Phosphodiesterase-4 inhibition improves corticosteroid insensitivity in pulmonary endothelial cells under oxidative stress.

Several clinical studies have shown that smoking in asthmatics and chronic obstructive pulmonary disease patients is closely associated with corticosteroid refractoriness. In this work, we have analyzed glucocorticoid insensitivity in human pulmonary artery endothelial cells (HPAECs) under cigarette smoke extract (CSE) exposure as well as the possible additive effects of the combination therapy with a phosphodiesterase (PDE)-4 inhibitor. Interleukin (IL)-8 was measured in cell supernatants by ELISA. Histone deacetylase (HDAC), histone acetylase (HAT), and intracellular cAMP levels were measured by colorimetric assays and enzyme immunoassay, respectively. PDE4 isotypes and glucocorticoid rec…

Late Breaking Abstract - CRAC channel inhibition by RP3128 triggers potent anti-inflammatory effects in COPD or asthmatic patient-derived primary cells

Introduction: Calcium release activated calcium channels inhibitors have a potent role in treatment of autoimmune disorders. RP3128 is a novel and potent inhibitor of Calcium Release Activated Calcium (CRAC) channel activity with demonstrated efficacy in several models of immune-inflammatory disorders. The objective of this study was to assess the effect of RP3128 and combinations in attenuating inflammatory responses associated with respiratory diseases. Methods: Inhibition of antigen-induced cytokine release in primary T-lymphocytes was estimated. Peripheral blood neutrophils or mononuclear cells were isolated from COPD or asthmatic patients, pre-incubated with RP3128 for 0.5 h, and stimu…

Efecto in vitro de la adición de resinas de intercambio iónico sobre la biodisponibilidad de electrolitos en fórmulas de nutrición enteral artificial

The in vitro effect of the addition of ion exchange resins on the bioavailability of electrolytes in artificial enteral feeding formulas Objective: To determine in vitro free ion concentration in three standard artificial enteral feeding formulas following the addition of ion exchange resins. Method: Three standard types of AEF were chosen: Osmolite HN®, Nutrison Standard® and Isosource Standard®. The ion exchange resins used were: Sodium Polystyrene Sulfonate and Calcium Polystyrene Sulfonate. 100 ml of AEF were mixed in a beaker with 1.5 g or 3 g of ion exchange resins for 48 hours at 37oC. Subsequently, the samples were precipitated and the supernatant obtained was used for determining t…

LATE-BREAKING ABSTRACT: Anti-inflammatory effect of RP6557, a dual PI3K δ/γ inhibitor, in glucocorticoid insensitive human neutrophils from chronic obstructive pulmonary disease patients

Rationale: Glucocorticoid function is markedly impaired in patients with chronic obstructive pulmonary disease (COPD). Class I PI3K enzymes play a key role in chronic lung inflammation of COPD patients. This study explored differential inhibitory effects of dexamethasone and RP6557, a dual PI3K δ/γ inhibitor, on inflammatory responses in human neutrophils from healthy and COPD patients. Methods: Peripheral blood neutrophils were isolated from COPD patients andhealthy subjects and pre-incubated with dexamethasone (DEX) or RP6557 for 1 h. Neutrophils were stimulated with 5% cigarette smoke extract (CSE) for 6 h. Supernatants were used to measure IL-8 while RNA from neutrophils was analyzed fo…

Additional file 1: of The JAK2 pathway is activated in idiopathic pulmonary fibrosis

Supplementary data. (DOCX 1218 kb)

The Role of JAK/STAT Molecular Pathway in Vascular Remodeling Associated with Pulmonary Hypertension

Pulmonary hypertension is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance (PVR), which leads to right ventricular failure and premature death. There are multiple clinical manifestations that can be grouped into five different types. Pulmonary artery remodeling is a common feature in pulmonary hypertension (PH) characterized by endothelial dysfunction and smooth muscle pulmonary artery cell proliferation. The current treatments for PH are limited to vasodilatory agents that do not stop the progression of the disease. Therefore, there is a need for new agents that inhibit pulmonary artery remodeling targeting the main genetic, molecular,…

