From Bibliometrics to Preliminary Clinical Evidence: TRP Channel-Mediated Neuroimmune Crosstalk in Temperature-Sensitive Airway Hyperresponsiveness.

INTRODUCTION: Temperature variability is a critical environmental trigger for airway hyperresponsiveness (AHR); however, the specific neuroimmune mechanisms linking thermal stress to respiratory inflammation remain underexplored. METHODS: We integrated a macroscopic bibliometric analysis of the global literature (1925-2024) with an exploratory clinical validation. To corroborate emergent bibliometric trends, nasal mucosal biopsies were collected from patients with temperature-sensitive AHR (n=9) and normal controls (NC, n=9). The localized expression of transient receptor potential (TRP) channels (TRPV1, TRPM8, and TRPA1) was evaluated using reverse transcription-quantitative PCR (RT-qPCR) and semi-quantitative immunohistochemistry (IHC). Furthermore, local neuroimmune interactions were assessed by evaluating the spatial co-localization of TRP channels with substance P (SP) via immunofluorescence (IF) and semi-quantitative analysis. RESULTS: Bibliometric mapping revealed a progressive paradigm shift from broad epidemiological associations toward specific molecular mechanisms, identifying TRP channels as central research hotspots. In the exploratory clinical cohort, both RT-qPCR and IHC analyses confirmed that TRPV1, TRPM8, and TRPA1 were significantly upregulated in the nasal mucosa of AHR patients compared to controls (all FDR-adjusted q < 0.05, supported by large effect sizes). Additionally, IF imaging demonstrated robust spatial co-localization of these overexpressed TRP channels with SP, structurally supporting the presence of local neurogenic inflammation. CONCLUSION: By bridging bibliometric trends with experimental corroboration, this study highlights TRP channels as pivotal "thermosensory switches" in AHR neuroimmune crosstalk. These findings provide preliminary clinical evidence that TRP-mediated pathways may drive the transition from external thermal fluctuations to mucosal inflammatory cascades. Given the exploratory nature of the current cohort size, our results offer a targeted biomolecular framework for future large-scale investigations into climate-sensitive respiratory diseases.