Alcohol and its metabolites dysregulate cellular bioenergetics and induce oxidative and endoplasmic reticulum stress in primary human bronchial epithelial cells.

Background: Chronic alcohol consumption/misuse is a significant risk factor for pneumonia and lung infection leading to the development of chronic pulmonary disorders such as chronic obstructive pulmonary disease (COPD) and lung fibrosis. In this study, we sought to delineate the mechanism of alcohol-associated lung disease. We did so by measuring in vitro mitochondrial, endoplasmic reticulum (ER) oxidative stress in human bronchial epithelial cells (hBECs) treated with ethanol and its oxidative (acetaldehyde) and nonoxidative (fatty acid ethyl esters or FAEEs) metabolites.

Omalizumab in Allergic Bronchopulmonary Aspergillosis: A Systematic Review and Meta-Analysis.

Background: An unmet clinical need exists in the management of treatment-refractory allergic bronchopulmonary aspergillosis (ABPA). Omalizumab has shown promising effects in case series and cohort studies; however, evidence to support its routine clinical use is lacking.

Objective: The aim of this systematic review and meta-analysis was to evaluate the clinical effectiveness and safety of omalizumab in patients with ABPA.

The new era of add-on asthma treatments: where do we stand?

Globally, a small proportion (5-12%) of asthma patients are estimated to have severe disease. However, severe asthma accounts for disproportionately high healthcare resource utilization. The Global Initiative for Asthma (GINA) management committee recommends treating patients with asthma with inhaled corticosteroids plus long-acting β-agonists and, when needed, adding a long-acting muscarinic receptor antagonist or biologic agent.

Optical biosensing of markers of mucosal inflammation.

We report the design and adaptation of iron/iron oxide nanoparticle-based optical nanobiosensors for enzymes or cytokine/chemokines that are established biomarkers of lung diseases. These biomarkers comprise ADAM33, granzyme B, MMP-8, neutrophil elastase, arginase, chemokine (C-C motif) ligand 20 and interleukin-6. The synthesis of nanobiosensors for these seven biomarkers, their calibration with commercially available enzymes and cytokines/chemokines, as well as their validation using bronchoalveolar lavage (BAL) obtained from a mouse model of TLR3-mediated inflammation are discussed here.

A Comprehensive Analysis of the Stability of Blood Eosinophil Levels.

Blood eosinophil counts are used to inform diagnosis/management of eosinophilic asthma. Examine blood eosinophil variability and identify factors affecting eosinophil levels to inform clinical interpretation. analysis to understand eosinophil variability using data from four randomized controlled asthma trials.

genotype identifies glucocorticoid responsiveness in severe asthma.

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma.

Ethanol Exposure Impairs AMPK Signaling and Phagocytosis in Human Alveolar Macrophages: Role of Ethanol Metabolism.

Background: Chronic alcohol consumption impairs alveolar macrophage's (AM) function and increases risk for developing lung infection and pneumonia. However, the mechanism and metabolic basis of alcohol-induced AM dysfunction leading to lung infection are not well defined, but may include altered ethanol (EtOH) and reactive oxygen species metabolism and cellular energetics. Therefore, oxidative stress, endoplasmic reticulum (ER) stress, the formation of fatty acid ethyl esters [FAEEs, nonoxidative metabolites of EtOH], AMP-activated protein kinase (AMPK) signaling, and phagocytic function were examined in freshly isolated AM incubated with EtOH.

Pharmacoproteomics reveal novel protective activity of bromodomain containing 4 inhibitors on vascular homeostasis in TLR3-mediated airway remodeling.

Small molecule inhibitors of the epigenetic regulator bromodomain-containing protein 4 (BRD4) are potential therapeutics for viral and allergen-induced airway remodeling. A limitation of their preclinical advancement is the lack of detailed understanding of mechanisms of action and biomarkers of effect. We report a systems-level pharmacoproteomics in a standardized murine model of toll-like receptor TLR3-NFκB/RelA innate inflammation in the absence or presence of a highly selective BRD4 inhibitor (ZL0454) or nonselective bromodomain and extraterminal domain inhibitor (JQ1).

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling.

