Dupilumab Efficacy in Patients with Type 2 Asthma with and without Elevated Blood Neutrophils.

Introduction: Elevated neutrophil counts in blood, sputum, or lung have been associated with poor clinical outcomes and more severe disease in patients with type 2 asthma. In the phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks compared with matched placebo significantly reduced severe asthma exacerbations and improved forced expiratory volume in 1 s (FEV) in patients with uncontrolled, moderate-to-severe asthma. This analysis explored the efficacy of dupilumab in patients with type 2 asthma enrolled in QUEST with or without elevated blood neutrophil counts.

Racial and Ethnic Minorities at the Highest Risk of Uncontrolled Moderate-to-Severe Asthma: A United States Electronic Health Record Analysis.

Purpose: The identification of risk factors associated with uncontrolled moderate-to-severe asthma is important to improve asthma outcomes. Aim of this study was to identify risk factors for uncontrolled asthma in United States cohort using electronic health record (EHR)-derived data.

Patients And Methods: In this retrospective real-world study, de-identified data of adolescent and adult patients (≥12 years old) with moderate-to-severe asthma, based on asthma medications within 12 months prior to asthma-related visit (index date), were extracted from the Optum Humedica EHR.

Tezacaftor/ivacaftor in people with cystic fibrosis who stopped lumacaftor/ivacaftor due to respiratory adverse events.

Background: Increased rates of respiratory adverse events have been observed in people ≥12 years of age with cystic fibrosis homozygous for the Phe508del-CFTR mutation treated with lumacaftor/ivacaftor, particularly in those with percent predicted forced expiratory volume in 1 s (ppFEV) of <40%. We evaluated the safety, tolerability, and efficacy of tezacaftor/ivacaftor in people with cystic fibrosis homozygous for Phe508del-CFTR who discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms.

Methods: Participants ≥12 years of age with cystic fibrosis homozygous for Phe508del-CFTR with ppFEV of ≥25% and ≤90% were randomized 1:1 and treated with tezacaftor/ivacaftor or placebo for 56 days.

Clinical burden of asynchrony in patients with asthma when using metered-dose inhalers for control.

Asynchrony, or lack of coordination between inhalation and actuation when using a pressurized metered-dose inhaler (MDI), could theoretically impact the delivery of inhaled medications and treatment efficacy. To assess the real-world association between asynchrony and clinical outcomes among patients with asthma who receive controller therapy delivered by MDIs. A cohort of patients was assembled via electronic health records.

Comparing Ran-Out Status of Inhaled Short-Acting Beta-Agonists in Emergency Department Patients with Acute Asthma: 1996-1998 versus 2015-2017.

Background: Medication nonadherence, including running out of inhaled asthma medications, is an important problem.

Objective: The objective of this study was to examine the changes in the proportion of adults with acute asthma who ran out of their short-acting beta-agonist (SABA) inhalers before presenting to the emergency department (ED) between 1996--1998 and 2015-2017.

Methods: We analyzed data from prospective multicenter observational cohort studies of ED adult patients (aged 18-54 years) with acute asthma.

Real-world health care utilization in asthma patients using albuterol sulfate inhalation aerosol (ProAir HFA) with and without integrated dose counters.

Background: Accurate tracking of the administered dose of asthma rescue inhalers is critical for optimal disease management and is related to reductions in rates of unscheduled health care utilization in asthma patients. There are few published data on the real-world impact of rescue inhalers with integrated dose counters (IDCs) on health care resource utilization (HRU) for asthma patients. This study evaluates HRU among users of ProAir hydrofluoroalkane (HFA) (albuterol sulfate inhalation aerosol), with IDC versus without IDC, in asthma patients.

Historical cohort study examining comparative effectiveness of albuterol inhalers with and without integrated dose counter for patients with asthma or chronic obstructive pulmonary disease.

Background: Using a metered-dose inhaler (MDI) beyond the labeled number of actuations may result in inadequate dosing of medication, which can lead to poor clinical outcomes. This study compared respiratory-related emergency department (ED) visit rates in patients with asthma, chronic obstructive pulmonary disease, or both when they used albuterol MDIs with versus without dose counters.

Methods: This retrospective study used US claims data to identify patients (ages 4-64 years) with asthma, chronic obstructive pulmonary disease, or both, using albuterol MDIs with or without an integrated dose counter.

