소아 천식환아에서 흡입용 fluticasone 및 tulobuterol의 병합치료와 두 배 용량 흡입용 fluticasone 치료의 효과 및 안전성 비교에 대한 다기관 연구
An open, Multi center, Randomized, Parallel Group Study to Compare the Effectiveness and Safety of Fluticasone Plus Tulobuterol Versus Twice the Dose of Fluticasone Alone in Asthmatic Children
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목 적 : 소아 천식 치료에서 흡입용 스테로이드의 용량을 증가시키는 것과 기존 용량의 흡입용 스테로이드에 기관지 확장제인 tulobuterol을 추가하는 것을 효과와 안전성 면에서 비교해 보고자 하였다. 방 법 : GINA 가이드라인에 따라 2단계(경증 지속성) 천식으로 진단받고 하루 50-100 µg의 저용량 흡입용 스테로이드(fluticasone)로 유지치료를 받고 있는 4-8세의 소아천식 환자 중에서 step-up 치료를 고려하는 53명을 대상으로 하였다. 이들을 무작위로 기존의 흡입용 fluticasone 용량(50-100 µg/일)에 tulobuterol (Hokunalin® patch 1 mg)을 추가한 군 (Flt＋Hk군)과 흡입용 fluticasone을 두 배 용량(100-200 µg/일)으로 늘린 군 (Flt군)으로 나누었다. 이들을 각각 4주간 치료하였으며 이후 치료의 효과와 부작용을 보기 위해 추적관찰하였다. 두 군에서 치료시작전과 치료 4주 후의 천식 증상 점수의 변화, 일중 최대호기유속의 변화, 야간 증상으로 잠을 깬 횟수, 증상완화제의 사용 횟수를 비교하였고 치료에 대한 보호자의 전체적인 만족도, 이상 반응의 횟수를 조사하였다. 결 과 : 추적관찰이 된 환자는 Flt＋Hk 군, Flt 군 각각 24명이었다. 치료시작전과 치료 4주 후 두 군간의 전체적인 천식증상점수 변화는 Flt＋Hk 군에서 -0.01±0.24 , Flt 군에서 -0.05±0.17로 두 군 간에 통계적으로 유의한 차이는 없었다.(P= 0.54) 아침 최대호기유속의 평균변화와 저녁 최대호기유속의 평균 변화는 통계적으로 큰 차이를 보이지 않았다.(P=0.83, P=0.83) 야간 증상으로 잠을 깬 횟수나 증상완화제의 사용 횟수, 치료에 대한 보호자의 전체적인 만족도도 두 군 간에 차이가 없었다.(P=0.17, P=0.32, P=0.63) 치료 중의 이상 증상의 경험 빈도 역시 통계학적으로 유의한 차이를 보이지 않았다.(P=1.00) 결 론 : 소아천식환아에서 흡입용 fluticasone propionate및 tulobuterol의 병합치료는 두 배 용량의 흡입용 fluticasone propionate 단독치료만큼 효과가 있으며 안전성도 비슷한 것으로 나타났다. 스테로이드 치료에 대한 거부감이나 잠재적 부작용에 대한 두려움을 가지고 있는 환자에서 흡입용 스테로이드의 용량을 늘리는 치료에 대한 대체치료로 tulobuterol의 병합치료를 고려할 수 있겠다.
Abstract
Purpose : We aim to compare the effectiveness and safety of fluticasone propionate (Flt) plus tulobuterol (Hk) versus high-dose Flt alone in controlling asthma in children. Methods : Fifty three children aged 4 to 8 years, who were diagnosed with mild persistent asthma and underwent maintenance therapy with a low dose of inhaled corticosteroid (Flt) of 50-100 µg/day were randomized to receive Flt plus Hk (Hokunalin® patch 1 mg, Abbott Japan, Tokyo, Japan), or Flt alone at twice the dosage. Patients underwent new treatment for 4 weeks. Asthma symptom scores, mean changes in morning and evening peak expiratory flow (PEF), the frequency of night awakenings, the use of reliever medication, caregiver's overall satisfaction and safety were evaluated and compared in each group. And they were followed-up again 4 week after treatment course for the evaluation of treatment- emergent adverse event (TEAE). Results : No significant difference was found between the groups in terms of mean changes in the morning and evening PEF, the frequency of night awakening, the use of rescue medication and caregiver's overall satisfaction (P=0.83, P=0.83, P=0.17, P=0.32 and P=0.63). Furthermore, no statistically significant difference was observed between 2 groups in the incidence of any TEAE (P=1.00). Conclusion : This study demonstrated that a combination of Flt and Hk was as effective as a high-dose Flt therapy in the management of mild persistent asthma in children. The results of this study suggest that tulobuterol add-on therapy can be considered as a reasonable substitute to an increase in the dosage of steroid in the patients with steroid-phobia and it might be used to reduce the risk of high dose steroid therapy.
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