Role of IL-11 in vascular function of pulmonary fibrosis patients

Pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) portends a poor prognosis. Currently, no therapy can improve survival of patients diagnosed with this disease. IL-11 molecular pathway is over-expressed in proliferative disorders, however, its role in PH- associated IPF is unknown. The aim of this study was to evaluated the expression of IL-11 in IPF patients with or without PH. Also we hypothesized that the stimulation of pulmonary artery smooth muscle cells (PASMCs) and human pulmonary artery microvascular endothelial cells (HMVEC-L) with IL-11 induced the transformation into invasive myofibroblast. Human pulmonary artery rings, parenchyma tissue, broncho-alveolar lavage …

Targeting Oxidative Stress as a Therapeutic Approach for Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by an abnormal reepithelialisation, an excessive tissue remodelling and a progressive fibrosis within the alveolar wall that are not due to infection or cancer. Oxidative stress has been proposed as a key molecular process in pulmonary fibrosis development and different components of the redox system are altered in the cellular actors participating in lung fibrosis. To this respect, several activators of the antioxidant machinery and inhibitors of the oxidant species and pathways have been assayed in preclinicalin vitroandin vivomodels and in different clinical trials. This review discusses the role of …

Nitric Oxide System and Bronchial Epithelium: More Than a Barrier

Airway epithelium forms a physical barrier that protects the lung from the entrance of inhaled allergens, irritants, or microorganisms. This epithelial structure is maintained by tight junctions, adherens junctions and desmosomes that prevent the diffusion of soluble mediators or proteins between apical and basolateral cell surfaces. This apical junctional complex also participates in several signaling pathways involved in gene expression, cell proliferation and cell differentiation. In addition, the airway epithelium can produce chemokines and cytokines that trigger the activation of the immune response. Disruption of this complex by some inflammatory, profibrotic, and carcinogens agents c…

Aclidinium inhibits cholinergic and tobacco smoke-induced MUC5AC in human airways.

Mucus hypersecretion and mucin MUC5AC overexpression are pathological features of chronic obstructive pulmonary disease (COPD). This study examines the inhibitory effect of aclidinium, a new long-acting muscarinic antagonist, on MUC5AC expression in human airway epithelial cells. MUC5AC mRNA (RT-PCR) and protein expression (ELISA and immunohistochemistry) were studied in human bronchial tissue and differentiated human airway epithelial cells activated with carbachol (100 μM) or cigarette smoke extract in the absence or presence of aclidinium. Carbachol increased MUC5AC mRNA and protein expression in human bronchus and cultured epithelial cells. Aclidinium inhibited the carbachol-induced MUC…

MUC4 overexpression correlates corticoid resistance in chronic rhinosinusitis with nasal polyps

Background: Some patients with chronic rhinosinusitis with nasal polyps (CRSwNP) are resistant to corticoids. Mucin 4 (MUC4) is a membrane anchored protein with a nuclear translocation domain which is modulated by corticoids. Because glucocorticoid receptor (GR) nuclear translocation is key to the anti-inflammatory effect of corticoids, we hypothesized that MUC4 is involved in the effectiveness of these drugs Objective: To analyze the role of MUC4 in corticoid effectiveness in different cohorts of patients with CRSwNP and elucidate the possible mechanisms involved Methods: 73 patients with CRSwNP took oral corticoids for 15 days. Corticoid resistance was evaluated by nasal endoscopy. The ex…

Role of JAK2/STAT3 pathway in vascular function of pulmonary fibrosis patients

Background: Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive lung disease with a life expectancy of 2-5 years. A proportion of IPF patients develop pulmonary hypertension (PH), characterized by vasoconstriction and remodeling of pulmonary arteries. Currently, no therapy can improve survival of patients diagnosed with this disease. JAK2/STAT3 molecular route is overexpressed in proliferative disorders, however, its role in PH- associated IPF is unknown. Objective: To analyze the role of JAK2/STAT3 in vascular function of IPF patients with PH. We hypothesized that inhibition of JAK2, STAT3 or JAK2/STAT3 may improve vascular function. Methods: Human precision cut lung slices and ar…

