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An association between overweight and asthma in children after early-life wheezing at late school age
S2
Oral Presentations / Paediatric Respiratory Reviews 11S1 (2010) S1–S78
O.1.2 An association between overweight and asthma in children after early-life wheezing at late school age V. Sidoroff1 , M. Korppi2 . 1 Kuopio University Hospital Department of Pediatrics – Kuopio, Finland; 2 Tampere University Hospital Pediatric Research Centre – Tampere, Finland Background: Overweight children may be at increased risk for asthma or they might create asthma like symptoms easier than normal weight children. The aim of the present study was to evaluate the association between overweight and asthma at the median ages of 4.0, 7.2 and 12.3 years in children with early-life wheezing. Material and Methods: From the 100 children hospitalized for wheezing at <24 months of age, 83 attended the control visit at 4.0 years, 81 at 7.2 years and 81 at 12.3 years of age. The visits consisted of medical examination supplemented exercise challenge test at school age. The weight status was assessed by calculating weight for height and body mass index (BMI) at all visits. In weight for height, the limit of overweight was 110% to 120% depending on age, and the limit of obesity was 120% to 140%, respectively. BMI >1.3 SD from age- and gender-specific references ment overweight and >2.0 SD obesity. Spearman’s correlation coefficient between weight for height and BMI was 0.973 at 7.2 years and 0.950 at 12.3 years in this cohort. Results: Doctor-diagnosed asthma was present in 45 (51.1%) study subjects at 4.0, in 33 (40.7%) at 7.2 and in 32 (39.5%) at 12.3 years of age. There was no significant association between asthma and current or previous overweight or obesity at 4.0 and 7.2 years of age. Likewise, previous obesity was not predictive for asthma at 12.3 years of age. However, at that age 43.8% of the children with asthma were overweight (vs. 24.5% of non-asthmatics, p = 0.070). In adjusted analyses (adjusted for atopic dermatitis in infancy, RSV etiology of bronchiolitis and age on admission), current overweight by weight for height was associated with asthma risk at 12.3 years of age (aOR 3.33; 95% CI 1.12–9.93). In addition, overweight by weight for height >120% at 12.3 years was associated with the use of inhaled steroids (aOR 3.5; 95% CI 1.1–11.3). There were no significant associations between weight status and bronchial reactivity at any age by any reactivity level. Conclusions: Preliminary evidence was found for an association between asthma and overweight after infantile wheezing at late school age, but not earlier, and previous overweight was not predictive for subsequent asthma. O.1.3 Association between candidate genes and spirometric variables in Chinese H.Y. Sy1 , F.W.S. Ko2 , H.Y. Chu2 , I.H.S. Chan3 , T.C. Liu1 , K.Y. Chan1 , C.W.K. Lam3 , G.W.K. Wong1 , D.S.C. Hui2 , T.F. Leung1 . 1 The Chinese University of Hong Kong Department of Pediatrics – Hong Kong, China; 2 The Chinese University of Hong Kong Department of Medicine and Therapeutics – Hong Kong, China; 3 The Chinese University of Hong Kong Department of Chemical Pathology – Hong Kong, China Background: Asthma is caused by complex interactions between multiple susceptibility genes and environmental factors. Three genes (ARG1, ADRB2 and CRHR2) were reported to be associated with bronchodilator response in Caucasians, whereas NOS1 and NOS3 were important components of the arginase 1 pathway. GSDM1 and TOP2A, located on chromosome 17q21 as a reproducible locus identified by asthma genome-wide association study in other ethnic groups, were also candidate genes for asthma and atopy in our Chinese children. This study investigated the associations between spirometric variables and single-nucleotide polymorphisms (SNPs) of these seven candidate genes. Methods: This study recruited both children (312 cases and 70 controls; aged 6–17 years) and adults (345 cases and 652 controls; aged ≥18 years). Spirometry was performed before
