中药喘敷灵三伏穴位贴敷防治儿童哮喘的临床研究
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摘要
目的
观察中药喘敷灵三伏穴位贴敷对缓解期哮喘儿童非特异性免疫球蛋白巨(IgE)，嗜酸性粒细胞(EOS)，白细胞介素习(IL-4)，干扰素γ(IFN-γ)浓度，体液免疫(IgA、IgG)的影响，探讨中药喘敷灵穴位贴敷防治哮喘的疗效及其可能的作用机制，为临床用药提供理论依据。
方法
选取120例缓解期哮喘患儿，随机分为四组：喘敷灵三伏穴位贴敷组(A组)30例，即分别在头伏、二伏、三伏的第一天穴位贴敷喘敷灵，共三次；西药酮替芬口服预防组(8组)30例，给予酮替芬1mg，每日两次，连服三月；普米克吸入预防组(C组)30例，给予普米克气雾剂吸入，5岁以下加用储雾罐(吸舒)；空白对照组(D组)30例，缓解期不给予任何治疗。四组患儿均于2001年及2002年三伏贴敷前测定IgA、IgG、IgE、EOS、IL-4、IFN-γ水平，比较治疗前后上述指标的变化情况。
结果
1．哮喘缓解期患儿血清体液免疫(IgA、IgG)，喘敷灵三伏贴敷组与空白对照组相比显著提高(P＜0.05)，而两西药治疗组则无此作用(P＞0.05)；2．三治疗组均能显著降低哮喘缓解期患儿异常增高的血清非特异性IgE和EOS(P＜0.01)；3．中药喘敷灵三伏穴位贴敷组在改善患儿临床症状、增高IFN-γ等方面疗效与酮替芬组、普米克+吸舒组相当(P＞0.05)；在降低患儿血清IL-4水平方面，略逊于普米克+吸舒组(P＜0.05)。
结论
1．喘敷灵可调节哮喘儿童免疫状态，增强抵抗力，减少感冒次数和哮喘发作次数，减轻哮喘发作程度。2．喘敷灵可显著抑制嗜酸性粒细胞浸润，减少炎性细胞募集，抑制炎性介质释放，抑制IgE合成，减轻气道炎症反应。4．随着储雾罐(吸舒)的使用，降低了技术上的难度，使糖皮质激素的疗效大大提高，仍是哮喘缓解期治疗的首选方法，但喘敷灵与之疗效接近，且使用经济、简便，值得临床推广应用。
Objective
To observe the influence of ChuanFuLing (CFL) by applying on the points (Dingchuan\Felshu\Pishu) on children patients in the asthma remission phase, to research the mechanism of CFL and provide experimental basis for clinical preventing and treating asthma effectively.
Methods
120 cases in asthma remission phase were randomly divided into 4 groups, and each group had 30 cases: A group was given CFL by applying on the points on dog-days; B group: ketotifen (1mg, Bid to 3 months )was given ;C group : inhaled corticosteroid and at the same time , spacer was given to the patients under 5 years old; D group : nothing was given in remission phase . The concentration of IgA, IgG, IgE, Eos, IL-4, IFN-r in blood were measured respectively before treatment and a year later to observe the change.
Results
The level of IgA , IgG in most of cases of 4 groups decreased in asthma children .After treatment ,A group turned to higher than that of D group (p<0. 05), but B and C group didn *t show the same effect (p>0. 05) ;2.All the 3 treatment groups remarkably decreased on the level of IgE and Eos , which both were quite high in Asthma patients (p<0. 01); 3. In bettering the symptoms of asthma patients and heightening IFN-y in serum ,A group had the same effect as B and C group (p>0. 05) ;In lowering the level of IL-4, C group had a better effect as to A group (p<0.05).
Conclusion
The TCM prescription of CFL applied on the points of the children patients in remission phase can control clinical symptoms of asthma , improve biochemistry indexes , and strengthen immune state . It is proved to be easily operated .economical and practical .
