Respiratory Research

http://respiratory-research.com/

List of Papers (Total 2,007)

Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study

Background Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven ...

The cellular kinetics of lung alveolar epithelial cells and its relationship with lung tissue repair after acute lung injury

Background Organ regeneration in mammals is hypothesized to require a functional pool of stem or progenitor cells, but the role of these cells in lung regeneration is unknown. Methods Based on the fact that postnatal regeneration of alveolar tissue has been attributed to alveolar epithelial cells, we established a hemorrhagic shock and Lipopolysaccharide (LPS) lung injury model. ...

‘The Microbiome and the Pathophysiology of Asthma’

Asthma is a chronic respiratory disease whose prevalence is increasing in the western world. Recently research has begun to focus on the role the microbiome plays in asthma pathogenesis in the hope of further understanding this respiratory disorder. Considered sterile until recently, the lungs have revealed themselves to contain a unique microbiota. A shift towards molecular ...

Lung bioengineering: physical stimuli and stem/progenitor cell biology interplay towards biofabricating a functional organ

A current approach to obtain bioengineered lungs as a future alternative for transplantation is based on seeding stem cells on decellularized lung scaffolds. A fundamental question to be solved in this approach is how to drive stem cell differentiation onto the different lung cell phenotypes. Whereas the use of soluble factors as agents to modulate the fate of stem cells was ...

Pulmonary hypertension and vascular remodeling in mice exposed to crystalline silica

Background Occupational and environmental exposure to crystalline silica may lead to the development of silicosis, which is characterized by inflammation and progressive fibrosis. A substantial number of patients diagnosed with silicosis develop pulmonary hypertension. Pulmonary hypertension associated with silicosis and with related restrictive lung diseases significantly reduces ...

Increased expression of TROP2 in airway basal cells potentially contributes to airway remodeling in chronic obstructive pulmonary disease

Background The airway epithelium of chronic obstructive pulmonary disease (COPD) patients undergoes aberrant repair and remodeling after repetitive injury following exposure to environmental factors. Abnormal airway regeneration observed in COPD is thought to originate in the stem/progenitor cells of the airway epithelium, the basal cells (BCs). However, the molecular mechanisms ...

Variable ventilation improves pulmonary function and reduces lung damage without increasing bacterial translocation in a rat model of experimental pneumonia

Background Variable ventilation has been shown to improve pulmonary function and reduce lung damage in different models of acute respiratory distress syndrome. Nevertheless, variable ventilation has not been tested during pneumonia. Theoretically, periodic increases in tidal volume (V T ) and airway pressures might worsen the impairment of alveolar barrier function usually seen in ...

Integrated safety and efficacy analysis of once-daily fluticasone furoate for the treatment of asthma

Background Fluticasone furoate is a once-daily inhaled corticosteroid. This report provides an overview of safety and efficacy data that support the use of once-daily fluticasone furoate 100 μg or 200 μg in adult and adolescent asthma patients. Methods Fourteen clinical studies (six Phase II and eight Phase III) were conducted as part of the fluticasone furoate global clinical ...

Respiratory viral infections and host responses; insights from genomics

Respiratory viral infections are a leading cause of disease and mortality. The severity of these illnesses can vary markedly from mild or asymptomatic upper airway infections to severe wheezing, bronchiolitis or pneumonia. In this article, we review the viral sensing pathways and organizing principles that govern the innate immune response to infection. Then, we reconstruct the ...

Pulmonary endothelial activation caused by extracellular histones contributes to neutrophil activation in acute respiratory distress syndrome

Background During the acute respiratory distress syndrome (ARDS), neutrophils play a central role in the pathogenesis, and their activation requires interaction with the endothelium. Extracellular histones have been recognized as pivotal inflammatory mediators. This study was to investigate the role of pulmonary endothelial activation during the extracellular histone-induced ...

Diagnostic accuracy of methacholine challenge tests assessing airway hyperreactivity in asthmatic patients - a multifunctional approach

Background There are few studies comparing diagnostic accuracy of different lung function parameters evaluating dose–response characteristics of methacholine (MCH) challenge tests (MCT) as quantitative outcome of airway hyperreactivity (AHR) in asthmatic patients. The aim of this retrospectively analysis of our database (Clinic Barmelweid, Switzerland) was, to assess diagnostic ...

Impaired anti-inflammatory action of glucocorticoid in neutrophil from patients with steroid-resistant asthma

Background Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve despite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers neutrophils, which are less responsive to glucocorticoid. The present study seeks to determine whether dexamethasone (DEX) has different effect on neutrophils ...

