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Respiratory Research

Bart de Brouwer, Marjolein Drent, Jody M W van den Ouweland, Petal A Wijnen, Coline H M van Moorsel, Otto Bekers, Jan C Grutters, Eric S White, Rob Janssen
Although chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) seem to be opposite entities from a clinical perspective, common initial pathogenic steps have been suggested in both lung diseases. Emphysema is caused by an elastase/anti-elastase imbalance leading to accelerated elastin degradation. Elastinolysis is however, also accelerated in the IPF patients' lungs. The amino acids desmosine and isodesmosine (DES) are unique to elastin. During the degradation process, elastases liberate DES from elastin fibers...
March 20, 2018: Respiratory Research
Valérie Besnard, Alain Calender, Diane Bouvry, Yves Pacheco, Catherine Chapelon-Abric, Florence Jeny, Hilario Nunes, Carole Planès, Dominique Valeyre
BACKGROUND: Sarcoidosis is a systemic disease characterized by the formation of immune granulomas in various organs, mainly the lungs and the lymphatic system. Exaggerated granulomatous reaction might be triggered in response to unidentified antigens in individuals with genetic susceptibility. The present study aimed to determine the genetic variants implicated in a familial case of sarcoidosis. METHODS: Sarcoidosis presentation and history, NOD2 profile, NF-κB and cytokine production in blood monocytes/macrophages were evaluated in individuals from a family with late appearance of sarcoidosis...
March 20, 2018: Respiratory Research
A Padilla-Galo, C Olveira, L Fernández de Rota-Garcia, I Marco-Galve, A J Plata, A Alvarez, F Rivas-Ruiz, A Carmona-Olveira, J J Cebrian-Gallardo, M A Martinez-Garcia
BACKGROUND: Some studies have reported a high prevalence of bronchiectasis in patients with uncontrolled asthma, but the factors associated with this condition are unknown. The objective of this study was to determine the prevalence of bronchiectasis in uncontrolled moderate-to-severe asthma and to identify risk factors and their correlation with bronchiectasis in these patients. METHODS: This is a prospective study of data from consecutive patients with uncontrolled moderate-to-severe asthma...
March 16, 2018: Respiratory Research
Luis G Vargas Buonfiglio, Jennifer A Borcherding, Mark Frommelt, Gavin J Parker, Bryce Duchman, Oriana G Vanegas Calderón, Ruth Fernandez-Ruiz, Julio E Noriega, Elizabeth A Stone, Alicia K Gerke, Joseph Zabner, Alejandro P Comellas
BACKGROUND: Smoking is a leading cause of respiratory infections worldwide. Tobacco particulate matter disrupts iron homeostasis in the lungs and increases the iron content in the airways of smokers. The airway epithelia secrete lactoferrin to quench iron required for bacteria to proliferate and cause lung infections. We hypothesized that smokers would have increased bacterial growth and biofilm formation via iron lactoferrin imbalance. METHODS: We collected bronchoalveolar lavage (BAL) samples from non-smokers and smokers...
March 10, 2018: Respiratory Research
Mingxing Yang, Maxie Kohler, Tina Heyder, Helena Forsslund, Hilde K Garberg, Reza Karimi, Johan Grunewald, Frode S Berven, Sven Nyrén, C Magnus Sköld, Åsa M Wheelock
BACKGROUND: Smoking is the main risk factor for chronic obstructive pulmonary disease (COPD). Women with COPD who smoke experienced a higher risk of hospitalization and worse decline of lung function. Yet the mechanisms of these gender-related differences in clinical presentations in COPD remain unknown. The aim of our study is to identify proteins and molecular pathways associated with COPD pathogenesis, with emphasis on elucidating molecular gender difference. METHOD: We employed shotgun isobaric tags for relative and absolute quantitation (iTRAQ) proteome analyses of bronchoalveolar lavage (BAL) cells from smokers with normal lung function (n = 25) and early stage COPD patients (n = 18)...
March 8, 2018: Respiratory Research
Mingxing Yang, Maxie Kohler, Tina Heyder, Helena Forsslund, Hilde K Garberg, Reza Karimi, Johan Grunewald, Frode S Berven, C Magnus Sköld, Åsa M Wheelock
BACKGROUND: Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). METHODS: To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort...
March 8, 2018: Respiratory Research
Yang Yang, Yan Jiang, Dong Xie, Ming Liu, Nan Song, Junjie Zhu, Jiang Fan, Chenfang Zhu
BACKGROUND: Our previous screening study suggested that the cell-adhesions protein Dihydropyrimidinase-like 3 (DPYSL3) was a candidate metastatic lung cancer related molecule. This study aimed to analyze the correlation between DPYSL3 and metastatic lung cancer. METHODS: Stable DPYSL3 knockdown Lewis lung carcinoma (LLC) cells were constructed with a retroviral system. Cell migration and invasion assays were performed to determine the role of DPYSL3 in LLC cells' migration and invasion changes...
