College of Pharmacy, Division of Molecular Pharmaceutics and Drug Delivery, The University of Texas at Austin, Austin, TX 78712, USA.
Respira Therapeutics, Inc., 1828 El Camino Real #806, Burlingame, CA 94010, USA.
Adv Drug Deliv Rev. 2020;165-166:127-141. doi: 10.1016/j.addr.2020.05.003. Epub 2020 May 14.
This review provides an assessment of post-inhalation cough with therapeutic aerosols. Factors that increase cough may be mitigated through design of the drug, formulation, and device. The incidence of cough is typically less than 5% for drugs with a nominal dose less than 1 mg, including asthma and COPD therapeutics. Cough increases markedly as the dose approaches 100 mg. This is due to changes in the composition of epithelial lining fluid (e.g., increases in osmolality, proton concentration). Whether an individual exhibits cough depends on their degree of sensitization to mechanical and chemical stimuli. Hypersensitivity is increased when the drug, formulation or disease result in increases in lung inflammation. Cough related to changes in epithelial lining fluid composition can be limited by using insoluble neutral forms of drugs and excipients.
本综述评估了吸入后咳嗽与治疗性气溶胶的关系。可通过药物设计、制剂和装置来减轻可能增加咳嗽的因素。通常情况下，对于名义剂量小于 1mg 的药物，包括哮喘和 COPD 治疗药物，咳嗽的发生率低于 5%。当剂量接近 100mg 时，咳嗽明显增加。这是由于上皮衬里液成分的变化（例如渗透压、质子浓度增加）所致。个体是否出现咳嗽取决于其对机械和化学刺激的敏感程度。当药物、制剂或疾病导致肺部炎症增加时，敏感性会增加。通过使用药物和赋形剂的不溶性中性形式，可以限制与上皮衬里液成分变化相关的咳嗽。
