Characteristics of Current Smokers versus Former Smokers with COPD and Their Associations with Smoking Cessation Within 4.5 Years: Results from COSYCONET.

Background: Many patients with chronic obstructive pulmonary disease (COPD) continue smoking. We used data from the "real-life" COSYCONET COPD cohort to evaluate whether these patients differed from patients with COPD who either had ceased smoking prior to inclusion or ceased during the follow-up time of the study.

Methods: The analysis was based on data from visits 1-5 (covering 4.

A Worm-Like Biomimetic Crawling Robot Based on Cylindrical Dielectric Elastomer Actuators.

In recent years the field of soft robotics has gained a lot of interest both in academia and industry. In contrast to rigid robots, which are potentially very powerful and precise, soft robots are composed of compliant materials like gels or elastomers (Rich et al., 2018; Majidi, 2019).

A small molecule neutrophil elastase inhibitor, KRP-109, inhibits cystic fibrosis mucin degradation.

Background: Neutrophil elastase (NE) rapidly degrades gel-forming airway mucins in cystic fibrosis (CF) sputum. We hypothesized that KRP-109, a small molecule NE inhibitor, would inhibit CF mucin degradation in vitro.

Methods: Sputa were collected from CF patients (n=5) chronically or intermittently infected with Pseudomonas aeruginosa (P.

Altered protease and antiprotease balance during a COPD exacerbation contributes to mucus obstruction.

Background: Proteases have been shown to degrade airway mucin proteins and to damage the epithelium impairing mucociliary clearance. There are increased proteases in the COPD airway but changes in protease-antiprotease balance and mucin degradation have not been investigated during the course of a COPD exacerbation. We hypothesized that increased protease levels would lead to mucin degradation in acute COPD exacerbations.

Impaired TLR4 and HIF expression in cystic fibrosis bronchial epithelial cells downregulates hemeoxygenase-1 and alters iron homeostasis in vitro.

Hemeoxygenase-1 (HO-1), an inducible heat shock protein, is upregulated in response to multiple cellular insults via oxidative stress, lipopolysaccharides (LPS), and hypoxia. In this study, we investigated in vitro the role of Toll-like receptor 4 (TLR4), hypoxia-inducible factor 1α (HIF-1α), and iron on HO-1 expression in cystic fibrosis (CF). Immunohistochemical analysis of TLR4, HO-1, ferritin, and HIF-1α were performed on lung sections of CFTR-/- and wild-type mice.

Secretory hyperresponsiveness and pulmonary mucus hypersecretion.

The term bronchial hyperresponsiveness is generally used to describe a heightened airway smooth muscle bronchoconstrictor response measured by bronchoprovocation testing. However, the airway also responds to inflammation or bronchoprovocation with increased mucus secretion. We use the term "secretory hyperresponsiveness" to mean increased mucus secretion either intrinsically or in response to bronchoprovocation.

Clarithromycin therapy for patients with cystic fibrosis: a randomized controlled trial.

The clinically significant actions of oral azithromycin in modifying progressive cystic fibrosis (CF) lung disease have been well documented. In vitro and clinical data suggests that clarithromycin has immunomodulatory properties similar to other 14-member macrolides, however two previously reported short term, open label trials of clairthromycin in small numbers of patients with CF failed to show significant benefits in modifying lung function or inflammation. We performed an international double blind, cross-over trial in which 63 subjects with CF were studied while receiving either placeo or 500 mg oral clarithromycin twice daily for 5 months, with a 1-month wash-out.

Reduced surface toll-like receptor-4 expression and absent interferon-γ-inducible protein-10 induction in cystic fibrosis airway cells.

ABSTRACT As part of the innate and adaptive immune system, airway epithelial cells secrete proinflammatory cytokines after activation of Toll-like receptors (TLRs) by pathogens. Nevertheless, cystic fibrosis (CF) airways are chronically infected with Pseudomonas aeruginosa, suggesting a modified immune response in CF. The authors have shown that in CF bronchial epithelial cells, a reduced surface expression of TLR-4 causes a diminished interleukin (IL)-8 and IL-6 response upon lipopolysaccharide (LPS) stimulation.

Serine proteases degrade airway mucins in cystic fibrosis.

Airway mucins are the major molecular constituents of mucus. Mucus forms the first barrier to invading organisms in the airways and is an important defense mechanism of the lung. We confirm that mucin concentrations are significantly decreased in airway secretions of subjects with cystic fibrosis (CF) who have chronic Pseudomonas aeruginosa infection.

High diagnostic yield from transbronchial biopsy of solitary pulmonary nodules using low-dose CT-guidance.

Background And Objective: The diagnostic yield from fluoroscopy-guided bronchoscopic transbronchial biopsy of small solitary pulmonary nodules is low. The hypothesis tested in the present study was that the diagnostic yield can be significantly increased by combining flexible bronchoscopy with CT-guidance using a dedicated low-dose protocol.

Methods: CT-guided transbronchial biopsies were performed in 15 patients with a newly diagnosed solitary peripheral pulmonary nodule and negative conventional bronchoscopic biopsies under fluoroscopic guidance.

TLR-4-mediated innate immunity is reduced in cystic fibrosis airway cells.

