Search results for "OPD"

Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoG…

2019

This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Avalglucosidase alfa was well-tolerated; no deaths…

GOLD Staging System is Appropriate to Predict Mortality in Older People With Chronic Obstructive Pulmonary Disease

2018

Abstract Introduction In the new GOLD classification the reduction of FEV1, expressed as percentage of predicted value (FEV1PP), is considered an important prognostic factor. However, the use of FEV1PP may introduce bias, especially if based on equations derived from populations different from the one under study. We evaluated how well the GOLD classification stratifies the mortality risk when FEV1PP is based on an equation developed in the same population that gave rise to cases, externally developed equations, or as FEV1 divided by cubed height (FEV1/Ht3). Methods We studied 882 participants aged ≥65 years. Bronchial obstruction was defined using a fixed cut-off of 0.7 for FEV1/FVC. Predi…

Pro-and anti-fibrotic molecule balance in the bronchial mucosa of stable COPD patients

2015

Background: The mechanisms of inducing fibrotic events and remodeling in the airways of COPD are incompletely studied. Objectives: To investigate the expression of cytokines involved in the pro- and anti-fibrotic events in stable COPD. Methods: Expression of CTGF, TGFβ1-2-3, TGFβRI, TGFβRII, LTBP-1, TRAP-1, BAMBI, PP2Cα, Smad2-3-6-7, pSmad2, pSmad3, pro-collagen-I and collagen-I was measured in the bronchial mucosa using immunohistochemistry and RT-qPCR. Results: TGFβ1 was increased in the epithelium and TGFβ3 in the submucosa of healthy smokers and mild/moderate COPD compared to healthy non-smokers. In all smokers and patients with COPD TGFβ3+ cells in the submucosa correlated significantl…

ANTI-INFLAMMATORY ACTIVITY OF HSP60 IN HUMAN BRONCHIAL EPITHELIAL CELLS AND ITS INVOLVEMENT IN CHRONIC OBSTRUCTIVE PULMUNARY DISEASE

IL-17A induces chromatin remodeling promoting IL-8 release in bronchial epithelial cells: Effect of Tiotropium

2016

Abstract Aims IL-17A plays a key role in the persistence of airway inflammation, oxidative stress, and reduction of steroid-sensitivity in COPD. We studied the effect of IL-17A on chromatin remodeling and IL-8 production. Main methods We measured the levels of IL-8 and IL-17A in induced sputum supernatants (ISS) from healthy controls (HCs), healthy smokers (HSs), and COPD patients by enzyme-linked immunosorbent assay (ELISA). A human bronchial epithelial cell line (16HBE) was stimulated with ISS from HCs, HSs, or COPD subjects. IL-8 was evaluated in 16HBE by Western blot and real-time polymerase chain reaction (PCR). Histone deacetylase 2 (HDAC2), acetyl histone H3 (Ac-His H3) (k9) and inhi…

Cigarette smoke alters IL-33 expression and release in airway epithelial cells

2014

AbstractAirway epithelium is a regulator of innate immune responses to a variety of insults including cigarette smoke. Cigarette smoke alters the expression and the activation of Toll Like Receptor 4 (TLR4), an innate immunity receptor. IL-33, an alarmin, increases innate immunity Th2 responses. The aims of this study were to explore whether mini-bronchoalveolar lavage (mini-BAL) or sera from smokers have altered concentrations of IL-33 and whether cigarette smoke extracts (CSE) alter both intracellular expression (mRNA and protein) and release of IL-33 in bronchial epithelial cells. The role of TLR4 in the expression of IL-33 was also explored.Mini-BALs, but not sera, from smokers show red…

Differences in the efficacy and safety among inhaled corticosteroids (ICS)/long-acting beta2-agonists (LABA) combinations in the treatment of chronic…

2015

Inhaled corticosteroids (ICS) are frequently recommended for the treatment of asthma and COPD, often in combination with long-acting beta2-agonists (LABA), depending on the severity of the disease and/or on the specific phenotype. Several ICS/LABA combinations are currently available that differ in their pharmacokinetic characteristics and dose of both components. Thus, this review assesses differences in the efficacy and the safety profiles of the ICS components in the two more frequently used ICS/LABA combinations (budesonide/formoterol and fluticasone/salmeterol) for the management of COPD. Whereas the basic mechanism of action is similar for all ICS (binding with the intracellular gluco…

Budesonide/formoterol for the treatment of asthma.

2003

Budesonide/formoterol (Symbicort), AstraZeneca plc) is a novel treatment for asthma, combining an inhaled corticosteroid - budesonide, and a long-acting beta(2)-agonist - formoterol, in a single inhaler, the Turbuhaler. Randomised, clinical studies in patients with asthma have demonstrated that budesonide/formoterol is more effective than the inhaled corticosteroids, budesonide and fluticasone alone, and at least as effective as both monocomponents in separate inhalers. Results from clinical studies suggest a synergistic effect when both drugs are administered via one inhaler, although the mechanisms for this are not fully understood. Budesonide/formoterol has a rapid onset of effect, appar…

Safety Considerations of Inhaled Corticosteroids in the Elderly

2014

Inhaled corticosteroids (ICSs) are widely used in the treatment of patients with chronic obstructive pulmonary diseases. However, high-dose regimens and long-term use of ICSs have the potential to cause a variety of local and systemic side effects such as candidiasis, cataracts, glaucoma, and osteoporosis. The use of ICSs can also be associated with the risk of bone fractures, diabetes mellitus and pneumonia. These ICS-related side effects are of particular importance in elderly patients due to the presence of comorbidities and age-related behavioral, cognitive, and psychological problems, which can all interact with inhaled treatment. We reviewed the available literature on the clinically …

Spirometric criteria to diagnose airway obstruction in the elderly: fixed ratio vs. lower limit of normal.

2015

COPD is the most common chronic lung disease. It becomes more prevalent with increasing age but remains under-diagnosed in the elderly. A heated debate concerns the most suitable way to diagnose airway obstruction in this age group. Most COPD guidelines recommend to use a FEV1/FVC of 0.70 as threshold to define an obstructive ventilatory defect. While the use of a 0.70 ratio may be simple, it may result in under-diagnosis of airflow obstruction in young people and over-diagnosis in the elderly due to an age-related decline in pulmonary volumes, especially in FEV1. This might lead to unnecessary use of medications and increased risk of adverse effects. A proposed strategy for reducing the mi…