The impact of expired and empty quick-relief asthma inhalers: The Asthma and Allergy Foundation of America's Asthma Inhaler Design Survey.

Background: Despite the available treatments, asthma remains a serious illness, with a considerable socioeconomic burden associated with a high number of unscheduled visits to the emergency department (ED). Poor adherence and inadequate inhaler technique are contributing factors to poor asthma management and control.

Objective: The Asthma Inhaler Design Survey assessed the behaviors, attitudes, needs, and preferences of patients with asthma and their caregivers with regard to quick-relief inhaler usage and device design.

Fluticasone propionate/salmeterol 250/50 μg versus salmeterol 50 μg after chronic obstructive pulmonary disease exacerbation.

Background: Inhaled long-acting beta2 agonists used alone and in combination with an inhaled corticosteroid reduce the risk of exacerbations in patients with stable COPD. However, the relative efficacy of these agents in preventing recurrent exacerbations in those recovering from an initial episode is not known. This study compared the rate of COPD exacerbations over the 26 weeks after an initial exacerbation in patients receiving the combination of fluticasone propionate and salmeterol (FP/SAL) or SAL alone.

Body mass index and response to asthma therapy: fluticasone propionate/salmeterol versus montelukast.

We studied the relationship between body mass index (BMI) on responses to asthma therapy using a retrospective analysis of four previously reported clinical trials. Fluticasone propionate (FP)/salmeterol via Diskus 100/50 microg twice daily and montelukast (MON) 10 mg daily were compared. BMI was classified as underweight (less than 20 kg/m(2)), normal (20-24.

Poly(ADP-ribose) polymerase-1 regulates vimentin expression in lung cancer cells.

Vimentin is one of the mammalian intermediate filament proteins. It is expressed in cells of mesenchymal origin and is characteristic of proliferating cells at the fetal stage. During malignancy, vimentin expression is activated in certain lung epithelial cells.

Identification of a hydrogen peroxide-induced PP1-JNK1-Sp1 signaling pathway for gene regulation.

Oxidative stress often results in changes in gene expression through the regulation of transcription factors. In this study, we examine how Sp1 phosphorylation is regulated by H(2)O(2) in a human alveolar epithelial cell line (HAE). Treatment of HAE cells with H(2)O(2) increases phosphorylation of Sp1 and activates JNK.

Sp1: regulation of gene expression by phosphorylation.

As the prototype of a family of transcription factors, Sp1 has been extensively studied and widely reported for its role in gene regulation. The first evidence of Sp1 phosphorylation was reported more than a decade ago. Since then, an increasing number of Sp1 phosphorylation events have been characterized.

Interferon-gamma regulates ClC-2 chloride channel in lung epithelial cells.

Epithelial Cl(-) channels mediate Cl(-) and fluid secretion in the lung. In cystic fibrosis, aberrant Cl(-) secretion is one of the major causes for lung fluid imbalance. Regulation of Cl(-) channels is therefore an important issue in the lung.

Improving adherence with antimicrobial therapy for respiratory tract infections: a discussion of directly observed therapy (DOT) and short-course therapies.

Although some of the variables associated with adherence (eg, patient age, place of residence) cannot be influenced, others are very amenable to modifications. Levels of adherence correlate with the convenience of dosage regimens, as shown in a number of clinical trials. Therefore, antimicrobial agents that are well accepted by patients should be considered whenever feasible.

Overview of national treatment guidelines for common respiratory tract infections.

CAP, ABECB, and AOM are common community-acquired infections accounting for many office visits and many prescriptions for antibacterial agents. In addition, bacterial resistance to common antibacterial agents is on the rise and is related to antibacterial usage rates. Therefore, careful consideration is required before prescribing an antibacterial agent for a patient suspected of having one of these infections.

Expression of alpha-ENaC2 is dependent on an upstream Sp1 binding motif and is modulated by protein phosphatase 1 in lung epithelial cells.

The amiloride-sensitive Na(+) channel ENaC is expressed in lung epithelium and plays a pivotal role in lung fluid clearance in the newborn. Multiple splice variants of the ENaC alpha-subunit have been reported. Among them, alpha-ENaC2 accounts for a considerable portion of alpha-ENaC transcripts in human lung and kidney, possesses channel functions similar to alpha-ENaC1, and is driven by a downstream promoter.