소아 기관지 천식 환아에서 발열과 기도 감염이 Theophylline 대사에 미치는 영향에 대한 연구

이영진(Young Jin Lee),오지섭(Ji Sub Oh),윤운기(Woon Ki Youn),전성실(Sung Sil Chun),조혜영(Hae Young Cho),차혜리 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 1996 소아알레르기 및 호흡기학회지 Vol.6 No.1

N/A Theophylline is widely used in pediatric patients for the treatment of asthma. To achieve adequate bronchodilation and avoid side effect, it is generally accepted that the serum theophylline concentration should be maintained between 10 and 20 ㎍/ml. Clinical effectiveness and toxicity are clearly related to some factors which might alter theophylline pharmacokinetics. Fever or respiratory infection, although it seems to be elevated serum level of theophylline, conflicting reports still appear in journals. Thus we studies retrospectively theophylline clearance, serum drug concentration(SDC), half life, volume distribution in 132 asthmatic children who were admitted to our hospital and received intravenous aminophylline and oral theophylline and tried to reveal the effect of fever or respiratory infection. The results are as follows; 1) In febrile children between 6month and 1 year old, there was no difference in theophylline serum concentration, half life, volume distribution, clearance, 2) In febrile respiratory infection children between 6month and 1 year old, there was no difference in theophylline serum concentration, half life, volume distrbution, clearance. 3) In febrile children, febrile respiratory children over 1 year old, theophylline serum concentration was significantly increased, volume distribution were significantly lower than without febrile, febrile respiratory infection. But, there was no difference in theophylline half life and clearance. As a result, it is suggested that fever, may decrease theophylline volume distribution and increase theophylline serum concentration.

흡입용 천식 치료제 사용후 발생한 역설적 기관지 수축에 미치는 Benzalkonium Choloride 의 영향

이영진(Young Jin Lee),오지섭(Ji Sub Oh),정종원(Jong Won Jung),차혜리(Hye Ri Cha),윤운기(Un Ki Yoon) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 1997 소아알레르기 및 호흡기학회지 Vol.7 No.1

