NEW research has revealed shared genetic drivers behind chronic dry cough and cough caused by angiotensin-converting enzyme (ACE) inhibitors, commonly prescribed blood pressure medications, highlighting a potential neurological basis for both conditions. The findings could help explain why some people develop persistent coughing without a clear cause and may pave the way for new treatment targets.
Chronic dry cough, often linked to common lung conditions like asthma or COPD, can also be a side effect of ACE inhibitors. In many cases, however, the cough remains unexplained, creating a diagnostic and therapeutic challenge. To investigate possible genetic factors, researchers conducted large genome-wide association studies using data from five population-based cohorts. They studied people reporting chronic dry cough, those with documented ACE inhibitor-induced cough, and individuals who had experienced both.
In total, seven novel genetic signals were discovered with strong statistical significance. These variants mapped to ten new genes not previously linked to cough, including several involved in neurological processes such as CTNNA1, KCNA10, and MAPKAP1. Researchers also identified three additional genes that had not been linked before to known cough-associated variants. The findings suggest that abnormal nerve signalling or sensitivity may play a key role in both chronic dry cough and medication-related coughing.
To understand broader health implications, the team then used polygenic scoring to examine how the identified genetic variants were related to other conditions. The strongest associations were with asthma, diabetes, and multi-site chronic pain, suggesting shared genetic risk factors may underlie seemingly unrelated conditions.
Importantly, the study provides new evidence that chronic dry cough and ACE inhibitor-induced cough may not be entirely separate entities, but rather share common biological roots. The results reinforce the idea of cough hypersensitivity as a neurological condition, not just a symptom of airway inflammation or irritation.
While the research does not yet translate into immediate clinical applications, the discovery of new genes and pathways provides a critical foundation for future drug development. These insights may help develop more targeted treatments for individuals who suffer from chronic cough, especially when standard therapies fail or when symptoms arise as a side effect of essential medications like ACE inhibitors.
Reference
Coley K et al; Genes & Health Research Team. Genomics of chronic dry cough unravels neurological pathways. Eur Respir J. 2025; DOI:10.1183/13993003.02341-2024.
