陳瑞英 孫婷 劉峰輝 馬小花 孫琳歌
【摘要】 目的 探討無(wú)創(chuàng)氣道正壓通氣(NPPV)治療對(duì)重疊綜合征(OS)患者肺功能、睡眠質(zhì)量和氧合狀態(tài)的影響。方法 88例阻塞性睡眠呼吸暫停(OSA)或慢性阻塞性肺疾病(COPD)或OS患者作為研究對(duì)象, 根據(jù)多導(dǎo)睡眠圖(PSG)和肺功能將其分為OSA組(30例), COPD組(28例)及OS組(30例)。三組患者入院后常規(guī)給予OSA和COPD相關(guān)知識(shí)宣教, 對(duì)COPD患者指導(dǎo)其學(xué)習(xí)掌握正確的吸入性藥物使用方法, 規(guī)范應(yīng)用支氣管舒張類(lèi)藥物, 必要時(shí)氧療。對(duì)OSA組和OS組患者給予夜間NPPV治療。比較OSA組和OS組治療前后肺功能[包括用力肺活量(FVC)、第1秒用力呼氣容積(FEV1)、FEV1/FVC]、睡眠質(zhì)量[呼吸暫停低通氣指數(shù)(AHI)]、氧合狀態(tài)[夜間最低血氧飽和度(LowSpO2)、夜間血氧飽和度<90%時(shí)間占總睡眠時(shí)間比(TST90)及日間動(dòng)脈血氧分壓(PaO2)、日間動(dòng)脈血二氧化碳分壓(PaCO2)]和Epworth嗜睡量表(ESS)評(píng)分;此外比較三組性別、年齡及治療前體質(zhì)量指數(shù)(BMI)、肺功能、日間氧合狀態(tài)、ESS評(píng)分、AHI、夜間氧合狀態(tài)。結(jié)果 三組患者年齡及治療前BMI、肺功能、日間氧合狀態(tài)、夜間氧合狀態(tài)、ESS評(píng)分、AHI比較差異具有統(tǒng)計(jì)學(xué)意義(P<0.05);三組患者性別比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。經(jīng)NPPV治療4周后, OSA組AHI、夜間LowSpO2、夜間TST90分別為(3.1±2.6)次/h、(91±4)%、(5.6±2.3)%, 較治療前的(41.6±15.2)次/h、(68±8)%、(57.4±10.4)%均顯著改善, 差異具有統(tǒng)計(jì)學(xué)意義(P<0.05), 而日間PaO2、PaCO2水平與治療前比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。經(jīng)NPPV治療4周后, OS組AHI、夜間LowSpO2、夜間TST90、日間PaO2、日間PaCO2水平均較治療前顯著改善, 差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。經(jīng)NPPV治療4周后, OSA組患者FVC、FEV1以及FEV1/FVC與治療前比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05), ESS評(píng)分較治療前顯著下降, 差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。經(jīng)NPPV治療4周后, OS組患者FVC、FEV1及ESS評(píng)分較治療前均明顯改善, 差異具有統(tǒng)計(jì)學(xué)意義(P<0.05), FEV1/FVC與治療前比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。結(jié)論 NPPV治療可以顯著改善OS患者夜間呼吸暫停低通氣事件, 改善氧合狀況, 糾正睡眠結(jié)構(gòu)紊亂, 提高肺功能, 改善日間嗜睡, 值得臨床進(jìn)一步研究。
【關(guān)鍵詞】 重疊綜合征;無(wú)創(chuàng)氣道正壓通氣;肺功能;睡眠質(zhì)量;氧合狀態(tài)
DOI:10.14163/j.cnki.11-5547/r.2019.19.006
【Abstract】 Objective? ?To discuss the effect of non-invasive positive airway pressure ventilation (NPPV) on pulmonary function, sleep quality and oxygenation status in patients with overlap syndrome (OS). Methods? ?A total of 88 patients with obstructive sleep apnea (OSA) or chronic obstructive pulmonary disease (COPD) or OS as study subjects, and they were divided into OSA group (30 