Review
Biochemistry & Molecular Biology
Patricia Ramos-Ramirez, Omar Tliba
Summary: Severe asthma patients may have poor response to inhaled glucocorticoid therapy, known as glucocorticoid insensitivity, which poses a challenge in asthma management. Airway smooth muscle cells, a target of glucocorticoid therapy in asthma, play a crucial role in bronchoconstriction, inflammation, and remodeling associated with asthma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Physiology
Dora (Jun Ping) Xiong, James G. Martin, Anne-Marie Lauzon
Summary: Asthma is a common chronic inflammatory disease of the airways that varies in its presentation and severity. Airway smooth muscle is the major contributor to airway narrowing and asthma symptoms. Various factors can contribute to the dysfunction of airway smooth muscle. Methodological limitations in studying the airways have hindered our understanding of asthma mechanisms.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Luigino Calzetta, Marina Aiello, Annalisa Frizzelli, Giuseppina Bertorelli, Beatrice Ludovica Ritondo, Paola Rogliani, Alfredo Chetta
Summary: AHR is a central pathophysiological feature of asthma, involving ASM with pro-inflammatory and immunomodulatory actions. mAbs target various inflammatory mediators to modulate ASM contractility, showing potential in treating severe asthma by preventing AHR.
Article
Cell Biology
Santosh K. Yadav, Pawan Sharma, Sushrut D. Shah, Reynold A. Panettieri, Taku Kambayashi, Raymond B. Penn, Deepak A. Deshpande
Summary: Inhibition of DGK activates PKA signaling pathway and induces COX expression and PGE(2) production in ASM cells, leading to attenuation of ASM contraction. This novel mechanism suggests DGK as a potential therapeutic target for effective bronchoprotection in asthma.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Miguel Angel Hernandez-Lara, Santosh K. Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn, Taku Kambayashi, Deepak A. Deshpande
Summary: Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. The inhibition of diacylglycerol kinase (DGK) reduces the conversion of diacylglycerol (DAG) into phosphatidic acid (PA) and inhibits ASM cell proliferation. These findings suggest that DGK may serve as a potential drug target for mitigating airway remodeling in asthma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Shengjie Xu, Nikhil Karmacharya, Joanna Woo, Gaoyuan Cao, Changjiang Guo, Andrew Gow, Reynold A. Panettieri, Joseph A. Jude
Summary: Bronchomotor tone modulation by airway smooth muscle shortening is a key mechanism that increases airway resistance in asthma. Altered glucose metabolism in inflammatory and airway structural cells is associated with asthma. This study revealed that glycolysis modulates excitation-contraction coupling in human airway smooth muscle cells, and inhibiting glycolysis can attenuate bronchoconstriction.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Endocrinology & Metabolism
Michael M. Grunstein
Summary: Homeostasis is the process by which the body maintains internal stability within a narrow range. Disrupted homeostasis at the tissue or systemic level leads to disease. In asthma, the pivotal site of disrupted homeostasis is the airway smooth muscle (ASM). This article proposes a novel mechanism in which the pro-asthmatic-exposed ASM independently generates its own active glucocorticoid and uses this molecular strategy to prevent induction of the asthmatic state.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Allergy
Thomas J. A. Maguire, Stephanie Yung, Elena Ortiz-Zapater, O. Stephanie Kayode, Stephen Till, Chris Corrigan, Leonard Q. C. Siew, Gregory A. Knock, Grzegorz Woszczek
Summary: S1P plays an important role in regulating airway smooth muscle reactivity and hyperplasia, potentially serving as a novel therapeutic target for asthma and other lung diseases.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Critical Care Medicine
Annika W. M. Goorsenberg, Julia N. S. D'Hooghe, Karthikan Srikanthan, Nick H. T. Ten Hacken, Els J. M. Weersink, Joris J. T. H. Roelofs, Samuel Kemp, Elisabeth H. Bel, Pallav L. Shah, Jouke T. Annema, Peter Bonta
Summary: The study shows that bronchial thermoplasty can significantly reduce airway smooth muscle mass and treatment response is associated with serum IgE and eosinophil levels, rather than baseline ASM mass.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Jin-Mei Xue, Yun-Fang An, Li-Min Suo, Li-Hua Mo, Gui Yang, Xiang-Qian Luo, Da-Bo Liu, Chang-Qing Zhao, Ping-Chang Yang
