Association Between Pathogens Detected Using Quantitative Polymerase Chain Reaction With Airway Inflammation in COPD at Stable State and Exacerbations

Barker, Bethan; Haldar, Koirobi; Patel, Hemu; Pavord, Ian D.; Barer, Michael R.; Brightling, Christopher E.; Bafadhel, Mona

doi:10.1378/chest.14-0764

Cited by 74 publications

(76 citation statements)

References 43 publications

(57 reference statements)

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“…Compatible with our results is the previous finding of a significantly lower level of sputum CCL13 (an eosinophil associated cytokine) in PPM positive COPD patients [26]. …”

Section: Discussionsupporting

confidence: 82%

Blood and sputum eosinophils in COPD; relationship with bacterial load

et al. 2017

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BackgroundSputum and blood eosinophil counts predict corticosteroid effects in COPD patients. Bacterial infection causes increased airway neutrophilic inflammation. The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain. We tested the hypothesis that bacterial load and eosinophil counts are inversely related.MethodsCOPD patients were seen at stable state and exacerbation onset. Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae. PPM positive was defined as total load ≥1 × 104copies/ml. Sputum and whole blood were analysed for differential cell counts.ResultsAt baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs. 1.25% respectively, p = 0.01). Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs. 0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples.ConclusionsThese findings indicate an inverse relationship between bacterial infection and eosinophil counts. Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-017-0570-5) contains supplementary material, which is available to authorized users.

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“…Compatible with our results is the previous finding of a significantly lower level of sputum CCL13 (an eosinophil associated cytokine) in PPM positive COPD patients [26]. …”

Section: Discussionsupporting

confidence: 82%

Blood and sputum eosinophils in COPD; relationship with bacterial load

et al. 2017

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“…In the 20-year prospective study noted above, in sputum samples from which M. catarrhalis was isolated, NTHi was isolated from 26.7%, S. pneumoniae was isolated from 5.7%, and Pseudomonas aeruginosa was isolated from 4.8% [22]. These data were combined with subsequent prospective studies in Figure 2, which highlights the role of M. catarrhalis as a co-pathogen in COPD [29–31]. Furthermore, M. catarrhalis is a co-pathogen in the setting of otitis media in children.…”

Section: Catarrhalis As a Co-pathogenmentioning

confidence: 96%

Potential impact of a Moraxella catarrhalis vaccine in COPD

Perez

Murphy

2019

Vaccine

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Moraxella catarrhalis is the second most common cause of exacerbations in adults with COPD, resulting in enormous morbidity and mortality in this clinical setting. Vaccine development for M. catarrhalis has lagged behind the other two important causes of exacerbations in COPD, nontypeable Haemophilus influenzae and Streptococcus pneumoniae. While no licensed vaccine is currently available for M. catarrhalis, several promising candidate vaccine antigens have been identified and characterized and are close to entering clinical trials. Key steps that are required to advance vaccines for M. catarrhalis along the translational pipeline include standardization of assay systems to assess candidate antigens, identification of a reliable correlate of protection and expansion of partnerships between industry, academia and government to overcome regulatory hurdles. A vaccine to prevent M. catarrhalis infections in COPD would have a major impact in reducing morbidity, mortality and healthcare costs in COPD.

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“…Although non-significant, we did identify a moderate correlation of H. influenzae individual pathogen-specific qPCR with PTX3 during an exacerbation but not at stable state. This is unsurprising as H. influenzae is a commonly isolated pathogen in COPD patients39 and is the main driver of inflammation 40. Further work is needed to fully investigate the role of individual pathogens in PTX3 expression.…”

Section: Discussionmentioning

confidence: 99%

Investigating the role of pentraxin 3 as a biomarker for bacterial infection in subjects with COPD

Thulborn¹,

Dilpazir²,

Haldar³

et al. 2017

COPD

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BackgroundPentraxin 3 (PTX3) is an acute phase protein, involved in antibacterial resistance. Recent studies have shown PTX3 levels to be elevated in the presence of a bacterial infection and in a murine sepsis model.ObjectiveWe aim to investigate if sputum PTX3 can be used as a biomarker for bacterial infection in subjects with COPD.Materials and methodsSputum samples from 142 COPD patients (102 men) with a mean (range) age of 69 years (45–85) and mean (SD) post-bronchodilator percentage predicted forced expiratory volume in 1 second (FEV1) of 50% (19) were analyzed for PTX3, using a commercial assay at stable state and during an exacerbation. Association with bacteria, from culture, quantitative real-time polymerase chain reaction (qPCR) and colony-forming units (CFU) was investigated.ResultsThe geometric mean (95% CI) PTX3 level at stable state was 50.5 ng/mL (41.4–61.7). PTX3 levels correlated with absolute neutrophil count in sputum (r=0.37; P<0.01), but not FEV1 or health status. There was a weak correlation between PTX3 and bacterial load (CFU: r=0.29, P<0.01; 16S qPCR: r=0.18, P=0.05). PTX3 was a poor predictor of bacterial colonization (defined as >105 CFU/mL at stable state) with a receiver-operating characteristic (ROC) area under the curve (AUC) of 0.59 and 95% confidence interval (CI) 0.43–0.76 (P=0.21). During an exacerbation, there was a modest increase in PTX3 (fold difference 0.15, 95% of difference 0.02–0.29; P=0.02), and PTX3 fared better at identifying a bacteria-associated exacerbation (ROC AUC 0.65, 95% CI 0.52–0.78, P=0.03).ConclusionPTX3 is associated with bacterial infection in patients with COPD, but its utility as a biomarker for identifying a bacteria-associated exacerbation warrants further studies.

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Association Between Pathogens Detected Using Quantitative Polymerase Chain Reaction With Airway Inflammation in COPD at Stable State and Exacerbations

Cited by 74 publications

References 43 publications

Blood and sputum eosinophils in COPD; relationship with bacterial load

Blood and sputum eosinophils in COPD; relationship with bacterial load

Potential impact of a Moraxella catarrhalis vaccine in COPD

Investigating the role of pentraxin 3 as a biomarker for bacterial infection in subjects with COPD

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