沙美特罗替卡松治疗咳嗽变异性哮喘及延缓复发的效果研究

Efficacy and Delay of Recurrence in Cough Variant Asthma Patients Treated with Salmeterol/Fluticasone

背景咳嗽变异性哮喘(CVA)是慢性咳嗽的重要病因,其病理生理特征与典型哮喘相似。CVA被认为是哮喘的早期阶段,所以建议及早联合应用吸入性糖皮质激素和支气管扩张剂,然而吸入皮质类固醇和β2肾上腺素激动剂联合治疗CVA的作用和机制尚未阐明。目的观察沙美特罗替卡松治疗CVA的临床疗效及对肺功能、外周血嗜酸粒细胞百分比(BER)、血清嗜酸粒细胞阳离子蛋白(ECP)、白介素5(IL-5)和诱导痰黏蛋白(MUC)5AC水平等气道炎性指标和CVA复发率的影响。方法选择2016年6月-2017年12月在漯河医学高等专科学校第三附属医院就诊的发作期CVA患者52例,采用随机数字表法将其分为对照组和观察组,各26例。对照组给予复方甲氧那明胶囊治疗,观察组给予沙美特罗替卡松粉吸入剂治疗。治疗期疗程8周,疗程结束后随访至治疗第24周。比较两组患者临床疗效;记录治疗前及治疗第8、24周的日间和夜间咳嗽症状评分、第1秒用力呼气末容积(FEV1)、最高呼气流量(PEF)、BER、ECP、IL-5和MUC5AC水平;生活质量采用中文版莱斯特咳嗽量表(LCQ-MC)于治疗前及治疗第8、24周进行评估;记录治疗期不良反应发生情况,随访期复发情况。结果对照组和观察组分别有2例和3例患者终止或脱落,两组实际有效例数分别为24例和23例。治疗8周后,观察组有效率为95.6%(22/23),高于对照组的75.0%(18/24)(P=0.047)。治疗第8、24周,观察组日间咳嗽症状评分、夜间咳嗽症状评分均低于对照组;两组治疗第8周日间咳嗽症状评分、夜间咳嗽症状评分均低于治疗前(P<0.05),第24周日间咳嗽症状评分、夜间咳嗽症状评分均高于第8周(P<0.05)。治疗第8、24周,观察组生理、心理、社会评分和总分均高于对照组(P<0.05);两组治疗第8周生理、心理、社会评分和总分均高于治疗前(P<0.05),第24周生理、心理、社会评分和总分均低于第8周(P<0.05)。治疗第8、24周,观察组ΔFEV1均高于对照组(P<0.05)。治疗第8周,观察组PEF高于对照组(P<0.05);两组治疗第8周PEF均高于治疗前(P<0.05),第24周PEF均低于第8周(P<0.05)。治疗第8周,观察组BER、ECP、IL-5、MUC5AC水平均低于对照组(P<0.05);治疗第24周,观察组IL-5水平低于对照组(P<0.05);观察组治疗第8周BER、ECP、IL-5、MUC5AC水平均低于治疗前(P<0.05),治疗第24周BER、ECP、IL-5、MUC5AC水平均高于第8周(P<0.05)。观察组和对照组不良反应发生率分别为13.0%(3/23)和8.3%(2/24),两组不良反应发生率比较,差异无统计学意义(P>0.05)。观察组复发率为26.1%(6/23),低于对照组的58.3%(14/24)(P<0.05)。结论沙美特罗替卡松可以有效改善CVA患者咳嗽症状,提高生活质量和改善肺功能指标,降低气道炎性反应,并且可以延缓停药治疗后肺功能下降、炎性反应指标反弹和CVA复发。

