The role of tiotropium in the management of asthma

Asthma is a chronic respiratory disease characterized by reversible airway obstruction that is secondary to an allergic inflammation and excessive smooth muscle contraction. Cholinergic signals were known to contribute significantly to the pathophysiology of asthma. However, the use of anti-cholinergic agents in asthma has been justified only in acute asthma exacerbations, until tiotropium bromide, a long-acting anti-cholinergic agent was introduced. Recent reports showing a promising role of tiotropium in the treatment of asthma have aroused interest of the use of anti-cholinergic agent for the management of asthma. This report describes pharmacological characteristics, potential effects on inflammatory cells, and the current status of tiotropium in the treatment of asthma

Targeting the protein-protein interactions of the HIV lifecycle

The human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS), relies heavily on protein-protein interactions in almost every step of its lifecycle. Targeting these interactions, especially those between virus and host proteins, is increasingly viewed as an ideal avenue for the design and development of new therapeutics. In this tutorial review, we outline the lifecycle of HIV and describe some of the protein-protein interactions that control and regulate each step of this process, also detailing efforts to develop therapies that target these interactions

Dual Antagonism of PDGF and VEGF in Neovascular Age-Related Macular Degeneration: A Phase IIb, Multicenter, Randomized Controlled Trial

Purpose: To assess the safety and efficacy of E10030 (Fovista; Ophthotech, New York, NY), a plateletderived growth factor (PDGF) antagonist, administered in combination with the antievascular endothelial growth factor (VEGF) agent ranibizumab (Lucentis; Roche, Basel, Switzerland) compared with ranibizumab monotherapy in patients with neovascular age-related macular degeneration (nAMD).Design: Phase IIb global, multicenter, randomized, prospective, double-masked, controlled superiority trial.Participants: Four hundred forty-nine patients with treatment-naive nAMD.Methods: Participants were randomized in a 1: 1: 1 ratio to 1 of the following 3 intravitreal treatment groups: E10030 0.3 mg in combination with ranibizumab 0.5 mg, E10030 1.5 mg in combination with ranibizumab 0.5 mg, and sham in combination with ranibizumab 0.5 mg (anti-VEGF monotherapy). Drugs were administered monthly in each of the groups for a total duration of 24 weeks.Main Outcome Measures: The prespecified primary end point was the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy [ETDRS] letters) from baseline to 24 weeks.Results: No significant safety issues were observed in any treatment group. The E10030 (1.5 mg) combination therapy regimen met the prespecified primary end point of superiority in mean VA gain compared with anti-VEGF monotherapy (10.6 compared with 6.5 ETDRS letters at week 24; P = 0.019). A dose-response relationship was evident at each measured time point commencing at 4 weeks. Visual acuity outcomes favored the E10030 1.5 mg combination therapy group regardless of baseline VA, lesion size, or central subfield thickness on optical coherence tomography. All clinically relevant treatment end points of visual benefit (>= 15 ETDRS letter gain, final VA >= 20/40 or >= 20/25) and visual loss (>= 1 ETDRS line loss, >= 2 ETDRS line loss, final VA >= 20/125 or >= 20/200) favored the E10030 1.5 mg combination group.Conclusions: In this phase IIb clinical trial, a 62% relative benefit from baseline was noted in the E10030 1.5 mg combination therapy group compared with the anti-VEGF monotherapy group. A favorable safety and efficacy profile of E10030 combination therapy for nAMD was evident across multiple clinically relevant end points. This highly powered study provides strong rationale for a confirmatory phase III clinical trial. Ophthalmology 2017; 124: 224-234 (C) 2016 by the American Academy of Ophthalmolog

An integrative review of systematic reviews related to the management of breathlessness in respiratory illnesses

Background: breathlessness is a debilitating and distressing symptom in a wide variety of diseases and still a difficult symptom to manage. An integrative review of systematic reviews of non-pharmacological and pharmacological interventions for breathlessness in non-malignant disease was undertaken to identify the current state of clinical understanding of the management of breathlessness and highlight promising interventions that merit further investigation.Methods: systematic reviews were identified via electronic databases between July 2007 and September 2009. Reviews were included within the study if they reported research on adult participants using either a measure of breathlessness or some other measure of respiratory symptoms.Results: in total 219 systematic reviews were identified and 153 included within the final review, of these 59 addressed non-pharmacological interventions and 94 addressed pharmacological interventions. The reviews covered in excess of 2000 trials. The majority of systematic reviews were conducted on interventions for asthma and COPD, and mainly focussed upon a small number of pharmacological interventions such as corticosteroids and bronchodilators, including beta-agonists. In contrast, other conditions involving breathlessness have received little or no attention and studies continue to focus upon pharmacological approaches. Moreover, although there are a number of non-pharmacological studies that have shown some promise, particularly for COPD, their conclusions are limited by a lack of good quality evidence from RCTs, small sample sizes and limited replication.Conclusions: more research should focus in the future on the management of breathlessness in respiratory diseases other than asthma and COPD. In addition, pharmacological treatments do not completely manage breathlessness and have an added burden of side effects. It is therefore important to focus more research on promising non-pharmacological intervention