Biomarkers and clinical outcomes in COPD: a systematic review and meta-analysis.

Abstract

Background: Conventional measures to evaluate chronic obstructive pulmonary disease (COPD) may fail to capture systemic problems particularly musculoskeletal weakness and cardiovascular disease. Identifying these manifestations and assessing their association with clinical outcomes (i.e. mortality, exacerbation, and COPD hospital admission) is of increasing clinical importance.

Objective: Assessing associations between six-minute walk distance (6MWD), heart rate, fibrinogen, C-reactive protein (CRP), white blood cell (WBC) count, interleukins 6 and 8 (IL-6, IL-8), tumour necrosis factor-alpha, quadriceps maximum voluntary contraction, sniff nasal inspiratory pressure, short physical performance battery, pulse wave velocity, carotid intima-media thickness and augmentation index, and clinical outcomes in stable COPD patients.

Methods: We systematically searched electronic databases (August 2018) and identified 61 studies, which were synthesised, including meta-analyses to estimate pooled hazard ratios (HRs), following MOOSE and PRISMA guidelines.

Results: Shorter 6MWD and elevated heart rate, fibrinogen, CRP, WBC count were associated with higher risk of mortality. HRs were 0.80 (95% CI 0.73-0.89) per 50m longer 6MWD, 1.10 (1.02-1.18) per 10bpm higher heart rate, 3.36 (2.24-5.02) per 2- fold increase in fibrinogen, 1.18 (1.07-1.29) per 2-fold increase in CRP, and 2.16 (1.31-3.56) per 2-fold increase in WBC count. Shorter 6MWD and elevated fibrinogen and CRP were associated with exacerbation, and shorter 6MWD and higher heart rate, CRP and IL-6 were associated with hospitalisation. Few studies examined associations with musculoskeletal measures.

Conclusion: Findings suggest 6MWD, heart rate, CRP, fibrinogen, and WBC are associated with clinical outcomes in stable COPD patients. Use of musculoskeletal measures to assess outcomes in COPD patients requires further investigation.