Tiotropium bromide as add-on therapy to inhaled corticosteroids for treating asthma

Matsuse, Hiroto; Yamagishi, Tohru; Kodaka, Norio; Miura, Atsuo; Kurose, Yoshiyuki; Nakano, Chihiro; Oshio, Takeshi

doi:10.1517/14656566.2015.1045877

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…Furthermore, other drugs [e.g., LAMA and LABA (98,99)] have also been shown to improve airway remodeling, whereas they have also only been performed in animal models of asthma. Besides, there have been no data assessing outcomes of airway remodeling in asthmatics treated with these drugs.…”

Section: Bronchial Thermoplastymentioning

confidence: 99%

Status and prospects: personalized treatment and biomarker for airway remodeling in asthma

Zhang

Dong

2020

J Thorac Dis

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Airway remodeling, as a major characteristic of bronchial asthma, is critical to the progression of this disease, whereas it is of less importance in clinical management. Complying with the current stepwise treatment standard for asthma, the choice of intervention on the clinical status is primarily determined by the patient's treatment response to airway inflammation. However, a considerable number of asthmatic patients, especially severe asthmatic subjects, remain uncontrolled though they have undergone fortified anti-inflammation treatment. In the past few years, a growing number of biologics specific to asthma phenotypes have emerged, bringing new hope for patients with refractory asthma and severe asthma. While at the same time, the effect of airway remodeling on asthma treatment has become progressively prominent.In the era of personalized treatment, it has become one of the development directions for asthma treatment to find reliable airway remodeling biomarkers to assist in asthma phenotypes classification, and to further combine multiple phenotypes to accurately treat patients. In the present study, the research status of airway remodeling in asthma is reviewed to show the basis for classifying and treating such disease. Besides, several selected airway remodeling biomarkers and possibility to use them in individual treatment are discussed as well. This study considers that continuously optimized mechanisms and emerging biomarkers for airway remodeling in the future may further support individual therapy for asthma patients.

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Section: Bronchial Thermoplastymentioning

confidence: 99%

Status and prospects: personalized treatment and biomarker for airway remodeling in asthma

Zhang

Dong

2020

J Thorac Dis

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“…However, the low concentration of budesonide (250μg/15ml) used in this study had a very limited anti-inflammatory efficacy without any significant impact on MMP-9 activity [ 38 ]. Evidence has revealed that LAMA elicited protective effects and reduced the incidence of acute exacerbation in patients with asthma who were resistant to ICS when it was used as an add-on therapy to ICS [ 39 , 40 ]. To observe the regulatory effects of the combination of a LAMA with an ICS on Cd-induced acute neutrophilic pulmonary inflammation, the low concentration of tiotropium (70μg/15ml) was administrated with budesonide (250μg/15ml).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats

Zhao

Yang

et al. 2018

PLoS ONE

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As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70μg/15ml or 350μg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70μg/15ml) or budesonide (250μg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness.

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“…Вміст ММР і TIMP-1 не змінювався під впливом TGF-β 1 та лікування, що свідчить про те, що терапія будесонідом і формотеролом не впливає на металопротеолітичний баланс, але протидіє підвищеній продукції колагену шляхом впливу на бронхіальні фібробласти і нормалізує продукцію протеогліканів [64]. Встановлено, що пролонговані М-холінолінолітики та БАТД частково гальмують процеси ре моделювання ДШ в експериментальних моделях астми [65].…”

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Matrix Metalloproteinases as Markers of Respiratory Tract Remodeling and Potential Therapeutic Target in Patients With Bronchial Asthma

Kachkovska

2021

EUMJ

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It is evidently known that chronic inflammatory process in the bronchi of patients with bronchial asthma is associated with the emergence and progression of airway remodeling, resulting in irreversible obstruction. However, the exact mechanisms of connection between inflammation and airway remodeling are not very well understood and that is the reason for delay of development new specific targeted drugs aimed to inhibit the process of inflammation and remodeling. Therefore, our goal was aimed to analyze and systematize data on the role of matrix metalloproteinases in the occurrence of airway remodeling in patients with bronchial asthma and the possibility of therapeutic effects on this process. Materials and methods: search for information on the role and mechanisms of influence of matrix metalloproteinases on airway remodeling processes in patients with bronchial asthma and the possibility of its pharmacological correction in electronic databases such as PubMed and Google Scholar over the past 25 years. Matrix metalloproteinase-9 and tissue proteinase-1 inhibitor have been shown to play the most important role in airway remodeling in the presence of bronchial asthma, supported by numerous experimental and clinical studies. Much attention is paid to the comparison of these indicators in bronchoalveolar lavage, induced sputum and blood on the background of exacerbation and in the presence of a stable course of the disease. The analysis of their content depending on the severity of the course, dysfunction of external respiration and the degree of reversibility of bronchial obstruction. Studies of the possibility of drug effects on the content of remodeling markers have shown low clinical efficacy. The results are contradictory, but most of them prove the important role of matrix metalloproteinase-9, tissue protease inhibitor-1 and their relationship in the occurrence and progression of airway remodeling and, consequently, the severity of the disease, which dictates the need to develop new additional treatments.

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Tiotropium bromide as add-on therapy to inhaled corticosteroids for treating asthma

Cited by 5 publications

References 38 publications

Status and prospects: personalized treatment and biomarker for airway remodeling in asthma

Status and prospects: personalized treatment and biomarker for airway remodeling in asthma

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats

Matrix Metalloproteinases as Markers of Respiratory Tract Remodeling and Potential Therapeutic Target in Patients With Bronchial Asthma

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