In vitro tracheal hyperresponsiveness to muscarinic receptor stimulation by carbachol in a rat model of bleomycin-induced pulmonary fibrosis

Summary 1 Bleomycin-induced lung injury is widely used as an experimental model to investigate the pathophysiology of pulmonary fibrosis but the alterations in the pharmacological responsiveness of airways isolated from bleomycin-exposed animals has been scarcely investigated. The aim of this study was to examine the in vitro tracheal responses to muscarinic receptor stimulation with carbachol in a rat bleomycin model. 2 Concentration–response curves to carbachol (10 nm to 0.1 mm) were obtained in tracheal rings isolated from Sprague–Dawley rats 14 days after endotracheal bleomycin or saline. The intracellular calcium signal in response to carbachol (10 μm) was measured by epifluorescence m…

Aclidinium Partially Prevents Human Lung Fibroblast Activation In Vitro

Evaluation of Mucociliary Clearance by Three Dimension Micro-CT-SPECT in Guinea Pig: Role of Bitter Taste Agonists

Different image techniques have been used to analyze mucociliary clearance (MCC) in humans, but current small animal MCC analysis using in vivo imaging has not been well defined. Bitter taste receptor (T2R) agonists increase ciliary beat frequency (CBF) and cause bronchodilation but their effects in vivo are not well understood. This work analyzes in vivo nasal and bronchial MCC in guinea pig animals using three dimension (3D) microCT-SPECT images and evaluates the effect of T2R agonists. Intranasal macroaggreggates of albumin-Technetium 99 metastable (MAA-Tc99m) and lung nebulized Tc99m albumin nanocolloids were used to analyze the effect of T2R agonists on nasal and bronchial MCC respecti…

Cigarette smoke exposure up-regulates endothelin receptor B in human pulmonary artery endothelial cells: molecular and functional consequences

BACKGROUND AND PURPOSE Pulmonary arteries from smokers and chronic obstructive pulmonary disease patients show abnormal endothelium-dependent vascular reactivity. We studied the effect of cigarette smoke extract (CSE) on endothelin receptor B (ETB) expression in human pulmonary artery endothelial cells (HPAECs) and its role in endothelial dysfunction. EXPERIMENTAL APPROACH ETB receptor expression was measured by real time RT-PCR, Western blot and immunofluorescence. Cell contraction, intracellular Ca2+, F/G-actin, RhoA activity, myosin light chain phosphorylation, ET, NO, thromboxane (Tx)A2 and reactive oxygen species (ROS) were measured by traction microscopy, fluorescence microscopy, phal…

Mucins as a New Frontier in Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pulmonary disease with a median survival of 3–5 years after diagnosis. Recent evidence identifies mucins as key effectors in cell growth and tissue remodeling processes compatible with the processes observed in IPF. Mucins are classified in two groups depending on whether they are secreted (secreted mucins) or tethered to cell membranes (transmembrane mucins). Secreted mucins (MUC2, MUC5AC, MUC5B, MUC6-8 and MUC19) are released to the extracellular medium and recent evidence has shown that a promoter polymorphism in the secreted mucin MUC5B is associated with IPF risk. Otherwise, transmembrane mucins (MUC1, MUC3,…

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

Mucin 1 deficiency mediates corticosteroid insensitivity in asthma

BACKGROUND: The loss of corticosteroid efficacy is an important issue in severe asthma management and may lead to poor asthma control and deterioration of airflow. Recent data indicate that Mucin 1 (MUC1) membrane mucin can mediate corticosteroid efficacy in chronic rhinosinusitis, but the role of MUC1 in uncontrolled severe asthma is unknown. The objective was to analyze the previously unexplored role of MUC1 on corticosteroid efficacy in asthma. METHODS: Mucin 1 expression was evaluated by real-time PCR in human bronchial epithelial cells (HBEC) and blood neutrophils from uncontrolled severe asthma (n=27), controlled mild asthma (n=16), and healthy subjects (n=13). IL-8, MMP9, and GM-CSF …

[The in vitro effect of the addition of ion exchange resins on the bioavailability of electrolytes in artificial enteral feeding formulas].

