Blood eosinophil (EOS) count, exacerbation rate and response to roflumilast in patients with severe COPD
Introduction: Studies suggest that high blood EOS count may be a marker of increased exacerbation risk in COPD patients (pts) with a history of exacerbations. We investigated the effect of blood EOS count on the efficacy of roflumilast (ROF) on COPD exacerbation rate.Methods: A post-hoc analysis was performed on two trials (REACT [NCT01329029], RE2SPOND [NCT01443845]) in which pts with severe COPD and ≥2 exacerbations in the previous year were randomised to ROF 500μg od or placebo (PBO) added to ICS/LABA±LAMA for 52 weeks. Primary endpoint was rate of moderate or severe COPD exacerbations/pt/year. Exacerbation...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Martinez, F. J., Rabe, K., Calverley, P., Fabbri, L., Sethi, S., Pizzichini, E., McIvor, A., Anzueto, A., Alagappan, V., Siddiqui, S., Reisner, C., Purkayastha, D., Roman, J., Rennard, S. Tags: Clinical Problems COPD Source Type: research

MISSION COPD: A novel model of integrated multidisciplinary COPD care that demonstrates significant reductions in unscheduled health care usage
Introduction: The MISSION COPD project delivered a one-stop carousel model of integrated COPD care to patients in Wessex in Autumn 2015.Methods: Patients were identified using the GRASP tool. Patients were subdivided in to a "case cohort" where no diagnosis was documented but COPD was suspected, and a "care cohort" where there was a pre-existing diagnosis. Data on healthcare usage for 12 months before the clinic and 6 months after (annualised to 12 months) were used to assess the efficacy of the clinic model.Results: 108 patients were reviewed, with 98 being included in the research project. Complete fo...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Lanning, E., Longstaff, J., Roberts, C., Jones, T., Neville, D., Storrar, W., Green, B., Brown, T., Chauhan, A. Tags: Clinical Problems COPD Source Type: research

Evaluation of roflumilast in COPD patients in a real-world European setting: results from the PROFILE EU study
Conclusions: These results suggest that the use of ROF in standard clinical practice may reduce the frequency of COPD exacerbations. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Vogelmeier, C., Tzanakis, N., Lassan, S., Genofre, E., Ding, B., Horton, J., Bakke, P. Tags: Clinical Problems COPD Source Type: research

Role of non-cystic fibrosis bronchiectasis in hospitalized patients with acute exacerbation of COPD
Conclusion: After elimination of confounding factors, our study demonstrates that the presence of NCFB does not influence the risk of death in a long-term follow-up. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Crisafulli, E., Guerrero, M., Ielpo, A., Huerta, A., Gabarrus, A., Soler, N., Chetta, A., Torres, A. Tags: Clinical Problems COPD Source Type: research

Determining SGRQ and TDI responder rates across the duration of clinical trials: Results from tiotropium + olodaterol in COPD
Conclusion: Analysing SGRQ and TDI responders using AUC and mean values allows investigation over a longer period of time and may be a better way to define responders than using only a single timepoint. The results consistently show an improved response of T+O compared to its mono-components. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Derom, E., Watz, H., Grönke, L., Voss, F., Buhl, R. Tags: Clinical Problems COPD Source Type: research

Validation of the GOLD 2017 classification in predicting exacerbations and mortality in COPD patients
Conclusions: The GOLD 2017 classification performed well by identifying individuals at risk of exacerbations, but its predictive ability for mortality was poor among COPD patients. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Chen, C.-Z., Hua, T.-H., Han, M.-Z., Tsai, S.-H., Hsiue, T.-R. Tags: Clinical Problems COPD Source Type: research

Population-based analysis of COPD patients in Catalonia: implications for case management
Conclusions: The predictive models stress the explanatory role of the covariate multimorbidity. The results highly encourage further developments fostering interoperability between health registries and electronic health records to enhance clinical risk prediction. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Baltaxe, E., Roca, J., Vela, E., Tenyi, A., Cano, I., Monterde, D., Claries, M., Garcia-Altes, A., Hernandez, C., Escarrabill, J. Tags: Clinical Problems COPD Source Type: research

Impact of comorbid bronchiectasis on COPD patients
According to the GOLD Guidelines, bronchiectasis (BE) is one of the comorbidities of COPD. It seems to have an important impact on the natural history of COPD.Aims: To determine the impact of coexistent bronchiectasis on COPD outcomes.Methods: A retrospective single-centre study of COPD patients with Bronchiectasis revealed by chest computed tomography. We compared 2 groups of patients: G1: COPD patients with BE (84 cases, 20%); G2: no BE at CTscan (339 cases, 80%). Clinical, functional and bacteriologic features were analyzed.Results: The study included 423 COPD patients (mean age 65+/-11 years, 97% males). No significant...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Ben Saad, A., Joobeur, S., Fahem, N., Cheikh Mhamed, S., Mribah, H., Rouatbi, N., El Kamel, A. Tags: Clinical Problems COPD Source Type: research

