PhD Thesis, Magdalena Muc i ii PhD Thesis, Magdalena Muc Departamento de Ciências da Vida Faculdade de Ciências e Tecnologia Universidade de Coimbra The association of childhood obesity with asthma and rhinitis symptoms in 6-8years old children living in the Coimbra district, Portugal: the role of environmental, family and socioeconomic factors. Magdalena Muc Advisor: Prof. Dr Cristina Maria Proença Padez (Departament of Life Sciences, Faculty of Sciences and Technology, University of Coimbra) Co-advisor: Professora Doutora Anabela Mota-Pinto (Institute of General Pathology, Faculty of Medicine, University of Coimbra) Thesis presented to the Faculty of Sciences and Technology of the University of Coimbra towards the attainment of the degree of Doctor in Biological Anthropology. iii iv PhD Thesis, Magdalena Muc Doctorate in Biological Anthropology Department of Life Sciences Faculty of Sciences and Technology University of Coimbra Title: The association of childhood obesity with asthma and rhinitis symptoms in 6-8 years old children living in the Coimbra district, Portugal: the role of environmental, family and socioeconomic factors. Advisors: Cristina Maria Proença Padez and Anabela Mota Pinto Year: 2014 Financial support: Fundação para a Ciência e a Tecnologia (SFRH/BD/66877/2009) Cover page: painting by Carla Graciana Soares v ' vi PhD Thesis, Magdalena Muc “But I don't want to go among mad people,' Alice remarked. 'Oh, you can't help that,' said the Cat: 'we're all mad here. I'm mad. You're mad.' 'How do you know I'm mad?' said Alice. 'You must be,' said the Cat, 'or you wouldn't have come here.” Lewis Carroll, “Alice’s Adventures in Wonderland” vii viii PhD Thesis, Magdalena Muc Abstract Introduction: The increase in the prevalence of obesity, asthma, and rhinitis in childhood suggests a link between them. Socio-demographic and early life risk factors, sedentary lifestyle, diet and tobacco exposure, among other factors, could be responsible for the increase in the number of obese asthmatics. There are two main phenotypes of obese asthmatics described so far and one includes children. The existence of obesity- related asthma and rhinitis means that obese children with asthma or rhinitis are not only different from healthy children, but also from normal-weight children with these diseases. Little is known about the effects of the risk factors on the different asthma phenotypes. Objectives: To investigate how common environmental, family and socioeconomic risk factors for obesity, asthma and rhinitis modulate the association between these diseases and to study whether birth weight (BW) values differ between overweight children with asthma/rhinitis and children with asthma/rhinitis and normal weight. Methods: This cross-sectional study was done in a sample of 1043 children 6-8 years old from the Coimbra district. Data on asthma (A), rhinitis (R) and environmental and family factors were obtained using the ISAAC (The International Study of Asthma and Allergies in Childhood) questionnaires. Obesity indicators were calculated: Body Mass Index (BMI); BMI z-score based on the World Health Organization’s (WHO) methodology; Waist to Height Ratio (WHtR) and the body fat percentage (%BF). Obesity (OB) and overweight (O) were defined using the WHO cut-off points. The cut-off point of WHtR=0.5 was used to define abdominal obesity (AOB). %BF values were categorized as normal, overfat (OF) and high fat (HF) using age and gender-specific percentiles. The risk factors studied were: BW; breastfeeding (BFD) ever, total (TBFD) and exclusive (EBFD); tobacco exposure in early life and in childhood; dietary patterns; vigorous physical activity (VPA); television (TV) watching; heavy truck traffic (HTT); degree of urbanization of the residential area and socioeconomic status (SES). Chi 2 tests were applied to calculate the prevalences of studied diseases. Logistic regressions were used to study the association between OB, A, and R with risk factors. Student’s T-test and one-way ANOVA means comparisons were applied to compare means. Logistic regressions were used to study the association of OB with A/R and the role of risk factors in these associations. One-way ANOVA was performed to compare means of BW between: 1. children with (+) A, wheeze (W) or R (A+/W+/R+) and O+/OF+; 2. children A+/W+/R+ but without (-) O or OF (O-/OF-); 3. O+/OF+ but A-/W-/R- and 4. children A-/W-/R- and O-/OF-. Results: Of all studied children, 23.3% were O, 10.8% OB. Factors related to a significant increase in OB risk were: high BW; being a girl; saturated fat diet; lower SES; never having been BFD or EBFD; anyone smoking at home; current maternal smoking (MS); MS>10cigarettes (cig.) /day and watching TV≥3h/day. Factors significantly increasing the risk of AOB were: female gender; lower SES; urban areas of residence (UR); MS>10cig/day and child watching