Do changes in spirometric indices and FeNO predict asthma outcomes in children? An individual patient data analysis using results from seven FeNO trials
Conclusions: Change in %FEV1 over a three month period may be useful as part of dynamic risk assessment. Whether a large change in FeNO may also be useful for dynamic risk assessment remains uncertain. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Turner, S., Fielding, S., Pijnenburg, M., De Jongste, J., Pike, K., Roberts, G., Petsky, H., Chang, A., Fritsch, M., Frischer, T., Szefler, S., Gergen, P., Vermeulen, F., Vael, R. Tags: Paediatric respiratory epidemiology Source Type: research

Bronchoalveolar lavage transcriptome and eicosanoid profiles reveal heterogeneity of lower airway inflammation in aspirin-exacerbated respiratory disease (AERD)
Background: AERD is characterized by asthma, chronic rhinosinusitis and hypersensitivity to aspirin and other cyclooxygenase 1 inhibitors. AERD patients are distinguished from aspirin tolerant asthmatics (ATA) by significantly higher baseline production of LTE4.Aims: We investigated inflammatory signature in the lower airways of AERD patients.Methods: Eicosanoid profiles (LC/MS) and focused transcriptome (real-time PCR) were measured in bronchoalveolar lavage fluid (BALF) samples from patients with AERD (n=23), ATA (n=22), and control subjects (n=12).Results: Eosinophilic phenotype in lower airways (>2% eosinophils) was...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Jakieła, B., Gielicz, A., Plutecka, H., Przybyszowski, M., Soja, J., Sładek, K., Bochenek, G. Tags: Allergy and immunology Source Type: research

The effect of Mepolizumab for not completely satisfied Omlizumab treated asthmatics.
Omalizumab anti IgE monoclonal antibody has beem used for severe asthmatics. Recent study held in Barmingham showed reduce the exacerbation around 50%. But a quarter of Omalizumab administered patients show not complete effects. Mepolizumab anti IL-5 anibody was commercially available at autumn 2016. It was used for high eosinophil counts. Most of the candidate for Omalizumab and Mepolizumab were overlapped (ie. IgE 30-1500IU/ml, eosinophils> 300/mm3). It is changeable for patients with no or unsatisfied effect of Omalizumab. In this paper we estimated Mepolizimab effect changed form Omalizumab with unsatisfied effect. ...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Kato, M. Tags: Allergy and immunology Source Type: research

Bacterial lysates in the prevention of asthma exacerbations in uncontrolled asthma: the Breathe study
Conclusion: L could be effective in the prevention of AE. Small clinical studies show positive effects; animal models show decreased allergic airway inflammation. The Breathe study is the first large RCT evaluating BL in patients with SA. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: de Boer, G. M., Braunstahl, G.-J., Hendriks, R. W., Tramper, G. A. Tags: Allergy and immunology Source Type: research

Safety profile of a novel peptide, PIN201104, with potential to act as a disease modifying, broad spectrum treatment for asthma
Conclusion: From these studies, 104 does not show potential to induce significant safety concerns going into clinical development. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Watson, J., Federici-Canova, D., Cooper, N., Burgess, C. Tags: Allergy and immunology Source Type: research

Triple combination of montelukast or tiotropium and inhaled corticosteroids plus long-acting ss2-agonist in persistent asthma
Background: Asthma often remains uncontrolled despite treatment with inhaled corticosteroids (ICS) alone, or ICS plus long-acting β2-agonist (LABA). The alternative option recommended is an addition of montelukast or tiotropium. However, no clinical data are available on comparing montelukast versus tiotropium.Aims and objective: The aim of the study was to compare the add-on effect of montelukast or tiotropium on airway inflammation and remodeling in asthma.Methods: 87 patients with asthma received ICS/LABA combination were randomly allocated to three groups to receive oral montelukast (10 mg/day), inhaled tiotropium...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Hoshino, M., Akitsu, K., Ohtawa, J. Tags: Allergy and immunology Source Type: research

Dupilumab shows rapid and sustained suppression of inflammatory biomarkers in asthma patients in LIBERTY ASTHMA QUEST
Conclusion: DPL showed rapid and sustained suppression of systemic and airway type 2 inflammatory biomarkers (including FeNO and IgE) in asthma pts, and was generally well tolerated. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Wenzel, S., Pavord, I. D., Rabe, K. F., Papi, A., Fitzgerald, J. M., Jagerschmidt, A., Brian, W., Dong, Q., Swanson, B. N., Hamilton, J. D., Amin, N., Pirozzi, G., Ruddy, M., Akinlade, B., Graham, N. M. H., Teper, A. Tags: Allergy and immunology Source Type: research

