ABSTRACT
Background: Obesity and asthma are highly associated, but the
mechanisms underlying the association remain unknown. We examined five
mediators linking obesity with childhood asthma: (1) pulmonary function
impairment, (2) airway inflammation, (3) physical fitness, (4)
sleep-disordered breathing (SDB), and (5) early puberty.
Methods: A Mendelian randomization (MR) study with mediation
analysis of data obtained from 5,965 children as part of the Taiwan
Children Health Study. Cross-sectional regression analysis, MR two-stage
least squares method, and MR sensitivity analysis were carried out to
investigate each causal pathway. Prospective cohort analyses were used
to confirm the findings.
Results: The increased asthma risk associated with obesity was
found to be mostly mediated through impaired pulmonary function, low
physical fitness, early puberty. In the MR analysis, body mass index was
negatively associated with FEV1/FVC and physical fitness index (β= −2.17
and −0.71; 95% CI, −3.92 to −0.42
and −1.30 to −0.13, respectively) and positively associated with early
puberty (OR, 1.09; 95% CI, 1.02–1.17). High FEV1/FVC and physical
fitness index reduced the risk of asthma (OR, 0.98 and 0.93; 95% CI,
0.97–0.99 and 0.88–0.98, respectively), whereas SDB and early puberty
increased the risk of asthma (OR, 1.03 and 1.22; 95% CI, 1.01–1.05 and
1.05–1.42, respectively). The three main mediators were low physical
fitness, impaired pulmonary function, and early puberty, with mediation
proportions of 91.4%, 61.6%, and 28.3%, respectively. Temporal
causality was further strengthened in prospective cohort analyses.
Conclusions: Interventions promoting physical fitness and
pulmonary function might effectively reduce obesity-induced asthma risk.
Keywords: Obesity; Asthma; Mediation analysis; Mendelian
randomization study; Pulmonary function