Clinical effect of different pneumococcal vaccination schedules in patients with chronic obstructive pulmonary disease (COPD): long-term follow-up results
Conclusion: After a 4-year follow-up the best effect of the vaccine was observed in the PCV13/PPV23 group. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Protasov, A., Kostinov, M., Zhestkov, A. Tags: Clinical Problems COPD Source Type: research

The allelic frequency for S and Z mutations in the SERPINA1 gene in NSCLC patients from Poland
Conclusions: The frequency of Pi*S and Pi*Z alleles in NSCLC patients differ noticeably from the general Polish population (Pi*Z 13.7/1000 and Pi*S 7.6/1000): the frequency of Pi*Z allele is lower whereas the frequency of Pi*S is higher. The NSCLC patients who carry AATD allele do not present reduced AAT concentration in blood as compared to the reference values from population studies. The study is on-going. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Komorowski, M., Szpechcinski, A., Debek, E., Duk, K., Zdral, A., Florczuk, M., Rudzinski, P., Kupis, W., Zaleska, J., Langfort, R., Orlowski, T., Roszkowski-Sliz, K., Chorostowska-Wynimko, J. Tags: Molecular Pathology and Functional Genomics Source Type: research

p.Leu747Pro mutation leads to misdiagnosis in EGFR mutation assessment - first Caucasian NSCLC patients reported
Epidermal growth factor receptor (EGFR) mutation assessment is essential for targeted therapy of non-small cell lung cancer (NSCLC) as predictive biomarker of the response to EGFR tyrosine kinase inhibitors (TKI).There is a number of well-known mutations in EGFR gene. Still infrequent or complex aberrations are also observed. p.Leu747Pro is one of rare mutations which might be misdiagnosed by commercial real-time PCR kits for EGFR mutation analysis. It is an inhibiting mutation. Importantly, it might be confused with an activating deletion in exon 19 of EGFR gene.The aim of the study was to assess the occurrence of p.Leu74...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Duk, K., Skronska, P., Skronski, M., Zdral, A., Chorostowska-Wynimko, J. Tags: Molecular Pathology and Functional Genomics Source Type: research

Transcriptomic profiling reveals M1-high tumour associated macrophages that orchestrate the adaptive Anti-tumour response in human lung cancer
We describe a novel set of M1high TAMs that simultaneously activate M1 and M2 signatures. M1high TAMs strongly activate antigen-presenting genes and express high levels of T-cell chemoattractants (CXCL9, 10 and 11), associating with a higher infiltration of anti-tumour CD8+ T-cells and a better clinical outcome. AIM2 and IL1beta levels are increased in M1high TAMs, indicating a direct involvement in pyroptosis and clearance of cancer cells. We provide a unique transcriptomic resource of TAMs in lung cancer and propose that TAMs can be used to improve immunotherapy due to a novel and pivotal role for M1high TAMs in orchestr...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Garrido-Martin, E. M., Ottensmeier, C., Vijayanand, P., Sanchez-Elsner, T. Tags: Molecular Pathology and Functional Genomics Source Type: research

Expression of Her-2/neu and Bcl-2 in patients with non-small cell lung cancer
The aim of this study: was to evaluate the expression of protein products of HER-2/neu and Bcl-2 in patients with non-small cell lung carcinoma (NSCLC), and to assess their clinicopathological and prognostic significance.Methods: HER-2/neu and Bcl-2 were investigated immunohistochemically using tumor semples obtained from 87 NSCLC patients. The immunohistochemical study was performed on formalin-fixed, paraffin-embedded sections using LCAB immunoperoxidase method with specific monoclonal antibody for HER-s/neu and Bcl-2.Results: The overall expression of HER-2/neu and Bcl-2 in 87 patients with NSCLC was 25,2% and 21,3% res...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Ilievska Poposka, B., Petrusevska, G. Tags: Molecular Pathology and Functional Genomics Source Type: research

Characterization of cultured primary/metastatic lung cancer cells obtained by percutaneous puncture
Conclusions: Primary culture of human lung tumor cells obtained by percutaneous puncture can be successfully achieved with the method described. These primary cultures of cancer cells showed rearrangements of chromosomes and change in their complement chromosomic typical of tumoral cells. Aditionally, Fluorescence in situ Hybridization analysis showed that three cultures showed amplification for EGFR. Finally the expression profiles of the CK7, Napsin A, TTF-1 and P63 genes allowed in most cases to confirm the tumor phenotype of the samples. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Rojas Moreno, A., Canas Arboleda, A., Herreno, A., Fernandez, M. J., Mejia, J. A., Moreno Nino, O. M., Rey, L., Bustos, F., Montecino, M. Tags: Molecular Pathology and Functional Genomics Source Type: research