목 적 : 최근 들어 기관지천식 환아들의 치료에 흔히 사용되는 흡입용 천식 치료제의 홉입후 역설적으로 기관지 수축이 일어나서 천식 중상이 악화되는 예들이 보고되고 있다. 저자들은 이 역설적인 기관지 수축의 원인이 흡입 치료제에 들어 있는 첨가 보존제인 benzalkonium chloride에 의한 것이라는 가설 하에 본 연구를 시행하였다. 방 법 : 현재 왈레스 기념 침례병원의 알레르기 클리닉에서 추적 관리 중인 만 4세 이상의 안정된 기관지천식 환아 30명을 대상으로 benzalkonium chloride가 포함된 salbutamol 제제인 Ventolin과 benzalkonium chloride가 포함되지 않은 salbutamol 제제인 Respolin autohaler를 흡입하고 각각 흡입 전과 흡입 후의 FEV_1(% Predicted)을 상호 비교하였다. 결 과: 1) 안정 상태에서 기초 검사로써 시행한 폐기능 검사치는 Ventolin 흡입군에서 FEV_1이 73±10(% predicted), Respolin autohaler 흡입군이 74±10(% predicted)으로 두 군간에 유의한 차이는 없었다. 2) Ventolin 흡입군에서는 대상 30명중 9명(30%)에서 FEV_1의 감소를 보였으며 Respolin autohaler 흡입군에서는 30명중 1명(3.3%)에서 FEV_1의 감소를 보여, FEV_1의 감소를 보인 비율은 Ventolin 흡입군에서 Respolin autohaler 흡입군에 비해 유의성 있게 높았다(p<0.005, 단측검종). 3) Ventolin과 Respolin autohaler 흡입후 기초 검사시보다 FEV_1이 감소하거나 변화가 없었던 경우를 제외한 나머지 경우에서 FEV_1의 증가 정도는 Ventolin 흡입군에서 9±7(% predicted), Respolin autohaler 흡입군에서 7±5(% predicted)로 두 군간에 유의한 차이는 없었다. 4) Ventolin에 의한 증상 유발은 FEV_1 10(% predicted) 이상 감소한 4명(13.3%)에서 기침 둥의 중상이 유발되었으나 이들은 자연 소실되었다. 결 론 : 이상의 결과로 기관지천식 환자에서 Ventolin 분무액 흡입시 나타나는 역설적인 기관지 수축 현상의 원인은 benzalkonium chloride에 기인한다고 생각되며, 이러한 기관지 수축 현상을 예방하기 위해서는 benzalkonium chloride가 첨가되지 않은 제제를 사용하거나 또는 benzalkonium chloride가 포함된 제제를 사용할 경우에는 깊은 주의를 요할 것으로 사료된다. Recently, some cases of paradoxical bronchoconstriction with the use of nebulized antiasthmatic respirator solutions have been reported. This study was performed to determine whether benzalkonium chloride, contained in several antiasthmatic respirator solutions as a preservative, may cause paradoxical bronchoconstriction. This was accomplished by comparing the FEV1 change after Ventolin (benzalkonium containing salbutamol) nebulization with the FEV1 change after Respolin autohaler (benzalkonium free salbutamol) inhalation within the same patient. This study consisted thirty patients with stable asthma who regularly attend the allergy clinic at Wallace Memorial Baptist Hospital. Patients were excluded from the study if they had respiratory disease or were taking any other medications. The results are as follows 1) The baseline FEV1 in the Ventolin group was 73±10(% predicted) and 74 10(% predicted) in the Respolin autohaler group, showing no statistical difference in baseline FEV1 between the two groups. 2) FEV1 was decreased in 9 subjects(30%) after Ventolin nebulization and in 1 subject(3.3%) after Respolin autohaler inhalation, showing that the incidence of FEV 1 fall was higher in the Ventolin group than in the Respolin autohaler group(p<0.005, one-tailed t-test). 3) Considering the cases with increased FEV1 after inhalation, FEV1 was increased by 9±7 (% predicted) in the Ventolin group and 7±5(% predicted) in the Respolin autohaler group, suggesting that bronchodilator effects of both medications are similar. 4) Mild coughing occurred in 4 subjects(13.3%), and mild chest tightness in 1 subject(3.3%) in the Ventolin group. These symptoms resolved without any treatment. No side effects were reported by subjects in the Respolin autohaler group. In conclusion, these results strongly suggest that the paradoxical bronchoconstriction occurring with nebulized antiasthmatic respirator solutions is due to the ingredient benzalkonium chloride. Therefore, we recommend that a benzalkonium free salbutamol product should be used for asthmatic patients, or if a product such as Ventolin which contains benzalkonium chloride must be used, we recommend that it should be administered cautiously.

소아 기관지 천식 환아에서 Prednisolone 이 Theophylline 의 대사에 미치는 영향에 관한 연구

정혜영(Hyea Yeong Chung),이희정(Hee Jung Lee),윤운기(Un Ki Youn),오지섭(Ji Sub Oh),류환선(Hwan Seon Ryu),손기호(Kie Ho Sohn),(Charies D . Sands) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 1993 소아알레르기 및 호흡기학회지 Vol.3 No.1

N/A Theophylline is widely used in pediatric patients for the treatment of asthma and neonatal apnea. To achieve adequate bronchodilation and avoid toxicity, it is generally accepted that the serum theophylline concentration should be maintained between 10 and 20㎍/ml. Concentrations greater than 20㎍/ml are associated with an increased incidence of toxicity. Clinical effectiveness and toxicity are clearly related to the serum concentrations. Thus, it is important to understand factors which might alter theophylline pharmacokinetics. Prednisolone has been reported to both increase and decrease theophylline serum concentrations. Clinical experience at our hospital (one case) suggested that there might be an interaction between prednisolone and theophylline that can potentially results in clinically significant changes in theophylline serum concentrations. Thus, we studied eleven asthmatic children, who were admitted to our hospital and received oral sustained release theophylline and prednisolone. The mean serum theophylline concentration of single therapy group (phase 1) was 8.10㎍/ml and of concomitant administered prednisolone group (phase 2) was 8.39㎍/ml. On basis of serum theophylline concentrations, we had taken the volume of distribution (Vd), half life (t1/2) and calculated clearance (Cl), in each of phase 1 and 2. The mean clearance of phase 1 was 67.37ml/㎏/hr and of phase 2 was 67.85ml/㎏/hr. The difference between mean serum theophylline concentration and clearance in the single therapy group (phase 1) compared with concomitant administered prednisolone therapy group (phase 2) was not statistically significant. (p>0.05) This suggests that prednisolone does not affect the metabolism of theophylline and does not alter serum concentration of theophylline.

