睡眠醫學二十八之阻塞性睡眠窒息症的顯型

我年青的時候很喜歡到書局打書釘，今天突然心血來潮要再扮” 偽”文青。想不到在書局的大眾心理學角落竟然遇到振華，他洋洋得意捧著一本關於「九型人格」的書。他興奮地分享從這本書學會將下屬分成九種類別，從而亦學會如何駕馭不同型格的下屬。但振華忽然問我能否同樣將阻塞性睡眠窒息症(OSA)分門別類，如此一來，醫治睡眠窒息症不就簡單直接得多了嗎?

雖然近年醫學界對OSA的認識增添了不少，但卻沒有制定什麼普世認同的分類。有個別學者把阻塞性睡眠窒息症分成多種顯型 (phenotypes is defined as an observable expression of an individual’s characteristics that result from the interaction between the individual’s genes (genotype)and the environment, without any implication of a mechanism) 。一如其名，顯型是指病人所顯露出來的表徵，而表徵是由遺傳因子和環境因素交錯而成的。

顯型的種類

年齡層

隨著病人年齡的增長，阻塞性睡眠窒息症愈見普遍，高峰期見於65歲，此後發病率大致平穩。病理是多樣化的(Reduced airway caliber due to preferential deposition of fat around the pharynx makes the aging population anatomically susceptible to OSA (1) Overnight rostral shift of fluids to the neck(2) higher surface tension of the upper airway(3) and decreases in lung volume tethering effect(4) also predispose the elderly population to OSA)。而老齡的OSA病人有別於年青的OSA病人(5):日間嗜睡較輕微；細的肺容量引起圈養後果(tethering contributes to airway collapsibility)；夜間咀唇液體移位(overnight rostral shift of fluid) 較普遍。

更年期

更年期後的婦女患上睡眠窒息症的機會大增(6)，有別於年青婦女患者，她們在Non Rapid Eye Movement [NREM] Sleep 時病情特別嚴重(7)，賀爾蒙補允藥有助減少更年期後的婦女患上OSA的機會(8) 。

種族

亞洲OSA患者較多有顱面骨架異常(Craniofacial skeletal restriction)，而美國非洲裔(African Americans)患者則多因肥胖引起發病，另外(Caucasians) 高加索人種患者同時因顱面骨架異常及肥胖引起發病(9)。所以有不少亞洲OSA患者並不如外國患者般肥胖(10,11) 。

睡眠階段

有個別患者的睡眠窒息主要(predominant)或單單(isolated)發生在Rapid Eye Movement , REM Sleep，約10至36% OSA病人屬這類別(12)。患者多為年長婦女而且她們的病情亦較嚴重(13,14)，這類的睡眠窒息症(REM-related OSA) 特別與高血壓有關(15)。

睡姿

與平臥有關(supine position -related) 的OSA 是相當常見的，其流行率(prevalence) 為20至60%(16)。病理主因乃上呼吸道結構及功能異常( It may be attributable to unfavorable upper airway anatomy, reduced lung volume, and inability of airway dilator muscles to compensate for the airway collapse in the supine position.)。患者多為年青男士，亦非肥胖，可是他們卻出現較嚴重的日間嗜睡(7)。治理這類型病人可考慮側睡(17)、鈄睡(18)。如果這屬病人不想使用連CONTINUOUS POSITIVE AIRWAY PRESSURE THERAPY[CPAP]/持續正壓呼吸機，亦可試用 Mandibular Advancement Devices (MAD)下頜前移矯治器。

上呼吸道狹窄症候群 (Upper Airway Resistance Syndrome)

病人由於上呼吸道狹窄，因而在睡眠中呼吸遇到阻力，最終引致睡夢中覺醒(Respiratory Effort Related Arousal) (19)，但病變機理又未符合睡眠窒息(Apnoea)或低通氣(Hypopnea) 的定義。典型患者是非肥胖年青人士，及有多種顱面骨架異常(Craniofacial abnormalities include low soft palate, long uvula, increased overbites, and a high and narrow hard palate)。

我輕輕拍了振華的膊頭，其實任何疾病的病人都不可能用幾種顯型就可慨括的! 唯一較實際的分類: 老闆(振華)及打工仔(小弟)。

參考文獻:

1.  Aging influences on pharyngeal anatomy and physiology: the predisposition to pharyngeal collapse. Am J Med. 2006;119:72.e9–e14.

