Aclidinium inhibits human lung fibroblast to myofibroblast transition

Background Fibroblast to myofibroblast transition is believed to contribute to airway remodelling in lung diseases such as asthma and chronic obstructive pulmonary disease. This study examines the role of aclidinium, a new long-acting muscarinic antagonist, on human fibroblast to myofibroblast transition. Methods Human bronchial fibroblasts were stimulated with carbachol (10 −8 to 10 −5  M) or transforming growth factor-β1 (TGF-β1; 2 ng/ml) in the presence or absence of aclidinium (10 −9 to 10 −7  M) or different drug modulators for 48 h. Characterisation of myofibroblasts was performed by analysis of collagen type I and α-smooth muscle actin (α-SMA) mRNA and protein expression as well as α…

Nursing Education in Catalonia: Novice Professionals’ Appraisal of Its Quality and Usefulness. Does Mobility Play a Role?

The present study aimed to examine the relationship between the quality of undergraduate education perceived by novice nurses and their retrospective satisfaction with their education. It also studied the relationships between the perceived usefulness of their education for their current jobs and the quality of the jobs held by novice nursing professionals. The moderator role of mobility in this relationship was also analyzed, as it reflects a boundary condition in which additional preparation or job opportunities may occur. The study used data from the graduates’ survey carried out by the Agència per a la Qualitat del Sistema Universitari de Catalunya (AQU) in 2017. The analysis of data fr…

Extracellular calcium-sensing receptor mediates human bronchial epithelial wound repair

The airway epithelium routinely undergoes damage that requires repair to restore epithelial barrier integrity. Cell migration followed by proliferation are necessary steps to achieve epithelial repair. Calcium-sensing receptor (CaSR) is implicated in cell migration and proliferation processes. Thus we hypothesized that CaSR mediates lung epithelial wound repair. We detected CaSR expression in human lung and in well-differentiated human bronchial epithelial cells (HBEC). To test the CaSR functionality, HBEC loaded with fura-2 were stimulated with extracellular Ca(2+) ([Ca(2+)](out)) which resulted in a concentration-dependent intracellular Ca(2+) ([Ca(2+)](i)) increase (potency approximately…

Neutrophils restrain allergic airway inflammation by limiting ILC2 function and monocyte-dendritic cell antigen presentation

Neutrophil mobilization, recruitment, and clearance must be tightly regulated as overexuberant neutrophilic inflammation is implicated in the pathology of chronic diseases, including asthma. Efforts to target neutrophils therapeutically have failed to consider their pleiotropic functions and the implications of disrupting fundamental regulatory pathways that govern their turnover during homeostasis and inflammation. Using the house dust mite (HDM) model of allergic airway disease, we demonstrate that neutrophil depletion unexpectedly resulted in exacerbated T helper 2 (TH2) inflammation, epithelial remodeling, and airway resistance. Mechanistically, this was attributable to a marked increas…

The COVID-19 Crisis: Skills That Are Paramount to Build into Nursing Programs for Future Global Health Crisis

The COVID-19 pandemic started at the end of 2019 and can be considered one of the most difficult health crises of the past century. It has had a devastating effect around the world, not only for public health, but also for the economy, labor market, and other facets of individual and societal life. Health systems have been put under high strain, and health professionals have experienced unusual and stressful work circumstances. With the aim of drawing lessons for nursing education, the present study analyzed, during the weeks of peak infection in Spain, the stress experience and coping strategies of a sample of 403 nurses from the Spanish health system. Specifically, we analyzed how tenure,…

Aclidinium Partially Prevents Human Lung Fibroblast Activation In Vitro

Cigarette Smoke-Induced Fibroblast Activation Is Attenuated By Aclidinium In Vitro

Simvastatin Increases the Ability of Roflumilast N-oxide to Inhibit Cigarette Smoke-Induced Epithelial to Mesenchymal Transition in Well-differentiated Human Bronchial Epithelial Cells in vitro.

Cigarette smoking contributes to epithelial-mesenchymal transition (EMT) in COPD small bronchi as part of the lung remodeling process. We recently observed that roflumilast N-oxide (RNO), the active metabolite of the PDE4 inhibitor roflumilast, prevents cigarette smoke-induced EMT in differentiated human bronchial epithelial cells. Further, statins were shown to protect renal and alveolar epithelial cells from EMT. To analyze how RNO and simvastatin (SIM) interact on CSE-induced EMT in well-differentiated human bronchial epithelial cells (WD-HBEC) from small bronchi in vitro. Methods: WD-HBEC were stimulated with CSE (2.5%). The mesenchymal markers vimentin, collagen type I and α-SMA, the e…

Neutrophil activation in severe, early-onset COPD patients versus healthy non-smoker subjects in vitro: effects of antioxidant therapy.

<i>Background:</i> Neutrophils and oxidative stress have been implicated in the pathogenesis of COPD. Severe, early-onset COPD is characterized by a rapid decline in the lung function at an early age; however, nothing is known about neutrophil activation in COPD patients. <i>Objectives:</i> The aim of this study was to evaluate peripheral blood neutrophil activation in severe, early-onset COPD patients versus healthy non-smokers and the effect of N-acetyl-<i>L</i>-cysteine (NAC) on neutrophil activation in vitro. <i>Methods:</i> Neutrophils were isolated from 15 severe, early-onset COPD patients and 15 age-matched healthy subjects and stimulat…

Authors' response to: epithelial mesenchymal transition (EMT) in small airways of COPD patient.

