馬 科,盧 蓉,寇 艷,賈鯤鵬,高 院,龐隨軍,李元霞
716000陜西省延安市,延安大學(xué)附屬醫(yī)院兒科(馬科,盧蓉,寇艷,賈鯤鵬,龐隨軍,李元霞),呼吸內(nèi)科(高院)
?
·論著·
利巴韋林聯(lián)合布地奈德霧化吸入治療小兒毛細(xì)支氣管炎的臨床療效及其對(duì)血清白介素4、干擾素γ水平的影響研究
馬 科,盧 蓉,寇 艷,賈鯤鵬,高 院,龐隨軍,李元霞
716000陜西省延安市,延安大學(xué)附屬醫(yī)院兒科(馬科,盧蓉,寇艷,賈鯤鵬,龐隨軍,李元霞),呼吸內(nèi)科(高院)
【摘要】目的 探究利巴韋林聯(lián)合布地奈德霧化吸入治療小兒毛細(xì)支氣管炎的臨床療效及其對(duì)血清白介素4(IL-4)、干擾素γ(IFN-γ)水平的影響。方法選取2012年3月—2015年3月延安大學(xué)附屬醫(yī)院兒科收治的毛細(xì)支氣管炎患兒69例,按照治療方法分為對(duì)照組34例和觀察組35例。兩組患兒入院后均給予吸氧、控制喘憋與抗病原體等常規(guī)治療,對(duì)照組患兒在常規(guī)治療基礎(chǔ)上給予利巴韋林注射液霧化吸入治療;觀察組患兒在常規(guī)治療基礎(chǔ)上給予利巴韋林注射液聯(lián)合布地奈德混懸液霧化吸入治療。比較兩組患兒臨床療效、臨床癥狀緩解/消失時(shí)間、心率恢復(fù)正常時(shí)間及住院時(shí)間,治療前后T淋巴細(xì)胞亞群細(xì)胞分?jǐn)?shù)細(xì)胞分?jǐn)?shù)細(xì)胞分?jǐn)?shù)細(xì)胞比值)和血清IL-4、IFN-γ水平。結(jié)果觀察組患兒臨床療效優(yōu)于對(duì)照組(u=1.772,P<0.05)。觀察組患兒氣促緩解時(shí)間、哮鳴音消失時(shí)間、濕啰音消失時(shí)間、咳嗽消失時(shí)間、心率恢復(fù)正常時(shí)間及住院時(shí)間均短于對(duì)照組(P<0.05)。兩組患兒治療前細(xì)胞分?jǐn)?shù)細(xì)胞分?jǐn)?shù)細(xì)胞分?jǐn)?shù)及細(xì)胞比值比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);觀察組患兒治療后細(xì)胞分?jǐn)?shù)細(xì)胞分?jǐn)?shù)細(xì)胞比值高于對(duì)照組,細(xì)胞分?jǐn)?shù)低于對(duì)照組(P<0.05)。兩組患兒治療前血清IL-4、IFN-γ水平比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);觀察組患兒治療后血清IL-4水平低于對(duì)照組,血清IFN-γ水平高于對(duì)照組(P<0.05)。結(jié)論利巴韋林聯(lián)合布地奈德霧化吸入治療小兒毛細(xì)支氣管炎的臨床療效確切,可有效調(diào)節(jié)血清IFN-γ、IL-4水平,改善免疫功能。
【關(guān)鍵詞】細(xì)支氣管炎;兒童;利巴韋林;布地奈德;治療結(jié)果;白介素4;干擾素γ
馬科,盧蓉,寇艷,等.利巴韋林聯(lián)合布地奈德霧化吸入治療小兒毛細(xì)支氣管炎的臨床療效及其對(duì)血清白介素4、干擾素γ水平的影響研究[J].實(shí)用心腦肺血管病雜志,2016,24(3):31-34.[www.syxnf.net]
Ma K,Lu R,Kou Y,et al.Clinical effect of atomization inhalation of ribavirin combined with budesonide in treating children with bronchiolitis and the impact on serum levels of IL-4 and IFN-γ[J].Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease,2016,24(3):31-34.