2.  Relationship between overnight rostral fluid shift and obstructive sleep apnea in nonobese men. Am J Respir Crit Care Med. 2009;179:241–246.

3.  Relationship between surface tension of upper airway lining liquid and upper airway collapsibility during sleep inobstructive sleep apnea hypopnea syndrome. J Appl Physiol (1985). 2003;95:1761–1766

4.  Effect of increased lung volume on sleep disordered breathing in patients with sleep apnoea. Thorax. 2006;61:435–439.

5.  Obstructive sleep apnea in older adults is a distinctly different physiological phenotype. Sleep. 2014;37:1227–1236

6.  Menopausal status and sleep-disordered breathing in the Wisconsin Sleep Cohort Study. Am J Respir Crit Care Med. 2003;167:1181–1185.

7.  Phenotypes of patients with mild to moderate obstructive sleep apnoea as confirmed by cluster analysis. Respirology 2012;17:99–107.

8.  Prevalence of sleepdisordered breathing in women: effects of gender. Am J Respir Crit Care Med. 2001;163:608–613.

9.  Obesity and craniofacial structure as risk factors for obstructive sleep apnoea: impact of ethnicity. Respirology 2012;17:213–222.

10.A community study of sleep-disordered breathing in middle-aged Chinese women in Hong Kong: prevalence and gender differences. Chest. 2004;125:127–134.

11.Excess weight and sleep-disordered breathing. J Appl Physiol (1985). 2005;99:1592–1599

12.Prevalence, clinical features, and CPAP adherence in REM-related sleep-disordered breathing: a cross-sectional analysis of a large clinical population. Sleep Breath. 2012;16:519–526.

13.Gender differences in the polysomnographic features of obstructive sleep apnea. Am J Respir Crit Care Med. 2000;161:1465–1472

14.Gender differences in obstructive sleep apnea and treatment implications. Sleep Med Rev. 2008;12:481–496.

15.Obstructive sleep apnea during REM sleep and hypertension results of the Wisconsin Sleep Cohort. Am J Respir Crit Care Med. 2014;190:1158–67

16.Prevalence and clinical significance of supine-dependent obstructive sleep apnea in patients using oral appliance therapy. J Clin Sleep Med. 2014;10:959–964.

17.Positional treatment vs continuous positive airway pressure in patients with positional obstructive sleep apnea syndrome. Chest. 1999;115:771–781.

18.Effects of sleep posture on upper airway stability in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 1997;155:199–204.

19.The upper airway resistance syndrome. Chest. 1999;115:1127–1139.

師公葉準師傅大壽2018

睡眠醫學二十七之誰有高風險?

閒來與振華(假名)去歡樂時光(Happy hour)輕鬆一下，忽然他想起我們的老朋友最近突然辭世，不敢悲從中來，他長嘆一聲:「若果人類可以預測某種疾病的來臨，那麼我們就可以避過一劫。」我亦表贊同: 「振華你可想起上一次要做膽石手術? 並不是每個睡眠窒息的病人都這麼幸運，能在手術前已被診斷出來! 否則在沒有充足準備下做手術，手術前後的風險可能會大增呢!」振華自然追問醫生在手術前有什麼方法可以篩查出那位病人患有睡眠窒息症。其實麻醉科醫生可使用以下幾種問卷調查-Berlin questionnaire, STOP-BANG, SACS or ASA checklist，如果發現病人屬高危一族，那最好還是替病人先進行睡眠測試，但大家要明白這些問卷並不能夠在手術前找出所有睡眠窒息症病人的(1)。

在日常臨床診斷中，醫生主觀的感覺或印象往往不能正確診斷出睡眠窒息症(2)，因此醫學界嘗試找出各種更客觀的方案，從而幫助醫護人員篩查出高風險病人。BERLINE QESTIONNAIRE 能成功找出86%的睡眠窒息病人(e.g AHI> 5), 有77% SPECIFICITY [特異性], a positive likelihood ratio of 3.79(3)。而STOP-BANG questionnaire是另一個有深厚醫學實據的問卷調查(4,5,6)，當問卷總分是3分或以上就能篩查出93%中度睡眠窒息症(AHI>15)及100%的嚴重睡眠窒息症(AHI>30)病人，若果總分達7或8分，填卷人士就有60%機會患上嚴重睡眠窒息症了!