cases), COPD group (28 cases) and OS group (30 cases) according to polysomnography (PSG) and pulmonary function. After admission, three groups received OSA and COPD related knowledge education, and COPD patients were instructed to learn the correct method of inhaled drug use, standardize their application of bronchodilators, and oxygen therapy if necessary. The patients in OSA group and OS group were treated with NPPV at night. Comparison were made on pulmonary function [including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC], quality of sleep [apnea hypopnea index (AHI)], oxygenation status [night minimum oxygen saturation (LowSpO2), nighttime oxygen saturation < 90% time to total sleep time ratio (TST90), daytime arterial oxygen partial pressure (PaO2), daytime arterial blood carbon dioxide partial pressure (PaCO2)], Epworth sleepiness scale (ESS) score in OSA group OS group. Gender, age, body mass index (BMI), pulmonary function, daytime oxygenation status, ESS score, AHI and nighttime oxygenation status before treatment were compared among the three groups. Results? ?Three groups had statistically significant difference in age, BMI, pulmonary function, daytime oxygenation status, ESS score, AHI before treatment (P<0.05). Three groups had no statistically significant difference in gender (P>0.05). After 4 weeks of NPPV therapy, OSA group had significantly improved AHI, nighttime LowSpO2 and nighttime TST90 respectively as (3.1±2.6)times/h, (91±4)% and (5.6±2.3)% than (41.6±15.2) times/h, (68±8)% and (57.4±10.4)% before treatment, and their difference was statistically significant (P<0.05). There was no statistically significant difference in daytime PaO2 and PaCO2, comparing with those before treatment (P>0.05). After 4 weeks of NPPV therapy, OS group had significantly improved AHI, nighttime LowSpO2, nighttime TST90, daytime PaO2 and day time PaCO2 than those before treatment, and their difference was statistically significant (P<0.05). After 4 weeks of NPPV therapy, OSA group had statistically significant difference in FVC、FEV1, FEV1/FVC, comparing with those before