scholarly journals The acute phase inflammatory response to maximal exercise testing in children and young adults with sickle cell anaemia

2015 ◽  
Vol 171 (5) ◽  
pp. 854-861 ◽  
Author(s):  
Robert I. Liem ◽  
Kasiemobi Onyejekwe ◽  
Marie Olszewski ◽  
Chisalu Nchekwube ◽  
Frank P. Zaldivar ◽  
...  
Keyword(s):  
Young Adults ◽  
Inflammatory Response ◽  
Sickle Cell ◽  
Acute Phase ◽  
Exercise Testing ◽  
Sickle Cell Anaemia ◽  
Maximal Exercise ◽  
Children And Young Adults

scholarly journals Reduced fitness and abnormal cardiopulmonary responses to maximal exercise testing in children and young adults with sickle cell anemia

2015 ◽  
Vol 3 (4) ◽  
pp. e12338 ◽  
Author(s):  
Robert I. Liem ◽  
Madhuri Reddy ◽  
Stephanie A. Pelligra ◽  
Adrienne P. Savant ◽  
Bo Fernhall ◽  
...  
Keyword(s):  
Young Adults ◽  
Sickle Cell ◽  
Exercise Testing ◽  
Sickle Cell Anemia ◽  
Maximal Exercise ◽  
Children And Young Adults

The Inflammatory Response To Cardiopulmonary Exercise Testing In Children and Young Adults With Sickle Cell Anemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2242-2242
Author(s):  
Kasiemobi Onyejekwe ◽  
Marie Olszewski ◽  
Frank P. Zaldivar ◽  
Shlomit Radom-Azik ◽  
Mark J. Rodeghier ◽  
...  
Keyword(s):  
Young Adults ◽  
Platelet Count ◽  
Inflammatory Response ◽  
Sickle Cell ◽  
Acute Phase ◽  
Research Funding ◽  
Children And Young Adults ◽  
Response To Exercise ◽  
D Dimer ◽  
Over Time

Abstract Sickle cell anemia (SCA) is associated with a pro-inflammatory state that worsens during disease complications. Although exercise limitation and poor physical functioning are prevalent in SCA, concerns about the adverse effects of physical exertion in SCA have hampered development of exercise guidelines in this population. The acute phase inflammatory response to moderate or high grade physical exertion has not been examined in SCA. We aimed to characterize the acute inflammatory response to exercise in children and young adults with SCA undergoing maximal cardiopulmonary exercise testing (CPET). Methods 60 subjects (mean age 15.1 ±3.4 years) with SCA (Hb SS or S/β0 thalassemia) and 25 race-matched, healthy controls (mean age 14.4 ±3.6 years) without sickle cell trait performed a maximal ramp cycle ergometry protocol. Blood was drawn at baseline before CPET (Pre) and at T0, T30, T60, and T120 min after CPET. Blood was analyzed for WBC, absolute neutrophil and monocyte counts, platelet count, CRP and D-dimer. Circulating levels of soluble vascular cell adhesion molecule (sVCAM) and IL-6 were determined by ELISA. Our primary outcome was the acute change in sVCAM from baseline to immediately after CPET (T0-Pre). Only subjects and controls with all available time points were analyzed. Continuous variables were compared between groups by Student t-test or Mann Whitney Wilcoxon Test. We used MANOVA to determine if inflammatory responses were similar in shape over time between groups. Results All subjects with SCA and controls met criteria for maximal effort on CPET. We found no difference in the acute sVCAM response to exercise challenge in subjects with SCA vs. controls. Mean sVCAM level was significantly higher at baseline in subjects with SCA vs. controls (1644 ±888 vs. 1118 ±529 ng/mL, p = 0.043), and this difference remained significant at each time point after CPET. However, mean change in sVCAM level from baseline to T0 (T0-Pre) was not significantly different between groups (120 ±241 vs. 65 ±216 ng/mL, p = 0.461) even after controlling for fitness level, defined by peak VO2 (Table). The mean difference in sVCAM between subjects with SCA and controls by MANOVA was constant over time (F(3.3, 167.1) = 1.12, p = 0.347), indicating the acute sVCAM response to CPET through recovery followed similar trends in both groups. We found the acute sVCAM response to exercise was related to fitness in subjects with SCA. Mean change in sVCAM (T0-Pre) was inversely related to peak VO2 (Pearson’s r = -0.41, p = 0.012) in subjects with SCA, supported by a downward trend in mean T0-Pre for sVCAM with increasing tertiles of fitness. We also examined the acute phase response to CPET of other inflammatory biomarkers. WBC, absolute neutrophil and monocyte counts, platelet count and D-dimer, but not IL-6 or CRP, were significantly higher at baseline in subjects with SCA vs. controls, and similar to sVCAM, this difference remained significant at each time point after CPET. Only the mean change from baseline to T0 (T0-Pre) for platelet count (8 ±59 vs. 42 ±23 x103/mL, p = 0.008) and D-dimer (0.13 ±0.28 vs. 0.01 ±0.09 mg/mL, p = 0.003) were significantly different between groups. We found no consistent relationship between secondary biomarkers and peak VO2 in subjects in SCA. Only the acute platelet response to CPET through recovery differed between groups over time (F(2.1, 153.8) = 4.07, p = 0.017) due to the greater mean T0-Pre for platelet count in controls. Conclusions Compared to peers, children and young adults with SCA have similar trends in their acute phase response to maximal CPET through recovery regardless of fitness level and despite elevated inflammatory biomarkers at baseline and after CPET. This suggests that maximal exercise challenge in SCA is not associated with any greater escalation of inflammation. Further studies evaluating exercise and physical activity, even at maximal levels, should be encouraged in this population. Disclosures: Thompson: Novartis: Consultancy, Research Funding; ApoPharma: Consultancy, Honoraria; Glaxo Smith Kline: Research Funding; Eli Lilly: Research Funding; Amgen: Research Funding; bluebird bio: Research Funding. Liem:NHLBI: Research Funding.

