Passive smoking alters circulating naïve/memory lymphocyte T-cell subpopulations in children

Vardavas CI, Plada M, Tzatzarakis M, Marcos A, Warnberg J, Gomez‐Martinez S, Breidenassel C, Gonzalez‐Gross M, Tsatsakis AM, Saris WH., Moreno LA, Kafatos AG. Passive smoking alters circulating naïve/memory lymphocyte T‐cell subpopulations in children.
Pediatr Allergy Immunol 2010: 21: 1171–1178.
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Published inPediatric allergy and immunology Vol. 21; no. 8; pp. 1171 - 1178
Main Authors Vardavas, Constantine I., Plada, Maria, Tzatzarakis, Manolis, Marcos, Ascension, Warnberg, Julia, Gomez-Martinez, Sonia, Breidenassel, Christina, Gonzalez-Gross, Marcela, Tsatsakis, Aristeidis M., Saris, Wim H., Moreno, Luis A., Kafatos, Anthony G.
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.12.2010
Blackwell
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Abstract Vardavas CI, Plada M, Tzatzarakis M, Marcos A, Warnberg J, Gomez‐Martinez S, Breidenassel C, Gonzalez‐Gross M, Tsatsakis AM, Saris WH., Moreno LA, Kafatos AG. Passive smoking alters circulating naïve/memory lymphocyte T‐cell subpopulations in children.
Pediatr Allergy Immunol 2010: 21: 1171–1178.
© 2010 John Wiley & Sons A/S While it has been indicated that exposure to second‐hand smoke (SHS) can cause a local in vivo response, limited evidence exists on its possible systemic effects from population‐based levels of exposure. We investigated into a possible systemic response in the immune parameters and lymphocyte subsets, i.e. B cell (CD19+), T cell (CD4+CD45RO+, CD4+CD45RA+, CD3+CD45RO+, CD3+CD45RA+) and natural killer (CD3+CD16CD56+) lymphocyte subsets relative to exposure to SHS. Blood was drawn from healthy, verified non‐smoker, adolescent subjects (n = 68, mean age 14.2) and analysed for cotinine, antioxidants and lymphocyte immunophenotyping. SHS exposure was assessed using serum cotinine. Biomarker quantified exposure to SHS was correlated with a linear dose–response reduction in the percentages of memory CD4+CD45RO+ (p = 0.005) and CD3+CD45RO+ T‐cell subsets (p = 0.005 and p = 0.003, respectively) and a linear increase in the percentage of naïve CD4+CD45RA+ and CD3+CD45RA+ T‐cell subsets (p = 0.006 and p = 0.003, respectively). Additionally, higher exposure to SHS was associated with a higher CD4+CD45RA+ count (532 vs. 409 cells/ml, p = 0.017). Moreover, after controlling for age, gender, body mass index and plasma antioxidants, SHS exposure was found to be associated with the percentage of circulating naïve and memory CD4+ and CD3+ T‐cell subpopulations, as revealed through a linear regression analysis. These findings indicate a systemic immunological response in healthy adolescents exposed to population‐based levels of SHS exposure and imply an additional biological pathway for the interaction between exposure to SHS and its adverse effects on human health.
