Objectives: Cigarette smoking (CS) induces mucus hypersecretion and coughing. Coughing after smoking cessation (SC) is also common. However, the mechanisms that underlie the effects of CS and SC on laryngeal mucus secretion remain elusive. We hypothesized that CS and SC cause laryngeal hypersecretion due to an increase in pro-inflammatory mediators. To test this hypothesis, we established smoking models of rats that involved administration of a cigarette smoke solution (CSS).

Methods: Firstly, we explored the effects of CS, short-term SC (four weeks), and long- term SC (three months) on laryngeal secretion and pro-inflammatory responses using histological analyses and quantitative real-time PCR analyses. Secondly, we investigated the effects of triamcinolone acetonide (TA) administration, which is one of glucocorticoids and have a long-lasting anti-inflammatory effect. Results: We found that both CS and short-term SC increased laryngeal secretion. This change coincided with an increase in the expression of mRNA for the inflammatory cytokines TNF-α, and IL-6. Concurrent upregulation of MUC5AC mRNA, which is involved in mucin production was also observed. Interestingly, the extent of mucus secretion in the short-term SC model was higher than in the CS model. However, inflammatory responses and laryngeal secretion were lower in the long-term SC model than in the short-term model. TA administration suppressed CSS-induced laryngeal mucus hypersecretion and pro-inflammatory cytokine production.

Conclusion: CSS induces laryngeal hypersecretion, while short-term SC causes further hypersecretion and upregulation of pro-inflammatory cytokines. These responses that occur during CS exposure and after SC represent promising targets for the treatment of cigarette smoke-associated prolonged cough and hypersecretion. TA may reduce expression of pro-inflammatory cytokines in the larynx and thus be useful for the treatment of CS- related symptoms.