We understand the reservations highlighted by Sohal and Walters in their letter in response to our recent work published.1 In their letter, Sohal and Walters argue that E-cadherin and ZO-1 are absent in our immunohistochemistry analysis of small bronchi of smokers and COPD patients, and that if disappeared completely epithelium would fall apart.1 In our study, we detected downregulation of E-cadherin and ZO-1 as well as a change of intercellular and apical distribution to diffuse cytoplasmic redistribution (figure 3B; in our work published in Thorax on 7 January 2013),2 but not …

Bafetinib inhibits functional responses of human eosinophils in vitro

Eosinophils play a prominent role in the process of allergic inflammation. Non-receptor associated Lyn tyrosine kinases generate key initial signals in eosinophils. Bafetinib, a specific Abl/Lyn tyrosine kinase inhibitor has shown a potent antiproliferative activity in leukemic cells, but its effects on eosinophils have not been reported. Therefore, we studied the effects of bafetinib on functional and mechanistic responses of isolated human eosinophils. Bafetinib was more potent than non-specific tyrosin kinase comparators genistein and tyrphostin inhibiting superoxide anion triggered by N-formyl-Met-Leu-Phe (fMLF; 100 nM) (−log IC50=7.25±0.04 M; 6.1±0.04 M; and 6.55±0.03 M, respectively).…

Mucin 1 downregulation associates with corticosteroid resistance in chronic rhinosinusitis with nasal polyps

Background A number of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) are resistant to oral corticosteroids. Mucin 1 (MUC1) shows anti-inflammatory properties, and its cytoplasmic tail (CT) interacts with transcription factors, facilitating their nuclear translocation. Because glucocorticoid receptor (GR) nuclear translocation is key to the anti-inflammatory effect of corticosteroids, we hypothesized that MUC1 is involved in the effectiveness of corticosteroids. Objective To analyze the role of MUC1 in corticosteroid effectiveness in different cohorts of patients with CRSwNP and elucidate the possible mechanisms involved. Methods Seventy-three patients with CRSwNP took oral…

Aclidinium inhibits cigarette smoke-induced lung fibroblast-to-myofibroblast transition.

Cigarette smoking contributes to lung remodelling in chronic obstructive pulmonary disease (COPD). As part of this remodelling, peribronchiolar fibrosis is observed in the small airways of COPD patients and contributes to airway obstruction. Fibroblast-to-myofibroblast transition is a key step in peribronchiolar fibrosis formation. This in vitro study examined the effect of cigarette smoke on bronchial fibroblast-to-myofibroblast transition, and whether aclidinium bromide inhibits this process. Human bronchial fibroblasts were incubated with aclidinium bromide (10 −9 –10 −7 M) and exposed to cigarette smoke extract. Collagen type I and α-smooth muscle actin (α-SMA) expression were measured …

Epithelial to mesenchymal transition is increased in patients with COPD and induced by cigarette smoke

Background Cigarette smoking contributes to lung remodelling in chronic obstructive pulmonary disease (COPD). As part of remodelling, peribronchiolar fibrosis is observed in the small airways of patients with COPD and contributes to airway obstruction. Epithelial to mesenchymal transition (EMT) appears to be involved in the formation of peribronchiolar fibrosis. This study examines the EMT process in human bronchial epithelial cells (HBECs) from non-smokers, smokers and patients with COPD as well as the in vitro effect of cigarette smoke extract (CSE) on EMT. Methods HBECs from non-smokers (n=5), smokers (n=12) and patients with COPD (n=15) were collected to measure the mesenchymal markers …

Roflumilast N-oxide inhibits bronchial epithelial to mesenchymal transition induced by cigarette smoke in smokers with COPD.

Abstract Background Epithelial to mesenchymal transition (EMT) is under discussion as a potential mechanism of small airway remodelling in COPD. In bronchial epithelium of COPD and smokers markers of EMT were described. In vitro, EMT may be reproduced by exposing well-differentiated human bronchial epithelial cells (WD-HBEC) to cigarette smoke extract (CSE). EMT may be mitigated by an increase in cellular cAMP. Objective This study explored the effects of roflumilast N-oxide, a PDE4 inhibitor on CSE-induced EMT in WD-HBEC and in primary bronchial epithelial cells from smokers and COPD in vitro. Methods WD-HBEC from normal donors were stimulated with CSE (2.5%) for 72 h in presence of roflum…

Anti-Inflammatory Effect Of Roflumilast N-Oxide In Glucocorticoid Insensitive Human Neutrophils From Chronic Obstructive Pulmonary Disease Patients

Nurses´ stressors and psychological distress during the COVID‐19 pandemic: The mediating role of coping and resilience

This study analyses the cross-sectional effect of sources of stress during the peak of COVID-19 pandemic on nurses´ psychological distress, focusing on the mediating role of coping strategies, both problem focused and emotion focused and resilience.Cross-sectional and quantitative analyses.Structural equation modelling was performed using survey data obtained during the period between 1 April-25 May 2020 in a sample of 421 nurses from 39 Spanish provinces.Results confirmed that: (a) All the stressors have a significant, direct, and negative relationship with nurses´ psychological distress; (b) Emotion-focused strategies is negatively related to nurses´ psychological distress directly and in…