Study protocol: A comparison of mobile and clinic-based spirometry for capturing the treatment effect in moderate asthma.

Several inefficiencies in drug development trial implementation may be improved by moving data collection from the clinic to mobile, allowing for more frequent measurements and therefore increased statistical power while aligning to a patient-centric approach to trial design. Sensor-based digital health technologies such as mobile spirometry (mSpirometry) are comparable to clinic spirometry for capturing outcomes, such as forced expiratory volume in 1 s (FEV1); however, the impact of remote spirometry measurements on the detection of treatment effect has not been investigated. A protocol for a multicenter, single-arm, open-label interventional trial of long-acting beta agonist (LABA) therapy among 60 participants with uncontrolled moderate asthma is described.

CC-90001, a c-Jun N-terminal kinase (JNK) inhibitor, in patients with pulmonary fibrosis: design of a phase 2, randomised, placebo-controlled trial.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal interstitial lung disease (ILD); other ILDs have a progressive, fibrotic phenotype (PF-ILD). Antifibrotic agents can slow but not stop disease progression in patients with IPF or PF-ILD. c-Jun N-terminal kinases (JNKs) are stress-activated protein kinases implicated in the underlying mechanisms of fibrosis, including epithelial cell death, inflammation and polarisation of profibrotic macrophages, fibroblast activation and collagen production.

Pilot Study of Peak Plasma Concentration After High-Dose Oral Montelukast in Children With Acute Asthma Exacerbations.

Acute asthma exacerbations are primarily due to airway inflammation and remain one of the most frequent reasons for childhood hospitalizations. Although systemic corticosteroids remain the mainstay of therapy because of their anti-inflammatory properties, not all inflammatory pathways are responsive to systemic corticosteroids, necessitating hospital admission for further management. Cysteinyl leukotrienes (LTs) are proinflammatory mediators that play an important role in systemic corticosteroids non-responsiveness.

Adverse events are rare after single-dose montelukast exposures in children.

Study Objective: Montelukast sodium is a leukotriene-receptor antagonist approved as a controller medication for chronic asthma and allergic rhinitis in children and adults. We sought to characterize adverse events associated with single montelukast exposures in children ages 5-17 years and to determine whether adverse events were dose related for all-dose and for ultra-high-dose (≥50 mg) exposures.

Methods: This is a retrospective analysis of data from the National Poison Data System for exposures that included montelukast in individuals aged 5-17 years for calendar years 2000-2016.

An Official American Thoracic Society Research Statement: Implementation Science in Pulmonary, Critical Care, and Sleep Medicine.

Background: Many advances in health care fail to reach patients. Implementation science is the study of novel approaches to mitigate this evidence-to-practice gap.

Methods: The American Thoracic Society (ATS) created a multidisciplinary ad hoc committee to develop a research statement on implementation science in pulmonary, critical care, and sleep medicine.

Predictors of asthma following severe respiratory syncytial virus (RSV) bronchiolitis in early childhood.

Background: We sought to identify predictors of asthma development following severe early childhood RSV bronchiolitis. Different definitions of asthma were also compared.

Methods: This longitudinal, observational study (N = 343) followed patients (<2 years old) from a placebo-controlled trial (N = 979) of montelukast after RSV bronchiolitis to identify clinical, demographic, or biochemical predictors of asthma, atopic disorders, and chronic asthma therapy use at 6 years of age (Clinical Trials Registry Number: NCT01140048).

Drug development for airway diseases: looking forward.

Advancing drug development for airway diseases beyond the established mechanisms and symptomatic therapies requires redefining the classifications of airway diseases, considering systemic manifestations, developing new tools and encouraging collaborations.

The asthma disease activity score: a discriminating, responsive measure predicts future asthma attacks.

Background: Classifying asthma severity or activity has evolved, but there are no published weighted composite measures of asthma disease activity that account for the relative importance of the many individual clinical variables that are widely used.

Objectives: We sought to develop a weighted and responsive measure of asthma disease activity.

Methods: Discriminant and multiple regression analyses based on 2 previously conducted clinical trials were used to develop the Asthma Disease Activity Score (ADAS-6).

Airway obstruction lability helps distinguish levels of disease activity in asthma.

Classifying disease activity in asthma relies on clinical and physiological variables, but these variables do not capture all aspects of asthma that distinguish levels of disease activity. We used data from two pivotal trials of montelukast in asthma to classify disease activity as "high" or "low". We performed a principal component analysis (PCA) of disease activity using 21 efficacy outcome variables, including several novel derived outcome variables reflecting clinical and airway obstruction lability.

The efficacy and tolerability of MK-0633, a 5-lipoxygenase inhibitor, in chronic asthma.

