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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. 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 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.
This article was published in the following journal.
Name: American journal of physiology. Lung cellular and molecular physiology
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A species of Bifidobacterium that occurs in the GASTROINTESTINAL TRACT of mammals and healthy humans from birth until late adulthood. It produces ANTI-VIRAL AGENTS and ANTI-INFLAMMATORY AGENTS and is used as a PROBIOTIC.
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An autosomal recessive trait with impaired cell-mediated immunity. About 15 human papillomaviruses are implicated in associated infection, four of which lead to skin neoplasms. The disease begins in childhood with red papules and later spreads over the body as gray or yellow scales.
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COPD (chronic obstructive pulmonary disease)
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