Smoking and cluster headache: clinical, gender, and treatment insights from a cross-sectional cluster analysis

Abstract

Background The association between smoking and cluster headache (CH) has been consistently documented, with high rates of tobacco exposure observed among CH patients and several studies reporting links between smoking status and differences in disease onset, clinical features, and treatment response. However, the biological basis of this association remains uncertain, and no causal relationship has been established. To better characterize this interaction, the present study investigates the relationship between smoking and CH using three complementary analytical approaches. Methods In this multicenter study, participants with confirmed CH diagnosis completed a comprehensive survey addressing smoking habits, clinical features, and treatment responses. The study employed three analytical approaches: comparing smokers versus non-smokers, examining gender differences among smokers, and performing cluster analysis to identify distinct patient subgroups. Results Among 318 participants (76.7% male), 78.6% were smokers (current or former). Smokers reported higher rates of autonomic symptoms and suicidal thoughts compared to non-smokers. Non-smokers demonstrated better response to oral triptans and ergotamine, while subcutaneous sumatriptan was more effective in smokers. Female smokers experienced longer attack durations, while male smokers showed better triptan responsiveness. Cluster analysis revealed two groups: Cluster 2 comprised predominantly smokers (85.7%), showed earlier disease onset, and experienced more intense autonomic symptoms and attack-associated features compared to Cluster 1. Conclusions This study identifies differences in treatment response profiles between smokers and non-smokers, gender-related variations, and distinct clinical patterns associated with smoking status in patients with CH. These findings point to the potential value of considering smoking status when characterizing CH subgroups and designing individualized management strategies. However, as this is an observational study, the associations reported here should not be interpreted as evidence of causality, and further prospective and mechanistic research is required to clarify the nature of these relationships.