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Hypoxia‐inducible factor and bacterial infections in chronic obstructive pulmonary disease


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COPD is a seriously disabling respiratory condition that
inexorably progresses to disability and mortality. It
affects approximately 10% of the population globally
with a greater prevalence at advanced ages. Airway bacterial infections complicate the disease course in most COPD patients, leading to increased symptoms, more
rapid decline in lung function, acute exacerbations and
reduced quality of life. With increasing bacterial resistance to antibiotics and adverse effects of conventional treatments, new effective non-antibiotic antimicrobial therapies are urgently needed to manage COPD. Hypoxia-inducible factor (HIF)-1α is an important transcriptional regulator of cellular responses to hypoxia, oxidants and inflammation, and is overexpressed in the lungs of COPD patients. Recent evidence shows that
increased HIF-1α expression can upregulate the
platelet-activating factor receptor (PAFR) on the airway
epithelial surface that is increased in smokers and particularly COPD patients. The receptor is utilized by
PAFR-dependent bacteria (Streptococcus pneumoniae,
Haemophilus influenzae and Pseudomonas aeruginosa)
to induce infection in both the respiratory and gastrointestinal (GI) tracts. However, the importance and mechanism of HIF-1α in augmenting PAFR-dependent
bacterial infections in COPD are poorly understood.
Here, we review the evidence for the roles of local tissue hypoxia-induced inflammation, HIF-1α and PAFR in
facilitating bacterial infections in COPD. Blocking PAFR
may provide a novel antimicrobial approach to manage
bacterial infections in COPD.

Item Type: Journal article
Uncontrolled Keywords: COPD, bacterial infections
Subjects: Q Science > QR Microbiology
R Medicine > RA Public aspects of medicine
Divisions: Schools > Centre for Health & Social Practice
Depositing User: Ronan Otoole
Date Deposited: 11 Feb 2020 01:30
Last Modified: 21 Jul 2023 08:41

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