小兒毛細(xì)支氣管炎是一種嬰幼兒較常見的以毛細(xì)支氣管炎癥為主的下呼吸道感染性疾病,多發(fā)于年齡<2歲的嬰幼兒[1]。小兒毛細(xì)支氣管炎最常見的病原體為呼吸道合胞病毒(RSV),此外還有其他病原體,如副流感病毒、流感病毒、鼻病毒以及腺病毒等[2]。目前,臨床常用 的小兒毛細(xì)支氣管炎的治療方法為吸氧、控制喘憋與抗病原體等,但是常規(guī)治療療效不甚理想[3-4]。本研究旨在探究利巴韋林聯(lián)合布地奈德霧化吸入治療小兒毛細(xì)支氣管炎的臨床療效及其對(duì)血清白介素4(IL-4)、干擾素γ(IFN-γ)水平的影響,現(xiàn)報(bào)道如下。
1資料與方法
1.1一般資料選取2012年3月—2015年3月延安大學(xué)附屬醫(yī)院兒科收治的毛細(xì)支氣管炎患兒69例,均符合《諸福棠實(shí)用兒科學(xué)》(第七版)中毛細(xì)支氣管炎的臨床診斷標(biāo)準(zhǔn)[5]。患兒均未行機(jī)械通氣治療,且就診時(shí)均存在咳嗽、喘憋、氣促、心率加快、肺部哮鳴音及呼吸加快等臨床癥狀及體征。排除標(biāo)準(zhǔn):(1)合并呼吸衰竭、心力衰竭患兒;(2)先天性心臟病、免疫系統(tǒng)疾病及淋巴結(jié)核等疾病患兒;(3)支氣管異物患兒;(4)嚴(yán)重心、肝、腎等臟器受損患兒;(5)入院前1個(gè)月內(nèi)使用過糖皮質(zhì)激素治療的患兒。按照治療方法將所有患兒分為對(duì)照組34例和觀察組35例。對(duì)照組中男19例,女15例;月齡2~25個(gè)月,平均月齡(10.3±0.3)個(gè)月;病程1~3 d,平均病程(1.9±0.4)d。觀察組中男20例,女15例;月齡2~29個(gè)月,平均月齡(10.4±0.4)個(gè)月;病程1~3 d,平均病程(1.9±0.5)d。兩組患兒性別(χ2=0.060)、月齡(t=1.177)、病程(t=1.563)比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),具有可比性。本研究經(jīng)延安大學(xué)附屬醫(yī)院倫理委員會(huì)批準(zhǔn),患兒家屬均知情同意并簽署知情同意書。
1.2治療方法兩組患兒入院后均給予吸氧、控制喘憋與抗病原體等常規(guī)治療。對(duì)照組患兒在常規(guī)治療的基礎(chǔ)上給予利巴韋林注射液(山西晉新雙鶴藥業(yè)有限責(zé)任公司生產(chǎn),國(guó)藥準(zhǔn)字H19999227)治療,即利巴韋林注射液30~50 mg/ml加入0.9%氯化鈉溶液3 ml中霧化吸入治療,10 min/次,2次/d,7 d為1個(gè)療程。觀察組患兒在常規(guī)治療基礎(chǔ)上給予利巴韋林注射液聯(lián)合布地奈德混懸液(阿斯利康制藥有限公司生產(chǎn),國(guó)藥準(zhǔn)字H20030410)治療,利巴韋林注射液用法用量同對(duì)照組,布地奈德混懸液0.5 ml加入0.9%氯化鈉溶液3 ml中霧化吸入治療,10 min/次,2次/d,7 d為1個(gè)療程。
比較兩組患兒臨床療效、臨床癥狀緩解/消失時(shí)間、心率恢復(fù)正常時(shí)間及住院時(shí)間,治療前后T淋巴細(xì)胞亞群和血清IL-4、IFN-γ水平。
1.4臨床療效判定標(biāo)準(zhǔn)顯效:治療后各種臨床癥狀均完全消失;有效:治療后各種臨床癥狀均明顯緩解;無(wú)效:治療后各種臨床癥狀無(wú)明顯改善,甚至有再發(fā)作趨勢(shì)[6]。
2結(jié)果