Summary: This study found that the apoptosis inhibitor Livin promotes the development of corticosteroid resistance (CR) in the airways by enhancing the expression of thymic stromal lymphopoietin (TSLP) and glucocorticoid receptor beta (GRβ) in epithelial cells, eosinophils, and neutrophils. Depletion of Livin or inhibition of TSLP effectively attenuated CR and airway allergy.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Review
Endocrinology & Metabolism
Gisela I. Mazaira, Graciela Piwien Pilipuk, Mario D. Galigniana
Summary: Steroid receptors form soluble heterocomplexes with the 90-kDa heat-shock protein (Hsp90) and other chaperones and co-chaperones. The assembly and composition of the oligomer is influenced by the presence and nature of the bound steroid. Steroid binding triggers the localization of receptors to the nucleus via the transportosome, a molecular machinery system that can also be utilized by other soluble proteins.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2021)
Review
Allergy
Yan Xie, Peter W. Abel, Thomas B. Casale, Yaping Tu
Summary: Asthma can be classified into T2 and non-T2 types, with non-T2 asthma being more severe and often unresponsive to treatment. Recent studies suggest that non-T2 asthma is associated with T(H)17 cell immune responses, which may contribute to corticosteroid insensitivity in asthma.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Nathalie Fuentes, Morgan McCullough, Reynold A. Panettieri, Kirk M. Druey
Summary: Asthma is a prevalent disorder characterized by chronic lung inflammation and reversible airways obstruction, with features including increased airway narrowing, excessive mucus secretion, airway remodeling, and airways hyperresponsiveness. Environmental factors such as allergens, viruses, and air pollution can promote asthma, leading to symptoms like cough, wheezing, and shortness of breath. G-protein-coupled receptors play a central role in asthma, with various treatments targeting these receptors to regulate airway smooth muscle tone and lung inflammation.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Immunology
Chun-Yu Lo, Chun-Hua Wang, Chih-Wei Wang, Chih-Jung Chen, Hung-Yu Huang, Fu-Tsai Chung, Yu-Chen Huang, Chang-Wei Lin, Chung-Shu Lee, Chun-Yu Lin, Chiung-Hung Lin, Po-Jui Chang, Ting-Yu Lin, Chih-Chen Heh, Jung-Ru He, Kian Fan Chung
Summary: This study found that the differential expression of IL-17 and up-regulation of GR-beta (a glucocorticoid receptor) are associated with corticosteroid sensitivity in different interstitial lung diseases. Patients with idiopathic pulmonary fibrosis had higher levels of IL-17 and GR-beta expression, and the radiographic progression after treatment was positively correlated with IL-17 expression and GR-beta/GR-alpha ratio.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Shengjie Xu, Reynold A. Panettieri, Joseph Jude
Summary: This review summarizes the current knowledge of asthma metabolomics at systemic and cellular levels. The findings demonstrate that various metabolic pathways related to energy metabolism, macromolecular biosynthesis, and redox signaling are differentially modulated in asthma. Airway smooth muscle cells play a crucial role in asthma by contributing to airway hyperreactivity, inflammatory mediator release, and remodeling.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Allergy
Franziska Roth-Walter, Ian M. Adcock, Cristina Benito-Villalvilla, Rodolfo Bianchini, Leif Bjermer, Onur Boyman, Gaetano Caramori, Luigi Cari, Kian Fan Chung, Zuzana Diamant, Ibon Eguiluz-Gracia, Edward F. Knol, Antonios Kolios, Francesca Levi-Schaffer, Giuseppe Nocentini, Oscar Palomares, Frank Redegeld, Betty Van Esch, Cristiana Stellato
Summary: Therapeutic advances using targeted biologicals and small-molecule drugs have achieved significant success in treating chronic inflammatory and autoimmune diseases, especially for some severe, treatment-resistant forms. T cell-based therapies aim to cure diseases by delivering engineered specific cytotoxic or regulatory T cells, revolutionizing the field of oncology and offering potential curative options for immune-driven disorders.
Article
Allergy
Angelica Tiotiu, Nazanin Zounemat Kermani, Yusef Badi, Stelios Pavlidis, Philip M. Hansbro, Yi-Ke Guo, Kian Fan Chung, Ian M. Adcock
Summary: The study found that the number of macrophages in severe asthma patients was significantly reduced, but in certain subsets with strong inflammatory pathways, the number and gene signatures of macrophages were enriched in sputum samples.
