RT Journal Article SR Electronic T1 Mice with immotile cilia spontaneously cough due to mechanical stimuli of postnasal drip JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 2807 VO 40 IS Suppl 56 A1 Toshiyuki Iwata A1 Isao Ito A1 Akio Niimi A1 Koji Ikegami A1 Satoshi Marumo A1 Naoya Tanabe A1 Hitoshi Nakaji A1 Hisako Matsumoto A1 Tsuyoshi Oguma A1 Hideki Inoue A1 Tomoko Tajiri A1 Tadao Nagasaki A1 Yoshihiro Kanemitsu A1 Junzo Kamei A1 Mitsutoshi Setou A1 Michiaki Mishima YR 2012 UL http://erj.ersjournals.com/content/40/Suppl_56/2807.abstract AB Background: The underlying mechanisms of cough in patients with rhinosinusitis are poorly understood. We reported that tubulin tyrosine ligase-like family member 1 gene (Ttll1) knockout (KO) mice showed disorders of ciliary motility resulting in rhinosinusitis together with cough reflex.Aim: To examine mechanisms of cough in Ttll1-KO mice.Methods and results: We pathologically searched for the causes of cough and examined structural changes of the airway in KO mice. Postnasal drip (PND) was observed in the pharynx. There was no evidence of inflammation and remodeling in the lower airway. Capsaicin cough sensitivity was increased in KO mice compared to WT mice. Moguisteine, which inhibits cough via suppression of rapidly adapting receptor (RAR), decreased cough, while capsazepine, an antagonist of the transient receptor potential vanilloid subfamily 1, did not. Tosufloxacin, a fluoroquinolone antibiotic, improved nasal inflammation but accumulation of mucus and cough remained. To prove that mucus stimuli evoke cough, artificial PND were made to evoke cough in WT mice. WT mice distinctly coughed due to artificial PND. Blue dye and contrast material were administered to study nasal clearance and movement of mucus. We confirmed that nasal ciliary clearance was decreased in KO mice. Further, blocking nasal discharge from flowing to the larynx completely inhibited cough of KO mice.Conclusions: Mechanical stimulation to larynx due to PND was transduced to the central nervous system via RAR and evoked cough in Ttll1-KO mice. Ttll1-KO mice may serve to reveal the mechanisms of cough in patients with PND and to develop new antitussive drugs.