measurements can be made with no harmful effects on patients, which is of extreme value in occupational medicine. Exhaled breath condensate has been obtained from both adult and children patients suffering from various pulmonary diseases such as asthma, cystic fibrosis, chronic obstructive pulmonary disease, and interstitial lung diseases. Several markers and mediators are detectable in breath condensate: hydrogen peroxide, thiobarbituric acid-reactive substances, isoprostanes, prostaglandins and leukotrienes. Nitric oxide-related markers have also been studied in the condensate. There is increasing body of evidence that changes in condensate markers reflect local abnormalities of airway lining fluid.

• Inflammatory response to sputum induction measured by exhaled markers.

  Authors: Adam Antczak, Sergei A Kharitonov, Paolo Montuschi, Pawel Gorski, Peter J Barnes

  Respiration; international review of thoracic diseases. 72(6):594-9.

  BACKGROUND: Sputum induction is increasingly used to study both cellular and biochemical composition of the airways. However, there is a significant rise in the percentage of neutrophils at 8 h afterBACKGROUND: Sputum induction is increasingly used to study both cellular and biochemical composition of the airways. However, there is a significant rise in the percentage of neutrophils at 8 h after inhalation with hypertonic saline. OBJECTIVE: The aim of this study was to assess whether markers of inflammation in exhaled air and exhaled air condensate change after sputum induction in normal and asthmatic subjects. METHODS: We measured leukotriene B(4) (LTB(4)) and a marker of oxidative stress, 8-isoprostane, (by enzyme immunoassay) in exhaled air condensate and exhaled nitric oxide (NO; by chemiluminescence analyzer) in 15 healthy subjects (8 females, mean age 35 +/- 4 years, FEV(1) 97.4% predicted) and in 8 mild asthmatic subjects (5 males, mean age 34 +/- 2 years, FEV(1) 70.5% predicted). RESULTS: LTB(4) was significantly higher compared with baseline at 6 h but did not remain increased at 24 h after sputum induction (134.3 +/- 30.15 and 75.4 +/- 14.32 vs. 64.6 +/- 11.6 pg/ml at baseline; p < 0.02 and p > 0.05, respectively) in healthy subjects. An inverse correlation between LTB(4) and exhaled NO at 6 h after sputum induction was observed in healthy subjects (r = -0.66, p < 0.03). No increase in LTB(4) levels was observed in asthmatic patients. Baseline 8-isoprostane levels were higher in asthmatic patients than in healthy subjects (47.3 +/- 37.1 vs. 17.5 +/- 8.8 pg/ml; p < 0.01). A trend towards increased levels of 8-isoprostane could be observed at 6 and 24 h after inhalation in healthy subjects (26.2 +/- 3.7 and 26.7 +/- 3.9 pg/ml; p = 0.09 and p = 0.07, respectively). In healthy subjects, exhaled NO was significantly higher compared with baseline at 6 h and remained increased 24 h after sputum induction (7.96 +/- 3.5 vs. 5.61 +/- 1.86 ppb; p < 0.01 and p < 0.05, respectively). Exhaled NO levels were increased in asthmatic patients but did not further increase after sputum induction. CONCLUSIONS: Sputum induction with hypertonic saline causes an inflammatory response which should be considered when using the technique to monitor airway inflammation.