Objective: To determine in vitro free ion concentration in 3 standard artificial enteral feeding formulas following the addition of ion exchange resins. Method: Three standard types of AEF were chosen: Osmolite HN®, Nutrison Standard®, and Isosource Standard®. The ion exchange resins used were: sodium polystyrene sulfonate and calcium polystyrene sulfonate. In a beaker were mixed 100 mL of AEF with 1.5 g or 3 g of ion exchange resins for 48 hours at 37oC. Subsequently, the samples were precipitated and the supernatant obtained was used for determining the concentrations of calcium, magnesium, sodium, and potassium ions. Results: The addition of sodium polystyrene sulfonate to different type…

Roflumilast N-Oxide Partially Prevents The Loss Of Ciliated Human Airway Epithelial Cells Secondary To Incubation With Cigarette Smoke Extracts In Vitro

LATE-BREAKING ABSTRACT: MUC1 downregulation induces corticosteroid resistance in asthma'sin vitroandin vivomodels

Background: Corticosteroids are in the first-line of Asthma treatment. However a subset of asthmatic patients is insensitive to anti-inflammatory effects of corticosteroids. Our previous data demonstrated that MUC1 downregulation correlates corticosteroid resistance in Nasal Polyposis and COPD. We hypothesized that MUC1 is also involved in corticosteroid resistance in Asthma. Objective: To analyze the role of MUC1 in the corticosteroid effectiveness in Asthma9s in vitro and in vivo models. Methods: 20 patients with steroid resistant Asthma were recruited. The expression of MUC1 was determined by real-time PCR in inflammatory cells from peripheral blood. HMVEC-L and U937 cells knockdown with…

Oxidative stress-induced glucocorticoid resistance is prevented by dual PDE3/PDE4 inhibition in human alveolar macrophages

Summary Background Oxidative stress is present in airway diseases such as severe asthma or Chronic Obstructive Pulmonary Disease and contributes to the low response to glucocorticoids through the down-regulation of histone deacetylase (HDAC) activity. Objective To study the effects of the phosphodiesterase (PDE)-3 and 4 inhibitors and their combination vs. glucocorticoids in a model of lipopolysaccharide (LPS)-induced cytokine release in alveolar macrophages under oxidative stress conditions. Methods Differentiated U937 or human alveolar macrophages were stimulated with H2O2 (10–1000 μm) or cigarette smoke extract (CSE, 0–15%) for 4 h before LPS (0.5 μg/mL, 24 h) addition. In other experime…

High-Speed Video Microscopy for Primary Ciliary Dyskinesia Diagnosis: A Study of Ciliary Motility Variations with Time and Temperature

Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/2075-4418/11/7/1301 Este artículo de investigación pertenece al número especial "Progress in Diagnosing and Managing Primary Ciliary Dyskinesia". Primary ciliary dyskinesia (PCD) is a rare disease resulting from a defect in ciliary function that generates, among other issues, chronic upper and lower respiratory tract infections. European guidelines recommend studying ciliary function (pattern (CBP) and frequency (CBF)), together with characteristic clinical symptoms, as one of the definitive tests. However, there is no “gold standard”. The present study aims to use high-speed video microscopy to describe how CBF…

Sphingosine-1-phosphate increases human alveolar epithelial IL-8 secretion, proliferation and neutrophil chemotaxis

Sphingosine-1-phosphate (S1P) has been presented recently as a pro-inflammatory agent in the airway epithelium since S1P levels are increased in bronchoalveolar lavage fluid of human asthmatics. However, the effects of S1P over the alveolar epithelium and neutrophil interactions are poorly understood. Here, we show that S1P increased interleukin 8 (IL-8) gene expression and protein secretion and proliferation in alveolar epithelial cells A549 at physiological concentrations (1 microM). At the same time, S1P increased intracellular Ca2+ concentration (potency 17.91 microM, measured by epifluorescence microscopy), phospholipase D (PLD) activity (measured by chemiluminiscence method) and extra…