scholarly journals Developmental Profile of Sleep and Its Potential Impact on Daytime Functioning from Childhood to Adulthood in Sickle Cell Anaemia

2020 ◽  
Vol 10 (12) ◽  
pp. 981
Author(s):  
Melanie Kölbel ◽  
Fenella J. Kirkham ◽  
Dagmara Dimitriou
Keyword(s):  
Young Adults ◽  
Sickle Cell ◽  
Sleep Disturbances ◽  
Sickle Cell Anaemia ◽  
Limb Movement ◽  
Sleep Onset Latency ◽  
Sleep Habits ◽  
Daytime Functioning ◽  
Children And Young Adults ◽  
Night Waking

Young individuals with sickle cell anaemia (SCA) experience sleep disturbances and often experience daytime tiredness, which in turn may impact on their daytime functioning and academic attainment, but there are few longitudinal data. Methods: Data on sleep habits and behaviour were taken on the same day as an in-hospital polysomnography. This study assesses the developmental sleep profiles of children and young adults aged 4–23 years old with SCA. We examined retrospective polysomnography (PSG) and questionnaire data. Results: A total of 256 children with a median age of 10.67 years (130 male) were recruited and 179 returned for PSG 1.80–6.72 years later. Later bedtimes and a decrease in total sleep time (TST) were observed. Sleep disturbances, e.g., parasomnias and night waking, were highest in preschool children and young adults at their first visit. Participants with lower sleep quality, more movement during the night and increased night waking experienced daytime sleepiness, potentially an indicator of lower daytime functioning. Factors influencing sleep quantity included age, hydroxyurea prescription, mean overnight oxygen saturation, sleep onset latency, periodic limb movement, socioeconomic status and night waking. Conclusion: Sleep serves an important role for daytime functioning in SCA; hence, quantitative (i.e., PSG for clinical symptoms, e.g., sleep-disordered breathing, nocturnal limb movement) and qualitative (i.e., questionnaires for habitual sleep behaviour) assessments of sleep should be mutually considered to guide interventions.

Decreased Fitness Is Associated with Abnormal Cardiopulmonary Response to Maximal Exercise in Pediatric Sickle Cell Anemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2109-2109
Author(s):  
Madhuri G. Reddy ◽  
Stephanie A. Pelligra ◽  
Alexis A. Thompson ◽  
Robert I. Liem
Keyword(s):  
Young Adults ◽  
Sickle Cell ◽  
Maximal Exercise ◽  
Ventilatory Threshold ◽  
Work Rate ◽  
Heart Rate Reserve ◽  
Ventilatory Efficiency ◽  
Exercise Limitation ◽  
Peak Vo2 ◽  
Children And Young Adults