振華忍不住打斷了我的講話，問有更簡單的方法嗎? 大家自然想起單單量度頸圍有用嗎? 雖然不同研究對這個方法會有不同結論，但一般都同意頸圍越粗風險就越大(7-10)，更有學者發現用頸圍與高度的比例( neck circumference –height ratio) 會更有用(11)。很久之前已有學者使用Mallampati score ( grades visibility of the posterior pharynx when the patient opens his mouth and stick out his tongue)來評估風險(9)。肥胖自然是另一個研究焦點(12-14)，同樣病人越肥胖就有越高風險患上睡眠窒息症。

 當然亦有學者使用高科技(craniofacial photographic analysis) 從頭部結構來預測病人患上睡眠窒息症的風險(15)。更有研究特別針對心臟病患者患上睡眠窒息症的風險(16,17)。但可惜至今沒有單一預測模式或方案是明顯優勝於他人(18)，值得醫學界一致推崇的。

這時有點醉意的振華冷不防說了一句:「人生根本就不能預測的!」對!不過我就能預測今晚我要送佢返屋企。

參考文獻

1.  Pre-operative screening for obstructive sleep apnoea. Eur Respir Rev 2017;26:160012

2.  Predictive value of clinical features in diagnosing obstructive sleep apnea. Sleep 1993;16(2):118-122

3.  Using Berlin questionnaire to identify patients at risk for the sleep apnoea syndrome. Ann Intern Med 1999;131:485-491.

4.  STOP-BANG questionnaire in obstructive apnea syndrome: a severity predictor. Eur Respir J 2015 46:PA2343

5.  STOP-BANG questionnaire. A practical approach to screen for obstructive sleep apnea. Chest 2016;149(3):631-638

6.  Predicting sleep disordered breathing in outpatients with suspected OSA. BMJ Open 2014;4:e004519

7.  Predictors of sleep disordered breathing in community dwelling adults; the sleep heart health study. Arch Intern Med 2002;162(8):893-900

8.  The occurrence of sleep disordered breathing among middle aged adults. N Engl J Med 1993;328(17):1230-1235

9.  A stepped approach for prediction of obstructive sleep apnea in overtly asymptomatic obese subjects: a hospital based study Sleep Med 2004;5(5):351-357

10.Predictors for presence and severity of obstructive sleep apnea in snoring patients: significance of neck circumference. J Sleep Med 2015;12(2)34-38

11.Neck circumference –height ratio as a predictor of sleep related breathing disorder in children and adults. J Clin sleep Med 2016;12(3):311-7

12.Predicting sleep apnea and excessive day sleepiness in the severely obese .Chest 2003; 123(4):1134-1141

13.Usefulness of truncal obesity indices as predictive factors for obstructive sleep apnea syndrome. Obesity 2008;16:113-8

14.Obesity stratification as a predictor for sleep apnea syndrome. Sleep Medicine 2013;Vol 14, Suppl 1 Pe207

15.Prediction of obstructive sleep apnea with craniofacial photographic analysis. Sleep 2009;3291):46-52

16.Prevalence and predictors of sleep apnea in patients with stable coronary artery disease: a cross sectional study. Therapeutics and clinical risk management 2017;13:1031-1042

17.Prevalence and predictors of sleep disordered breathing in patients with stable chronic heart failure. JACC: Heart Failure 2016.Vol 4,No2

18.Systematic review and meta-analysis of the literature regarding the diagnosis of sleep apnea. Sleep 2000;23:519-532

                                                  

睡眠醫學二十六之心肺健康

今晚如常到體育館練拳，迎面而來的竟是身型龐大的振華(假名)，我自不然要椰榆一下這位運動場稀客! 偉民當然亦不甘示弱，表示知道勤做運動可以提昇心肺健康，奈何自己患有糖尿病，高血壓同睡眠窒息症(OSA)，所以不能太操勞，實在身不由己!