Roflumilast N-oxide combined with PI3Kδ inhibitor improves the phenotype of early-onset COPD

Background: Severe, early-onset COPD (Chronic Obstructive Pulmonary Disease) is characterized by a rapid decline in lung function at an early age with neutrophil over-activation. Roflumilast is approved as treatment for moderate and severe COPD at risk of exacerbation as add on therapy. Recent evidence indicates that the combination of PDE4 and PI3Kδ inhibitors show synergic anti-inflammatory properties. Objectives: To explore the effects from adding a selective PI3Kδ inhibitor to roflumilast N-oxide (RNO) in neutrophils isolated from peripheral blood of severe, early-onset COPD patients in in vitro models. Methods: Neutrophils were isolated from peripheral blood of 20 severe, early-onset C…

Roflumilast N- oxide combined with sildenafil reverses cellular remodeling on IPF models

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a rapid progressive lung decline and premature death after its diagnosis. Roflumilast displayed anti-fibrotic effects in animal and cellular models. Recent studies indicate that the combination of PDE4 and PDE5 inhibitors (sildenafil) potentiates anti-fibrotic properties of each drug, suggesting potential beneficts of this combination. Objectives: To study the effects from adding sildenafil to roflumilast N-oxide (RNO) inhibiting TGFβ1-induced human alveolar type II (AECII) epithelial-to-mesenchymal transition (EMT) and human fibrocyte to myofibroblast transition in vitro. Methods: AECII and fibrocytes were isolated from he…

Role of MUC1 in idiopathic pulmonary fibrosis: mechanistic insights

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible form of fibrotic interstitial lung disease. MUC1, a membrane-bound O-glycoprotein, is considered as oncogenic molecule by altering signaling pathways involved in cellular processes related to IPF. In previous studies we have observed an up-regulation of MUC1 and its phosphorylated forms in IPF lung tissue. However the exact participation of MUC1 in IPF is currently unknown. Objective: To analyze the mechanism of MUC1-induced lung fibrosis in different cellular and animal models of IPF. Methods: The intracellular mechanism of MUC1 was evaluated by western blot, immunoprecipation and immunofluorescence …

Role of MUC1 in idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible form of fibrotic intersticial lung disease, characterized by uncontrolled fibroblast proliferative processes and alveolar type II epithelial dysfunction. MUC1 is considered as oncogenic molecule by altering signaling pathways involved in cellular proliferation and cell death. Objective: To analyze the implication of MUC1 in IPF Methods: Lung tissue from 14 healthy and 14 IPF patients was obtained. The expression of MUC1 cytoplasmic tail (CT) and its phosphorylation forms in T-1224 and Y-1229 residues were analyzed by western blot and immunohistochemistry. The effect of MUC1 on TGFβ1-Iinduced epithelia…

DPP-4 is overexpressed in lung tissue from idiopathic pulmonary patients and activates lung fibroblasts

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible form of fibrotic interstitial lung disease, characterized by uncontrolled fibroblast invasion. Dipeptidyl peptidase-4 (DPP-4)/ glucagon-like peptide 1 (GLP-1) system is involved in multiple effects, including cardiac, liver or kidney fibrosis. However, its implication in IPF has not been described. Objective: To analyse the implication of DPP4/GLP1 system in IPF. Methods: Protein expression of DPP4, GLP-1 and GLP-1 receptor was analyzed in lung tissues from 7 IPF patients. TGFβ1-induced fibroblast to myofibroblast transition (FMT), epithelial to mesenchymal transition (EMT) and mesothelial to mesenchymal trans…

Role of JAK/STAT in Interstitial Lung Diseases; Molecular and Cellular Mechanisms