Leukotriene B4 (LTB(4)) is a potent inflammatory mediator in asthma, and is increased in more severe asthma. Targeting LTB(4), in addition to cysteinyl leukotrienes, could be beneficial in asthma. This was a randomized, double-blind trial of once-daily MK-0633, a potent 5-lypoxygenase inhibitor, 10 mg, 50 mg, and 100 mg, and placebo in patients 18-70 years with a history of chronic asthma, and FEV(1) ≥45 and ≤85% predicted.

Intermittent or daily montelukast versus placebo for episodic asthma in children.

Background: No standard, optimal treatment exists for severe intermittent (ie, episodic) asthma in children. However, evidence suggests that both daily and episode-driven montelukast are effective for this phenotype.

Objective: To assess the regimen-related efficacy of montelukast in treating pediatric episodic asthma.

The efficacy and tolerability of inhaled montelukast plus inhaled mometasone compared with mometasone alone in patients with chronic asthma.

Background: The efficacy of oral montelukast in chronic asthma is well established. Montelukast is also an effective adjunctive therapy to inhaled corticosteroids (ICS) in asthma uncontrolled on ICS alone. Inhaled montelukast was recently shown to provide significant bronchodilation compared with placebo in patients with chronic asthma.

MK-0633, a potent 5-lipoxygenase inhibitor, in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is associated with neutrophil-mediated inflammation, a potential target for treatment in COPD. We evaluated MK-0633, a 5-lipoxygenase inhibitor in patients with COPD. This was a 12 week, randomized, double-blind, multicenter study comparing MK-0633 100 mg and placebo in patients 40-75 years of age (N = 266) with COPD, post-β-agonist forced expiratory volume in 1 s (FEV(1)) 25%-75% predicted, and an FEV(1)/forced vital capacity ratio (FVC) ≤ 70%.

A phase I randomized, placebo-controlled, dose-exploration study of single-dose inhaled montelukast in patients with chronic asthma.

Background: The efficacy of oral montelukast has been well established in asthma and allergic rhinitis in adults and children. The purpose of this study was to evaluate dose-related bronchodilation and tolerability of inhaled montelukast.

Methods: Randomized, double-blind, crossover, adaptive-design study comparing single-dose administration of inhaled montelukast versus placebo in patients age 15-65 years with chronic asthma (n = 68).

A randomized placebo-controlled study of intravenous montelukast for the treatment of acute asthma.

Background: Current treatments for acute asthma provide inadequate benefit for some patients. Intravenous montelukast may complement existent therapies.

Objective: To evaluate efficacy of intravenous montelukast as adjunctive therapy for acute asthma.

Clinical studies of combination montelukast and loratadine in patients with seasonal allergic rhinitis.

Background: Concomitant use of montelukast and loratadine may improve symptoms of seasonal allergic rhinitis (SAR) more than treatment with either drug alone.

Objective: We compared the efficacy of this combination versus placebo, nasal beclomethasone, montelukast, and loratadine in study 1 and versus placebo, montelukast, and loratadine in study 2.

Methods: Patients were randomly allocated to double-blind treatment with intranasal beclomethasone 200 mu g/twice daily (study 1 only), placebo, montelukast 10 mg+loratadine 10 mg, montelukast 10 mg, or loratadine 10 mg once daily.

Analysis of behavior-related adverse experiences in clinical trials of montelukast.

Background: Frequencies of behavior-related adverse experiences (BRAEs) in controlled clinical studies of leukotriene modifier drugs have not been summarized.

Objective: We sought to compare the frequency of BRAEs in patients receiving montelukast or placebo in a retrospective analysis of Merck clinical trial data.

Methods: An adverse experience database was constructed to include all double-blind, placebo-controlled trials of montelukast meeting prespecified criteria.

Clinical studies of the DP1 antagonist laropiprant in asthma and allergic rhinitis.

Background: Prostaglandin D(2) is a proinflammatory mediator believed to be important in asthma and allergic rhinitis (AR). Allelic variants in the prostaglandin D(2) receptor type 1 (DP1) gene (PTGDR) have been suggested to be associated with asthma susceptibility.

Objectives: We sought to investigate the efficacy of the DP1 antagonist laropiprant (alone or with montelukast) in asthma and seasonal AR and explore whether sequence variations in PTGDR are associated with asthma severity.

A randomized study comparing the effect of loratadine added to montelukast with montelukast, loratadine, and beclomethasone monotherapies in patients with chronic asthma.

Background: Loratadine added to montelukast has been suggested to improve endpoints of asthma.

Objective: This study investigated the additive effects of concomitant montelukast and loratadine when compared with montelukast, loratadine, and inhaled beclomethasone monotherapies in asthma. Methods.