Biomarkers of inflammation and infections in chronic obstructive pulmonary disease: utility of disease stratification and management

Abstract

Exacerbations landmark the natural course of COPD and are associated with worsening airway obstruction, impact patients health status and have a considerable socio-economic impact. There is a gap in our understanding of different phenotypes of COPD exacerbations and therefore the strategies for treatment of exacerbations have remained unaltered for many years. Diagnosing an exacerbation event is largely subjective and depends on the assessment of presenting symptoms. Treatment of an exacerbation event is often generic and does not take into account different inflammatory mechanisms and underlying aetiological factors. The aim of this work was to determine whether clinically available airway and blood biomarkers can be used, separately or jointly, to identify exacerbations of COPD and in particular bacterial infection at exacerbations.

The analyses were conducted on data collected from the Acute Exacerbation and Respiratory InfectionS in COPD cohort (AERIS) - a longitudinal observational study conducted from 2011-2014. The cohort consisted of patients with moderate to very severe COPD with a previous history of at least one moderate exacerbation. Patients were seen during clinical stability on a monthly basis and at exacerbations. Exacerbation events were monitored prospectively and patients were seen within 72 hours of an onset of the exacerbation event. Pulmonary function was assessed, and sputum samples were collected on a monthly basis and at exacerbations. Sputum samples were processed for microbiology and biomarkers. Blood samples were collected quarterly and at exacerbations and processed for biomarkers. The AERIS study was delivered at the standard of a randomised controlled trial with the rigorous monitoring and data cleaning, therefore, the data quality and the study conclusion are sufficiently robust to set up the vaccine study.

This work for the first time describes an association between the persistence of eosinophilic inflammation in COPD during clinical stability with an increased likelihood of eosinophilic exacerbations, and an association between eosinophilic inflammation, seasonality and bacterial presence. Namely, bacterial infection at exacerbation was higher in the Winter than Summer in patients with predominantly blood eosinophils≥2% at stable visits. A larger proportion of the exacerbations with raised blood eosinophil ≥2% were observed during the Summer compared to Winter season. The findings confirm that sputum purulence can be examined by the five-graded Southampton sputum colour chart and the sputum colour grade was associated with airway neutrophils and airway bacterial presence at exacerbations. The numeric change in sputum colour was associated with airway bacterial presence; the higher the numeric change the greater was the frequency of airway bacterial detection. Higher sputum colour, higher CRP, higher fibrinogen, higher blood neutrophils and lower blood eosinophils were useful in identifying an exacerbation event with airway bacteria.

Therefore, these observations support the view that there are markers that are readily accessible in routine clinical care. These biomarkers reflect airway and systemic inflammation, they can be used in the diagnosis of airway bacterial infection at exacerbations and so may aid the management of COPD exacerbations. Further work to confirm the impact of these findings in improving clinical outcomes in intervention studies is required.

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Identifiers

ORCID for Karl Staples: orcid.org/0000-0003-3844-6457

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