and 30 minutes following salbutamol inhalation. Their forced expiratory volume in 1-second (FEV1 ) and forced vital capacity (FVC) were then measured. Thirteen SNPs of ARG1, ADRB2, CRHR2, NOS1, NOS3, GSDM1 and TOP2A were genotyped by TaqMan SNP genotyping assays using ABI Prism 7900HT thermocycler, and their associations with spirometric variables in our subjects were analyzed by multivariate linear regression. Results: All SNPs followed Hardy–Weinberg equilibrium. In our adults, the minor allele of rs3756780 on ARG1 was associated with an additive protective effect against asthma (odds ratio 0.71, 95% confidence interval 0.54–0.93; P = 0.013). Multivariate linear regression revealed FEV1 to be associated with SNPs of ARG1, CRHR2, GSDM1 and TOP2A (P = 0.002–0.044), whereas FEV1 /FVC was associated with SNPs of ARG1 and TOP2A (P = 0.021–0.050). No significant association was found between spirometric variables and ADRB2. Among our children, FEV1 reversibility was associated with rs1003929 of CRHR2 and rs1007654 of GSDM1 (P = d 0.014 and 0.004, respectively). Conclusions: This study identifies discrepant genetic associations for spirometric parameters between Chinese adults and children. Both CRHR2 and GSDM1 are associated with FEV1 in adults and FEV1 reversibility in children, whereas ARG1 and TOP2A are associated with FEV1 and FEV1 /FVC only in adults. These findings highlight the importance of these candidate genes in modulating airflow limitation. None of ADRB2, NOS1 or NOS3 is a major gene for spirometric variables in the Chinese population. Funding: RGC General Research Fund (grant no. 470909) of Hong Kong SAR O.1.4 The reciprocal influences of asthma and obesity on lung function, AHR and bronchial inflammation in prepubertal children N.P. Consilvio1 , S. Di Pillo1 , T. de Giorgis2 , A. Cingolani1 , A. Scaparrotta1 , D. Rapino1 , F. Masuccio2 , A. Mohn2 , F. Chiarelli3 , M. Verini1 . 1 University of Chiety Department of Pediatrics Children’s Allergological and Pneumological Unity – Chieti, Italy; 2 University of Chieti Department of Pediatrics Children Obesity Clinic – Chieti, Italy; 3 University of Chieti Department of Pediatrics – Chieti, Italy As the incidence of obesity and asthma increase consistently, the reciprocal influences of both on lung function, airways hyperresponsiveness (AHR) and bronchial inflammation were analyzed in a group of 118 Caucasian prepubertal children. Anthropometric measurements and respiratory parameters [Flow/Volume curves, “free run” Exercise Challenge Test, Fractional exhaled Nitric Oxide (FeNO)] were evaluated and the study population was divided into four groups according to Body Mass Index and the presence or absence of asthma: Obese Asthmatic (ObA), Normal-weight Asthmatic (NwA), Obese non-Asthmatic (Ob), Normalweight non-Asthmatic children (Nw). MEF75% (Maximal Expiratory Flows at 75% of the Forced Vital Capacity) was significantly lower in obese asthmatic and obese non-asthmatic children compared to healthy controls and the influence of obesity on MEF75% was confirmed by multiple linear regression. After the “free-run” Exercise Challenge Test all analyzed respiratory parameters decreased significantly in asthmatic obese and asthmatic normal weight children, in contrast in non-asthmatic obese children no differences were found [Table 1]. Respiratory parameters of the study population ObA
NwA
Ob
Baseline Respiratory Functional Parameters PEF (%) 104.71±17.94 110.96±20.08 101.72±15.51 MEF75 (%) 96.34±17.61 111.34±23.67 90.42±27.36 Respiratory Functional Parameters after “free run” Exercise Challenge Test PEF (%)post85.35±22.45 94.17±24.90 96.54±19.21 MEF75 (%)post83.30±21.79 91.12±26.72 92.71±15.70
Nw
p†
113.86±15.54 114.03±16.11
0.031 0.001
112.02±11.85 107.21±10.31
0.013 0.010
Values are means (± SD). † Kruskal Wallis Test. PEF = Peack Expiratory Flow; MEF75–50–25 = Maximal Expiratory Flows at 75%, 50% and 25% of the Forced Vital Capacity. (all the tests are expressed as a percentage of the theoretical values for height, age and sex).
