王述紅　黃小波　劉　翱　何正光

慢性阻塞性肺疾病患者急性加重頻率與高分辨率CT參數(shù)的相關(guān)性研究

王述紅1黃小波2劉翱3何正光1

慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)具有異質(zhì)性的特點(diǎn)，在臨床工作中不難發(fā)現(xiàn)有部分患者，其肺功能測(cè)定氣流受限嚴(yán)重程度相似，然而對(duì)治療的反應(yīng)、預(yù)后、急性加重頻率等相差甚遠(yuǎn)[1-10]。COPD的急性加重，需要改變基礎(chǔ)的治療方案甚至需要住院治療，嚴(yán)重者需入住ICU搶救，反復(fù)發(fā)生急性加重是COPD患者死亡的主要原因。利用高分辨率CT(HRCT)重建圖像對(duì)COPD患者肺氣腫及支氣管管壁增厚程度進(jìn)行評(píng)估，并將其分型，研究不同表型的特點(diǎn)，有助于指導(dǎo)臨床醫(yī)師進(jìn)對(duì)患者行個(gè)體化治療[11-19]。本研究主要探討不同HRCT表型的COPD患者上一年急性加重次數(shù)的特點(diǎn)，及其與HRCT肺氣腫及支氣管管壁厚度參數(shù)的相關(guān)性，旨在為COPD患者的治療提供幫助。

資料與方法

一、一般資料

本研究納入2012年8月至2014年3月成都軍區(qū)昆明總醫(yī)院收治的臨床及肺功能檢查確診為COPD男性穩(wěn)定期患者共159例，最終滿足要求的COPD患者共72例。年齡43～86歲，平均(68.11±8.52)歲。吸煙者65例(90.28%)，吸煙量(52.85±30.29)包/年。其中肺功能1級(jí)者2例，2級(jí)者29例，3級(jí)者24例，4級(jí)者17例。病例入選標(biāo)準(zhǔn)：符合2011年COPD全球倡議(GLOD)診斷標(biāo)準(zhǔn)[20]。嚴(yán)格排除明確有肺部疾病、胸腔疾病及心功能不全者，全身各系統(tǒng)急性疾病狀態(tài)者，不能配合吸氣末屏氣下進(jìn)行胸部HRCT掃描者。

二、方法

1. HRCT檢查及圖像分析： 采用GE公司Light Speed掃描儀。指導(dǎo)患者最大吸氣末屏氣，從肺尖到肺底行快速螺旋CT掃描。設(shè)置掃描電流220 mA，電壓120kV。肺窗采用Lung重建，縱膈窗采用Soft重建，重建圖像層距及層厚為0.625 mm。

在軸位圖像中，合格圖像的標(biāo)準(zhǔn)即無呼吸運(yùn)動(dòng)偽影。利用GE公司AW4.5工作站自帶軟件對(duì)Soft重建圖像進(jìn)行圖像數(shù)據(jù)分析，通過軟件處理及人工校正，得到全肺的三維立體圖像，然后顯示CT值-面積曲線圖。將CT值設(shè)定低于-950HU的區(qū)域?yàn)榉螝饽[區(qū)。方法為將平行于縱軸的直線移動(dòng)至CT值為-950HU處，通過縱軸直接計(jì)算出圖像中CT值低于-950HU的區(qū)域所占整個(gè)肺體積的百分比，即為像素指數(shù)-950(PI-950)，見圖1。

注：A：全肺三維立體圖；B：CT值-面積曲線圖

2．肺氣腫評(píng)估：選取3個(gè)解剖層面進(jìn)行觀察，即靠近主動(dòng)脈弓上緣1 cm、隆突水平下1 cm、右側(cè)橫膈上3 cm。三個(gè)解剖層面6個(gè)肺野中的密度減低區(qū)域面積(low attenuation areas, LAA)通過計(jì)算機(jī)自帶軟件，計(jì)算各層面LAA在該肺野中所占面積的比率。根據(jù)各層面LAA在該肺野中所占面積的比率進(jìn)行LAA評(píng)分： 0分：LAA<5%，1分：5%≤LAA<25%，2分：25%≤LAA<50%，3分：50%≤LAA<75%，4分：LAA≥75%[21]。根據(jù)6個(gè)視野的評(píng)分總和對(duì)肺氣腫程度進(jìn)行分級(jí)：0：總和為0分，1級(jí)：總和為1～6分，2級(jí)：總和為7～12分，3級(jí)：總和為13～18分，4級(jí)：總和為19～24分。將≥2級(jí)者定為肺氣腫型，見圖2。

