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Marked skeletal muscle deficits are associated with 6-minute walk distance in paediatric pulmonary hypertension

Published online by Cambridge University Press:  11 February 2021

Catherine M. Avitabile Open the ORCID record for Catherine M. Avitabile [Opens in a new window] ,
Sofia Saavedra ,
Nithya Sivakumar ,
Elizabeth Goldmuntz ,
Stephen M. Paridon  and
Babette S. Zemel
Catherine M. Avitabile*
Affiliation:
Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA Division of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Sofia Saavedra
Affiliation:
Division of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Nithya Sivakumar
Affiliation:
Division of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Elizabeth Goldmuntz
Affiliation:
Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA Division of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Stephen M. Paridon
Affiliation:
Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA Division of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Babette S. Zemel
Affiliation:
Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
*
Author for correspondence: Catherine Avitabile, MD, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, 8NW49 Philadelphia, PA 19104. Phone: 215-590-4040. E-mail: avitabilec@email.chop.edu
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Abstract

Background:

Poor growth is common in children with pulmonary hypertension; however, skeletal muscle deficits have not been described and the association between muscle deficits and functional status is unknown.

Methods:

Patients aged 8–18 years with pulmonary hypertension (diagnostic Groups 1, 2, or 3) and World Health Organization functional class I or II underwent dual-energy absorptiometry to measure leg lean mass Z-score (a surrogate for skeletal muscle). Muscle strength was assessed using dynamometry. Physical activity questionnaires were administered. Clinical data, including 6-minute walk distance, were reviewed. Relationships between skeletal muscle, physical activity score, and 6-minute walk distance were assessed by correlations and linear regression.

Results:

Sixteen patients (12.1 ± 3.2 years, 50% female, 56% Group 1, 56% functional class II) were enrolled. Leg lean mass Z-score was significantly less than reference data (−1.40 ± 1.12 versus 0.0 ± 0.9, p < 0.001) and worse in those with functional class II versus I (−2.10 ± 0.83 versus −0.50 ± 0.73, p < 0.01). Leg lean mass Z-score was positively associated with right ventricular systolic function by tricuspid annular plane systolic Z-score (r = 0.54, p = 0.03) and negatively associated with indexed pulmonary vascular resistance (r = −0.78, p < 0.001). Leg lean mass Z-score and forearm strength were positively associated with physical activity score. When physical activity score was held constant, leg lean mass Z-score independently predicted 6-minute walk distance (R2 = 0.39, p = 0.03).

Conclusions:

Youth with pulmonary hypertension demonstrate marked skeletal muscle deficits in association with exercise intolerance. Future studies should investigate whether low leg lean mass is a marker of disease severity or an independent target that can be improved.