AbstractList While it has been indicated that exposure to second-hand smoke (SHS) can cause a local in vivo response, limited evidence exists on its possible systemic effects from population-based levels of exposure. We investigated into a possible systemic response in the immune parameters and lymphocyte subsets, i.e. B cell (CD19+), T cell (CD4+CD45RO+, CD4+CD45RA+, CD3+CD45RO+, CD3+CD45RA+) and natural killer (CD3+CD16CD56+) lymphocyte subsets relative to exposure to SHS. Blood was drawn from healthy, verified non-smoker, adolescent subjects (n = 68, mean age 14.2) and analysed for cotinine, antioxidants and lymphocyte immunophenotyping. SHS exposure was assessed using serum cotinine. Biomarker quantified exposure to SHS was correlated with a linear dose-response reduction in the percentages of memory CD4+CD45RO+ (p = 0.005) and CD3+CD45RO+ T-cell subsets (p = 0.005 and p = 0.003, respectively) and a linear increase in the percentage of naïve CD4+CD45RA+ and CD3+CD45RA+ T-cell subsets (p = 0.006 and p = 0.003, respectively). Additionally, higher exposure to SHS was associated with a higher CD4+CD45RA+ count (532 vs. 409 cells/ml, p = 0.017). Moreover, after controlling for age, gender, body mass index and plasma antioxidants, SHS exposure was found to be associated with the percentage of circulating naïve and memory CD4+ and CD3+ T-cell subpopulations, as revealed through a linear regression analysis. These findings indicate a systemic immunological response in healthy adolescents exposed to population-based levels of SHS exposure and imply an additional biological pathway for the interaction between exposure to SHS and its adverse effects on human health.While it has been indicated that exposure to second-hand smoke (SHS) can cause a local in vivo response, limited evidence exists on its possible systemic effects from population-based levels of exposure. We investigated into a possible systemic response in the immune parameters and lymphocyte subsets, i.e. B cell (CD19+), T cell (CD4+CD45RO+, CD4+CD45RA+, CD3+CD45RO+, CD3+CD45RA+) and natural killer (CD3+CD16CD56+) lymphocyte subsets relative to exposure to SHS. Blood was drawn from healthy, verified non-smoker, adolescent subjects (n = 68, mean age 14.2) and analysed for cotinine, antioxidants and lymphocyte immunophenotyping. SHS exposure was assessed using serum cotinine. Biomarker quantified exposure to SHS was correlated with a linear dose-response reduction in the percentages of memory CD4+CD45RO+ (p = 0.005) and CD3+CD45RO+ T-cell subsets (p = 0.005 and p = 0.003, respectively) and a linear increase in the percentage of naïve CD4+CD45RA+ and CD3+CD45RA+ T-cell subsets (p = 0.006 and p = 0.003, respectively). Additionally, higher exposure to SHS was associated with a higher CD4+CD45RA+ count (532 vs. 409 cells/ml, p = 0.017). Moreover, after controlling for age, gender, body mass index and plasma antioxidants, SHS exposure was found to be associated with the percentage of circulating naïve and memory CD4+ and CD3+ T-cell subpopulations, as revealed through a linear regression analysis. These findings indicate a systemic immunological response in healthy adolescents exposed to population-based levels of SHS exposure and imply an additional biological pathway for the interaction between exposure to SHS and its adverse effects on human health.
Vardavas CI, Plada M, Tzatzarakis M, Marcos A, Warnberg J, Gomez‐Martinez S, Breidenassel C, Gonzalez‐Gross M, Tsatsakis AM, Saris WH., Moreno LA, Kafatos AG. Passive smoking alters circulating naïve/memory lymphocyte T‐cell subpopulations in children.
Pediatr Allergy Immunol 2010: 21: 1171–1178.
© 2010 John Wiley & Sons A/S While it has been indicated that exposure to second‐hand smoke (SHS) can cause a local in vivo response, limited evidence exists on its possible systemic effects from population‐based levels of exposure. We investigated into a possible systemic response in the immune parameters and lymphocyte subsets, i.e. B cell (CD19+), T cell (CD4+CD45RO+, CD4+CD45RA+, CD3+CD45RO+, CD3+CD45RA+) and natural killer (CD3+CD16CD56+) lymphocyte subsets relative to exposure to SHS. Blood was drawn from healthy, verified non‐smoker, adolescent subjects (n = 68, mean age 14.2) and analysed for cotinine, antioxidants and lymphocyte immunophenotyping. SHS exposure was assessed using serum cotinine. Biomarker quantified exposure to SHS was correlated with a linear dose–response reduction in the percentages of memory CD4+CD45RO+ (p =   0.005) and CD3+CD45RO+ T‐cell subsets (p =   0.005 and p =   0.003, respectively) and a linear increase in the percentage of naïve CD4+CD45RA+ and CD3+CD45RA+ T‐cell subsets (p =   0.006 and p =   0.003, respectively). Additionally, higher exposure to SHS was associated with a higher CD4+CD45RA+ count (532 vs. 409 cells/ml, p =   0.017). Moreover, after controlling for age, gender, body mass index and plasma antioxidants, SHS exposure was found to be associated with the percentage of circulating naïve and memory CD4+ and CD3+ T‐cell subpopulations, as revealed through a linear regression analysis. These findings indicate a systemic immunological response in healthy adolescents exposed to population‐based levels of SHS exposure and imply an additional biological pathway for the interaction between exposure to SHS and its adverse effects on human health.