話說回來，睡眠窒息症如何影響心肺健康( cardiorespiratory fitness, CRF) 也是百家爭鳴，其實這是個十分重要的健康問題，低的CRF值常常與心血管疾病及死亡率扯上關係(1-2)。CRF值比其他常引用的心血管疾病風險指標(Cardiovascular risk factor) 更能預測死亡風險(mortality)及願境(prognosis)(3-4)，CRF值通常用metabolic equivalents (METS) 或 peak oxygen consumption (V′O2peak)作單位的。

最近有學者(5)透過系統評價(systemic review)及薈萃分析(meta-analysis)對此醫學難題作出研究，發現睡眠窒息症病人的V′O2peak值真的較常人差。不論年青(五十歲以下) 或年長(五十歲以上)的睡眠窒息症病人也是如此。奇怪的是較瘦的睡眠窒息症病人(BMI<30Kg.m-2)較肥的OSA病人有更低的CRF值! 低的心肺健康值( cardiorespiratory fitness, CRF)正好解釋為何睡眠窒息症病人會出現較弱的體能和不濟的生活質素(6-10)。同一組學者(11)亦發現OSA病人每天的平均運動量(mean number of steps per day of 5388 )遠遠低於醫學界倡議的運動量(每天行一萬步)。其實運動訓練就算在沒有改善病人BMI下，仍能大幅改善睡眠窒息的頻率(Apnea-hypopnoea index)，日間嗜睡(Sleepiness)及提昇V′O2peak值的。究竟睡眠窒息症如何影響病人的運動量(exercise capacity) 不得而知，可能是OSA病人平日的運動量不足因而引致低CRF值吧。因此將來可能要考慮將運動治療(follower-up physical exercise programmes)納入醫治睡眠窒息症的常規方案。

夜了，正想搭振華的順風車回家，不過他說要去附近的東菇亨吃夜宵。唉!真的沒他辦法! 好在陳X記已經搬走了，費事話佢知先!

參考文獻:

1. Exercise capacity and mortality in black and white men. Circulation 2008;117: 614–622.

2. Cardiorespiratory fitness versus physical activity as predictors of all-cause mortality in men. Am Heart J 2018; 196: 156–162.

3. Importance of assessing cardiorespiratory fitness in clinical practice: a case for fitness as a clinical vital sign: a scientific statement from the American Heart Association. Circulation 2016; 134: e653–e699.

4. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002; 346: 793–801.

5. Maximal exercise capacity in patients with obstructive sleep apnoea syndrome: a systematic review and meta-analysis. Eur Respir J 2018; 51: 1702697.

6. Influence of gender on associations of obstructive sleep apnea symptoms with chronic conditions and quality of life. Int J Environ Res Public Health 2018; 15: 930.

7. Association between polysomnographic sleep measures and health-related quality of life in obstructive sleep apnea. J Sleep Res 2001; 10: 303–308.

8. Quality of life among untreated sleep apnea patients compared with the general population and changes after treatment with positive airway pressure. J Sleep Res 2015; 24:328–338.

9 Undiagnosed obstructive sleep apnea is independently associated with reductions in quality of life in middle-aged, but not elderly men of a population cohort. Sleep Breath 2015; 19: 1309–1316.

10. Quality of life in obstructive sleep apnea is related to female gender and comorbid insomnia. Sleep Breath 2018; in press [https://doi.org/10.1007/s11325-018-1621-y].

11. Obstructive sleep apnea syndrome, objectively measured physical activity and exercise training interventions: a systematic review and meta-analysis. Front Neurol 2018; 9: 73.