Evaluation of the use of Swedish integrated electronic health records and register health care data as support clinical trials in severe asthma: the PACEHR study

Background In the development of new drugs for severe asthma, it is a challenge from an ethical point of view to randomize severe asthma patients to placebo, and to obtain long-term safety data due to discontinuations. The aim of this study was to evaluate the feasibility of using electronic health record (EHR) data to create a real-world reference population of uncontrolled ...

The impact of low-frequency, low-force cyclic stretching of human bronchi on airway responsiveness

Background In vivo, the airways are constantly subjected to oscillatory strain (due to tidal breathing during spontaneous respiration) and (in the event of mechanical ventilation) positive pressure. This exposure is especially problematic for the cartilage-free bronchial tree. The effects of cyclic stretching (other than high-force stretching) have not been extensively ...

Disharmony between wake- and respiration-promoting activities: effects of modafinil on ventilatory control in rodents

Background Modafinil is a wake-promoting drug and has been widely used for daytime sleepiness in patients with narcolepsy and other sleep disorders. A recent case series reported that daily oral modafinil alleviated hypercapnic respiratory failure in patients with COPD. However, the precise action of modafinil on respiration such as hypercapnic and/or hypoxic ventilatory responses ...

Rising total costs and mortality rates associated with admissions due to COPD exacerbations

Background To examine trends in mortality, costs and in-hospital management and outcomes of severe COPD exacerbations admitted in France. Methods Patients hospitalized from 2007 to 2012 with COPD exacerbation as the primary diagnosis were identified from the exhaustive French medico-administrative hospitalizations database records. Four groups of severe COPD exacerbations were ...

Circulating biomarkers of oxidative stress in chronic obstructive pulmonary disease: a systematic review

Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airflow limitation associated with an abnormal inflammatory response of the lungs to noxious particles and gases, caused primarily by cigarette smoking. Increased oxidative burden plays an important role in the pathogenesis of COPD. There is a delicate balance between the toxicity of oxidants ...

Spirometric variability in smokers: transitions in COPD diagnosis in a five-year longitudinal study

Background Spirometrically-defined chronic obstructive pulmonary disease (COPD) is considered progressive but its natural history is inadequately studied. We hypothesized that spirometrically-defined COPD states could undergo beneficial transitions. Methods Participants in the Lovelace Smokers’ Cohort (n = 1553), primarily women, were longitudinally studied over 5 years. ...

Administration of JTE013 abrogates experimental asthma by regulating proinflammatory cytokine production from bronchial epithelial cells

Background Sphingosine-1-phosphate (S1P) is a bioactive phospholipid that acts as a signal transducer by binding to S1P receptors (S1PR) 1 to 5. The S1P/S1PRs pathway has been associated with remodeling and allergic inflammation in asthma, but the expression pattern of S1PR and its effects on non-immune cells have not been completely clarified. The aim of this study was to examine ...

Non-neuronal cholinergic system contributes to corticosteroid resistance in chronic obstructive pulmonary disease patients

Background Inhaled corticosteroid (ICS) with long-acting beta-2 agonists is a well-documented combination therapy for chronic obstructive pulmonary disease (COPD) based on its additive anti-inflammatory properties. By contrast, the recommendation of ICS in combination with long-acting muscarinic antagonist (LAMA) is not evidence-based. In this study, neutrophils obtained from COPD ...

Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis

Background The abnormal epithelial-mesenchymal restorative capacity in idiopathic pulmonary fibrosis (IPF) has been recently associated with an accelerated aging process as a key point for the altered wound healing. The advanced glycation end-products (AGEs) are the consequence of non-enzymatic reactions between lipid and protein with several oxidants in the aging process. The ...

Differential DNA methylation marks and gene comethylation of COPD in African-Americans with COPD exacerbations

Background Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide. Identifying COPD-associated DNA methylation marks in African-Americans may contribute to our understanding of racial disparities in COPD susceptibility. We determined differentially methylated genes and co-methylation network modules associated with COPD in African-Americans ...

EIF2AK4 mutation as “second hit” in hereditary pulmonary arterial hypertension

Background Mutations in the eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4) gene have recently been identified in recessively inherited veno-occlusive disease. In this study we assessed if EIF2AK4 mutations occur also in a family with autosomal dominantly inherited pulmonary arterial hypertension (HPAH) and incomplete penetrance of bone morphogenic protein receptor 2 ...