| Abstract: | 近年來，雖然氣喘和過敏性鼻炎被認為是同一種疾病，但是仍有許多疑問無法回答。具有特異性體質的人中，為什麼有些人只產生氣喘的症狀，而其他的人卻產生過敏性鼻炎的症狀呢？具有特異性體質的人，在各種不同過敏病發展過程中，其顯性的表現哪一種因素扮演重要的角色呢？我們提出一個假設認為血管收縮素轉換[angiotensin-converting enzyme(ACE)]基因多型性可能是擔當過敏性鼻炎病童是否會合併氣喘症狀的一個重要角色。
本次研究共收集106位只具有過敏性鼻炎的病童和105位在年齡、性別和種族相一致的過敏性鼻炎同時併有氣喘的病童，此兩組病童都具有相同過敏免疫反應和對相同過敏原敏感，我們也收集了102位年齡、種族相符合且本人及其家族都沒有過敏病之兒童作為對照組；我們採用聚合酵素連鎖反應(PCR)來決定ACE基因型，同時測定血液中IgE和抗原特異性IgE抗體的濃度和eosinophil的數目。結果發現ACE基因多型性中DD基因型出現頻率在過敏性鼻炎合併有氣喘的病童，比只有過敏性鼻炎的病童有較高的出現率[P=0.018 odd ratio(OR)=3.257; (1.222~8.680)]，因此我們認為ACE基因多型性中DD基因型在過敏性鼻炎病童是否發生氣喘症狀扮演一個非常重要的角色。
依據GINA (Global Initiative For Asthma)指引，治療氣喘有許多藥物，包括口服或吸入型乙二型支氣管擴張劑、口服或吸入類固醇、茶鹼、白三烯素受體拮擴劑等。雖然如此，在長期使用藥物，尤其要考慮病童其順從度的問題，因此在效果的評估可能要加以斟酌，而且我們必須再次強調，藥物僅針對氣喘的症狀加以治療，在治療過程中或停藥後可能會再發病。皮下減敏治療的應用已超過80年，同時皮下減敏也是目前主要採用的減敏方法，但是此方法因皮下注射較不方便，且可能會有全身不良反應的副作用風險，因此最近許多研究都嘗試局部給予過敏原的方式：包括經口、鼻腔、舌下和支氣管等路徑。舌下減敏被認為是治療氣喘另一種有價值的療法，因此我們採用雙盲試驗且以安慰劑作對照組，歷經6個月的時間評估舌下減敏對塵過敏病童在臨床上和免疫學上療效的評估。隨機從6-12歲具有輕度到中度氣喘病童，且只有對塵 (D.p., D.f.) 過敏者分成二組，一組接受塵舌下減敏，另一組接受安慰劑，劑量為50/50萃取物，最高劑量介於41824 IR相當於1.7毫克的D.p.和3.0毫克的D.f.過敏原，在治療的整個過程中評估氣喘的症狀和是否給予其他氣喘治療藥物，並在治療前、中、後測量血液中IgE抗體，Eosinophil數目，ECP值、特異性IgE和IgG抗體，同時做皮膚過敏測試。共有20位病童完成本次研究，治療前所有病童在臨床症狀、給予其他氣喘治療藥物、皮膚測試和過敏免疫反應數值，沒有顯著差別。6個月治療之後，治療組在夜間氣喘症狀和特異性IgG抗體(p<0.05)比對照組有顯著差別；而在治療組中，治療後白天氣喘症狀，給予其他氣喘治療藥物，血清IgE抗體，Eosinophil數目，第一秒呼氣容積，夜間峰速計值比治療前有顯著改善，且整個過程中並沒有副作用產生，因此我們認為舌下減敏可能成為治療氣喘另一種方便且有效方法。
Although allergic asthma and allergic rhinitis have recently been considered to be a single disease, many questions remain unanswered. Why do some atopic patients develop asthma symptoms and others develop allergic rhinitis symptoms Which factors play a role in the development of different allergic phenotypes We hypothesized that angiotensin-converting enzyme (ACE) gene polymorphism might play a role in the development of asthma phenotypes in children with allergic rhinitis.
The study sample included 106 children with allergic rhinitis, but no asthma, and 105 age- and gender-matched children with allergic rhinitis and asthma. Subjects of both groups exhibited the same systemic immunologic changes and allergen sensitivities. Controls consisted of 102 healthy children. The ACE genotype was determined by polymerase chain reaction. The serum total immunoglobulin E (IgE) level, allergen-specific IgE sensitivity, and eosinophil count were also measured. The frequencies of the DD genotype were significantly higher in the children with both allergic rhinitis and asthma than in the children with allergic rhinitis but no asthma [P=0.018; odds ratio (OR)= 3.257; (1.222~8.680)]. Results of this study suggest that ACE gene polymorphism DD genotype might play a role in the development of the asthma phenotype in children with allergic rhinitis.
Guidelines from the Global Initiative for Asthma (GINA) mention several medications for the treatment of asthma. These medications include oral and inhaled beta-2 agonists, oral and inhaled corticosteroids, xanthines, leukotriene receptor antagonists, and their combinations. The cases of using long-term pharmacological treatment can nevertheless cause problems of compliance, under the incidences for the efficacy to non-negligible cases. It is crucial to emphasize that pharmacological treatment is only for symptomatic treatment, which the symptoms of the diseases may re-appear during the course of the treatment. Immunotherapy by Subcutaneous injection of increasing doses of allergens has been part of allergy treatment for more than 80 years. The subcutaneous injections of allergens demonstrate the major application of allergen-specific immunotherapy (AIT). As this route of application is inconvenient and occasionally associated with severe systemic adverse effects. Several trials have been conducted with local allergen-specific immunotherapy by ether oral, nasal, sublingual, or bronchial routes. Immunotherapy through sublingual routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6–12 years) with mild to moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D. p.)/D. farinae (D. f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D. p. and 3.0 mg of D. f allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein (ECP), specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (P < 0.05) in the SLIT group compared to the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 second, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (P < 0.05). No severe adverse effects were reported. So we think that sublingual immunotherapy might be more convenient and more effective and an alternative regimen. |