TV≥3h/day. Factors increasing the risk of having a HBF were: ix being a boy; lower SES; UR; current MS; MS>10cig/day and watching TV≥3h/day. The prevalence of A ever was 10.4%, R ever 22.8%. Factors increasing the risk of A symptoms were: family history of A; higher SES; high BW; never BFD; shorter periods of TBFD and EBFD; MS>10cig/day; MS during pregnancy and during the 1st year of the child’s life; ≥2people smoking in the household and the child never or occasionally practicing VPA. Factors increasing the risk of R symptoms were: family history of R; high BW; not being BFD or being TBFD and EBFD for shorter periods; MS during pregnancy and during the 1st year of the child’s life; watching TV≥3h/day and HTT. We found that being OB or O increased the risk for all A and R symptoms, with a significant result for W 12m (OR=1.79; p=0.01). OB had a stronger effect on A symptoms for girls than for boys. AOB did not show any significant association with A or R. HBF was the strongest predictor of A and R, significantly increasing the risk of exercise-induced A (OR=2.06; p=0.02) and R ever (OR=1.57; p=0.02). HBF showed a stronger impact on A in girls and on R in boys. Phenotypes (BW comparison): Mean BW was the highest for the A+O+ (3.442kg) and the lowest for A-O- (diff. =0.258kg; p= 0.001). The difference was also statistically significant between the group A-O+ and A+O+ (diff.=0.160kg; p=0.04). W+O+ had the highest mean of BW (3.357kg), significantly higher than W-O- (diff.=0.166kg; p<0.001). Body fat: the highest mean BW was observed for A+OF+ (3.397kg), significantly higher than A- OF- (diff.=0.206kg; p<0.01). The difference was borderline significant between A+OF+ and A-OF+ (diff. =0.140kg; p=0.07). The highest BW mean was observed for W+OF+ 3.323kg and the lowest for W+OF- (3.196kg) with a difference of 0.127kg (p=0.01). Patterns observed in the case of A and W were not reproduced for R, although children with R+OB+/OF+ were also born with the highest mean BW. Conclusion: We showed that childhood obesity and especially high body fat levels increase the risk of asthma and rhinitis, which seemed to be independent of common risk factors. Obesity showed a stronger effect on asthma for girls than for boys. Results suggest that the overweight/obese asthmatics might already be born with a predisposition to this phenotype, which might indicate its prenatal origin. High level of asthma heterogeneity highlights the need for individualized, phenotype- or patient-specific prevention, intervention, and treatment strategies. Key words: childhood obesity, asthma, rhinitis, environmental factors, socioeconomic status, birth weight x PhD Thesis, Magdalena Muc Resumo Introdução: O aumento da prevalência da obesidade, asma e rinite na infância, sugere uma ligação entre eles. Os fatores sócio-demográficos, de início da vida, o sedentarismo, a dieta e a exposição ao fumo de tabaco, entre outros, podem ter aumentando o número de asmáticos obesos. Existem dois principais fenótipos de asmáticos obesos descritos e um deles inclui crianças. A existência de asma e rinite relacionada com a obesidade, significa que crianças com este fenotipo não só são diferentes das crianças saudáveis, mas também das crianças com asma e rinite e peso normal. Objetivos: Investigar como os fatores ambientais, socioeconómicos e familiares que são comuns para a obesidade, asma e rinite modelam a associação entre estas doenças e estudar se os valores do peso ao nascimento diferem entre crianças com fenotipos diferentes de asma e rinite. Métodos: Este estudo transversal foi realizado numa amostra de 1043 crianças entre 6-8 anos do distrito de Coimbra. Os dados sobre asma (A), rinite (R) e os fatores ambientais e socioeconómicos foram obtidos utilizando os questionários do ISAAC (The International Study of Asthma and Allergies in Childhood). Indicadores de adiposidade usados: Índice de Massa Corporal (IMC); IMC z-score estandardizado para o sexo e a idade (Organização Mundial de Saúde-OMS); a relação cintura estatura (do inglês Waist to Height Ratio - WHtR) e a % de gordura corporal (ing.% of Body Fat - %BF). A obesidade (OB) e exesso de peso (ing.Overweight – O) foram definidos aplicando os pontos de corte da OMS. A obesidade abdominal (AOB) foi definida como WHTR>0.5. O exesso de gordura (ing.Overfat – OF) e gordura elevada (ing.High Fat – HF) foram classificados utilizando os percentis específicos para a idade e sexo. Os fatores de risco estudados foram: peso ao nascimento (ing.Birth Weight – BW); aleitamento materno (ing.Breast feeding – BFD) e períodos de aleitamento total (ing.Total breast feeding –TBFD) e exclusivo (ing.Exclusive breast feeding – EBFD); dieta; atividade física vigorosa (ing.vigorous physical activity -VPA); tempo de ver televisão (TV); tráfego de camiões na área de residência; grau de urbanização da área residencial e nível socioeconómico (ing.