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      Research advances in airway remodeling in asthma: a narrative review

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          Abstract

          Background and Objective

          Asthma is a common chronic disorder of the airway, and its disability and mortality rates continue to increase each year. Due to the lack of an ideal treatment, asthma control in China remains unsatisfactory. Airway remodeling is the pathological basis for the eventual development of the fixed airflow limitation in asthmatic patients. Early diagnosis and the prevention of airway remodeling has the potential to decrease disease severity, to improve control, and to prevent disease expression.

          Methods

          This article presents an overview. The literature was combed through via CNKi and PubMed according to the listed keywords. We considered Chinese and English original publications (basic science and clinical), reviews and abstracts of 21th Century.

          Key Content and Findings

          We review the pathological features and pathogenesis of, and the interventional treatment options for airway remodeling in asthmatic patients, emphasizing the importance of airway remodeling in asthma and providing novel insights into the prevention and control of asthma.

          Conclusions

          Thus, there have been research advances in airway remodeling, especially in the areas of slowing down or reversing airway remodeling. As growing studies showed, treating airway remodeling is a promising strategy in preventing the occurrence and progression of asthma. Breakthroughs in these difficulties airway remodeling still facing will open up new avenues in the research and treatment of asthma.

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          Most cited references75

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          Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial.

          Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle. To evaluate the effectiveness and safety of BT versus a sham procedure in subjects with severe asthma who remain symptomatic despite treatment with high-dose inhaled corticosteroids and long-acting beta(2)-agonists. A total of 288 adult subjects (Intent-to-Treat [ITT]) randomized to BT or sham control underwent three bronchoscopy procedures. Primary outcome was the difference in Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to average of 6, 9, and 12 months (integrated AQLQ). Adverse events and health care use were collected to assess safety. Statistical design and analysis of the primary endpoint was Bayesian. Target posterior probability of superiority (PPS) of BT over sham was 95%, except for the primary endpoint (96.4%). The improvement from baseline in the integrated AQLQ score was superior in the BT group compared with sham (BT, 1.35 +/- 1.10; sham, 1.16 +/- 1.23 [PPS, 96.0% ITT and 97.9% per protocol]). Seventy-nine percent of BT and 64% of sham subjects achieved changes in AQLQ of 0.5 or greater (PPS, 99.6%). Six percent more BT subjects were hospitalized in the treatment period (up to 6 wk after BT). In the posttreatment period (6-52 wk after BT), the BT group experienced fewer severe exacerbations, emergency department (ED) visits, and days missed from work/school compared with the sham group (PPS, 95.5, 99.9, and 99.3%, respectively). BT in subjects with severe asthma improves asthma-specific quality of life with a reduction in severe exacerbations and healthcare use in the posttreatment period. Clinical trial registered with www.clinialtrials.gov (NCT00231114).
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            Airway remodeling in asthma: what really matters

            Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and “endotyped” human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.
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              The sentinel role of the airway epithelium in asthma pathogenesis.

              The adoption of the concept that asthma is primarily a disease most frequently associated with elaboration of T-helper 2 (Th2)-type inflammation has led to the widely held concept that its origins, exacerbation, and persistence are allergen driven. Taking aside the asthma that is expressed in non-allergic individuals leaves the great proportion of asthma that is associated with allergy (or atopy) and that often has its onset in early childhood. Evidence is presented that asthma is primarily an epithelial disorder and that its origin as well as its clinical manifestations have more to do with altered epithelial physical and functional barrier properties than being purely linked to allergic pathways. In genetically susceptible individuals, impaired epithelial barrier function renders the airways vulnerable to early life virus infection, and this in turn provides the stimulus to prime immature dendritic cells toward directing a Th2 response and local allergen sensitization. Continued epithelial susceptibility to environmental insults such as viral, allergen, and pollutant exposure and impaired repair responses leads to asthma persistence and provides the mediator and growth factor microenvironment for persistence of inflammation and airway wall remodeling. Increased deposition of matrix in the epithelial lamina reticularis provides evidence for ongoing epithelial barrier dysfunction, while physical distortion of the epithelium consequent upon repeated bronchoconstriction provides additional stimuli for remodeling. This latter response initially serves a protective function but, if exaggerated, may lead to fixed airflow obstruction associated with more severe and chronic disease. Dual pathways in the origins, persistence, and progression of asthma help explain why anti-inflammatory treatments fail to influence the natural history of asthma in childhood and only partially does so in chronic severe disease. Positioning the airway epithelium as fundamental to the origins and persistence of asthma provides a rationale for pursuit of therapeutics that increase the resistance of the airways to environmental insults rather than concentrating all effort on suppressing inflammation. © 2011 John Wiley & Sons A/S.
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                Author and article information

                Journal
                Ann Transl Med
                Ann Transl Med
                ATM
                Annals of Translational Medicine
                AME Publishing Company
                2305-5839
                2305-5847
                September 2022
                September 2022
                : 10
                : 18
                : 1023
                Affiliations
                [1 ]deptDepartment of Respiratory and Critical Care Medicine , The Eighth Affiliated Hospital of Sun Yat-sen University , Shenzhen, China;
                [2 ]deptDepartment of Respiratory and Critical Care Medicine , Shenzhen People’s Hospital , Shenzhen, China
                Author notes

                Contributions: (I) Conception and design: C Qiu; (II) Administrative support: C Qiu; (III) Provision of study materials or patients: Y Huang; (IV) Collection and assembly of data: Y Huang; (V) Data analysis and interpretation: Y Huang; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors.

                Correspondence to: Chen Qiu. No. 1017, Dongmen North Road, Luohu District, Shenzhen, China. Email szchester@ 123456163.com .
                Article
                atm-10-18-1023
                10.21037/atm-22-2835
                9577744
                36267708
                7d979b62-7e39-49e3-99b7-aa9436e1a89a
                2022 Annals of Translational Medicine. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 30 May 2022
                : 06 September 2022
                Categories
                Review Article

                asthma,airway remodeling,pathological features,treatment

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