Respiratory Pathogens at Exacerbation in Chronic Bronchitis With Airway Bacterial Colonisation: A Cohort Study.

Background And Objective: COPD and bronchiectasis are common causes of morbidity, particularly around exacerbation. Colonisation with respiratory pathogens can increase the frequency and severity of exacerbations. However, bacterial and viral presence at exacerbation in people with airway colonisation has not been well studied.

Heparin, Low Molecular Weight Heparin, and Non-Anticoagulant Derivatives for the Treatment of Inflammatory Lung Disease.

Unfractionated heparin has multiple pharmacological activities beyond anticoagulation. These anti-inflammatory, anti-microbial, and mucoactive activities are shared in part by low molecular weight and non-anticoagulant heparin derivatives. Anti-inflammatory activities include inhibition of chemokine activity and cytokine synthesis, inhibitory effects on the mechanisms of adhesion and diapedesis involved in neutrophil recruitment, inhibition of heparanase activity, inhibition of the proteases of the coagulation and complement cascades, inhibition of neutrophil elastase activity, neutralisation of toxic basic histones, and inhibition of HMGB1 activity.

Elexacaftor-Tezacaftor-Ivacaftor improves exercise capacity in adolescents with cystic fibrosis.

Objective: Elexacaftor/Tezacaftor/Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator with the potential to improve exercise capacity. This case series of three adolescents with CF aimed to investigate whether 6 weeks treatment with Elexacaftor/Tezacaftor/Ivacaftor could improve exercise capacity in CFTR modulator naive adolescents with CF.

Methods: Three adolescents (14.

CFTR limits F-actin formation and promotes morphological alignment with flow in human lung microvascular endothelial cells.

Micro- and macrovascular endothelial dysfunction in response to shear stress has been observed in cystic fibrosis (CF), and has been associated with inflammation and oxidative stress. We tested the hypothesis that the cystic fibrosis transmembrane conductance regulator (CFTR) regulates endothelial actin cytoskeleton dynamics and cellular alignment in response to flow. Human lung microvascular endothelial cells (HLMVEC) were cultured with either the CFTR inhibitor GlyH-101 (20 µM) or CFTRinh-172 (20 µM), tumor necrosis factor (TNF)-α (10 ng/ml) or a vehicle control (0.

Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3.

Platelet activation and pulmonary recruitment occur in patients with asthma and in animal models of allergic asthma, in which leukocyte infiltration, airway remodeling, and hyperresponsiveness are suppressed by experimental platelet depletion. These observations suggest the importance of platelets to various characteristics of allergic disease, but the mechanisms of platelet migration and location are not understood. The aim of this study was to assess the mechanism of platelet recruitment to extravascular compartments of lungs from patients with asthma and after allergen challenge in mice sensitized to house dust mite (HDM) extract (contains the DerP1 [ extract peptidase 1] allergen); in addition, we assessed the role of chemokines in this process.

Critical analysis of the utility of initial pleural aspiration in the diagnosis and management of suspected malignant pleural effusion.

Introduction: Current guidelines recommend an initial pleural aspiration in the investigation and management of suspected malignant pleural effusions (MPEs) with the aim of establishing a diagnosis, identifying non-expansile lung (NEL) and, at times, providing a therapeutic procedure. A wealth of research has been published since the guidelines suggesting that results and outcomes from an aspiration may not always provide sufficient information to guide management. It is important to establish the validity of these findings in a 'real world' population.

Circulating biomarkers of antioxidant status and oxidative stress in people with cystic fibrosis: A systematic review and meta-analysis.

Introduction: Oxidative stress may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to quantify CF-related redox imbalances.

Methods: Systematic searches of the Medline, CINAHL, CENTRAL and PsycINFO databases were conducted.

The implications of dysglycaemia on aerobic exercise and ventilatory function in cystic fibrosis.

Background: The development of cystic fibrosis (CF)-related diabetes (CFRD) in paediatric groups is associated with a reduced aerobic fitness. However, this has yet to be investigated in adults with more severe lung disease.

Methods: Cardiopulmonary exercise and glycaemic control tests were retrospectively analysed in 46 adults with CF (age: 26.

Cardiopulmonary exercise testing with supramaximal verification produces a safe and valid assessment of V̇o in people with cystic fibrosis: a retrospective analysis.

The validity and safety of using supramaximal verification (S) to confirm a maximal effort during cardiopulmonary exercise testing (CPET) in people with cystic fibrosis (CF) and/or those with severe disease has been questioned. Therefore, this study aimed to investigate these concerns in children, adolescents, and adults with mild-to-severe CF lung disease. Retrospective analysis of 17 pediatric and 28 adult participants with CF [age range: 9.

Targeting matrix metalloproteinase-13 in bronchial epithelial repair.

Background: Viral infection of the bronchial epithelium disrupts the barrier properties of the epithelium in healthy individuals and those with lung disease. Repair of the bronchial epithelium is dependent of the formation of a provisional fibrin matrix and migration of epithelial cells to cover denuded areas, followed by proliferation and differentiation.