Article
Allergy
Rui Chen, Charalambos Michaeloudes, Yingmin Liang, Pankaj K. Bhavsar, Kian Fan Chung, Mary S. M. Ip, Judith C. W. Mak
Summary: This study found that ORMDL3 expression was upregulated in airway smooth muscle cells (ASMCs) of smokers and COPD patients. ORMDL3 may mediate the activation of unfolded protein response pathways in response to cigarette smoke exposure, leading to ASMC injury.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Charalambos Michaeloudes, Hisham Abubakar-Waziri, Ramzi Lakhdar, Katie Raby, Piers Dixey, Ian M. Adcock, Sharon Mumby, Pankaj K. Bhavsar, Kian Fan Chung
Summary: The lungs are exposed to reactive oxygen species (ROS) produced from various sources, including inhalation of oxygen, smoke, and air pollutants. Intracellular ROS play a role in cell signaling and are regulated by various cellular components. In asthma, over-production of ROS and impaired antioxidant responses lead to oxidative stress, which contributes to airway inflammation and hyper-responsiveness. Understanding the complex role of ROS in asthma pathogenesis is important for developing targeted redox therapies.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Review
Respiratory System
Qi Liu, Hai Zhang, Baohui Han, Handong Jiang, Kian Fan Chung, Feng Li
Summary: This review article discusses the importance of recognizing interstitial lung abnormalities (ILAs) which can progress into interstitial lung disease (ILD) without intervention. Literature review on ILAs prevalence, etiology, symptoms, diagnostic biomarkers, clinical associations, and management was conducted from 2008 to 2020. Timely diagnosis, close monitoring, and appropriate intervention are essential for effectively managing ILAs, and further research is needed to improve management strategies.
EXPERT REVIEW OF RESPIRATORY MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Julia Frankenberg Garcia, Andrew Rogers, Judith C. W. Mak, Andrew J. Halayko, Christopher K. M. Hui, Bingling Xu, Kian Fan Chung, Tristan Rodriguez, Charalambos Michaeloudes, Pankaj K. Bhavsar
Summary: Mitochondrial transfer from mesenchymal stem cells to airway smooth muscle cells can attenuate oxidative stress-induced damage in COPD. However, it is not known whether structural cells in the lungs can also exchange mitochondria and what role this plays in modulating bioenergetics and cellular function. Here, researchers found that airway smooth muscle cells in both healthy ex-smokers and COPD patients can exchange mitochondria, partially through extracellular vesicles. Exposure to cigarette smoke induces mitochondrial dysfunction and increases mitochondrial donation by the smooth muscle cells, suggesting it may be a stress response mechanism. Moreover, the study showed that the received mitochondria enhance mitochondrial biogenesis and respiration while reducing cell proliferation in healthy ex-smoker airway smooth muscle cells.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Environmental Sciences
Ramzi Lakhdar, Sharon Mumby, Hisham Abubakar-Waziri, Alexandra Porter, Ian M. Adcock, Kian Fan Chung
Summary: Air pollution has a detrimental effect on respiratory health, and different types of particulate matter can activate various biological processes. However, most studies on the molecular mechanisms of air pollution-induced toxicity have been conducted in cell lines rather than primary cells from healthy individuals or patients with airway diseases. This review highlights the importance of studying the impact of submicron-sized pollutants on primary human cells derived from the respiratory tract to better understand the pathophysiological pathways activated by different particulate matter.
ENVIRONMENTAL POLLUTION
(2022)
Article
Respiratory System
Stephany Sanchez-Ovando, Stelios Pavlidis, Nazanin Zounemat Kermani, Katherine Joanne Baines, Daniel Barker, Peter G. Gibson, Lisa G. Wood, Ian M. Adcock, Kian Fan Chung, Jodie Louise Simpson, Peter A. B. Wark
Summary: This study identified differentially expressed pathways in severe asthma patients compared to mild/moderate asthma patients and healthy controls. The results suggest that CD4(+) T cells, mast cells, and pathways linked to ongoing airway remodelling play a crucial role in the pathogenesis of severe asthma.
Article
Medicine, General & Internal
Kian Fan Chung, Lorcan McGarvey, Woo-Jung Song, Anne B. Chang, Kefang Lai, Brendan J. Canning, Surinder S. Birring, Jaclyn A. Smith, Stuart B. Mazzone
Summary: Chronic cough is a prevalent and challenging condition with various underlying causes. It is associated with cough hypersensitivity, characterized by excessive coughing in response to stimuli, resulting in significant impact on patients' quality of life. Advances in understanding the mechanisms of cough hypersensitivity have led to the development of new therapies for chronic cough in adults. Personalized treatment approaches and phenotyping cough patients may hold promise for future management.
