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研究生： 廖信閔
Liao, Xin-Min
論文名稱： 氣喘慢性肺阻塞重疊症候群的患者會有較高的風險得到阻塞型睡眠呼吸中止症，且睡眠呼吸中止症的嚴重度會影響此類患者的臨床預後
Patients With Asthma COPD Overlap Syndrome (ACOS) Have Higher Risk of Obstructive Sleep Apnea (OSA) And The Severity of OSA May Affect Outcomes of ACOS Patients
指導教授： 謝奇璋
Shieh, Chi-Chang
林聖翔
Lin, Sheng-Hsiang
學位類別： 碩士
Master
系所名稱： 醫學院 - 臨床醫學研究所碩士在職專班
Institute of Clinical Medicine(on the job class)
論文出版年： 2017
畢業學年度： 105
語文別： 英文
論文頁數： 51
中文關鍵詞： 氣喘肺阻塞重疊症 、阻塞型睡眠呼吸中止症 、單相陽壓呼吸器
外文關鍵詞： Asthma-COPD overlap syndrome, obstructive sleep apnea, continuous positive airway pressure
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    • 目的：本研究要探討氣喘肺阻塞重疊症的患者相較於單一肺阻塞疾患之患者得到阻塞型睡眠呼吸中止症的風險高低，以及在此類患者產生的阻塞型睡眠呼吸中止症嚴重度和其臨床預後有關聯。
    實驗設計：本次研究為一個回顧性的世代研究。從臺灣健保資料庫中選取於2000年至2011年被診斷為氣喘肺阻塞重疊症的病人，並且曾經接受睡眠生理檢查並診斷有阻塞型睡眠呼吸中止症作為後續臨床預後分析。透過利用Cox比例風險模式合併競爭風險分析的方法來比較氣喘肺阻塞重疊症患者和單一阻塞型肺疾患者得到阻塞型睡眠呼吸中止症的風險性。另外我們也要評估長期全身性類固醇治療是否會影響氣喘肺阻塞重疊症患者後續產生阻塞型睡眠呼吸中止症的風險。最後，我們以單相陽壓呼吸器的有無使用代表此類患者得到阻塞型睡眠呼吸中止症的嚴重度，進而探討阻塞型睡眠呼吸中止症的嚴重度是否影響到此類患者的後續急性發作，影響其臨床預後。
    結果：本次研究在公元2000年至2011年期間總共收入10,622位氣喘肺阻塞重疊症患者進入後續分析，其中過半為男性患者(52.8%)且在收案的各年齡分層皆為男性居多，在分析阻塞型睡眠呼吸中止症風險的情形下，共有172位氣喘肺阻塞的患者於追蹤期間產生阻塞型睡眠呼吸中止症，相較於控制組，氣喘肺阻塞重疊症、氣喘、慢性肺阻塞患者得到阻塞型睡眠呼吸中止症的風險分別為3.55倍、2.54倍以及2.19倍；氣喘肺阻塞重疊症患者若得到阻塞型睡眠呼吸中止症，往後產生急性發作的風險將是沒有得到阻塞型睡眠呼吸中止症患者的2.07倍；最後在這群同時具有氣喘慢性肺阻塞及阻塞型睡眠呼吸中止症的患者裡面作分析，可以發現此族群若得到重度阻塞型睡眠呼吸中止症，未來產生急性發作的風險將是得到輕度阻塞型睡眠呼吸中止症患者的4.75倍。
    結論：本研究發現在氣喘肺阻塞重疊症患者相較於單一肺阻塞疾病的患者有較高產生阻塞型睡眠呼吸中止症的風險，此類患者不論是否接受長期全身性類固醇治療，日後產生阻塞型睡眠呼吸中止症的狀況並沒有顯著差異，最後我們發現此類患者若得到嚴重的阻塞型睡眠呼吸中止症，將增加日後其阻塞型肺疾急性發作的風險。

    Purpose: The present study aimed to determine the increased risk of obstructive sleep apnea (OSA) development induced by asthma-COPD overlap syndrome (ACOS) and the severity of OSA would influence the acute exacerbation rate of ACOS patients.