treatment (P>0.05). OSA group had significantly decreased ESS score than those before treatment, and the difference was statistically significant (P<0.05). After 4 weeks of NPPV therapy, OS group had obviously better FVC, FEV1 and ESS score than those before treatment, and the difference was statistically significant (P<0.05). There was no statistically significant difference in FEV1/FVC, comparing with those before treatment (P>0.05). Conclusion? ?NPPV therapy can significantly improve the nocturnal apnea and hypopnea events, improve oxygenation status, correct sleep disorders, improve pulmonary function and daytime sleepiness in OS patients, and it is worthy of further clinical study.
【Key words】 Overlap syndrome; Non-invasive positive airway pressure ventilation; Pulmonary function; Sleep quality; Oxygenation status
OS被定義為COPD患者在繼發(fā)于上氣道阻塞的睡眠期間呼吸暫?;虻屯獾墓泊鎇1]。Shawon等[2]最近的一篇綜述文獻(xiàn)總結(jié)COPD患者的OS患病率為2.9%~65.9%。COPD患者睡眠期間因肋間肌松弛和胸壁活動(dòng)度降低等因素導(dǎo)致主要在快眼動(dòng)(REM)睡眠期發(fā)生夜間低氧血癥和低通氣。OSA患者則因睡眠期間上呼吸道塌陷、胸內(nèi)壓降低和交感神經(jīng)系統(tǒng)激活等導(dǎo)致呼吸暫停和低通氣、夜間覺(jué)醒和白天多睡[1]。兩種疾病重疊時(shí), 上、下氣道均存在動(dòng)態(tài)氣流受限和阻力增高, 并交互影響。Mermigkis等[3]的研究顯示, 基于圣喬治呼吸問(wèn)卷調(diào)查, 與單純COPD患者相比, OS患者胸悶和白天嗜睡更明顯、睡眠及生活質(zhì)量更差。故維持夜間氧合、減少低氧血癥和低通氣發(fā)作、改善睡眠質(zhì)量是降低OS病死率, 減少心腦血管合并癥, 降低住院率, 提高患者生活質(zhì)量的關(guān)鍵。無(wú)創(chuàng)氣道正壓通氣(noninvasive positive airway pressure ventilation, NPPV)是成人OSA患者首選治療方法, 有助于降低AHI和覺(jué)醒指數(shù), 消除夜間低氧, 糾正睡眠結(jié)構(gòu)紊亂, 改善白天嗜睡, 提高睡眠和生活質(zhì)量[4]。對(duì)于OS患者, 有研究表明NPPV可以改善OSA同時(shí)改善COPD臨床和預(yù)后[5]。本研究擬觀察NPPV治療對(duì)OS患者肺功能、氧合狀態(tài)、睡眠質(zhì)量和嗜睡的影響, 報(bào)告如下。
1 資料與方法
1. 1 一般資料 選取2015年1月~2017年2月在鄭州大學(xué)第一附屬醫(yī)院呼吸睡眠科就診的OSA或COPD或OS患者88例。納入標(biāo)準(zhǔn):①年齡18~70歲;②COPD患者符合中華醫(yī)學(xué)會(huì)呼吸病學(xué)分會(huì)2013年修訂版COPD診斷標(biāo)準(zhǔn)[6];③OSA患者符合中華醫(yī)學(xué)會(huì)呼吸病學(xué)分會(huì)2011年修訂版OSA診斷標(biāo)準(zhǔn)[7];④OS患者同時(shí)滿(mǎn)足COPD和OSA的標(biāo)準(zhǔn);⑤對(duì)本研究知情同意并配合相關(guān)治療、評(píng)定, 同時(shí)本研究也得到鄭州大學(xué)第一附屬醫(yī)院倫理委員會(huì)審核批準(zhǔn)。排除標(biāo)準(zhǔn):合并嚴(yán)重心腦血管疾病、嚴(yán)重呼吸衰竭、近1個(gè)月內(nèi)COPD急性加重者及不能耐受NPPV治療者等。將患者分為OSA組(30例)、COPD組(28例)和OS組(30例);其中OSA組、OS組均為中重度患者(AHI≥15次/h)。
