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Mediating analysis of the relationship between obesity and childhood asthma

Mediating analysis of the relationship between obesity and childhood asthma
   Obesity and asthma are two significant public health problems with increasing prevalence during childhood. Prospective studies have suggested that obesity precedes the development of asthma. Several possible mechanisms have been postulated to explain this relationship, including an obesity-related reduction in lung volume, inflammatory mediators, obesity-related changes in hormone levels, and dyslipidemia. Based on our baseline Taiwan Children Health Study (TCHS) cohorts, we performed prospective follow-up evaluations using parent and child questionnaires, obesity measures, physical fitness levels, and pulmonary function tests.

We applied a novel approach to investigate the pathogenic mechanisms. Using the structural equation model (SEM), we successfully constructed models of the relationships between obesity and physical fitness, sedentary time, and childhood asthma. The SEM, first used in social science research during the 1980s, is a type of polybasic statistical model that combines factor analysis and pathway analysis and can be used with different types of variables and hierarchical data structures for causal inference. By applying the SEM to our TCHS dataset, we found that low physical fitness and high sedentary time were the leading factors associated with central obesity in children and subsequent asthma development. We also applied the widely used generalized estimating equation and conducted the survival analysis of longitudinal data in three-year measurements, and the results were consistent with the conclusion that low physical fitness levels and increased sedentary time were the leading causes of childhood obesity and asthma (Figure 1). This study is the first to apply the SEM to investigate the interrelationship between obesity and human diseases.

We further used the SEM to investigate the mediating pathways underlying the mechanisms for the progression from central obesity to childhood asthma. Positive correlations were found between atopy and airway inflammation and between airway inflammation and pulmonary function. The direct links between central obesity and childhood asthma in both models were positive but not significant. The total effects and the indirect effects via the three mediators were all significant in both models. In the model of active asthma, the percentage of mediation was 28.6% for pulmonary function, 18.1% for atopy, and 5.7% for airway inflammation. The indirect effect via pulmonary function was 40.2% in the model of lifetime wheezing. Pulmonary function was responsible for the greatest percentage of mediation among the three mediators in both models (Figure 2). Pulmonary function screening should be applied to obese children to prevent future asthma risks.

1. Yang-Ching Chen, Yu-Kang Tu, Kuo-Chin Huang, Pau-Chung Chen, Da-Chen Chu, and Yungling Leo Lee. (2014). Pathway from central obesity to childhood asthma. Physical fitness and sedentary time are leading factors. American Journal of Respiratory and Critical Care Medicine. 189(10), 1194-1203. DOI: 10.1164/rccm.201401- 0097OC
2. An-Hsuan Chih, Yang-Ching Chen, Yu-Kang Tu, Kuo-Chin Huang, Tai-Yuan Chiu, Yungling Leo Lee. (2016). Mediating Pathways from Central Obesity to Childhood Asthma: a population-based longitudinal study. European Respiratory Journal. 48, 748-757. DOI: 10.1183/13993003.00226-2016.

Associate Professor Yungling Leo Lee
Institute of Epidemiology and Preventive Medicine