Breathe Well Live Well
Condition: Asthma
Interventions: Drug: dupilumab SAR231893/REGN668; Drug: placebo; Drug: fluticasone propionate and salmeterol; Drug: budesonide and formoterol; Drug: mometasone furoate and formoterol
Sponsors: Sanofi; Regeneron Pharmaceuticals
Not yet recruiting – verified October 2015
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Roflumilast Reduces Airway Inflammation in Asthma Patients
Lung Disease News Inhaled corticosteroids (ICS) are recommended as the most effective treatment for asthma – ICS acts by reducing inflammation in lungs' airways and sputum production via the bronchial tubes – but their prolonged use is associated with both local and … |
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Roflumilast reduces allergen-induced airway inflammation in patients with asthma
Healio “The studies presented here show that roflumilast has no acute bronchodilator actions in patients with mild to moderate asthma,” Philip Bardin, PhD, the director of the lung and sleep unit at Monash Health in Australia, and colleagues wrote. “This … |
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Soluble Guanylate Cyclase Modulators Blunt Hyperoxia Effects on Calcium Responses of Developing Human Airway Smooth Muscle.
Am J Physiol Lung Cell Mol Physiol. 2015 Aug 7;:ajplung.00232.2015
Authors: Britt RD, Thompson MA, Kuipers I, Stewart A, Vogel ER, Thu J, Martin RJ, Pabelick CM, Prakash YS
Abstract
Exposure to moderate hyperoxia in prematurity contributes to subsequent airway dysfunction and increases the risk of developing recurrent wheeze and asthma. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic GMP (cGMP) axis modulates airway tone by regulating airway smooth muscle (ASM) intracellular Ca(2+) ([Ca(2+)]i) and contractility. However, the effects of hyperoxia on this axis in the context of Ca(2+)/contractility are not known. In developing human ASM, we explored the effects of novel drugs that activate sGC independent of NO, on alleviating hyperoxia (50% oxygen)-induced enhancement of Ca(2+) responses to bronchoconstrictor agonist. Treatment with BAY 41-2272 (sGC stimulator) and BAY 60-2770 (sGC activator) increased cGMP levels during exposure to 50% O2. Although 50% O2 did not alter sGC?1 and sGC?1 expression, BAY 60-2770 did increase sGC?1 expression. BAY 41-2272 and BAY 60-2770 blunted Ca(2+) responses to histamine in cells exposed to 50% O2. The effects of BAY 41-2272 and BAY 60-2770 were reversed by protein kinase G inhibition. These novel data demonstrate that BAY 41-2272 and BAY 60-2770 stimulate production of cGMP and blunt hyperoxia-induced increases in Ca(2+) responses in developing ASM. Accordingly, sGC stimulators/activators may be a useful therapeutic strategy in improving bronchodilation in preterm infants.
PMID: 26254425 [PubMed – as supplied by publisher]
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Lung Disease News |
Airway Resistance Measurements Shown to Help Effectively Differentiate …
Lung Disease News To examine the contribution of RAW and sGAW to a diagnosis of obstructive airways disease and their role in differentiating asthma from COPD, in the study titled “Airways resistance and specific conductance for the diagnosis of obstructive airways … |
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Ambient air pollution, lung function, and airway responsiveness in asthmatic children.
J Allergy Clin Immunol. 2015 Jun 29;
Authors: Ierodiakonou D, Zanobetti A, Coull BA, Melly S, Postma DS, Boezen HM, Vonk JM, Williams PV, Shapiro GG, McKone EF, Hallstrand TS, Koenig JQ, Schildcrout JS, Lumley T, Fuhlbrigge AN, Koutrakis P, Schwartz J, Weiss ST, Gold DR, Childhood Asthma Management Program Research Group
Abstract
BACKGROUND: Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthmatic patients are lacking.
OBJECTIVE: We sought to investigate pollution effects in a longitudinal asthma study and effect modification by controller medications.
METHODS: We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide, and sulfur dioxide concentrations in 1003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to ZIP/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and forced vital capacity (FVC) percent predicted, FEV1/FVC ratio, and PC20, adjusting for seasonality and confounders.
