劉露 錢小軍 李紀(jì)煌 袁明華 謝紹華
[摘要] 目的 通過(guò)比較穴位注射、可待因片以及穴位注射聯(lián)合可待因片三種不同治療方式對(duì)中央型肺癌引起咳嗽的治療效果及安全性。 方法 收集2018年1月至2021年1月宜春市人民醫(yī)院呼吸與危重醫(yī)學(xué)科60例診斷為中央型肺癌患者,隨機(jī)分為可待因組、穴位注射組、可待因+穴位注射組,每組各20例。經(jīng)過(guò)三種治療方式后,通過(guò)比較治療前、治療5 d后、治療10 d后行咳嗽問(wèn)卷評(píng)分,包括萊斯特咳嗽問(wèn)卷、咳嗽特異性生活質(zhì)量問(wèn)卷、咳嗽視覺(jué)模擬量表、咳嗽癥狀評(píng)分;血清SP-D水平及PARC/CCL-18趨化因子。 結(jié)果 治療5、10 d后,三組患者咳嗽問(wèn)卷評(píng)分、咳嗽特異性生活質(zhì)量問(wèn)卷評(píng)分較治療前有所升高,三組患者咳嗽視覺(jué)模擬量表評(píng)分及咳嗽癥狀評(píng)分較治療前有所降低,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療5、10 d后,穴位注射組咳嗽問(wèn)卷評(píng)分、咳嗽特異性生活質(zhì)量問(wèn)卷評(píng)分及咳嗽視覺(jué)模擬量表評(píng)分明顯低于可待因組,可待因+穴位注射組咳嗽問(wèn)卷評(píng)分、咳嗽特異性生活質(zhì)量問(wèn)卷評(píng)分及咳嗽視覺(jué)模擬量表評(píng)分明顯高于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。治療5、10 d后,穴位注射組咳嗽癥狀評(píng)分明顯高于可待因組,可待因+穴位注射組咳嗽癥狀評(píng)分明顯低于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。治療5、10 d后,三組血清肺表面活性蛋白D(SP-D)較治療前明顯下降,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療5、10 d后,穴位注射組血清肺表面活性蛋白D(SP-D)明顯高于可待因組,可待因+穴位注射組血清肺表面活性蛋白D(SP-D)明顯低于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。治療5、10 d后,三組肺部活化調(diào)節(jié)趨化因子(CCL18)較治療前明顯下降,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療5 、10 d后,穴位注射組肺部活化調(diào)節(jié)趨化因子(CCL18)明顯低于可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療5 d后,可待因+穴位注射組肺部活化調(diào)節(jié)趨化因子(CCL18)明顯低于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療10 d后,可待因+穴位注射組肺部活化調(diào)節(jié)趨化因子(CCL18)明顯低于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。 結(jié)論 中央型肺癌咳嗽與PARC/CCL-18趨化因子、血清SP-D有關(guān),穴位注射聯(lián)合可待因組治療效果優(yōu)于可待因組和穴位注射組。
[關(guān)鍵詞] 穴位注射;可待因片;中央型肺癌;咳嗽
[中圖分類號(hào)] R259.3? ? ? ? ? [文獻(xiàn)標(biāo)識(shí)碼] B? ? ? ? ? [文章編號(hào)] 1673-9701(2021)28-0054-05
Efficacy evaluation of acupoint injection combined with codeine tablets in the treatment of cough with central lung cancer
LIU Lu? ?QIAN Xiaojun? ?LI Jihuang? ?YUAN Minghua? ?XIE Shaohua
Department of Respiratory and Critical Care Medicine,Yichun People's Hospital in Jiangxi Province,Yichun? ?336000,China
[Abstract] Objective To compare and evaluate the therapeutic effect and safety of three different treatment methods of acupoint injection,codeine tablets,and acupoint injection combined with codeine tablets on cough caused by central type lung cancer. Methods A total of 60 patients with central lung cancer diagnosed in the Department of Respiratory and Critical Care