March 7, 2018: Respiratory Research
Edward M Kerwin, Selwyn Spangenthal, Christine Kollar, Earl St Rose, Colin Reisner
BACKGROUND: Long-acting muscarinic antagonist (LAMA) and long-acting β2 -agonist (LABA) bronchodilators are key to the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). This Phase IIb study investigated the safety and efficacy of four doses of the LAMA glycopyrronium (GP) delivered using co-suspension delivery technology via metered dose inhaler (MDI). The study was part of a wider clinical trial program performed to determine the optimal dose of GP MDI, the LABA formoterol fumarate dihydrate (FF) MDI, and glycopyrronium/formoterol fumarate dihydrate (GFF) MDI fixed-dose combination to be taken forward into Phase III studies...
March 5, 2018: Respiratory Research
Hye Yun Park, Suh-Young Lee, Danbee Kang, Juhee Cho, Hyun Lee, Seong Yong Lim, Ho Il Yoon, Seung Won Ra, Ki Uk Kim, Yeon-Mok Oh, Don D Sin, Sang-Do Lee, Yong Bum Park
BACKGROUND: The recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased. Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD. METHODS: COPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort. ACO was defined based on 3 major criteria: 1) airflow limitation in individuals 40 years of age and older, 2) ≥10 pack-years of smoking history, and 3) a history of asthma or bronchodilator response of > 400 mL in forced expiratory volume in 1 s (FEV1 ) at baseline; and at least 1 minor criterion: 1) history of atopy or allergic rhinitis, 2) two separated bronchodilator responses of ≥12% and 200 mL in FEV1 , or 3) peripheral blood eosinophils ≥300 cells/μL...
March 2, 2018: Respiratory Research
Xiuqin Ye, Wei Hong, Binwei Hao, Gongyong Peng, Lingmei Huang, Zhuxiang Zhao, Yumin Zhou, Mengning Zheng, Chenglong Li, Chunxiao Liang, Erkang Yi, Jinding Pu, Bing Li, Pixin Ran
BACKGROUND: The contribution of airway remodeling in chronic obstructive pulmonary disease (COPD) has been well documented, with airway smooth muscle cell proliferation and migration playing a role in the remodeling process. Here, we aimed to verify the effects of fine particulate matter (PM2.5) on human bronchial smooth muscle cell (HBSMC) migration and to explore the underlying signaling pathways. METHODS: HBSMC apoptosis, proliferation and migration were measured using flow cytometry, cell counting and transwell migration assays, respectively...
March 2, 2018: Respiratory Research
Luigi Mario Castello, Mattia Bellan
We would like to comment on the article entitled "Prognostic and diagnostic significance of copeptin in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from ACE 2 study" by Jacob A. Winther and colleagues, in the light of the results of a multicentric study published in 2014 by Vetrone F. et al., in which 336 patients with dyspnea were enrolled in the Emergency Departments of three University Hospitals in Italy.These two studies confirm the prognostic role of copeptin in patients with dyspnea due to heart failure but, while Winther et al...
March 1, 2018: Respiratory Research
Youhei Takahashi, Atsushi Saito, Hirofumi Chiba, Koji Kuronuma, Kimiyuki Ikeda, Tomofumi Kobayashi, Shigeru Ariki, Motoko Takahashi, Yasushi Sasaki, Hiroki Takahashi
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe form of idiopathic interstitial pneumonias. Although IPF has not been thought to be associated with bacterial communities, recent papers reported the possible role of microbiome composition in IPF. The roles of microbiomes in respiratory functions and as clinical biomarkers for IPF remain unknown. In this study, we aim to identify the relationship between the microbial environment in the lung and clinical findings...
February 27, 2018: Respiratory Research
Amanda Giesler, Manali Mukherjee, Katherine Radford, Luke Janssen, Parameswaran Nair
BACKGROUND: Asthma and obesity, two growing epidemics worldwide, may share an underlying causal relationship. Airway hyperresponsiveness (AHR), a defining component of asthma, has been documented in both 'obese' animal models and non-asthmatic obese individuals. However, there is a paucity of evidence that obesity-derived factors directly affect human airway smooth muscles (ASM). METHODS: Experiments were designed with primary ASM and adipocytes isolated from the same human tissue explants (n = 6)...
