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Objective: We wished to determine the effect of an acute coronary syndrome (ACS) on putative endothelial progenitor cell (EPC) populations, and define their relationship to coronary artery disease (CAD) severity and clinical outcome, in order to clarify their clinical relevance., Design and Setting: A prospective cohort study conducted in a tertiary referral cardiac centre., Patients: Two-hundred-and-one patients undergoing coronary angiography for suspected angina or ACS., Main Outcome Measures: Putative EPC populations were determined by flow cytometry. CAD was quantified using the Gensini scoring system. Survival free from revascularisation, recurrent myocardial infarction and death were determined at 3 years., Results: Circulating CD34(+)VEGFR-2(+) and CD34(+)VEGFR-2(+)CD133(+) cells were rare (<0.007% of mononuclear cells), were not increased in patients with ACS, and were unrelated CAD severity or clinical outcome (p>0.1 for all). By contrast, CD34(+)CD45(-) cells were increased in patients with CAD compared with those with normal coronary arteries (p=0.008) and correlated with atheroma burden (r=0.44, p<0.001). Increased concentrations of circulating CD34(+)CD45(-) cells were associated with a shorter cumulative event-free survival (p<0.02). Proangiogenic monocytes (CD14(+)VEGFR-2(+)Tie-2(+)) and endothelial cell-colony forming units were increased in patients with ACS (p<0.01 for both), however, concentrations reflected myocardial necrosis, and did not predict the extent of CAD or clinical outcome., Conclusions: Traditional EPC populations, CD34(+)VEGFR-2(+) and CD34(+)VEGFR-2(+)CD133(+) are not related to the extent of CAD or clinical outcome. However, CD34(+)CD45(-) cells are increased in patients with CAD and predict future cardiovascular events. It is likely that CD34(+)CD45(-) concentrations reflect the extent of vascular injury and atheroma burden.

Objectives: Endothelial progenitor cells (EPCs) are circulating mononuclear cells with the capacity to mature into endothelial cells and contribute to vascular repair. We assessed the effect of local vascular injury during percutaneous coronary intervention (PCI) on circulating EPCs in patients with coronary artery disease., Design and Setting: Prospective case-control study in a university teaching hospital., Patients: 54 patients undergoing elective coronary angiography., Interventions and Main Outcome Measures: EPCs were quantified by flow cytometry (CD34(+)KDR(+) phenotype) complemented by real-time polymerase chain reaction (PCR), and the colony forming unit (CFU-EC) functional assay, before and during the first 24 hours after diagnostic angiography (n = 27) or PCI (n = 27)., Results: Coronary intervention, but not diagnostic angiography, resulted in an increase in blood neutrophil count (p<0.001) and C-reactive protein concentrations (p = 0.001) in the absence of significant myocardial necrosis. Twenty-four hours after PCI, CFU-ECs increased threefold (median [IQR], 4.4 [1.3-13.8] vs 16.0 [2.1-35.0], p = 0.01), although circulating CD34(+)KDR(+) cells (0.019% (SEM 0.004%) vs 0.016% (0.003%) of leucocytes, p = 0.62) and leucocyte CD34 mRNA (relative quantity 2.3 (0.5) vs 2.1 (0.4), p = 0.21) did not. There was no correlation between CFU-ECs and CD34(+)KDR(+) cells., Conclusions: Local vascular injury following PCI results in a systemic inflammatory response and increases functional CFU-ECs. This increase was not associated with an early mobilisation of CD34(+)KDR(+) cells, suggesting these cells are not the primary source of EPCs involved in the immediate response to vascular injury.

Objective: To investigate the clinical, serological, and environmental features of a work related inhalational fever associated with exposure to an aerosol generated from a biologically contaminated 130,000 gallon water pool in a building used for testing scientific equipment., Method: Cross sectional survey of all exposed subjects (n = 83) by symptom questionnaire, clinical examination, spirometry, and serology for antibody to Pseudomonads, pool water extract, and endotoxin. In symptomatic patients diffusion capacity was measured, and chest radiology was performed if this was abnormal. Serial peak flow was recorded in those subjects with wheeze. Bacterial and fungal air sampling was performed before and during operation of the water pool pump mechanism. Endotoxin was measured in the trapped waters and in the pumps. Serum cotinine was measured as an objective indicator of smoking., Results: Of the 20 symptomatic subjects, fever was most common in those with the highest exposure (chi 2 42.7, P < 0.001) in the sump bay when the water was (torrentially) recirculated by the water pumps. Symptoms occurred late in the working day only on days when the water pumps were used, and were independent of the serum cotinine. Pulmonary function was normal in most subjects (spirometry was normal in 79/83, diffusion capacity was low in five subjects, chest radiology was normal). Peak flow recording did not suggest a work relation. The bacterial content of the aerosol rose from 6 to > 10,000 colony forming units per cubic metre (cfu/m3) (predominantly environmental Pseudomonads) when the pumps were operating. High endotoxin concentrations were measured in the waters and oil sumps in the pumps. Low concentrations of antibody to the organisms isolated were detected (apart from two subjects with high antibody) but there was no relation to exposure or the presence of symptoms and similar antibody was found in the serum samples from a non-exposed population. The fever symptoms settled completely with the simple expedient of changing the water and cleaning the pumps., Conclusion: Given the results of our study, the development of inhalational fever in this unique environment and clearly restricted cohort was closely related to the degree of exposure to contaminated aerosol and mainly occurred in the absence of distinct serological abnormality and independent of cigarette smoking.