While it has been indicated that exposure to second-hand smoke (SHS) can cause a local in vivo response, limited evidence exists on its possible systemic effects from population-based levels of exposure. We investigated into a possible systemic response in the immune parameters and lymphocyte subsets, i.e. B cell (CD19+), T cell (CD4+CD45RO+, CD4+CD45RA+, CD3+CD45RO+, CD3+CD45RA+) and natural killer (CD3+CD16CD56+) lymphocyte subsets relative to exposure to SHS. Blood was drawn from healthy, verified non-smoker, adolescent subjects (n = 68, mean age 14.2) and analysed for cotinine, antioxidants and lymphocyte immunophenotyping. SHS exposure was assessed using serum cotinine. Biomarker quantified exposure to SHS was correlated with a linear dose-response reduction in the percentages of memory CD4+CD45RO+ (p = 0.005) and CD3+CD45RO+ T-cell subsets (p = 0.005 and p = 0.003, respectively) and a linear increase in the percentage of naïve CD4+CD45RA+ and CD3+CD45RA+ T-cell subsets (p = 0.006 and p = 0.003, respectively). Additionally, higher exposure to SHS was associated with a higher CD4+CD45RA+ count (532 vs. 409 cells/ml, p = 0.017). Moreover, after controlling for age, gender, body mass index and plasma antioxidants, SHS exposure was found to be associated with the percentage of circulating naïve and memory CD4+ and CD3+ T-cell subpopulations, as revealed through a linear regression analysis. These findings indicate a systemic immunological response in healthy adolescents exposed to population-based levels of SHS exposure and imply an additional biological pathway for the interaction between exposure to SHS and its adverse effects on human health.
Vardavas CI, Plada M, Tzatzarakis M, Marcos A, Warnberg J, Gomez‐Martinez S, Breidenassel C, Gonzalez‐Gross M, Tsatsakis AM, Saris WH., Moreno LA, Kafatos AG. Passive smoking alters circulating naïve/memory lymphocyte T‐cell subpopulations in children.
Pediatr Allergy Immunol 2010: 21: 1171–1178.
© 2010 John Wiley & Sons A/S While it has been indicated that exposure to second‐hand smoke (SHS) can cause a local in vivo response, limited evidence exists on its possible systemic effects from population‐based levels of exposure. We investigated into a possible systemic response in the immune parameters and lymphocyte subsets, i.e. B cell (CD19+), T cell (CD4+CD45RO+, CD4+CD45RA+, CD3+CD45RO+, CD3+CD45RA+) and natural killer (CD3+CD16CD56+) lymphocyte subsets relative to exposure to SHS. Blood was drawn from healthy, verified non‐smoker, adolescent subjects (n = 68, mean age 14.2) and analysed for cotinine, antioxidants and lymphocyte immunophenotyping. SHS exposure was assessed using serum cotinine. Biomarker quantified exposure to SHS was correlated with a linear dose–response reduction in the percentages of memory CD4+CD45RO+ (p = 0.005) and CD3+CD45RO+ T‐cell subsets (p = 0.005 and p = 0.003, respectively) and a linear increase in the percentage of naïve CD4+CD45RA+ and CD3+CD45RA+ T‐cell subsets (p = 0.006 and p = 0.003, respectively). Additionally, higher exposure to SHS was associated with a higher CD4+CD45RA+ count (532 vs. 409 cells/ml, p = 0.017). Moreover, after controlling for age, gender, body mass index and plasma antioxidants, SHS exposure was found to be associated with the percentage of circulating naïve and memory CD4+ and CD3+ T‐cell subpopulations, as revealed through a linear regression analysis. These findings indicate a systemic immunological response in healthy adolescents exposed to population‐based levels of SHS exposure and imply an additional biological pathway for the interaction between exposure to SHS and its adverse effects on human health.