Dupilumab improves mental health measures in patients with chronic rhinosinusitis and nasal polyposis (CRSwNP)
Conclusion: Dupilumab added to MFNS significantly improves mental health in patients with CRSwNP, as assessed by SF-36 MCS scores. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Bachert, C., Naclerio, R., Hellings, P., Guillonneau, S., Taniou, C., Maroni, J., Rowe, P., Mannent, L., Amin, N., Kamat, S., Khan, A. Tags: Allergy and immunology Source Type: research

Dupilumab shows rapid and sustained suppression of inflammatory biomarkers in corticosteroid (CS)-dependent severe asthma patients in LIBERTY ASTHMA VENTURE
Conclusion: Systemic and airway type 2 inflammatory biomarkers remain elevated in OCS-dependent severe asthma pts. DPL improved FEV1 and showed rapid and sustained suppression of biomarkers despite larger OCS reduction, and was generally well tolerated. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Rabe, K. F., Brusselle, G., Castro, M., Sher, L., Zhu, H., Dong, Q., Hamilton, J. D., Brian, W., Jagerschmidt, A., Pirozzi, G., Amin, N., Ruddy, M., Akinlade, B., Graham, N. M. H., Teper, A. Tags: Allergy and immunology Source Type: research

Mast cell tryptase induce alarmin release and secretion of pro-inflammatory cytokines from bronchial epithelial cells
Conclusion: Our results suggest that tryptase released from MCs may play a direct role in inducing an inflammatory response and a damaged barrier function in BECs which may have an important role in the progression of asthma pathology. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Ramu, S., Bjermer, L., Erjefält, J., Uller, L., Andersson, C. Tags: Allergy and immunology Source Type: research

A novel house dust mite-induced asthma model in guinea pigs driven by mast cells
Guinea pigs exhibit many anatomical and physiological features similar to human airways. The aim of the study was to develop an in vivo asthma model in the guinea pig by the use of the relevant allergen house dust mite (HDM) to obtain a model which resembles the early asthmatic response (EAR), accumulation of eosinophils and expression of increased airway hyperresponsiveness (AHR).Guinea pigs were sensitized intranasally twice with HDM extract and intranasally challenged once per week over five weeks. EAR was monitored after each challenge in unrestrained animals using whole-body plethysmography giving Penh recordings. Com...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Ramos-Ramirez, P., Noreby, M., Liu, J., Gregory, J., Petren, A., Olsson, H. K., Nilsson, G., Dahlen, S.-E., Adner, M. Tags: Allergy and immunology Source Type: research

Inflammatory mediators in eosinophilic COPD phenotype and asthma with fixed airflow obstruction
Background: Eosinophils and neutrophils play roles in asthma and COPD severity and treatment response. Cellular mediators are promising treatment targets. However, their roles in asthma and COPD phenotypes have never been investigated.Objective: To investigate eosinophilic and neutrophilic mediators in asthma with and without fixed airflow obstruction (FAO) and COPD with and without blood eosinophilia (BE).Materials and methods: Asthma, COPD patients and healthy subjects were recruited from 2016 to 2017. Spirometry and reversibility test were performed. ACT, modified MRC and CAT were assessed. Blood eosinophils, neutrophil...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Onnipa, J., Kawamatawong, T., Pitidhammabhorn, D., Setthaudom, C. Tags: Allergy and immunology Source Type: research

Mechanisms of impaired anti-bacterial Th1 responses in patients with chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is the most common respiratory disorder worldwide. Some COPD patients experience acute exacerbation of COPD (AECOPD) which are associated with pulmonary bacterial infections and accelerated disease progression. We hypothesised that the expression of co-inhibitory molecules on T-cells (CTLA-4, PD-1 and CD39) are increased in COPD patients and so limit protective T-helper type 1 (Th1) responses.We investigated expression of T-cell CTLA-4, PD-1, CD39 and Foxp3 in resected lung washout samples from COPD and non-COPD subjects by flow cytometry. Phagocytosis by airway monocytes was me...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Tan, D., Singh, D., Walters, H., Wark, P., Moodley, Y. Tags: Allergy and immunology Source Type: research

Unraveling the role of miR-223-3p in the regulation of airway inflammation in asthma
In conclusion, we confirmed increased expression of miR-223-3p in airways of asthma patients compared to healthy controls. Overexpression of miR-223-3p in human bronchial epithelial cells resulted in higher CCL20 levels. This suggests that increased levels of miR-223-3p in asthma, e.g. when secreted in exosomes may contribute to the release of the pro-inflammatory CCL20 by airway epithelial cells. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Roffel, M., Boudewijn, I., Guryev, V., Brandsma, C.-A., Van Den Berge, M., Bracke, K., Maes, T., Heijink, I. Tags: Allergy and immunology Source Type: research