February 27, 2018: Respiratory Research
Giacomo Sgalla, Bruno Iovene, Mariarosaria Calvello, Margherita Ori, Francesco Varone, Luca Richeldi
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease characterized by the aberrant accumulation of fibrotic tissue in the lungs parenchyma, associated with significant morbidity and poor prognosis. This review will present the substantial advances achieved in the understanding of IPF pathogenesis and in the therapeutic options that can be offered to patients, and will address the issues regarding diagnosis and management that are still open. MAIN BODY: Over the last two decades much has been clarified about the pathogenic pathways underlying the development and progression of the lung scarring in IPF...
February 22, 2018: Respiratory Research
Kristoffer Ostridge, Nicholas P Williams, Viktoriya Kim, Stephen Harden, Simon Bourne, Stuart C Clarke, Emmanuel Aris, Sonia Mesia-Vela, Jeanne-Marie Devaster, Andrew Tuck, Anthony Williams, Stephen Wootton, Karl J Staples, Tom M A Wilkinson
BACKGROUND: COPD is a complex, heterogeneous disease characterised by progressive development of airflow limitation. Spirometry provides little information about key aspects of pathology and is poorly related to clinical outcome, so other tools are required to investigate the disease. We sought to explore the relationships between quantitative CT analysis with functional, inflammatory and infective assessments of disease to identify the utility of imaging to stratify disease to better predict outcomes and disease response...
February 20, 2018: Respiratory Research
Fernando Sergio Leitao Filho, Seung Won Ra, Andre Mattman, Robert S Schellenberg, Gerard J Criner, Prescott G Woodruff, Stephen C Lazarus, Richard Albert, John E Connett, Meilan K Han, Fernando J Martinez, Janice M Leung, S F Paul Man, Shawn D Aaron, Robert M Reed, Don D Sin
BACKGROUND: The literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD. We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts. METHODS: We measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653)...
February 14, 2018: Respiratory Research
Maurizio Turzo, Julian Vaith, Felix Lasitschka, Markus A Weigand, Cornelius J Busch
BACKGROUND: ATP-regulated potassium channels (KATP) regulate pulmonary vascular tone and are involved in hypoxic pulmonary vasoconstriction (HPV). In patients with inflammation like sepsis or ARDS, HPV is impaired, resulting in a ventilation-perfusion mismatch and hypoxia. Since increase of vascular KATP channel Kir6.1 has been reported in animal models of endotoxemia, we studied the expression and physiological effects of Kir6.1 in murine endotoxemic lungs. We hypothesized that inhibition of overexpressed Kir6...
February 13, 2018: Respiratory Research
Lian Li, Fangyuan Ren, Chao Qi, Leiqian Xu, Yinshan Fang, Maoli Liang, Jing Feng, Baoyuan Chen, Wen Ning, Jie Cao
BACKGROUND: Recently, increased tumor incidence and cancer-related mortality have been reported among patients with obstructive sleep apnea (OSA). Intermittent hypoxia (IH), the hallmark feature of OSA, contributes to the metastasis of tumors. However, the molecular mechanisms by which tumor metastasis is accelerated by OSA-like IH remain to be elucidated. METHODS: C57BL/6 J male mice were subjected to intravenous injection of B16F10 melanoma cells before receiving IH treatment...
February 12, 2018: Respiratory Research
Jiawen Lv, Junchao Zeng, Fukun Guo, Yiran Li, Mengying Xu, Yuanxiong Cheng, Lin Zhang, Shaoxi Cai, Yinghua Chen, Yi Zheng, Guodong Hu
BACKGROUND: Endothelial cell (EC) regeneration is essential for inflammation resolution and vascular integrity recovery after inflammatory vascular injury. Cdc42 is a central regulator of cell survival and vessel formation in EC development. However, it is unknown that whether Cdc42 could be a regulating role of EC repair following the inflammatory injury in the lung. The study sought to test the hypothesis that Cdc42 is required for endothelial regeneration and vascular integrity recovery after LPS-induced inflammatory injury...
February 8, 2018: Respiratory Research
Kate M Johnson, Stirling Bryan, Shahzad Ghanbarian, Don D Sin, Mohsen Sadatsafavi
BACKGROUND: A significant proportion of patients with chronic obstructive pulmonary disease (COPD) remain undiagnosed. Characterizing these patients can increase our understanding of the 'hidden' burden of COPD and the effectiveness of case detection interventions. METHODS: We conducted a systematic review and meta-analysis to compare patient and disease factors between patients with undiagnosed persistent airflow limitation and those with diagnosed COPD. We searched MEDLINE and EMBASE for observational studies of adult patients meeting accepted spirometric definitions of COPD...
February 7, 2018: Respiratory Research
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