睡眠醫學二十五之男女大不同

我再次到振華(假名)家中作客，飽餐一頓後，振華太座Virginia 還端上一大盤水果，我當然大表渼慕! 振華卻不以為然並自嘲道:「我有糖尿、血壓高、失眠同睡眠窒息症喎! 梗係要好好照顧我啦，Virginia就晚晚不知瞓得幾好，日日鬼咁幾好精神。」這時我的正義感突然爆發:「華哥，我要為女士講句公道話，其實女士們也有很多睡眠問題的!」

當女性進入青春期，女性荷爾蒙(estradiol and progesterone) 週期性在血液中倍增，影響睡眠及多項身體功能(1)。隨著初潮(menarche) 來臨，女性比男性多兩倍風險患上情緒問題(2)，在十五至三十歲的年齡層中，女性亦比男性多28%機會有失眠現象(3)。

當女性懷孕，巨大的生理變化大大影響了她們的睡眠(4,5)，舉例說胃酸倒流現象會隨著懷孕惡化，且影響睡眠質素(6)。孕婦的骨絡因要為嬰兒出生作出變化，此等改變亦對睡眠有不良影響(7)。孕婦身體內的鐵質及葉酸含量同樣起了變動，亦引發了更多的腿不寧症(restless legs syndrome)(8)。孕婦睡眠的長短及質素亦隨著懷孕進展不斷變化(9)，當女性進入第二妊娠期(third trimester)，有28%的孕婦會睡少過七小時(10)。當孕婦進入第三妊娠期(third trimester)，她們的睡眠時間會比同齡的女士少三十分鐘(11) ，睡眠質素亦變得差了(12) 。研究發現較短的睡眠時間會產生較高機會需要剖腹產子(13,14) 及較長的生產時間(15)。

若果懷孕期間不幸患上睡眠窒息症的話，就會大增妊娠糖尿(16,17) 和妊娠高血壓問題(16-18) 。失眠(19) 及 睡眠窒息症(20,21) ，甚至劣質睡眠(22) 也可導致嬰兒早產!

當女性進入更年期，約四至六成婦女會出現睡眠問題，比較多發生在本身有抑鬱、嗜睡及使用精神科藥物的女士(23)。更年期的典型病徵如潮熱(hot flush) 及夜汗(night sweat) 就會嚴重影響睡眠質素(24,25) 。病徵越嚴重，就越大机會出現失眠現象(26,27)。若能妥善處理此等病徵，就可大大改善睡眠質素(28,29)。另外抑鬱亦常見於踏入更年期的女士(30,31)，而抑鬱當然也會影響睡眠。

人年紀大了，的確會容易出現失眠、淺睡、少了 Slow Wave Sleep 同REM sleep、易醒、睡眠效率減少等等(32) 。老年婦女更會經常難於入睡，睡得少、常常平夜驚醒(33) 。一般來說，超過一半更年期後的婦女都有不同程度的睡眠問題(34, 35) ，不可不知，此等劣質睡眠可引起炎症(36)，循環系統及新陳代謝毛病(37,38) 。

說到此時，振華突然良心發現，跑去幫太座洗碗!

**為保障個人私隱及達到教育效果，因此文中案例可能由真實及/或虛構病例改編而成***

參考文獻:

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9. Sleep quality and nocturnal sleep duration in pregnancy and risk of gestational diabetes mellitus. Sleep. 2017;40(2).

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12. Sleep quality during pregnancy: a meta-analysis. Sleep Med Rev. 2018;38: 168-176.

13. Sleep disturbance in late pregnancy and type and duration of labour. J Obstet Gynaecol. 2011;31(6):489-491.

14. Sleep trajectories among pregnant women and the impact on outcomes: a population-based cohort study. Matern Child Health J. 2017;21(5):1139-1146

15. Nighttime sleep, daytime napping, and labor outcomes in healthy pregnant women in Taiwan. Res Nurs Health. 2013;36(6):612-622.

16. Obstructive sleep apnea and severe maternal-infant morbidity/mortality in the United States, 1998-2009. Sleep. 2014;37(5):843-849.

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19. Sleep disorder diagnosis during pregnancy and risk of preterm birth. Obstet Gynecol. 2017;130(3):573-581

20.. Obstructive sleep apnea in gestational diabetes: a pilot study of the role of the hypothalamic pituitary adrenal axis. J Clin Sleep Med. 2018;14:87-93.

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