The new approach to understand the role of IL-15 and BMP proteins in asthma remodelling based on methacholine challenge test evidence.
Conclusions: The higher serum levels of BMP4 and BMP7 in asthmatic patients suggest that these cytokines are involved in inflammation and fibrosis in the airwaysIL-15 increased the expression of BMP4 and BMP7 regardless of the provocative factorIL-15 increased the expression of BMP4 and BMP7 under the influence of methacholine and the potency of the correlation increased in time after the stimulus triggering in the inflammatory reaction (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Kocwin, M., Jonakowski, M., Mokros, L., Panek, M., Szemraj, J., Kuna, P. Tags: Allergy and immunology Source Type: research

Variants in IL17A and IL17F are risk factors to uncontrolled asthma
The aim of this study was to investigate the association between polymorphisms in IL17A and IL17F and asthma control. This work was performed with participants from ProAR case-control study in Salvador, Brazil. Asthma control was defined according to Global Initiative for Asthma. In this work were included 209 subjects with controlled asthma, 522 with poor control of asthma and 225 with uncontrolled asthma. The rs2275913, rs3819024, rs763780 and rs2397084 were genotyped in genomic DNA of these individuals using TaqMan probe- based 5-nuclease assays technology. Logistic regressions were performed using PLINK software 1.9, u...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Silva, M., Santos, R., Brandao, I., Fonseca, H., Medeiros, E., Cardoso, L., Fernandes, J., Espinheira, R., Alcantara-Neves, N., Cruz, A., Costa, R., Figueiredo, C. Tags: Allergy and immunology Source Type: research

FOXP3 genetic variants are associated with asthma severity in Brazilian women.
The aim of this study was to verify the associations between variants in FOXP3, with different asthma phenotypes and the expression of this molecule in CD4+CD25hiFOXP3+ T lymphocytes. DNA was extracted from the peripheral blood of the 1,418 individuals recruited in to ProAR, case-control study in Salvador, Brazil. The SNPs included in FOXP3 (rs2280883, rs2294021, rs3761548, rs2232365) were genotyped using the TaqMan probe. Analyzes for genetic associations were performed by logistic regressions using PLINK 1.9 software for men and women, separately, and adjusted for age and skin color. The expression of FOXP3 in CD4+CD25hi...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Figueiredo, C., Carneiro, N., Fiuza, B., Da Silva, H., Da Silva, R., Carneiro, T., Silva, M., Carneiro, V., Costa, R., Fernandes, J., Cardoso, L., Cruz Filho, A., Freitas, H. Tags: Allergy and immunology Source Type: research

Th-17 cytokine profile in a Greek asthmatic population. Correlation with asthma severity and biomarkers of inflammation.
Objective: The aim of the present study was to investigate the Th-17 pathway in asthmatic patients and the relation to asthma severity and biomarkers of inflammation.Methods: 51 patients with severe, 21 patients with mild asthma and 19 healthy controls, mean age 53 ± 15.1, 45.5 ± 15 and 44± 16 years respectively were included. Skin prick tests, blood eosinophils (bleos), total serum IgE and exhaled FeNO were evaluated. Serum levels of IL-6, IL-17A, IL-23 and TGFβ1 were determined using a panel kit (AimPlex Biosciences) tested by Flow Cytometry.Results: Serum levels of IL-6, IL-17A and IL-23 were h...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Domvri, K., Porpodis, K., Tzimagiorgis, G., Chatzopoulou, F., Ioannidou, D., Fouka, E., Kyriazis, G., Kontakiotis, T., Papakosta, D. Tags: Allergy and immunology Source Type: research

Increased pro-inflammatory regulatory T Cells correlate with the plasticity of T helper cell differentiation in asthma
Background: Human regulatory T cells (Tregs) are a heterogeneous population which consists of three distinct subpopulations: CD25+CD45RA+ resting Treg (rTreg) cells, D25hiCD45RA– activated Treg (aTreg) cells, which are both suppressive, and CD25+CD45RA– cytokine-secreting T cells with proinflammatory capacity.Objective: We investigated variation in peripheral Treg subpopulations of asthma and explored their potential roles in asthma inflammation.Methods: Twenty-eight mild asthma patients, 26 moderate asthma patients, 18 severe asthma patients, and 36 healthy controls were recruited for a cross-sectional study. ...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Hou, J., Xin, L., Gao, J., Tian, C., Ma, W., Tian, Z., Zheng, X. Tags: Allergy and immunology Source Type: research

