Muraki Masato, Wada Shota, Ohno Takeshi, Hanada Souichirou, Sawaguchi Hirochiyo, Iwanaga Takashi, Kume Hiroaki, Tohda Yuji
Department of Respiratory Medicine and Allergology, Nara Hospital, Kinki University Faculty of Medicine , Ikoma , Japan and.
Drug Deliv. 2014 Aug;21(5):321-7. doi: 10.3109/10717544.2013.846434. Epub 2013 Oct 23.
The systemic administration of theophylline is useful for asthma treatment. However its narrow therapeutic range makes it difficult to use. Little is known about its potential in inhalation therapy, particularly repeated inhalation.
The purpose of this study is to investigate the therapeutic usefulness of inhaled aminophylline in an asthma model.
The effects of pretreatment with inhaled aminophylline (25 mg/mL for 30 min/dose) on airway response and inflammation after an ovalbumin (OVA) challenge and airway hypersensitivity to acetylcholine (Ach) were evaluated using guinea pigs sensitized with OVA.
Aminophylline relaxed the ACh-induced contraction of tracheal smooth muscle in vitro in a concentration-dependent manner. Pretreatment with single-dose aminophylline inhalation suppressed OVA-induced airway constriction to the same extent as the intraperitoneal pretreatment with high-dose aminophylline (10-20 mg/kg). However, pretreatment with single-dose aminophylline inhalation did not suppress eosinophil infiltration into airways (neither bronchoalveolar lavage [BAL] fluid nor lung tissue) and did not suppress airway hyperreactivity to ACh, 24 h after OVA challenge. Repeated inhalation of aminophylline (twice daily for 7 days) suppressed the infiltration of eosinophils and suppressed airway hypersensitivity to ACh. In addition, high concentrations of aminophylline inhibited production of oxygen radicals by BAL cells.
Single-dose inhalation treatment with aminophylline has transient but relatively strong bronchodilating effects due to delivery of high doses into local airways. Repeated inhalation treatment suppressed airway inflammation and hypersensitivity induced by allergens. Therefore, inhaled aminophylline may be useful for asthma treatment.
茶碱的全身给药对哮喘治疗有用。然而，其狭窄的治疗窗使其使用困难。关于其在吸入治疗中的潜力，尤其是重复吸入，了解甚少。
本研究旨在探讨吸入用氨茶碱在哮喘模型中的治疗效用。
使用经卵清蛋白（OVA）致敏的豚鼠，评估吸入用氨茶碱（25 mg/mL，每次剂量30分钟）预处理对OVA激发后气道反应和炎症以及对乙酰胆碱（Ach）气道高反应性的影响。
氨茶碱在体外以浓度依赖的方式松弛Ach诱导的气管平滑肌收缩。单剂量氨茶碱吸入预处理抑制OVA诱导的气道收缩程度与高剂量氨茶碱（10 - 20 mg/kg）腹腔预处理相同。然而，单剂量氨茶碱吸入预处理在OVA激发后24小时并未抑制嗜酸性粒细胞浸润到气道（支气管肺泡灌洗[BAL]液和肺组织），也未抑制对Ach的气道高反应性。重复吸入氨茶碱（每日两次，共7天）抑制了嗜酸性粒细胞浸润并抑制了对Ach的气道高反应性。此外，高浓度的氨茶碱抑制BAL细胞产生氧自由基。
由于高剂量药物输送到局部气道，单剂量吸入氨茶碱治疗具有短暂但相对较强的支气管舒张作用。重复吸入治疗抑制了变应原诱导的气道炎症和高反应性。因此，吸入用氨茶碱可能对哮喘治疗有用。
