https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48016 To the Editor: The major 17q12-21 asthma susceptibility and exacerbation locus1 has been identified as the only genetic locus that is also reproducibly associated with total white blood cell count.2 However, it is not known whether there is a common gene within this locus that links these phenotypic traits. The colony-stimulating factor-3 (CSF3) gene, alternatively known as G-CSF, resides within this locus. CSF3 binds exclusively to CSF3 receptor (CSF3R, or CD114/G-CSFR), which is highly expressed on mature neutrophils and to a lesser extent on mononuclear cells, platelets, and lung interstitial stromal cells. Although CSF3R/CD114 signaling can dictate the intensity of the host defense inflammatory response during bacterial infection by regulating neutrophil granulopoiesis and trafficking, its role in the infection-dependent transition to persistent, severe asthma has not been investigated. Neonatal colonization of the nasopharynx by potentially pathogenic bacteria including Streptococcus pneumoniae is also a risk factor for asthma development.3 The Childhood Asthma Study found that children with atopy and chronic wheeze at age 5 years were twice as likely to have been colonized with S pneumoniae as neonates.4 The authors suggest that transient incursions of nasopharyngeal bacteria into the lower airways triggered by a fever-causing viral respiratory infection (respiratory syncytial virus or influenza virus) increases the risk of developing persistent asthma in atopic children. However, a plausible mechanism linking these cofactors is yet to be identified. In this study, we tested the hypothesis that CSF3-CSF3R signaling dictates the severity of infectiondependent asthma at a cellular and molecular level.]]> Wed 15 Feb 2023 10:19:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55876 Wed 03 Jul 2024 14:09:42 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43636 Tue 27 Sep 2022 09:39:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52014 Tue 26 Sep 2023 11:42:59 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39820 Tue 26 Jul 2022 11:33:21 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46351 n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. Results: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. Conclusion: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.]]> Tue 15 Nov 2022 15:15:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47015 Tue 13 Dec 2022 11:55:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30756 Thu 03 Feb 2022 12:22:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51768 Mon 18 Sep 2023 14:30:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37632 Fri 21 Jan 2022 09:39:15 AEDT ]]>