Asthma Linked to Increased Risk of Sepsis, finds Mendelian Randomized Study

Asthma is a chronic respiratory disease with characteristics of airway inflammation and hyperresponsiveness. Although some of the previous observational studies have postulated a potential association between asthma and sepsis, a clear causal link is still quite uncertain. In addressing this gap in knowledge, the current study used a genetic variant-based instrumental variable method to explore possible causal links between asthma and sepsis. This has a clear advantage over the observational studies, as it has minimum confounding effects and reduced bias.

They used asthma-associated single-nucleotide polymorphisms as instrumental variables derived from a meta-analysis involving a genome-wide association study of sufficient size. There were three methods in this MR study: inverse-variance weighted, MR-Egger regression, and weighted median analysis. The study summarized the main results with combined odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for overall and by-type sepsis, and their relationships with asthma. We conducted sensitivity analyses regarding the validity of the instrumental variables and a potential pleiotropic bias. In addition, we performed reverse MR analysis to explore whether there was a possible directed consequence of asthma on sepsis.

Key Findings

• The study found a statistically significant relationship between asthma and increased chances of sepsis (OR=1.18, P<0.05), and the paper suggests that asthma can become a risk factor for developing sepsis.

Specific Types of Sepsis:

• Streptococcal sepsis (OR=1.23, P=0.04)

• Pneumonia-related sepsis (OR=1.57, P<0.05.

• There was no causal relationship between sepsis and asthma in the reverse MR, thus ruling out that sepsis has a contribution to the development of asthma.

The findings of the study provide evidence for asthma as a cause of increasing the risk of various types of sepsis, including those due to streptococcal and pneumococcal infections. Higher odds ratios observed in ICU settings raised the possibility of severe forms of sepsis in asthma patients. These results emphasized that early detection and management of sepsis in asthma patients can significantly reduce the risk of a severe outcome. The study also provided an important view about the relationship regarding its directionality because it did not find any reverse causality from sepsis to asthma.

Reference:

Luo, J., Liu, P., & Luo, Y. (2024). Genetic prediction of asthma increases multiple sepsis risks: A Mendelian randomization study. The World Allergy Organization Journal, 17(8), 100937. https://doi.org/10.1016/j.waojou.2024.100937