观察中药喘敷灵三伏穴位贴敷对缓解期哮喘儿童非特异性免疫球蛋白巨(IgE)，嗜酸性粒细胞(EOS)，白细胞介素习(IL-4)，干扰素γ(IFN-γ)浓度，体液免疫(IgA、IgG)的影响，探讨中药喘敷灵穴位贴敷防治哮喘的疗效及其可能的作用机制，为临床用药提供理论依据。
方法
选取120例缓解期哮喘患儿，随机分为四组：喘敷灵三伏穴位贴敷组(A组)30例，即分别在头伏、二伏、三伏的第一天穴位贴敷喘敷灵，共三次；西药酮替芬口服预防组(8组)30例，给予酮替芬1mg，每日两次，连服三月；普米克吸入预防组(C组)30例，给予普米克气雾剂吸入，5岁以下加用储雾罐(吸舒)；空白对照组(D组)30例，缓解期不给予任何治疗。四组患儿均于2001年及2002年三伏贴敷前测定IgA、IgG、IgE、EOS、IL-4、IFN-γ水平，比较治疗前后上述指标的变化情况。
结果
1．哮喘缓解期患儿血清体液免疫(IgA、IgG)，喘敷灵三伏贴敷组与空白对照组相比显著提高(P＜0.05)，而两西药治疗组则无此作用(P＞0.05)；2．三治疗组均能显著降低哮喘缓解期患儿异常增高的血清非特异性IgE和EOS(P＜0.01)；3．中药喘敷灵三伏穴位贴敷组在改善患儿临床症状、增高IFN-γ等方面疗效与酮替芬组、普米克+吸舒组相当(P＞0.05)；在降低患儿血清IL-4水平方面，略逊于普米克+吸舒组(P＜0.05)。
结论
1．喘敷灵可调节哮喘儿童免疫状态，增强抵抗力，减少感冒次数和哮喘发作次数，减轻哮喘发作程度。2．喘敷灵可显著抑制嗜酸性粒细胞浸润，减少炎性细胞募集，抑制炎性介质释放，抑制IgE合成，减轻气道炎症反应。4．随着储雾罐(吸舒)的使用，降低了技术上的难度，使糖皮质激素的疗效大大提高，仍是哮喘缓解期治疗的首选方法，但喘敷灵与之疗效接近，且使用经济、简便，值得临床推广应用。
Objective
To observe the influence of ChuanFuLing (CFL) by applying on the points (Dingchuan\Felshu\Pishu) on children patients in the asthma remission phase, to research the mechanism of CFL and provide experimental basis for clinical preventing and treating asthma effectively.
Methods
120 cases in asthma remission phase were randomly divided into 4 groups, and each group had 30 cases: A group was given CFL by applying on the points on dog-days; B group: ketotifen (1mg, Bid to 3 months )was given ;C group : inhaled corticosteroid and at the same time , spacer was given to the patients under 5 years old; D group : nothing was given in remission phase . The concentration of IgA, IgG, IgE, Eos, IL-4, IFN-r in blood were measured respectively before treatment and a year later to observe the change.
Results
The level of IgA , IgG in most of cases of 4 groups decreased in asthma children .After treatment ,A group turned to higher than that of D group (p<0. 05), but B and C group didn *t show the same effect (p>0. 05) ;2.All the 3 treatment groups remarkably decreased on the level of IgE and Eos , which both were quite high in Asthma patients (p<0. 01); 3. In bettering the symptoms of asthma patients and heightening IFN-y in serum ,A group had the same effect as B and C group (p>0. 05) ;In lowering the level of IL-4, C group had a better effect as to A group (p<0.05).
Conclusion
The TCM prescription of CFL applied on the points of the children patients in remission phase can control clinical symptoms of asthma , improve biochemistry indexes , and strengthen immune state . It is proved to be easily operated .economical and practical .