Interstitial lung diseases (ILDs) comprise different fibrotic lung disorders characterized by cellular proliferation, interstitial inflammation, and fibrosis. The JAK/STAT molecular pathway is activated under the interaction of a broad number of profibrotic/pro-inflammatory cytokines, such as IL-6, IL-11, and IL-13, among others, which are increased in different ILDs. Similarly, several growth factors over-expressed in ILDs, such as platelet-derived growth factor (PDGF), transforming growth factor β1 (TGF-β1), and fibroblast growth factor (FGF) activate JAK/STAT by canonical or non-canonical pathways, which indicates a predominant role of JAK/STAT in ILDs. Between the different JAK/STAT iso…

IL-11 promotes pulmonary vascular remodeling and lung fibrosis through the activation of endothelial to mesenchymal transition

Background: Pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) portends a poor prognosis and currently there is no approved therapy for hypoxemic PH. IL-11 is a novel lung fibrosis mediator but its role on vascular function is unknown. Objective: To analyze the role of IL-11 on pulmonary artery remodeling and lung fibrosis in vitro and in vivo. Methods: IL-11 expression was evaluated in pulmonary arteries and lung sections of control subjects and patients with IPF, IPF+PH and idiopathic PH (PAH). Human pulmonary artery endothelial cells and smooth muscle cells were stimulated with IL-11. Endothelial to mesenchymal transition was evaluated measuring the increase of mesenchyma…

Functional Profile Of Aclidinium Bromide In Isolated Human Bronchi And Left Atria

Hawthorn extract inhibits human isolated neutrophil functions.

Hawthorn extract is a popular herbal medicine given as adjunctive treatment for chronic heart failure. In contrast to the cardiac properties of hawthorn extract, its anti-inflammatory effect has been scarcely investigated. This study examines the effects of a dry extract of leaves and flowers of Crataegus laevigata on various functional outputs of human neutrophils in vitro. Incubation of human neutrophils obtained from peripheral blood of healthy donors with C. laevigata extract (0.75-250 microg/ml) inhibited N-formyl-Met-Leu-Phe (FMLP)-induced superoxide anion generation, elastase release and chemotactic migration with potency values of 43.6, 21.9, and 31.6 microg/ml, respectively. By con…

MUC1-CT mediates corticosteroid responses in COPD

Background: Corticosteroid resistance is an acquired condition in chronic obstructive pulmonary disease (COPD) patients and a challenge to develop new anti-inflammatory therapies. In previous reports we showed that cytoplasmic tail of the membrain tethered mucin 1 (MUC1-CT) interacts with glucocorticoid receptor (GR) mediating corticosteroid anti-inflammatory efficacy. Objectives: To analyze the role of MUC1-CT as a key marker of corticosteroid efficacy in COPD Methods: The expression of MUC1-CT and the anti-inflammatory role of dexamethasone were evaluated in neutrophils and bronchial epithelial cells from healthy and COPD patients. Anti-inflammatory effects of dexamethasone and glucocorti…

Osimertinib in first-line treatment of advanced EGFR-mutated non-small-cell lung cancer: a cost–effectiveness analysis

Aim: Osimertinib improves progression-free survival in first-line EGFR mutation–positive non-small-cell lung cancer. Materials & methods: A Markov cohort model including costs, utilities and disutilities, was conducted to estimate quality-adjusted life-year (QALY) and incremental cost–effectiveness ratio when treating with osimertinib versus standard first-line tyrosine kinase inhibitors (TKIs). Results: Osimertinib presented higher QALYs (0.61) compared with standard EGFR–TKIs (0.42). Osimertinib costs were €83,258.99, in comparison with €29,209.45 for the standard EGFR–TKIs. An incremental cost–effectiveness ratio of €273,895.36/QALY was obtained for osimertinib. Conclusion: Osimerti…

Aclidinium, a New Long-Acting Antimuscarinic, Inhibits Cholinergic and Cigarette Smoke-Induced Up Regulation of Mucin MUC5AC Expression in Human Airway Epithelial Cells

Additional file 1: of MUC1 deficiency mediates corticosteroid resistance in chronic obstructive pulmonary disease

