Myeloid-derived suppressor cell-like fibrocytes are increased and associated with preserved lung function in chronic obstructive pulmonary disease.

BACKGROUND: The role of fibrocytes in chronic obstructive pulmonary disease (COPD) is unknown. We sought to enumerate blood and tissue fibrocytes in COPD and determine the association of blood fibrocytes with clinical features of disease. METHODS: Utilizing flow cytometry to identify circulating, collagen type 1+ cells, we found two populations: (i) CD45+ CD34+ (fibrocytes) and (ii) CD45+ CD34- [myeloid-derived suppressor cell (MDSC)-like fibrocytes] cells in stable COPD (n = 41) and control (n = 29) subjects. Lung resection material from a separate group of subjects with (n = 11) or without (n = 11) COPD was collected for tissue fibrocyte detection. We examined circulating fibrocyte populations for correlations with clinical parameters including quantitative computed tomography (qCT) and determined pathways of association between correlated variables using a path analysis model. RESULTS: Blood and tissue fibrocytes were not increased compared to control subjects nor were blood fibrocytes associated with lung function or qCT, but were increased in eosinophilic COPD. Myeloid-derived suppressor cell-like fibrocytes were increased in COPD compared to controls [2.3 (1.1-4.9), P = 0.038]. Our path analysis model showed that collagen type 1 intensity for MDSC-like fibrocytes was positively associated with lung function through associations with air trapping, predominately in the upper lobes. CONCLUSION: We have demonstrated that two circulating populations of fibrocyte exist in COPD, with distinct clinical associations, but are not prevalent in proximal or small airway tissue. Blood MDSC-like fibrocytes, however, are increased and associated with preserved lung function through a small airway-dependent mechanism in COPD.

Cardiopulmonary exercise testing and survival after elective abdominal aortic aneurysm repair†.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is increasingly used in the preoperative assessment of patients undergoing major surgery. The objective of this study was to investigate whether CPET can identify patients at risk of reduced survival after abdominal aortic aneurysm (AAA) repair. METHODS: Prospectively collected data from consecutive patients who underwent CPET before elective open or endovascular AAA repair  (EVAR) at two tertiary vascular centres between January 2007 and October 2012 were analysed. A symptom-limited maximal CPET was performed on each patient. Multivariable Cox proportional hazards regression modelling was used to identify risk factors associated with reduced survival. RESULTS: The study included 506 patients with a mean age of 73.4 (range 44-90). The majority (82.6%) were men and most (64.6%) underwent EVAR. The in-hospital mortality was 2.6%. The median follow-up was 26 months. The 3-year survival for patients with zero or one sub-threshold CPET value ([Formula: see text] at AT<10.2 ml kg(-1) min(-1), peak [Formula: see text]<15 ml kg(-1) min(-1) or [Formula: see text] at AT>42) was 86.4% compared with 59.9% for patients with three sub-threshold CPET values. Risk factors independently associated with survival were female sex [hazard ratio (HR)=0.44, 95% confidence interval (CI) 0.22-0.85, P=0.015], diabetes (HR=1.95, 95% CI 1.04-3.69, P=0.039), preoperative statins (HR=0.58, 95% CI 0.38-0.90, P=0.016), haemoglobin g dl(-1) (HR=0.84, 95% CI 0.74-0.95, P=0.006), peak [Formula: see text]<15 ml kg(-1) min(-1) (HR=1.63, 95% CI 1.01-2.63, P=0.046), and [Formula: see text] at AT>42 (HR=1.68, 95% CI 1.00-2.80, P=0.049). CONCLUSIONS: CPET variables are independent predictors of reduced survival after elective AAA repair and can identify a cohort of patients with reduced survival at 3 years post-procedure. CPET is a potentially useful adjunct for clinical decision-making in patients with AAA.

Preoperative cardiopulmonary exercise testing and risk of early mortality following abdominal aortic aneurysm repair.

BACKGROUND: Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity. The aim of this study was to assess whether preoperative CPET identifies patients at risk of early death following elective open and endovascular abdominal aortic aneurysm (AAA) repair. METHODS: Prospective data were collected from a pilot study between September 2005 and February 2007, and from all patients who underwent CPET before elective AAA repair at two vascular centres between February 2007 and November 2011. Symptom-limited, maximal CPET was performed on each patient. Univariable and multivariable analyses were used to identify risk factors for 30- and 90-day mortality. RESULTS: Some 415 patients underwent CPET before elective AAA repair. Anaerobic threshold (AT), peak oxygen consumption (peak V.O(2) ) and ventilatory equivalents for carbon dioxide were associated with 30- and 90-day mortality on univariable analysis. On multivariable analysis, open repair (odds ratio (OR) 4·92, 95 per cent confidence interval 1·55 to 17·00; P = 0·008), AT below 10·2 ml per kg per min (OR 6·35, 1·84 to 29·80; P = 0·007), anaemia (OR 3·27, 1·04 to 10·50; P = 0·041) and inducible cardiac ischaemia (OR 6·16, 1·48 to 23·07; P = 0·008) were associated with 30-day mortality. Anaemia, inducible cardiac ischaemia and peak V.O(2) less than 15 ml per kg per min (OR 8·59, 2·33 to 55·75; P = 0·005) were associated with 90-day mortality on multivariable analysis. Patients with two or more subthreshold CPET values were at increased risk of both 30- and 90-day mortality. CONCLUSION: An AT below 10·2 ml per kg per min, peak V.O(2) less than 15 ml per kg per min and at least two subthreshold CPET values identify patients at increased risk of early death following AAA repair.