Airway epithelial cells contribute to the inflammatory response of the lung, and their innate immune response is primarily mediated via Toll-like receptor (TLR) signaling. Cystic fibrosis (CF) airways are chronically infected with Pseudomonas aeruginosa, suggesting a modified immune response in CF. We investigated the TLR-4 expression and the inflammatory profile (IL-8 and IL-6 secretion) in CF bronchial epithelial cell line CFBE41o- and its CF transmembrane ion condcutance regulator (CFTR)-corrected counterpart grown under air-liquid interface conditions after stimulation with lipopolysaccharide (LPS) from gram-negative bacteria.

Macrolide antibiotics as immunomodulatory medications: proposed mechanisms of action.

Macrolide antibiotics administered in sub-antimicrobial doses improve pulmonary function and decrease exacerbation frequency for persons with diffuse panbronchiolitis or cystic fibrosis. Data also suggest a beneficial effect of macrolide antibiotics in the treatment of steroid dependent asthma. Many potential immunomodulatory effects of macrolide antibiotics have been reported including the ability to down-regulate prolonged inflammation, decreasing airway mucus secretion, inhibiting bacterial biofilm, decreasing the production of reactive oxygen species, inhibiting neutrophil activation and mobilization, accelerating neutrophil apoptosis, and blocking the activation of nuclear transcription factors.

The role of DNA and actin polymers on the polymer structure and rheology of cystic fibrosis sputum and depolymerization by gelsolin or thymosin beta 4.

Mucus clearance is the first line of pulmonary defense against inhaled irritants, microorganisms, and allergens. In health, the gel-forming mucins are the principal polymeric components of airway mucus but in cystic fibrosis (CF), the necrotic death of inflammatory and epithelial cells releases a network of copolymerized extracellular DNA and filamentous (F-) actin-producing secretions that are similar to pus and difficult to clear by cilia or airflow. The large amounts of F-actin in CF sputum suggested that thymosin beta4 (Tbeta4) or gelsolin could depolymerize the secondary polymer network of CF sputum.

Mucolytics in cystic fibrosis.

Mucus accumulation in the lower airways is a key feature of cystic fibrosis (CF) lung disease. The major component of mucus in CF is not mucin derived from mucus producing cells but rather pus that includes viscous material such as polymerized DNA derived from degraded neutrophils. This has important implications for mucolytic therapy aiming to improve mucus clearance from the airways, since degradation of mucin may not be a suitable treatment strategy.

MUC5AC and MUC5B mucins increase in cystic fibrosis airway secretions during pulmonary exacerbation.

Rationale: Cystic fibrosis (CF) is believed to be associated with mucus hypersecretion; thus, the principal airway gel-forming mucins, MUC5AC and MUC5B, are also expected to be increased relative to non-CF secretions. However, we have shown that these mucins are decreased during stable CF disease.

Objectives: In this study, we determine if these mucins increase during a pulmonary exacerbation of CF.

The role of airway secretions in COPD--clinical applications.

It has been established that mucus hypersecretion and decreased mucus clearance contribute to the morbidity of chronic obstructive pulmonary disease (COPD). Indeed, the classic definition of chronic bronchitis relies on determining the frequency and duration of sputum expectoration. Despite the well recognized importance of this symptom, there are few therapies routinely used to decrease the sputum production or to improve clearance.

Up-regulation of S100A8 and S100A9 protein in bronchial epithelial cells by lipopolysaccharide.

Increased serum levels of the S100A8 (MRP-8) protein have been reported in inflammatory conditions including bacterial infection, arthritis, and cystic fibrosis (CF). This protein is expressed constitutively with S100A9 (MRP-14) in neutrophils and is regulated by inflammatory stimulants. It has been hypothesized that increased inflammatory response to persistent bacterial infection is a major feature of CF lung disease.

Mucus properties in children with primary ciliary dyskinesia: comparison with cystic fibrosis.

Objective: It has been assumed that cystic fibrosis (CF) lung disease is due in part to abnormal airway mucus. Primary ciliary dyskinesia (PCD) is a form of bronchiectasis that is similar to CF in many ways but is caused by congenital defects in mucociliary clearance. Our objective was to compare the biophysical and transport properties of CF and PCD sputa in subjects matched for age and degree of lung function impairment.

MUC5AC and MUC5B Mucins Are Decreased in Cystic Fibrosis Airway Secretions.

Cystic fibrosis (CF) is characterized by progressive airway obstruction. Although it has been postulated that this is due in part to mucus hypersecretion, there are no published data showing an increase in the gel-forming mucins MUC5AC or MUC5B in CF secretions. We used confocal microscopy to assess the amount of mucin-like glycoprotein and DNA in CF sputum and found more mucin in bronchitis sputum and a much greater amount of DNA in CF sputum.

Immunomodulatory activity and effectiveness of macrolides in chronic airway disease.

The use of troleandomycin as adjunctive therapy for the treatment of patients with corticosteroid-dependent asthma first suggested an immunomodulatory effect of the macrolide antibiotics. This led to studies of the macrolides in other chronic airway diseases, such as diffuse panbronchiolitis (DPB), a disease occurring primarily in East Asia. The use of macrolides for the therapy of patients with DPB has led to dramatic improvements in pulmonary function and prolonged survival.

Human deep tissue infection with an entomopathogenic Beauveria species.

Beauveria spp. are ubiquitous fungal entomopathogens that are commercially distributed as biological insecticides worldwide. In this paper we describe the clinical manifestation, diagnosis, and therapy of the first documented human deep tissue infection with an entomopathogenic Beauveria species in a patient receiving immunosuppressive therapy and describe the morphological and molecular characterization of the mold.