Summary of main findings in different biomarker ECLIPSE studies
| Type of biomarker | Main findings |
|---|---|
| Cellular biomarkers | |
| Sputum neutrophils | 3.5% variability at 1-year follow-up3 |
| Sputum neutrophils | Weak/absent association with FEV1%, SGRQ, emphysema, systemic inflammatory markers, exacerbation frequency or lung function decline3 |
| Circulating WBC | Associated with persistent systemic inflammation,4 frequent exacerbations5 and mortality6 |
| Blood protein biomarkers | |
| Fibrinogen | Significantly associated with symptoms, exercise capacity, exacerbation rate and BODE index.6 10 Currently undergoing a regulatory qualification process11 |
| CC16 | Weakly associated with lung function decline, emphysema and depression12–15 |
| SP-D | Weak association with COPD exacerbations5 16; sensitive to treatment with oral and inhaled corticosteroids16 |
| CCL18 (PARC) | Increased risk of cardiovascular hospitalisation or mortality17 |
| sRAGE | Lower circulating sRAGE levels are associated with emphysema severity, and genetic polymorphisms in the AGER locus are associated with circulating sRAGE levels22 |
| Inflammome* | Patients with persistent systemic inflammation (16%) had higher mortality and exacerbation rate than patients without inflammation (30%).4 Systemic inflammation was also associated with heart disease, hypertension and diabetes18 |
| Adipokines | Leptin and adiponectin levels were (+) and (−) related to CRP, respectively; BMI and gender were the strongest determinants of both adipokines20 |
| Vitamin D | Low levels of vitamin D were related to emphysema, 6MWD, airways reactivity and CC-16 levels21 |
| Sputum transcriptomics | |
| Airflow limitation | 277 genes associated with the severity of airflow limitation (GOLD stage)48 |
| Emphysema | 198 genes associated with the presence of emphysema48 |
| Blood biomarkers | SNPs affecting circulating CC16 protein levels were significantly associated with sputum mRNA expression of SCGB1A1, the CC16 coding gene on chromosome 1147 |
| COPD susceptibility | An integrative genomics approach located potential functional variants in two genes located within a COPD GWAS locus on chromosome 15 (CHRNA5 and IREB2) and one locus in the HLA-C region on chromosome 651 |
| Serum metabolomics | |
| Serum profile | Results indicate that52 53: (1) there is increased protein turnover in all COPD patients; (2) increased protein degradation in individuals with emphysema and cachexia |
| Exhaled breath condensate | |
| pH | Lower pH in COPD and smoking controls, but not related to FEV1 or sputum leucocyte counts and not responsive to steroid treatment54 |
| Adenosine/purines | Increased concentrations in COPD patients and adenosine levels correlated with FEV155 |
*Inflammome: combined panel of six inflammatory markers in serum (WBC, CRP, interleukin 6, interleukin 8, tumour necrosis factor α and fibrinogen).
BMI, body mass index; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; FEV1, forced expiratory volume in 1 s; FFMI, fat-free mass index; GWAS, genome-wide association studies; 6MWD, 6-minute walking distance; PARC, pulmonary and activation-regulated chemokine; SGRQ, St George's Respiratory Questionnaire; SNP, single nucleotide polymorphism; sRAGE, soluble receptor for advanced glycation end products; WBC, white blood cell.