Research Article Cardiopulmonary Exercise Capacity and Preoperative Markers of Inflammation Pervez Sultan, 1 Mark R. Edwards, 1 Ana Gutierrez del Arroyo, 1 David Cain, 1 J. Robert Sneyd, 2 Richard Struthers, 2 Gary Minto, 2 and Gareth L. Ackland 1 1 Clinical Physiology, Division of Medicine, University College London, London WC1E 6BT, UK 2 Department of Anaesthesia, Derriford Hospital and Peninsula Medical School, Plymouth PL6 8DH, UK Correspondence should be addressed to Gareth L. Ackland; g.ackland@ucl.ac.uk Received 11 April 2014; Revised 10 June 2014; Accepted 11 June 2014; Published 26 June 2014 Academic Editor: Jonathan Peake Copyright © 2014 Pervez Sultan et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Explanatory mechanisms for the association between poor exercise capacity and infections following surgery are underexplored. We hypothesized that aerobic ftness—assessed by cardiopulmonary exercise testing (CPET)—would be associated with circulating infammatory markers, as quantifed by the neutrophil-lymphocyte ratio (NLR) and monocyte subsets. Te association between cardiopulmonary reserve and infammation was tested by multivariable regression analysis with covariates including anaerobic threshold (AT) and malignancy. In a frst cohort of 240 colorectal patients, AT was identifed as the sole factor associated with higher NLR ( = 0.03) and absolute and relative lymphopenia ( = 0.01). Preoperative leukocyte subsets and monocyte CD14 + expression (downregulated by endotoxin and indicative of chronic infammation) were also assessed in two further cohorts of age-matched elective gastrointestinal and orthopaedic surgical patients. Monocyte CD14 + expression was lower in gastrointestinal patients ( = 43) compared to age-matched orthopaedic patients ( = 31). Te circulating CD14 + CD16 - monocyte subset was reduced in patients with low cardiopulmonary reserve. Poor exercise capacity in patients without a diagnosis of heart failure is independently associated with markers of infammation. Tese observations suggest that preoperative infammation associated with impaired cardiorespiratory performance may contribute to the pathophysiology of postoperative outcome. 1. Introduction Immune dysregulation is a key feature of low cardiac output states. Absolute numbers, as well as function, of monocytes and T-cells are markedly altered in cardiac failure [1]. Severe heart failure is associated with higher levels of circulating endotoxin [2] and lymphopenia [3]. Systemic infammation driven by exposure to endotoxin in patients with heart failure results in downregulation of monocyte CD14 + expression and increased soluble CD14 through shedding of this receptor from the cellular membrane. Alterations in three distinct CD14 + monocyte subsets occur in various pathophysiological states, as defned by CD16 (FcRIII) expression. Te function of these subsets appears to be highly context-specifc, with CD16 + subsets frequently expanded in chronic infamma- tory conditions. Notably, in patients with chronic systolic heart failure, the nonclassical CD14 dim CD16 + subset is more prevalent and inversely associated with worsening cardiac performance [4]. By contrast, reduced levels of the classical CD14 ++ CD16 - monocyte subset are reported in heart failure, compatible with remodelling roles for diferent subsets [5]. Poor exercise capacity in surgical patients, as measured objectively by preoperative cardiopulmonary exercise [6– 12], is associated with poorer postoperative outcomes— including infection—following surgery [13]. Plausible mech- anisms that explain the link between poor exercise capacity and poorer postoperative outcomes remain underexplored. Whether preoperative exercise capacity in surgical patients is similarly independently linked to markers of infammation, as reported in heart failure, remains unclear. We there- fore hypothesized that impaired cardiovascular performance (as defned by cardiopulmonary exercise testing) would be associated with biomarkers for infammation (neutrophil- lymphocyte ratio and absolute and relative lymphopenia) Hindawi Publishing Corporation Mediators of Inflammation Volume 2014, Article ID 727451, 8 pages http://dx.doi.org/10.1155/2014/727451