T helper 17 cells and related cytokines after allergen inhalation challenge in allergic asthmatics.

Background: T helper (Th)17 cells may play a role in allergic asthma. This study assessed the effect of allergen inhalation challenge on circulating Th17 cells and related cytokines in allergic asthmatics.

Methods: Peripheral blood mononuclear cells were collected from 16 atopic asthmatics before and 24 h after allergen challenge, as well as from 10 atopic nonasthmatics and 10 normal controls.

Development and validation of a novel risk score for asthma exacerbations: The risk score for exacerbations.

Background: Identifying patients at risk of future severe asthma exacerbations, those whose asthma might be less treatment responsive, or both might guide treatment selection.

Objective: We sought to investigate predictors for failure to achieve Global Initiative for Asthma (GINA)-defined good current asthma control and severe exacerbations on treatment and to develop a simple risk score for exacerbations (RSE) for clinical use.

Methods: A large data set from 3 studies comparing budesonide/formoterol maintenance and reliever therapy with fixed-dose inhaled corticosteroid/long-acting β2-agonist therapy was analyzed.

HIV status and sexual behaviour among gay men in Ottawa: considerations for public health.

Objectives: HIV prevention efforts, particularly among men who have sex with men (MSM), have not achieved maximum effectiveness. A survey of MSM in Ottawa, Canada was completed to ascertain whether there were differences in how the perceived HIV status of participants and their partners influenced sexual practices.

Methods: Self-directed surveys were administered to a convenience sample of 721 MSM in Ottawa, Canada from November 2011 through May 2012.

Fluticasone furoate-vilanterol 100-25 mcg compared with fluticasone furoate 100 mcg in asthma: a randomized trial.

Background: The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β2-agonist vilanterol (VI) is under development for the treatment of asthma and chronic obstructive pulmonary disease.

Objective: To compare the efficacy and safety of FF-VI and FF in patients (≥ 12 years old) with persistent asthma.

Methods: In a randomized, double-blind, parallel-group study, patients (n = 609) (intent-to-treat population) received FF-VI 100-25 mcg, FF 100 mcg, or placebo once daily (evening) by using a dry powder inhaler for 12 weeks.

Efficacy and safety of once-daily fluticasone furoate 50 mcg in adults with persistent asthma: a 12-week randomized trial.

Background: Fluticasone furoate (FF) is a novel, once-daily inhaled corticosteroid (ICS) that has been shown to improve lung function vs. placebo in asthma patients. This study evaluated the efficacy and safety of FF 50 mcg compared with placebo in asthma patients uncontrolled by non-ICS therapy.

Counselling about HIV serological status disclosure: nursing practice or law enforcement? a Foucauldian reflection.

Recently, focus groups and qualitative interviews with nurses who provide frontline care for persons living with HIV highlighted the contentiousness surrounding the seemingly innocuous activity of counselling clients about HIV-status disclosure, hereafter disclosure counselling. These empirical studies highlighted that while some nurses felt they should instruct clients to disclose their HIV-positive status if HIV transmission were possible, other nurses were equally adamant that such counselling was outside the nursing scope of practice. A review of these opposing perceptions about disclosure counselling, including an examination of the empirical evidence which supports each point, revealed that the dichotomous arguments needed to be nuanced.

Once-daily fluticasone furoate 50 mcg in mild-to-moderate asthma: a 24-week placebo-controlled randomized trial.

Background: Inhaled glucocorticosteroids (ICS) are the mainstay of treatment in asthma. Fluticasone furoate (FF) is a novel, once-daily ICS asthma therapy. This study investigated the efficacy and safety of FF 50 mcg in patients with mild-to-moderate persistent asthma.

Th17/Treg ratio derived using DNA methylation analysis is associated with the late phase asthmatic response.

Background: The imbalance between Th17 and Treg cells has been studied in various diseases including allergic asthma but their roles have not been fully understood in the development of the late phase asthmatic response.