Background Cough variant asthma(CVA)is an important cause of chronic cough,and pathophysiological features of the disease appear to be similar to typical asthma.Being recognized as the early stage of asthma,CVA is recommended to be treated with anti-inflammatory agents in combination with bronchodilators as early as possible.However,the effect and mechanism of inhaled corticosteroids andβ2 agonists in the treatment of CVA has not been elucidated.Objective To observe the overall efficacy of salmeterol/fluticasone,and its impact on pulmonary function,airway inflammatory markers〔percentage of peripheral blood eosinophils(BER),serum eosinophil cationic protein(ECP),interleukin 5(IL-5)and MUC5AC〕and recurrence rate in CVA patients.Methods 52 patients with CVA in ictal phase treated in The Third Affiliated Hospital of Luohe Medical College during June 2016 to December 2017 were recruited and were equally randomized into the control group(orally administered compound methoxyphenamine capsules)and observation group(inhaled fluticasone propionate/salmeterol xinafoate powder).Both groups were treated for 8 weeks,and were followed up for 24 weeks(8-week treatment plus subsequent 16 weeks without the above-mentioned treatment).Main outcome measures for the overall efficacy were changes in daytime and nighttime cough symptom scores,FEV1,peak expiratory flow(PEF),percentage of peripheral blood BER,ECP,IL-5 and MUC5AC at the end of 8th and 24th weeks in comparison with the baseline status.Quality of life was measured by the Mandarin Chinese Version of the Leicester Cough Questionnaire(LCQ-MC)at baseline,and at the end of 8th and 24th weeks of intervention.Adverse reactions during treatment and recurrence rate during follow-up were recorded.Results Except 2 cases in the control group and 3 cases in the observation group who dropped out of the study or were lost to follow up,the other cases were included for final analysis.At the end of 8-week treatment,the observation group showed a higher overall response rate than the control group〔95.6%(22/23)vs 75.0%(18/24)〕(P=0.047).The mean daytime and nighttime cough symptom scores of the observation group were all lower than those of the control group at the end of 8th and 24th weeks of intervention(P<0.05).In both groups,the mean daytime and nighttime cough symptom scores decreased after intervention.Specifically,the mean daytime and nighttime cough symptom scores at the end of the 8th week of intervention were much lower compared with the baseline scores,and compared with the scores at the end of 24 weeks of intervention(P<0.05).In both groups,mean scores of LCQ-MC and its three physical,psychological and social domains increased after intervention,specifically,mean scores of LCQ-MC and physical,psychological and social domains at the end of the 8th week of intervention were much higher compared with the baseline levels,and compared with the levels at the end of the 24th week of intervention(P<0.05).The observation group showed higher mean scores of LCQ-MC and physical,psychological and social domains than the control group at the end of 8 and 24 weeks of intervention(P<0.05).At the end of the 8th and 24th weeks of intervention,theΔFEV1 in the observation group was greater than that in the control group(P<0.05).In both groups,mean PEF increased after intervention.Specifically,mean PEF at the end of 8 weeks of intervention was much higher compared with the baseline level,and compared with the level at the end of 24 weeks of intervention(P<0.05).At the end of the 8th week of intervention,the mean PEF of the observation group was higher than that of the control group(P<0.05).Compared with the control group,the observation group demonstrated lower mean percentage of peripheral blood BER,ECP,IL-5 and MUC5AC at the 8th week of intervention,and demonstrated lower mean IL-5 at the 24th week of intervention(P<0.05).In the observation group,the mean percentage of peripheral blood BER,ECP,IL-5 and MUC5AC at the 8th week of intervention were lower than the baseline levels,and were lower than the levels at the 24th week of intervention(P<0.05).The incidence of adverse reactions in the observation group and control group was 13.0%(3/23)and 8.3%(2/24),respectively,without significant difference(P>0.05).The recurrence rate of the observation group was 26.1%(6/23),which was lower than that of the control group〔58.3%(14/24)〕(P<0.05).Conclusion Inhaling fluticasone propionate/salmeterol xinafoate powder provides further improvements in cough symptoms,quality of life,pulmonary function and airway inflammation in patients with CVA,and may delay the decline of pulmonary functions,rebound of inflammatory markers as well as CVA recurrence caused by the discontinuation of the therapy.