    Experimental Design: We set a retrospective cohort study. Patients who had been diagnosed as ACOS during 2000-2011 and had received polysomnography (PSG) for diagnosing obstructive sleep apnea from National Health Insurance Research Database (NHIRD) in Taiwan were enrolled in experimental group. The Cox proportional hazard regression analysis with adjust and competing risk regression (CRR) was computed to compare the risk of OSA in ACOS and non-ACOS patients. The impact of long-term systemic corticosteroids therapy for OSA development in ACOS population would be evaluated considering its effects of anti-inflammation. Furthermore, we want to know if the presence of OSA in AOCS group would lead to higher acute exacerbation rate of ACOS. Finally, the severity of OSA will be assessed in view of continuous positive airway pressure (CPAP) use if it is related to the acute exacerbation rate in ACOS subjects with OSA.
    Results: We included 10,622 individuals with ACOS during the period of 2000-2011. Male predominant (52.8%) was noted and age distribution were 34.7%, 26%, 39.3% at 40-60, 60-70, above 70 year-old, respectively. Of 10,566 ACOS subjects, 172 patients acquired obstructive sleep apnea during the follow-up time. When the risk of OSA is compared between asthma, COPD, ACOS and healthy control, the adjusted HR were 3.55 for ACOS (95% CI: 2.89-4.35), 2.54 for asthma and 2.19 for COPD. The ACOS patients who have OSA as well will suffer higher risk at 2.07 folds (95% CI: 1.11-3.85) of acute exacerbation of their underlying ACOS in the future. Among those with both ACOS and OSA population, more severe OSA will lead to higher acute exacerbation rate of ACOS at 4.75 folds (95% CI: 3.28-6.87) in the future.

    TABLE OF CONTENTS ABSTRACT I 中文摘要 III 誌謝 V TABLE OF CONTENTS VI LIST OF TABLES VII LIST OF FIGURES IX ABBREVIATION X CHAPTER 1. INTRODUCTION 1 1.1. Introduction of asthma-COPD overlap syndrome 1 1.2. inflammatory mechanism of asthma and COPD 1 1.3. Introduction of sleep apnea 2 1.4. Prevalence of OSA in obstructive lung diseases 4 1.5. Worse clinic outcomes in severe OSA subjects 4 1.6. Hypothesis and specific aims 5 CHAPTER 2. MATERIALS AND METHODS 7 2.1. Study design 7 2.2. Database 7 2.3. Study sample and matching 8 2.4. Prevalence and development of OSA in obstructive lung diseases 9 2.5. The influence of OSA development is ACOS subjects 10 2.6. Statistical analysis 11 CHAPTER 3. RESULTS 12 3.1. Baseline demographic of ACOS, asthma, COPD subjects and comparison 12 3.2. The increased risk of OSA in ACOS subjects 12 3.3. Long-term steroids therapy did not lower risk of OSA in ACOS subjects 14 3.4. More acute exacerbation in ACOS with OSA 15 3.5. Severe OSA in ACOS leads to worse clinic outcomes 16 CHAPTER 4. DISCUSSION 17 4.1. Contributions 17 4.2. The differences between our study and previous literature 18 4.3. Systemic steroids therapy is ineffective for OSA prevention 18 4.4. The tentative mechanism of OSA development in ACOS subjects 19 4.5. Limitations 20 CHAPTER 5 CONCLUSIONS 22 CHAPTER 6. REFERENCES 24

    1. Global Initiative for Asthma. Global strategy for asthma management and prevention. (updated 2015)
    2. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. (updated 2015)
    3. Barker BL, Brightling CE. Phenotyping the heterogeneity of chronic obstructive pulmonary disease. Clin Sci (Lond) 2013; 124: 371-87.
    4. Sin DD, Miravitlles M, Mannino DM, et al. What is asthma-COPD overlap syndrome? Towards a consensus definition from a round table discussion. Eur Respir J. 2016 Sep;48(3):664-73.
