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New Frontiers in Asthma Treatment & Management
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New Frontiers in Asthma Treatment & Management

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pulmonology".

Deadline for manuscript submissions: closed (31 October 2020) | Viewed by 46939

Special Issue Editor

Dr. Tetsuya Homma

E-Mail Website
Guest Editor
Lecturer of Department of Medicine, Department of Allergology and Respiratory Medicine, University of Showa School of Medicine, Tokyo, Japan
Interests: asthma; COPD; IPF; CRSwNP; frailty; infection; allergy; biologics; epithelial cells; elder patients

Special Issue Information

Dear Colleagues,

Asthma is a mainly allergic respiratory disease with an increasing prevalence around the world and consists of different endotypes and phenotypes, all of which make asthma a great study topic. Asthmatic endotypes are defined by a combination of immune responses and memory of individual cells, transcriptome (gene expression), metabolome, and proteome. Several phenotypes were proposed in the past, such as Th2 inflammation, obesity, responsiveness to a bronchodilator, and recently, microbiomes. Comorbid diseases are also in variety, such as chronic rhinosinusitis with nasal polyp (CRSwNP), chronic obstructive pulmonary disease (COPD), aspirin exacerbated respiratory disease (AERD), eosinophilic granulomatosis with polyangiitis (EGPA), and allergic bronchopulmonary aspergillosis (ABPA). Interventions with monoclonal antibody therapy and bronchial thermoplasty have benefitted severe asthmatic patients, but still 5% to 10% of patients with this disease find that it is resistant even with optimal treatment. Therefore, asthma is a common and heterogenous airway disease that needs to be explored more in both clinical and basic studies.

In this Special Issue, we would like to move this field forward by inviting every original clinical and basic research, meta-analysis, and state-of-the-art review related to what was mentioned above. This Special Issue also aims at advancing precision medicine for patients with asthma by identifying phenotypes and endotypes and translating basic cell-based research to clinical practice. We will be grateful to receive your submissions to move the field of asthma forward.

Dr. Tetsuya Homma

Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • allergic respiratory disease
  • asthma
  • comorbidities
  • precision medicine
  • biomarkers
  • endotypes
  • phenotypes

Published Papers (10 papers)