Medicine of Yichun People's Hospital from January 2018 to January 2021 were collected and randomly divided into the codeine group,the acupoint injection group,and codeine combined with acupoint injection group,with 20 cases in each group. After three treatments,the scores of the cough questionnaire before treatment,5 days after treatment,and 10 days after treatment,including Leicester Cough Questionnaire,Cough Specific Quality of Life Questionnaire,Cough Visual Analog Scale,Cough Symptom Score,serum SP-D level and PARC/CCL-18 chemokine were compared. Results 5 d,10 d after treatment,the scores of Leicester Cough Questionnaire and Cough-Specific Quality of Life Questionnaire among the three groups were higher than those before the treatment,the scores of Cough Visual Analog Scale and Cough Symptom Score among the three groups were lower than those before the treatment,with significant differences (P<0.05). 5 d,10 d after treatment,the scores of Leicester Cough Questionnaire,Cough-Specific Quality of Life Questionnaire and Cough Visual Analog Scale in the acupoint injection group were lower than those in the codeine group,and the above scores in the acupoint injection combined with codeine group were higher than those in the acupoint injection group and the codeine group, with significant differences (P<0.05). 5 d,10 d after treatment,the scores of Cough Symptom Score in the acupoint injection group were higher than those in the codeine group,and the scores of Cough Symptom Score in the acupoint injection combined with codeine group were lower than those in the acupoint injection group and the codeine group, with significant differences (P<0.05). 5 d,10 d after treatment,the level of serum SP-D among the three groups were lower than those before the treatment, with significant differences (P<0.05). 5 d,10 d after treatment,the level of serum SP-D in the acupoint injection group were higher than those in the codeine group,and the level of serum SP-D in the acupoint injection combined with codeine group were lower than those in the acupoint injection group and the codeine group, with significant differences (P<0.05). 5 d,10 d after treatment,the level of serum PARC/CCL-18 chemokines among the three groups were lower than those before the treatment, with significant differences (P<0.05). 