    5. Dirkje S. Postma, and Klaus F. Rabe. The Asthma–COPD Overlap Syndrome. N Engl J Med 2015; 373: 1241-9.
    6. Lauren Cohn, Robert J. Homer, Anthony Marinov. Induction of Airway Mucus Production by T Helper 2 (Th2) Cells: A Critical Role For Interleukin 4 In Cell Recruitment But Not Mucus Production. J. Exp. Med. Volume 186, Number 10, November 17, 1997 1737–1747.
    7. Jean Bousquet, Pascal Chanez, Jean Yves Lascoste, et al. Eosinophilic Inflammation in Asthma. N Engl J Med 1990; 323: 1033-1039.
    8. James AL, Elliot JG, Jones RL, et al. Airway Smooth Muscle Hypertrophy And Hyperplasia in Asthma. Am J Respir Crit Care Med. 2012 May 15;185(10):1058-1064.
    9. Jennifer Kathleen Quint, and Jadwiga Anna Wedzicha. The neutrophil in chronic obstructive pulmonary disease. J Allergy Clin Immun. May 2007, Volume 119, Issue 5, Pages 1065–1071.
    10. Freeman CM, Han MK, Martinez FJ, et al. Cytotoxic potential of lung CD8+ T cells increases with COPD severity and with in vitro stimulation by IL-18 or IL-15. J Immunol. 2010 June 1; 184(11): 6504–6513.
    11. Marco Chilosi1, Venerino Poletti and Andrea Rossi. The pathogenesis of COPD and IPF: Distinct horns of the same devil? Respiratory Research 2012, 13:3
    12. Marvin Dewar, and R. Whit Curry, Jr. Chronic Obstructive Pulmonary Disease: Diagnostic Considerations. American Family Physician February 15, 2006 Volume 73, Number 4.
    13. Seiichi Kobayashi, Masakazu Hanagama, Shinsuke Yamanda, et al. Inflammatory Biomarkers in Asthma-COPD Overlap Syndrome. International Journal of COPD 2016:11 2117–2123.
    14. American Academy of Sleep Medicine. Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline. (updated 2013)
    15. Abel Romero-Corral, Sean M. Caples, and Francisco Lopez-Jimenez, et al. Interactions Between Obesity and Obstructive Sleep Apnea. Chest 2010; 137 (3): 711 – 719
    16. Alan R. Schwartz, Susheel P. Patil, Alison M. Laffan, et al. Obesity and Obstructive Sleep Apnea Pathogenic Mechanisms and Therapeutic Approaches. Proc Am Thorac Soc Vol 5. pp 185–192, 2008.
    17. Shiroh Isono, John E. Remmers, Atsuko Tanaka, et al. Anatomy of Pharynx in Patients with Obstructive Sleep Apnea and in Normal Subjects. J. Appl. Physiol. 82(4): 1319–1326.
    18. Richard W. W. Lee, Kate Sutherland, Andrew S. L. Chan, et al. Relationship Between Surface Facial Dimensions and Upper Airway Structures in Obstructive Sleep Apnea. Sleep 2010;33(9):1249-1254.
    19. Patrick J. Strollo, Jr, Ryan J. Soose, Joachim T. Maurer, et al. Upper-Airway Stimulation for Obstructive Sleep Apnea. N Engl J Med 2014; 370: 139-49.
    20. Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine. Clinical Guideline for the Evaluation, Management and Long-term Care of Obstructive Sleep Apnea in Adults. J Clin Sleep Med 2009;5(3):263-276.
    21. Jiang, Kryger, Meir H, Zorick, Frank J, et al. Mortality and Apnea Index in Obstructive Sleep Apnea: Experience in 385 Male Patients. Chest, Volume 94, Issue 1, July 1988, Pages 9-14.
    22. Julio A. Chirinos, Indira Gurubhagavatula, Karen Teff, et al. CPAP, Weight Loss, or Both for Obstructive Sleep Apnea. N Engl J Med 2014; 370: 2265-75.
