Evolution of Asthma Concept and Effect of Current Asthma Management Guidelines

Makino, Sohei; Sagara, Hironori

doi:10.4168/aair.2010.2.3.172

Cited by 10 publications

(7 citation statements)

References 15 publications

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“…Instead, airway remodeling is now thought to proceed in parallel with disease development 3456. At the same time, the treatment strategy for asthma is changing because of the limited ability of inhaled corticosteroids to reverse airway remodeling 3789…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of Resveratrol on Airway Remodeling by Transforming Growth Factor-β/Smad Signaling Pathway in Chronic Asthma Model

Lee

Kim

Yoon

et al. 2017

Allergy Asthma Immunol Res

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PurposeAsthma is a chronic airway disease characterized by airway remodeling, leading to a progressive decline in lung function. Therapeutic agents that attenuate airway remodeling can complement the limited effects of traditional glucocorticoids. In this study, we investigated the effect of resveratrol on allergic airway inflammation and remodeling in a murine model of chronic bronchial asthma.MethodsPeribronchial smooth muscle thickening that developed in mice challenged with a 3-month repeated exposure to ovalbumin (OVA) was used to study airway remodeling. Oral resveratrol was administered daily during the OVA challenge. The expression of TGF-β1/Smad signaling proteins and downstream mesenchymal markers in the presence or absence of resveratrol was examined in bronchial epithelial cells.ResultsOVA sensitization and chronic challenge increased airway hyperresponsiveness, inflammation, goblet cell hyperplasia, α-smooth muscle actin (SMA), and collagen deposition. Resveratrol effectively suppressed OVA-induced airway inflammation and remodeling. The expression of TGF-β1/phosphorylated Smad2/3 was increased in the lung tissues of OVA-challenged mice but effectively inhibited by resveratrol. In bronchial epithelial cells, the TGF-β1-induced expression of the mesenchymal markers snail, slug, vimentin, and α-SMA was suppressed by resveratrol treatment.ConclusionsResveratrol effectively ameliorated both airway inflammation and airway structural changes in a mouse model of bronchial asthma. These effects were mediated by decreased TGF-β1 expression, in turn suppressing TGF-β1/Smad signaling and the epithelial-mesenchymal transition process. Our results demonstrate the potential benefits of resveratrol for the treatment of airway remodeling associated with bronchial asthma.

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Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of Resveratrol on Airway Remodeling by Transforming Growth Factor-β/Smad Signaling Pathway in Chronic Asthma Model

Lee

Kim

Yoon

et al. 2017

Allergy Asthma Immunol Res

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“…Airway remodeling is a key feature of severe asthma that affects 300 million people worldwide (1), and is associated with significant morbidity and health costs (2). Airway remodeling is characterized as epithelial detachment, subepithelial fibrosis, increased smooth muscle mass, goblet cell hyperplasia, and angiogenesis (3).…”

Section: Introductionmentioning

confidence: 99%

Lyn Mitigates Mouse Airway Remodeling by Downregulating the TGF-β3 Isoform in House Dust Mite Models

Fox

Liu

et al. 2013

The Journal of Immunology

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Chronic airway remodeling is a serious consequence of asthma, which is caused by complex but largely unknown mechanisms. Despite versatile functions, the role of Lyn in chronic airway remodeling remains undefined. Using Lyn−/− mice, we show that continual exposure (for 8 weeks) of house dust mite (HDM) extracts induced a severe phenotype of chronic airway remodeling including exacerbated mucus production, collagen deposition, dysregulated cytokine secretion, and elevated inflammation. Strikingly, a significant increase in TGF-β3 rather than TGF-β1 was observed in Lyn−/− mouse lungs compared to wild-type mice. Furthermore, TGF-β3 neutralizing antibodies not only inhibited the expression of STAT6 and Smad2/3, but also decreased phosphorylation of Smad2 and NFκB in Lyn−/− mouse lungs. In addition, both recombinant and adenoviral TGF-β3 significantly promoted epithelial to mesenchymal transition (EMT) and intensified collagen I production and MUC5AC expression. Further examining chronic asthma patients showed that a decreased Lyn correlated with the severity of airway inflammation and mucus hypersecretion. Finally, Lyn may critically regulate airway remodeling by directly interacting with TGF-β3. Collectively, these findings revealed that Lyn regulates TGF-β3 isoform and modulates the development of airway remodeling, which may have therapeutic indications for severe chronic asthma.

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“…It is defined as a chronic inflammation that narrows the airways, causing airflow obstruction, leading to wheezing, chest tightness and coughing [ 1 ]. The disease affects more than 235 million people worldwide [ 2 ] and it was responsible for 255,000 deaths in 2005, according to the World Health Organization [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

I feel you-monitoring environmental variables related to asthma in an integrated real-time frame

Berenguer

2015

BMC Res Notes

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The study of asthma and other complex diseases has proven to be a “moving target” for researchers due to its complex aetiology, difficulty in definition, and immeasurable environmental effects. A large number of studies regarding the contribution of both genetic and environmental factors often result in contradictory results, in part due to the highly heterogeneous nature of asthma. Recent literature has focused on the epigenetic signatures of asthma caused by environmental factors, highlighting the importance of environment. However, unlike the genetic techniques, environmental assessment still lacks accuracy. A plausible solution for this problem would be an individual-based environmental exposure assessment, relying on new technologies such as personal real-time environmental sensors. This could prove to enable the assessment of the whole environmental exposure—or exposome—matching in terms of precision the genome that is emphasized in most studies so far. In addition, the measurement of the whole array of biological molecules, in response to the environment action, could help understand the context of the disease. The current perspective comprises a beyond-genetics integrated vision of omics technology coupled with real-time environmental measures targeting to enhance our comprehension of the disease genesis.

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Evolution of Asthma Concept and Effect of Current Asthma Management Guidelines

Cited by 10 publications

References 15 publications

Inhibitory Effects of Resveratrol on Airway Remodeling by Transforming Growth Factor-β/Smad Signaling Pathway in Chronic Asthma Model

Inhibitory Effects of Resveratrol on Airway Remodeling by Transforming Growth Factor-β/Smad Signaling Pathway in Chronic Asthma Model

Lyn Mitigates Mouse Airway Remodeling by Downregulating the TGF-β3 Isoform in House Dust Mite Models

I feel you-monitoring environmental variables related to asthma in an integrated real-time frame

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