注：A：主動(dòng)脈弓1 cm層面圈出右肺野；B：CT值-面積曲線圖

3．采用Roberts等[22]評(píng)估方法對(duì)支氣管管壁增厚程度進(jìn)行評(píng)估。支氣管管壁厚度/相鄰肺動(dòng)脈直徑<30%定為0級(jí)，30%≤支氣管管壁厚度/相鄰肺動(dòng)脈直徑<50%定為1級(jí)，支氣管管壁厚度/相鄰肺動(dòng)脈直徑≥50%定為2級(jí)。將≥1級(jí)者定為支氣管管壁增厚型。

4．HRCT分型：結(jié)合兩者綜合分型將患者分為A型、E型、M型三型，A型：LAA≤1級(jí),支氣管管壁厚度評(píng)估<1級(jí);E型：LAA≥2級(jí)，支氣管管壁厚度評(píng)估<1級(jí);M型：LAA≥2級(jí)，支氣管管壁增厚≥1級(jí)。

三、統(tǒng)計(jì)學(xué)方法

結(jié)果

一、 COPD患者HRCT參數(shù)及表型

所有受檢者在整個(gè)檢查過程中配合較好，順利完成HRCT掃描，均獲得了分析圖像。最終入組72例COPD患者，入組患者過去一年中急性加重次數(shù)0～3次，平均為(1.50±0.95)次；像素指數(shù)PI-950的數(shù)據(jù)范圍為(0.4～43.10)%，中位數(shù)為18.75%；支氣管管壁厚度/相鄰肺動(dòng)脈的數(shù)據(jù)范圍為(17.48～41.53)%，中位數(shù)為28.35%。按HRCT參數(shù)分型，無肺氣腫型32例，肺氣腫型40例；無支氣管管壁增厚型40例，支氣管管壁增厚型32例；A型32例，E型19例，M型21例

二、 COPD患者HRCT參數(shù)與急性加重次數(shù)的相關(guān)性分析

相關(guān)性分析顯示，HRCT參數(shù)PI-950和支氣管管壁厚度/相鄰肺動(dòng)脈直徑比值與上一年急性加重頻率均呈正相關(guān)(r=0.28,P=0.017；r=0.416,P=0.000)。

三、不同HRCT表型患者的急性加重次數(shù)的比較

肺氣腫型患者平均上一年急性加重次數(shù)為(1.83±0.81)次，顯著高于無肺氣腫型(1.09±0.96)次(t=3.494，P=0.001)；支氣管管壁增厚型患者急性加重次數(shù)為(1.81±0.86)次，顯著高于無支氣管管壁增厚型(1.25±0.95)次(t=2.597,P=0.011)；A型患者急性加重次數(shù)為(1.09±0.96)次，顯著低于E型(1.63±0.761)次及M型(2.00±0.84)次(q=3.006，P<0.05；q=5.225，P<0.001)，E型與M型之間比較差異無統(tǒng)計(jì)學(xué)意義(q=1.884，P>0.05)。

討論

在20世紀(jì)60年代已有學(xué)者提出對(duì)COPD進(jìn)行分型[23]，西塞爾內(nèi)科學(xué)也曾對(duì)A型(肺氣腫型)和B型(紫腫型)提出過鑒別。近年來，隨著Han等[24]對(duì)COPD表型概念的提出，表型已成為目前COPD研究的熱詞。通過肺結(jié)構(gòu)的改變(如肺氣腫、氣道壁厚度和支氣管擴(kuò)張程度等)可預(yù)測(cè)患者對(duì)治療的反應(yīng)及預(yù)后。由于胸部HRCT可評(píng)估肺氣腫及氣道病變，目前HRCT已被應(yīng)用于COPD表型的研究[25]。采用密度減低區(qū)域面積對(duì)肺氣腫程度進(jìn)行評(píng)估，通過測(cè)量患者支氣管管壁厚度/相鄰肺動(dòng)脈直徑，可判別支氣管管壁增厚程度?？紤]LAA評(píng)分只針對(duì)3個(gè)解剖層面6肺野進(jìn)行評(píng)估，存在一定誤差，因此本研究選擇PI-950作為代表肺氣腫量化的指標(biāo)，進(jìn)行相關(guān)性分析。入選的72例患者，按肺氣腫程度分為無肺氣腫型32例，肺氣腫型40例；按支氣管管壁增厚程度分為無支氣管管壁增厚型40例，支氣管管壁增厚型32例；結(jié)合兩者分為A型32例，E型19例，M型21例。

