The influence of childhood asthma on adult height: evidence from the UK Biobank

Abstract

Background To elucidate the influence of childhood asthma on adult height after consideration of genetic heterogeneity in height. Methods Based on the UK Biobank, we conducted a matched cohort study, including 13,602 European individuals with asthma diagnosed before 18 years old and 136,008 matched unexposed individuals without such an experience. Ascertainment of asthma was based on self-reported data (97.6%) or clinical diagnosis in healthcare registers (2.4%). We studied three height outcomes, including (1) the attained adult height (in centimeters), (2) the height deviation measured as the difference between a person’s rank of genetically determined height (based on generated polygenetic risk score) and their rank of attained adult height in the study population (deviation in % of height order after standardization), and (3) the presence of height deficit comparing genetically determined and attained height (yes or no). We applied linear mixed-effect models to assess the associations of asthma diagnosed at different ages with attained adult height and height deviation, and conditional logistic regression models to estimate the associations of asthma with the risk of height deficit. Results 40.07% (59,944/149,610) of the study participants were born before 1950, and most of them were men (57.65%). After controlling for multiple covariates, childhood asthma was associated with shorter attained adult height, irrespective of age at asthma diagnosis. However, in the analysis of height deviation (deviation in %), we observed the greatest height deviation among individuals with asthma diagnosed before 4 years of age (− 2.57 [95% CI − 4.14 to − 1.00] and − 2.80 [95% CI − 4.06 to − 1.54] for the age of ≤ 2 and 3–4 years, respectively). The magnitude of height deviation in relation to asthma declined thereafter and became null after age 6. Similarly, there was a statistically significant height deficit in relation to an asthma diagnosis at ages ≤ 2 and 3–4 (odds ratios = 1.21, 95% CI 1.04 to 1.40, and 1.15, 95% CI 1.02 to 1.29) but not thereafter. The result pattern was similar when separately analyzing asthma with or without inhaled glucocorticoid (ICS) use, despite that the estimates were consistently stronger among asthma individuals who used ICS. Conclusions Our results suggest a notable association of childhood asthma, primarily asthma diagnosed at an early age, with adult height, after consideration of genetic heterogeneity in height and use of ICS. This finding highlights the need for surveillance on the growth problems among children with asthma.

Recommendations for asthma monitoring in children: A PeARL document endorsed by APAPARI, EAACI, INTERASMA, REG, and WAO

“…It is well-established that long-term oral and/or inhaled corticosteroid use may affect growth in children. [55][56][57] The longer and higher doses have more ability to impact growth and bone turnover. 58,59 Therefore, in a chronic condition such as asthma, which often requires daily inhaled corticosteroids, other topical corticosteroids treatments to treat comorbidities (allergic rhinitis, atopic dermatitis) and potentially frequent systemic corticosteroids bursts, there is strong rationale in frequent growth monitoring, particularly for children with less frequent monitoring intervals.…”

“…It is well‐established that long‐term oral and/or inhaled corticosteroid use may affect growth in children 55–57 . The longer and higher doses have more ability to impact growth and bone turnover 58,59 .…”

Effects of urinary tract infection during the first years of life in subsequent growth: a nationwide comparative matched cohort study

“…Childhood infectious diseases modulate weight gain and linear growth by influencing metabolism, nutrition, and the microbiome ( 7 , 8 ). Notably, several childhood diseases, such as allergic disorders, inflammatory bowel disease, and dental caries, have been associated with impaired future growth ( 9 - 11 ). Furthermore, CKD and kidney scar resulting from UTIs are known to have a detrimental impact on growth in childhood through various mechanisms, including anorexia, malnutrition, and decreased insulin-like growth factor-1 expression ( 12 ).…”

Variants in JAZF1 are associated with asthma, type 2 diabetes, and height in the United Kingdom biobank population

“…There is evidence that shorter individuals have an increased risk for developing T2D ( Shrestha et al, 2019 ) and individuals with childhood onset asthma have shorter stature as adults compared to non-asthmatics. ( Chen et al, 2022 ).…”