Background: Lung function growth occurs in most asthmatic children. A subgroup has subnormal lung function trajectory, but such data are limited in children. This prospective study characterized longitudinal changes of spirometric indices and fractional exhaled nitric oxide level (FeNO) among asthmatic children and identified their genetic and environmental determinants.
Methods: Chinese asthmatic children recruited from pediatric clinics underwent 5-year follow-up for pre-bronchodilator spirometric indices and FeNO. Fourteen asthma-associated single nucleotide polymorphisms (SNPs) were genotyped. Generalized estimating equation was used to analyze longitudinal changes of spirometric indices and FeNO.
Results: One hundred and ninety-three asthmatic children, aged 9.7 (1.9) years, had significant annual decline of 1.3% for forced vital capacity (FVC) and annual increase of 1.2% and 3.6% for FEV1 /FVC and FEF25-75 , respectively. Patients who received inhaled corticosteroid (ICS) had 2.4% lower baseline FEV1 /FVC but 0.81% higher annual increase in FEV1 . Body mass index (BMI) was associated inversely with FEV1 /FVC but positively with FEV1 % and FVC% changes. Asthma exacerbation was associated with lower FEV1 % and FVC% but not their longitudinal changes. When classified by FEV1 curve, one-quarter of patients had reduced lung function growth which was associated with female gender and lower spirometric and higher FeNO values at baseline. IL33_rs1342326 was associated with spirometric indices and FeNO, whereas GSDMB_rs2305480 was significantly associated with FEV1 /FVC change.
Conclusion: Asthmatic children have annual decline in FVC and increase in FEV1 /FVC and FEF25-75 . Their lung function trajectory is influenced by gender, ICS treatment, BMI, and asthma exacerbations. IL33 and GSDMB may be candidate genes for their lung function growth.
Keywords: asthma; determinant; exhaled nitric oxide; genetics; lung function trajectory.
© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.