Adriana Rozy

Does urinary peptide content differ between COPD patients with and without inherited alpha-1 antitrypsin deficiency?

Differentiating between chronic obstructive pulmonary disease (COPD) patients with normal (PiMM) or deficient (PiZZ) genetic variants of alpha-1 antitrypsin (A1AT) is important not only for understanding the pathobiology of disease progression but also for improving personalized therapies. This pilot study aimed to investigate whether urinary peptides reflect the A1AT-related phenotypes of COPD. Urine samples from 19 clinically stable COPD cases (7 PiMM and 12 PiZZ A1AT) were analyzed by capillary electrophoresis coupled to mass spectrometry. We identified 66 peptides (corresponding to 36 unique proteins) that differed between PiZZ and PiMM COPD. Among these, peptides from the collagen family were the most abundant and divergent. A logistic regression model based on COL1A1 or COL5A3 peptides enabled differentiation between PiMM and PiZZ groups, with a sensitivity of 100% and specificity of 85.71% for COL1A1 and a sensitivity of 91.67% and specificity of 85.71% for COL5A3. Furthermore, patients with PiZZ presented low levels of urinary peptides involved in lipoproteins/lipids and retinoic acid metabolism, such as apolipoprotein A-I and C4, retinol-binding protein 4 and prostaglandin-H2 D-isomerase. However, peptides of MDS1 and EVII complex locus, gelsolin and hemoglobin alpha were found in the urine of COPD cases with PiZZ, but not with PiMM. These capillary electrophoresis coupled to mass spectrometry-based results provide the first evidence that urinary peptide content differs between PiMM and PiZZ patients with COPD.

Clarithromycin Decreases IL-6 Concentration in Serum and BAL Fluid in Patients with Cryptogenic Organizing Pneumonia

BACKGROUND Inflammatory cytokines are involved in the development of cryptogenic organizing pneumonia (COP). It has been shown that macrolides inhibit cytokine production in the alveolar macrophages of COP patients. OBJECTIVES The aim of the study was to assess the concentrations of interleukin 1β (IL-1β), IL-6, IL-8 and transforming growth factor β (TGF-β) in serum and in bronchoalveolar lavage fluid (BAL-f) in COP patients treated with clarithromycin (CAM). MATERIAL AND METHODS The study involved 26 patients (18 women and 8 men, mean age 56.46 ± 8.83 years) with biopsy-proven COP. After being treated with CAM, a complete recovery was achieved in 22 patients, while four patients did not respond to the treatment. The ELISA method was used to measure the serum and BAL-f concentrations of IL-1β, IL-6, IL-8 and TGF-β. RESULTS Before treatment, the serum IL-1β1, IL-6, IL-8 and TGF-β1 concentrations were similar in responders and non-responders. Significant decreases in serum concentrations of IL-6 (8.98 ± 13.26 pg/mL vs. 3.1 ± 6.95 pg/mL; p = 0.005), IL-8 (20.14 ± 25.72 pg/mL vs. 10.14 ± 6.8 pg/mL; p = 0.007) and TGF-β1 (37.89 ± 12.49 ng/mL vs. 26.49 ± 12.45 ng/mL; p = 0.001) were found after treatment, as well as a significant decrease in the BAL-f concentration of IL-6 (30.56 ± 56.78 pg/mL vs. 4.53 ± 5.84 pg/mL; p = 0.036). Clarithromycin treatment resulted in a significantly lower mean value of serum IL-6 responders than non-responders. CONCLUSIONS In COP patients, response to clarithromycin treatment was associated with decreases in serum concentrations of IL-6, IL-8 and TGF-β, and of rations, and of the BAL-f concentration of IL-6.

Cryptogenic organizing pneumonia- IL1-β, IL-6, IL-8, and TGF- β concentrations in serum in patients treated with clarithromycin

Cryptogenic organizing pneumonia (COP) is a distinct clinicopathological entity with unknown etiology. The goal of the study was to assess concentrations of selected inflammatory cytokines in a serum in COP patients treated with clarithromycin (CAM), and correlation of it with response to treatment. Material and methods: In a 12-year period, 39 patients with COP (28 women and 11 men) in age 36-74 years, were enrolled to the study. CAM in a dose of 500 mg twice daily orally was administered to all patients for 3 months. Complete response was noted in 31 patients. Patients who did not respond or respond partially (2 and 6 patients respectively) were regarded as a non-responders (NR). The serum concentration of IL-1β, IL-6, IL-8 and TGF-β were assessed by ELISA method (R&D Systems) before and after the treatment. Results: CAM treatment was associated with significant decreasing of IL-6, IL-8, and TGF- β serum concentrations. It was particularly due to decreasing of serum concentrations of this cytokines in patients who respond to treatment. IL-1β serum concentrations was similar in R and NR, and CAM treatment did not influence on them. Serum concentrations of IL-6 and TGF-β did not drop significantly during treatment in NR, but significant decreasing of IL-8 serum concentration was noted in this patients. Conclusions: The study supports hypothesis regarding role of IL-6, IL-8 and TGF1β in pathogenesis of COP and it was proved that decreasing of its concentrations was connected with response to CAM treatment.

The prognostic importance of the protease-antiprotease imbalance in development of chronic obstructive pulmonary disease comorbid with chronic pancreatitis

Background: chronic obstructive pulmonary disease (COPD) is frequently comorbid with chronic pancreatitis (CP). One of the genes that could play a role in occurrence of that comorbidity by controlling protease-antiprotease balance, is a gene encoding alpha-1-antitrypsin (AAT). Aim: to find markers of susceptibility to CP in COPD patients. Methods: the serum levels of AAT, its genotype, tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9) and MMP-3 in serum were measured in COPD patients with/without CP in equal groups of 60 subjects each. Results: heterozygous carriers of deficient alleles were found in 5% of patients with comorbidity COPD and CP (group 1), while in the group without CP (group 2) - only 1.67%. Moreover, in group 1 there were a large number of people - 18.3% (11 of 60 patients) compared with data of group 2 - 8.3% (5 of 60) in whom the pathology of the respiratory and digestive systems was associated with a lack production of AAT. A significantly higher serum MMP-9 level was observed in patients from group 1 (median - 242.92 ng/ml vs. 131.15 ng/ml). Changes of TIMP 1 had multidirectional character - among 30.56% of patients from group 1 there were increased serum level of TIMP 1, whereas in 16.67% of patients from group 2 this indicator was marked decreased. There were no statistically significant differences in MMP-3 serum levels between the studied groups. Conclusions. Heterozygosity for PiM- polymorphisms and especially both serum AAT and MMP-9 levels are valuable biomarkers for verification predisposition to the occurrence CP among COPD patients.