2.1兩組患兒臨床療效比較觀察組患兒臨床療效優(yōu)于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(u=1.772,P<0.05,見表1)。
2.2兩組患兒臨床癥狀緩解/消失時(shí)間、心率恢復(fù)正常時(shí)間及住院時(shí)間比較觀察組患兒氣促緩解時(shí)間、哮鳴音消失時(shí)間、濕啰音消失時(shí)間、咳嗽消失時(shí)間、心率恢復(fù)正常時(shí)間及住院時(shí)間均短于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05,見表2)。
表1 兩組患兒臨床療效比較〔n(%)〕
Table 2Comparison of remission/disappearance of clinical symptoms,recovery time of heart rate and hospital stays between the two groups
組別例數(shù)氣促緩解時(shí)間哮鳴音消失時(shí)間濕啰音消失時(shí)間咳嗽消失時(shí)間心率恢復(fù)正常時(shí)間住院時(shí)間對(duì)照組343.02±0.804.43±0.906.25±1.026.16±1.182.92±0.728.07±2.01觀察組352.29±0.623.08±0.754.83±0.965.20±0.942.20±0.556.68±1.21t值4.4915.1823.9284.6933.3923.726P值0.0380.0270.0400.0350.0420.042
2.4兩組患兒治療前后血清IL-4、IFN-γ水平比較兩組患兒治療前血清IL-4、IFN-γ水平比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05);觀察組患兒治療后血清IL-4水平低于對(duì)照組,血清IFN-γ水平高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05,見表4)。
Table4ComparisonofserumlevelsofIL-4andIFN-γbetweenthetwogroupsbeforeandaftertreatment
組別例數(shù)IL-4(μg/L)治療前 治療后IFN-γ(ng/L)治療前 治療后對(duì)照組3429.59±4.2422.29±3.08a136.88±15.49159.27±17.12a觀察組3529.37±3.92 8.10±1.34a 135.88±14.53206.72±22.19at值0.22224.6910.27611.032P值0.8240.0000.7820.000
注:與治療前比較,aP<0.05;IL-4=白介素4,IFN-γ=干擾素γ
3討論
小兒毛細(xì)支氣管炎主要以喘憋、三凹征和喘鳴為主要臨床特征[7],因此,臨床治療時(shí)需盡快解除患兒喘憋癥狀,提高氣道順應(yīng)性,消除氣道炎性反應(yīng),改善低氧血癥。霧化吸入是目前常見且高效的治療方法,其能將藥物分散成微小的霧滴,并伴隨吸氣呼氣進(jìn)入肺組織,從而增大藥物與肺泡、呼吸道的接觸面積,使其局部藥物溶解度迅速升高到最大值,且藥效持續(xù)時(shí)間較長(zhǎng),應(yīng)用方便,不良反應(yīng)發(fā)生率低[8]。