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Research

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14 pages, 1891 KiB  
Article
Clinical Characterization of the Frequent Exacerbator Phenotype in Asthma
by Andrea Elio Sprio, Vitina Carriero, Stefano Levra, Carlotta Botto, Francesca Bertolini, Antonino Di Stefano, Mauro Maniscalco, Giorgio Ciprandi and Fabio Luigi Massimo Ricciardolo
J. Clin. Med. 2020, 9(7), 2226; https://doi.org/10.3390/jcm9072226 - 14 Jul 2020
Cited by 12 | Viewed by 2090
Abstract
Background: Asthma exacerbation is episodic worsening of respiratory symptoms in conjunction with the deterioration of lung function, which may occur independently from the asthma severity hampering asthmatics’ quality of life. This study aimed to characterize the patient phenotype more prone to asthma exacerbation [...] Read more.
Background: Asthma exacerbation is episodic worsening of respiratory symptoms in conjunction with the deterioration of lung function, which may occur independently from the asthma severity hampering asthmatics’ quality of life. This study aimed to characterize the patient phenotype more prone to asthma exacerbation (oral corticosteroid burst ≥2 per year) to allow the proper identification of such patients. Methods: This real-life, observational, cross-sectional study evaluated 464 asthmatic patients stratified according to the asthma exacerbations experienced in the previous year. Clinical, functional, and blood parameters were retrieved from chart data and were representative of patients in stable conditions. Results: The frequent asthma exacerbator was more commonly female, suffered from chronic rhinosinusitis with nasal polyposis, had reduced lung function and peripheral oxygen saturation, and had increased daily activity limitations. These patients often had severe asthma and more frequently needed hospitalization in their lives. Furthermore, the frequent asthma exacerbator had higher concentrations of serum immunoglobulin E (IgE) and exhaled nitric oxide with cut-off risk values of 107.5 kU/L (OR = 4.1) and 43.35 ppb (OR = 3.8), respectively. Conclusions: This study illustrates the clinical features of the frequent asthma exacerbator phenotype. Nevertheless, serum IgE and exhaled nitric oxide could allow the identification of this phenotype and the establishment of an appropriate therapeutic approach. Full article
(This article belongs to the Special Issue New Frontiers in Asthma Treatment & Management)
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9 pages, 658 KiB  
Article
Discrepancy between Lung Function Measurements at Home and in the Hospital in Children with Asthma and CF
by Frederick L.G.R. Gerzon, Quirijn Jöbsis, Michiel A.G.E. Bannier, Bjorn Winkens and Edward Dompeling
J. Clin. Med. 2020, 9(6), 1617; https://doi.org/10.3390/jcm9061617 - 26 May 2020
Cited by 20 | Viewed by 2481
Abstract
The Coronavirus pandemic stresses the importance of eHealth techniques to monitor patients at home. Home monitoring of lung function in asthma and cystic fibrosis (CF) may help to detect deterioration of lung function at an early stage, but the reliability is unclear. We [...] Read more.
The Coronavirus pandemic stresses the importance of eHealth techniques to monitor patients at home. Home monitoring of lung function in asthma and cystic fibrosis (CF) may help to detect deterioration of lung function at an early stage, but the reliability is unclear. We investigated whether lung function measurements at home were comparable to measurements during clinical visits. We analysed prospectively collected data of two one-year observational cohort studies in 117 children (36 with CF and 81 with asthma). All patients performed forced expiratory volume in one second (FEV1) measurements with a monitor at home. Paired FEV1 measurements were included if the measurement on the home monitor was performed on the same day as the FEV1 measurement on the pneumotachometer during a two monthly clinical visit. Bland-Altman plots and linear mixed model analysis were used. The mean difference (home measurement was subtracted from clinical measurement) in FEV1 was 0.18 L in CF (95% confidence interval (CI) 0.08–0.27 L; p < 0.001) and 0.12 L in asthma (95%CI 0.05–0.19 L; p < 0.001). FEV1 measurements at home were significantly lower than clinically obtained FEV1 measurements, which has implications for the application of this technique in the daily clinical situation. Full article
(This article belongs to the Special Issue New Frontiers in Asthma Treatment & Management)
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10 pages, 1656 KiB  
Article
Sirtuin 1: Endocan and Sestrin 2 in Different Biological Samples in Patients with Asthma. Does Severity Make the Difference?
by Zoe Tsilogianni, Jonathan R Baker, Anastasia Papaporfyriou, Andrianna I Papaioannou, Evgenia Papathanasiou, Nikolaos G Koulouris, Leah Daly, Kazuhiro Ito, Georgios Hillas, Spyridon Papiris, Petros Bakakos and Stelios Loukides
J. Clin. Med. 2020, 9(2), 473; https://doi.org/10.3390/jcm9020473 - 09 Feb 2020
Cited by 12 | Viewed by 2227
Abstract
Background: Sestrin 2, Endocan, and Sirtuin 1 are distinct molecules with some biologic actions associated with asthma pathophysiology. The aim of the present study was to determine the molecular level differences attributable to underlying asthma severity. Methods: We initially recruited 85 asthmatics with [...] Read more.
Background: Sestrin 2, Endocan, and Sirtuin 1 are distinct molecules with some biologic actions associated with asthma pathophysiology. The aim of the present study was to determine the molecular level differences attributable to underlying asthma severity. Methods: We initially recruited 85 asthmatics with a wide spectrum of severity. All of the patients were optimally treated according to current guidelines. Demographics, test results of lung function, and treatment regimes of all patients were recorded. Sestrin 2, Endocan, and Sirtuin 1 were measured in different biological samples (sputum with two processing methods and serum). Results: A total of 60 patients (35 with severe asthma) were analyzed, since 25 patients failed to produce an adequate sample of sputum. Patients with severe asthma showed significantly higher values for Sestrin 2 [pg/mL], measured in both sputum supernatant and cell pellet, compared to those with mild to moderate asthma [9524 (5696, 12,373) vs. 7476 (4265, 9273) p = 0.029, and 23,748 (15,280, 32,742) vs. 10,084 (3349, 21,784), p = 0.008, respectively]. No other significant differences were observed. No significant associations were observed between biomarkers, inflammatory cells, and lung function. Conclusion: Sestrin 2 is increased in patients with severe asthma as part of a mechanism that may modify structural alterations through the imbalance between oxidative stress and antioxidant activity. Full article
(This article belongs to the Special Issue New Frontiers in Asthma Treatment & Management)
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Review

