BibTex format
@article{Singanayagam:2019:10.1152/ajplung.00253.2019,
author = {Singanayagam, A and Loo, S-L and Calderazzo, MA and Finney, LJ and Trujillo, Torralbo M-B and Bakhsoliani, E and Girkin, J and Veerati, PC and Pathinayake, PS and Nichol, KS and Reid, AT and Footitt, J and Johnston, SL and Bartlett, NW and Mallia, P},
doi = {10.1152/ajplung.00253.2019},
journal = {American Journal of Physiology: Lung Cellular and Molecular Physiology},
pages = {L893--L903},
title = {Antiviral immunity is impaired in COPD patients with frequent exacerbations},
url = {http://dx.doi.org/10.1152/ajplung.00253.2019},
volume = {317},
year = {2019}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub-group requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (>2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the anti-viral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro RV-infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 weeks following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate anti-microbial immunity in the lung could be a viable strategy for prevention/treatment of frequent exacerbations.
AU - Singanayagam,A
AU - Loo,S-L
AU - Calderazzo,MA
AU - Finney,LJ
AU - Trujillo,Torralbo M-B
AU - Bakhsoliani,E
AU - Girkin,J
AU - Veerati,PC
AU - Pathinayake,PS
AU - Nichol,KS
AU - Reid,AT
AU - Footitt,J
AU - Johnston,SL
AU - Bartlett,NW
AU - Mallia,P
DO - 10.1152/ajplung.00253.2019
EP - 903
PY - 2019///
SN - 1040-0605
SP - 893
TI - Antiviral immunity is impaired in COPD patients with frequent exacerbations
T2 - American Journal of Physiology: Lung Cellular and Molecular Physiology
UR - http://dx.doi.org/10.1152/ajplung.00253.2019
UR - https://www.ncbi.nlm.nih.gov/pubmed/31513433
UR - http://hdl.handle.net/10044/1/73626
VL - 317
ER -