Glycaemic variability indices are associated with increased pulmonary function decline in people with cystic fibrosis
Conclusion: In the first study to assess GV and outcomes in CF we found that increased GV appears to be associated with more severe pulmonary function and also accelerated pulmonary decline in the preceding 12 months. Further evaluation of these indices is warranted. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Frost, F., Dyce, P., Wat, D., Walshaw, M., Nazareth, D. Tags: Cystic fibrosis Source Type: research

Comparison between the 1-minute sit-to-stand test and quadriceps strength in patients with cystic fibrosis
Conclusion: The 1STST is a good alternative to the Microfet2dynamometer to estimate quadriceps strength in stable patients with CF. This test is also positively correlated to disease severity contrarily to quadriceps strength, as shown by others (ERJ 2009; 33:99-106). This test could be useful to detect muscular weakness in this population, notably during the routine visit in the CF centres or in primary care. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Hardy, S., Berardis, S., Reychler, G., Gohy, S. Tags: Cystic fibrosis Source Type: research

The effect of inhaled lung volume on ventilation heterogeneity in CF using 3He MRI
Background: Hyperpolarised gas ventilation MRI provides sensitive regional analysis of ventilation in CF. The effect of lung volume on ventilation imaging has not been assessed. We hypothesised that ventilation defects would decrease at increased lung volume and the degree of change would relate to disease severity.Method: Children and adults with CF performed separate 3He-MRI assessments at inspired lung volumes of (1) FRC+inhaled gas volume (baseline) and (2) total lung capacity (TLC). Inhaled gas volume was scaled from height. The percentage of non-ventilated lung (VDP) and coefficient of variance of signal intensity (C...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Smith, L., Collier, G., Marshall, H., Hughes, P., Bray, J., Rodgers, O., Aldag, I., West, N., Wildman, M., Horsley, A., Wild, J. Tags: Cystic fibrosis Source Type: research

Repeatability of ventilation and perfusion assessment by functional MRI in children with CF
Conclusions: In addition to easy application without breathing maneuvers or contrast agent, the good short-term repeatability make this a promising method for early detection of CF lung disease. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Nyilas, S., Bauman, G., Pusterla, O., Stranzinger, E., Ramsey, K., Singer, F., Yammine, S., Casaulta, C., Bieri, O., Latzin, P. Tags: Cystic fibrosis Source Type: research

Lung clearance index and lung ultrasound in cystic fibrosis children
Background: An important percentage of CF patients associates structural lung damages associated with impaired lung function. Lung ultrasound (LUS) can detect structural features like emphysema, consolidation, interstitial inflammation or bronchiectasis while the most accurate parameter of the lung function in cystic fibrosis is the lung clearance index(LCI), therefore it would be important to evaluate the relation between the two parameters.Aim: To evaluate the relation between LUS score and lung function expressed by LCI among children with CF.Methods: Forty-two children with CF (mean age 13.93± 5.1years) who unde...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Ciuca, I. M., Dediu, M., Pop, L. L. Tags: Cystic fibrosis Source Type: research

Do deviations in tidal breathing impact multiple breath washout measurements?
Background: During Multiple Breath Washout (MBW) subjects are to maintain quiet, tidal breathing and avoid sighs. Most children naturally breathe at 8-13mL/kg of ideal body weight (IBW; Horton et al. 2017 Abstract) and breathing far outside this range may impact MBW results (Yammine et al. J Cyst Fibros 2014).Objective: To identify the distribution of tidal volumes during MBW testing in children and to assess whether natural deviations from the ideal range affect MBW results.Methods: 7100 MBW trials from two multicentre clinical studies without leaks and meeting end of test criteria were analyzed (43% male, median 8.1 year...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: McDonald, R., Stanojevic, S., Jensen, R., Ratjen, F. Tags: Cystic fibrosis Source Type: research

Blocking IL-20 pathway limits the development of bacteria induced exacerbation in mice chronically exposed to cigarette smoke.
COPD is a public health burden mainly due to cigarette smoking (CS). It is now well recognized that respiratory infections are important triggers for the progression and exacerbation of the disease, consecutive to a defective immune responses. Since IL-20 cytokines (IL-19, IL-20 and IL-24) inhibits cutaneous antibacterial responses, we evaluated their implication during COPD exacerbation in order to restore an efficient immune response.C57BL/6 mice were daily exposed to CS during 12 weeks before infection by Streptococcus pneumoniae (Sp). Moreover, human monocyte-derived dendritic cells (MDDC) were treated with IL-20 cytok...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Kone, B., Madouri, F., Barada, O., Kervoaze, G., Vilain, E., Pichavant, M., Gosset, P. Tags: Airway Cell Biology and Immunopathology Source Type: research