Oral Presentations / Paediatric Respiratory Reviews 11S1 (2010) S1–S78
O.1.2 An association between overweight and asthma in children after early-life wheezing at late school age V. Sidoroff1 , M. Korppi2 . 1 Kuopio University Hospital Department of Pediatrics – Kuopio, Finland; 2 Tampere University Hospital Pediatric Research Centre – Tampere, Finland Background: Overweight children may be at increased risk for asthma or they might create asthma like symptoms easier than normal weight children. The aim of the present study was to evaluate the association between overweight and asthma at the median ages of 4.0, 7.2 and 12.3 years in children with early-life wheezing. Material and Methods: From the 100 children hospitalized for wheezing at <24 months of age, 83 attended the control visit at 4.0 years, 81 at 7.2 years and 81 at 12.3 years of age. The visits consisted of medical examination supplemented exercise challenge test at school age. The weight status was assessed by calculating weight for height and body mass index (BMI) at all visits. In weight for height, the limit of overweight was 110% to 120% depending on age, and the limit of obesity was 120% to 140%, respectively. BMI >1.3 SD from age- and gender-specific references ment overweight and >2.0 SD obesity. Spearman’s correlation coefficient between weight for height and BMI was 0.973 at 7.2 years and 0.950 at 12.3 years in this cohort. Results: Doctor-diagnosed asthma was present in 45 (51.1%) study subjects at 4.0, in 33 (40.7%) at 7.2 and in 32 (39.5%) at 12.3 years of age. There was no significant association between asthma and current or previous overweight or obesity at 4.0 and 7.2 years of age. Likewise, previous obesity was not predictive for asthma at 12.3 years of age. However, at that age 43.8% of the children with asthma were overweight (vs. 24.5% of non-asthmatics, p = 0.070). In adjusted analyses (adjusted for atopic dermatitis in infancy, RSV etiology of bronchiolitis and age on admission), current overweight by weight for height was associated with asthma risk at 12.3 years of age (aOR 3.33; 95% CI 1.12–9.93). In addition, overweight by weight for height >120% at 12.3 years was associated with the use of inhaled steroids (aOR 3.5; 95% CI 1.1–11.3). There were no significant associations between weight status and bronchial reactivity at any age by any reactivity level. Conclusions: Preliminary evidence was found for an association between asthma and overweight after infantile wheezing at late school age, but not earlier, and previous overweight was not predictive for subsequent asthma. O.1.3 Association between candidate genes and spirometric variables in Chinese H.Y. Sy1 , F.W.S. Ko2 , H.Y. Chu2 , I.H.S. Chan3 , T.C. Liu1 , K.Y. Chan1 , C.W.K. Lam3 , G.W.K. Wong1 , D.S.C. Hui2 , T.F. Leung1 . 1 The Chinese University of Hong Kong Department of Pediatrics – Hong Kong, China; 2 The Chinese University of Hong Kong Department of Medicine and Therapeutics – Hong Kong, China; 3 The Chinese University of Hong Kong Department of Chemical Pathology – Hong Kong, China Background: Asthma is caused by complex interactions between multiple susceptibility genes and environmental factors. Three genes (ARG1, ADRB2 and CRHR2) were reported to be associated with bronchodilator response in Caucasians, whereas NOS1 and NOS3 were important components of the arginase 1 pathway. GSDM1 and TOP2A, located on chromosome 17q21 as a reproducible locus identified by asthma genome-wide association study in other ethnic groups, were also candidate genes for asthma and atopy in our Chinese children. This study investigated the associations between spirometric variables and single-nucleotide polymorphisms (SNPs) of these seven candidate genes. Methods: This study recruited both children (312 cases and 70 controls; aged 6–17 years) and adults (345 cases and 652 controls; aged ≥18 years). Spirometry was performed before