A metabolite of prostaglandin D2, 15-deoxy-?12,14-prostaglandin J2 (15d-PGJ2), in exhaled breath condensate (EBC) of asthma patients
Conclusion: The content of 15d-PGJ2 in EBC is higher than 11β-PGF2α, as found earlier, thus making it more preferable for the estimation of the level of unstable PGD2 in EBC.Supported by Russian Science Foundation (grant No.14-25-00019). (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Perelman, J. M., Nekrasov, E. V., Prikhodko, A. G., Makarova, G. A. Tags: Molecular Pathology and Functional Genomics Source Type: research

The role of glucocorticoid receptor {alpha} and {beta} isoforms in exacerbations of asthma, COPD, and ACOS
Background: Glucocorticoid receptor (GR) β is a well-known antagonist of GR α and it may cause a steroid resistance (SR) in patients with chronic inflammatory or oncological diseases. However, the role of GR α and β in non-SR patients is not determined.Aim: to evaluate GR α, β expression and its clinical role in exacerbations of asthma, COPD, and ACOS.Materials and Methods: The levels of GR α, β mRNAs were measured by real-time PCR in 89 subjects aged 63.4±10.7, namely 22 exacerbated BA, 21 exacerbated COPD, 26 exacerbated ACOS, and 20 controls. DNA samples from all patien...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Belash, V., Mironova, Z., Trofimov, V., Vsevolodskaia, E., Zaraiski, M., Sazanov, A., Ulitina, A., Pchelina, S. Tags: Molecular Pathology and Functional Genomics Source Type: research

Association between pentanucleotide repeat polymorphism in NOS2 promoter and asthma exacerbations
Introduction: Polymorphisms of inducible nitric oxide synthase (NOS2) gene is related to fractional exhaled nitric oxide (FeNO) level in steroid-naive patients with asthma, but its association with treatment outcomes remains unclear.Aims and objectives: We investigated the association of NOS2 polymorphism with exacerbations in patients with asthma.Methods: NOS2 pentanucleotide repeat (CCTTT)n polymorphisms were genotyped in 136 patients with moderate/severe asthma. Cross-sectionally, we evaluated NOS2 mRNA expression levels in peripheral blood mononuclear cells, FeNO levels, white blood cell counts and lung function. Exace...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Hirai, K., Shirai, T., Suzuki, M., Tsuji, D., Inoue, K., Itoh, K. Tags: Molecular Pathology and Functional Genomics Source Type: research

Clustering of patients with bronchial asthma with regard to the genotypes for Bcl1 polymorphism in the glucocorticoid receptor gene
Conclusions: Cluster analysis of BA patients with regard to the genotypes of VcI1 polymorphism demonstrated 3 different BA subphenotypes that differed from each other in sex, BA course and control, values of respiratory function, BMI and inflammatory markers. These can contribute to individual approach to diagnostics and treatment of BA in the future. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Kmyta, V., Prystupa, L. Tags: Molecular Pathology and Functional Genomics Source Type: research

Transcriptional factors F???3,?-Maf, GATA3 and T-bet in different variants of bronchial asthma
Predominance of Th-cells populations has been previously shown in patients with differtentvariants of bronchial asthma. To investigate cross-talk interactions between lymphocyte transcriptional factors Foxp3, c-Maf, GATA3 and T-bet we evaluated blood samples of 47 healthy volunteers and 82 patients with bronchial asthma. mRNA expression of Fop3, c-Maf, GATA3 and T-bet was measured by RT-PCR, the levels of associated cytokines were analyzed by ready-to-use ELISA kits. We revealed high levels of GATA3, c-Maf, IL-4, IL-13 and IgE in patients with allergic bronchial asthma. On the contrary, in non-allergic bronchial asthma T-b...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Eremeeva, A., Sorokina, L., Mineev, V., Nyoma, M., Trofimov, V. Tags: Molecular Pathology and Functional Genomics Source Type: research

A hypothesis driven approach investigating the interleukin-6 pathway in UBIOPRED severe asthma patients
In this study, we investigated whether sputum IL-6 pathway activity is aberrant in a subgroup of asthma patients and is associated with particular clinical characteristics. We used a hypothesis driven analysis by investigating sputum transcriptomics (n=77), sputum and blood proteomics and clinical data from UBIOPRED consortium severe asthma cohort. As asthma is a heterogeneous disease, we used a clustering approach to identify subgroups of patients using genes correlated with IL6R sputum mRNA.The analysis identified two subgroups with high (n=33) and low (n=28) IL6R expression. Mean IL6R expression level in the high IL6R group was 2.8-fold (p
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Turan, N., Bates, S., Edwards, M., Shaw, D. E., Chung, K. F., James, A., Loza, M. J., Van Oosterhout, A. J., UBIOPRED study group Tags: Molecular Pathology and Functional Genomics Source Type: research

