Causal relationships between allergic diseases and significant declines in lung function: a multivariable Mendelian randomization study

Background: Asthma and other allergic diseases are increasing globally each year, with some patients experiencing the co-occurrence of two or more conditions, significantly impacting their quality of life. While these diseases may share certain immune mechanisms, the independent causal relationships between them and lung function remain unclear. Objective: This study aims to investigate the independent and interactive effects of allergic asthma, atopic dermatitis, allergic rhinitis, and allergic conjunctivitis on significant declines in lung function. By elucidating the potential causal relationships between these allergic diseases and reduced lung function, we hope to provide valuable scientific evidence for managing asthma patients who are co-morbid with multiple allergic conditions. Methods: In this study, we conducted Mendelian randomization (MR) analysis using data from the FinnGen database and the UK Biobank. We rigorously selected instrumental variables (IVs) based on established criteria and employed both univariable and multivariable MR approaches to investigate the relationship between various allergic diseases and significant declines in lung function. Results: In univariable MR analysis, the inverse variance-weighted (IVW) method or the weighted median approach indicated a causal relationship between allergic conjunctivitis, atopic dermatitis, and allergic asthma with significant declines in lung function. However, in multivariable MR analysis, the independent effects of atopic dermatitis and allergic conjunctivitis on lung function were no longer significant. Only allergic asthma continued to show a significant causal relationship with decreased lung function (OR [95%CI]: 1.019 [1.008-1.030], p < .001). Conclusions: This study suggests that while atopic dermatitis and allergic conjunctivitis may indirectly affect lung function and lead to significant declines, their independent effects are not notable when asthma is well-controlled. Therefore, clinicians should recognize that acute exacerbations of allergic diseases are unlikely to be the primary reason for significant declines in lung function among asthma patients with multiple allergic conditions, provided that their asthma is well-managed.