    23. José Antonio Pinto, Davi Knoll Ribeiro, Andre Freitas da Silva Cavallini, et al. Comorbidities Associated with Obstructive Sleep Apnea: a Retrospective Study. Int Arch Otorhinolaryngol 2016; 20: 145–150.
    24. Harding SM. Complications and Consequences of Obstructive Sleep Apnea. Curr Opin Pulm Med. 2000 Nov;6(6):485-9.
    25. Stephen Tregear, James Reston, Karen Schoelles, et al. Obstructive Sleep Apnea and Risk of Motor Vehicle Crash: Systematic Review and Meta-Analysis. J Clin Sleep Med 2009;5(6):573-581.
    26. Mahssa Karimi, Jan Hedner, Henrike Häbel, et al. Sleep Apnea Related Risk of Motor Vehicle Accidents is Reduced by Continuous Positive Airway Pressure: Swedish Traffic Accident Registry Data. SLEEP 2015;38(3):341–349.
    27. Rashid Nadeem, Janos Molnar, Essam M. Madbouly, et al. Serum Inflammatory Markers in Obstructive Sleep Apnea: A Meta-Analysis. J Clin Sleep Med 2013;9(10):1003-1012.
    28. Mohammad Badran, Najib Ayas, Ismail Laher. Cardiovascular Complications of Sleep Apnea: Role of Oxidative Stress. Oxidative Medicine and Cellular Longevity Volume 2014, Article ID 985258, 10 pages.
    29. Won Lee, Swamy Nagubadi, and Meir H. Kryger, et al. Epidemiology of Obstructive Sleep Apnea: A Population-based Perspective. Expert Rev Respir Med. 2008 June 1; 2(3): 349–364.
    30. Xavier Soler, Eduardo Gaio, Frank L. Powell, et al. High Prevalence of Obstructive Sleep Apnea in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease. Ann Am Thorac Soc Vol 12, No 8, pp 1219–1225.
    31. Jose M. Marin, Joan B. Soriano, and Santiago J. Carrizo, et al. Outcomes in Patients with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea. Am J Respir Crit Care Med Vol 182. pp 325–331, 2010.
    32. Mihaela Teodorescu, Jodi H. Barnet, and Erika W. Hagen, et al. Association Between Asthma and Risk of Developing Obstructive Sleep Apnea. JAMA. 2015;313(2):156-164.
    33. Patrick J. Strollo, and Robert M. Rogers. Obstructive Sleep Apnea. N Engl J Med 1996; 334:99-104.
    34. Redline S, Strohl KP: Recognition and consequences of obstructive sleep apnea hypopnea syndrome. Clin Chest Med. 1998 Mar;19(1):1-19.
    35. Aikens JE, Caruana-Montaldo B, Vanable PA, et al.: MMPI correlates of sleep and respiratory disturbance in obstructive sleep apnea. Sleep 1999, 22:362–366.
    36. Chien IC, Chou YJ, Lin CH, Bih SH, Chou P. Prevalence of psychiatric disorders among National Health Insurance enrollees in Taiwan. Psychiatr Serv 2004; 55: 691-697.
    37. Hsu YC, Lin JT, Chen TT, Wu MS, Wu CY. Long-term risk of recurrent peptic ulcer bleeding in patients with liver cirrhosis: a 10-year nationwide cohort study. Hepatology 2012; 56: 698-705.
    38. Hsu YC, Lin JT, Ho HJ, et al. Antiviral treatment for hepatitis C virus infection is associated with improved renal and cardiovascular outcomes in diabetic patients. Hepatology 2014; 59: 1293-1302.
    39. Chiang CW, Chen CY, Chiu HF, Wu HL, Yang CY. Trends in the use of antihypertensive drugs by outpatients with diabetes in Taiwan, 1997-2003. Pharmacoepidemiol Drug Saf 2007; 16: 412-421.
