• Clinical and Experimental Pediatrics
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• 제49권6호
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• pp.581-588
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• 2006

Asthma is a chronic inflammation of the airway associated with increased bronchial hyperresponsiveness that leads to recurrent episodes of cough, wheezing, breathless, chest tightness. According the recent studies, repeated airway inflammation leads to structural changes so called 'airway remodeling' and associated with decreased pulmonary function. Airway remodeling begins form the early stage of asthma and the early diagnosis and management is very important to prevent airway remodeling. Medication for asthma can be classified into acute symptom reliever and chronic controller. Short acting beta2 agonist is a well-known reliever that reduced asthma symptoms within minutes. Controllers should be taken daily as a long-term basis to control airway inflammation. Inhaled corticosteroid(ICS) is the most effective controller in current use. However, in some patients ICS monotherapy is not sufficient to control asthma. In those cases, other medications such as long acting beta2 agonist, leukotriene modifier or sustained-release theophylline should be added to ICS, which called Add-on-Therapy. Combination inhaler devices are easy to use. Oral leukotriene modifier has a good compliance especially in children. Finally, as asthma is a chronic disease, the development of on-going partnership among health care professionals, the patients, and the patients' family is necessary for the effective management of asthma.

• Tuberculosis and Respiratory Diseases
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• 제81권3호
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• pp.198-215
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• 2018

Bronchodilators provide improvements in lung function and reductions in symptoms and exacerbations, and are the mainstay of pharmacological management of chronic obstructive pulmonary disease (COPD). The Global Initiative for Chronic Obstructive Lung Disease strategy recommends the use of a combination of long-acting ${\beta}_2-agonist$/long-acting muscarinic antagonists (LABA/LAMA) as the first-line treatment option in the majority of symptomatic patients with COPD. This review provides an indirect comparison of available LABA/LAMA fixed-dose combinations (FDCs) through discussion of important efficacy and safety data from the key literature, with the objective of providing physicians with a framework for informed decision-making. LABA/LAMA FDCs provided greater benefits compared with placebo and similar or greater benefits compared with tiotropium and salmeterol/fluticasone in improving lung function, dyspnea, health-related quality of life, reducing rescue medication use and preventing exacerbations, although with some variability in efficacy between individual FDCs; further, tolerability profiles were comparable among LABA/LAMA FDCs. However, there is a disparity in the amount of evidence generated for different LABA/LAMA FDCs. Thus, this review shows that all LABA/LAMA FDCs may not be the same and that care should be taken when extrapolating individual treatment outcomes to the entire drug class. It is important that physicians consider the efficacy gradient that exists among LABA/LAMA FDCs, and factors such as inhaler devices and potential biomarkers, when choosing the optimal bronchodilator treatment for long-term management of patients with COPD.

• 말소리와 음성과학
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• 제2권2호
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• pp.101-108
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• 2010

An inhaled salbutamol and salmeterol for chronic obstructive pulmonary disease(COPD) and asthma have been used worldwidely. But there has been few study about the voice change evoked from the post-medicine effect. To evaluate the voice influenced of short-acting and long-acting ${\beta}_2$-agonists, two experiments were carried out: one was salbutamol experiment 1 with eight patients, the other was salmeterol experiment 2 with six patients. Experiment 1 was made of two stages: premedication & postmedication. Experiment 2 was four stages: stageI was premedication, stageII was postmedication & pregaggling, stageIII was postmedication & postgaggling(100 ml with water), and stageIV was postmedication & 30 minutes later. Measured parameters were F0, F0_SD, Jitter_rap, Shimmer_apq11, HNR, BW(1, 2, 3), Intensity, and H1-H2. The mean data collected from 3 repetitions each was statistically analyzed by Wilcoxon signed rank test for experiment 1 and repeated measures ANOVA for experiment 2. In experiment 1, significant differences were found in the Jitter_rap(Z= -2.10, p=0.036). The findings indicated that the postmedicated voice was worse than premedicated voice. In experiment 2, there wasn't significant difference, but values of parameters related to voice quality(Jitter_rap, Shimmer_apq11, HNR, and H1-H2) showed changes toward stageⅣ, that is, the voice quality was worse under medication.