5 d,10 d after treatment,the level of serum PARC/CCL-18 chemokines in the acupoint injection group were lower than those in the codeine group,with significant differences (P<0.05). 5 d after treatment,the level of serum PARC/CCL-18 chemokines in the acupoint injection combined with codeine group were lower than those in the acupoint injection group and the codeine group, with significant differences (P<0.05). 10 d after treatment,the level of serum PARC/CCL-18 chemokines in the acupoint injection combined with codeine group were lower than those in the acupoint injection group and the codeine group, with significant differences (P<0.05). Conclusion Central lung cancer cough is related to PARC/CCL-18 chemokine and serum SP-D. The therapeutic effect of acupoint injection combined with codeine group is better than that of codeine group.
[Key words] Acupoint injection;Codeine tablets;Central lung cancer;Cough
原發(fā)性支氣管癌(簡(jiǎn)稱肺癌),是一種起源于支氣管腺體或黏膜的惡性腫瘤,其主要包括小細(xì)胞肺癌和非小細(xì)胞肺癌[1]。肺癌是一種發(fā)病率高、死亡率高的惡性腫瘤,是中國(guó)常見(jiàn)的惡性腫瘤[2]。明確肺癌診斷需要細(xì)胞和組織病理學(xué)依據(jù)。通過(guò)影像學(xué)檢查肺癌分為早期肺癌、細(xì)支氣管-肺泡細(xì)胞癌、中央型肺癌和周圍性肺癌[3]。肺癌常見(jiàn)的癥狀包括咳嗽、咯血、消瘦、乏力、短氣、胸痛等,患者最早出現(xiàn)癥狀為咳嗽[4]。47%~86%肺癌患者伴隨咳嗽癥狀[5]。肺癌咳嗽原因主要有兩類:一類是原發(fā)肺癌引起的早期咳嗽,癥狀為少痰的咳嗽,或無(wú)痰的刺激性干咳,后期表現(xiàn)為刺激性咳嗽,聽診為金屬音,是由于腫瘤阻塞氣道造成氣道狹窄。二類是肺癌經(jīng)過(guò)手術(shù)后,或腫瘤經(jīng)過(guò)放、化療后出現(xiàn)的咳嗽,原因多為體質(zhì)虛弱后感染引起。本研究目的通過(guò)比較穴位注射、可待因片以及穴位注射聯(lián)合可待因片三種不同治療方式對(duì)中央型肺癌后咳嗽的治療效果及安全性,現(xiàn)報(bào)道如下。
1 資料與方法
1.1 一般資料
收集2018年1月至2021年1月宜春市人民醫(yī)院呼吸科病理診斷為肺癌,通過(guò)影像學(xué)檢查診斷為中央型肺癌患者60例。其中男36例,女24例,年齡32~75 歲,中位年齡58歲。將60例中央型肺癌患者按照隨機(jī)化分組原則分為可待因組、穴位注射組及可待因+穴位注射組,每組各20例。納入標(biāo)準(zhǔn):①原發(fā)疾病均經(jīng)病理組織病理證實(shí)者;②均為原發(fā)性肺癌,無(wú)伴隨其他部位惡性腫瘤及嚴(yán)重的心、腦、肝、腎疾病者;③研究前均拒絕接受化療、放療、靶向、免疫等相關(guān)治療者。排除標(biāo)準(zhǔn):①合并肺部感染(包括真菌、結(jié)核桿菌、非結(jié)核桿菌、病毒、支原體、衣原體等)咳嗽者;②藥物過(guò)敏者;③精神病者;④病情危急,對(duì)治療的安全性和有效性造成干擾者;⑤無(wú)法耐受腕踝針、體針、頭針、穴位注射療法者。觀察中止標(biāo)準(zhǔn):①拒絕合作、臨床依從性不配合、醫(yī)生多次解釋仍不配合者;②研究期間出現(xiàn)病情逐漸惡化,需立即采取緊急治療者;③由于各種理由要求退出研究者;④已超過(guò)1/2療程應(yīng)進(jìn)入研究統(tǒng)計(jì)者。本研究已獲得醫(yī)院醫(yī)學(xué)倫理委員會(huì)批準(zhǔn),患者及其家屬均知情同意。
1.2 方法
1.2.1 可待因組? 口服磷酸可待因片(國(guó)藥集團(tuán)工業(yè)有限公司,國(guó)藥準(zhǔn)字H20103357,10#/2板)1片/次,3次/d[6]。
1.2.2 穴位注射組? 取雙側(cè)足三里穴,暴露并指切患者穴位留痕后,用75%酒精棉球常規(guī)消毒,術(shù)者作自我手部消毒后,用5號(hào)注射器垂直刺入穴位1.5~2.0 cm,用強(qiáng)刺激法使患者有酸脹感后,抽吸無(wú)回血,緩慢注入0.9%生理鹽水注射液2 mL;再取雙肺俞穴,大致方法同雙足三里,需注意的是,對(duì)準(zhǔn)肺俞穴呈15°角斜刺入0.5~0.8 cm,進(jìn)針避免直刺,深度不能超過(guò)2 cm;再取雙側(cè)定喘穴,大致方法同雙足三里,需注意對(duì)準(zhǔn)定喘穴呈90°直刺1.2~2.0 cm;再取雙側(cè)大杼穴,大致方法同雙足三里,需注意呈30°角度直刺1.2~2.0 cm,本經(jīng)背部諸穴,不易深刺,以免傷及內(nèi)部重要臟器;再取雙側(cè)風(fēng)門穴,大致方法同雙足三里,需注意呈70° 1.2~2.0 cm。每日1次,10次為1個(gè)療程。