한국 소아 기관지 천식 환아에서 연령에 따른 Theophylline 의 대사 변화에 관한 연구

이희정(Hee Jeong Lee),조혜영(Hye Young Cho),윤운기(Un Ki Youn),오지섭(Ji Sub Oh),류환선(Hwan Seon Ryu),손기호(Kie Ho Sohn),(Charles D . Sands) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 1995 소아알레르기 및 호흡기학회지 Vol.5 No.1

N/A Theophylline is widely used in Korean pediatric patients in the treatment of asthma. To achieve adequate bronchodilation and avoid side effects , it is generally accepted that the serum theophylline concentration should be maintained between 10 and 20mcg/ml . Concentrations greater than 20mcg/ml are associated with an increased incidence of toxicity . Clinical effectiveness and toxicity are clearly related to understand factors which might altel theophylline pharmacokinetics . Age has been reported as a factor which might alter theophylline clearance. Thus we studied 287 asthmatic children who were admitted to our hospital and received intravenous aminophylline and oral theophylline. The average total clearance of theophylline was 30.00ml/kg/h in the infants under 6 months old and 53.14ml/kg/h in the infants between the age of 6 and 12 months . The average total clearance of theophylline was significantly increased in infants above 6 months old(p<0.001) . The average total clearance of theophylline of the children aged between 1 to 12 years was 65.77ml/kg/h and no significant difference according to age was noticed in this group . These suggest that age may be a factor which affects clearance of theophylline under 12 months old .

개인용 컴퓨터를 이용한 알레르기 질환 환자관리의 전산화

최경희(Kyeong Hee Choi),최덕철(Deok Cheol Choi),윤운기(Un Ki Youn),오지섭(Ji Sub Oh),황호연(Ho Yeon Hwang),김중석(Jung Suck Kim) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 1996 소아알레르기 및 호흡기학회지 Vol.6 No.2

목적 : 알레르기 질환은 증상이 반복되고 치료가 장기화되는 만성 질환으로 환자의 관리에 있어 그 내용이 방대하고, 지속적인 추적 관리를 요한다. 이에 저자들은 현재 병원에서 외래를 동해 추적관리 중인 알레르기 환자의 진료 정보 관리를 위한 프로그램을 개발하여 이를 기술하였다. 방법 : 이 프로그램은 100㎒, 16MB, 펜터엄 프로세스의 IBM 호환 컴퓨터를 이용, Windows 95운영체계 하에서 Access 2.0의 data base와 Visual Basic 4.0 언어로 작성되었다. 철과 : 프로그램의 구성은 크게 자료관리, 코드관리, 출력관리 및 조회관리로 나뉘어지고 자료관리의 내용중 핵심은 증상일기 및 증상일기 그래프의 작성이며 그외에 환자 신상관리, 병력관리, 소견관리 부분이 있다 코드 관리는 진단 및 주소관리로 구성되며 여기서 관리하는 내용은 신상관리 및 병력관리 화면에서 입력없이 바로 이용할 수 있다. 또한 환자 특정인의 특정 병력 내용 확인이나 다수의 유사 내용연구 및 역학 연구시에는 조회관리를 통해 사용자 자유자재로 진료정보에 빨리 접근할 수 있다. 결론 : 이 프로그램은 환자의 접수에서부터 진료까지에 이르는 시간을 단축할 수 있고, 현재까지의 환자관리 내용과 현재 환자의 상태를 한 눈에 파악할 수 있어 사용자의 입장에서는 환자관리가 쉽고 정확하며 시간이 단축되고, 환자 및 보호자의 입장에서는 자신의 질병상태를 가시화할 수 있어, 그 관리에 미치는 효율성 이 크다고 생각된다. The authors developed a computer program for easy management of the allergic patient, who are being administered outside the hospital. The program was 100 ㎒, 16MB and IBM mutual response computer of pentiumprocess. and was written with data base in Access 2.0 and Visual Basic 4.0 language under the Windows 95 operating system. The program have four main sections-material administration, code administration,output administration, and reference administration. Material administration involves personal check up, disease record check up, daily symptoms check up graph and opinion check up. In code administration section, the users checks the diagnosis code and residence code, the contents of which can be immediately used in personal check up and disease record check up scene. They can have advantages of access to the goal by using referance administration. When the users want to identify some specific contents of patients and to study similar conditions of many people. The program shortens the time which is needed from patient`s reception to his medical care, so the user has advantage of easy check-out his up-to condition and of not wast of time, and in patient`s and his helper`s places, he has advantage of looking over his disease record with his own eyes. We think there are many shortcomings in this program and we will have to add many other complex functions that reveals in the course of studying and applying to everyday`s medical care.