RESULTS: Same-day and 1-week average CO concentrations were negatively associated with postbronchodilator percent predicted FEV1 (change per interquartile range, -0.33 [95% CI, -0.49 to -0.16] and -0.41 [95% CI, -0.62 to -0.21], respectively) and FVC (-0.19 [95% CI, -0.25 to -0.07] and -0.25 [95% CI, -0.43 to -0.07], respectively). Longer-term 4-month CO averages were negatively associated with prebronchodilator percent predicted FEV1 and FVC (-0.36 [95% CI, -0.62 to -0.10] and -0.21 [95% CI, -0.42 to -0.01], respectively). Four-month averaged CO and ozone concentrations were negatively associated with FEV1/FVC ratio (P < .05). Increased 4-month average nitrogen dioxide concentrations were associated with reduced postbronchodilator FEV1 and FVC percent predicted. Long-term exposures to sulfur dioxide were associated with reduced PC20 (percent change per interquartile range, -6% [95% CI, -11% to -1.5%]). Treatment augmented the negative short-term CO effect on PC20.
CONCLUSIONS: Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications might not protect but rather worsens the effects of CO on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.
PMID: 26187234 [PubMed – as supplied by publisher]
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Forced oscillometry bested spirometry in detecting airway function in asthma …
Healio Although spirometry is common in assessing airway function in bronchial asthma, this method has limitations, according to Manal Refaat Hafez, MD, of the chest department at Al-Azhar University in Cairo, Egypt, and colleagues. They therefore sought to … |
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Rhinovirus-Induced Airway Disease: A Model To Understand the Antiviral and Th2 Epithelial Immune Dysregulation in Childhood Asthma.
J Investig Med. 2015 Jun 8;
Authors: Perez GF, Rodriguez-Martinez CE, Nino G
Abstract
Rhinovirus (RV) infections account for most asthma exacerbations among children and adults, yet the fundamental mechanism responsible for why asthmatics are more susceptible to RV than otherwise healthy individuals remains largely unknown. Nonetheless, the use of models to understand the mechanisms of RV-induced airway disease in asthma has dramatically expanded our knowledge about the cellular and molecular pathogenesis of the disease. For instance, ground-breaking studies have recently established that the susceptibility to RV in asthmatic subjects is associated with a dysfunctional airway epithelial inflammatory response generated after innate recognition of viral-related molecules, such as double-stranded RNA. This review summarizes the novel cardinal features of the asthmatic condition identified in the past few years through translational and experimental RV-based approaches. Specifically, we discuss the evidence demonstrating the presence of an abnormal innate antiviral immunity (airway epithelial secretion of types I and III interferons), exaggerated production of the master Th2 molecule thymic stromal lymphopoietin, and altered antimicrobial host defense in the airways of asthmatic individuals with acute RV infection.
PMID: 26057561 [PubMed – as supplied by publisher]
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Nanotubes Connect CD4+ T Cells to Airway Smooth Muscle Cells: Novel Mechanism of T Cell Survival.
J Immunol. 2015 May 1;
Authors: Al Heialy S, Zeroual M, Farahnak S, McGovern T, Risse PA, Novali M, Lauzon AM, Roman HN, Martin JG
Abstract
Contact between airway smooth muscle (ASM) cells and activated CD4(+) T cells, a key interaction in diseases such as asthma, triggers ASM cell proliferation and enhances T cell survival. We hypothesized that direct contact between ASM and CD4(+) T cells facilitated the transfer of anti-apoptotic proteins via nanotubes, resulting in increased survival of activated CD4(+) T cells. CD4(+) T cells, isolated from PBMCs of healthy subjects, when activated and cocultured with ASM cells for 24 h, formed nanotubes that were visualized by immunofluorescence and atomic force microscopy. Cell-to-cell transfer of the fluorescent dye calcein-AM confirmed cytoplasmic communication via nanotubes. Immunoreactive B cell lymphoma 2 (Bcl-2) and induced myeloid leukemia cell differentiation protein (Mcl-1), two major anti-apoptotic proteins, were present within the nanotubes. Downregulation of Mcl-1 by small interfering RNA in ASM cells significantly increased T cell apoptosis, whereas downregulation of Bcl-2 had no effect. Transfer of GFP-tagged Mcl-1 from ASM cells to CD4(+) T cells via the nanotubes confirmed directionality of transfer. In conclusion, activated T cells communicate with ASM cells via nanotube formation. Direct transfer of Mcl-1 from ASM to CD(+) T cells via nanotubes is involved in T cell survival. This study provides a novel mechanism of survival of CD4(+) T cells that is dependent on interaction with a structural cell.
PMID: 25934863 [PubMed – as supplied by publisher]
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Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness …
Science Magazine Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma. Polina L. Yarova,*,; Alecia L. Stewart,*,; Venkatachalem Sathish,*,; Rodney D. Britt Jr.,*,; Michael A. Thompson,; Alexander P. P. Lowe, … |
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