Distinctive gene signature of allergen-specific CD4+T cells in allergic patients
Allergic patients display abnormal immune responses to harmless antigens, including abnormal Th2 polarization and induction of allergen-specific T and B cells, resulting in development of allergy instead of tolerance. Allergen-specific immunotherapy (AIT) is currently the only causative treatment of allergic disorders. Yet, understanding of the underlying differences in allergen-specific responses between allergy and tolerance is lacking. We investigated whole-genome transcriptomics of circulating birch and grass specific CD4+ T cells in patients before and during AIT, as well in non-allergic healthy controls. Detailed imm...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Sokolowska, M., Boonpiyathad, T., Eljaszewicz, A., Castro Giner, F., Ruchti, F., Globinska, A., Ruckert, B., Dreher, A., Radzikowska, U., Morita, H., Jansen, K., Rinaldi, A., Gschwend, A., Meyer, N., Helbling, A., Negoias, S., Hool, S.-L., Borner, U., Kwo Tags: Molecular Pathology and Functional Genomics Source Type: research

Urinary metabolomics-based molecular sub-phenotyping of the U-BIOPRED asthma cohort
Introduction: Asthma is heterogeneous disease consisting of multiple sub-phenotypes that are poorly definedAim: To investigate the utility of the urinary metabolome to identify sub-phenotypes of severe asthma via molecular phenotypingMethods: Spot urine was collected from healthy controls (HC, n=108), mild-to-moderate asthmatics (MMA, n=87), severe asthmatics (SA); including both non-smokers (SAns, n=310) and smokers (SAs, n=108) from the U-BIOPRED cohort (Shaw et al, Eur Respir J. 2015; 46:1308). Metabolomics data were acquired using liquid chromatography coupled to mass spectrometry. Data were analysed using Principal Co...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Wheelock, C., Naz, S., Reinke, S., Chaleckis, R., Schofield, J., Skipp, P., Bigler, J., Loza, M., Baribaud, F., Bakke, P., Caruso, M., Chanez, P., Fowler, S., Horvath, K., Krug, N., Montuschi, P., Sanak, M., Sandstrom, T., Shaw, D., Chung, F., Djukanovic, Tags: Molecular Pathology and Functional Genomics Source Type: research

Late Breaking Abstract - The "one airway, one disease" concept at the light of Th2 inflammation
Conclusions: Nasal and bronchial epithelia display distinct transcriptional signatures. In AR group, but not in R group, nasal cells can be used as bronchial surrogates to assess Th2 inflammation. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Giovannini-Chami, L., Paquet, A., Sanfiorenzo, C., Pons, N., Cazareth, J., Magnone, V., Le Brigand, K., Chevalier, B., Julia, V., Leroy, S., Marquette, C.-H., Barbry, P., Marcet, B. Tags: Molecular Pathology and Functional Genomics Source Type: research

Propolis reverts cigarette smoke-induced emphysema through macrophage alternative activation
Emphysema is an incurable and progressive disease, and cigarette smoke (CS) is the main risk factor. Natural extracts have shown antioxidant and anti-inflammatory properties that can prevent acute lung inflammation and emphysema, but there are almost no reports in literature about therapeutics approaches to emphysema. We hypothesized if supplementation with propolis would repair lung damage in emphysema caused by CS exposure. C57BL/6 mice were exposed to 60 days of CS and then treated or not with propolis extract orally for more 60 days. Histological analysis revealed significant improvement in lung histoarchiteture, with ...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Deus, M., Barroso, M., Cavalieri, I., Gitirana, L. d. B., Fautrel, A., Lagente, V., Schmidt, M., Porto, L. C., Souza, B. R. d., Valenca, S. d. S. Tags: Mechanisms of Lung Injury and Repair Source Type: research

Different microenvironment stimuli results in distinct patterns of macrophages polarization comparing elastase- and cigarette smoke - induced models of emphysema
Rationale: Depending on microenvironment stimuli, macrophages can be polarized into M1("classical") or M2 ("alternative")phenotypes.Aim:To verify M1 and M2 phenotypes in the CS- and elastase- induced models.Methods: Mice were submitted to CS exposure (CS Group)and the Control group were maintained in ambient air for 3 months or animals received elastase instillation (50 μL;0,667UI)(PPE Group) and their control received saline solution(Sal Group) and euthanized at the 28th day. In lungs, real-time PCR were performed to evaluate M1-(CXCL9, CXCL10, IL-12b) and M2-(FIZZ-1, ARG-1)genes expression, M2- (IL...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Benini Kohler, J., Cervilha, D. A. B., Ito, J. T., Moreira, A. R., Santana, F. R., Farias, T. M., Alonso- Vale, M. I. C., Prado, C. M., Arruda Martins, M., Lopes, F. D. T. Q. S., Franca, L. E. Tags: Mechanisms of Lung Injury and Repair Source Type: research