Keywords

Skeletal musclelean massdensitometrymuscle strength6-minute walk testphysical activity
Type
Original Article
Information
Cardiology in the Young , Volume 31 , Issue 9 , September 2021 , pp. 1426 - 1433
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Mullen, MP, Andrus, J, Labella, MH, et al. Quality of life and parental adjustment in pediatric pulmonary hypertension. Chest 2014; 145: 237–244.CrossRefGoogle ScholarPubMed
Ploegstra, MJ, Ivy, DD, Wheeler, JG, et al. Growth in children with pulmonary arterial hypertension: a longitudinal retrospective multiregistry study. Lancet Respir Med 2016; 4: 281–290.CrossRefGoogle ScholarPubMed
Avitabile, CM, Leonard, MB, Zemel, BS, et al. Lean mass deficits, vitamin D status and exercise capacity in children and young adults after Fontan palliation. Heart 2014; 100: 1702–1707.CrossRefGoogle Scholar
Avitabile, CM, Goldberg, DJ, Leonard, MB, et al. Leg lean mass correlates with exercise systemic output in young Fontan patients. Heart 2018; 104: 680–684.CrossRefGoogle ScholarPubMed
Burnham, JM, Shults, J, Dubner, SE, et al. Bone density, structure, and strength in juvenile idiopathic arthritis: importance of disease severity and muscle deficits. Arthritis Rheum 2008; 58: 2518–2527.CrossRefGoogle ScholarPubMed
Thayu, M, Denson, LA, Shults, J, et al. Determinants of changes in linear growth and body composition in incident pediatric Crohn’s disease. Gastroenterology 2011; 139: 430–438.CrossRefGoogle Scholar
Wetzsteon, RJ, Kalkwarf, HJ, Shults, J, et al. Volumetric bone mineral density and bone structure in childhood chronic kidney disease. J Bone Miner Res 2011; 26: 2235–2244.CrossRefGoogle ScholarPubMed
Foster, BJ, Kalkwarf, HJ, Shults, J, et al. Association of chronic kidney disease with muscle deficits in children. J Am Soc Nephrol 2011; 22: 377–386.CrossRefGoogle ScholarPubMed
Bauer, R, Dehnert, C, Schoene, P, et al. Skeletal muscle dysfunction in patients with idiopathic pulmonary arterial hypertension. Respir Med 2007; 101: 2366–2369.CrossRefGoogle ScholarPubMed
Duvall, MG, Pikman, Y, Kantor, DB. Pulmonary hypertension associated with scurvy and vitamin deficiencies in an autistic child. Pediatrics 2013; 132: e1699–e1703.CrossRefGoogle Scholar
Zijlstra, WMH, Ploegstra, MJ, Vissia-Kazemier, T. Physical activity in pediatric pulmonary arterial hypertension measured by accelerometry. A candidate clinical endpoint. Am J Respir Crit Care Med 2017; 196: 220–227.CrossRefGoogle ScholarPubMed
Haddad, F, Zaldivar, F, Cooper, DM, et al. IL-6-induced skeletal muscle atrophy. J Appl Physiol 2005; 98: 911–917.CrossRefGoogle ScholarPubMed
Janssen, SPM, Gayan-Ramirez, G, Van Den Bergh, A, et al. Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats. Circulation 2005; 111: 996–1005.CrossRefGoogle ScholarPubMed
Reid, MB, Lännergren, J, Westerblad, H. Respiratory and limb muscle weakness induced by tumor necrosis factor-α. Am J Respir Crit Care Med 2002; 166: 479–484.CrossRefGoogle ScholarPubMed
Franssen, FM, Wouters, EF, Schols, AM. The contribution of starvation, deconditioning, and ageing to the observed alterations in peripheral skeletal muscle in chronic organ disease. Clin Nutr 2002; 21: 1–14.CrossRefGoogle Scholar
Dimopoulos, S, Tzanis, G, Manetos, C, et al. Peripheral muscle microcirculatory alterations in patients with pulmonary arterial hypertension: a pilot study. Respir Care 2013; 58: 2134–2141.CrossRefGoogle ScholarPubMed
Barbosa, PB, Ferreira, EM, Arakaki, JS, et al. Kinetics of skeletal muscle O2 delivery and utilization at the onset of heavy-intensity exercise in pulmonary arterial hypertension. Eur J Appl Physiol 2011; 111: 1851–1861.CrossRefGoogle Scholar
