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Categorical data were evaluated using Pearson's chi-square test and Fisher's exact test where appropriate. Continuous data were analyzed using Student t-tests with the Mann�CWhitney-Wilcoxon test used for variables with unequal variance or a nonnormal distribution. Linear regression was performed for the entire group of subjects and controls and for subjects, separately, using weight-adjusted peak VO2 as the dependent variable and age, sex, body mass index (BMI), hydroxyurea use, baseline hemoglobin, and white blood cell (WBC) count as covariates. All analyses were performed using IBM SPSS Statistics (Version 20, Chicago, IL, IBM). Results Participant characteristics and CPET safety A total of 60 subjects with SCA and matched 30 controls without SCA or sickle cell trait successfully completed CPET during the study period. There was no significant difference in age or distribution of sex between the two groups, although subjects with SCA learn more had lower BMI (21?��?4 vs. 24?��?7?kg/m2, P?=?0.013) (Table?(Table1).1). Baseline Hb (8.7?��?1.3 vs. 12.9?��?1.3?g/dL, P?Ficain 60 (100%) subjects with SCA and 22/30 (73%) controls met criteria for a maximal test, defined as an RER �� 1.1, and in all, testing was terminated due to excessive participant fatigue. In 10/60 (17%) subjects, but no controls, SpO2 was ��95% at either baseline or peak exercise, or SpO2 significantly dropped from baseline to peak exercise. No serious adverse event occurred during or up to 2?weeks after CPET in any subject or control. Only 1/60 (2%) subjects reported vaso-occlusive pain during a weeklong dance camp after her study visit. She required hospitalization for her pain 13?days after CPET, but the episode was determined to be unrelated to study participation. Cardiopulmonary responses to maximal exercise Small molecule library cell assay testing Nearly all the major indicators of CPET performance and gas exchange were adversely affected in subjects with SCA when compared with controls without SCA. The removal of controls who did not meet criterion for a maximal test from the analysis did not significantly alter our results (data not shown). On average, total exercise time was significantly lower in subjects with SCA when compared with controls without SCA (5.6?��?1.3 vs. 7.8?��?2.0?min, P?