布地奈德具有抑制氣道炎性反應(yīng)、局部抗炎、降低呼吸道高反應(yīng)性以及腺體分泌量等作用,是一種合成的腎上腺皮質(zhì)激素,其霧化吸入可作用于全肺,從而緩解支氣管痙攣、修復(fù)氣道損傷、緩解黏膜水腫以及降低毛細(xì)血管通透性。利巴韋林即病毒唑,屬于人工合成的廣譜類強(qiáng)效抗病毒類藥物,對(duì)于多種RNA與DNA病毒均有抑制效果,特別是對(duì)流感病毒、丙肝病毒以及RSV等RNA病毒和皰疹病毒、痘病毒等DNA病毒,但是單純使用利巴韋林治療效果一般,且長(zhǎng)期使用會(huì)產(chǎn)生免疫及骨髓抑制。利巴韋林對(duì)病毒腺苷激酶的依賴性強(qiáng),容易產(chǎn)生耐藥性而限制了其臨床使用[9]。利巴韋林霧化吸入能夠使得藥物形成更小的顆粒,使其能直接作用于病變位置,從而減少RSV,增加動(dòng)脈血氧飽和度。本研究結(jié)果顯示,觀察組患兒臨床療效優(yōu)于對(duì)照組,心率恢復(fù)正常時(shí)間、氣促緩解時(shí)間、哮鳴音消失時(shí)間、濕啰音消失時(shí)間、咳嗽消失時(shí)間及住院時(shí)間均短于對(duì)照組;表明利巴韋林聯(lián)合布地奈德治療小兒毛細(xì)支氣管炎的臨床療效確切,且能有效縮短患兒的住院時(shí)間和臨床癥狀改善時(shí)間。
表3 兩組患兒治療前后T淋巴細(xì)胞亞群比較±s)
注:與治療前比較,aP<0.05
綜上所述,利巴韋林聯(lián)合布地奈德霧化吸入治療小兒毛細(xì)支氣管炎的臨床療效確切,可有效調(diào)節(jié)血清IL-4、IFN-γ水平,改善免疫功能,值得臨床推廣使用。
作者貢獻(xiàn):馬科進(jìn)行實(shí)驗(yàn)設(shè)計(jì)與實(shí)施、資料收集整理、撰寫論文、成文并對(duì)文章負(fù)責(zé);馬科、盧蓉、寇艷、賈鯤鵬、高院進(jìn)行實(shí)驗(yàn)實(shí)施、評(píng)估、資料收集;龐隨軍、李元霞進(jìn)行質(zhì)量控制及審較。
本文無(wú)利益沖突。
參考文獻(xiàn)
[1]陳濤.布地奈德聯(lián)合沙丁胺醇霧化吸入治療毛細(xì)支氣管炎的臨床效果及對(duì)喘息發(fā)作的影響[J].實(shí)用心腦肺血管病雜志,2013,21(4):46-47.
[2]王華,閆燕,程士樟.小兒毛細(xì)支氣管炎的四種表型[J].中國(guó)全科醫(yī)學(xué),2011,14(3):912.
[3]周明琪.布地奈德霧化吸入輔助治療毛細(xì)支氣管炎的療效觀察[J].山東醫(yī)藥,2011,51(23):91-92.
[4]谷峰.布地奈德佐治小兒毛細(xì)支氣管炎的療效觀察[J].當(dāng)代醫(yī)學(xué),2012,18(17):13-14.
[5]胡亞美.諸福棠實(shí)用兒科學(xué)[M].7版.北京:人民衛(wèi)生出版社,2005:1025-1027.
[6]萬(wàn)慧賢,吳麗娟.布地奈德聯(lián)合西咪替丁輔助治療小兒毛細(xì)支氣管炎的療效研究[J].臨床合理用藥,2014,7(9):45-46.
[7]江志貴,吳潔,劉玲,等.毛細(xì)支氣管炎患兒血清25-(OH)D3與免疫球蛋白水平的變化[J].中國(guó)當(dāng)代兒科雜志,2012,14(8):578-580.
[8]Choi J,Callaway Z,Kim HB,et al.The role of TNF-alpha in eosinophilic inflammation saaociated with RSV bronchiolitis[J].Pediatr Allergy Immunol,2010,21(3):474-479.
[9]張本金,呂有道.孟魯司特鈉對(duì)小兒反復(fù)呼吸道感染患者免疫指標(biāo)及促炎因子的影響觀察[J].中國(guó)現(xiàn)代醫(yī)藥雜志,2013,15(8):59-61.