and 30 minutes following salbutamol inhalation. Their forced expiratory volume in 1-second (FEV1 ) and forced vital capacity (FVC) were then measured. Thirteen SNPs of ARG1, ADRB2, CRHR2, NOS1, NOS3, GSDM1 and TOP2A were genotyped by TaqMan SNP genotyping assays using ABI Prism 7900HT thermocycler, and their associations with spirometric variables in our subjects were analyzed by multivariate linear regression. Results: All SNPs followed Hardy–Weinberg equilibrium. In our adults, the minor allele of rs3756780 on ARG1 was associated with an additive protective effect against asthma (odds ratio 0.71, 95% confidence interval 0.54–0.93; P = 0.013). Multivariate linear regression revealed FEV1 to be associated with SNPs of ARG1, CRHR2, GSDM1 and TOP2A (P = 0.002–0.044), whereas FEV1 /FVC was associated with SNPs of ARG1 and TOP2A (P = 0.021–0.050). No significant association was found between spirometric variables and ADRB2. Among our children, FEV1 reversibility was associated with rs1003929 of CRHR2 and rs1007654 of GSDM1 (P = d 0.014 and 0.004, respectively). Conclusions: This study identifies discrepant genetic associations for spirometric parameters between Chinese adults and children. Both CRHR2 and GSDM1 are associated with FEV1 in adults and FEV1 reversibility in children, whereas ARG1 and TOP2A are associated with FEV1 and FEV1 /FVC only in adults. These findings highlight the importance of these candidate genes in modulating airflow limitation. None of ADRB2, NOS1 or NOS3 is a major gene for spirometric variables in the Chinese population. Funding: RGC General Research Fund (grant no. 470909) of Hong Kong SAR O.1.4 The reciprocal influences of asthma and obesity on lung function, AHR and bronchial inflammation in prepubertal children N.P. Consilvio1 , S. Di Pillo1 , T. de Giorgis2 , A. Cingolani1 , A. Scaparrotta1 , D. Rapino1 , F. Masuccio2 , A. Mohn2 , F. Chiarelli3 , M. Verini1 . 1 University of Chiety Department of Pediatrics Children’s Allergological and Pneumological Unity – Chieti, Italy; 2 University of Chieti Department of Pediatrics Children Obesity Clinic – Chieti, Italy; 3 University of Chieti Department of Pediatrics – Chieti, Italy As the incidence of obesity and asthma increase consistently, the reciprocal influences of both on lung function, airways hyperresponsiveness (AHR) and bronchial inflammation were analyzed in a group of 118 Caucasian prepubertal children. Anthropometric measurements and respiratory parameters [Flow/Volume curves, “free run” Exercise Challenge Test, Fractional exhaled Nitric Oxide (FeNO)] were evaluated and the study population was divided into four groups according to Body Mass Index and the presence or absence of asthma: Obese Asthmatic (ObA), Normal-weight Asthmatic (NwA), Obese non-Asthmatic (Ob), Normalweight non-Asthmatic children (Nw). MEF75% (Maximal Expiratory Flows at 75% of the Forced Vital Capacity) was significantly lower in obese asthmatic and obese non-asthmatic children compared to healthy controls and the influence of obesity on MEF75% was confirmed by multiple linear regression. After the “free-run” Exercise Challenge Test all analyzed respiratory parameters decreased significantly in asthmatic obese and asthmatic normal weight children, in contrast in non-asthmatic obese children no differences were found [Table 1]. Respiratory parameters of the study population ObA
NwA
Ob
Baseline Respiratory Functional Parameters PEF (%) 104.71±17.94 110.96±20.08 101.72±15.51 MEF75 (%) 96.34±17.61 111.34±23.67 90.42±27.36 Respiratory Functional Parameters after “free run” Exercise Challenge Test PEF (%)post85.35±22.45 94.17±24.90 96.54±19.21 MEF75 (%)post83.30±21.79 91.12±26.72 92.71±15.70
Nw
p†
113.86±15.54 114.03±16.11
0.031 0.001
112.02±11.85 107.21±10.31
0.013 0.010
Values are means (± SD). † Kruskal Wallis Test. PEF = Peack Expiratory Flow; MEF75–50–25 = Maximal Expiratory Flows at 75%, 50% and 25% of the Forced Vital Capacity. (all the tests are expressed as a percentage of the theoretical values for height, age and sex).