本研究中肺氣腫型及支氣管管壁增厚型的患者COPD急性加重頻繁，A型的患者急性加重頻率低。E型與M型兩者間進(jìn)行比較，其過去一年中急性加重次數(shù)無統(tǒng)計(jì)學(xué)意義。有研究發(fā)現(xiàn)COPD急性發(fā)作頻率及急性加重次數(shù)分別與肺氣腫占雙肺的百分比、段支氣管管壁厚度呈正相關(guān)[26]。本研究中PI-950、支氣管管壁厚度/相鄰肺動(dòng)脈直徑比值上一年度越明顯，其急性加重越頻繁，患者肺功能下降速度越快，生活質(zhì)量越差。有實(shí)驗(yàn)數(shù)據(jù)顯示以肺氣腫和氣道壁增厚為主的表現(xiàn)型存在家庭聚集現(xiàn)象，同時(shí)發(fā)現(xiàn)兩者之間呈負(fù)相關(guān)[27]。因此，E、M型兩型急性加重頻率未發(fā)現(xiàn)統(tǒng)計(jì)學(xué)差異，需要進(jìn)一步加大樣本進(jìn)行研究。同時(shí)提示對(duì)其機(jī)制行深入分析，尋找其主要影響因素，阻斷主要影響因素可能會(huì)減少患者急性加重頻率。

總之，COPD患者PI-950及支氣管管壁厚度/相鄰肺動(dòng)脈直徑比值與上一年急性加重次數(shù)呈正相關(guān)。HRCT表型為肺氣腫型及支氣管管壁增厚型的患者COPD急性加重頻繁，A型的患者急性加重頻率較低。因此，對(duì)于肺實(shí)質(zhì)破壞和/或支氣管管壁增厚明顯的患者，應(yīng)積極采用多種措施，對(duì)肺氣腫為主的患者可采用多種支氣管擴(kuò)張劑聯(lián)合治療。小劑量阿奇霉素長(zhǎng)期口服治療支氣管管壁增厚型COPD患者，可以減輕氣道炎癥，減緩肺功能下降速率，并減少急性加重頻率，提高生活質(zhì)量[28]。本研究采用手動(dòng)測(cè)量支氣管管壁增厚程度，選擇測(cè)量支氣管也不盡相同，測(cè)量中存在個(gè)人差異，因此，需進(jìn)一步探索更客觀統(tǒng)一的測(cè)量方法。

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(本文編輯：王亞南)

王述紅，黃小波，劉翱，等. 慢性阻塞性肺疾病患者急性加重頻率與高分辨率CT參數(shù)的相關(guān)性研究[J/CD]. 中華肺部疾病雜志： 電子版， 2015， 8(3)： 308-312.

·論著·

【摘要】目的探討不同高分辨率CT(HRCT)表型慢性阻塞性肺疾病(COPD)患者上一年急性加重次數(shù)的特點(diǎn)，及與HRCT參數(shù)的相關(guān)性。 方法收集COPD穩(wěn)定期患者159例，對(duì)最終滿足標(biāo)準(zhǔn)的72例COPD患者完成HRCT檢查，并記錄上一年急性加重次數(shù)。根據(jù)HRCT影像中肺氣腫程度或(和)支氣管管壁增厚情況進(jìn)行分型，并測(cè)定PI-950和支氣管管壁厚度與相鄰肺動(dòng)脈直徑的比值。結(jié)果COPD表型分別為：無肺氣腫型32例，肺氣腫型40例；無支氣管管壁增厚型40例，支氣管管壁增厚型32例；A型32例，E型19例，M型21例。COPD患者的HRCT參數(shù)EI和支氣管管壁厚度/相鄰肺動(dòng)脈直徑比值與上一年急性加重頻率均呈正相關(guān)(r=0.28,P=0.017; r=0.416,P=0.000)。HRCT表型為肺氣腫型的患者平均上一年急性加重次數(shù)為(1.83±0.81)次，高于無肺氣腫型[(1.09±0.96)次，P=0.001]；支氣管管壁增厚型患者急性加重次數(shù)為(1.81±0.86)次，高于無支氣管管壁增厚型[(1.25±0.95)次,P=0.011)]；A型急性加重次數(shù)為(1.09±0.96)次，低于E型及M型[(1.63±0.761)次，(2.00±0.84)次，P=0.002]，E型與M型之間比較差異無統(tǒng)計(jì)學(xué)意義。結(jié)論COPD患者PI-950及支氣管管壁厚度/相鄰肺動(dòng)脈直徑比值與上一年急性加重次數(shù)呈正相關(guān)。HRCT表型多為肺氣腫型及支氣管管壁增厚型的患者，且COPD急性加重頻繁，而A型患者的急性加重頻率較低。