Koestenberger, M, Ravekes, W, Everett, AD, et al. Right ventricular function in infants, children and adolescents: reference values of the tricuspid annular plane systolic excursion (TAPSE) in 640 healthy patients and calculation of z score values. J Am Soc Echocardiogr 2009; 22: 715–719.CrossRefGoogle ScholarPubMed
ATS Committee on proficiency standards for clinical pulmonary function laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166: 111–117.CrossRefGoogle Scholar
Morris, NM, Udry, JR. Validation of a self-administered instrument to assess stage of adolescent development. J Youth Adol 1980; 9: 271–280.CrossRefGoogle ScholarPubMed
Burnham, JM, Shults, J, Semeao, E, et al. Body-composition alterations consistent with cachexia in children and young adults with Crohn disease. Am J Clin Nutr 2005; 82: 413–420.CrossRefGoogle Scholar
Dougherty, KA, Schall, JI, Rovner, AJ, et al. Attenuated maximal muscle strength and peak power in children with sickle cell disease. J Pediatr Hematol Oncol 2011; 33: 93–97.CrossRefGoogle ScholarPubMed
Lee, DY, Wetzsteon, RJ, Zemel, BS, et al. Muscle torque relative to cross-sectional area and the functional muscle-bone unit in children and adolescents with chronic disease. J Bone Miner Res 2015; 30: 575–583.CrossRefGoogle ScholarPubMed
Leggin, BG, Neuman, RM, Iannotti, JP, et al. Intrarater and interrater reliability of three isometric dynamometers in assessing shoulder strength. J Shoulder Elbow Surg 1996; 5: 18–24.CrossRefGoogle ScholarPubMed
Marino, BS, Shera, D, Wernovsky, G, et al. The development of the pediatric cardiac quality of life inventory: a quality of life measure for children and adolescents with heart disease. Qual Life Res 2008; 17: 613–626.CrossRefGoogle ScholarPubMed
Crocker, PR, Bailey, DA, Faulkner, RA, et al. Measuring general levels of physical activity: preliminary evidence for the Physical Activity Questionnaire for Older Children. Med Sci Sports Exercise 1997; 29: 1344–1349.CrossRefGoogle Scholar
Kowalski, KC, Crocker, PRE, Faulkner, RA. Validation of a physical activity questionnaire for older children. Pediatr Exercise Sci 1997; 9: 174–186.CrossRefGoogle Scholar
Kowalski, KC, Crocker, PRE, Kowalski, NP. Convergent validity of the physical activity questionnaire for adolescents. Pediatr Exercise Sci 1997; 9: 342–352.CrossRefGoogle Scholar
Saenger, AK, Laha, TJ, Bremmer, DE, et al. Quantification of serum 25-hydroxyvitamin D(2) and D(3) using HPLC-tandem mass spectrometry and examination of reference intervals for diagnosis of vitamin D deficiency. Am J Clin Pathol 2006; 125: 914–920.CrossRefGoogle Scholar
Ross, AC. The 2011 report on dietary reference intakes for calcium and vitamin D. Public Health Nutr 2011; 14: 938–939.CrossRefGoogle ScholarPubMed
Ogden, CL, Kuczmarski, RJ, Flegal, KM, et al. Centers for disease control and prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 2002; 109: 45–60.CrossRefGoogle Scholar
Zemel, BS, Kalkwarf, HJ, Gilsanz, V, et al. Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study. J Clin Endocrinol Metab 2011: 96: 3160–3169.CrossRefGoogle ScholarPubMed
Kalkwarf, HJ, Zemel, BS, Gilsanz, V, et al. The bone mineral density in childhood study: bone mineral content and density according to age, sex, and race. J Clin Endocrinol Metab 2007; 92: 2087–2099.CrossRefGoogle Scholar
Zemel, BS, Leonard, MB, Kelly, A, et al. Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children. J Clin Endocrinol Metab 2010; 95: 1265–1273.CrossRefGoogle ScholarPubMed
Cole, TJ. The LMS method for constructing normalized growth standards. Eur J Clin Nutr 1990; 44: 45–60.Google ScholarPubMed