    40. Kuo HW, Tsai SS, Tiao MM, Yang CY. Epidemiological features of CKD in Taiwan. Am J Kidney Dis 2007; 49: 46-55.
    41. Longitudinal Health Insurance Database 2000. [cited 2013 Aug]. Available from: http:// nhird.nhir.org.tw/en/Data_Subsets.html#S3.
    42. Wei-Sheng Chung, Cheng-Li Lin, and Chia-Hung Kao. Comparison of Acute Respiratory Events Between Asthma – COPD Overlap Syndrome and COPD Patients: A Population-Based Cohort Study. Medicine 94(17): e755
    43. Umurs Hatipoglu, and Loutfi S. Aboussouan. Treating and Preventing Acute Exacerbations of COPD. Cleveland Clinic Journal of Medicine 83; 4: April 2016.
    44. Donaldson GC, Seemungal TA, and Bhowmik A, et al. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002; 57:847–852.
    45. Seemungal TA, Donaldson GC, and Paul EA, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157:1418–1422.
    46. Ford ES, Murphy LB, and Khavjou O, et al. Total and State-specific Medical and Absenteeism Costs of COPD Among Adults Aged ≥ 18 Years in The United States for 2010 and Projections Through 2020. Chest 2015; 147:31–45.
    47. Shiao TH, Liu CJ, and Luo JC, et al. Sleep Apnea and Risk of Peptic Ulcer Bleeding: A Nationwide Population-based Study. Am J Med. 2013 Mar; 126(3): 249-255.
    48. P. Jennum and R.L. Riha. Epidemiology of sleep apnoea/hypopnea syndrome and sleep-disordered breathing. Eur Respir J 2009; 33: 907–914.
    49. Naresh M. Punjabi. The Epidemiology of Adult Obstructive Sleep Apnea. Proc Am Thorac Soc Vol 5. pp 136–143, 2008.
    50. Keele E. Wurst, Tara R. Rheault, and Lisa Edwards, et al. A comparison of COPD patients with and without ACOS in the ECLIPSE study. European Respiratory Journal 2016; DOI: 10.1183/13993003.02045-2015.
    51. Jun-Jun Yeh, Yu-Chiao Wang, Chia-Hung Kao. Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome Associated with Risk of Pulmonary Embolism. PLoS ONE 11(9): e0162483. doi: 10.1371/journal.pone.0162483.
    52. Peter J. Barnes. New Anti-inflammatory Targets for Chronic Obstructive Pulmonary Disease. Nature Reviews Drug Discovery 12, 543–559 (2013).
    53. Seamus Grundy, Jonathan Plumb, and Manminder Kaur, et al. Additive anti-inflammatory effects of corticosteroids and phosphodiesterase-4 inhibitors in COPD CD8 cells. Respiratory Research (2016) 17:9.
    54. R O’Donnell, D Breen, and S Wilson, et al. Inflammatory cells in the airways in COPD. Thorax 2006; 61: 448–454.
    55. Bracke KR1, D'hulst AI, and Maes T, et al. Cigarette smoke-induced pulmonary inflammation and emphysema are attenuated in CCR6-deficient mice. J Immunol. 2006 Oct 1;177(7):4350-9.
    56. Bart N Lambrecht and Hamida Hammad. The Immunology of Asthma. Nature Immunology 16, 45–56 (2015).
    57. Miriam Barrecheguren, Cristina Esquinas and Marc Miravitlles. The asthma-COPD overlap syndrome: a new entity? COPD Research and Practice (2015) 1:8.
    58. Norman Wolkove, Marc Baltzan, and Hany Kamel, et al. Long-term compliance with continuous positive airway pressure in patients with obstructive sleep apnea. Can Respir J 2008;15(7):365-369.
    59. Russo-Magno P, O'Brien A, and Panciera T, et al. Compliance with CPAP therapy in older men with obstructive sleep apnea. J Am Geriatr Soc. 2001 Sep; 49(9): 1205-1211.
    60. Terri E. Weaver and Ronald R. Grunstein. Adherence to Continuous Positive Airway Pressure Therapy. Proc Am Thorac Soc Vol 5. pp 173–178, 2008.

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