Objective: The objective was to test the hypothesis that poly I:C, a model of viral infection, limits epithelial repair through the stimulated release of matrix metalloproteinase-13 (MMP-13).

Therapeutic use of heparin and derivatives beyond anticoagulation in patients with bronchial asthma or COPD.

In this review, we identify potential targets for the therapeutic effects of heparin in asthma and chronic obstructive pulmonary disease (COPD), consider the safety and delivery modalities of this therapeutic approach. Specifically, we point to the anti-inflammatory, antioxidant and mucolytic effects of unfractionated heparin with potential to modify disease progression in COPD and asthma when administered via the inhaled route. Inhaled heparin may represent an effective add-on therapy in COPD and asthma patient groups, especially when taking into consideration the relative deficiency in endogenous heparin reported in asthma patients.

Inhaled nebulised unfractionated heparin improves lung function in moderate to very severe COPD: A pilot study.

Background: COPD is an inflammatory airway disease characterised by progressive airflow limitation and air trapping, leading to lung hyperinflation and exercise limitation. Acute worsening of symptoms, including dyspnea, cough and sputum production, occurs during exacerbations which are associated with significantly reduced health related quality of life, and increased morbidity and mortality. Chronic bronchial mucus production and productive cough are risk factors for exacerbations.

Physiological and biological predictors of length of stay and recovery in adults with acute asthma: An observational cohort study.

Introduction: Asthma is a prevalent, chronic disease associated with significant risk to patients and cost to healthcare systems. Accurate estimates of length of stay and recovery are important for patient information, physician prognostication, and management of inpatient beds.

Objectives: To assess factors affecting length of stay and time to recovery in adults with acute asthma.

Heparin derivatives for the targeting of multiple activities in the inflammatory response.

An attractive strategy for ameliorating symptoms arising from the multi-faceted processes of excessive and/or continual inflammation would be to identify compounds able to interfere with multiple effectors of inflammation. The well-tolerated pharmaceutical, heparin, is capable of acting through several proteins in the inflammatory cascade, but its use is prevented by strong anticoagulant activity. Derivatives of heparin involving the periodate cleavage of 2,3 vicinal diols in non-sulfated uronate residues (glycol-split) and replacement of N-sulphamido- with N-acetamido- groups in glucosamine residues, capable of inhibiting neutrophil elastase activity in vitro, while exhibiting attenuated anticoagulant properties, have been identified and characterised.

Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA) derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology.

Objectives: Ulcerative colitis (UC) is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA)) are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX) inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids) within the inflammatory milieu in UC.

Altered colonic mucosal availability of n-3 and n-6 polyunsaturated fatty acids in ulcerative colitis and the relationship to disease activity.

Background And Aims: The polyunsaturated fatty acids (PUFA) arachidonic acid (AA, n-6) and eicosapentaenoic acid (EPA, n-3) are precursors of eicosanoids and other lipid mediators which have critical roles in inflammation. The mediators formed from the different PUFA have different potencies. We hypothesised that metabolic changes associated with colonic mucosal inflammation would modify the bioavailability of the eicosanoid precursors AA and EPA.

Cytokine mucosal expression in ulcerative colitis, the relationship between cytokine release and disease activity.

Background: Ulcerative colitis (UC) is an inflammatory bowel disease with conflicting evidence from studies on the roles of TNFα, IL-8, TGFβ and other cytokines and characterised by neutrophil infiltration and tissue destruction.

Aim: To compare cytokine profiles of inflamed and non-inflamed mucosa in patients with distal UC, and matched controls.

Methods: Patients were prospectively recruited, mucosal biopsies at flexible sigmoidoscopy (FS) were taken from UC patients within macroscopically inflamed and non-inflamed proximal mucosa, and from age-sex matched controls undergoing FS.

A copper-hydrogen peroxide redox system induces dityrosine cross-links and chemokine oligomerisation.

The activity of the chemoattractant cytokines, the chemokines, in vivo is enhanced by oligomerisation and aggregation on glycosaminoglycan (GAG), particularly heparan sulphate, side chains of proteoglycans. The chemokine RANTES (CCL5) is a T-lymphocyte and monocyte chemoattractant, which has a minimum tetrameric structure for in vivo activity and a propensity to form higher order oligomers. RANTES is unusual among the chemokines in having five tyrosine residues, an amino acid susceptible to oxidative cross-linking.

Up-regulation of the extrinsic coagulation pathway in acute asthma--a case study.

Introduction: In the normal airway, the hemostatic balance is antithrombotic and favors fibrinolysis. Acute asthma is associated with inflammatory cell infiltrate and plasma exudation in the airways. Postmortem specimens following status asthmaticus suggest a role for the activation of the extrinsic coagulation cascade and intraluminal fibrin formation.

Alveolar inflammation in cystic fibrosis.

Background: In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release and ceramide accumulation. We sought to investigate CF lung inflammation in the alveoli.

Methods: Lung tissue from 14 CF patients and four healthy individuals was analyzed for numbers of effector cells, elastin and collagen concentrations, inflammatory markers and density of Pseudomonas aeruginosa.