Research Topic

Intra/Extracellular Dynamics of the Respiratory System and Global Airway Disease

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Chronic airway inflammatory diseases such as allergic and non-allergic rhinitis, chronic rhinosinusitis, asthma, chronic obstructive pulmonary disease, primary ciliary dyskinesia, cystic fibrosis, and bronchiectasis have accounted for a substantial healthcare burden worldwide. There are multiple factors and ...

Chronic airway inflammatory diseases such as allergic and non-allergic rhinitis, chronic rhinosinusitis, asthma, chronic obstructive pulmonary disease, primary ciliary dyskinesia, cystic fibrosis, and bronchiectasis have accounted for a substantial healthcare burden worldwide. There are multiple factors and conditions, ranging from mild to severe, that affect the development, onset and progression of these diseases, as well as their response to medical intervention and therapies. Recently, global airways disease (GAD) is the new concept that upper and lower airways form a single functional unit, with upper and lower airway diseases frequently co-occurring. The etiology of GAD remains elusive, however there is growing evidence that the immune response may be implicated.

Various molecular mechanisms linking the upper and lower airways exist, including aspiration of nasal inflammatory cells and mediators into the tracheobronchial tree, hematogenous propagation of inflammatory mediators from one part of the airway to another, stimulation of bone marrow progenitor cells, or the nasobronchial reflex. Airway inflammation is important in the pathogenesis of many upper and lower airway diseases. It is a dynamic trait which varies over time and is modulated by factors such as treatment, infection, environmental exposure and natural progression of disease. Consequently, identification and quantification of the molecular basis of airway inflammation can help to direct appropriate treatment.

The nasal cavity is lined with pseudostratified columnar ciliated epithelium that is also found in the lining of the trachea and upper respiratory tract. In recent years, we have seen several advances in our understanding of the host defense mechanisms of the nasal epithelium. The combined function of ciliated epithelial and secretory cells maintaining efficient mucociliary clearance and a variety of other molecular host defense mechanisms can be considered integral in the fight against airborne pathogens. In addition, the concept on the “immune barrier hypothesis” proposes that defects in the coordinated mechanical barrier and/or the innate immune response of the sinonasal epithelium underlie the pathophysiology of chronic rhinosinusitis. Some interesting data are presented from more advanced studies, which describe the role of epithelial cells during innate and adaptive immune responses to infections caused by respiratory viruses, bacteria and other pathogens in the lung.

In this Research Topic, we will be holistically covering the cellular level, genome, transcriptome and proteome of the bio-physiology and pathophysiological profiles of GAD from clinical to basic research. We aim to accurately assign specific molecular signatures to each endotype and sub-endotype, with implications for bench-to-bedside, rapid diagnosis for precision treatment and improved treatment prediction of biologics usage. It is hoped that this will greatly reduce the workflow of clinical practice in devising the best treatment for GAD patients, improving patient’s quality of life and reducing unnecessary healthcare cost for GAD management.

Potential topics include, but are not limited to:

o Concordance of phenotype and genotype of airway diseases
o Cellular and molecular mechanisms linking the upper and lower airways diseases
o Respiratory epithelium and innate immunity
o Role of respiratory epithelium: bio-physiological and immune barrier hypothesis
o Respiratory epithelium: Host defense against Viral/bacterial/fungal infections
o Destruction of respiratory epithelium in common airway diseases
o Cellular or molecular mechanisms underlying primary or secondary cilia dyskinesia
o Impairment of motile cilia architecture and ciliogenesis in airways diseases
o Intra/extracellular dynamics and markers in study of ciliopathies or ciliogenesis
o Regulation of tissue homeostasis and remodeling in airway epithelium
o Nasal epithelial progenitor and stem cell research
o Regulation and integration of cell-to-cell junctions in airway epithelium
o Intra and extraextracellular regulation of mucin proteins in airway
o Interaction between mucins and cilia in driving chronic airway inflammation
o Transcriptomic or proteomic mechanisms of defective barrier function and inflammation linking upper and lower airway diseases
o Artificial Intelligence (AI)-based analyses on transcriptome, network or biomarkers


Keywords: Global Airway Disease, Intracellular Dynamics, Extracellular Dynamics, Respiratory System, Epithelium, Immune Barrier


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