Author Warnberg, Julia
Tsatsakis, Aristeidis M.
Gomez-Martinez, Sonia
Saris, Wim H.
Plada, Maria
Kafatos, Anthony G.
Moreno, Luis A.
Vardavas, Constantine I.
Marcos, Ascension
Gonzalez-Gross, Marcela
Tzatzarakis, Manolis
Breidenassel, Christina
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Vardavas, Constantine I
Protoyeraki, Eva
Viskadourou, Anna
Hatzis, Christos
Sarri, Katerina
Sbokos, Manolis
Kafatos, Anthony
Fasoulaki, Maria
Plada, Maria
Kiriakakis, Michael
Papadaki, Angeliki
Tsibinos, George
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Copyright 2010 John Wiley & Sons A/S
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Issue 8
Keywords Human
Immunopathology
Pediatrics
Memory disorder
Cognitive disorder
Immune response
lymphocytes
Naive cell
second-hand smoke
Hand
Cell subpopulation
Memory lymphocyte
Immunology
children
T-Lymphocyte
Passive smoking
Child
Language English
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CC BY 4.0
2010 John Wiley & Sons A/S.
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Heraklion HELENA study group members: Anthony Kafatos, Caroline Codrington, Marıa Plada, Angeliki Papadaki, Katerina Sarri, Anna Viskadourou, Christos Hatzis, Michael Kiriakakis, George Tsibinos, Constantine I. Vardavas, Manolis Sbokos, Eva Protoyeraki and Maria Fasoulaki.
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PublicationTitle Pediatric allergy and immunology
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References Han YY, Lee YL, Guo YL. Indoor environmental risk factors and seasonal variation of childhood asthma. Pediatr Allergy Immunol 2009; 20(8): 748-56.
Xepapadaki P, Manios Y, Liarigkovinos T, et al. Association of passive exposure of pregnant women to environmental tobacco smoke with asthma symptoms in children. Pediatr Allergy Immunol 2009: 20: 423-9.
Moffatt RJ, Chelland SA, Pecott D, Stamford BA. Acute exposure to environmental tobacco smoke reduces HDL-C and HDL2-C. Prev Med 2004: 38: 637-41.
Yuan H, Wong LS, Bhattacharya M, et al. The effect of secondhand smoke on biological processes important in atherogenesis. BMC Cardiovasc Disord 2007: 8: 1.
Bhalla D, Hirata F, Rishi A, Gairola CG. Cigarette smoke, inflammation, and lung injury: a mechanistic perspective. J Toxicol Environ Health B 2009: 12: 45-69.
Benowitz NL. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev 1996: 18: 188-204.
Nakata A, Tanigawa T, Araki S, Sakurai S, Iso H. Lymphocyte subpopulations among passive smokers. JAMA 2004: 291: 1699-700.
Leone A, Giannini D, Bellotto C, Balbarini A. Passive smoking and coronary heart disease. Curr Vasc Pharmacol 2004: 2: 175-82.
Luppi P, Lain KY, Jeyabalan A, DeLoia JA. The effect of cigarette smoking on circulating maternal leukocytes during pregnancy. J Immunol 2007: 122: 214-9.
Al-Delaimy WK, Willet WC. Measurement of tobacco smoke exposure: comparison of toenail nicotine biomarkers and self reports. Cancer Epidemiol Biomarkers Prev 2008: 17: 1255-61.
Kosecik M, Erel O, Sevinc E, Selek S. Increased oxidative stress in children exposed to passive smoking. Int J Cardiol 2005: 100: 61-4.
Béghin L, Castera M, Manios Y, et al. Quality assurance of ethical issues and regulatory aspects relating to good clinical practices in the HELENA Cross Sectional Study. Int J Obes (Lond) 2008: 32 (Suppl. 5): S12-8.
Bramer SL, Kallungal BA. Clinical considerations in study designs that use cotinine as a biomarker. Biomarkers 2003: 8: 187-203.
World Health Organization (1999) Consultation report. World Health Organization Division of Non communicable Disease, Tobacco Free Initiative. International Consultation on Environmental Tobacco Smoke (ETS) and Child Health, Geneva 1999. http://www.who.int/tobacco/research/en/ets_report. Viewed 3 March 2009.