NATURE REVIEWS DISEASE PRIMERS
(2022)
Review
Respiratory System
Anna Rattu, Ekaterina Khaleva, Chris Brightling, Sven-Erik Dahlen, Apostolos Bossios, Louise Fleming, Kian Fan Chung, Erik Melen, Ratko Djukanovic, Rekha Chaudhuri, Andrew Exley, Gerard H. Koppelman, Arnaud Bourdin, Franca Rusconi, Celeste Porsbjerg, Courtney Coleman, Clare Williams, Hanna Nielsen, Elizabeth Davin, Phil Taverner, Sofia Romagosa Vilarnau, Graham Roberts
Summary: The recommendations of the National Institutes of Health (NIH) on outcome measurement instruments for asthma are widely used in clinical practice and research. However, there is no consensus on which outcome measures are important to patients with severe asthma and are valid for this population. Guidelines recommend the use of patient-reported outcome measures (PROMs) to evaluate treatment response, but do not provide specific instruments. Additionally, the outcomes that patients consider important, such as quality of life, are not consistently considered by physicians when evaluating treatment response.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Review
Respiratory System
Ekaterina Khaleva, Anna Rattu, Chris Brightling, Andrew Bush, Arnaud Bourdin, Apostolos Bossios, Kian Fan Chung, Rekha Chaudhuri, Courtney Coleman, Ratko Djukanovic, Sven-Erik Dahlen, Andrew Exley, Louise Fleming, Stephen J. Fowler, Atul Gupta, Eckard Hamelmann, Gerard H. Koppelman, Erik Melen, Vera Mahler, Paul Seddon, Florian Singer, Celeste Porsbjerg, Valeria Ramiconi, Franca Rusconi, Valentyna Yasinska, Graham Roberts
Summary: This study systematically reviewed the definitions of response to biologics for severe asthma and found that although high-quality definitions are available, most are based on minimal clinically important difference (MCID) or minimal important difference (MID), which may not be sufficient to justify the cost-effectiveness of continuing biologics.
Review
Allergy
Isabella Annesi-Maesano, Lorenzo Cecchi, Benedetta Biagioni, Kian Fan Chung, Bernard Clot, Martine Collaud Coen, Gennaro D. Amato, Athanasios Damialis, Javier Dominguez-Ortega, Carmen Galan, Stefanie Gilles, Stephen Holgate, Mohamed Jeebhay, Stelios Kazadzis, Nikolaos G. Papadopoulos, Santiago Quirce, Joaquin Sastre, Fiona Tummon, Claudia Traidl-Hoffmann, Jolanta Walusiak-Skorupa, Pablo Alonso-Coello, Carlos Canelo-Aybar, Yahveth Cantero-Fortiz, David Rigau, Josefina Salazar, Francisca Verdugo-Paiva, Marek Jutel, Cezmi A. Akdis, Ioana Agache
Summary: This study aimed to investigate the impact of pollen exposure on asthma exacerbations and found that outdoor pollen exposure may have an effect on asthma exacerbation, particularly in children under 18 years of age. Further research is needed to evaluate the effects of pollen on asthma exacerbation, considering factors such as pollen sensitization, hay fever, air pollution, green spaces, and pre-existing medications, in order to improve preventive measures.
Article
Virology
Hung-Yu Huang, Chun-Yu Lo, Fu-Tsai Chung, Yu-Tung Huang, Po-Chuan Ko, Chang-Wei Lin, Yu-Chen Huang, Kian Fan Chung, Chun-Hua Wang
Summary: This study aimed to investigate the clinical outcomes and identify risk factors associated with hospitalization and mortality following influenza infection in adult patients with bronchiectasis. The results showed that patients with bronchiectasis had higher hospitalization rates and mortality rates in influenza-related infection. Influenza infection exacerbated the severity of bronchiectasis, and older patients, those with high bronchiectasis aetiology comorbidity index (BACI), and previous exacerbations were more likely to be hospitalized and have higher mortality rates.
Article
Allergy
Han-Kyul Kim, Ji-One Kang, Ji Eun Lim, Tae-Woong Ha, Hae Un Jung, Won Jun Lee, Dong Jun Kim, Eun Ju Baek, Ian M. M. Adcock, Kian Fan Chung, Tae-Bum Kim, Bermseok Oh
Summary: Using the UK Biobank dataset, we identified four distinct asthma subtypes based on onset age and lung function. Our study revealed that early onset asthma with reduced lung function had the highest genetic predisposition. Furthermore, clusters with reduced lung function were genetically distinct from clusters with normal lung function.
CLINICAL AND TRANSLATIONAL ALLERGY
(2023)
Article
Allergy
Yu Ri Kang, Ji-Yoon Oh, Ji-Hyang Lee, Peter M. Small, Kian Fan Chung, Woo-Jung Song
Summary: This paper describes a case of long-COVID severe refractory cough and discusses its characteristics, management, and clinical implications. Currently, there is limited understanding of the clinical features and course of long-COVID cough, and evidence-based treatment is lacking.
ASIA PACIFIC ALLERGY
(2022)