BPI Fold Containing Family A Member 1 (BPIFA1) regulates mucosal microbiota and basal Interferon signaling
Introduction: BPIFA1 is an abundant airway antimicrobial protein with immunomodulatory properties. BPIFA1 decreases during respiratory infection and airway inflammation.Aims/Objectives: We hypothesized that decreases in BPIFA1 alter the airway microbiota and disrupt basal innate immune activation.Objectives: 1) Define microbiome differences in bpifa1-/- mice, 2) Correlate these changes with differential expression of immune response genes.Methods: Mice: 8 week-old bpifa1-/- (n=10) and WT (n=10). Microbiome: Nasal, bronchoalveolar lavage (BAL), skin, cecum samples. 16S rRNA gene V4 region sequenced and analyzed with QIIME. ...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Britto, C., Khanal, S., Wu, B., Li, Y., Segal, L. Tags: Airway Cell Biology and Immunopathology Source Type: research

Pseudomonas aeruginosa LasB subverts innate immunity in alveolar macrophages and epithelial cells
Conclusion: We demonstrate that the effect of LasB in vivo can be recapitulated in vitro on AMs & epithelial cells and we show that LasB targets an IL-17/IL-22 dependent anti-microbial pathway (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Kheir, S., Villeret, B., Serafini, N., Voulhoux, R., Garcia Verdugo, I., Di Santo, J., Sallenave, J.-M. Tags: Airway Cell Biology and Immunopathology Source Type: research

The effect of dietary fatty acids on respiratory infection in human lung cells
This study investigated the effect of dietary fatty acids on infection in primary pulmonary fibroblasts and the bronchial epithelial cell line (BEAS-2B) in vitro and investigated the underlying mechanisms.Cells were challenged with BSA-conjugated fatty acids (-6 PUFAs, -3 PUFAs or SFAs) with or without the viral mimic polyinosinic:polycytidylic acid (POLYI:C) or the bacterial compound lipoteichoic acid (LTA) and release of the pro-inflammatory cytokines, IL-6 and CXCL8, was measured. We found that in fibroblasts and epithelial cells challenge with the -6 PUFA arachidonic acid (AA) in combination with POLYI:C or LTA leads t...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Rutting, S., Horvat, J., Wood, L., Hansbro, P., Oliver, B. Tags: Airway Cell Biology and Immunopathology Source Type: research

The effect of double-stranded RNA on extracellular matrix deposition in an in vitro model of the airway mucosa
Bronchial epithelial cells (BECs) and fibroblasts form an epithelial-mesenchymal trophic unit (EMTU) that maintains tissue homeostasis and activates repair responses following injury. In asthma, activation of the EMTU by viral infection is proposed to be linked to disease exacerbation. We hypothesised that viral infection activates BECs to induce repair processes within the EMTU.An EMTU model incorporating polarised BECs (16HBE14o-) and fibroblasts (MRC-5) grown on the apical and basolateral surface of a nanoporous membrane respectively was established and apically challenged with dsRNA (a molecular pattern that mimics vir...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Banas, C., Hill, A. R., Blume, C., Davies, D., Swindle, E. Tags: Airway Cell Biology and Immunopathology Source Type: research

The activation of NLRP3 inflammasome pathway in COPD is limited in local airways
Background: The elevation of IL-1β levels in COPD patients is involved in the inflammatory response of the disease. However, the upstream mechanism remains unclear and NLRP3 inflammasome activation might be implicated.Objective: To examine the hypothesis that the NLRP3 inflammasome pathway is upregulated which leads to an over-production of IL-1β in COPD.Methods: A total of 61 participants were recruited including patients with stable COPD (n=29) and healthy controls (HC, n=32). Patients with stable COPD were re-recruited at acute exacerbations. Spirometry, sputum induction were performed and blood was collected ...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Fu, J.-J., Mao, B., Wang, S.-J., Xiao, W., Li, G.-H., Wu, L.-H. Tags: Airway Cell Biology and Immunopathology Source Type: research

Cigarette smoke extracts decrease basal and lipopolysaccharide-induced expression of macrophage receptor with collagenous structure via degradation of p300
In this study, we investigated the effect of CSE on the expression of MARCO and its regulatory mechanism in RAW264.7 cells. CSE decreased both basal and lipopolysaccharide (LPS)-induced expressions of MARCO mRNA and protein. LPS-induced up-regulation of MARCO is nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent. Knockdown of Nrf2 using siRNAs completely suppressed LPS-induced increase in MARCO transcripts. CSE did not block nuclear translocation of Nrf2 in LPS-treated cells, but rather CSE strongly accumulated Nrf2 in the nucleus via degradation of its cytoplasmic inhibitor, Keap1. Histone acetyltransferase p300...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Lee, K.-H., Lee, C.-H., Yoo, C.-G. Tags: Airway Cell Biology and Immunopathology Source Type: research

