Tag: Airway

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STAT1 Attenuates Murine Allergen-Induced Airway Remodeling and Exacerbation by Carbon Nanotubes.

STAT1 Attenuates Murine Allergen-Induced Airway Remodeling and Exacerbation by Carbon Nanotubes.

Am J Respir Cell Mol Biol. 2015 Mar 25;

Authors: Thompson EA, Sayers BC, Glista-Baker EE, Shipkowski KA, Ihrie MD, Duke KS, Taylor AJ, Bonner JC

Abstract
Asthma is characterized by a T-helper 2 (Th2) phenotype and by chronic allergen-induced airway inflammation (AAI). Environmental exposure to air pollution ultrafine particles (i.e., nanoparticles) exacerbates AAI and a concern is possible exacerbation posed by engineered nanoparticles generated by emerging nanotechnologies. STAT1 is a transcription factor that maintains Th1 cell development. However, the role of STAT1 in regulating AAI or exacerbation by nanoparticles has not been explored. In this study, mice with whole body knock-out of the Stat1 gene (Stat1-/-) or wild type (WT) mice were sensitized to ovalbumin (OVA) allergen and then exposed to multi-walled carbon nanotubes (MWCNTs) by oropharygneal aspiration. In Stat1-/- and WT mice, OVA increased eosinophils in bronchoalveolar lavage fluid (BALF), while MWCNTs increased neutrophils. Interestingly, OVA sensitization prevented MWCNT-induced neutrophilia and caused only eosinophilic inflammation. Stat1-/- mice displayed increased IL-13 in BALF 1 day compared to WT mice after treatment with OVA or OVA and MWCNT. At 21 days the lungs of OVA-sensitized Stat1-/- mice displayed increased eosinophilia, goblet cell hyperplasia, airway fibrosis, and subepithelial apoptosis. MWCNTs further increased OVA-induced goblet cell hyperplasia, airway fibrosis, and apoptosis in Stat1-/- mice at 21 days. These changes corresponded to increased levels of pro-fibrogenic mediators (TGF-?1, TNF-?, OPN) but decreased IL-10 in Stat1-/- mice. Finally, fibroblasts isolated from the lungs of Stat1-/- mice produced significantly more collagen mRNA and protein in response to TGF-?1 compared to WT lung fibroblasts. Our results support a protective role for STAT1 in chronic AAI and exacerbation of remodeling caused by MWCNTs.

PMID: 25807359 [PubMed – as supplied by publisher]

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Effects of weight loss on airway responsiveness in obese asthmatics: Does weight loss lead to reversibility of asthma?

Effects of weight loss on airway responsiveness in obese asthmatics: Does weight loss lead to reversibility of asthma?

Chest. 2015 Mar 12;

Authors: Pakhale S, Baron J, Dent R, Vandemheen K, Aaron SD

Abstract
Background: Growing epidemics of obesity and asthma are major public health concerns. Despite that asthma-obesity links are widely studied, the effects of weight loss on asthma severity measured by airway hyper-responsiveness (AHR) have received limited attention. Our main study objective was to examine whether weight reduction reduces asthma severity in adult obese-asthmatics.
Methods: In a prospective controlled parallel group study, we followed 22 obese-asthmatic subjects aged 18-75 years, with a body mass index (BMI) >32.5kg/m2 and airway hyper-responsiveness (PC20<16mg/mL of methacholine). Sixteen subjects followed a behavioural weight reduction program for 3 months and 6 subjects were controls. The primary outcome was change in AHR over 3 months. Changes in lung function, asthma control and quality of life were secondary outcomes.
Results: At study entry, subjects’ mean age was 44 years (SD±9), 95% were females with mean BMI of 45.7kg/m2 (SD±9.2). After 3 months, mean weight loss was 16.5kg (SD± 9.9) in the weight loss group but controls had a mean weight gain of 0.6kg (SD±2.6). There were significant improvements in PC20 to methacholine (p=0.009), FEV1 (p=0.009), FVC (p=0.010), asthma-control (p<0.001) and asthma quality of life (p=0.003) in the intervention group whilst these parameters remained unchanged in the control group. Physical activity levels also increased significantly in the intervention group but not in the controls.
Conclusion: Weight loss in obese-asthmatics can improve asthma severity and result in improvements in AHR, asthma control, lung function, and quality of life. These findings support the need to actively pursue healthy weight loss measures in obese-asthmatics.

PMID: 25763936 [PubMed – as supplied by publisher]

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Explaining More About Airway Closure During Asthma Attacks – Bioscience Technology


Bioscience Technology

Explaining More About Airway Closure During Asthma Attacks
Bioscience Technology
(Source: UCSF) The molecular regulation of smooth-muscle contraction is an important determinant of airway responses during an acute asthmatic attack. In acute asthma, various triggers, including viral illnesses and aeroallergens, can cause acute …

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