目的 观察丙酸氟替卡松（Flu）、孟鲁斯特钠（Mon）与酮替芬（Ket）的不同联合用药方案治疗儿童咳嗽变异性哮喘（CVA）的效果。方法 将2015年6月至2018年1月于呼吸科门诊收治的280例CVA患儿随机分为Flu+Mon+Ket组、Flu+Mon组、Flu+Ket组、Mon+Ket组、Flu组、Mon组、Ket组（n=40）。每组根据各自的用药方案给予相应药物，疗程均为3个月。评估患儿在治疗后2个月及3个月时的咳嗽情况及评分、肺功能和药物不良反应，并随访复发情况。结果 随治疗时间，7组患儿咳嗽评分均呈下降趋势，第1秒用力呼气容积占预计值的百分比（FEV1%）、最大呼气流量占预计值的百分比（PEF%）均呈上升趋势。治疗2个月后，Flu+Mon+Ket组咳嗽评分均低于其他组，FEV1%、PEF%均高于其他组（P < 0.05）；治疗2个月后及治疗3个月后，Ket组咳嗽评分明显高于其他组，FEV1%、PEF%明显低于其他组（P < 0.05）；其他各组在治疗3个月后，组间咳嗽评分、FEV1%、PEF%比较差异均无统计学意义（P > 0.05）。7组不良反应发生率低且差异无统计学意义（P > 0.05）。Ket组咳嗽复发率明显高于其他组（P < 0.001），其他各组间咳嗽复发率比较差异无统计学意义（P > 0.0024）。结论 Flu、Mon、Ket三药联合使用治疗儿童CVA在2个月时的疗效较两药联用及单药使用显著，且用药安全；但用药3个月后，单用Flu或单用Mon的疗效不差于联合用药；单用Ket疗效不佳，且停药后复发率较高。
Abstract
Objective To study the clinical effect of different combinations of fluticasone propionate (Flu), montelukast sodium (Mon) and ketotifen (Ket) in the treatment of children with cough variant asthma (CVA). Methods A total of 280 children with CVA who were admitted to the department of respiratory medicine from June 2015 to January 2018 were randomly divided into Flu+Mon+Ket, Flu+Mon, Flu+Ket, Mon+Ket, Flu, Mon and Ket groups, with 40 children in each group. The children in each group were given corresponding drug(s), and the course of treatment was 3 months for all groups. The condition of cough, cough symptom score, pulmonary function and adverse drug reactions were evaluated after 2 and 3 months of treatment. The children were followed up to observe recurrence. Results After treatment, cough symptom score tended to decrease in all 7 groups, with increases in percentage of forced expiratory volume in 1 second (FEV1%) and percentage of predicted peak expiratory flow (PEF%). After 2 months of treatment, the Flu+Mon+Ket group had a significantly lower cough symptom score and significantly higher FEV1% and PEF% than the other groups (P < 0.05). After 2 and 3 months of treatment, the Ket group had a significantly higher cough symptom score and significantly lower FEV1% and PEF% than the other groups (P < 0.05). After 3 months of treatment, there were no significant differences in cough symptom score, FEV1% and PEF% among the other groups (P > 0.05). There was a low incidence rate of adverse events in all 7 groups, and there was no significant difference among the 7 groups (P > 0.05). The Ket group had a significantly higher recurrence rate of cough than the other groups (P < 0.001), while there was no significant difference in this rate among the other groups (P > 0.0024). Conclusions For children with CVA, a combination of Flu, Mon and Ket has a better clinical effect than a combination of two drugs and a single drug at 2 months of treatment and is safe. After 3 months of treatment, Flu or Mon alone has a similar effect to drug combination. Ket alone has a poor clinical effect and a high recurrence rate after drug withdrawal.
关键词
咳嗽变异性哮喘 /
丙酸氟替卡松 /
孟鲁司特钠 /
酮替芬 /
临床疗效 /
儿童
Key words
Cough variant asthma /
Fluticasone propionate /
Montelukast sodium /
Ketotifen /
Clinical effect /
Child
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参考文献
[1] Tang W, Zhou J, Miao L, et al. Clinical features in patients of cough variant asthma with normal andhigh level of exhaled fractional nitric oxide[J]. Clin Respir J, 2018, 12(2):595-600.
[2] Saito N, Itoga M, Tamaki M, et al. Cough variant asthma patients are more depressed and anxious than classic asthma patients[J]. J Psychosom Res, 2015, 79(1):18-26.
[3] Terasaki G, Paauw DS. Evaluation and treatment of chronic cough[J]. Med Clin North Am, 2014, 98(3):391-403.
[4] 吴艳玲, 张海邻. 儿童咳嗽变异性哮喘诊治进展[J]. 中华儿科杂志, 2016, 54(4):314-317.
