The management of asthma in the phenotype and biomarker era: The proposal of a new diagnostic-therapeutic model

Blasi, Francesco; Bettoncelli, Germano; Canonica, Giorgio Walter; Centanni, Stefano; Crimi, Nunzio; Dimaria, G.; Gasparini, Stefano; Gentili, Gilberto; Girbino, Giuseppe; Mereu, Carlo; Minghetti, Paola; Nardini, S; Paggiaro, Pierluigi; Papi, Alberto; Rossi, Andrea

doi:10.3109/02770903.2016.1140774

Cited by 10 publications

(9 citation statements)

References 17 publications

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“…Bronchial asthma usually remains uncontrolled even with treatment with ICS, long-acting beta (2)-agonists or both, and additional treatments are ultimately still required [24]. Although tremendous efforts have been made to improve asthma therapy, due to the heterogenicity and complexity of asthma, effectively controlling asthma remains difficult [25]. These findings suggest that more effective treatments are urgently needed.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-485 Modulates the TGF-β/ Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Chronic respiratory conditions continue to plague millions of people worldwide. We aimed to elucidate the detailed mechanisms of microRNA-485 (miR-485) in airway smooth muscle cell (ASMC) proliferation and apoptosis in chronic asthmatic mice. Methods: A mouse model of chronic asthma was established. Ovalbumin was used to induce chronic asthma in the mice. The levels of transforming growth factor β (TGF-β), interleukin (IL)-4, IL-5, IL-13 and IL-17 in bronchoalveolar lavage fluid in mice were measured by enzyme-linked immunoassays (ELISAs). ASMCs were transfected with miR-485 mimic, miR-485 inhibitor and siRNA-Smurf2. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were applied to detect the mRNA and protein levels of Smurf2, α-SMA, TGF-β1 and decapentaplegic homolog (Smads). The MTT assay was utilized for cell proliferation, while flow cytometry was conducted to assess cell cycle distribution and apoptosis. Results: Lower expression of miR-485 and higher expression levels of TGF-β1, IL-4, IL-5, IL-13 and IL-17 were detected in mice with chronic asthma. Smurf2 was identified as the target gene of miR-485. Upregulation of miR-485 mimic and downregulation of Smurf2 decreased expression levels of Smurf2, α-SMA, TGF-β1 and Smad3, inhibited cell proliferation and increased apoptosis, while contrary results were observed in ASMCs transfected with miR-485 inhibitor. Conclusion: Overexpressed miR-485 inhibits cell proliferation and promotes apoptosis of ASMCs through the Smurf2-mediated TGF-β/Smads signaling pathway in mice with chronic asthma.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-485 Modulates the TGF-β/ Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2

Wang

et al. 2018

Cell Physiol Biochem

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“…As a consequence of the modern eating habits associated with a sedentary lifestyle, the prevalence of obesity worldwide has been increasing [4]. With the growing prevalence of obesity, a concomitant rise in the incidence of bronchial asthma has been observed in the last few years [5, 6]. Obesity is known to contribute to a low-grade chronic inflammation with higher numbers of mast cells, macrophages, T- and B-cells, and neutrophils in adipose tissue [7, 8].…”

Section: Introductionmentioning

confidence: 99%

Obesity May Provide Pro-ILC3 Development Inflammatory Environment in Asthmatic Children

Yue

et al. 2018

Journal of Immunology Research

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The prevalence of obesity in children has dramatically increased in the last few decades, and obesity has also emerged as an important risk factor for asthma. Innate mechanisms have been shown to be involved in both diseases, particularly through the recently described innate lymphoid cells (ILCs), in which ILC3s have been linked to obesity both in human and in murine models. The aim of this study was to explore whether being overweight in asthmatic children was associated with elevated circulating ILC3 or elevated messenger RNA (mRNA) levels of RORC, IL-17A, and IL-22. Our results showed significantly elevated ILC3 frequencies in overweight asthmatic children compared with nonoverweight controls based on the detection of Lin+CD127+IL-23R+ cells by flow cytometry. Moreover, elevated ILC3 frequencies positively correlated with the mRNA expression of RORC which has been identified as a transcription factor of ILC3s. The relative mRNA expression level of IL-17A was also upregulated in overweight compared to nonoverweight children, as was the relative mRNA level of IL-22. However, there were no correlations between ILC3 frequencies or the expressions of RORC, IL-17A, and IL-22 and asthma severity. These results suggested that childhood obesity is an independent factor that is associated with an elevated frequency of circulating ILC3s and higher expressions of RORC, IL-22, and IL-17A.

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Section: Introductionmentioning

confidence: 99%

“…In the last decade the paradigm of asthma control has been evolving along with the increased awareness that any intervention employed to obtain the disease control should consider the management of patients’ future risk [29, 30]. The latter should include, among others, the minimization of adverse events while providing the optimal treatment coverage, the prevention of lung function decline and reduced lung growth in children and, most importantly, the prevention of recurrent exacerbation and especially severe relapses leading to emergency department access and hospitalization [4, 30]. Major risk factors related to future exacerbations are represented by a previous history of exacerbations, increased use of oral corticosteroids and rescue medications, obesity, worse lung function, poor adherence to inhaled therapy, low Asthma Control Questionnaire (ACQ-7) score, co-morbid diseases, chronic sinusitis and cigarette smoke (Table 1) [3, 31–43].…”

Section: Introductionmentioning

confidence: 99%

The evidence on tiotropium bromide in asthma: from the rationale to the bedside

Radovanovic

Santus

Blasi

et al. 2017

Multidiscip Respir Med

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Severe and poorly controlled asthma still accounts for a great portion of the patients affected. Disease control and future risk management have been identified by international guidelines as the main goals in patients with asthma. The need for new treatment approaches has led to reconsider anticholinergic drugs as an option for asthma treatment. Tiotropium is the first anticholinergic drug that has been approved for children and adults with poorly controlled asthma and is currently considered as an option for steps 4 and 5 of the Global Initiative for Asthma. In large randomized clinical trials enrolling patients with moderate to severe asthma, add-on therapy with tiotropium has demonstrated to be efficacious in improving lung function, decreasing risk of exacerbation and slowing the worsening of disease; accordingly, tiotropium demonstrated to be non inferior compared to long acting beta-agonists in the maintenance treatment along with medium to high inhaled corticosteroids. In view of the numerous ancillary effects acting on inflammation, airway remodeling, mucus production and cough reflex, along with the good safety profile and the broad spectrum of efficacy demonstrated in different disease phenotypes, tiotropium can represent a beneficial alternative in the therapeutic management of poorly controlled asthma. The present extensive narrative review presents the pharmacological and pathophysiological basis that guided the rationale for the introduction of tiotropium in asthma treatment algorithm, with a particular focus on its conventional and unconventional effects; finally, data on tiotropium efficacy and safety. from recent randomized clinical trials performed in all age categories will be extensively discussed.

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The management of asthma in the phenotype and biomarker era: The proposal of a new diagnostic-therapeutic model

Cited by 10 publications

References 17 publications

MicroRNA-485 Modulates the TGF-β/ Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2

MicroRNA-485 Modulates the TGF-β/ Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2

Obesity May Provide Pro-ILC3 Development Inflammatory Environment in Asthmatic Children

The evidence on tiotropium bromide in asthma: from the rationale to the bedside

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