Is a Genetic Predisposition to Higher BMI Enough to Increase Asthma Risk?

Evaluated Data

Data were collected from the Danish clinical research unit for childhood asthma, COPSAC, whose goal is to improve prevention, diagnosis, and treatment of pediatric asthma. Specifically, two ongoing cohort studies involving mothers and their children were analyzed: COPSAC2000 and COPSAC2010. Replication was also carried out in the Integrative Psychiatric Research (iPSYCH) project, using a very large dataset that combined iPSYCH 2012 and 2015 cohorts, including data on hospitalizations and asthma.

Hospitalizations for asthma, wheezing, and lower respiratory tract infections (LRTI) were identified through national patient registries. A polygenic risk score (PRS) for BMI in adulthood (PRS BMI) was calculated for each child.

Findings

The researchers included 974 (87.7%) of the 1,111 children participating in the COPSAC cohorts. They found that PRS BMI in adulthood was significantly associated with the incidence of LRTI, antibiotic prescriptions in the first three years of life, and episodes of severe wheezing in the first six years. LRTI partially mediated the relationship between PRS BMI in adulthood and severe wheezing. Interestingly, the association with LRTI and severe wheezing was independent of the child’s current BMI, and PRS was not associated with an asthma diagnosis or reduced lung function up to 18 years of age.

These relationships were replicated in the extensive iPSYCH dataset (n = 114,283). In the independent cohort based on registry data, the associations were observed in preschool age for asthma/wheezing and LRTI and persisted up to 18 years. This highlights a common underlying genetic predisposition to higher BMI, respiratory infections, and severe wheezing, which are not solely caused by the consequences of increased BMI. These findings point to shared genetic pathways and contribute to understanding the link between asthma and obesity.

Familiar Players – Inflammation and Immune Changes

The relationship between obesity and childhood asthma is well documented. It has been shown that children with asthma are often shorter in stature, have more subcutaneous fat tissue, and less muscle mass. This relationship has been attributed to factors such as reduced physical activity and potential effects of inhaled or oral corticosteroid treatment. Similarly, infections during early childhood have been linked to an increased risk of childhood obesity later in life.

Conversely, higher BMI has been associated with an increased risk of infections in adults. Even in children, obesity has been linked to impaired cellular immune responses. Various mechanisms are considered in explaining these relationships, with inflammation and immune changes playing a significant role.

“In this study, we demonstrated that genetic predisposition to higher BMI increased the risk of LRTI and severe wheezing already in early childhood, independently of current BMI, suggesting that different mechanisms are at play other than increased adipose tissue mass. PRS BMI has previously been associated with elevated CRP and IL-6 levels in adulthood, but we did not find such an association in early childhood. It therefore appears that genetic predisposition to higher BMI causes a low level of inflammation in childhood, and our findings do not seem to be explained by an increased rate of systemic inflammation,” the study authors concluded.

Editorial Team, Medscope.pro

Source:

Jensen S. K., Tingskov Pedersen C. E., Fischer-Rasmussen K. et al. Genetic predisposition to high BMI increases risk of early life respiratory infections and episodes of severe wheeze and asthma. Eur Respir J 2024 Sep 5; 64 (3): 2400169, doi: 10.1183/13993003.00169-2024.