The protective effects of thymoquinone on lung damage developed by cigarette smoke
This study aims to investigate the preventive and curative effects of TQ on lung damage created by cigarette smoke on rats. Fifty adult male Wistar albino rats were included in this study. Thirty subjects were randomized to exposure to tobacco smoke every day for 3 months. Intraperitoneal(IP) TQ was administered every day to ten subjects to investigate the protective effects of TQ, and on the last 21 days to ten subjects to investigate the curative effect. Ten subjects received IP saline for last 21 days. Ten subjects were enrolled as control group. Ten controls received IP TQ for last 10 days. Close circuit cage apparatus...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: yetkin, N. A., Büyükoglan, H., Sönmez, M. F., Tutar, N., Yilmaz, I., Gulmez, I. Tags: Mechanisms of Lung Injury and Repair Source Type: research

Regulatory T cells in COPD development: How the animal model resembles the human pathophysiological features
Background: We demonstrated in patients that COPD is associated with an increase in CD4+ and CD8+Tcells and interleukin (IL)-17+cells with a decrease in the regulatory T cells (Treg)+ and a reduction of inhibitory interleukin (IL-10+) in the airways (Sales, DS et al. Inflamm Res.2015;64, Suppl2:S228).Aims: To verify T cells subtypes in COPD development.Methods: Mice were exposed to cigarette smoke (CS) for 1, 3 and 6 months. We performed functional (tissue damping:Gtis and tissue elastance:Htis) and structural analysis (mean linear intercept:Lm). We quantified positive cells stained for TCD4, TCD8, Treg, IL-17 and IL-10 in...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Ito, J. T., Cervilha, D. A. d. B., Silva, L. E. d. F., Lourenco, J. D., Moreira, A. R., Kohler, J. B., Negri, E. M., Macchione, M., Mauad, T., Martins, M. A., Lopes, F. D. T. Q. d. S. Tags: Mechanisms of Lung Injury and Repair Source Type: research

Detection and inhibition of ENaC-activating proteases associated with airway dehydration in COPD
The objective of this study was to determine TL-CAP activity in primary COPD airway epithelial cells (AECs) and to assess the effectiveness of a highly novel in-house inhibitor, NAP858 compared to our established compound QUB-TL1 (Reihill et al, AJRCCM 2016;194(6):701-10).Secreted TL-CAP activity was determined in conditioned media recovered from primary differentiated COPD and healthy AECs treated in the presence and absence of QUB-TL1 and NAP858 by the hydrolysis of BOC-QAR-NH2Mec over 60 min.COPD AECs were found to secrete ~40% more TL-CAP activity than healthy cell controls. These activities were highly sensitive to QU...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Martin, L., Reihill, J., Douglas, L., Ferguson, T., Walker, B. Tags: Mechanisms of Lung Injury and Repair Source Type: research

Therapeutic effects of human perivascular stem cells in an emphysema mouse model
Conclusions: We demonstrated that lung injury was ameliorated by PVC-CM, which could be an alternative source for cell-based therapy in pulmonary diseases (This research was supported by Global PH.D Fellowship Program through the National Research Foundation of Korea funded by the Ministry of Education (2016R1A2B4014890 and 2016H1A2A1909769)). (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Hong, S.-H., Heo, H.-R., Kim, J. Y., Kim, J., Yang, S.-R., Lee, H., Kim, K.-S., Kim, W. J. Tags: Mechanisms of Lung Injury and Repair Source Type: research

FPS-ZM1-induced blocking of RAGE alleviates elastase-induced emphysema development by preventing RAGE-DAMP-Nrf2 signaling
Conclusions: Our data indicated for the first time that RAGE inhibition has an essential protective role in COPD. Our observation provided new insight into the therapeutic target in emphysema/COPD.Acknowledgments: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2014R1A2A2A01003737) (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Lee, H., Heo, H.-R., Kim, J. Y., Kim, W. J., Hong, S.-H., Yang, S.-R. Tags: Mechanisms of Lung Injury and Repair Source Type: research