Moledina, S, Hislop, AA, Foster, H, et al. Childhood idiopathic pulmonary arterial hypertension: a national cohort study. Heart 2010; 96: 1401–1406.CrossRefGoogle ScholarPubMed
Barst, RJ, McGoon, MD, Elliott, CG, et al. Survival in childhood pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Circulation 2012; 125: 113–122.CrossRefGoogle ScholarPubMed
Ploegstra, M, Zijlstra, WMH, Douwes, JM, et al. Prognostic factors in pediatric pulmonary arterial hypertension: a systematic review and meta-analysis. Int J Cardiol 2015; 184: 198–207.CrossRefGoogle ScholarPubMed
Hales, CM, Carroll, MD, Fryar, CD, et al. Prevalence of obesity among adults and youth: United States, 2015–2016. NCHS Data Brief 2017; 288: 1–8.Google Scholar
Calella, P, Valerio, G, Thomas, M, et al. Association between body composition and pulmonary function in children and young people with cystic fibrosis. Nutrition 2018; 48; 73–76.CrossRefGoogle Scholar
Calella, P, Valerio, G, Brodlie, M, et al. Cystic fibrosis, body composition, and health outcomes: a systematic review. Nutrition 2018; 55–56: 131–139.CrossRefGoogle ScholarPubMed
Lee, D, Lewis, JD, Shults, J, et al. The association of diet and exercise with body composition in pediatric Crohn’s disease. Inflamm Bowel Dis 2018; 24: 1368–1375.CrossRefGoogle ScholarPubMed
Dougherty, KA, Bertolaso, C, Schall, JI, et al. Muscle strength, power, and torque deficits in children with type SS sickle cell disease. J Pediatr Hematol Oncol 2018; 40: 348–354.CrossRefGoogle ScholarPubMed
Guyton, AC, Douglas, BH, Langston, JB, et al. Instantaneous increase in mean circulatory pressure and cardiac output at onset of muscular activity. Circ Res 1962; 11: 431–441.CrossRefGoogle ScholarPubMed
Breda, AP, de Albuquerque, ALP, Jardim, C, et al. Skeletal muscle abnormalities in pulmonary arterial hypertension. PLoS One 2014; 9: e114101.CrossRefGoogle ScholarPubMed
Batt, J, Ahmed, SS, Correa, J, et al. Skeletal muscle dysfunction in idiopathic pulmonary arterial hypertension. Am J Respir Cell Mol Biol 2014; 50: 74–86.Google ScholarPubMed
Mainguy, V, Maltais, F, Saey, D, et al. Peripheral muscle dysfunction in idiopathic pulmonary arterial hypertension. Thorax 2010; 65: 113–117.CrossRefGoogle ScholarPubMed
Tolle, J, Waxman, A, Systrom, D. Impaired systemic oxygen extraction at maximum exercise in pulmonary hypertension. Med Sci Sports Exercise 2008; 40: 3–8.CrossRefGoogle ScholarPubMed
Abman, SH, Hansmann, G, Archer, SL, et al. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society. Circulation 2015; 132: 2037–2099.CrossRefGoogle ScholarPubMed
del Cerro, MJ, Abman, S, Diaz, G, et al. A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: report from the PVRI pediatric taskforce, Panama 2011. Pulm Circ 2011; 1: 286–989.CrossRefGoogle Scholar
Jackman, RW, Kandarian, SC. The molecular basis of skeletal muscle atrophy. Am J Physiol Cell Physiol 2004; 287: 834–843.CrossRefGoogle ScholarPubMed
D’Antona, G, Pellegrino, MA, Adami, R, et al. The effect of ageing and immobilization on structure and function of human skeletal muscle fibres. J Physiol 2003; 552: 499–511.CrossRefGoogle ScholarPubMed
Trappe, S, Trappe, T, Gallagher, P, et al. Human single muscle fibre function with 84 day bed-rest and resistance exercise. J Physiol 2004; 557: 501–513.CrossRefGoogle ScholarPubMed
Voss, C, Dean, PH, Gardner, RF, et al. Validity and reliability of the Physical Activity Questionnaire for Children (PAQ-C) and Adolescents (PAQ-A) in individuals with congenital heart disease. PLoS One 2017; 12: e0175806. https://doi.org/10.1371/journal.pone.0175806 CrossRefGoogle ScholarPubMed