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BTS/BLF/BALR Young investigators symposium
T6 Acute exacerbations of chronic obstructive pulmonary disease: identification of phenotype-specific biomarkers and biological clusters
  1. M Bafadhel1,
  2. S McKenna1,
  3. S Terry1,
  4. V Mistry1,
  5. C Reid1,
  6. P Haldar1,
  7. M McCormick2,
  8. K Haldar3,
  9. T Kebadze4,
  10. A Duvoix5,
  11. K Lindbald6,
  12. P Rugman2,
  13. P Dodson2,
  14. M Jenkins2,
  15. P Newbold2,
  16. P Venge6,
  17. R H Green1,
  18. D A Lomas5,
  19. M R Barer3,
  20. S L Johnston4,
  21. I D Pavord1,
  22. C E Brightling1
  1. 1Institute for Lung Health, Leicester, UK
  2. 2AstraZeneca R&D Charnwood, Loughborough, UK
  3. 3Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, UK
  4. 4Department of Respiratory Medicine, National Heart & Lung Institute, Centre for Respiratory Infections, Imperial College, London, UK
  5. 5Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
  6. 6Department of Medical Sciences, Clinical Chemistry, University of Uppsala, Uppsala, Sweden

Abstract

Background Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous in their aetiology and inflammatory response. We investigated the presence of biological phenotypes of COPD exacerbations and biomarker associations with pathogens and inflammation.

Method Patients with COPD were observed for 1 year at stable and exacerbation visits. Spirometry, health quality assessments, blood and sputum (for differential cell counts) were collected at each visit. A large panel of biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biomarkers that differentiated exacerbations associated with bacteria, viruses or eosinophilic airway inflammation were investigated. Biological phenotypes were explored using cluster analysis.

Result 145 patients (101 men, 44 women) entered the study. 182 exacerbations were captured from 86 patients. 55%, 26% and 28% met our definitions for bacteria, virus or sputum eosinophil associated exacerbations. Respectively each of the associated exacerbations were best identified by sputum IL-1β (area under receiver operator curve 0.89 (95% CI 0.83 to 0.95), serum CXCL10 (IP-10) 0.83 (0.70 to 0.96), and percentage peripheral blood eosinophils 0.85 (0.78 to 0.93). The odds ratio (95% CI) of an eosinophil or bacteria associated exacerbation was 2.7 (1.3 to 5.7) and 4.9 (2.4 to 9.9) if a sputum eosinophilia or bacterial pathogen was detected on ≥1 occasion at stable state. Four biological clusters were identified which validated the subgroups of exacerbations associated with bacteria, virus or sputum eosinophilia.

Conclusion COPD exacerbation heterogeneity can be defined. Sputum IL-1β, serum CXCL10 (IP-10) and percentage peripheral blood eosinophils could be used to identify bacteria, virus or eosinophil associated exacerbations of COPD. Whether these biomarkers can be applied to direct therapy warrants further investigation.

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