Impairment of respiratory host defence resulting from cigarette smoke-induced changes in airway epithelial cell differentiation
Cigarette smoking (CS) is known to increase susceptibility to respiratory tract infections and alter differentiation of airway epithelial cells. Host defence proteins (HDPs) are key mediators of mucosal host defence. We hypothesized that CS-induced alterations in epithelial differentiation result in a decrease in constitutively expressed HDPs, thus rendering the host more susceptible to infection. Primary bronchial epithelial cells (PBEC) were cultured at the air-liquid interface (ALI) and during differentiation daily exposed to whole CS. Gene expression and protein levels of HDPs and epithelial cell-specific markers were ...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: van der Does, A. M., Amatngalim, G. D., Schrumpf, J. A., Dishchekenian, F., Mertens, T. C. J., Ninaber, D. K., Van Der Linden, A. C., Pilette, C., Taube, C., Hiemstra, P. S. Tags: Airway Cell Biology and Immunopathology Source Type: research

Effect of Hypertonic Saline Solution on cultures of human respiratory epithelium infected by respiratory syncytial virus
Introduction: nebulizations with hypertonic saline solution (HSS) has been incorporated in treatment of infant bronchiolitis but is currently a subject of controversy. Experimental studies on models of RSV infection have not been published.Objectives: to study the effect of HST in cultures of human respiratory epithelium infected with respiratory syncytial virus (RSV).Materials and Methods: Human respiratory epithelial cells (Hep-2 and Calu-3 lines) were cultured in monolayer. Cultures were divided into 3 groups: G1-control cells; G2-cells exposed to RSV for 3 hours, after which the culture medium was replaced by fresh med...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Figueroa, J. M., Primrose, D., Vdugour, A., Ochoa, V., Bitler, J., Erra Diaz, F. Tags: Airway Cell Biology and Immunopathology Source Type: research

Human rhinovirus 16 infection of human macrophages impairs their clearance ability by perturbing phagosome maturation
Conclusion: Our results demonstrate HRV16 impairs intracellular clearance in macrophages by perturbing the endocytic machinery and affecting microtubule dynamics. They could explain why COPD patients show virus induced exacerbations and secondary bacterial infections. Further analysis of how HRV16 hijacks these pathways offers the potential to design novel therapeutics to treat COPD exacerbations. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Jubrail, J., Africano-Gomez, K., Herit, F., Burgel, P.-R., Oberg, L., Israelsson, E., Thorn, K., Mayer, G., Cunoosamy, D., Kurian, N., Niedergang, F. Tags: Airway Cell Biology and Immunopathology Source Type: research

Human rhinovirus 16 infection of human macrophages impairs internalisation via disrupting the actin cytoskeleton
Conclusion: Our results demonstrate that HRV16 infection impairs various macrophage internalisation pathways by disruption of the actin cytoskeleton and affects the expression of key actin regulators. Addressing these key regulators of actin function disrupted by HRV16 highlights a unique opportunity to therapeutically target macrophage cellular pathways to improve patient outcome in COPD. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Jubrail, J., Africano-Gomez, K., Herit, F., Burgel, P.-R., Oberg, L., Israelsson, E., Thorn, K., Mayer, G., Cunoosamy, D., Kurian, N., Niedergang, F. Tags: Airway Cell Biology and Immunopathology Source Type: research

Microarray analysis of poly(I:C) and IL-13 co-stimulated human airway epithelium
This study aimed at examining the epithelial response early during an asthma exacerbation using an in vitro model of primary human bronchial epithelial cells (HBEs).HBEs were cultured at air-liquid interface (ALI)-conditions. Asthma features were induced by treatment with human interleukin-13 (IL-13). Stimulation with poly(I:C) was used to mimic a virus triggering exacerbation in vitro. Gene expression profiling was performed by microarray analysis.Viruses are recognized e.g. by the receptors RIG-1 and MDA-5. These proteins are encoded by DDX58 (DExD/H-box helicase 58) and IFIH1 (interferon induced with helicase C domain 1...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Ehlers, J. C., Vock, C., Fehrenbach, H. Tags: Airway Cell Biology and Immunopathology Source Type: research