Flouris MD, Metsios GS, Carrillo AE, et al. Acute and short-term effects of secondhand smoke on lung function and cytokine production. Am J Respir Crit Care Med 2009: 179: 1029-33.
Biagini JM, LeMasters GK, Ryan PH, et al. Environmental risk factors of rhinitis in early infancy. Pediatr Allergy Immunol 2006: 17: 278-84.
Nakata A, Takahashi M, Irie M, Fujioka Y, Haratani T, Araki S. Relationship between cumulative effects of smoking and memory CD4+ T lymphocyte subpopulations. Addict Behav 2007: 32: 1526-31.
Hockertz S, Emmendorffer A, Scherer G, et al. Acute effects of smoking and high experimental exposure to environmental tobacco smoke (ETS) on the immune system. Cell Biol Toxicol 1994: 10: 177-90.
Zhou X. CD4+ T cells in atherosclerosis. Biomed Pharmacother 2003: 57: 287-91.
Vardavas CI, Tzatzarakis M, Tsatsakis A, et al. Biomarkers of passive smoking among Greek preschool children. Eur J Pediatr 2006: 165: 891-6.
Heis C, Amabile N, Lee AC, et al. Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function. J Am Coll Cardiol 2008: 51: 1760-71.
Gonzalez-Gross M, Breidenassel C, Gomez-Martinez S, et al. Sampling and processing of fresh blood samples within a European multicenter nutritional study: evaluation of biomarker stability during transport and storage. Int J Obes 2008: 32: S66-75.
Moreno L, González-Gross M, Kersting M, et al. Assessing, understanding and modifying nutritional status, eating habits and physical activity in European adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Public Health Nutr 2008: 11: 288-99.
Halvorsen B, Otterdal K, Dahl TB, et al. Atherosclerotic plaque stability-what determines the fate of a plaque? Prog Cardiovasc Dis 2008: 51: 183-94.
Rubin RN, Navon L, Cassano PA. Relationship of serum antioxidants to asthma prevalence in youth. Am J Respir Crit Care Med 2004: 169: 393-8.
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References_xml – reference: Heis C, Amabile N, Lee AC, et al. Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function. J Am Coll Cardiol 2008: 51: 1760-71.
– reference: Han YY, Lee YL, Guo YL. Indoor environmental risk factors and seasonal variation of childhood asthma. Pediatr Allergy Immunol 2009; 20(8): 748-56.
– reference: Moffatt RJ, Chelland SA, Pecott D, Stamford BA. Acute exposure to environmental tobacco smoke reduces HDL-C and HDL2-C. Prev Med 2004: 38: 637-41.
– reference: Béghin L, Castera M, Manios Y, et al. Quality assurance of ethical issues and regulatory aspects relating to good clinical practices in the HELENA Cross Sectional Study. Int J Obes (Lond) 2008: 32 (Suppl. 5): S12-8.
– reference: Bhalla D, Hirata F, Rishi A, Gairola CG. Cigarette smoke, inflammation, and lung injury: a mechanistic perspective. J Toxicol Environ Health B 2009: 12: 45-69.
– reference: Hockertz S, Emmendorffer A, Scherer G, et al. Acute effects of smoking and high experimental exposure to environmental tobacco smoke (ETS) on the immune system. Cell Biol Toxicol 1994: 10: 177-90.
– reference: Luppi P, Lain KY, Jeyabalan A, DeLoia JA. The effect of cigarette smoking on circulating maternal leukocytes during pregnancy. J Immunol 2007: 122: 214-9.
– reference: Yuan H, Wong LS, Bhattacharya M, et al. The effect of secondhand smoke on biological processes important in atherogenesis. BMC Cardiovasc Disord 2007: 8: 1.
– reference: Rubin RN, Navon L, Cassano PA. Relationship of serum antioxidants to asthma prevalence in youth. Am J Respir Crit Care Med 2004: 169: 393-8.
– reference: Al-Delaimy WK, Willet WC. Measurement of tobacco smoke exposure: comparison of toenail nicotine biomarkers and self reports. Cancer Epidemiol Biomarkers Prev 2008: 17: 1255-61.
