Cardiopulmonary Function in Healthy Individuals and in Patients After Hematopoietic Cell Transplantation

Background: The cardiopulmonary exercise test (CPET) is the gold standard of clinical exercise tests, combining conventional stress testing with measurement of oxygen uptake and carbon dioxide production. In order to interpret CPET findings, adequate reference values are needed. Currently, no Swedish reference values exist. Hematopoietic cell transplantation (HCT) is an established treatment for childhood leukemia, with a growing number of long-term survivors. This increases the importance of identifying and treating this therapy’s late cardiac and pulmonary consequences. Aims: The main aim of Study I was to compare the peak oxygen uptake (VO2peak) of healthy, 50-year-old Swedes with four commonly used international reference values. Secondary aims were to analyze peak workload and VO2peak in regard to achieved respiratory exchange ratio (RER), and the significance of breathing reserve (BR) at peak exercise in healthy individuals. The main aim of Studies II–IV was to investigate long-term cardiopulmonary effects in a group of patients, in median 18 years after HCT including preparative chemotherapy and total body irradiation. Methods: A group of healthy, 50-year-old Swedes (n = 181; 91 females) were investigated in Study I, using CPET. The investigated subjects in Studies II–IV were aged 17–37 years and were compared with an age- and sex-matched control group. Cardiac function and pulmonary function were studied through echocardiography, spirometry and CPET at a single occasion. Results: All reference values analyzed in Study I underestimated VO2peak in women. VO2peak was best predicted, for both men and women, using reference values by Jones et al. No evidence was found that RER > 1.1 would be better than RER > 1.0 as an indicator of good exercise performance in healthy individuals. In healthy individuals, lower BR is likely a response to higher workloads. In Studies II–IV, all echocardiographic parameters were within normal range in patients after HCT. However, systolic and diastolic left ventricular function, and right ventricular function, were reduced in comparison with healthy controls. Exercise tests and CPET showed that long-term survivors after HCT, when compared with healthy individuals, had significantly decreased exercise capacity and reduced VO2peak and other CPET parameters, reflecting effects on both the cardiac and the pulmonary functions. Conclusions: All investigated reference values underestimated VO2peak in 50-year-old Swedes, suggesting a need for Swedish reference values. HCT-treated leukemia patients displayed reduced exercise capacity and VO2peak. Regular follow-up of these patients with CPET could contribute to early detection of functional impairment