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11 pages, 218 KiB  
Review
Role of Cytokines in EGPA and the Possibility of Treatment with an Anti-IL-5 Antibody
by Takeo Isozaki, Tetsuya Homma, Hironori Sagara and Tsuyoshi Kasama
J. Clin. Med. 2020, 9(12), 3890; https://doi.org/10.3390/jcm9123890 - 30 Nov 2020
Cited by 11 | Viewed by 3093
Abstract
Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of systemic vasculitis with eosinophilia in the peripheral blood, which is preceded by bronchial asthma or allergic disease. EGPA is pathologically characterized by microangiopathy granulomatosis vasculitis. Vasculitis can be exacerbated and cause central nervous system [...] Read more.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of systemic vasculitis with eosinophilia in the peripheral blood, which is preceded by bronchial asthma or allergic disease. EGPA is pathologically characterized by microangiopathy granulomatosis vasculitis. Vasculitis can be exacerbated and cause central nervous system and cardiovascular disorders and gastrointestinal perforation. Histological examination reveals eosinophil infiltration and granulomas in lesions in areas such as the lung, nervous system, and skin. Laboratory tests show inflammatory findings such as C-reactive protein (CRP) elevation, increased eosinophils, elevated serum IgE, and elevated myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA). MPO-ANCA is positive in approximately 40–70% of cases of this disease. EGPA is a necrotizing vasculitis that affects small- and medium-sized blood vessels; however, it differs from other types of ANCA-related vasculitis (such as microscopic polyangiitis and granulomatosis) because it is preceded by bronchial asthma and eosinophilia in the blood and tissues. Treatment with immunosuppressive agents such as steroids or cyclophosphamide depends on the Five Factor Score, which predicts the prognosis and severity of the condition. If the effect of appropriate treatment with steroids is insufficient, the anti-interleukin-5 antibody mepolizumab can be administered. The combination of mepolizumab with standard treatment leads to a significantly longer duration of remission, a higher proportion of patients who achieve sustained remission, and less steroid use than with a placebo. Full article
(This article belongs to the Special Issue New Frontiers in Asthma Treatment & Management)
18 pages, 1139 KiB  
Review
Precision Medicine in House Dust Mite-Driven Allergic Asthma
by Ibon Eguiluz-Gracia, Francisca Palomares, Maria Salas, Almudena Testera-Montes, Adriana Ariza, Ignacio Davila, Joan Bartra, Cristobalina Mayorga, Maria Jose Torres and Carmen Rondon
J. Clin. Med. 2020, 9(12), 3827; https://doi.org/10.3390/jcm9123827 - 26 Nov 2020
Cited by 7 | Viewed by 2905
Abstract
House dust mites (HDMs) are the allergenic sources most frequently involved in airway allergy. Nevertheless, not every sensitized patient develops respiratory symptoms upon exposure to HDM, and there is a clinical need to differentiate allergic asthmatics (AAs) from atopic non-allergic asthmatics with HDM [...] Read more.
House dust mites (HDMs) are the allergenic sources most frequently involved in airway allergy. Nevertheless, not every sensitized patient develops respiratory symptoms upon exposure to HDM, and there is a clinical need to differentiate allergic asthmatics (AAs) from atopic non-allergic asthmatics with HDM sensitization. This differentiation sometimes requires in vivo provocations like the bronchial allergen challenge (BAC). Interestingly, recent data demonstrate that non-atopic patients with asthma can also develop positive BAC results. This novel phenotype has been termed local allergic asthma (LAA). The interest in identifying the allergic triggers of asthma resides in the possibility of administering allergen immunotherapy (AIT). AIT is a disease-modifying intervention, the clinical benefit of which persists after therapy discontinuation. Recently, new modalities of sublingual tablets of HDM immunotherapy registered as pharmaceutical products (HDM-SLIT tablets) have become commercially available. HDM-SLIT tablets have demonstrated a robust effect over critical asthma parameters (dose of inhaled corticosteroids, exacerbations, and safety), thus being recommended by international guidelines for patients with HDM-driven AA. In this review, we will summarize the current knowledge on the phenotype and endotype of HDM-driven AA, and LAA, address the difficulties for BAC implementation in the clinic, and discuss the effects of AIT in AA and LAA. Full article
(This article belongs to the Special Issue New Frontiers in Asthma Treatment & Management)
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15 pages, 546 KiB  