• Molecules and Cells
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• 제37권8호
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• pp.585-591
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• 2014

The ${\beta}_2$ adrenergic receptor (ADRB2) is a G protein-coupled transmembrane receptor expressed in the human respiratory tract and widely recognized as a pharmacological target for treatments of asthma and chronic obstructive pulmonary disorder (COPD). Although a number of ADRB2 agonists have been developed for use in asthma therapy, indacaterol is the only ultra-long-acting inhaled ${\beta}_2$-agonist (LABA) approved by the FDA for relieving the symptoms in COPD patients. The precise molecular mechanism underlying the pharmacological effect of indacaterol, however, remains unclear. Here, we show that ${\beta}$-arrestin-2 mediates the internalization of ADRB2 following indacaterol treatment. Moreover, we demonstrate that indacaterol significantly inhibits tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced NF-${\kappa}B$ activity by reducing levels of both phosphorylated-IKK and -$I{\kappa}B{\alpha}$, thereby decreasing NF-${\kappa}B$ nuclear translocation and the expression of MMP-9, an NF-${\kappa}B$ target gene. Subsequently, we show that indacaterol significantly inhibits TNF-${\alpha}$/NF-${\kappa}B$-induced cell invasiveness and migration in a human cancer cell line. In conclusion, we propose that indacaterol may inhibit NF-${\kappa}B$ activity in a ${\beta}$-arrestin2-dependent manner, preventing further lung damage and improving lung function in COPD patients.

• 한국임상약학회지
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• 제26권4호
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• pp.298-305
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• 2016

Background: This study is to investigate the prescription patterns and factors related to the number of medications treating chronic obstructive pulmonary disease (COPD) in patients under 65 years old according to GOLD guidelines. Methods: We retrospectively analyzed the medical records of patients aged 40-64 years with a diagnosis of COPD from January to March 2016. Patients were classified by combined assessment of COPD (grades A, B, C, D) using spirometry, exacerbation history, mMRC, and/or CAT results. We analyzed prescribed medications, treatment options and factors related to the numbers of COPD medications. Results: The total number of prescriptions were 251. About 35.5% of patients were classified as GOLD A, 34.2% as GOLD B, 17.1% as GOLD C and 13.2% as GOLD D. Inhaled bronchodilator was prescribed for 86.9% of patients and the most frequent COPD medication was long-acting muscarinic antagonist (LAMA) followed by inhaled corticosteroids/long acting beta agonist (ICS/LABA). The majority of low risk patients (GOLD A/B) were prescribed a monotherapy with LAMA or LABA. For high risk patients (GOLD C/D), combination treatment with ICS+LAMA+LABA was mostly prescribed. The 21.2% of patients in GOLD D received systemic corticosteroid. The average number of medications per prescription was 3.7, and this number increased with increasing COPD grade, COPD duration and lung function reduction ($FEV_1$, $FEV_1/FVC$). Conclusion: Generally high adherence to GOLD guideline recommendations was reported. Given the progressive nature of the disease, results suggest that closer attention to respiratory symptoms for early detection, diagnosis, and appropriate treatment of COPD is warranted.

• Tuberculosis and Respiratory Diseases
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• 제59권2호
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• pp.164-169
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• 2005

연구배경 : ICS/LABA는 천식에서 효과가 입증되었으나 COPD에서는 덜 알려져 있다. 최근 COPD 환자에서 고용량의 ICS/LABA의 사용시 급성악화를 줄인다고 보고되고 있다. 본 연구는 중등도와 고용량의 ICS/LABA사용시 용량에 차이에 따른 COPD의 급성악화를 비교하였다. 방 법 : 2001년 1월 1일부터 2004년 8월 31일 사이에 고대안암병원에 내원하여 진단된 46명의 중등증 이상의 COPD 환자를 대상으로 하였다. flu/sal $250{\mu}g/50{\mu}g$ 하루 2번 사용한 군(A군)과 flu/sal $500{\mu}g/50{\mu}g$ 하루 2번 사용한 군(B군)으로 나누어 1년 기간 동안 급성악화의 횟수 및 입원 횟수, 처음악화까지 걸린 기간을 분석하였다. 결 과 : A 군 26명중 11명에서 급성악화를 경험하였고, 평균 악화 횟수는 0.96회, 입원횟수는 0.15 회였다. B군 20명중 11명에서 급성 악화를 경험하였고 평균 악화 횟수는 1.05회, 입원횟수는 0.30 회였다. 두 군간에 통계적으로 유의한 차이가 없었고 처음악화까지 걸린 시간도 차이가 없었다. 결 론 : 중등증 이상의 COPD 환자에서 ICS 와 LABA 복합제제를 사용 할 때 고농도와 중등도 용량에서 급성 악화에 미치는 영향은 통계적으로 차이가 없었다. 향후 COPD 에서 ICS/LABA 사용시 효과적인 용량에 대한 연구가 좀 더 필요할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제63권4호
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• pp.337-345
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• 2007