1. 2 方法 三組患者入院后常規(guī)給予OSA和COPD相關(guān)知識(shí)宣教, 對(duì)COPD患者指導(dǎo)其學(xué)習(xí)掌握正確的吸入性藥物使用方法, 規(guī)范應(yīng)用支氣管舒張類(lèi)藥物, 必要時(shí)氧療。對(duì)OSA組和OS組患者給予夜間NPPV治療。對(duì)患者進(jìn)行各項(xiàng)檢測(cè), 并進(jìn)行記錄。
1. 2. 1 多導(dǎo)睡眠監(jiān)測(cè) 采用美國(guó)Alice4及SandmanElite多導(dǎo)睡眠監(jiān)測(cè)儀行整夜PSG監(jiān)測(cè), 包括腦電圖、心電圖、眼動(dòng)圖、下頜與雙側(cè)脛前肌動(dòng)圖、口鼻氣流、胸腹式呼吸、指脈氧飽和度。PSG記錄時(shí)間>7 h, 睡眠分期及睡眠相關(guān)事件的判讀采用美國(guó)睡眠醫(yī)學(xué)會(huì)(American Academy of Sleep Medicine, AASM)判讀手冊(cè)[8]。根據(jù)AHI將OSA分為輕、中、重度, 5次/h≤AHI<15次/h為輕度;15次/h≤AHI<30次/h為中度;AHI≥30次/h為重度。
1. 2. 2 動(dòng)脈血?dú)夥治?患者靜息30 min, 未吸氧狀態(tài)下抽取橈動(dòng)脈血2 ml, 以美國(guó)GEM Premier 3000血?dú)夥治鰞x行動(dòng)脈血?dú)夥治鰴z查, 并記錄pH、PaO2、PaCO2指標(biāo)。部分患者治療期間如多次檢查則采用4周NPPV治療結(jié)束時(shí)最后1次檢查結(jié)果。
1. 2. 3 肺功能檢測(cè) 采用德國(guó)Jaeger公司MasterScreen-Body/Diff肺功能儀。每例患者均測(cè)試3次, 各項(xiàng)肺功能指標(biāo)均取最大值, 包括FEV1、FVC和FEV1/FVC, 同時(shí)行支氣管舒張?jiān)囼?yàn)[9]。COPD分級(jí)依據(jù)COPD全球創(chuàng)議[10]。
1. 2. 4 NPPV 對(duì)OSA、OS兩組患者給予夜間NPPV治療。于首夜滴定出治療每1例OSA及OS患者的最佳有效正壓, 于夜間安靜休息時(shí)佩戴無(wú)創(chuàng)呼吸機(jī), 每晚帶機(jī)治療時(shí)間>5 h, 連續(xù)治療4周后復(fù)查PSG。
1. 2. 5 ESS評(píng)分 用于評(píng)估每日8種情況下入睡傾向, 嗜睡狀況的可能性分別按0~3級(jí)評(píng)分(0:從不打瞌睡, 1=輕度可能打瞌睡, 2:中度可能打瞌睡, 3:經(jīng)??赡艽蝾?。積分越高表示嗜睡越嚴(yán)重。ESS評(píng)分范圍為0~24分, 評(píng)分≥10分表示白天過(guò)度嗜睡[11]。
1. 3 觀察指標(biāo) 比較OSA組和OS組治療前后肺功能(FVC、FEV1、FEV1/FVC)、睡眠質(zhì)量(AHI)、氧合狀態(tài)(夜間LowSpO2、夜間TST90及日間PaO2、日間PaCO2)和ESS評(píng)分;此外比較三組性別、年齡及治療前BMI、肺功能、日間氧合狀態(tài)、ESS評(píng)分、AHI、夜間氧合狀態(tài)。
1. 4 統(tǒng)計(jì)學(xué)方法 采用SPSS22.0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, 組間比較采用方差分析, 組內(nèi)比較采用獨(dú)立樣本t檢驗(yàn);計(jì)數(shù)資料采用χ2檢驗(yàn)。P<0.05表示差異具有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2. 1 三組患者性別、年齡及治療前BMI、肺功能、日間氧合狀態(tài)、ESS評(píng)分、AHI、夜間氧合狀態(tài)比較 三組患者年齡及治療前BMI、肺功能、日間氧合狀態(tài)、夜間氧合狀態(tài)、ESS評(píng)分、AHI比較差異具有統(tǒng)計(jì)學(xué)意義(P<0.05);三組患者性別比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見(jiàn)表1。