보존제 Benzalkonium 에 의한 역설적인 기관지 수축과 Cromolyn sodium 의 그 보호 효과

주현기(Hyun Ki Joo),최덕철(Duk Cheol Choi),윤운기(Woon Ki Yoon),오지섭(Ji Sub Oh),손기호(Kie Ho Son),차혜리(Hye Ri Cha) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 1995 소아알레르기 및 호흡기학회지 Vol.5 No.2

N/A Benzalkonium chloride has been used as a preservative in some antiasthmatic respirator solutions but is known to cause bronchoconstriction in asthmatic subjects. We studied the protective effect of cromolyn sodium on the bronchoconstriction of benzalkonium chloride by comparison of baseline pulmonary function (FEV1) with those after ventolin nebulization and mixed ventolin and clesin nebulization. Subjects were all from the Allergy Clinic of Wallace Memorial Baptist Hospital and free of respiratory disease and medication, 63 stable asthma patients. The results are as follows; 1) The falls in FEV1 were seen in 20 subjects (31.7%), over 10 (%predicted) falls in FEV1 in 7 subjects (11.1%) and over 20 (%predicted) falls in FEV1 in 4 subjects (6.3%) after ventolin nebulization. 2) Symptoms were provoked in 9 subjects (14.2%) as coughing. Mild dyspnea or chest tightness were seen in 2 subjects (3.1%) but these were solved within 20-30 minutes. 3) Protective effect with cromolyn sodium: increases in FEV1 (%predicted) were 7.7 after ventolin with clesin (0.4 cc) and 9.4 after ventolin with clesin (0.8 cc) nebulization than ventolin nebulization only. There was significant increase in FEV1 in ventolin with clesin than ventolin nebulization only. 4) Changes in protective effect depending on the doses of cromolyn sodi um: in all subjects, increases in FEV1 (%predicted) were 7.7 in clesin 0.4 cc group and 9.4 in clesin 0.8 cc group and in subjects with fall in FEV1, increases in FEV1 (%predicted) were 14.1 after ventolin with clesin (0.4 cc) and 17.5 after ventolin with clesin (0.8 cc) nebulization than ventolin nebulizationonly. There was no significant difference in FEV1 between clesin 0.4 cc and 0.8 cc groups. 5) Protective effect of cromolyn sodium on the degree of falls in FEV: increase in FEV1 (%predicted) after ventolin with clesin than ventolin nebulization in subjects with fall in FEV1 over 20 and others were 36, 6.6 in clesin 0.4 cc group and 36.5, 6.9 in clesin 0.8 cc group. There was significant increase in FEV1 in subjects with fall in FEV1 20 than others. So, we recommend that benzalkonium free salbutamol product should be used or cromolyn sodium should be added in ventolin respirator solution to protect the possibility of paradoxical bronchoconstriction by benzalkonium chloride and for the synergistic effect of salbutamol and cromolyn sodium

1 세 미만의 한국 소아에서 Theophylline 의 치료 용량과 투여 공식에 관한 연구

최덕철(Deok Cheol Choi),정영혜(Young Hye Jung),윤운기(Un Ki Youn),오지섭(Ji Sub Oh),박연주(Yeun Ju Park),차혜리(Hye Ri Cha),(Charles D Sands) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 1997 소아알레르기 및 호흡기학회지 Vol.7 No.1

