“困难哮喘”的临床定义最近已扩展到包括越来越多的患者,这些患者的症状无法通过常规手段控制。迫使医学界开发创新的治疗方法。咖啡对哮喘患者的有益作用,主要是甲基黄嘌呤成分的作用,早就被描述过了。甲基黄嘌呤,包括茶碱和咖啡因,抑制磷酸二酯酶和下游cAMP信号以防止肥大细胞脱颗粒,同时促进免疫调节.1,11咖啡因也是苦味受体激动剂,在释放钙使气道平滑肌膜超极化之前与TAS2R结合,诱导支气管扩张10,38茶碱通常用于治疗哮喘,然而,根据文献,口服咖啡因所需的剂量已得到适度改善。我们试图确定将超细咖啡因颗粒(2.5-4μm)直接雾化到接受乙酰甲胆碱攻击的易感A/J小鼠的肺部是否会通过强制振荡技术改善肺功能。此外,我们评估了咖啡因雾化吸入是否会导致肺部病理生理学和支气管肺泡灌洗细胞谱的变化.我们发现,接受雾化咖啡因的小鼠在最大气道阻力方面具有统计学上的显着降低(6.3vs.3.9cmH2O。62.5mg/mL咖啡因时s/mL;CI=-4.3,-0.4;P=0.02),以及与对照组相比,达到最大阻力所需的时间显着延迟(64.7vs.在62.5mg/mL的咖啡因下为172.1秒,CI=96.0、118.9;P<0.0001)。雾化的咖啡因在一系列剂量下对气道高反应性产生一致的影响,而没有明显的病理学证据,相对于媒介物对照。
The clinical definition of \"difficult asthma\" has expanded recently to include an ever-growing subset of patients with symptoms that cannot be controlled by conventional means, forcing the medical community to develop innovative therapeutics. Beneficial effects of coffee for subjects with asthma, primarily the effect of methylxanthine components, have long been described. Methylxanthines, including theophylline and caffeine, inhibit phosphodiesterases and downstream cAMP signaling to prevent mast cell degranulation while promoting immunomodulation (Peleman RA, Kips JC, Pauwels RA. Clin Exp Allergy 28: 53-56, 1998; Deshpande DA, Wang WCH, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JSK, Liggett SB. Nat Med 16: 1299-1304, 2010). Caffeine is also a bitter taste receptor agonist, binding to taste-sensing type 2 receptors (
TAS2R) before releasing calcium to hyperpolarize airway smooth muscle membranes, inducing bronchodilation (Workman AD, Palmer JN, Adappa ND, Cohen NA. Curr Allergy Asthma Rep 15: 72, 2015; Devillier P, Naline E, Grassin-Delyle S. Pharmacol Ther 155: 11-21, 2015). Theophylline is conventionally used to treat asthma, whereas, according to the literature, the dosage required for orally administered caffeine has yielded modest improvement (Alfaro TM, Monteiro RA, Cunha RA, Cordeiro CR. Clin Respir J 12: 1283-1294, 2018). We sought to determine whether aerosolization of ultrafine caffeine particles (2.5-4 μm) directly to the lungs of susceptible A/J mice challenged with methacholine would improve pulmonary function via forced oscillation technique. In addition, we assessed whether nebulization of caffeine leads to changes in lung pathophysiology and bronchoalveolar lavage cell profiles. We found that mice that received aerosolized caffeine had statistically significant decreases in maximum airway resistance [6.3 vs. 3.9 cmH2O·s/mL at 62.5 mg/mL caffeine; confidence interval (CI) = -4.3, -0.4; P = 0.02] and significant delays in the time required to reach maximum resistance compared with that of controls (64.7 vs. 172.1 sec at 62.5 mg/mL caffeine, CI = 96.0, 118.9; P < 0.0001). Nebulized caffeine yielded a consistent effect on airway hyperresponsiveness at a range of doses without evidence of significant pathology relative to vehicle control.NEW & NOTEWORTHY For decades, coffee has been shown to improve symptoms in patients with asthma. One component, theophylline, is conventionally used to treat asthma, whereas the dosage required for orally administered caffeine has yielded modest improvement. We sought to determine whether aerosolization of caffeine directly to the lungs of susceptible A/J mice challenged with methacholine would alter pulmonary function via forced oscillation technique. We found nebulized caffeine yielded a consistent improvement on murine AHR.