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Brain Structural Remodeling and Longitudinal Gray Matter Changes in Adults With Chronic Cough: Evidence from a
Shuojia Xie1, Mingyu Zhong1, Zikai Lin1
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Background:
Chronic cough (CC) is increasingly recognized as a hypersensitivity syndrome involving maladaptive neuroregulatory changes; however, large-scale evidence regarding macroscale structural brain alterations and their longitudinal trajectories remains scarce.
Research Question:
Is CC associated with specific regional gray matter volume (GMV) alterations and an accelerated rate of brain atrophy over time?
Study Design And Methods:
This retrospective longitudinal cohort study used individual-level data from the UK Biobank involving 38,638 participants with baseline brain MRI scan (4,676 patients with CC) and a subset of 2,798 participants who underwent repeated imaging. Regional GMV across 139 areas was quantified from T1-weighted structural images. Cross-sectional associations were assessed using multivariable logistic regression with 3 prespecified sensitivity analyses evaluating cough duration, medication-related cough, and major comorbid conditions. Longitudinal changes were evaluated using 1:3 propensity score matching and linear mixed-effects models.
Results:
CC was associated with significantly reduced GMV in 63 brain regions, with the strongest associations observed in the right ventral striatum (OR, 0.44; 95% CI, 0.32-0.59). Sex-stratified analysis revealed more extensive, left-lateralized structural remodeling in females (P interaction < .05). Chronic dry cough was specifically associated with reduced GMV in the bilateral postcentral gyrus (both ORs < 1). Furthermore, longitudinal analysis suggested that CC may be associated with a faster rate of GMV decline in 7 regions, particularly within the cerebellum.
Interpretation:
Our results show that CC is associated with significant widespread structural brain alterations and accelerated atrophy within brain regions, supporting the possibility that CC may be associated with dynamic neurostructural change potentially related to altered central neural processing.
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