Montelukast降低罹患細支氣管炎嬰兒哮喘再發風險

作者：Deborah Brauser  
出處：WebMD醫學新聞

　　March 10, 2010（紐奧良）－根據一項韓國研究結果，罹患呼吸融合病毒（RSV）感染後細支氣管炎的嬰兒，接受montelukast（Singular，默克藥廠）治療顯示，嗜伊紅性球去顆粒化作用減少，且哮喘再發事件較少。
　　
　　來自大韓民國首爾Inje醫院Paik醫院過敏中心與兒童及氣喘部門的Hyo-Bin Kim醫師在美國過敏、氣喘與免疫醫學會（AAAAI）2010年年會壁報展示會中表示，這個領域是很重要的，因為目前並沒有細支氣管炎確切、直接的治療；我們只有間接治療。
　　
　　Kim醫師表示，我們認為白三烯素受體拮抗劑可以透過降低去顆粒化作用與避免哮喘而對病理生成有重大影響。
　　
　　【EDN濃度、哮喘降低】
　　研究者們收納200位年齡介於6至24個月的嬰兒，在這些嬰兒中，150位因為急性RSV細支氣管炎首次發作住院，而被隨機分派接受4 mg的montelukast顆粒（共79位）、或是相對應的安慰劑（共71個月）治療3個月。另有50位健康成人被納入這項研究的控制組。
　　
　　主要試驗終點為血清嗜伊紅性球相關神經毒素（EDN）濃度；12個月之間再次哮喘發作為次要終點。
　　
　　Kim醫師指出，在3 個月結束時的研究結果顯示，相較於試驗前，安慰劑組的EDN濃度顯著上升（P<0.0001），且治療組的濃度顯著降低（P<0.01）。
　　
　　她附帶表示，因此，此時兩組之間的EDN濃度顯著不同（P<0.0001），且在12個月的後續追蹤期間都維持這個差異。
　　
　　相較於安慰劑組，治療組在12個月的後續追蹤期間，累積哮喘再發次數顯著較少（P=0.039）。
　　
　　Kim醫師總結，我想對罹患RSV細支氣管炎的嬰兒、或是出生不久的嬰兒，該項治療顯示在1年時，或許2年時，哮喘發作次數是降低的。我們必須避免哮喘演變為氣喘，這可能以montelukast治療達成。
　　
　　她表示，研究者們希望繼續追蹤這些試驗病患，以評估長期效益。
　　
　　【不足以改變臨床執業】
　　加州沙加緬度Capital過敏與呼吸疾病中心的兒童胸腔學家與過敏學家Bradley Chipps醫師表示，我知道還有另外3篇研究已經使用montelukast治療細支氣管炎，其中1篇結果是正面的，另外2篇是負面的。
　　
　　他表示，根據他們的發現，montelukast不建議作為RSV引發細支氣管炎病患的治療。這項發表在AAAAI的研究有非常有趣的觀察，但是這並未提供這個藥物使用於這個族群的理由。
　　
　　未參與這項研究的Chipps醫師結論，這證實免疫現象確實發生，但這並不一定轉化為這個疾病臨床進程的變化。
　　
　　這項研究部分由韓國研究基金會贊助，部分由默克研究者發起的研究計畫經費贊助。Kim醫師與Chipps醫師表示已無相關資金上的往來。


Montelukast Reduces Recurrent Wheezing in Infants With Bronchiolitis

By Deborah Brauser
Medscape Medical News

March 10, 2010 (New Orleans, Louisiana) — Infants with postrespiratory syncytial virus (RSV) bronchiolitis who are treated with montelukast (Singulair, Merck) show reduced eosinophil degranulation and fewer recurrent wheezing episodes, according to a new study from Korean investigators.

"This area is important because there is currently no exact, direct treatment for bronchiolitis; we only have indirect treatment," said Hyo-Bin Kim, MD, from the Allergy Center and Department of Pediatrics and Asthma at Inje University Paik Hospital in Seoul, Republic of Korea, during a poster presentation here at the American Academy of Allergy, Asthma and Immunology (AAAAI) 2010 Annual Meeting.

"We think this leukotriene-receptor antagonist can have an important effect on the pathogenesis by decreasing degranulation and preventing wheezing," said Dr. Kim.

EDN Levels, Wheezing Decreased

The investigators enrolled 200 infants between the ages of 6 and 24 months. Of these, 150 who were hospitalized with their first episode of acute RSV bronchiolitis were randomized to receive either a 4?mg dose of montelukast granules (n?= 79) or a matching placebo (n?= 71) for 3 months. A total of 50 healthy control subjects were also enrolled in the study.

The primary end point was serum eosinophil-derived neurotoxin (EDN) levels; recurrent wheezing over 12 months was a secondary outcome.

Findings at the end of 3 months showed significantly elevated EDN levels for the placebo group (P?< .0001) and significantly decreased levels for the treatment group (P?< .01), "compared with their initial levels," reported Dr. Kim.

"As a result, EDN levels between the 2 groups significantly differed [P?< .0001] at this point and remained so for the entire 12-month follow-up period," she added.

The treatment group also had significantly fewer cumulative recurrent wheezing episodes at 12 months (P?= .039) than the placebo group.

"We think that for infants, very young infants, who suffer from RSV bronchiolitis, [this treatment] can show decreased wheezing for 1, maybe 2, years," summarized Dr. Kim. "We have to prevent the wheezing to keep it from going into asthma, which could possibly be accomplished with montelukast treatment."

She reported that the investigators hope to continue following the study patients to evaluate long-term effects.

Not Enough to Change Clinical Course

"There have been 3 [other] trials I know of that have looked at bronchiolitis treated with montelukast, with 1 of them being positive and 2 being negative," said Bradley Chipps, MD, pediatric pulmonologist and allergist at Capital Allergy Respiratory Disease Center in Sacramento, California.

"Based on their findings, montelukast is not recommended as therapy in patients with RSV-induced bronchiolitis," he noted. "This study [presented at AAAAI] has interesting observations but it does not give a reason to use this drug in this patient population."

"It does show that there is an immunologic phenomenon that occurs but it doesn't translate into a change in the clinical course in this disease," concluded Dr. Chipps, who was not involved with the study.

This study was funded in part by grants from the Korean Research Foundation and from the Investigator-Initiated Studies Program of Merck. Dr. Kim and Dr. Chipps have disclosed no relevant financial relationships.

American Academy of Allergy, Asthma and Immunology (AAAAI) 2010 Annual Meeting: Abstract?255. Presented February?28, 2010.