Murine model for investigating virus-induced exacerbations of COPD-related inflammation - preclinical biomarker validation
Conclusion: A significantly exaggerated inflammatory response was observed in CS-exposed mice additionally receiving poly (I:C). The major cytokines increased in BALF were the same reported from COPD patients with exacerbation. We suggest that our model can be used to reveal novel candidate biomarkers predicting exacerbations as well as also to further investigate mechanisms underlying viral-induced exacerbations.Financial support by the BMBF (FKZ: 13N13862) is gratefully acknowledged. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Wolff, M., El-Merhie, N., Bartel, S., Fehrenbach, H., Reuter, S., Krauss-Etschmann, S. Tags: Airway Cell Biology and Immunopathology Source Type: research

Host defence functions of BPIFA1 against Non-typeable Haemophilus influenzae
BPIFA1 is an abundantly secreted protein of the upper respiratory tract that plays a pleiotropic role in airway defence that includes antibacterial and bacteriostatic functions. The mechanism by which BPIFA1 exhibits these diverse activities is not fully resolved. Non-typeable Haemophilus influenzae (NTHi) is a common pathogen in a variety of respiratory diseases. We directly investigated the role of BPIFA1 in host defence against NTHi. Intranasal NTHi inoculation did not result in nasal colonisation or frank infection even in the absence of bpifa1. We then used in vitro approaches to investigate if BPIFA1 plays a role in ...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Caikauskaite, R., Mulay, A., Hood, D., Brown, S., Stewart, J., Bingle, L., Bingle, C. Tags: Airway Cell Biology and Immunopathology Source Type: research

Club cell secretory protein: a key mediator in Mycoplasma pneumoniae infection.
Conclusions: Our findings highlight a previously unidentified role for CC16 in protection against a common asthma-exacerbating agent, Mp. We further discovered that in the absence of CC16, persistence of Mp infection and the associated inflammation may drive airways remodeling. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Ledford, J., Guerra, S., Martinez, F., Kraft, M. Tags: Airway Cell Biology and Immunopathology Source Type: research

Investigation of the very early immune response in viral induced experimental asthma exacerbation
Virus triggered acute asthma exacerbations are distinct clinical manifestations during chronic disease. They are defined as progressive worsening of disease symptoms and account for unscheduled emergency department visits or hospitalizations and require a systemic use of corticosteroids and short-acting β-agonists. Therefore, early detection of developing asthma exacerbations are needed for early intervention strategies.Thus, our aim is to analyse the early virus-induced specific immune response in asthmatic mice. Therefore, we used an established mouse model of experimental asthma exacerbation. Experimental asthma wa...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Bodenstein-Sgro, R., Webering, S., Wegmann, M. Tags: Airway Cell Biology and Immunopathology Source Type: research

Modeling exacerbation using ozone exposure in COPD patients: CO3PD pilot study
Conclusions: Ozone exposure in COPD patients may be safely performed and could be utilized as an experimental model to study airway inflammation in exacerbation. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Arjomandi, M., Vasudevan, S., Wong, H., Dalton, S., Zeng, S. Tags: Airway Cell Biology and Immunopathology Source Type: research

Serum hyaluronidase-1 is increased in COPD exacerbations and is associated with COPD severity and outcomes
Hyaluronic acid (HA) is a dynamic glycosaminoglycan of the lung with high daily turnover. Hyaluronidases (HYAL) degrade HA in small fragments that have pro-inflammatory properties and are implicated in lung diseases including COPD. We have previously shown that acute exacerbations of COPD are associated with increased levels and activity of HYAL in bronchoalveolar lavage. Here, we assessed serum levels of HYAL-1, the main HYAL in serum, in 638 COPD patients, at stable state, at exacerbation and 4 weeks after exacerbations, using ELISA. Substrate zymography was used to evaluate the activity of HYAL in serum.Serum levels of ...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Papakonstantinou, E., Bonovolias, I., Karakioulakis, G., Tamm, M., Louis, R., Milenkovic, B., Boersma, W., Kostikas, K., Blasi, F., Aerts, J., Rohde, G., Lakoma, A., Torres, A., Welye, T., Stolz, D. Tags: Airway Cell Biology and Immunopathology Source Type: research

Obstructive sleep apnea as risk factor for incident metabolic syndrome: a multicentric prospective epidemiological study
Aims and Objectives: To investigate the effect of obstructive sleep apnea (OSA) on the risk of developing metabolic syndrome (MetS) in a general population sample.Methods: This is an observational prospective study of 2 merged population-based samples (Episono and HypnoLaus) evaluated over 8 and 5 years, respectively. At baseline, all participants underwent clinical evaluation and blood collection for assays. MetS was assessed according to the JIS criteria. Polysomnography (PSG) was performed at both baseline and follow-up in Episono, and at baseline in HypnoLaus. OSA was defined according to 2012 AASM apnea-hypopnea index...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Hirotsu, C., Haba-Hubio, J., Marques-Vidal, P., Togeiro, S., Vollenweider, P., Waeber, G., Preisig, M., Bittencourt, L., Tufik, S., Heinzer, R. Tags: Sleep and control of breathing Source Type: research