引文
1. National heart, lung,and blood institute.Global initiative for asthma:global strategy for asthma management and prevention [NHLBI/WHO report].Bethesda (MD):National institutes of health;1995 jan.publication No.:95～3659
2. Clark TJH.Godfrey S.Lee TH.Asthma,3rd ed. London. Chapman 1992:416～48
3．李明华，殷凯生，朱栓立主编．哮喘病学．第1版，北京：人民卫生出版社，1998：255～345
4．戴家熊．合理应用糖皮质激素防治支气管哮喘．新药与临床，1995；14(2)：35～40
5．韩连书，戴家熊．糖皮质激素防治儿童哮喘进展．临床儿科杂志，1996；14(5)：347～348
6. Heinig JH, Bouler LP, Croonenborghs L, et al. The effect of high-dose fluticasone peopionate and budesonide on lung function and asthma exacerbations in patients with severe asthma. Respir Med. 1999;93(9):613～620
7. Meijer RT, Kerstjens HAM, Arends LR, et al. Effect of inhaled Fluficasone and oral prednisolone on clinical and inflammatory paramenters in patients with asthma.Thorax, 1999;54:894～899
8．喻宁芬，余力．吸入丙酸氟替卡松治疗儿童哮喘．广东医学，2002；23(01)：86～87
9. Kuzemko JA. Twenty years of sodium cromoglycate treatment,a short review.Respir Med. 1989;83(suppl A):11～4
10. Edwards A, Holgate S, Weinberg E. Sodium eromoglycate in childhood asthma.Thorax.2001 Apr.56(4):331～2
11. Pauwels R. The current place of nedocromil sodium in the treatment of asthma.J Allergy Clin Immunol. 1996,98:151～5
12．钟南山，府军，朱元钰．现代呼吸病进展(M)．广州：中国医药科技出版社，1994，353～361
13．Ann T Woolcock．处理哮喘严重程度的评价，吸入β_2-受体激动剂的治作用．哮喘与肺部疾病杂志，1997；(2)：37～40
14. Weinberge M and Hendeles L. Theophyline in asthma. N Eng J Med.1996;334:1380
15. Barnes PJ, Pauwels RA. Eur Respir J. 1994,7:579
16. Azelastine-Asthma Study Group. An evaluation of the efficacy and safety of azelastine in patients with chronic asthma .J Allergy Clin Immunol, 1996,Jun:97(6): 1218～24
17．李明华，杨丽华．西替利嗪防治过敏性哮喘的研究现状．中国新药与临床杂志，1998；02(增刊)：88～90
18． 朱彦暄．酮替芬预防哮喘发作临床观察．白求恩医科大学学报，1995(6) ：573
19． Floreani A, Robbins R, Melson J, et al. Inhibitory effect of LTD4 receptor antagonist 'Accolate' on agonist-induced bronchoconstriction in asthma subjects. Ann Allergy 1996,76:98
20． Spector SL, Smith LJ, Glass M. Effect of 6 weeks therapy with oral doses of ICI 204,219,a leukotriene D4-receptor antagonist, insubjects with bronchial asthma. Am J Respir Crit Care Med, 1994,150:618
21． Isreal E,Cohn J,Dubel L,et al. Effect of treatment with zileutona-5lipoxygenase inhibitor,in patients with asthma.JAMA, 1996,275:931
22． Strek ME, Solway J,Saller L. et al. Am J Respir Crit Care Med ,1995;151:A377
23． Storms W, Friedman BS, Zhang J. et al .Am J Respir Crit Care Med. 1995;151:A377
24． 陈卓焕．胸腺肽治疗及预防支气管哮喘复发120例疗效观察．右江民族医学院学报，1996；2：208-209
25． Douglass JA, Thien FC, O'Hehir Re. Immunotherapy in asthma(J). Thorax ,1997; 52(suppl 3) :822
26． Creticos P, Burk J, Smith L, et al. The use of twice daily nedocromi sodium in the treatment of asthma (J). J Allergy Clin Immunol ,1995;95(4) :829
27． Patterson R.The role of immunotherapy in respiratory allergic diseases (J). J Allergy Clin Immunol, 1998;101(2 pt2) :S403
28． Ober C.Do genetics play a role in the pathogenesis of asthma ? J Allergy Clin Immunol ,1998;101(2pt2) :S417
29． MacGlashan DM Jr, Bochner BS, Adehnan DC ,et al . Down-regulation of Fc(epsilon)R I expression on human basophils during in vivo treatment of atopy patients with anti-IgE antibody. J Immunol ,1997;158(3) :1438