【關(guān)鍵詞】肺疾病，慢性阻塞性；CT，高分辨率；頻率，急性加重；表型

Correlation of high-resolution CT data with the number of exacerbation in patients with chronic obstructive pulmonary diseaseWangShuhong1,HuangXiaobo2,LiuAo3,HeZhengguang1.1DepartmentofRespiratoryMedicine,CentralHospitalofSuining,Suining629000,China;2DepartmentofRadiology,KunmingGeneralHospitalofChengduMilitaryCommandofChinesePLA,Kunming650032,China;3DepartmentofRespiratoryMedicine,KunmingGeneralHospitalofChengduMilitaryCommandofChinesePLA,Kunming650032,China)

Correspondingauthor：LiuAo,Email:ynkm43@126.com

【Abstract】ObjectiveTo classify the high resolution computed tomography (HRCT) phenotypes of chronic obstructive pulmonary disease (COPD) , and to investigate the acute exacerbation frequency characteristics of various phenotypes and the relationship with HRCT parameters. Methodsseventy-two consecutive COPD patients underwent HRCT and their the number of acute exacerbations last year were recorded. COPD subjects were classified into different phenotypes based on the visual HRCT findings (with or without emphysema and/or bronchial wall thickening).With the volumetric HRCT data, the total lung volume(TLV) was calculated automatically by Extended Brilliance WorkspaceTM, the total emphysema volume(TEV) was obtained by applying density thresholds of -950HU, and the TEV/TLV was calculated as an emphysema index(EI). Emphysema threshold was set to -950HU, then find out the corresponding percentage, it was the pixel index-950(PI-950). We measured the bronchial wall thickness and the adjacent pulmonary artery diameter and calculated their ratio. ResultsWe divided the cases into different phenotypes: emphysematous phenotype (40 cases), non-emphysematous phenotype (32 cases); bronchial wall thickening phenotype(32 cases) and non-bronchial wall thickening phenotype(40 cases); A phenotype(32 cases), E phenotype (19 cases), M phenotype (21 cases). The PI-950 and the ratio of bronchial wall thickening and adjacent pulmonary artery diameter were positively correlated with the number of acute exacerbation history in previous year(r=0.28,P=0.017; r=0.416,P=0.000). The number of acute exacerbation history in previous year of non-emphysematous phenotype and emphysematous phenotype is 1.09±0.96, 1.83±0.81 respectively, and has statistical difference (t=-3.494, P=0.001). Non-bronchial wall thickening phenotype and bronchial wall thickening phenotype is 1.25±0.95, 1.81±0.86 respectively, and has statistical difference (t=-2.597, P=0.011). A phenotype is 1.09±0.96, E phenotype is 1.63±0.76 and M phenotype is 2.00±0.84.There is significant difference among three phenotypes (F=7.051, P=0.002). Comparison between two groups, there are differences between A phenotype and two other groups, no differences between E phenotype and M phenotype. ConclusionThe PI-950 and the ratio of bronchial wall thickening and adjacent pulmonary artery diameter are positively correlated with the number of acute exacerbation history in previous year in COPD patients. The number of acute exacerbation of emphysematous phenotype and bronchial wall thickening phenotype compared with non-emphysematous phenotype and non-bronchial wall thickening phenotype have more frequently. HRCT phenotype A compared with phenotype B and C is associated with a lower the acute exacerbation frequency in COPD patients.

【Key words】Chronic obstructive pulmonary disease;High resolution computed tomography (HRCT);Acute exacerbation frequency;Phenotype

收稿日期：(2014-08-26)

文獻(xiàn)標(biāo)識(shí)碼：中圖法分類號(hào)： R563 A

通訊作者：劉翱， Email: ynkm43@126.com

DOI：作者單位： 629000 四川，遂寧市中心醫(yī)院呼吸內(nèi)科1;650032 昆明，成都軍區(qū)昆明總醫(yī)院影像科2、呼吸內(nèi)科3