Review
Airway Epithelial Dysfunction in Asthma: Relevant to Epidermal Growth Factor Receptors and Airway Epithelial Cells
by Hideki Inoue, Kaho Akimoto, Tetsuya Homma, Akihiko Tanaka and Hironori Sagara
J. Clin. Med. 2020, 9(11), 3698; https://doi.org/10.3390/jcm9113698 - 18 Nov 2020
Cited by 32 | Viewed by 3424
Abstract
Airway epithelium plays an important role as the first barrier from external pathogens, including bacteria, viruses, chemical substances, and allergic components. Airway epithelial cells also have pivotal roles as immunological coordinators of defense mechanisms to transfer signals to immunologic cells to eliminate external [...] Read more.
Airway epithelium plays an important role as the first barrier from external pathogens, including bacteria, viruses, chemical substances, and allergic components. Airway epithelial cells also have pivotal roles as immunological coordinators of defense mechanisms to transfer signals to immunologic cells to eliminate external pathogens from airways. Impaired airway epithelium allows the pathogens to remain in the airway epithelium, which induces aberrant immunological reactions. Dysregulated functions of asthmatic airway epithelium have been reported in terms of impaired wound repair, fragile tight junctions, and excessive proliferation, leading to airway remodeling, which contributes to aberrant airway responses caused by external pathogens. To maintain airway epithelium integrity, a family of epidermal growth factor receptors (EGFR) have pivotal roles in mechanisms of cell growth, proliferation, and differentiation. There are extensive studies focusing on the relation between EGFR and asthma pathophysiology, which describe airway remodeling, airway hypermucus secretion, as well as immunological responses of airway inflammation. Furthermore, the second EGFR family member, erythroblastosis oncogene B2 (ErbB2), has been recognized to be involved with impaired wound recovery and epithelial differentiation in asthmatic airway epithelium. In this review, the roles of the EGFR family in asthmatic airway epithelium are focused on to elucidate the pathogenesis of airway epithelial dysfunction in asthma. Full article
(This article belongs to the Special Issue New Frontiers in Asthma Treatment & Management)
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15 pages, 890 KiB  
Review
Hypercapnia: An Aggravating Factor in Asthma
by Masahiko Shigemura, Tetsuya Homma and Jacob I Sznajder
J. Clin. Med. 2020, 9(10), 3207; https://doi.org/10.3390/jcm9103207 - 05 Oct 2020
Cited by 6 | Viewed by 10601
Abstract
Asthma is a common chronic respiratory disorder with relatively good outcomes in the majority of patients with appropriate maintenance therapy. However, in a small minority, patients can experience severe asthma with respiratory failure and hypercapnia, necessitating intensive care unit admission. Hypercapnia occurs due [...] Read more.
Asthma is a common chronic respiratory disorder with relatively good outcomes in the majority of patients with appropriate maintenance therapy. However, in a small minority, patients can experience severe asthma with respiratory failure and hypercapnia, necessitating intensive care unit admission. Hypercapnia occurs due to alveolar hypoventilation and insufficient removal of carbon dioxide (CO2) from the blood. Although mild hypercapnia is generally well tolerated in patients with asthma, there is accumulating evidence that elevated levels of CO2 can act as a gaso-signaling molecule, triggering deleterious effects in various organs such as the lung, skeletal muscles and the innate immune system. Here, we review recent advances on pathophysiological response to hypercapnia and discuss potential detrimental effects of hypercapnia in patients with asthma. Full article
(This article belongs to the Special Issue New Frontiers in Asthma Treatment & Management)
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21 pages, 1676 KiB  
Review
Virus-Induced Asthma Exacerbations: SIRT1 Targeted Approach
by Yosuke Fukuda, Kaho Akimoto, Tetsuya Homma, Jonathan R Baker, Kazuhiro Ito, Peter J Barnes and Hironori Sagara
J. Clin. Med. 2020, 9(8), 2623; https://doi.org/10.3390/jcm9082623 - 13 Aug 2020
Cited by 10 | Viewed by 5274
Abstract
The prevalence of asthma has increased worldwide. Asthma exacerbations triggered by upper respiratory tract viral infections remain a major clinical problem and account for hospital admissions and time lost from work. Virus-induced asthma exacerbations cause airway inflammation, resulting in worsening asthma and deterioration [...] Read more.
