Brain Structure, Cough Hypersensitivity May Be Linked in Adults With Chronic Cough

An area of the brain that contributes to cough suppression was found to be smaller in volume in adults with chronic cough than those without, demonstrating a possible connection between brain structure changes and cough hypersensitivity.

The anterior cingulate cortex, a part of the brain included in cough suppression, was found to be smaller in volume in adults with chronic cough, possibly indicating a link between structural brain changes and cough hypersensitivity, found a study in CHEST.

In addition, a negative correlation between chronic cough and anterior cingulate cortex volume was more apparent in men and in the left hemisphere.

Currently, chronic cough is linked with significant physical and psychosocial problems that worsen underlying medical conditions. It constitutes an immense financial and clinical burden on patients and health care systems. This study was conducted because it is known that adults with cough hypersensitivity have more central neural responses to tussive stimuli that may develop maladaptive morphometric changes in cough-producing brain areas.

Researchers were trying to determine if the volume of the cough hypersensitivity regions of the brain were different in adults with chronic cough compared to those without. Participants from the Rotterdam Study, a population-based study, were interviewed for chronic cough following magnetic resonance imaging (MRI) between 2009 and 2014. Chronic cough was defined as at least 3 months of daily coughing. Brain regions measured included the frontal pole, inferior frontal, insula, middle frontal, middle temporal, prefrontal cortices, and the anterior cingulate cortex.

To analyze the data, FreeSurfer software was used to quantify brain volumes. A literature review was used to identify and study the 7 brain regions. Multivariable regression models were used to analyze the connection between chronic cough and regional brain volumes.

Out of 3620 study participants (mean [SD] age 68.5, [9.0] years; 54.6% women), chronic cough prevalence was 9.6% (n = 349).

Those with chronic cough possessed significantly smaller anterior cingulate cortex volume than participants without (mean difference: –20 to –126.16 mm3; 95% CI, –245.67 to –6.66; P = .039). No significant volume differences in the other measured brain regions were found based on chronic cough status. The left hemisphere of the ACC had a more pronounced volume difference (mean difference: –88.11 23 mm3; 95% CI, –165.16 to –11.06, P = .025) and was more evident in men (mean difference: –242.58 mm3; 95% CI, –428.60 to –56.55, P = .011).

In this study, differences in brain volume related to chronic cough were only found in the anterior cingulate cortex region of the brain, unlike other clinical studies observing functional differences in more than one brain region. Despite this, researchers said that their findings are consistent with past research.

Also, changes in smaller middle frontal volume in participants with chronic cough were found but determined not to be statistically significant.

The brain volume areas affected linked with chronic cough were discovered in an area previously associated with dysfunctional cough suppression and emotional cough processing, demonstrating that hindered cough control and cough input amplification are core components of chronic cough in adults. Morphometric alterations related to chronic cough in the anterior cingulate cortex were found to be primarily driven by people with risk factors or treatable chronic cough traits, hinting at more structural brain changes in this group.

In addition, these findings might assist in the implementation of possible therapeutic targets for adults with chronic cough. This study contributes to the understanding of neuropathological changes in chronic cough and gives epidemiologic evidence of likely neuroplasticity in chronic cough, but more research is needed to understand what these findings mean and how people with chronic cough can be treated.

This research, according to the authors, is the first large population-based observational study using brain MRI to examine structural brain volume differences in adults with chronic cough.

One limitation cited by the authors is that the cross-sectional study design limits the ability to determine if there is a causal relationship between chronic cough and anterior cingulate cortex volume differences, so researchers suggest that a longitudinal study of brain volumetric changes in chronic cough be conducted to confirm the present findings. They also noted that the study may have had disease misclassifications and that patients with chronic cough had more suboptimal MRI scans compared with those without chronic cough.


Arinze JT, Vinke EJ, Verhamme KMC, et al. Chronic cough-related differences in brain morphometry in adults: apopulation-based study. Chest. Published online February 10, 2023. doi:10.1016/j.chest.2023.02.007

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