In this section
@article{Singanayagam:2019:10.1101/632372,
author = {Singanayagam, A and Loo, S-L and Calderazzo, M and Finney, LJ and Trujillo, Torralbo M-B and Bakhsoliani, E and Girkin, J and Veerati, P and Pathinayake, PS and Nichol, KS and Reid, A and Foottit, J and Johnston, SL and Bartlett, NW and Mallia, P},
doi = {10.1101/632372},
title = {Anti-microbial immunity is impaired in COPD patients with frequent exacerbations},
url = {http://dx.doi.org/10.1101/632372},
year = {2019}
}
TY - JOUR
AB - <jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations.<jats:italic>Ex vivo</jats:italic>immune responses to rhinovirus infection in differentiated 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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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. RV-induction of interferon and ISGs<jats:italic>ex vivo</jats:italic>was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators also had reduced sputum levels of the anti-microbial peptide mannose-binding lectin (MBL)-2 with an associated increase in sputum bacterial loads at 2 weeks following virus-associated exacerbation onset. MBL-2 levels correlated negatively with bacterial loads during exacerbation.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These data imp
AU - Singanayagam,A
AU - Loo,S-L
AU - Calderazzo,M
AU - Finney,LJ
AU - Trujillo,Torralbo M-B
AU - Bakhsoliani,E
AU - Girkin,J
AU - Veerati,P
AU - Pathinayake,PS
AU - Nichol,KS
AU - Reid,A
AU - Foottit,J
AU - Johnston,SL
AU - Bartlett,NW
AU - Mallia,P
DO - 10.1101/632372
PY - 2019///
TI - Anti-microbial immunity is impaired in COPD patients with frequent exacerbations
UR - http://dx.doi.org/10.1101/632372
ER -
CBRB
Imperial College London
Flowers Building
Exhibition Road
London SW7 2AZ