Effect of ultrafine particle matter on human peripheral blood mononuclear cells of chronic obstructive pulmonary disease patients: involvement of the inflammasome
Inflammation is central to the development of chronic obstructive pulmonary disease (COPD), caused by inhalation of noxious particles or gas, especially cigarette smoke (CS). Emerging genetic and pharmacological evidence suggests that IL-1-like cytokines are highly detected in the sputum and broncho-alveolar lavage (BAL) of COPD patients, implying the involvement of the multiprotein complex inflammasome. In order to understand the role of this complex in COPD, we isolated PBMCs from healthy volunteers (smoker and non-smoker) and COPD patients. To mimic environmental pollution, PBMCs were treated with ultrafine particulate matter (UFP,
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Colarusso, C., De Falco, G., Terlizzi, M., Imitazione, P., Commodo, M., Sirignano, M., DAnna, A., Aquino, R. P., Pinto, A., Molino, A., Sorrentino, R. Tags: Mechanisms of Lung Injury and Repair Source Type: research

ATRvD1 reverts cigarette smoke-induced emphysema by pro-resolutive and antioxidant effects
In conclusion, ATRvD1 has a pro-resolutive effect contributing to tissue repair. Some antioxidant action is evident by increasing enzymatic and non-enzymatic antioxidant response in this model being a potent therapeutic agent. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Daher de Deus, M. L., Vergel Posso, S., Quesnot, N., Barroso, M. V., Kennedy Feitosa, E., Vasconcelos, F. M., Gitirana, L. d. B., Valenca, S. d. S. Tags: Mechanisms of Lung Injury and Repair Source Type: research

SIRT 1 and oxidative stress in COPD pathogenesis
Background: Increasing evidence indicates that oxidative stress and inflammation are strictly correlated to cellular senescence and aging. SIRT1, an anti-aging, anti-oxidative and anti-inflammatory protein, represents a connecting link among these processes characterizing COPD.Objectives: 1) to compare the expression and activity of SIRT 1 in the peripheral blood mononuclear cells (PBMC) of smokers, non smokers and COPD patients; 2) to investigate the association between SIRT1 and markers of oxidative stress and inflammation and 3) to assess the correlation between the markers of oxidative stress, SIRT1 and lung function.M...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Vitale, C., Conti, V., Maglio, A., Manzo, V., Malangone, P., Corbi, G., Cotugno, R., Capaccio, D., Filippelli, A., Vatrella, A. Tags: Airway Cell Biology and Immunopathology Source Type: research

Irisin stimulates the secretion of hyaluronic acid by airway smooth muscle cells from patients with chronic obstructive pulmonary disease
Irisin is a recently discovered myokine, which has been proposed to mediate the beneficial effects of exercise as it increases total body energy expenditure, reduces body weight and increases insulin sensitivity. Physical activity has been emphasized as one of the principal targets for the treatment of COPD. Hyaluronic acid (HA) plays a key role in airway remodeling, which is a hallmark in COPD.The aim of our study was to investigate the effect of irisin on the secretion of HA by primary human airway smooth muscle cells (ASMC) from patients with COPD.We established primary cultures of ASMC from endo-bronchial biopsies of p...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Papakonstantinou, E., Roth, M., Fang, L., Tamm, M., Stolz, D. Tags: Airway Cell Biology and Immunopathology Source Type: research

Organophosphorus pesticides increase inflammatory cytokines by activating macrophage Mac-1
Conclusion: OPs promote inflammatory cytokine production in the airway through macrophage Mac-1 activation. Mac-1 is a promising therapeutic target for prevention of OP-related asthma.FUNDING: NIH: ES017592, HL124165, HL113023, AR061567. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Proskocil, B., Lein, P., Jacoby, D., Fryer, A. Tags: Airway Cell Biology and Immunopathology Source Type: research

Insulin acutely potentiates M3 muscarinic receptor function in rat and human airway smooth muscle
Conclusions: In addition to increasing acetylcholine release via loss of M2 function, insulin may also contribute to airway hyperreactivity in obesity induced asthma by increasing M3 receptor mediated contraction of airway smooth muscle.Grants: R01HL131525, R01HL113023, R01AR061567, R01HL124165, R01ES017592, Health Effects Institute. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Nie, z., Jacoby, D., Fryer, A. Tags: Airway Cell Biology and Immunopathology Source Type: research

Irisin is associated with clinical outcomes and up-regulated by long-acting anticholinergics in COPD
Irisin is a myokine suggested to regulate energy expenditure and exercise capacity. It is regulated by peroxisome proliferator-activated receptor- coactivator-1-α (PGC1-a) and is proteolytically cleaved from fibronectin-type-III domain-containing protein-5 (FNDC5).The aim of our study was to investigate whether circulating irisin is associated with clinically relevant outcomes in COPD.Irisin was assessed in serum of 506 patients with COPD, GOLD grades II-IV at stable state and at exacerbation. The effect of inhaled long-acting muscarinic antagonists (LAMA) on serum irisin levels was subsequently evaluated in a proof-...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Papakonstantinou, E., Roth, M., Mandal, J., Sun, Q., Costa, L., Boeck, L., Scherr, A., Rakic, J., Louis, R., Milenkovic, B., Boersma, W., Kostikas, K., Blasi, F., Aerts, J., Rohde, G., Lacoma, A., Torres, A., Welte, T., Stolz, D., Tamm, M. Tags: Airway Cell Biology and Immunopathology Source Type: research

