Background: Previous studies have shown an association between chronic rhinosinusitis (CRS) and gastroesophageal reflux disease (GERD). However, the findings of these studies are controversial, and evaluating this association could help in the treatment of CRS. Thus, we aimed to clarify the relationship between GERD and CRS. Methods: We conducted a Mendelian randomization (MR) study. Pooled data on CRS, GERD, and their associated risk factors were extracted from large genome-wide association studies. Independent single-nucleotide polymorphisms were rigorously screened as instrumental variables. Causal associations between GERD and CRS were assessed, and mediation analyses were performed using multivariate and 2-step MR. Asthma served as a mediator because of its association with both CRS and GERD. Sensitivity tests were also performed. Results: MR analysis showed that genetically predicted GERD was associated with an increased risk of CRS (P < .001). Multivariate MR analysis showed that the effect of GERD on CRS was relatively independent. Mediation analysis showed that asthma mediated the association with a mediation effect of 21.07% (95% CI, 2.70%-40.18%). Sensitivity analyses did not reveal any significant effects of pleiotropy and heterogeneity. Conclusions: We found a causal relationship between genetically predicted GERD and an increase in the risk of CRS. As a mediator, asthma contributed to the effect of GERD on CRS. This study provides high-quality causal evidence for the prevention of CRS.

Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus. LPRD commonly presents with sym-ptoms such as hoarseness, cough, sore throat, a feeling of throat obstruction, excessive throat mucus. This complex condition is thought to involve both reflux and reflex mechanisms, but a clear understanding of its molecular mechanisms is still lacking. Currently, there is no standardized diagnosis or treatment protocol. Therapeutic strategies for LPRD mainly include lifestyle modifications, proton pump inhibitors and endoscopic surgery. This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms, patho-physiology and treatment of LPRD. We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) and chronic rhinosinusitis (CRS) have been shown to be potentially closely related, but the relationship between these conditions, particularly the possibility of a causal link, is not fully understood. This study used Mendelian randomization (MR) to assess the causal relationship between these two disorders.

We extracted genome-wide association study data sets for GERD and CRS from publicly available gene summaries, and used MR to conduct a causal inference analysis. The main robustness test used in this study included MR-Egger regression, a leave-one-out sensitivity test, and multivariate MR (MVMR).

GERD increased the risk of developing CRS by 36%, based on the inverse-variance weighted method, a statistically significant association (odds ratio [OR] 1.360, 95% confidence interval [CI] 1.179-1.568, P < 0.001). Other MR assessment methods, such as weighted median, simple mode, and weighted mode, similarly observed a significant increase in the risk of CRS occurrence (OR 1.434, 95% CI 1.186-1.734, P < 0.001; OR 1.927, 95% CI 1.166-3.184, P = 0.013; and OR 1.910, 95% CI 1.222-2.983, P = 0.006, respectively). No significant bias was found in the heterogeneity or pleiotropy tests (P = 0.071 and P = 0.700, respectively). Even after excluding possible mediators using MVMR, GERD appeared to significantly increase the risk of developing CRS (OR 1.013, 95% CI 1.008-1.023, P = 0.002).

This study provides new, significant evidence that GERD is genetically associated with a higher incidence rate of CRS. However, further research is needed to elucidate the potential underlying biological mechanisms of this relationship.