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Cardiopulmonary Function in Healthy Individuals and in Patients After Hematopoietic Cell Transplantation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. , p. 63
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1621
Keywords [en]
hematopoietic stem cell transplantation, echocardiography, cardiopulmonary execise testing, stress testing, onchology, childhood leukemia, healthy adults, breathing reserve, oxygen uptake
National Category
Clinical Medicine
Research subject
Clinical Physiology
Identifiers
URN: urn:nbn:se:uu:diva-398070ISBN: 978-91-513-0832-6 (print)OAI: oai:DiVA.org:uu-398070DiVA, id: diva2:1376095
Public defence
2020-02-12, Enghoffsalen, Akademiska sjukhuster, Ingång 50, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2020-01-17 Created: 2019-12-07 Last updated: 2020-03-25
List of papers
1. Exercise capacity in young adults after hematopoietic cell transplantation in childhood.
Open this publication in new window or tab >>Exercise capacity in young adults after hematopoietic cell transplantation in childhood.
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2018 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 18, no 2, p. 417-423Article in journal (Refereed) Published
Abstract [en]

A symptom-limited incremental cycle ergometer test was performed in 17 young adult patients treated with hematopoietic cell transplantation and total body irradiation for hematologic malignancies during childhood. These 17 young adult patients were compared with 17 sex- and age-matched healthy control subjects. Assessments of pulmonary function, cardiac function, body composition, and levels of growth hormone were made. The median follow-up was 17.7 years. Patients achieved 63.2% of the predicted peak workload, whereas controls achieved 96.1% (P < .001). All patients, but only 1 control, failed to achieve a peak workload >80% (P < .001). Fat-free mass was significantly lower (43.5 vs 57.6 kg, P < .001) and fat mass percentage was significantly higher (31.8% vs 24.2%, P = .011) in the patients. The peak workload adjusted for fat-free mass was significantly lower in the patients (3.3 vs 4.3, P < .001). In the patients, peak workload correlated significantly with total lung capacity (r = .54, P = .025). In summary, long-term survivors have significantly decreased exercise capacity compared with healthy individuals. Together with their altered body composition, this may predispose them to cardiovascular disease.

Keywords
bone marrow/hematopoietic stem cell transplantation, cancer/malignancy/neoplasia: hematogenous/leukemia/lymphoma, cardiovascular disease, clinical research/practice, complication: medical/metabolic, hematology/oncology, lung (native) function/dysfunction, metabolic syndrome, pediatrics
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-343519 (URN)10.1111/ajt.14456 (DOI)000423666200016 ()28787762 (PubMedID)
Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2019-12-07Bibliographically approved
2. Long-term effects on cardiopulmonary exercise testing parameters in young adults treated with stem cell transplantation in childhood
Open this publication in new window or tab >>Long-term effects on cardiopulmonary exercise testing parameters in young adults treated with stem cell transplantation in childhood
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(English)Manuscript (preprint) (Other academic)
National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-398069 (URN)
Available from: 2019-12-01 Created: 2019-12-01 Last updated: 2019-12-07
3. Cardiac Function After Hematopoietic Cell Transplantation: An Echocardiographic Cross-Sectional Study in Young Adults Treated in Childhood
Open this publication in new window or tab >>Cardiac Function After Hematopoietic Cell Transplantation: An Echocardiographic Cross-Sectional Study in Young Adults Treated in Childhood
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2015 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 62, no 1, p. 143-147Article in journal (Refereed) Published
Abstract [en]

BackgroundHematopoietic cell transplantation (HCT) including preparative regimens with chemotherapy and total body irradiation (TBI) is an accepted treatment for many malignant disorders but may have side-effects for several organs, including the cardiovascular system. The aim of this study was to study very long-term consequences on cardiac function after childhood HCT. ProcedureCardiac function was evaluated using echocardiography and levels of NT-proBNP and growth hormone (GHmax) in 18 patients, at a median of 18 years after HCT including TBI, and in 18 matched controls. ResultsPatients after HCT had cardiac dimensions, volumes, and left ventricular ejection fractions within normal range after correction for body size. However, compared with the control group, patients after HCT had significantly lower E/A ratio, as a measure of left ventricular diastolic function, significantly lower fractional shortening and mitral annular plane systolic excursion, as measures of left ventricular systolic function, significantly lower tricuspid annular plane systolic excursion, as a measure of right ventricular function, and significantly higher NT-proBNP, as a measure of total cardiac function. Also, pulmonary flow acceleration time was shorter in the group after HCT, indicating possible pulmonary involvement. Heart rate was significantly higher and GHmax significantly lower in patients after HCT. ConclusionsAlmost two decades after HCT, including preparative regimens with TBI, cardiac function in patients was found to be within normal range. However, when compared with a healthy control group, patients after HCT showed lower systolic and diastolic left ventricular function as well as lower right ventricular function. Pediatr Blood Cancer 2015;62:143-147.

Keywords
cardiac function, children, echocardiography, hematopoietic cell transplantation, total body irradiation
National Category
Hematology Pediatrics
Identifiers
urn:nbn:se:uu:diva-240060 (URN)10.1002/pbc.25135 (DOI)000345319300026 ()25251023 (PubMedID)
Available from: 2015-01-08 Created: 2015-01-05 Last updated: 2019-12-07Bibliographically approved
4. Commonly used reference values underestimate oxygen uptake in healthy, 50-year-old Swedish women.
Open this publication in new window or tab >>Commonly used reference values underestimate oxygen uptake in healthy, 50-year-old Swedish women.
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2018 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 1, p. 25-33Article in journal (Refereed) Published
Abstract [en]

Cardiopulmonary exercise testing (CPET) is the gold standard among clinical exercise tests. It combines a conventional stress test with measurement of oxygen uptake (VO2 ) and CO2 production. No validated Swedish reference values exist, and reference values in women are generally understudied. Moreover, the importance of achieved respiratory exchange ratio (RER) and the significance of breathing reserve (BR) at peak exercise in healthy individuals are poorly understood. We compared VO2 at maximal load (peakVO2 ) and anaerobic threshold (VO2@AT ) in healthy Swedish individuals with commonly used reference values, taking gender into account. Further, we analysed maximal workload and peakVO2 with regard to peak RER and BR. In all, 181 healthy, 50-year-old individuals (91 women) performed CPET. PeakVO2 was best predicted using Jones et al. (100·5%), while SHIP reference values underestimated peakVO2 most: 112·5%. Furthermore, underestimation of peakVO2 in women was found for all studied reference values (P<0·001) and was largest for SHIP: women had 128% of predicted peakVO2 , while men had 104%. PeakVO2 was similar in subjects with peak RER of 1-1·1 and RER > 1·1 (2 328·7 versus 2 176·7 ml min(-1) , P = 0·11). Lower BR (≤30%) related to significantly higher peakVO2 (P<0·001). In conclusion, peakVO2 was best predicted by Jones. All studied reference values underestimated oxygen uptake in women. No evidence for demanding RER > 1·1 in healthy individuals was found. A lowered BR is probably a normal response to higher workloads in healthy individuals.

National Category
Cardiac and Cardiovascular Systems Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-312359 (URN)10.1111/cpf.12377 (DOI)000417877700005 ()27312352 (PubMedID)
Available from: 2017-01-09 Created: 2017-01-09 Last updated: 2019-12-07Bibliographically approved

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