Esophageal hyposensitivity: A key link to aspiration pneumonia in patients with achalasia

Introduction: Aspiration pneumonia (AP) is a serious complication of achalasia; however, its risk factors and mechanisms remain unclear. We aimed to identify the clinical characteristics associated with AP and explore its underlying pathophysiology. Methods: This retrospective single-center study was included 70 patients diagnosed with achalasia using high-resolution manometry (HRM) between 2016 and 2022. Patients were categorized into non-AP (n = 42) and AP (n = 28) groups based on chest computed tomography findings. Clinical symptoms (Eckardt score), esophagographic findings, and HRM parameters were compared. Propensity score matching (PSM) was performed to adjust for age and disease duration. In a matched sub-cohort, esophageal mucosal biopsies were analyzed using quantitative real-time PCR to compare mechanosensory/chemosensory channels and inflammatory cytokines. Results: Patients with AP were older and tended to have a longer disease duration than those without AP. The Eckardt score was significantly lower in the AP group, despite no differences in HRM-defined or morphological subtypes on contrast esophagography. This difference remained significant after PSM. Expression levels of TRPV1, TRPV4, and PIEZO1 were significantly reduced in the achalasia (comprising both non-AP and AP patients) group compared with controls and were further decreased in the AP group compared with the non-AP group. Cytokine levels did not differ between the non-AP and AP groups. Conclusion: Esophageal hyposensitivity is a key risk factor for AP in achalasia, independent of HRM-defined or morphological subtypes. Downregulation of TRPV1, TRPV4, and PIEZO1 may underlie reduced symptom perception, providing novel insights into the pathophysiology of aspiration in achalasia.