Lanz M J, Eisenlohr C, Llabre M M, Toledo Y, Lanz M A
Allergy, Asthma, Atopic Dermatitis, Rhinitis, Sinusitis Clinical Research Center, Pan American Hospital Asthma and Allergy Center, Coral Gables, Florida, USA.
Ann Allergy Asthma Immunol. 2001 Oct;87(4):283-8. doi: 10.1016/S1081-1206(10)62241-7.
Exhaled nitric oxide (ENO) is a noninvasive marker of ongoing inflammation in asthmatic patients. Comparison between inhaled and oral anti-inflammatory medications in reduction of ENO in asthmatic patients has not been performed.
We measured changes in ENO, spirometry, need for rescue medication, quality of life (QOL), and diary scores (DS) after inhaled and oral anti-inflammatory therapy in adults with moderate asthma.
A randomized, double-blind, placebo-controlled, crossover design with 4-week washout periods was used. A plateau level of ENO, measured in parts per billion (ppb), was obtained by chemiluminescence with a Sievers 280NOA as per American Thoracic Society recommendations. Eighteen asthmatic adults (15 Hispanic, with a percentage predicted forced expiratory volume in 1 second (FEV1%) of 50% to 85%) on bronchodilators (beta2) only were studied. Subjects used fluticasone propionate (FP) metered-does inhaler (44 microg), two puffs twice daily, and matching placebo (PB) for 4 weeks. Eight of the asthmatic patients (7 Hispanic, FEV1% 50% to 85%) on bronchodilators only then received blinded zafirlukast (ZK) 20 mg and matching PB twice daily for 4 weeks.
Low-dose inhaled FP resulted in significant improvements in ENO, spirometry, QOL, DS, and beta2 use. A significant difference in mean ENO was found (P < 0.01) before and after FP from 34+/-7 ppb to 13+/-3 ppb. A significant improvement was found (P < 0.05) with FEV1% from 75+/-3 to 85+/-3 with FP treatment. The other measured parameters, percentage predicted of peak expiratory flow rate, beta2 need, DS, and QOL measurements, were improved with low-dose FP treatment. No significant reduction was found in ENO with oral ZK for 4 weeks. After oral ZK washout and the second extension arm of placebo, ENO significantly increased back to 47+/-14 ppb (P < 0.05), but spirometry measures did not worsen. Significant improvements were found with DS and beta2 use with oral ZK therapy.
These results reveal ENO is reduced with only low-dose inhaled FP in asthmatic patients not on anti-inflammatory medication. In the smaller extension study, ENO was reduced with FP and not with oral ZK treatment, and ENO levels increased back to near prestudy levels after ZK washout and the second extension arm of placebo. As a marker of inflammation, ENO levels reveal an improvement with anti-inflammatory medication and worsening when it is discontinued.
呼出一氧化氮（ENO）是哮喘患者炎症活动的无创性标志物。尚未对吸入性和口服抗炎药物降低哮喘患者ENO水平的效果进行比较。
我们测量了中度哮喘成年患者在吸入和口服抗炎治疗后ENO、肺功能、急救药物需求、生活质量（QOL）和日记评分（DS）的变化。
采用随机、双盲、安慰剂对照、交叉设计，洗脱期为4周。按照美国胸科学会的建议，使用Sievers 280NOA化学发光法以十亿分之一（ppb）为单位测量ENO的稳定水平。仅对18名仅使用支气管扩张剂（β2）的哮喘成年患者（15名西班牙裔，1秒用力呼气量（FEV1%）预计值为50%至85%）进行了研究。受试者使用丙酸氟替卡松（FP）定量吸入器（44微克），每日两次，每次两喷，以及匹配的安慰剂（PB），为期4周。其中8名仅使用支气管扩张剂的哮喘患者（7名西班牙裔，FEV1% 50%至85%）随后接受了盲法扎鲁司特（ZK）20毫克治疗，每日两次，每次两喷，以及匹配的PB，为期4周。
低剂量吸入FP可显著改善ENO、肺功能、QOL、DS以及β2的使用情况。FP治疗前后平均ENO有显著差异（P < 0.01），从34±7 ppb降至13±3 ppb。FP治疗后FEV1%从75±3显著提高至85±3（P < 0.05）。低剂量FP治疗还改善了其他测量参数，如呼气峰值流速预计值百分比、β2需求、DS和QOL测量值。口服ZK 4周后ENO无显著降低。口服ZK洗脱后以及第二个安慰剂延长治疗期后，ENO显著回升至47±14 ppb（P < 0.05），但肺功能指标并未恶化。口服ZK治疗可显著改善DS和β2的使用情况。
这些结果表明，对于未使用抗炎药物的哮喘患者，仅低剂量吸入FP即可降低ENO水平。在规模较小的延长研究中，FP可降低ENO水平，而口服ZK则不能，且ZK洗脱后以及第二个安慰剂延长治疗期后，ENO水平回升至接近研究前水平。作为炎症标志物，ENO水平随抗炎药物治疗而改善，停药后则恶化。
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