THE ASSOCIATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR GENE POLYMORPHISM WITH OBSTRUCTIVE SLEEP APNEA SYNDROME and OBESITY
In conclusion: BDNF 196G/A genotype was found to be more frequent among obese patients compared to the non-obese individuals; but it was not significantly related to OSAS in the present study. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Tutar, N., Yüksekkaya, M., Dündar, M., Yilmaz, I., Gulmez, I., Oymak, F. S., Balta, B., Korkmaz, K. Tags: Sleep and control of breathing Source Type: research

Depression and response to CPAP treatment in coronary artery disease patients with sleepy vs nonsleepy obstructive slee apnoea
This study was a secondary analysis of the RICCADSA trial, conducted in Sweden between 2005 and 2013. For the current protocol, 229 CAD patients with OSA (apnoea-hypopnoea index ≥15/h) on cardiorespiratory polygraphy, who had answered Epworth Sleepiness Scale (ESS) and Zung Self-Rating Depression Scale (SDS) questionnaires at baseline and after one-year, were included. Patients with nonsleepy OSA (ESS
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Balcan, B., Thunström, E., Peker, Y. Tags: Sleep and control of breathing Source Type: research

Polysomnographic characteristics and cardiac function in coronary artery disease patients with nonsleepy obstructive sleep apnoea
We compared polysomnography (PSG) results and cardiac function in patients with nonsleepy vs sleepy obstructive sleep apnoea (OSA) in a coronary artery disease (CAD) cohort.For the current protocol, 384 PSG recordings of CAD patients with OSA (apnea-hypopnea index [AHI] ≥15/h on cardiorespiratory polygraphy) from the RICCADSA trial, conducted in Sweden between 2005 and 2013, were evaluated. In all, 234 patients were nonsleepy (Epworth Sleepiness Scale [ESS] score
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Peker, Y., Balcan, B., Glantz, H., Thunström, E. Tags: Sleep and control of breathing Source Type: research

Mild obstructive sleep apnoea (OSA) and arterial hypertension in the EuropeanSleep Apnoea Database (ESADA) cohort study.
Background: Mild obstructive sleep apnoea (OSA) is highly prevalent, however its association with important clinical outcomes like arterial hypertension remains unknown.Aims and Objectives: To investigate the association between mild OSA and arterial hypertension in the European Sleep Apnoea Database (ESADA) cohort after adjusting for relevant confounding factors.Methods: A multicentric sample of 4974 adults from the ESADA cohort who showed simple snoring or mild OSA at cardiorespiratory polygraphy was studied. We compared the predictive value of mild OSA (AHI 5-
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Bouloukaki, I., Steiropoulos, P., Bonsignore, M., Mcnicholas, W., Hedner, J., Grote, L., Marrone, O., Verbraecken, J., Basoglu, O., Parati, G., Lombardi, C., Pataka, A., Schiza, S. Tags: Sleep and control of breathing Source Type: research

Sleep determinants of incident hypertension in a population-based cohort: the CoLaus/HypnoLaus study
Aims and objectives: To analyze the sleep determinants of incident hypertension (HT) in a population-based cohort.Methods: CoLaus is a prospective population-based cohort in which cardiovascular profile was assessed at baseline and 2 subsequent follow-ups. HT was defined as systolic blood pressure (SBP) ≥140 mmHg, diastolic blood pressure (DBP) ≥90 mmHg, or anti-HT drug use. HypnoLaus study analyzed sleep characteristics in a subset of CoLaus population at the first follow-up. All HypnoLaus participants underwent a full polysomnography (PSG) at home. The autonomic activation during sleep was assessed using pulse wave...
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Hirotsu, C., Marques-Vidal, P., Vollenweider, P., Waeber, G., Betta, M., Bernardi, G., Siclari, F., Haba-Hubio, J., Heinzer, R. Tags: Sleep and control of breathing Source Type: research

Hypoxia and cardiovascular comorbidity in the ESADA OSA patients with insomnia symptoms
Conclusions: Insomnia-like symptoms and signs of nocturnal hypoxemia should alert clinicians to a high prevalence of CVD in patients with OSA. This finding also emphasizes the importance of clinical phenotyping in the management of OSA. (Source: European Respiratory Journal)
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Anttalainen, U., Hedner, J., Ryan, S., Riha, R., Fietze, I., Staats, R., Grote, L., Saaresranta, T. Tags: Sleep and control of breathing Source Type: research