1. 慢阻肺炎症和哮喘炎症存在显著不同,激素治疗 COPD 改善肺功能、缓解呼吸困难症状的作用有限。2. 提高糖皮质激素治疗 COPD 敏感性应以恢复其功能为主,而不是加大剂量。3. 糖皮质激素增加 COPD 肺炎风险,治疗取舍遵循 GOLD 治疗建议。 总的来讲,COPD 对激素治疗不敏感性的发病机制、治疗策略方面仍有许多欠缺,部分治疗仍在探索中,但临床实践中应注意对病史、用药史的收集、分析,以及辅检结果的应用,避免出现本文患者这样盲目的或尝试性的治疗,尤其大剂量糖皮质激素或广谱抗菌药的应用,既增加不良反应风险,又增加患者经济负担。 合理使用糖皮质激素从识别可能从激素治疗中获益的患者开始,如果不能正确定位的话,根据目前的 GOLD 治疗建议,对于病情较严重(症状较多的D组患者)、急性加重风险较高 (≥2 次中度急性加重或 ≥1 次导致住院)、有哮喘病史或嗜酸性粒细胞增多患者应考虑使用糖皮质激素,并严格控制剂量。 策划 | 小舒克 绪国投稿 | drugs@dxy.cn题图 | 站酷海洛 参考文献:[1] 崔德建.支气管哮喘与慢性阻塞性肺疾病气道炎症及气道重塑的异同[J].感染、炎症、修复,2015,16(1):7-9.[2] Barnes P J. Mechanisms in COPD: Differences From Asthma[J]. Chest, 2000, 117(2):10S-14S.[3] BarnesPJ.Newmoleculartargetsforthetreatmentofneutrophilic diseases[J].JAllergy ClinImmunol,2007.119:l055-1062.[4] PujolsL, Mullol J, Roca-Ferrer J, et a1. Expression of glueocortieoid receptoralpha-andbeta-isoforms inhamancellsand tissues[J].Am JPhysiolCellPhysiol,2002.283:C1324-CI331.[5] 辛晓峰.慢性阻塞性肺疾病气道炎症对糖皮质激素不敏感的机制及对策[J].中华结核与呼吸杂志,2011,34(11):852-854.[6] OSOATA G, YAMAMURA S, ITO M, et al.Nitration of distinct tyrosine residues causes inactivation ofhistone deacetylase 2[J].BiochemBiophy Res Commun, 2009, 384:366-371.[7] RahmanI,GilmourPS,JimenezLA,eta1.Oxidativestressand TNF-alpha induce histone acetylation and NF-kappaB/AP-l activationin alveolarepithelialcells:potentialmechanism in gene transcription in lunginflammation[J].MolCellBiochem,2002,234-235:239-248.[8] RendaT,BaraldoS,PelaiaG,eta1.Increasedactivationofp38 MAPKinCOPD[J].EurRespirJ.2008,31:62-69.[9] IMarwiek JA,Caramori GCasolari P, eta1. A role for phosphoinositol3-kinasedelta in the impairmentofglucocorticoid responsiveness in patients with chronic obstructive pulmonary disease[J].JAllergy ClinImmunol,2010,125:1146-l153.[10] Cosio BG,Tsaprouni L,Ito K eta1.Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages[J].J Exp Med,2004,200(5):689-695.[11] Ford PA,Durham AL,Russell RE,eta1, Freatment efects of low-dose theophylline combined with an inhaled eorticosteroid in COPD[J].Chest,2010,137:1338-344.[12] To Y,Ito K,Kizawa Y,eta1.Targeting phosphoinositide-3-kinase-deha with theophylline reverses corticosteroid insensitivity in chronic obstructive pulmonary disease[J].Am J Respir Cril Care Med,2010,182:897904.[13] Singh D,Smyth L,Borrill Z,eta1.A randomized,placebo-controlled study of the effects of the p38 MAPK inhibitor SB-681323 on blood biomarkers of inflammation in COPD patients[J].J Clin Pharmaeol,2010,50:94-100.[14] Macnee W,Allan RJ,Jones I,eta1.Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease:a randomised clinical trial[J].Thorax,2013,68(8):738-745.[15] RahmanI,Adcock IM,Oxidative stress and redox regulation of lung inflammation in COPD[J].Eur Respir J,2006,28(1):219-242.[16] Thomas M,Bold P,Bjorhall K,eta1.Redefining the asthma treatment paradigm using a locally administered dual PI3Kgd inhibitor[J].Eur Respir J,2016,48(suppl60):OA468.[17] Ito K, Ito M, Elliott W M, et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease.[J]. Expert Opin Ther Targets, 2005, 9(6):1111-1121.[18] Kew KM, et al. Cochrane Database Syst Rev. 2014 ;10;(3):CD010115.[19] Contoli M, Pauletti A, Rossi M R, et al. Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD[J]. European Respiratory Journal, 2017, 50(4):1700451.