[10]奚旭陽(yáng),凌杰.孟魯司特對(duì)哮喘患兒血漿炎癥細(xì)胞因子水平的影響和療效觀察[J].中國(guó)藥物與臨床,2011,11(9):1057-1058.
[11]李溫慈,邵山鷹.細(xì)菌溶解產(chǎn)物聯(lián)合孟魯司特鈉對(duì)哮喘患兒血清免疫球蛋白、干擾素γ和白細(xì)胞介素4的影響及臨床療效分析[J].中國(guó)醫(yī)師進(jìn)修雜志,2010,33(22):4-6.
[12]閆曉燕,高曉增,逯春潔,等.布地奈德霧化吸入對(duì)哮喘患兒外周血調(diào)節(jié)性T細(xì)胞和Th1/Th2平衡的影響[J].中國(guó)煤炭工業(yè)醫(yī)學(xué)雜志,2013,16(5):706-707.
(本文編輯:毛亞敏)
Clinical Effect of Atomization Inhalation of Ribavirin Combined With Budesonide in Treating Children With Bronchiolitis and the Impact on Serum Levels of IL-4 and IFN-γ
MAKe,LURong,KOUYan,etal.DepartmentofPediatrics,theAffiliatedHospitalofYan′anUniversity,Yan′an716000,China
【Abstract】ObjectiveTo explore the clinical effect of atomization inhalation of ribavirin combined with budesonide in treating children with bronchiolitis and the impact on serum levels of IL-4 and IFN-γ.Methods From March 2012 to March 2015,a total of 69 children with bronchiolitis were selected in the Department of Pediatrics,the Affiliated Hospital of Yan′an University,and they were divided into control group(n=34)and observation group(n=35)according to therapeutic methods.Children of both groups received conventional treatment after admission,including oxygen inhalation,asthma control,anti- pathogen treatment and so on,children of control group received extra atomization inhalation of ribavirin injection based on conventional treatment,while children of observation group received atomization inhalation of ribavirin combined with budesonide based on conventional treatment.Clinical effect,remission/disappearence time of clinical symptoms,recovery time of heart cell cell cell cell ratio,serum levels of IL-4 and IFN-γ before and after treatment were compared between the two groups.Results The clinical effect of observation group was statistically significantly better than that of control group(u=1.772,P<0.05).Remission time of anhelation,disappearence time of wheezing,disappearence time of moist rale,disappearence time of cough,recovery time of heart rate and hospital stays of observation group were statistically significantly shorter than those of control group(P<0.05).No statistically significant differences of cell cell cell percentage or cell ratio was found between the two groups before treatment(P>0.05);after cell cell percentage and cell ratio of observation group were statistically significantly higher than those of control group,while cell percentage of observation group was statistically significantly lower than that of control group(P<0.05).No statistically significant differences of serum level of IL-4 or IFN-γ was found between the two groups before treatment(P>0.05);after treatment,serum IL-4 level of observation group was statistically significantly lower than that of control group,while serum IFN-γ level of observation group was statistically significantly higher than that of control group(P<0.05).ConclusionAtomization inhalation of ribavirin combined with budesonide has certain clinical effect in treating children with bronchiolitis,can effectively adjust the serum levels of IL-4 and IFN-γ,improve the immunologic function.
【Key words】Bronchiolitis;Child;Ribavirin;Budesonide;Treatment outcome;Interleukin-4;Interferon-gamma
(收稿日期:2015-12-03;修回日期:2016-03-10)
【中圖分類號(hào)】R 562.21
【文獻(xiàn)標(biāo)識(shí)碼】A
doi:10.3969/j.issn.1008-5971.2016.03.009
通信作者:寇艷,716000陜西省延安市,延安大學(xué)附屬醫(yī)院兒科,E-mail:1324667058@qq.com