1.2.3 可待因+穴位注射組? 服藥方法同可待因組,穴位注射法同穴位注射組。
1.3觀察指標(biāo)及評(píng)價(jià)標(biāo)準(zhǔn)
1.3.1 臨床癥狀? 治療前、治療5 d后、治療10 d后行咳嗽問(wèn)卷評(píng)分,包括萊斯特咳嗽問(wèn)卷[7-9]、咳嗽特異性生活質(zhì)量問(wèn)卷[10]、咳嗽視覺(jué)模擬量表[11-13]及咳嗽癥狀評(píng)分[14]。
1.3.2 實(shí)驗(yàn)室檢查? 檢測(cè)三組血清肺表面活性蛋白D(SP-D)和肺部活化調(diào)節(jié)趨化因子(CCL18)水平,晨起空腹經(jīng)肘靜脈采血約3 mL,3000 r/min離心10 min,取上清液置于-20℃待測(cè);按試劑盒說(shuō)明書于治療前后采用酶聯(lián)免疫吸附法檢測(cè)。
1.4 統(tǒng)計(jì)學(xué)方法
采用SPSS 20.0統(tǒng)計(jì)學(xué)軟件進(jìn)行數(shù)據(jù)分析。計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,組內(nèi)前后比較采用配對(duì)t檢驗(yàn),組間比較采用單因素方差分析;計(jì)數(shù)資料以[n(%)]表示 ,組間比較采用χ2檢驗(yàn)。運(yùn)用雙側(cè)檢驗(yàn),α=0.05 設(shè)定為檢驗(yàn)標(biāo)準(zhǔn),P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2.1 三組患者不同時(shí)間點(diǎn)咳嗽問(wèn)卷評(píng)分比較
治療5、10 d后,三組患者咳嗽問(wèn)卷評(píng)分較治療前有所升高,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療5 、10 d后,穴位注射組咳嗽問(wèn)卷評(píng)分明顯低于可待因組,可待因+穴位注射組咳嗽問(wèn)卷評(píng)分明顯高于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見(jiàn)表1。
2.2 三組患者不同時(shí)間點(diǎn)咳嗽特異性生活質(zhì)量問(wèn)卷評(píng)分比較
治療5、10 d后,三組患者咳嗽特異性生活質(zhì)量問(wèn)卷評(píng)分較治療前有所升高,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療5、10 d后,穴位注射組咳嗽特異性生活質(zhì)量問(wèn)卷評(píng)分明顯低于可待因組,可待因+穴位注射組咳嗽問(wèn)卷評(píng)分明顯高于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見(jiàn)表2。
2.3 三組患者不同時(shí)間點(diǎn)咳嗽視覺(jué)模擬量表評(píng)分比較
治療5、10 d后,三組患者咳嗽視覺(jué)模擬量表評(píng)分較治療前有所降低,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療5、10 d后,穴位注射組咳嗽視覺(jué)模擬量表評(píng)分明顯低于可待因組,可待因+穴位注射組咳嗽視覺(jué)模擬量表評(píng)分明顯高于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見(jiàn)表3。
2.4三組患者不同時(shí)間點(diǎn)咳嗽癥狀評(píng)分比較
治療5、10 d后,三組患者咳嗽癥狀評(píng)分較治療前有所降低,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療5、10 d后,穴位注射組咳嗽癥狀評(píng)分明顯高于可待因組,可待因+穴位注射組咳嗽癥狀評(píng)分明顯低于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見(jiàn)表4。
2.5 三組患者不同時(shí)間點(diǎn)血清肺表面活性蛋白D(SP-D)和肺部活化調(diào)節(jié)趨化因子(CCL18)水平比較
治療5、10 d后,三組血清肺表面活性蛋白D(SP-D)較治療前下降,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療5、10 d后,穴位注射組血清肺表面活性蛋白D(SP-D)明顯低于可待因組和可待因組,可待因+穴位注射組血清肺表面活性蛋白D(SP-D)明顯低于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見(jiàn)表5。
2.6 三組患者不同時(shí)間點(diǎn)肺部活化調(diào)節(jié)趨化因子(CCL18)比較