Figure S1. Acute cigarette smoke/ lipopolysaccharide lung inflammatory animal model showed resistance to dexamethasone improving lung resistance and bronchoalveolar inflammatory cell extravasation in Muc1 KO animals. Figure S2. IL-8 and IL-13 bronchoalveolar fluid content in Muc1 KO mice exposed to acute cigarette smoke/ lipopolysaccharide is resistant to dexamethasone. Figure S3. Inflammatory lung cell infiltration secondary to acute lipopolysaccharide/ cigarette smoke exposure is resistant to dexamethasone in MUC1 KO mice. (DOCX 1611 kb)

Molecular and Clinical Predictors of Quality of Life in Chronic Rhinosinusitis with Nasal Polyps

(1) Background: Factors influencing the quality of life (QoL) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) are poorly understood. We set out to determine the predictive factors on patients’ QoL using the Sino-Nasal Outcome Test-22 (SNOT-22); (2) Methods: An ambispective analysis of data from patients diagnosed with CRSwNP in our institution. All the patients underwent a nasal polyp biopsy and completed the SNOT-22 questionnaire. Demographic and molecular data as well as the SNOT-22 scores were collected. Patients were classified in six subgroups considering the presence of asthma, non-steroidal drugs (NSAID) intolerance and corticosteroid resistance; (3) Results: Th…

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

Additional file 1: of Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients

Supplementary Table S1. Maximal percentage of inhibition of IL-8, MMP-9, CCL-5, GM-CSF and IL-1β release from neutrophils of healthy subjects and COPD patients. Neutrophils were incubated with aclidinium (Acl; 0.1nM-1 μM), fluticasone (Flut; 0.1nM-1 μM), formoterol (Form; 0.01nM-100nM) or salmeterol (Salm; 0.1nM-1 μM) in response to LPS (1 μg/ml) or cigarette smoke extract (CSE 5 %). The levels of different cytokines in the cell supernatant were determined and the maximal percent of inhibitions were calculated. Values are mean ± SD of 3 independent experiments run in triplicate. *p 

Crataegus laevigata decreases neutrophil elastase and has hypolipidemic effect: a randomized, double-blind, placebo-controlled trial.

Crataegus laevigata is a medicinal plant most commonly used for the treatment of heart failure and psychosomatic disorders. Based on previous experimental findings, this double-blind placebo-controlled study was aimed at finding beneficial effects of C. laevigata on biomarkers of coronary heart disease (CHD). The study included 49 diabetic subjects with chronic CHD who were randomly assigned to the treatment for 6 months with either a micronized flower and leaf preparation of C. laevigata (400 mg three times a day) or a matching placebo. Blood cell count, lipid profile, C-reactive protein, neutrophil elastase (NE) and malondialdehyde were analyzed in plasma at baseline, at one month and six…

The role of mucin 1 in respiratory diseases

Recent evidence has demonstrated that mucin 1 (MUC1) is involved in many pathological processes that occur in the lung. MUC1 is a transmembrane protein mainly expressed by epithelial and hematopoietic cells. It has a receptor-like structure, which can sense the external environment and activate intracellular signal transduction pathways through its cytoplasmic domain. The extracellular domain of MUC1 can be released to the external environment, thus acting as a decoy barrier to mucosal pathogens, as well as serving as a serum biomarker for the diagnosis and prognosis of several respiratory diseases such as lung cancer and interstitial lung diseases. Furthermore, bioactivated MUC1-cytoplasmi…

Additional file 2: of Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients

Supplementary Figure E1. Effects of formoterol and salmeterol on pro-inflammatory markers. Concentration-dependent inhibition of lipopolysaccharide (LPS)-induced cytokines or MMP-9 release by formoterol (Form) and salmeterol (Salm) from peripheral blood neutrophils of healthy subjects and COPD patients. Neutrophils were preincubated with Salm (0.1nM-1 μM) or form (0.01nM-100nM) for 1 h followed by cell stimulation with LPS (1 μg/ml) for 6 h. Results are expressed as means ± SD of n = 3 (3 cell healthy and 3 cell COPD populations run in triplicate) independent experiments. Two-way ANOVA was followed by the post hoc Bonferroni test. *p