Abstract Abstract 2109 The clinical burden of sickle cell anemia (SCA) has a tremendous impact on physical functioning, including cardiopulmonary fitness, among affected individuals. However, the physiologic basis of exercise limitation remains poorly understood in this population. The objective of our study was to characterize the cardiopulmonary response to maximal exercise and to delineate the physiologic mechanisms responsible for decreased fitness among children and young adults with SCA. Methods: We prospectively performed maximal cardiopulmonary exercise testing (CPET) on 60 subjects with SCA (hemoglobin SS or S/β0 thalassemia) and 20 controls without SCA or sickle cell trait matched for race and gender. CPET was completed using a graded, symptom-limited cycle ergometry protocol with breath-by-breath, gas exchange analysis and pre/post spirometry. The primary outcome of fitness was defined by weight-adjusted, peak oxygen consumption (peak VO2). Slopes for determining oxygen uptake kinetics and ventilatory efficiency were calculated using 10-second averages of data points. We used the V-slope method to determine ventilatory threshold. Bivariate comparisons of continuous data were performed using Student's t-test for independent samples (IBM, SPSS V20). We used multivariate analysis to derive a model for determining independent contributors to peak VO2 in subjects. Results: There was no difference in gender distribution among subjects and controls, but subjects were older (15.1 ± 3.44 vs. 13.2 ±2.9 years, p = 0.03) and had lower hemoglobin (8.8 ±1.3 vs. 12.8 ±1.5 g/dL, p < 0.0001). All subjects met criteria for a maximal test as defined by a respiratory exchange ratio (RER) ≥ 1.1, and in all, testing was terminated due to excessive fatigue. No major adverse events occurred during CPET in any subject. Only 1/60 (1.7%) subjects developed vaso-occlusive pain requiring hospitalization in the 2-week follow-up period after testing. Nearly all of the major indicators of CPET performance and gas exchange were adversely affected in our subjects. Compared to controls, subjects demonstrated significantly lower mean peak VO2 (26.9 ±6.9 vs. 40.6 ±8.2 mL/kg/min, p < 0.0001), even after adjustment for age and hemoglobin. Average total test time (5.6 ±1.3 vs. 7.8 ±2.2 min, p = 0.012) and peak work rate (108 ±37 vs. 151 ±57 watts, p = 0.011) were similarly reduced as was ventilatory threshold (1.01 ±0.29 vs. 1.34 ±0.34 L/min, p < 0.0001), indicating earlier transition to anaerobic metabolism during exercise. Heart rate reserve, the difference between achieved maximal and baseline heart rates, was significantly lower (99 ±14 vs. 111 ±15, p = 0.002) in subjects. Slopes calculated using minute ventilation (VE), expired CO2 (VCO2), VO2 and work rate also indicated significantly reduced ventilatory efficiency (ΔVE/ΔVCO2), oxygen delivery (ΔVO2/ΔWR) and oxygen uptake (ΔVO2/ΔVE) kinetics in subjects versus controls. To examine the physiologic contributors to peak VO2 in subjects with SCA alone, we developed a multivariate model that included age, baseline hemoglobin, heart rate reserve, maximal VE, pre-exercise forced expiratory volume in 1 second, and ventilatory threshold. This model explained 67% of the variability observed in peak VO2 in subjects, with age, maximal VE and ventilatory threshold retaining independent contributions to peak VO2 and ventilatory threshold making the largest contribution with an non-standardized β coefficient of 11.9 (SE ±3.2), p < 0.0001. Conclusions: Maximal CPET is safe in children and young adults with SCA, suggesting that acute exercise challenge is well tolerated in this population even at high levels of exercise intensity and physical exertion. When compared to their peers, children and young adults with SCA demonstrate significantly reduced fitness levels. Exercise limitation in SCA may be attributed to complex derangements in the cardiopulmonary and metabolic responses to exercise that are independent of anemia. Our findings highlight the need to develop targeted exercise training strategies aimed at improving fitness in this population and to assess its impact on overall disease severity. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Some Experiences in Managing Sickle-cell Anaemia in Children and Young Adults, Using Alkalis and Magnesium

BMJ ◽  
1964 ◽  
Vol 2 (5403) ◽  
pp. 226-229 ◽  
Author(s):  
K. Hugh-Jones ◽  
H. Lehmann ◽  
J. M. McAlister
Keyword(s):  
Young Adults ◽  
Sickle Cell ◽  
Sickle Cell Anaemia ◽  
Children And Young Adults

Heart Rate Recovery Is Impaired After Maximal Exercise Challenge in Pediatric Sickle Cell Anemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3220-3220
Author(s):  
Anthony M. Alvarado ◽  
Stephanie A. Pelligra ◽  
Kendra M. Ward ◽  
Alexis A. Thompson ◽  
Robert I. Liem
Keyword(s):  
Sickle Cell ◽  
Exercise Testing ◽  
Maximal Exercise ◽  
Heart Rate Recovery ◽  
Cardiopulmonary Exercise Testing ◽  
Recovery Phase ◽  
Qtc Interval ◽  
Post Exercise ◽  
Children And Young Adults ◽  
The Difference