The prevalence of asthma has increased worldwide. Asthma exacerbations triggered by upper respiratory tract viral infections remain a major clinical problem and account for hospital admissions and time lost from work. Virus-induced asthma exacerbations cause airway inflammation, resulting in worsening asthma and deterioration in the patients’ quality of life, which may require systemic corticosteroid therapy. Despite recent advances in understanding the cellular and molecular mechanisms underlying asthma exacerbations, current therapeutic modalities are inadequate for complete prevention and treatment of these episodes. The pathological role of cellular senescence, especially that involving the silent information regulator 2 homolog sirtuin (SIRT) protein family, has recently been demonstrated in stable and exacerbated chronic respiratory disease states. This review discusses the role of SIRT1 in the pathogenesis of bronchial asthma. It also discusses the role of SIRT1 in inflammatory cells that play an important role in virus-induced asthma exacerbations. Recent studies have hypothesized that SIRT1 is one of major contributors to cellular senescence. SIRT1 levels decrease in Th2 and non-Th2-related airway inflammation, indicating the role of SIRT1 in several endotypes and phenotypes of asthma. Moreover, several models have demonstrated relationships between viral infection and SIRT1. Therefore, targeting SIRT1 is a novel strategy that may be effective for treating virus-induced asthma exacerbations in the future. Full article
(This article belongs to the Special Issue New Frontiers in Asthma Treatment & Management)
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27 pages, 2339 KiB  
Review
The Hidden Burden of Severe Asthma: From Patient Perspective to New Opportunities for Clinicians
by Nicola Scichilone, Peter John Barnes, Salvatore Battaglia, Alida Benfante, Robert Brown, Giorgio Walter Canonica, Gaetano Caramori, Mario Cazzola, Stefano Centanni, Antonella Cianferoni, Angelo Corsico, Giuseppe De Carlo, Fabiano Di Marco, Mina Gaga, Catherine Hawrylowicz, Enrico Heffler, Maria Gabriella Matera, Andrea Matucci, Pierluigi Paggiaro, Alberto Papi, Todor Popov, Paola Rogliani, Pierachille Santus, Paolo Solidoro, Alkis Togias and Louis-Philippe Bouletadd Show full author list remove Hide full author list
J. Clin. Med. 2020, 9(8), 2397; https://doi.org/10.3390/jcm9082397 - 27 Jul 2020
Cited by 7 | Viewed by 4368
Abstract
Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the [...] Read more.
Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the “International Course on Severe Asthma” that took place in Palermo, Italy, on May 10–11, 2019. Emerging topics in severe asthma were addressed and discussed among experts, with special focus on patient’s needs and research opportunities, with the aim to highlight the unanswered questions in the diagnostic process and therapeutic approach. Full article
(This article belongs to the Special Issue New Frontiers in Asthma Treatment & Management)
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19 pages, 711 KiB  
Review
Physical Activity: A Missing Link in Asthma Care
by Marios Panagiotou, Nikolaos G. Koulouris and Nikoletta Rovina
J. Clin. Med. 2020, 9(3), 706; https://doi.org/10.3390/jcm9030706 - 05 Mar 2020
Cited by 45 | Viewed by 9723
Abstract
Asthma is the commonest respiratory disease and one of unceasingly increasing prevalence and burden. As such, asthma has attracted a major share or scientific interest and clinical attention. With the various clinical and pathophysiological aspects of asthma having been extensively investigated, the important [...] Read more.
Asthma is the commonest respiratory disease and one of unceasingly increasing prevalence and burden. As such, asthma has attracted a major share or scientific interest and clinical attention. With the various clinical and pathophysiological aspects of asthma having been extensively investigated, the important association between asthma and physical activity remains underappreciated and insufficiently explored. Asthma impacts adversely on physical activity. Likewise, poor physical activity may lead to worse asthma outcomes. This concise clinical review presents the current recommendations for physical activity, discusses the available evidence on physical activity in asthma, and examines the causes of low physical activity in adult asthmatic patients. It also reviews the effect of daily physical activity and exercise training on the pathology and clinical outcomes of asthma. Finally, it summarizes the evidence on interventions targeting physical activity in asthma. Full article
(This article belongs to the Special Issue New Frontiers in Asthma Treatment & Management)
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