近幾年來發展出許多可阻斷第二型發炎反應的生物製劑，證實對第二型氣喘病人的症狀控制有很大的助益，但生物製劑昂貴，健保使用規範嚴格，病人需有過去一年有4次或以上，因急性惡化需使用全身性類固醇，且至少一次因氣喘惡化到急診或住院治療才符合申請資格，有些病人有符合第二型氣喘特徵，但抽血檢驗數值不符合或接近臨界點族群，臨床上藥物治療方針是比較模糊跟值得研究的。長效抗膽鹼能支氣管擴張劑(Long-acting Muscarinic Antagonists; LAMA)製劑，可作為吸入型類固醇（inhaled corticosteroid,ICS）或ICS加LABA維持治療的附加劑，為嚴重氣喘者在開始任何生物製劑或全身性類固醇治療之前的優化步驟，許多大型研究證實，LAMA能有效改善肺功能、降低氣喘急性發作頻次，進而降低類固醇使用劑量，提升病人生活品質。
本研究分析長效抗膽鹼能支氣管擴張劑(Long-acting Muscarinic Antagonists; LAMA)吸入劑於不同的生物標記及檢驗值高低下，比較第二型氣喘跟非第二型氣喘急性發作及延長發作的顯著性，研究發現，嗜酸性球在300/μL以上者，建議可以考慮生物製劑治療；若為嗜酸性球在300/μL以下者，可繼續附加LAMA作為氣喘控制藥物。

In recent years, many biological agents that can block type 2 inflammatory response have been developed, which have proved to be efficacious to the symptom control of type 2 asthma patients. However, biological agents are costly, and the payment systems of health insurance are strictly regulated. Patients who are qualified for using biologics need to meet the requirement of using four times and more of systemic steroids for acute exacerbations, and at least one emergency visit or hospitalization due to exacerbation of asthma. Some patients have characteristics of type 2 asthma, but blood tests do not meet or close to the critical value. It’s hard to follow the treatment guidelines but simultaneously worth studying. Long-acting muscarinic antagonists (LAMA) preparations, available as an add-on to inhaled corticosteroids (ICS) or ICS plus long-acting β2 agonists (LABA) maintenance therapy, can be used as an adjunct therapy for severe asthma patients before biologics or systemic steroid therapy. The results showed if the eosinophil counts of patient are above 300/μL, it is recommended to consider biologic therapy; otherwise, LAMA can continue to be an add-on drug for treating asthma.

摘要 2
ABSTRACT III
誌謝 V
目錄 VI
圖目錄 VIII
表目錄 IX
第一章 緒論 10
1-1 研究背景 10
1-2 研究動機 11
1-3 研究目的 11
1-4 研究架構 12
第二章 文獻探討 12
2-1 嚴重氣喘簡介 13
2.1.1嚴重氣喘定義 13
2.1.2 表型內型與生物標記 14
2.1.3 免疫路徑機轉 17
2-2氣喘治療 18
2.2.1階梯式治療 18
2.2.2 急性發作 22
2-3 LAMA於氣喘治療角色 22
2-4氣喘慢性阻塞性肺疾病重疊綜合症(ACO) 24
第三章 研究方法 27
3-1研究對象 27
3-2 研究執行步驟 27
3.2.1 建立「原始資料檔」: 27
3.2.2 分組「檢驗數值」: 28
3.2.3 統計「急性發作次數跟時間間隔」: 29
3.3統計方法 30
第四章 結果 31
4-1 研究族群基本特性 31
4-2 氣喘急性發作危險因子 32
4-3 不同檢驗數值之氣喘病人臨床特性及急性發作比較 34
4.3.1第一組「以血清Total IgE > 100 IU/ml」作為T2氣喘病人之標準 35
4.3.2第二組「以血清Total IgE > 100 IU/ml且血液Eosinophil count >140/µl」作為T2氣喘病人之標準 36
4.3.3第三組「以血清Total IgE > 100 IU/ml 或血液Eosinophil count >140/µl」作為T2氣喘病人之標準 38
4.3.4第四組「以血液Eosinophil count >150/µl」作為T2氣喘病人之標準 39
4.3.5第五組「以血液Eosinophil count >300/µl」作為T2氣喘病人之標準 41
4.3.6第六組「以血液Eosinophil count > 400/µl」作為T2氣喘病人之標準 43
4.3.7第七組「以血清Total IgE > 100 IU/ml 或血液Eosinophil count >300/µl」作為T2氣喘病人之標準 44
4.3.8 綜合整理 46
4.3.9 血液Eosinophil count 跟血清Total Ig相關性分析 47
第五章 結論與未來發展 48
5-1 結論 48
5-2 研究限制 48
5-3未來研究方向 49
附錄表 50
附錄一、氣喘治療藥物表 50
附錄二、國際疾病分類碼第九版&第十版 51
附錄三、國泰綜合醫院人體試驗審查委員會核准函 (案號: CGH-P110048) 52
附錄四、 成人與青少年氣喘診療指引 53
附錄五、新竹國泰醫院氣喘吸入劑品項 55
英文文獻 56
中文文獻 60

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