MicroRNA profiling of asthmatic bronchial epithelial cells
Conclusions: Medications with up-regulating effect on the identified microRNAs might be worthy to develop as a novel anti-asthmatic treatment. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Tsai, M.-J., Chang, W.-A., Sheu, C.-C., Hung, J.-Y., Tsai, Y.-C., Hsu, Y.-L., Kuo, P.-L., Chong, I.-W. Tags: Airway Cell Biology and Immunopathology Source Type: research

T helper cells subtypes and their cytokine gene expression affected by carvacrol in sensitized mice administered during sensitization period
Carvacrol showed various pharmacological effects including anti-inflammatory property. In the present study, the effects of carvacrol on Th1, Th2, Th17 and T reulatory subpopulations as well as their cytokine gene expressions in sensitized mice were examined. Mice were sensitized by ovalbumin injection and inhalation. Animal were randomly assigned to: control, sensitize (S), S treated with dexamethasone (0.1mM), and carvacrol (75, 150 and 300 mg/kg) during sensitization period. Spleen cells were then extracted and gene expressions of IL-4, IFN-, TGF-β, FOXP3, and IL-17 mRNA were assessed by Real time PCR. In addition,...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Boskabady, M. H., Kianmehr, M., Ghorani, V. Tags: Airway Cell Biology and Immunopathology Source Type: research

Anti-inflammatory role of myeloid-derived suppressor cells in asthma in vivo
Conclusions: Collectively, our results demonstrate that MDSCs suppress Th2-dominant inflammation and improve lung function in asthmatic mice in vivo. Adoptive cellular transfer of MDSCs may represent an attractive therapeutic strategy for allergic asthma. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Kolahian, S., Nowroozi Larki, N., Halit Öz, H., Schroth, C., Shahbazfar, A. A., Glück, M., Nürnberg, B., Hartl, D. Tags: Airway Cell Biology and Immunopathology Source Type: research

Central role for phosphoinositide-3-kinase gamma/delta dependent signalling in eosinophilic pulmonary inflammation driven by innate lymphoid cells
Severe eosinophilic asthma remains a clinical burden, potentially due to the multiple mechanisms by which type 2 inflammation can arise. Here we show how epithelial alarmin stimulation of innate lymphoid type 2 cells (ILC2s) can promote Th2 cell activity and subsequent eosinophil influx to the lung via mechanisms dependent upon PI3K and isoform activity.A PI3Kgamma and delta (PI3K) mRNA signature identified a Ubiopred severe asthmatic patient segment with high sputum eosinophil content and a Th2/ILC2/alarmin endotype. Evaluation of potent PI3K inhibitors with , or dual isoform selectivity supported a role in this endotype ...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Thomas, M., Bjorhall, K., Collins, M., Israelsson, E., Krutrok, N., LammBergstrom, E., Maciewicz, R., Muthas, D., Nordberg, M., Perry, M., RodrigoBlomqvist, S., Saarne, T., Winkler, C., Karabelas, K., Malmgren, A., Adcock, I., Chung, F., Wymann, M. Tags: Airway Cell Biology and Immunopathology Source Type: research

Phosphoinositide-3-kinase gamma/delta isoform signalling defines a mixed T cell severe asthmatic endotype
Severe asthma remains a clinical burden despite the emergence of antibody therapies. Complex disease drivers, which shift between T2, T1 and T17 driven inflammation, termed mixed T cell asthma, likely contribute to ineffective disease control in this population. Here we dissect the mechanisms underlying severe asthma to reveal a potential role (s) for both PI3Kgamma and delta (PI3K and ) isoform activity in asthmatics with a mixed T cell endotype.A PI3K gene signature was generated from next generation sequencing of IL-8/GM-CSF-stimulated monocytes where PI3K signalling was inhibited. This mRNA signature was used to interr...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Thomas, M., Bjorhall, K., Israelsson, E., LammBergstrom, E., Horvat, J., Kim, R., Maciewicz, R., Muthas, D., Nordberg, M., RodrigoBlomqvist, S., Saarne, T., Winkler, C., Karabelas, K., Adcock, I., Chung, F., Hansbro, P., Malmgren, A., Perry, M. Tags: Airway Cell Biology and Immunopathology Source Type: research

