Patient considerations in the treatment of COPD: focus on the new combination inhaler umeclidinium/vilanterol.

Medication adherence among patients with chronic diseases, such as COPD, may be suboptimal, and many factors contribute to this poor adherence. One major factor is the frequency of medication dosing. Once-daily dosing has been shown to be an important variable in medication adherence in chronic diseases, such as COPD. New inhalers that only require once-daily dosing are becoming more widely available. Combination once-daily inhalers that combine any two of the following three agents are now available: 1) a long-acting muscarinic antagonist; 2) a long acting beta2 agonist; and 3) an inhaled corticosteroid. A new once-daily inhaler with both a long-acting muscarinic antagonist, umeclidinium bromide, and a long acting beta2 agonist, vilanterol trifenatate, is now available worldwide for COPD treatment. It provides COPD patients convenience, efficacy, and a very favorable adverse-effects profile. Additional once-daily combination inhalers are available or will soon be available for COPD patients worldwide. The use of once-daily combination inhalers will likely become the standard maintenance management approach in the treatment of COPD because they improve medication adherence

Bench-to-bedside review: Rare and common viral infections in the intensive care unit – linking pathophysiology to clinical presentation

Viral infections are common causes of respiratory tract disease in the outpatient setting but much less common in the intensive care unit. However, a finite number of viral agents cause respiratory tract disease in the intensive care unit. Some viruses, such as influenza, respiratory syncytial virus (RSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), are relatively common. Others, such as adenovirus, severe acute respiratory syndrome (SARS)-coronavirus, Hantavirus, and the viral hemorrhagic fevers (VHFs), are rare but have an immense public health impact. Recognizing these viral etiologies becomes paramount in treatment, infection control, and public health measures. Therefore, a basic understanding of the pathogenesis of viral entry, replication, and host response is important for clinical diagnosis and initiating therapeutic options. This review discusses the basic pathophysiology leading to clinical presentations in a few common and rare, but important, viruses found in the intensive care unit: influenza, RSV, SARS, VZV, adenovirus, CMV, VHF, and Hantavirus

Immunobiology of the Critical Asthma Syndrome

It is now recognized that asthma incorporates a broad spectrum of syndromes with varying clinical manifestations. Future improvements in asthma treatment will require a clear characterization of these asthma phenotypes and the cellular mechanisms underlying these clinical manifestations. Herein, we will describe the current knowledge of asthma biology. This will include a review of the early pioneers in asthma and allergy, how this work led to our understanding of TH1 and TH2 cytokines, and the development of the "hygiene hypothesis." We will discuss the utility and limitations of the TH1-TH2 model of asthma in animal and human studies, and how this knowledge addresses controversies surrounding the hygiene hypothesis and other competing models. We will discuss novel therapies that have been developed based on mechanistic understanding of asthma pathobiology, including successes and shortcomings of these therapies. We will review the early work that led to the recognition of "asthma phenotypes." This will include the early discovery of various inflammatory subtypes in asthma and how these inflammatory subtypes correlate with response to therapy. Finally, we will describe recent discoveries in asthma biology that will include the role of the airway epithelium in asthma pathogenesis, novel cytokines important in asthma that may serve as novel therapeutic targets, and the identification of newly described innate immune cells and their role in asthma. Improved understanding of the complex biology underpinning the various asthma phenotypes is critical for our ability to optimize treatment for all patients that suffer from asthma and critical asthma syndromes

Bench-to-bedside review: rare and common viral infections in the intensive care unit--linking pathophysiology to clinical presentation.

Viral infections are common causes of respiratory tract disease in the outpatient setting but much less common in the intensive care unit. However, a finite number of viral agents cause respiratory tract disease in the intensive care unit. Some viruses, such as influenza, respiratory syncytial virus (RSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), are relatively common. Others, such as adenovirus, severe acute respiratory syndrome (SARS)-coronavirus, Hantavirus, and the viral hemorrhagic fevers (VHFs), are rare but have an immense public health impact. Recognizing these viral etiologies becomes paramount in treatment, infection control, and public health measures. Therefore, a basic understanding of the pathogenesis of viral entry, replication, and host response is important for clinical diagnosis and initiating therapeutic options. This review discusses the basic pathophysiology leading to clinical presentations in a few common and rare, but important, viruses found in the intensive care unit: influenza, RSV, SARS, VZV, adenovirus, CMV, VHF, and Hantavirus

DUOX-Mediated Signaling Is Not Required for LPS-Induced Neutrophilic Response in the Airways

<div><p>Oxidant production from DUOX1 has been proposed to lead to neutrophil recruitment into the airways when lung homeostasis is compromised. The objective of this study was to determine whether DUOX-derived hydrogen peroxide is required for LPS-induced neutrophil recruitment, using a functional DUOX knock out mouse model. We found that LPS induced profound neutrophilic lung inflammation in both Duoxa+/+ and Duoxa-/- mice between 3h and 24h. Duoxa-/- mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-α) between the two groups. These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium.</p></div

Patient considerations in the treatment of COPD: focus on the new combination inhaler umeclidinium/vilanterol.

Medication adherence among patients with chronic diseases, such as COPD, may be suboptimal, and many factors contribute to this poor adherence. One major factor is the frequency of medication dosing. Once-daily dosing has been shown to be an important variable in medication adherence in chronic diseases, such as COPD. New inhalers that only require once-daily dosing are becoming more widely available. Combination once-daily inhalers that combine any two of the following three agents are now available: 1) a long-acting muscarinic antagonist; 2) a long acting beta2 agonist; and 3) an inhaled corticosteroid. A new once-daily inhaler with both a long-acting muscarinic antagonist, umeclidinium bromide, and a long acting beta2 agonist, vilanterol trifenatate, is now available worldwide for COPD treatment. It provides COPD patients convenience, efficacy, and a very favorable adverse-effects profile. Additional once-daily combination inhalers are available or will soon be available for COPD patients worldwide. The use of once-daily combination inhalers will likely become the standard maintenance management approach in the treatment of COPD because they improve medication adherence

Time course of LPS-induced airway inflammation.

<p>Leukocytes were collected from the airway compartment by BAL at various timepoints up to 7 days (168h) after intratracheal instillation of 1μg LPS. The number of live cells was determined by trypan blue exclusion. Live cell counts are displayed for PBS control and LPS-exposed <i>Duoxa</i>^<i>-/-</i> (-/-) and <i>Duoxa</i>^<i>+/+</i> (+/+) mice as indicated. Data are shown as mean ± SEM for six mice in each group; * = p< 0.05 between LPS-treated and PBS-treated controls, # = p<0.05 between LPS-treated <i>Duoxa</i>^<i>+/+</i> and <i>Duoxa</i>^<i>-/-</i> mice.</p