30． Nimmagadda SE, Spahn JD, Surs W, et al. Allergn exposure decreases glucocorticoid receptor binding affinity and steroid responsiveness in atopic asthmatics . Am J Respir Cell Mol Biol. 1997． 155:87-93
31． Van Oosterhout A, Ladenius A, Saveloul H, et al. Effect of anti-EL-5 and IL-5 on airway hyperactivity and eosinophils in guinea pigs. Am Respir Dis ,1993;147:548-552
32． Lukas NW, Strieter RM, Chaklee CL, et al. MIP-1 a influence eosinophil recruitment in antigen-specific airway inflammation .Eur J Immunol. 1995 ;25:245-251
33． Okada S, Inoue H, Yamauchi K, et al. Potential Pole of IL-4 in allergn induced late asthmatic reactions in guinea pigs : IL-4 receptor antagonist on late asthmatic reactions. J Allergy Clin Immunol, 1995;95:1236-1245
34． Jirapong sanamuruk O, Leung DYM, Clinical applications of cytokines mew directions in the therapy of atopic disease . Am Allergy Asthma Immunol .1997;79:5-20
35． Gavett S, O'Hearn D, Lix, et al . Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation and Th2 cytokine expression, in mice. J Exp Med.1995;182:1527-1536
36． Boguniewicz M , Martin RJ, Martin D, et al. The effects of nebulized recombinant interferon gamma in asthmatic airways. J Allergy Clin Immunol, 1995;95:133-135
37．邓嘉成．小儿哮喘诊治体会．四川中医，1998；16(1)：7～8
38．张勇．参苓白术散在小儿哮喘缓解期的临床运用．四川中医，1997；15(3)：44
39．韩芳华．中药治疗小儿哮喘缓解期67例．辽宁中医杂志，1998；25(10)：474
40．范华，熊学银．三子散穴位敷贴治疗儿童哮喘150例临床观察．时珍国医国药，2000；11(10)：874
41．郑安宁，王玉祥．针刺四缝穴治疗小儿哮喘138例疗效观察．安徽中医临床杂志，1998；10(3)：192
42．杜克宽．中药内外合治儿童哮喘．湖北中医杂志，1999；21(1)：27
43．万力生，陈陶后，向希雄．中药内外合治改善哮喘儿童肺功能的临床观察．中医杂志，1999；40(6)：355～356
44．崔洪岭，胡文杰，曹久玲．酮替芬加中药治疗儿童哮喘缓解期疗效观察(附25例报告)．中国厂矿医学，2000；13(4)：299～300
45．赵岚．穴位注射治疗儿童哮喘的临床疗效．中国临床医生，2001；29(5)：36～37
2. Clark TJH.Godfrey S.Lee TH.Asthma,3rd ed. London. Chapman 1992:416～48
3．李明华，殷凯生，朱栓立主编．哮喘病学．第1版，北京：人民卫生出版社，1998：255～345
4．戴家熊．合理应用糖皮质激素防治支气管哮喘．新药与临床，1995；14(2)：35～40
5．韩连书，戴家熊．糖皮质激素防治儿童哮喘进展．临床儿科杂志，1996；14(5)：347～348
6. Heinig JH, Bouler LP, Croonenborghs L, et al. The effect of high-dose fluticasone peopionate and budesonide on lung function and asthma exacerbations in patients with severe asthma. Respir Med. 1999;93(9):613～620
7. Meijer RT, Kerstjens HAM, Arends LR, et al. Effect of inhaled Fluficasone and oral prednisolone on clinical and inflammatory paramenters in patients with asthma.Thorax, 1999;54:894～899
8．喻宁芬，余力．吸入丙酸氟替卡松治疗儿童哮喘．广东医学，2002；23(01)：86～87
9. Kuzemko JA. Twenty years of sodium cromoglycate treatment,a short review.Respir Med. 1989;83(suppl A):11～4
10. Edwards A, Holgate S, Weinberg E. Sodium eromoglycate in childhood asthma.Thorax.2001 Apr.56(4):331～2
11. Pauwels R. The current place of nedocromil sodium in the treatment of asthma.J Allergy Clin Immunol. 1996,98:151～5
12．钟南山，府军，朱元钰．现代呼吸病进展(M)．广州：中国医药科技出版社，1994，353～361
13．Ann T Woolcock．处理哮喘严重程度的评价，吸入β_2-受体激动剂的治作用．哮喘与肺部疾病杂志，1997；(2)：37～40
14. Weinberge M and Hendeles L. Theophyline in asthma. N Eng J Med.1996;334:1380
15. Barnes PJ, Pauwels RA. Eur Respir J. 1994,7:579
16. Azelastine-Asthma Study Group. An evaluation of the efficacy and safety of azelastine in patients with chronic asthma .J Allergy Clin Immunol, 1996,Jun:97(6): 1218～24
17．李明华，杨丽华．西替利嗪防治过敏性哮喘的研究现状．中国新药与临床杂志，1998；02(增刊)：88～90