– reference: Biagini JM, LeMasters GK, Ryan PH, et al. Environmental risk factors of rhinitis in early infancy. Pediatr Allergy Immunol 2006: 17: 278-84.
– reference: Zhou X. CD4+ T cells in atherosclerosis. Biomed Pharmacother 2003: 57: 287-91.
– reference: Nakata A, Takahashi M, Irie M, Fujioka Y, Haratani T, Araki S. Relationship between cumulative effects of smoking and memory CD4+ T lymphocyte subpopulations. Addict Behav 2007: 32: 1526-31.
– reference: Bramer SL, Kallungal BA. Clinical considerations in study designs that use cotinine as a biomarker. Biomarkers 2003: 8: 187-203.
– reference: Flouris MD, Metsios GS, Carrillo AE, et al. Acute and short-term effects of secondhand smoke on lung function and cytokine production. Am J Respir Crit Care Med 2009: 179: 1029-33.
– reference: Leone A, Giannini D, Bellotto C, Balbarini A. Passive smoking and coronary heart disease. Curr Vasc Pharmacol 2004: 2: 175-82.
– reference: Xepapadaki P, Manios Y, Liarigkovinos T, et al. Association of passive exposure of pregnant women to environmental tobacco smoke with asthma symptoms in children. Pediatr Allergy Immunol 2009: 20: 423-9.
– reference: Benowitz NL. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev 1996: 18: 188-204.
– reference: Gonzalez-Gross M, Breidenassel C, Gomez-Martinez S, et al. Sampling and processing of fresh blood samples within a European multicenter nutritional study: evaluation of biomarker stability during transport and storage. Int J Obes 2008: 32: S66-75.
– reference: Vardavas CI, Tzatzarakis M, Tsatsakis A, et al. Biomarkers of passive smoking among Greek preschool children. Eur J Pediatr 2006: 165: 891-6.
– reference: Kosecik M, Erel O, Sevinc E, Selek S. Increased oxidative stress in children exposed to passive smoking. Int J Cardiol 2005: 100: 61-4.
– reference: Moreno L, González-Gross M, Kersting M, et al. Assessing, understanding and modifying nutritional status, eating habits and physical activity in European adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study. Public Health Nutr 2008: 11: 288-99.
– reference: Halvorsen B, Otterdal K, Dahl TB, et al. Atherosclerotic plaque stability-what determines the fate of a plaque? Prog Cardiovasc Dis 2008: 51: 183-94.
– reference: Nakata A, Tanigawa T, Araki S, Sakurai S, Iso H. Lymphocyte subpopulations among passive smokers. JAMA 2004: 291: 1699-700.
– reference: World Health Organization (1999) Consultation report. World Health Organization Division of Non communicable Disease, Tobacco Free Initiative. International Consultation on Environmental Tobacco Smoke (ETS) and Child Health, Geneva 1999. http://www.who.int/tobacco/research/en/ets_report. Viewed 3 March 2009.
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Snippet Vardavas CI, Plada M, Tzatzarakis M, Marcos A, Warnberg J, Gomez‐Martinez S, Breidenassel C, Gonzalez‐Gross M, Tsatsakis AM, Saris WH., Moreno LA, Kafatos AG....
While it has been indicated that exposure to second-hand smoke (SHS) can cause a local in vivo response, limited evidence exists on its possible systemic...
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SubjectTerms Adolescent
Antigens, CD - metabolism
Antigens, Differentiation - metabolism
Biological and medical sciences
Biomarkers - blood
Child
children
Cotinine - blood
Europe
Fundamental and applied biological sciences. Psychology
Fundamental immunology
General aspects
Humans
immune response
Immunologic Memory
Immunophenotyping
lymphocytes
Medical sciences
passive smoking
Population Groups
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
second-hand smoke
T-Lymphocyte Subsets - drug effects
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
T-Lymphocyte Subsets - pathology
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
T-Lymphocytes - pathology
Tobacco Smoke Pollution - adverse effects
Tobacco Smoke Pollution - prevention & control
Title Passive smoking alters circulating naïve/memory lymphocyte T-cell subpopulations in children
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