Childhood asthma tied to T1D, IBD development

Children diagnosed with asthma between ages 5 and 7 years may have an increased risk of developing type 1 diabetes (T1D) and inflammatory bowel diseases (IBD; Crohn’s disease and ulcerative colitis), a Danish nationwide registry study suggests.

“[In our study, we defined childhood asthma] as a minimum of two collections of doctor-prescribed anti-asthmatic inhaled corticosteroids [at] age 5–7 years,” said the researchers. “[We found that] childhood asthma increased the risk of both diseases by 20–30 percent, which was robust for case definitions, confounder adjustments, and stratifications.”

Of the 366,200 children included in the study population, 18,012 had childhood asthma. About two thirds (69 percent) of those with asthma had persistent asthma during follow up, while 10 percent had allergic asthma (n=2,934). [Sci Rep 2022 Dec 16;12:21728]

During follow up, 1,556 children had a hospitalization with T1D. Childhood asthma was associated with an increased risk of developing T1D (hazard ratio [HR], 1.28; p=0.021). This effect was sustained after adjusting for all covariates* (HR, 1.23; p=0.055).

The effect was stronger in boys than girls (HR, 1.35 vs 1.10) but the interaction between sex and asthma was nonsignificant (p=0.38). There was also a stronger association between T1D and persistent asthma (HR, 1.30) than childhood asthma (HR, 1.19) but without statistical significance (p=0.75).

A total of 2,064 children had at least one hospitalization with IBD during follow-up. Childhood asthma increased the risk of developing IBD, after stratifying for sex and birthyear (HR, 1.26; p=0.012) and for all covariates (HR, 1.28; p=0.008).

The effect was also stronger in boys than girls (HR,1.38 vs 1.09) but no interaction was found (p=0.21). The association was primarily driven by persistent vs childhood asthma (HR, 1.45 vs 0.86), and the difference was significant (p=0.02).

Underlying mechanisms

“These associations are interesting from an aetiological and mechanistic viewpoint, since the diseases have different pathology and clinical presentations,” the researchers noted. “[O]ur findings thereby dismiss the null hypothesis that these differing inflammatory trajectories cannot co-occur … and suggest common mechanisms for these three chronic inflammatory diseases.”

The associations may also be due to shared genetic and environmental risk factors, the researchers noted. “Asthma and T1D have strong genetic components … In contrast, IBD are far less heritable … We previously found shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared disease mechanisms which could explain the associations.” [J Allergy Clin Immunol 2017;140:771-781]

Other factors that might shed light on the associations between childhood asthma and IBD are Caesarean section and parental smoking during pregnancy or the early life of the child. [Pediatrics 2015;135;e92-e98; J Allergy Clin Immunol 2010;126:626-630; Gut 2005;54:1500-1501]

Moreover, some early life risk factors may have persistent effects on the inflammatory system, triggering diseases later in life, they added.

Shared aetiology, different pathology

“Together, these findings suggest complex and shared aetiology of chronic inflammatory diseases despite their different pathology and clinical presentations,” said the researchers.

It is important to note however that while the associations are vital in understanding complex disease aetiologies, the estimated attributable risk fractions for both T1D and IBD were small, and the clinical relevance for individual patients is negligible, they stressed. The findings may have also been limited by the ethnically homogeneous population and follow up period.

“[Nonetheless,] our findings imply that an efficient prevention of childhood asthma (eg, micronutrient supplementation in pregnancy) may also reduce the risk of other chronic inflammatory diseases,” they concluded.