Asthma

○Currie GP, et al. Effects of montelukast on surrogate inflammatory markers in corticosteroid-treated patients with asthma. Am J Respir Crit Care Med 2003;167:1232–1238.

吸入ステロイドFP+LABA(サルメテロール)はFP+抗ロイコトリエンよりも呼吸機能改善みられるが抗炎症作用は失われてしまう

We evaluated whether montelukast conferred additive effects in patients with asthma receiving fluticasone/salmeterol (FP/SM) combination and FP alone. Twenty-two patients with mild to moderate asthma completed a double-blind, placebo-controlled study. After a 2-week run-in using FP 250 µg/SM 50 µg 1 puff twice daily, patients entered a randomized crossover period to receive additional montelukast 10 mg daily or placebo for 3 weeks each. For the first 2 weeks, they received FP/SM 1 puff BID, and then they received FP 250 µg 1 puff BID for the 3rd week. The primary outcome was adenosine monophosphate challenge threshold and recovery time; secondary outcomes included surrogate inflammatory markers and lung function. Compared with FP/SM run-in, adding montelukast to FP/SM was better (p < 0.05) than placebo for inflammatory markers but not for lung function. For adenosine monophosphate threshold, recovery, exhaled nitric oxide, and blood eosinophils, there were 1.4 (95% confidence interval, 1.1–1.8) geometric mean fold, 10 minutes (3–17 minutes), 2.1 parts per billion (0.2–3.9 parts per billion), and 88 (34–172) x 106/L differences, respectively. The combination of FP plus montelukast was superior to FP/SM for inflammatory markers but was inferior for lung function. Thus, in patients taking FP/SM or FP, montelukast conferred complimentary effects on surrogate inflammatory markers, which were dissociated from lung function. Further studies are required to evaluate whether these effects of montelukast translate into clinical benefits.



○EPR-3 guideline 低用量ICS+LABA(e.g. アドエア) or 中用量ICS(e.g. パルミコート)
・β2 agonistには炎症悪化のマスキング作用あり Th1/Th2インバランスの助長作用あり
・β2 agonistの遺伝子多型によって一部の症例ではLABA長期投与は安全でない可能性が残る
・中用量吸入ステロイドの方が安全でかつ確実な臨床効果あり

○有害事象
　パルミコート<フルタイド
　ただしフルタイドは粒子径が大きく中枢気道の炎症に対する効果が中心
　末梢まで炎症抑制するには<2µmが理想的

○ブデゾニド
持続性喘息患者に対して、維持療法に加えてブデゾニド-フォルモテロールを頓用（必要に応じて使用）すると、長時間作用性β2刺激薬（LABA）単独の頓用に比べ、重症の増悪が有意に減少することが、オランダにおける12カ月の比較試験で示された。オランダ・ライデン大学のKlaus Rabe氏らの研究成果で、詳細はLancet誌2006年8月26日号に報告された。
Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study

○オマリズマブ
step5, 6といった重症では抗IgE抗体(オマリズマブ)も考慮

○GINA guideline
○EPR-3 guideline