Anthony Kicic1, Emma de Jong2, Kak-Ming Ling3, Kristy Nichol4, Denise Anderson2, Peter A B Wark4, Darryl A Knight5, Anthony Bosco2, Stephen M Stick6. 1. Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, Australia; Occupation and Environment, School of Public Health, Curtin University, Perth, Australia; School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Australia; Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Nedlands, Australia. Electronic address: Anthony.Kicic@telethonkids.org.au. 2. Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, Australia. 3. School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia. 4. School of Medicine and Public Health, University of Newcastle, Callaghan, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, Australia. 5. School of Medicine and Public Health, University of Newcastle, Callaghan, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, Australia; Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada. 6. Telethon Kids Institute, Centre for Health Research, The University of Western Australia, Nedlands, Australia; School of Biomedical Sciences, The University of Western Australia, Nedlands, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Australia; Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, The University of Western Australia and Harry Perkins Institute of Medical Research, Nedlands, Australia.
Abstract
BACKGROUND: Emerging evidence suggests that disease vulnerability is expressed throughout the airways, the so-called unified airway hypothesis, but the evidence to support this is predominantly indirect. OBJECTIVES: We sought to establish the transcriptomic profiles of the upper and lower airways and determine their level of similarity irrespective of airway symptoms (wheeze) and allergy. METHODS: We performed RNA sequencing on upper and lower airway epithelial cells from 63 children with or without wheeze and accompanying atopy, using differential gene expression and gene coexpression analyses to determine transcriptional similarity. RESULTS: We observed approximately 91% homology in the expressed genes between the 2 sites. When coexpressed genes were grouped into modules relating to biological functions, all were found to be conserved between the 2 regions, resulting in a consensus network containing 16 modules associated with ribosomal function, metabolism, gene expression, mitochondrial activity, and antiviral responses through IFN activity. Although symptom-associated gene expression changes were more prominent in the lower airway, they were reflected in nasal epithelium and included IL-1 receptor like 1, prostaglandin-endoperoxide synthase 1, CCL26, and periostin. Through network analysis we identified a cluster of coexpressed genes associated with atopic wheeze in the lower airway, which could equally distinguish atopic and nonatopic phenotypes in upper airway samples. CONCLUSIONS: We show that the upper and lower airways are significantly conserved in their transcriptional composition, and that variations associated with disease are present in both nasal and tracheal epithelium. Findings from this study supporting a unified airway imply that clinical insight regarding the lower airway in health and disease can be gained from studying the nasal epithelium.
BACKGROUND: Emerging evidence suggests that disease vulnerability is expressed throughout the airways, the so-called unified airway hypothesis, but the evidence to support this is predominantly indirect. OBJECTIVES: We sought to establish the transcriptomic profiles of the upper and lower airways and determine their level of similarity irrespective of airway symptoms (wheeze) and allergy. METHODS: We performed RNA sequencing on upper and lower airway epithelial cells from 63 children with or without wheeze and accompanying atopy, using differential gene expression and gene coexpression analyses to determine transcriptional similarity. RESULTS: We observed approximately 91% homology in the expressed genes between the 2 sites. When coexpressed genes were grouped into modules relating to biological functions, all were found to be conserved between the 2 regions, resulting in a consensus network containing 16 modules associated with ribosomal function, metabolism, gene expression, mitochondrial activity, and antiviral responses through IFN activity. Although symptom-associated gene expression changes were more prominent in the lower airway, they were reflected in nasal epithelium and included IL-1 receptor like 1, prostaglandin-endoperoxide synthase 1, CCL26, and periostin. Through network analysis we identified a cluster of coexpressed genes associated with atopic wheeze in the lower airway, which could equally distinguish atopic and nonatopic phenotypes in upper airway samples. CONCLUSIONS: We show that the upper and lower airways are significantly conserved in their transcriptional composition, and that variations associated with disease are present in both nasal and tracheal epithelium. Findings from this study supporting a unified airway imply that clinical insight regarding the lower airway in health and disease can be gained from studying the nasal epithelium.
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Authors: Matthew C Altman; Agustin Calatroni; Sima Ramratnam; Daniel J Jackson; Scott Presnell; Mario G Rosasco; Peter J Gergen; Leonard B Bacharier; George T O'Connor; Megan T Sandel; Meyer Kattan; Robert A Wood; Cynthia M Visness; James E Gern Journal: J Allergy Clin Immunol Date: 2021-03-10 Impact factor: 10.793
Authors: Jessica Hillas; Denby J Evans; Sherlynn Ang; Thomas Iosifidis; Luke W Garratt; Naomi Hemy; Elizabeth Kicic-Starcevich; Shannon J Simpson; Anthony Kicic Journal: ERJ Open Res Date: 2021-06-07
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Authors: Rebecca L Watkinson; Kevin Looi; Ingrid A Laing; Antonella Cianferoni; Anthony Kicic Journal: Front Immunol Date: 2021-11-29 Impact factor: 7.561
Authors: Thomas Iosifidis; Erika N Sutanto; Samuel T Montgomery; Patricia Agudelo-Romero; Kevin Looi; Kak-Ming Ling; Nicole C Shaw; Luke W Garratt; Jessica Hillas; Kelly M Martinovich; Elizabeth Kicic-Starcevich; Shyan Vijayasekaran; Francis J Lannigan; Paul J Rigby; Darryl A Knight; Stephen M Stick; Anthony Kicic Journal: J Pers Med Date: 2021-12-07