Objectives: To determine changes in Th17 and Treg cell numbers between isolated early responders (ERs) and dual responders (DRs) undergoing allergen inhalation challenge. To identify gene expression profiles associated with Th17 and Treg cells.

Targeting membrane-expressed IgE B cell receptor with an antibody to the M1 prime epitope reduces IgE production.

Elevated serum levels of both total and allergen-specific immunoglobulin E (IgE) correlate with atopic diseases such as allergic rhinitis and allergic asthma. Neutralization of IgE by anti-IgE antibodies can effectively treat allergic asthma. Preclinical studies indicate that targeting membrane IgE-positive cells with antibodies against M1 prime can inhibit the production of new IgE and significantly reduce the levels of serum IgE.

Comparison of vilanterol, a novel long-acting beta2 agonist, with placebo and a salmeterol reference arm in asthma uncontrolled by inhaled corticosteroids.

Background: Current maintenance therapies for asthma require twice-daily dosing. Vilanterol (VI) is a novel long-acting beta2 agonist, under development in combination with fluticasone furoate, a new inhaled corticosteroid (ICS). Findings from a previous 4-week study suggested that VI has inherent 24-hour activity and is therefore suitable for once-daily dosing.

Part Two: Evaluation of N-methylbupropion as a Potential Bupropion Prodrug.

N-methylbupropion was selected as a potential prodrug from our in vitro screening of analogues of bupropion described in the preceding paper. This study describes in vivo pharmacokinetics of N-methylbupropion in the guinea-pig animal model, which is reported to best predict human metabolism of bupropion. The suitability of the guinea pig was established by studying N-demethylation of N-methylbupropion using S9 liver fractions.

Effects of an anti-TSLP antibody on allergen-induced asthmatic responses.

Background: Thymic stromal lymphopoietin (TSLP) is an epithelial-cell-derived cytokine that may be important in initiating allergic inflammation. AMG 157 is a human anti-TSLP monoclonal immunoglobulin G2λ that binds human TSLP and prevents receptor interaction.

Methods: In this double-blind, placebo-controlled study, we randomly assigned 31 patients with mild allergic asthma to receive three monthly doses of AMG 157 (700 mg) or placebo intravenously.

Synthesis, screening and pharmacokinetic evaluation of potential prodrugs of bupropion. Part one: in vitro development.

In general, prodrugs are developed to circumvent deficiencies associated with the absorption, distribution, metabolism, excretion or toxicological (ADMET) profile associated with the active drug. In our study, we select bupropion, a drug with broad pharmacology incorporating dopaminergic, noradrenergic, nicotinic and cytokine modulation properties, but which is rapidly metabolized in vivo. we exploited its carbonyl and secondary amine functionality to facilitate the synthesis of bioprecursor prodrug forms with the sole objective of identifying analogues with enhanced properties over bupropion.

Overviewing a Nurse-Led, Community-Based HIV PEP Program: Applying the Extant Literature in Frontline Practice.

This clinical concept paper overviews a program to facilitate access to postexposure prophylaxis (PEP) for gay, bisexual, and other men who have sex with men. The project, which was a collaborative initiative involving the local School of Nursing, public health unit, AIDS service organization, hospital-based HIV clinic, and an outpatient pharmacy, was implemented to circumvent common barriers to care identified in the literature. In this project, persons who present to one of the two participating clinics after having come, or likely having come, into contact with HIV within the previous 72 hr, are offered rapid HIV testing, also known as point-of-care (POC) testing, to rule out existing HIV infection, and provided with a follow-up appointment booked at the HIV clinic.

Social Marginalization and Internal Exclusion: Gay Men's Understandings and Experiences of Community.

A total of 27 gay and bisexual men were interviewed about how they perceived the criminal prosecution of persons living with HIV who do not disclose their HIV status. The stories that emerged from the interviews raise questions about the nature of the gay community. The findings centre on the participants' descriptions of (1) the heterosexual meta-culture, (2) the locales of gay life, and (3) unsupportive elements in the gay community.

Myeloid dendritic cells type 2 after allergen inhalation in asthmatic subjects.