治療5、10 d后,三組肺部活化調(diào)節(jié)趨化因子(CCL18)較治療前下降,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療5 、10 d后,穴位注射組肺部活化調(diào)節(jié)趨化因子(CCL18)明顯低于可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療5 d后,可待因+穴位注射組肺部活化調(diào)節(jié)趨化因子(CCL18)明顯低于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療10 d后,可待因+穴位注射組肺部活化調(diào)節(jié)趨化因子(CCL18)明顯低于穴位注射組和可待因組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見(jiàn)表6。
3 討論
肺癌常伴有咳嗽癥狀,大多數(shù)為早期癥狀。據(jù)數(shù)據(jù)統(tǒng)計(jì),47%~86%的肺癌患者伴隨咳嗽癥狀,臨床表現(xiàn)為無(wú)痰或少痰的刺激性干咳[15]。
中文版萊斯特咳嗽量表用于評(píng)估肺癌患者的咳嗽狀況和生活質(zhì)量情況。用于評(píng)估的疾病包括慢性、急性咳嗽以及慢性阻塞性肺疾病、肺癌等引起的咳嗽[16]。咳嗽特異性生活質(zhì)量問(wèn)卷是一項(xiàng)包括6個(gè)領(lǐng)域、28個(gè)條目的調(diào)查問(wèn)卷,包括的領(lǐng)域?yàn)檐|體不適、社會(huì)心理問(wèn)題、極端軀體不適、自身健康焦慮、情感幸福及功能狀況??人砸曈X(jué)模擬量表在慢性和急性咳嗽中表現(xiàn)為良好的可靠性、反應(yīng)性和重復(fù)性,近期用于研究埃索美拉唑治療慢性咳嗽及沙利度胺治療特發(fā)性肺纖維化相關(guān)咳嗽患者的臨床試驗(yàn)??人园Y狀評(píng)分分為日間及夜間評(píng)分兩部分[17],每部分均按照不同的嚴(yán)重程度劃分為6個(gè)等級(jí)。該評(píng)分包括咳嗽的頻率、強(qiáng)度以及咳嗽對(duì)生活質(zhì)量影響的情況。不論成人或兒童,日間評(píng)分主要與咳嗽次數(shù)顯著相關(guān),但夜間評(píng)分反映咳嗽監(jiān)測(cè)指標(biāo)欠佳。本研究結(jié)果顯示,穴位注射聯(lián)合可待因組治療效果優(yōu)于穴位注射組(P<0.05);通過(guò)比較血清PARC/CCL-18趨化因子結(jié)果顯示,治療10 d后穴位注射聯(lián)合可待因組PARC/CCL-18明顯低于穴位注射組和可待因組(P<0.05)。
肺癌的發(fā)病機(jī)制是致癌物誘導(dǎo)的細(xì)胞基因損傷的多步驟過(guò)程,包括啟動(dòng)、促進(jìn)和發(fā)展階段[18]。肺癌發(fā)病率隨著年齡增長(zhǎng)逐步增長(zhǎng),以及吸煙者支氣管上皮從不典型增生到原位癌的病理改變。有大量研究表明,具有致癌作用的因素包括煙霧中的尼古丁、苯并芘和放射性元素釙等,最常見(jiàn)的是鱗狀上皮細(xì)胞癌和未分化小細(xì)胞癌[19]。有研究表明,煙霧中含有的成分均可引起細(xì)胞存活率降低、支氣管炎癥和細(xì)胞凋亡等。呼吸道受外界刺激后可引起呼吸道細(xì)胞損傷、細(xì)胞凋亡和炎癥,如IL-6、SP-D、PARC/CCL-18等分泌參與自身免疫、炎癥過(guò)程[20]。
肺部活化調(diào)節(jié)趨化因子/趨化因子配體18(PARC/CCL-18)又稱趨化因子配體-18(CCL18)是一種在血清發(fā)現(xiàn)的肺部表達(dá)占相對(duì)優(yōu)勢(shì)的炎癥蛋白。CCL18 mRNA在淋巴組織如淋巴結(jié)、胸腺和闌尾中低水平表達(dá),在肺臟中呈持續(xù)高水平表達(dá)[21]。在多種肺部疾病中表現(xiàn)為CCL18 高水平表達(dá),尤其是在肺癌或特發(fā)性肺纖維化疾病中,CCL18來(lái)源于淋巴細(xì)胞附近的間質(zhì)炎癥細(xì)胞[22-25],通過(guò)原位雜交和免疫組化技術(shù)體現(xiàn)。CCL18在抗炎和促炎等免疫系統(tǒng)的重要生理過(guò)程中,與腫瘤、過(guò)敏性疾病、COPD等密切有關(guān)。
肺組織分泌SP-D并參與肺部疾病發(fā)生時(shí)的機(jī)體炎癥調(diào)節(jié)和免疫功能,故可作為肺部疾病的特異性標(biāo)志物[26]。SP-D在阻止細(xì)菌及真菌感染、保護(hù)致癌物誘導(dǎo)細(xì)菌損傷等方面作用顯著[27]。
綜上所述,通過(guò)比較咳嗽問(wèn)卷評(píng)分,包括萊斯特咳嗽問(wèn)卷、咳嗽特異性生活質(zhì)量問(wèn)卷、咳嗽視覺(jué)模擬量表及咳嗽癥狀評(píng)分,可以比較可待因+穴位注射組、可待因組及穴位注射組治療中央型肺癌后咳嗽的效果。中央型肺癌后咳嗽與血清PARC/CCL-18趨化因子、血清SP-D相關(guān),主要考慮煙霧引起氣道炎癥,進(jìn)一步影響炎癥因子,但其具體作用機(jī)制需要進(jìn)一步深入研究。
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(收稿日期:2021-04-03)