18． 朱彦暄．酮替芬预防哮喘发作临床观察．白求恩医科大学学报，1995(6) ：573
19． Floreani A, Robbins R, Melson J, et al. Inhibitory effect of LTD4 receptor antagonist 'Accolate' on agonist-induced bronchoconstriction in asthma subjects. Ann Allergy 1996,76:98
20． Spector SL, Smith LJ, Glass M. Effect of 6 weeks therapy with oral doses of ICI 204,219,a leukotriene D4-receptor antagonist, insubjects with bronchial asthma. Am J Respir Crit Care Med, 1994,150:618
21． Isreal E,Cohn J,Dubel L,et al. Effect of treatment with zileutona-5lipoxygenase inhibitor,in patients with asthma.JAMA, 1996,275:931
22． Strek ME, Solway J,Saller L. et al. Am J Respir Crit Care Med ,1995;151:A377
23． Storms W, Friedman BS, Zhang J. et al .Am J Respir Crit Care Med. 1995;151:A377
24． 陈卓焕．胸腺肽治疗及预防支气管哮喘复发120例疗效观察．右江民族医学院学报，1996；2：208-209
25． Douglass JA, Thien FC, O'Hehir Re. Immunotherapy in asthma(J). Thorax ,1997; 52(suppl 3) :822
26． Creticos P, Burk J, Smith L, et al. The use of twice daily nedocromi sodium in the treatment of asthma (J). J Allergy Clin Immunol ,1995;95(4) :829
27． Patterson R.The role of immunotherapy in respiratory allergic diseases (J). J Allergy Clin Immunol, 1998;101(2 pt2) :S403
28． Ober C.Do genetics play a role in the pathogenesis of asthma ? J Allergy Clin Immunol ,1998;101(2pt2) :S417
29． MacGlashan DM Jr, Bochner BS, Adehnan DC ,et al . Down-regulation of Fc(epsilon)R I expression on human basophils during in vivo treatment of atopy patients with anti-IgE antibody. J Immunol ,1997;158(3) :1438
30． Nimmagadda SE, Spahn JD, Surs W, et al. Allergn exposure decreases glucocorticoid receptor binding affinity and steroid responsiveness in atopic asthmatics . Am J Respir Cell Mol Biol. 1997． 155:87-93
31． Van Oosterhout A, Ladenius A, Saveloul H, et al. Effect of anti-EL-5 and IL-5 on airway hyperactivity and eosinophils in guinea pigs. Am Respir Dis ,1993;147:548-552
32． Lukas NW, Strieter RM, Chaklee CL, et al. MIP-1 a influence eosinophil recruitment in antigen-specific airway inflammation .Eur J Immunol. 1995 ;25:245-251
33． Okada S, Inoue H, Yamauchi K, et al. Potential Pole of IL-4 in allergn induced late asthmatic reactions in guinea pigs : IL-4 receptor antagonist on late asthmatic reactions. J Allergy Clin Immunol, 1995;95:1236-1245
34． Jirapong sanamuruk O, Leung DYM, Clinical applications of cytokines mew directions in the therapy of atopic disease . Am Allergy Asthma Immunol .1997;79:5-20
35． Gavett S, O'Hearn D, Lix, et al . Interleukin 12 inhibits antigen-induced airway hyperresponsiveness, inflammation and Th2 cytokine expression, in mice. J Exp Med.1995;182:1527-1536
36． Boguniewicz M , Martin RJ, Martin D, et al. The effects of nebulized recombinant interferon gamma in asthmatic airways. J Allergy Clin Immunol, 1995;95:133-135
37．邓嘉成．小儿哮喘诊治体会．四川中医，1998；16(1)：7～8
38．张勇．参苓白术散在小儿哮喘缓解期的临床运用．四川中医，1997；15(3)：44
39．韩芳华．中药治疗小儿哮喘缓解期67例．辽宁中医杂志，1998；25(10)：474
40．范华，熊学银．三子散穴位敷贴治疗儿童哮喘150例临床观察．时珍国医国药，2000；11(10)：874
41．郑安宁，王玉祥．针刺四缝穴治疗小儿哮喘138例疗效观察．安徽中医临床杂志，1998；10(3)：192
42．杜克宽．中药内外合治儿童哮喘．湖北中医杂志，1999；21(1)：27
43．万力生，陈陶后，向希雄．中药内外合治改善哮喘儿童肺功能的临床观察．中医杂志，1999；40(6)：355～356
44．崔洪岭，胡文杰，曹久玲．酮替芬加中药治疗儿童哮喘缓解期疗效观察(附25例报告)．中国厂矿医学，2000；13(4)：299～300
45．赵岚．穴位注射治疗儿童哮喘的临床疗效．中国临床医生，2001；29(5)：36～37