연구배경: 천식 치료의 근간을 이루고 있는 흡입용 스테로이드제에 대한 반응은 천식 환자마다 다양하다. 또한, 코르티코스테로이드가 천식의 기도염증에서 중요한 매개체인 류코트리엔을 효과적으로 억제하지 못하는 것으로 보고되었다. 이에 저자들은 흡입용 스테로이드와 지속성 베타2 항진제의 병용요법으로도 증상이 완전히 조절되지 않는 지속성 천식 환자에서 montelukast를 추가하였을 때의 유효성을 평가하고자 하였다. 방법: 4주간의 준비기간을 거쳐서 흡입용 스테로이드와 지속성 베타2 항진제의 병용요법으로도 증상이 완전히 조절되지 않는 지속성 천식 환자 198명을 선정하여 8주 동안 montelukast 10mg 정을 1일 1회 취침 전 복용토록 하였다. ACQ 증상 점수와 $FEV_1%$ 치를 montelukast 치료 전후로 각각 측정하였으며, 치료 후에 환자와 연구자 각각 천식과 비염에 대하여 '호전되었음, 변화없음, 악화되었음' 중의 하나로 평가하도록 하였다. 결과: 8주간 montelukast를 추가한 후 ACQ 증상 점수의 평균 변화량은 -4.8점[95% CI (-5.7,-3.9)]으로, 유의하게 천식 증상이 호전됨을 보였다 (p<0.001). $FEV_1%$치는 증가하는 경향을 보였으나 통계적으로 유의하지는 않았다(p>0.05). 방문 2시점에서 시행한 천식에 대한 환자와 연구자의 종합 평가에서 각각 약 60%의 환자와 연구자가 '개선되었음'으로 평가하였으며(${\kappa}=0.85$), 비염의 종합 평가에서 각각 55%의 환자와 51%의 연구자가 '개선되었음'으로 평가하였다(${\kappa}=0.93$). 결론: 흡입용 스테로이드 및 지속성 베타2 항진제의 병용제제로도 천식증상이 완전히 조절되지 않는 중등증 이상의 지속성 천식 환자에서 류코트리엔 조절제의 추가는 천식의 조절을 향상시킬 수 있다.

• Tuberculosis and Respiratory Diseases
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• 제84권2호
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• pp.96-104
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• 2021

Background: Many chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 ㎍ to indacaterol/glycopyrronium (IND/GLY) 110/50 ㎍ once daily in COPD patients in Korea. Methods: This was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 ㎍ once daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted post-bronchodilator forced expiratory volume in 1 second (FEV₁) ≥50%, post-bronchodilator FEV₁/forced vital capacity <0.7 and smoking history of ≥10 pack-years were included. Eligible patients were randomized in a 1:1 ratio to either IND/GLY or TIO. The primary objective was to demonstrate superiority of IND/GLY over TIO in pre-dose trough FEV₁ at week 12. Secondary endpoints included transition dyspnea index (TDI) focal score, COPD assessment test (CAT) total score, and rescue medication use following the 12-week treatment, and safety assessment. Results: Of the 442 patients screened, 379 were randomized and 347 completed the study. IND/GLY demonstrated superiority in pre-dose trough FEV₁ versus TIO at week 12 (least squares mean treatment difference [Δ], 50 mL; p=0.013). Also, numerical improvements were observed with IND/GLY in the TDI focal score (Δ, 0.31), CAT total score (Δ, -0.81), and rescue medication use (Δ, -0.09 puffs/day). Both treatments were well tolerated by patients. Conclusion: A direct switch from TIO to IND/GLY provided improvements in lung function and other patient-reported outcomes with an acceptable safety profile in patients with mild-to-moderate airflow limitation.

