Chronic cough may be associated with reduced gray matter volume (GMV) across multiple brain regions, according to results of a study published in CHEST.

The study findings come from a retrospective longitudinal cohort analysis that was conducted between 2006 and 2010 and involved individual-level data captured from 38,638 patients aged 40 to 69 years.

Patients were invited for initial and follow-up magnetic resonance imaging (MRI) assessments, and those with baseline brain MRI data, chronic cough status, and relevant covariate information were enrolled in the study. Researchers used a complete-case analytical approach for cross-sectional analyses, stratifying patients into a healthy control group and a chronic cough group. An online respiratory questionnaire was used to identify patients with chronic cough, which was defined as daily coughing for at least 3 months. 

The researchers quantified regional GMV across 139 predefined cortical, subcortical, and cerebellar areas via T1-weighted structural images that were segmented into tissue-type partial-volume maps. They also examined cross-sectional associations between baseline regional GMV and chronic cough via multivariable logistic regression with 3 prespecified sensitivity analyses of cough duration, medication-related cough, and major comorbid conditions. Longitudinal changes were also assessed via 1:3 propensity score matching and linear mixed-effects models.

These findings warrant validation in larger longitudinal cohorts and may help inform future efforts to develop imaging-derived biomarkers for monitoring longitudinal disease-related changes and evaluating responses to neuromodulatory therapies.

Among the total patient population, 4676 (12.3%) were diagnosed with chronic cough (median age, 68 years; 48% men). Compared with healthy control individuals, patients in the chronic cough group were older, more likely to be men, and had significantly reduced total brain volume (1470.11 vs 1481.15 cm3; all P <.001).

Patients in the chronic cough group showed significantly decreased mean GMV across 120 regions when compared with healthy control individuals (P <.05). The relative between-group difference in GMV ranged from approximately 0.5% to 3.0%. Further analysis revealed 63 brain regions as significantly associated with chronic cough, and regional GMV in these areas was inversely related to chronic cough risk (odds ratio [OR], all <1.0).

The strongest associations were noted in the right ventral striatum (OR, 0.44; 95% CI, 0.32-0.59) and in specific areas within the cerebellum, including VIIIb cerebellum vermis (OR, 0.53; 95% CI, 0.36-0.78) and IX cerebellum vermis (OR, 0.54; 95% CI, 0.38-0.77).

In a sex-stratified analysis, 41 brain regions were associated with chronic cough, of which 37 were female- and 4 were male-specific regions. Sex interaction testing in these regions showed 4 areas with significant sex-based differences in associated effects (P for interaction <.05). For female patients, significant inverse associations were noted in the right insular cortex, left lingual gyrus, left anterior temporal fusiform cortex, and left thalamus. For male participants, however, no significant associations were noted in these regions.

In the longitudinal analysis, 7 brain regions had significant interaction effects between GMV atrophy rate and chronic cough (PFDR <.20). The right VIIIa cerebellum had the most consistent interaction effects in both primary and sensitivity analyses.

Study limitations include the use of self-reported questionnaire data; potential lack of generalizability to other populations due to differences in neurologic, environmental, and clinical factors associated with chronic cough; and reduced statistical power for the longitudinal analysis.

“These findings warrant validation in larger longitudinal cohorts and may help inform future efforts to develop imaging-derived biomarkers for monitoring longitudinal disease-related changes and evaluating responses to neuromodulatory therapies,” the study authors concluded.

This article originally appeared on Pulmonology Advisor