Activation of protease-activated receptor 2 elicits epithelial-mesenchymal transition in HBE cells via ROS signaling
As a critical event involved in the airway remodeling, epithelial-mesenchymal transition (EMT) of bronchial epithelial cells occurs in a range of respiratory disorders such as asthma and pulmonary fibrosis. Since protease-activated receptor 2 (PAR2) is well documented to be implicated in airway disorders, little is known about its role in EMT so far. Our study was to determine the impact of PAR2 activation on EMT and the underlying mechanisms. We used human bronchial epithelial (HBE) cells to be challenged by tryptase (a nature agonist of PAR2) and the synthetic peptide of SLIGKV-NH2 (a specific agonist of PAR2). The resul...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Gu, H., Ge, A., Gu, Y., Zeng, X. Tags: Airway Cell Biology and Immunopathology Source Type: research

TGF-{beta}1-Mediated CTGF Upregulation Through Transactivation of EGFR in Fibrocytes of Chronic Obstructive Asthma
Circulating fibrocytes are increased in chronic obstructive asthma (COA) with a higher capacity of proliferation and differentiation by TGF-β1. Our previous study highlighted a potential involvement of connective tissue growth factor (CTGF) in fibrocyte transformation. We evaluated the role of epidermal growth factor receptor (EGFR) and a disintegrin and metalloproteinase 17 (ADAM17) in mediating TGF-β1-induced CTGF activation of fibrocytes. Fibrocytes were isolated from asthmatics with normal pulmonary function (NPF) (n=14) and COA (n=13). Fibrocytes expressing CD45, collagen I, EGFR, ADAM17, CTGF, or α-SM...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Wang, C.-H., Weng, C.-M., Chung, K. F., Kuo, H.-P. Tags: Airway Cell Biology and Immunopathology Source Type: research

Pharmacological Rescue of Conventional Primary Equine Bronchial Epithelial Cells
Conclusion: The ability to rapidly generate many primary EBE cells from bronchial specimens provides significant opportunities for cell-based diagnostics and therapeutics. This study confirms the benefits of Y-27632 to provide the opportunity to culture primary EBEC for extended periods of culture. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Abraham, G., Engelmann, J., Kacza, J., Bonicelli, J. Tags: Airway Cell Biology and Immunopathology Source Type: research

RAGE-dependent VCAM-1 expression in the pulmonary endothelium mediates IL-33 induced asthma pathogenesis
Conclusion: This study demonstrates that RAGE mediates pulmonary ILC2 accumulation, eosinophilic inflammation and mucus metaplasia, by promoting VCAM-1 expression on pulmonary endothelial cells. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Perkins, T., Oczypok, E., Dutz, R., Oury, T. Tags: Airway Cell Biology and Immunopathology Source Type: research

Inhibition of CFTR-specific miRNAs in CF bronchial epithelial cells
Cystic fibrosis (CF) is an autosomal recessive disease originated by mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene. CFTR expression is modulated by a set of lead microRNAs (miRNAs), whose levels are increased in CF bronchial epithelium (Oglesby IK, et al. J Immunol 2013; 190: 3354-62). A new therapeutic strategy could be undertaken by blocking miRNA-mediated inhibition of CFTR, thereby leading to increased levels of CFTR expression and function. Target Site Blockers (TSBs) were designed to specifically compete with nine predicted binding sites for a set of endogenous lead miRNAs within th...
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: De Santi, C., Fernandez Fernandez, E., Greene, C. Tags: Airway Cell Biology and Immunopathology Source Type: research

Kaempferol-induced HO-1 expression attenuated inflammation in human pulmonary alveolar epithelial cells
Conclusions: KPR could be a potential intervention against inflammation by up-regulating HO-1 expression and down-regulating ICAM-1 expression in HPAEpiCs. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Chen, Y.-W., Yang, C. Tags: Airway Cell Biology and Immunopathology Source Type: research

CD18-mediated adhesion is required for lung inflammation induced by cell derived microparticles
Conclusions: TNF-α activation of alveolar cells causes an increase in MP adhesion that is mediated by CD18. CD18-mediated adhesion of MP to alveolar cells is essential for their proinflammatory effect. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Neri, T., Scalise, V., Balia, C., Passalacqua, I., Pedrinelli, R., Paggiaro, P., Celi, A. Tags: Airway Cell Biology and Immunopathology Source Type: research

Anti-fibrotic and antioxidant effects of Ailanthus altissima wood aqueous extract against bleomycin-induced lung fibrosis in rat
Conclusion: These findings provide an insight into the therapeutic potential of Awe treatment in the treatment of PF. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 6, 2017 Category: Respiratory Medicine Authors: Abidi, A., Aissani, N., Sebai, H., Ben Khamsa, S. Tags: Airway Cell Biology and Immunopathology Source Type: research