• Tuberculosis and Respiratory Diseases
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• 제80권1호
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• pp.52-59
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• 2017

Background: Inhaled indacaterol (Onbrez Breezhaler), a long-acting ${\beta}_2$-agonist, is approved in over 100 countries, including South Korea, as a once-daily bronchodilator for maintenance and treatment of chronic obstructive pulmonary disease (COPD). Here, we present an interim analysis of a post-marketing surveillance study conducted to evaluate the real-world safety and effectiveness of indacaterol in the Korean population. Methods: This was an open-label, observational, prospective study in which COPD patients, who were newly prescribed with indacaterol (150 or $300{\mu}g$), were evaluated for 12 or 24 weeks. Safety was assessed based on the incidence rates of adverse events (AEs) and serious adverse events (SAEs). Effectiveness was evaluated based on physician's assessment by considering changes in symptoms and lung function, if the values of forced expiratory volume in 1 second were available. Results: Safety data were analyzed in 1,016 patients of the 1,043 enrolled COPD patients receiving indacaterol, and 784 patients were included for the effectiveness analysis. AEs were reported in 228 (22.44%) patients, while 98 (9.65%) patients reported SAEs. The COPD condition improved in 348 patients (44.4%), while the condition was maintained in 396 patients (50.5%), and only 40 patients (5.1%) exhibited worsening of ailment as compared with baseline. During the treatment period, 90 patients were hospitalized while nine patients died. All deaths were assessed to be not related to the study drug by the investigator. Conclusion: In real-life clinical practice in South Korea, indacaterol was well tolerated in COPD patients, and can be regarded as an effective option for their maintenance treatment.

• Tuberculosis and Respiratory Diseases
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• 제44권4호
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• pp.815-821
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• 1997

연구배경 : ${\beta}_2$-수용체에 매우 선택성을 가지고 있는 salmeterol은 작용시간이 길고 부작용이 적어 최근 기관지 천식의 치료에 많이 사용되며 특히 야간성 발작이 있는 환자에서 좋은 효과가 있다고 보고되고 있다. 이에 저자는 경증 또는 중증도의 가역성이 있는 천식 환자에서 salmeterol과 salbutamol을 흡입 투여 하였을 때의 효과와 안정성을 비교 평가하고자 본 연구를 시행하였다. 방 법 : 대상환자 35명을 무작위추출 개방시험 방법으로 salmeterol 투여군과 salbutamol 투여군으로 나누어 시행하였다. 모든 대상환자들은 2주간의 치료 준비동안, 필요한 경우 salbutamol 100g씩 2회를 흡입하는 경우를 제외하고는 어떤 기관지 천식 약제를 금지시켰으며 그 후 6주간의 치료기간을 설정하여 salmeterol 군에서는 salmeterol 50g을 1일 2회, 기상직후와 취침직전에 흡입하도록 하였고, salbutamol군에서는 salbutamol 200g을 1일 4회, 기상직후 부터 4시간 간격으로 흡입하도록 하였다. 그후 2주동안은 규칙적인 흡입제를 중단하고 증상에 따라 salbutamol을 임식적으로 사용하였다. 결 과 : 주간 및 야간 천식 증상 평가에 있어서 salmeterol 치료군이 salbutamol 치료군에 비해 유의 있는 호전이 있었다(p<0.05). 추가 salbutamol 사용횟수나 사용날짜는 주간이나 야간에서 salmeterol 치료군에서 사용횟수 및 사용 날짜를 줄일 수 있었다(p<0.05). 폐기능검사에 있어서 $FEV_1$의 증가율은 2-4주간의 흡입 후에 salmeterol군에서 유의하게 높게 나타났다. Salmererol에 대한 부작용은 일부환자에서 경미한 손떨림이나 두근거림이 있었지만 salbutamol 군과는 차이가 없었으며 치료를 중단한 환자는 없었다. 결 론 : 이상의 실험 결과로 흡입용 salmeterol은 부작용이 비교적 적고 안전하며 효과적임을 알 수 있고, 특히 야간성 발작성 천식에 매우 효과적인 기관지 확장제로 생각된다.