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.

Benefits of Airway Androgen Receptor Expression in Human Asthma.

Androgens are potentially beneficial in asthma, but (androgen receptor) has not been studied in human airways. To measure whether and its ligands are associated with human asthma outcomes. We compared the effects of expression on lung function, symptom scores, and fractional exhaled nitric oxide (Fe) in adults enrolled in SARP (Severe Asthma Research Program).

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.

Chronic Respiratory Disease and Cognitive Impairment in Older Mexican Adults.

Background: Cognitive impairment has emerged as an important concern in clinical practice in aging population. Several comorbid factors contribute to etiopathogenesis; one disease of interest is chronic respiratory disease.

Aim: The aim of this study is to investigate the association of chronic respiratory disease with risk of cognitive impairment in older Mexicans.

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.

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.

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).