Background: COPD phenotypes have been identified according to patient clinical characteristics and, more recently, to their immunological markers. However, the role of these biomarkers in relation to exacerbations in different COPD phenotypes is not yet clear. Thus it is important to continue investigating this topic to plan the most appropriate treatment, to contrast the decline of respiratory function and to reduce subsequent exacerbations in COPD patients.

Therefore the aim of this study was to assess whether biomarkers are only predictors of exacerbations and mortality in COPD patients or instead play a causal role in these adverse COPD developments.

Methods: COPD phenotypes were identified according to patient clinical characteristics or immunological markers. Immunological and inflammatory biomarkers were identified as predictors of mortality and exacerbations.
COPD patients were identified from the hospital discharge register of Pisa (Italy) in 2000-2006, on the basis of diagnoses and a FEV1/FVC < 0.70, and enrolled in 2003-2006 according to a longitudinal approach. They were characterized at enrollment by age, sex, comorbidities, immunological and inflammatory biomarkers. The phenotype was assigned at enrollment as eosinophilic (eosinophils>2%) or neutrophilic (leukocytes>11.0x109/L and/or neutrophils>65%). Mortality and exacerbations registered in the period 2003-2012 were assessed by phenotype and other possible predictors in regression models.

Results: Mortality rates reached 43.3% in COPD patients: 69.1% and 36.5% in neutrophilic and eosinophilic, respectively. The exacerbation rate was higher in neutrophilic (54.4%) than in eosinophilic patients (48.4%). Uni-variable regression confirmed that mortality was related to age, Congestive Heart Failure (CHF), Ischemic Heart Disease (IHD), elevated neutrophil count and Neutrophil to Lymphocyte Ratio (NLR). At multivariable analysis only age was associated with mortality, whereas inflammatory biomarkers induced exacerbations.

Conclusion: Mortality was influenced by phenotype and age, exacerbations by COPD severity and NLR to suggest that an appropriate treatment and the biomarker’s monitoring might help prevent exacerbations.