목 적 : Theophylline의 제거는 신생아기에 아주 늦으며 영아기를 지나면서 점점 빨라진다. 연구에 의하면 한국의 영아에서 외국의 영아에 비해 theophylline의 청소율이 낮음을 알 수있다. 이에 따라 한국 영아의 특성에 맞는 theophylline의 투여 공식이 필요할 것으로 사료된다. 대상 및 방법 : 1993년 1월부터 1995년 12월까지 기관지천식으로 진단된 1세 미만의 환아중 theophylline의 대사에 영향을 끼칠 수 있는 경우를 제외한 111명의 환아를 대상으로 조사하였다. 이에 theophylline의 유효 혈중 농도는 5-15㎍/m1로 정하였으며 이는 National Institutes of Health Expert Panel Recommendations을 참고로 하였다. 유효 혈중 농도에 도달된 99명외 환자를 대상으로 나이별 유효 혈중 농도에 도달할 때의 투여 용량을 그래프로 그렸으며, 이를 단순 선형 회기 분석을 이용하여 투여용량 공식을 산출하였다. 또한 1세이전에 2회 이상 혈중 농도를 측정한 7명의 환아를 대상으로 theophylline 반감기의 변화를 측정하였다. 결 과 : 나이와 유효 혈중 농도 5-15㎍/m1률 유지하기 위해 투여한 용량과의 관계를 단순 선형 회기 분석에 의해 다음과 같은 공식을 산출하였다. Dose (㎎/㎏/day) = 5.57 + 0.14 × (times age in weeks) (r= 0.67, p<0.0001) 동일한 환아에서 연속적인 theophylline의 혈중 반감기를 측정하여 감소됨을 확인하였다(Fig, 3). Theophylline으로 치료를 받은 1세 미만의 기관지천식 환아에서 혈중 농도 10-l2㎍/ml에서 75%에서 부작용을 나타내었고 유효 혈중 농도의 범위는 대개 5-10㎍/ml로 확인 되었다. 결 론 : 한국의 영아에서늘 외국의 영아에 비해 theophylline의 대사에 차이가 었고 이러한 차이에 대처하기 위해, 유효 혈중 농도의 범위가 비교적 좀은 theophylline의 투여에 대해서 한국 영아에 맞는 새로운 투여공식이 필요하겠으며 더 나아가 한국 환아의 독성을 고려한 대사와 부작용 및 영향을 주는 인자에 대한 연구가 좀 더 이루어져야 할 것으로 사료된다. It has been reported that theophylline clearance is lower in Korean infants than in Americans, suggesting that dose requirements for theophylline in Korean infants will be lower than those in Americans. Therefore, we reviwed patients charts retrospectively to formulate the new theophylline dosing equation appropiate to Korean infants. We reviewed patient charts of 111 asthmatic infants who received intravenous aminophylline and oral theophylline in Wallace Memorial Baptist Hospital. We set the therapeutic serum concentration at 5-15㎍/ml in Korean infants based on response rate to theophylline therapy, which is supported by National Institute of Health Expert Panel Recommendations. Doses required to achieve a therapeutic serum concentration increased with age. The mean dose among the infants less than 4 months of age was 5.78±1.64 ㎎/㎏/day and increased to 10.12±1.78㎎/㎏/day after 8 months (p<0.0001). The relationship between age and dosage requirements can be expressed by the least squares determination of the linear regression : Dose (㎎/㎏/day) = 5.57 + 0.14 × (age in weeks). The coefficient of correlation for this relationship is 0.67(p<0.0001). Half-lives of elimination among the infants studied correspondingly decreased with age. In conclusion, this study showed that the relationship between age and dosage requirements in Korean infants may be different from those in Americans. Therefore, we strongly suggest that it is required to formulate a new theophylline dosing equation appropriate for Korean infants through well-designed prospective studies.

韓國 健康 學童에서 調査한 蛋白質

吳賢秀,金義卿,吳智燮,姜眞無 金原出版 1975 小兒科 Vol.16 No.9

進行性 筋萎縮症의 臨床的 觀察

蔣信炯,趙在寶,吳智燮,琴東爀,申東鶴 金原出版 1974 小兒科 Vol.15 No.10

先天性 腸閉鎖症

金義卿,吳賢秀,吳智燮,申東鶴 金原出版 1975 小兒科 Vol.16 No.12