Pharmacogenetic studies of long-acting beta agonist and inhaled corticosteroid responsiveness in randomised controlled trials of individuals of African descent with asthma.

Background: Pharmacogenetic studies in asthma cohorts, primarily made up of White people of European descent, have identified loci associated with response to inhaled beta agonists and corticosteroids (ICSs). Differences exist in how individuals from different ancestral backgrounds respond to long-acting beta agonist (LABA) and ICSs. Therefore, we sought to understand the pharmacogenetic mechanisms regulating therapeutic responsiveness in individuals of African descent.

Preventing asthma in high risk kids (PARK) with omalizumab: Design, rationale, methods, lessons learned and adaptation.

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma.

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.

Background: Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.

Methods: We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults.

Obesity's effect on asthma extends to diagnostic criteria.

Background: The use of inflammatory biomarkers to delineate the type of lung inflammation present in asthmatic subjects is increasingly common. However, the effect of obesity on these markers is unknown.

Objectives: We aimed to determine the effect of obesity on conventional markers of inflammation in asthmatic subjects.

Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial.

Importance: In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency.

Objective: To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels.

Effects of inhaled fluticasone on upper airway during sleep and wakefulness in asthma: a pilot study.

Study Objective: Obstructive sleep apnea is prevalent among people with asthma, but underlying mechanisms remain unknown. Inhaled corticosteroids may contribute. We tested the effects of orally inhaled fluticasone propionate (FP) on upper airway (UAW) during sleep and wakefulness.

Researching asthma across the ages: insights from the National Heart, Lung, and Blood Institute's Asthma Network.

Clinical asthma studies across different age groups (ie, cross-age studies) can potentially offer insight into the similarities, differences, and relationships between childhood and adult asthma. The National Institutes of Health's Asthma Research Network (AsthmaNet) is unique and innovative in that it has merged pediatric and adult asthma research into a single clinical research network. This combination enhances scientific exchange between pediatric and adult asthma investigators and encourages the application of cross-age studies that involve participants from multiple age groups who are generally not studied together.

Predictors of response to tiotropium versus salmeterol in asthmatic adults.

Background: Tiotropium has activity as an asthma controller. However, predictors of a positive response to tiotropium have not been described.

Objective: We sought to describe individual and differential responses of asthmatic patients to salmeterol and tiotropium when added to an inhaled corticosteroid, as well as predictors of a positive clinical response.

Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial.

Context: No consensus exists for adjusting inhaled corticosteroid therapy in patients with asthma. Approaches include adjustment at outpatient visits guided by physician assessment of asthma control (symptoms, rescue therapy, pulmonary function), based on exhaled nitric oxide, or on a day-to-day basis guided by symptoms.

Objective: To determine if adjustment of inhaled corticosteroid therapy based on exhaled nitric oxide or day-to-day symptoms is superior to guideline-informed, physician assessment-based adjustment in preventing treatment failure in adults with mild to moderate asthma.

Tiotropium bromide step-up therapy for adults with uncontrolled asthma.

Background: Long-acting beta-agonist (LABA) therapy improves symptoms in patients whose asthma is poorly controlled by an inhaled glucocorticoid alone. Alternative treatments for adults with uncontrolled asthma are needed.

Methods: In a three-way, double-blind, triple-dummy crossover trial involving 210 patients with asthma, we evaluated the addition of tiotropium bromide (a long-acting anticholinergic agent approved for the treatment of chronic obstructive pulmonary disease but not asthma) to an inhaled glucocorticoid, as compared with a doubling of the dose of the inhaled glucocorticoid (primary superiority comparison) or the addition of the LABA salmeterol (secondary noninferiority comparison).

Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial.

Background: Some studies suggest that patients with asthma who are homozygous for arginine at the 16th amino acid position of the beta2-adrenergic receptor (B16 Arg/Arg) benefit less from treatment with longacting beta2 agonists and inhaled corticosteroids than do those homozygous for glycine (B16 Gly/Gly). We investigated whether there is a genotype-specific response to treatment with a longacting beta2 agonist in combination with inhaled corticosteroid.

Methods: In this multicentre, randomised, double-blind, placebo-controlled trial, adult patients with moderate asthma were enrolled in pairs matched for forced expiratory volume in 1 s and ethnic origin, according to whether they had the B16 Arg/Arg (n=42) or B16 Gly/Gly (n=45) genotype.

Combination therapy with a long-acting beta-agonist and a leukotriene antagonist in moderate asthma.

Rationale: Long-acting beta-agonists (LABAs) and inhaled corticosteroids administered together appear to be complementary in terms of effects on asthma control. The elements of asthma control achieved by LABAs (improved lung function) and leukotriene receptor antagonists (LTRAs; protection against exacerbations) may be complementary as well.

Objective: We sought to determine whether the combination of the LTRA montelukast and the LABA salmeterol could provide an effective therapeutic strategy for asthma.

Differential release of cardiac enzymes after percutaneous coronary intervention.

We hypothesized that using calcium channel blockers (CCBs) that dilate microvasculature during percutaneous coronary intervention (PCI) would result in lower postprocedural creatine phosphokinase (CPK). PCI can be complicated by elevated CPK that has been associated with impaired microvascular perfusion. Nitroglycerin (NTG), the conventional PCI vasodilator, dilates epicardial arteries but does not affect the microvasculature.

Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial.

Background: The issue of whether regular use of an inhaled beta2-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial. Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine (Arg/Arg), rather than glycine (Gly/Gly), at aminoacid residue 16 of the beta2-adrenergic receptor. However, the existence of any genotype-dependent difference has not been tested in a prospective clinical trial.

Factors affecting surgical risk in elderly patients with inflammatory bowel disease.

The operative treatment of elderly patients with inflammatory bowel disease (IBD) has often been avoided in favor of medical management because of a perceived increase in surgical risk. This study sought to define the following in the elderly IBD patient population: (1) the risk of surgical management and (2) those factors affecting risk. Thirty patients with IBD, aged 60 years or more, who were surgically managed by a single surgeon over a 10-year period, were retrospectively matched to 75 patients with IBD who were less than 60 years of age; patients were matched according to sex, date of surgery, and type of surgery performed.

Systemic effect comparisons of six inhaled corticosteroid preparations.

The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses.

The effects of sex steroids on spatial performance: a review and an experimental clinical investigation.

Males typically surpass females in spatial performance, an outcome that may be linked to testosterone and estrogen. The authors (a) review physiological mechanisms, developmental periods, and past empirical work relevant to sex steroids' effects on human spatial performance and (b) report an experimental study of the role of actively circulating sex steroids in adolescents being treated for delayed puberty (N = 55; mean age = 13.70 years).