Background: Frequent exacerbations of allergic asthma lead to airway remodeling and a decrease in pulmonary function, producing morbidity. Cat dander is an aeroallergen associated with asthma risk.

Objective: We sought to elucidate the mechanism of cat dander-induced inflammation-remodeling.

Post-transplant native pneumonectomy for interstitial fibrosis and small cell lung cancer.

Lung transplantation is a definitive treatment for select patients with end-stage pulmonary disease. Following transplantation, the reported rate of lung cancer is between 1-9% and is associated with a variety of risk factors, including smoking history and chronic immunosuppression. The majority of post-transplant lung cancer reported in the literature is histologically classified as non-small cell lung carcinoma (NSCLC).

National estimates of 30-day readmissions among children hospitalized for asthma in the United States.

Objective: Previous single-center studies have reported that up to 40% of children hospitalized for asthma will be readmitted. The study objectives are to investigate the prevalence and timing of 30-day readmissions in children hospitalized with asthma, and to identify factors associated with 30-day readmissions.

Methods: Data (n = 12,842) for children aged 6-18 years hospitalized for asthma were obtained from the 2013 Nationwide Readmission Database (NRD).

Diagnosis and Management of Asthma in Adults: A Review.

Importance: Asthma affects about 7.5% of the adult population. Evidence-based diagnosis, monitoring, and treatment can improve functioning and quality of life in adult patients with asthma.

Activation of Human Peripheral Blood Eosinophils by Cytokines in a Comparative Time-Course Proteomic/Phosphoproteomic Study.

Activated eosinophils contribute to airway dysfunction and tissue remodeling in asthma and thus are considered to be important factors in asthma pathology. We report here comparative proteomic and phosphoproteomic changes upon activation of eosinophils using eight cytokines individually and in selected cytokine combinations in time-course reactions. Differential protein and phosphoprotein expressions were determined by mass spectrometry after 2-dimensional gel electrophoresis (2DGE) and by LC-MS/MS.

Biologic Therapy in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is common worldwide. The predominant cause in most COPD is environmental exposure to toxicants. The inflammatory processes in COPD are multifactorial, complex, and interacting, leading to many potential therapeutic targets.

Race is associated with differences in airway inflammation in patients with asthma.

Background: African American subjects have a greater burden from asthma compared with white subjects. Whether the pattern of airway inflammation differs between African American and white subjects is unclear.

Objective: We sought to compare sputum airway inflammatory phenotypes of African American and white subjects treated or not with inhaled corticosteroids (ICSs; ICS+ and ICS-, respectively).

Cytokine-Induced Glucocorticoid Resistance from Eosinophil Activation: Protein Phosphatase 5 Modulation of Glucocorticoid Receptor Phosphorylation and Signaling.

The mechanisms contributing to persistent eosinophil activation and poor eosinopenic response to glucocorticoids in severe asthma are poorly defined. We examined the effect of cytokines typically overexpressed in the asthmatic airways on glucocorticoid signaling in in vitro activated eosinophils. An annexin V assay used to measure eosinophil apoptosis showed that cytokine combinations of IL-2 plus IL-4 as well as TNF-α plus IFN-γ, or IL-3, GM-CSF, and IL-5 alone significantly diminished the proapoptotic response to dexamethasone.

Biologic therapy in the management of asthma.

Purpose Of Review: Current asthma management relies on inhaled corticosteroids, but some asthma is not well controlled with inhaled steroids alone or in combination with long-acting bronchodilators or leukotriene pathway inhibitors. The field of biologic therapy has grown dramatically in the past two decades, with current availability of three molecules, with two distinct and highly selective approaches to interfering with the allergic and eosinophilic airway inflammation common to most asthma. This review summarizes current and future options for incorporating biologic therapy into the overall management of asthma.

Impact of Age and Sex on Outcomes and Hospital Cost of Acute Asthma in the United States, 2011-2012.

Background: Worldwide, asthma is a leading cause of morbidity, mortality and economic burden, with significant gender and racial disparities. However, little attention has been given to the independent role of age on lifetime asthma severity and hospitalization. We aimed to assess the effect of age, gender, race and ethnicity on indicators of asthma severity including asthma related hospitalization, mortality, hospital cost, and the rate of respiratory failure.