Abstract Abstract 3220 Slow heart rate recovery (HRR) after exercise, particularly at 1 and 2 minutes during recovery, is a strong indicator of autonomic nervous system (ANS) imbalance and represents an important risk factor for increased cardiovascular morbidity and mortality in the general population. Recent evidence suggests cardiovascular ANS dysfunction and vagal tone impairment also exist in individuals with sickle cell anemia (SCA). Despite the known impact of disease burden on exercise capacity and overall fitness in SCA, post-exercise HRR has not previously been studied in this population. The objective of this study was to examine HRR in the post-exercise recovery phase following maximal exercise testing in a cohort of children and young adults with SCA. Methods We prospectively performed maximal cardiopulmonary exercise testing using a ramp, cycle ergometry protocol in 60 subjects with SCA (hemoglobin SS and S-β0 thalassemia) and 20 controls without SCA or sickle cell trait matched for race and gender. Data from standard 12-lead electrocardiography (ECG) was assessed during a 10-minute recovery phase, and HR and corrected QT (QTc) interval measured from tracings obtained at 1-minute intervals. A single investigator performed all measurements manually using leads II, V5, and V6. Final values were averaged from 3 independent measurements. The difference between maximal HR and both HR at 1-minute (ΔHR1min) and 2-minute (ΔHR2min) recovery was our primary outcome. Between-group differences were compared using Mann-Whitney U testing (IBM, SPSS V20). The relationship between ΔHR1min and exercise parameters was examined using Spearman's rank correlation coefficient. Results Post-exercise ECG data from 58 subjects with SCA (median age 15.5 years) and 20 controls without SCA (median age 12 years) were interpretable for this analysis. A total of 30/58 (52%) and 22/58 (38%) subjects were male and on hydroxyurea, respectively. There was no significant difference in median baseline HR or QTc interval in subjects versus controls. Median peak HR was also not significantly different in the 2 groups. When compared to controls, subjects with SCA demonstrated significantly lower HR reserve (100 vs. 111 bpm, p = 0.005), representing the difference between peak and baseline HR. Impaired HRR, defined by slower declines in HR during recovery, was also evident among subjects with SCA following maximal exercise challenge. Although the absolute HR measured at each minute of recovery did not differ significantly in the 2 groups, subjects demonstrated significantly smaller median ΔHR1min (21 vs. 33 bpm, p < 0.0001) and ΔHR2min (39 vs. 51 bpm, p = 0.003), even after adjustment for age between groups. Significantly smaller ΔHR values were also noted in subjects at each minute up to 8 minutes throughout recovery. When compared to subjects not on hydroxyurea, subjects on treatment had significantly greater median ΔHR1min (25 vs. 19 bpm, p = 0.037) but similar ΔHR2min. In subjects with SCA, ΔHR1min correlated inversely with age (−0.41, p = 0.001) and directly with peak oxygen consumption (peak VO2) (0.30, p = 0.03) and oxygen delivery (ΔVO2/Δwork rate) (0.46, p < 0.0001), but not with baseline QTc interval or hemoglobin. Through mono-exponential curve fitting, we found that the time constant associated with HR decline over the first 5 minutes of recovery was greater in subjects with SCA versus controls (T = 128 sec, 95% CI [123, 134] versus 104 sec, 95% [97, 110]). Conclusions Compared to controls without SCA, children and young adults with SCA demonstrate impaired HRR following maximal cardiopulmonary exercise testing, as evidenced by smaller decrements in HR at 1 and 2 minutes during recovery and exponential time constants that indicate a longer period of time over which HR declines. Slower HRR is also associated with decreased fitness and measures of oxygen delivery during exercise testing in subjects with SCA. Although the mechanisms are not well understood, prolonged HRR in this population may in part be explained by ANS imbalance, suggesting either inadequate sympathetic withdrawal or suboptimal parasympathetic reactivation in the post-exercise period. Future studies should focus on delineating the role of the ANS in post-exercise HRR and assessing the prognostic potential of this marker as it relates to disease severity and outcomes in SCA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Heterogeneity of respiratory disease in children and young adults with sickle cell disease

Thorax ◽  
2017 ◽  
Vol 73 (6) ◽  
pp. 575-577 ◽  
Author(s):  
Alan Lunt ◽  
Lucy Mortimer ◽  
David Rees ◽  
Sue Height ◽  
Swee Lay Thein ◽  
...  
Keyword(s):  
Young Adults ◽  
Sickle Cell Disease ◽  
Lung Disease ◽  
Respiratory Disease ◽  
Sickle Cell ◽  
Elevated Serum ◽  
Serum Lactate Dehydrogenase ◽  
Cell Disease ◽  
Restrictive Lung Disease ◽  
Children And Young Adults

To detect and characterise different phenotypes of respiratory disease in children and young adults with sickle cell disease (SCD), 11 lung function and haematological biomarkers were analysed using k-means cluster analysis in a cohort of 114 subjects with SCD aged between 5 and 27 years. Three clusters were detected: cluster 1 had elevated pulmonary capillary blood volume, mixed obstructive/restrictive lung disease, hypoxia and moderately severe anaemia; cluster 2 were older patients with restrictive lung disease; and cluster 3 were younger patients with obstructive lung disease, elevated serum lactate dehydrogenase and bronchodilator reversibility. These results may inform more personalised management strategies to improve outcomes.

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