2. 2 OSA組及OS組患者NPPV治療前后AHI及夜間和日間氧合狀態(tài)比較 經(jīng)NPPV治療4周后, OSA組AHI、夜間LowSpO2、夜間TST90分別為(3.1±2.6)次/h、(91±4)%、(5.6±2.3)%, 較治療前的(41.6±15.2)次/h、(68±8)%、(57.4±10.4)%均顯著改善, 差異具有統(tǒng)計(jì)學(xué)意義(P<0.05), 而日間PaO2、PaCO2水平與治療前比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。經(jīng)NPPV治療4周后, OS組AHI、夜間LowSpO2、夜間TST90、日間PaO2、日間PaCO2水平均較治療前顯著改善, 差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。見(jiàn)表2。
2. 3 OSA組及OS組患者NPPV治療前后肺功能及ESS評(píng)分比較 經(jīng)NPPV治療4周后, OSA組患者FVC、FEV1以及FEV1/FVC與治療前比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05), ESS評(píng)分較治療前顯著下降, 差異具有統(tǒng)計(jì)學(xué)意義(P<0.05)。經(jīng)NPPV治療4周后, OS組患者FVC、FEV1及ESS評(píng)分較治療前均明顯改善, 差異具有統(tǒng)計(jì)學(xué)意義(P<0.05), FEV1/FVC與治療前比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見(jiàn)表3。
3 討論
呼吸困難、疲倦和睡眠障礙是影響COPD患者生活質(zhì)量的三大常見(jiàn)因素[12]。夜間低氧血癥則是COPD睡眠障礙的主要后果, 其機(jī)制涉及睡眠期間肺泡通氣量不足、通氣-血流灌注比例不匹配和呼氣末容積減少(ERV)。與單純COPD患者相比, OS患者的睡眠障礙更加嚴(yán)重, 夜間嚴(yán)重低氧血癥風(fēng)險(xiǎn)增加, 常導(dǎo)致呼吸衰竭和高碳酸血癥。本研究中, 單純OSA組和COPD組患者均顯示出夜間低氧血癥, 而OS組患者與上述兩組患者相比, 其夜間LowSpO2、夜間TST90均較OSA組和COPD組患者更為嚴(yán)重。表明OS患者不僅存在嚴(yán)重的夜間瞬時(shí)低氧, 且低氧總持續(xù)時(shí)間更長(zhǎng), 疊加作用導(dǎo)致的低氧性損害更易造成惡性臨床事件。此外, 本研究中OS患者動(dòng)脈血?dú)釶aO2均數(shù)水平在70 mm Hg左右, 顯示重疊綜合征患者即使日間亦存在低氧血癥。
相比單純OSA或COPD患者, OS患者具有心血管死亡風(fēng)險(xiǎn)、肺動(dòng)脈高壓和右心衰竭風(fēng)險(xiǎn)[13-16]。改善夜間氧飽和度, 防止多次喚醒, 并改善生活質(zhì)量, 可能有助于降低與OS相關(guān)死亡率[17]。NPPV可有效改善COPD急性加重期高碳酸血癥性呼吸衰竭, 改善COPD患者的夜間低氧血癥和睡眠質(zhì)量, 在COPD中已很好確定了NPPV的治療地位[17], 但關(guān)于NPPV在OS中益處的文獻(xiàn)非常有限。本研究中, OSA和OS組患者接受了4周的NPPV治療, 治療后兩組患者的AHI、夜間LowSpO2指標(biāo)均顯著改善(P<0.05), 達(dá)到或接近正常標(biāo)準(zhǔn), 夜間TST90%由30%左右的嚴(yán)重水平降至輕微程度。隨著夜間缺氧的改善, OS組患者日間PaO2水平也明顯升高, 氧合狀況得到改善。提示NPPV在OS患者治療中具有可靠的糾正夜間睡眠事件和低氧的作用[18, 19]。
有研究表明NPPV治療除有效改善OS患者PaO2, PaCO2和平均肺動(dòng)脈壓外, 還有助于改善患者肺功能指標(biāo)[20]。本研究中, OS組患者經(jīng)治療后肺通氣功能指標(biāo)FEV1、FVC明顯改善, 與治療前比較, 差異有統(tǒng)計(jì)學(xué)意義(P<0.05);治療后FEV1/FVC無(wú)明顯變化, 差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05), 提示OS患者有氣流受限不可逆特性, 不能通過(guò)短期NPPV治療逆轉(zhuǎn)。本研究還顯示, 隨著夜間睡眠質(zhì)量改善、夜間氧合狀態(tài)改善和肺功能提高, ESS評(píng)分隨之改善, 與治療前比較, 差異有統(tǒng)計(jì)學(xué)意義(P<0.05), 提示NPPV對(duì)日間嗜睡的改善作用。
綜上所述, NPPV治療可以顯著改善OS患者夜間呼吸暫停低通氣事件, 改善氧合狀況, 糾正睡眠結(jié)構(gòu)紊亂, 提高肺功能, 改善日間嗜睡, 值得臨床進(jìn)一步深入研究。
參考文獻(xiàn)
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[收稿日期:2019-03-08]