Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease

Abstract

BackgroundThere has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.MethodsWe prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012. Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.ResultsAirway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively). Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05). Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads. Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs. No association was observed between inflammation and health status (p > 0.05).ConclusionsAirway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique. The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae. However, discordance between inflammation and health status was observed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users.

Haemophilus, Antibiotic Therapy and the Airway Microbiome in Chronic Obstructive Pulmonarydisease

“…The quarter of patients in whom H. influenzae dominated the microbiota exhibited much higher levels of inflammatory cytokines and bacterial load than other cases. This is consistent with previous reports (24) using species-specific techniques but has not previously been shown in the full context of the airway microbiome. Airway inflammation predicts exacerbation frequency (25) and lung function decline (26), and these patients are therefore at high risk.…”

Potential impact of a Moraxella catarrhalis vaccine in COPD

“…Cumulative results from prospective COPD studies [22, 30, 31]. In each study, bacterial species were differentiated by culture or qPCR.…”

Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management

“…The beneficial effect of azithromycin (reduction in risk for exacerbation) is accompanied by a reduction in plasma sTNFrII levels which also suggests a possible surrogate outcome measure (72). Ultimately, since different bacteria can elicit different host responses (73–75), optimal endotyping of COPD based on bacterial colonization may depend on methods that are specific for pathogenic species.…”