Background: Dendritic cells (DCs) are professional antigen-presenting cells that mediate the response to inhaled allergen. A major division in DC ontogeny exists between myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). A subtype of mDC expressing thrombomodulin, termed myeloid DCs type 2 (mDC2s), has been identified in both the circulation and lung and has recently been suggested to have a role in allergic asthma.

A GM-CSF/IL-33 pathway facilitates allergic airway responses to sub-threshold house dust mite exposure.

Allergic asthma is a chronic immune-inflammatory disease of the airways. Despite aeroallergen exposure being universal, allergic asthma affects only a fraction of individuals. This is likely related, at least in part, to the extent of allergen exposure.

Global differences in lung function by region (PURE): an international, community-based prospective study.

Background: Despite the rising burden of chronic respiratory diseases, global data for lung function are not available. We investigated global variation in lung function in healthy populations by region to establish whether regional factors contribute to lung function.

Methods: In an international, community-based prospective study, we enrolled individuals from communities in 17 countries between Jan 1, 2005, and Dec 31, 2009 (except for in Karnataka, India, where enrolment began on Jan 1, 2003).

EAACI position statement on asthma exacerbations and severe asthma.

Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult-to-treat asthma and severe treatment-resistant asthma.

Interleukin-18 expression, CD8(+) T cells, and eosinophils in lungs of nonsmokers with fatal asthma.

Background: The process of airway inflammation in the lungs of nonsmokers who die of asthma (fatal asthma) has not been reported in detail.

Objective: To examine nonsmokers who had died of asthma to exclude chronic obstructive pulmonary disease and investigate pulmonary inflammatory cells and the expression of interleukin-18 (IL-18) and its receptor in lung tissues compared with those in patients with well-controlled mild asthma and nonsmokers.

Methods: Lung tissues were obtained at autopsy examination from 12 nonsmokers with fatal asthma, excluding cases of chronic obstructive pulmonary disease, and from 5 nonsmokers with well-controlled mild asthma and 10 nonsmokers who had undergone surgical resection for lung cancer.

Efficacy and safety of fluticasone furoate 100 μg once-daily in patients with persistent asthma: a 24-week placebo and active-controlled randomised trial.

Inhaled corticosteroids (ICSs) improve asthma disease control; once-daily ICS administration may have advantages for patients. Our objective was to assess the efficacy and safety of the novel ICS fluticasone furoate (FF) over 24 weeks versus placebo. This was a 24-week double-blind, double-dummy, placebo- and active-controlled study (NCT01159912) of 343 asthma patients (≥12 years) not controlled by their current ICS.

Once-daily fluticasone furoate (FF)/vilanterol reduces risk of severe exacerbations in asthma versus FF alone.

Background: Combination therapy with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) is recommended for patients with asthma symptomatic on ICS alone. However, there is ongoing debate regarding the risk-benefit ratio of using LABA in asthma.

Objective: To evaluate the effect of the addition of a novel LABA, vilanterol (VI), to a once-daily ICS, fluticasone furoate (FF), on the risk of severe asthma exacerbations in patients with uncontrolled asthma.

IL-25 and IL-25 receptor expression on eosinophils from subjects with allergic asthma.

Background: Allergic asthma is an inflammatory airway disease in which Th2 cytokines play an important role. Epithelial-derived interleukin (IL)-25 has been suggested to be important in the maintenance of Th2-type responses. The effects of IL-25 are mediated by the IL-25 receptor, composed of two subunits, IL-17RA and IL-17RB.

OX40L blockade and allergen-induced airway responses in subjects with mild asthma.

Background: The OX40/OX40L interaction contributes to an optimal T cell response following allergic stimuli and plays an important role in the maintenance and reactivation of memory T effector cells.

Objective: We tested whether treatment with an anti-OX40L monoclonal antibody (MAb) would inhibit allergen-induced responses in subjects with asthma.

Methods: Twenty-eight mild, atopic asthmatic subjects were recruited for a double-blind, randomized, placebo-controlled, parallel-group trial (ClinicalTrials.