[5] 中国儿童慢性咳嗽病因构成比研究协作组. 中国儿童慢性咳嗽病因构成比多中心研究[J]. 中华儿科杂志, 2012, 50(2):83-92.
[6] 中华医学会儿科学分会呼吸学组慢性咳嗽协作组, 中华儿科杂志编辑委员会. 中国儿童慢性咳嗽诊断与治疗指南(2013年修订)[J]. 中华儿科杂志, 2014, 52(3):184-188.
[7] 中华医学会呼吸病学分会哮喘学组. 咳嗽的诊断与治疗指南(2015)[J]. 中华结核和呼吸杂志, 2016, 39(5):323-354.
[8] 刘军艳, 刘晓娟. 咳嗽变异性哮喘与支气管哮喘的关系[J]. 吉林医学, 2014, 35(2):255-256.
[9] Quirt J, Hildebrand KJ, Mazza J, et al. Asthma[J]. Allergy Asthma Clin Immunol, 2018, 14(Suppl 2):50.
[10] Ishiura Y, Fujimura M, Kasahara K. Eosinophilic bronchial disorders presenting chronic cough; atopic cough, cough variant asthma and non-asthmatic eosinophilic bronchitis[J]. J Genet Syndr Gene Ther, 2014, 5:2.
[11] Bonvini SJ, Birrell MA, Smith JA, et al. Targeting TRP channels for chronic cough:from bench to bedside[J]. Naunyn Schmiedebergs Arch Pharmacol, 2015, 388(4):401-420.
[12] 中华医学会呼吸病学分会哮喘学组. 支气管哮喘防治指南(2016年版)[J]. 中华结核和呼吸杂志, 2016, 39(9):675-697.
[13] 中华医学会儿科学分会呼吸学组, 中华儿科杂志编辑委员会. 儿童支气管哮喘诊断与防治指南(2016年版)[J]. 中华儿科杂志, 2016, 54(3):167-181.
[14] Global Initiative for Asthma. Global strategy for asthma management and prevention (updated 2018)[EB/OL]. https://ginasthma.org/wp-content/uploads/2018/04/wms-GINA-2018-report-V1.3-002.pdf.
[15] Du W, Zhou L, Ni Y, et al. Inhaled corticosteroids improve lung function, airway hyper-responsiveness and airway inflammation but not symptom control in patients with mild intermittent asthma:a meta-analysis[J]. Exp Ther Med, 2017, 14(2):1594-1608.
[16] Tagaya E, Kondo M, Kirishi S, et al. Effects of regular treatment with combination of salmeterol/fluticasone propionate and salmeterol alone in cough variant asthma[J]. J Asthma, 2015, 52(5):512-518.
[17] 刘传合. 正确使用哮喘治疗药物[J]. 临床药物治疗杂志, 2018, 16(6):1-3.
[18] Morina N, Haliti A, Iljazi A, et al. Comparison of effect of leukotriene biosynthesis blockers and inhibitors of phosphodiesterase enzyme in patients with bronchial hyperreactivity[J]. Open Access Maced J Med Sci, 2018, 6(5):777-781.
[19] 王莹莹. 孟鲁司特与氯苯那敏治疗小儿咳嗽变异性哮喘效果分析[J]. 吉林医学, 2018, 39(6):1085-1087.
[20] 韩玲, 李颖, 王晓飞, 等. 白细胞介素-23受体基因多态性与变应性鼻炎易感性的相关性研究[J]. 中国耳鼻咽喉颅底外科杂志, 2018, 24(4):346-349.
[21] 冯伟静, 周文娣, 焦常海. 孟鲁司特联合沙美特罗替卡松粉吸入剂治疗儿童咳嗽变异性哮喘疗效观察[J]. 儿科药学杂志, 2014, 20(6):26-28.
[22] Liu M, Yokomizo T. The role of leukotrienes in allergic diseases[J]. Allergol Int, 2015, 64(1):17-26.
[23] 严能兵, 罗鸿. 白三烯的研究进展与临床意义[J]. 国际检验医学杂志, 2014, 35(6):721-723.
[24] 中华医学会儿科学分会呼吸学组. 白三烯受体拮抗剂在儿童常见呼吸系统疾病中的临床应用专家共识[J]. 中华实用儿科杂志, 2016, 13(13):973-977.
[25] 宁宁, 丁国标, 黎海燕. 酮替芬联合孟鲁司特钠治疗儿童咳嗽变异性哮喘的临床效果及安全性观察[J]. 中国当代医药, 2015, 22(27):99-101.
[26] Yamauchi K, Shikanai T, Nakamura Y, et al. Roles of histamine in the pathogenesis of bronchial asthma and reevaluation of the clinical usefulness of antihistamines[J]. Yakugaku Zasshi, 2011, 131(2):185-191.
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