Efficacy and safety of salmeterol/fluticasone compared with montelukast alone (or add-on therapy to fluticasone) in the treatment of bronchial asthma in children and adolescents: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma.@*METHODS@#A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible.@*RESULTS@#Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC.@*CONCLUSIONS@#SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.@*PROSPERO REGISTRATION NUMBER@#CRD42019133156.

Systematic review and Meta-analysis on efficacy and safety of Liujunzi Decoction combined with Western medicine for stable chronic obstructive pulmonary disease / 中国中药杂志

To systematically review the efficacy and safety of Liujunzi Decoction combined with Western medicine in the treatment of stable chronic obstructive pulmonary disease(COPD). Three English databases and four Chinese databases were systematically searched from the database establishment to April 1, 2020. We screened randomized controlled trial(RCT) according to the pre-determined inclusion and exclusion criteria, then extracted data. Methodological quality of included studies was assessed with Cochrane bias risk evaluation tool. Data were analyzed by using RevMan 5.3. A total of 401 articles were retrieved and finally 17 RCTs were included in this study, involving 1 447 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in reducing traditional Chinese medicine symptom score, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing the grade of modified medical research council(mMRC), Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing COPD assessment test(CAT) score, Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone. In delaying the decline of forced expiratory volume in one second(FEV_1) or % in the expected value, Liujunzi Decoction combined with conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation was superior to conventional Western medicine or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In delaying the decline of ratio of FEV_1 to forced vital capacity(FEV_1/FVC), Liujunzi Decoction combined with conventional Western medicine was superior to conventional Western medicine alone, but there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. In reducing acute exacerbation rate, there was no statistical difference between Liujunzi Decoction combined with Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation and Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation alone. On the other outcome measures of Liujunzi Decoction combined with other Western medicine, Meta-analysis could not be conducted and conclusions due to the inclusion of only one study. In terms of the occurrence of adverse reactions, some studies did not mention, so the safety of Liujunzi Decoction combined with Wes-tern medicine could not be determined in this paper. Due to the limitations of the quality and quantity of inclu-ded studies, the efficacy of Liujunzi Decoction combined with Western medicine for COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.

Treatment adherence and level of control in moderate persistent asthma in children and adolescents treated with fluticasone and salmeterol / Adesão ao tratamento e nível de controle da asma persistente moderada em crianças e adolescentes tratados com fluticasona e salmeterol

Abstract Objective: There is a scarcity of studies that assessed the association between adherence to combination therapy and asthma control in pediatric patients. The authors investigated the association between adherence to fluticasone propionate/salmeterol xinafoate combination-metered aerosol and the level of asthma control in children. Methods: This was a prospective observational study of 84 patients aged 5-16 years with moderate persistent asthma, who remained uncontrolled despite the use of 1000 µg/day of inhaled nonextrafine-hydrofluoric alkane-beclomethasone dipropionate in the three months prior to study enrollment. Participants were prescribed two daily doses of FP (125 µg)/salmeterol xinafoate (25 µg) combination by metered aerosol/spacer for six months. Adherence rates were assessed using the device's dose counter after the 2nd, 4th, and 6th months of follow up. Asthma control was assessed using a simplified Global Initiative for Asthma 2014 Report classification. Results: Mean adherence rates after the second, fourth, and sixth months were 87.8%, 74.9%, and 62.1% respectively, for controlled asthma, and 71.7%, 56.0%, and 47.6% respectively, for uncontrolled asthma (all p-values ≤ 0.03). The proportion of children achieving asthma control increased to 42.9%, 67.9% and 89.3% after the 2nd, 4th and 6th months of follow-up, respectively (p ≤ 0.001). Conclusion: Adherence rates between 87.8% in the 2nd month and 62.1% in the 6th month were strong determinants of asthma control.

Resumo Objetivo: São escassos os estudos que avaliaram a relação entre a taxa de adesão à combinação de proprionato de fluticasona/xinafoato de salmeterol e o nível de controle da asma na infância. O presente estudo teve como objetivo avaliar essa relação. Métodos: Estudo prospectivo observacional com 84 participantes, de 5 a 16 anos, todos eles com asma persistente moderada que permaneceram não controlados apesar do uso de 1.000 µg/dia de dipropionato de beclometasona em partículas não extrafinas nos três meses que antecederam a admissão no estudo. Os participantes receberam prescrição de 125 µg de propionato de fluticasona e 25 µg xinafoato de salmeterol através de inalador pressurizado, duas vezes ao dia, e foram avaliados após o 2°, 4° e 6° meses de tratamento. A taxa de adesão foi obtida por meio do contador analógico de doses incorporado ao inalador. A classificação do nível de controle da asma foi baseada numa simplificação das recomendações da Global Initiative for Asthma. Resultados: As taxas de adesão aos 2, 4 e 6 meses para a asma controlada foram 87,8%, 74,9% e 62,1% e para a asma não controlada de 71,7%, 56,0% e 47,6% (p ≤ 0,03), respectivamente. A proporção de pacientes com asma controlada elevou- se para 42,9%, 67,9% e 89,3% nas três avaliações subsequentes (p ≤ 0,001). Conclusões: Taxas de adesão entre 87,8% no 2° mês e de 62,1% no 6° mês foram determinantes para o nível de controle da asma.

Add-on Tiotropium in Chinese Patients With Moderate Asthma: A Pooled Subgroup Analysis of MezzoTinA-Asthma 1 and 2

PURPOSE: Asthma affects approximately 30 million patients in China; however, tiotropium data for Chinese patients is limited. This study aimed to assess the efficacy and safety of tiotropium in Chinese patients with moderate symptomatic asthma. METHODS: A post hoc subgroup analysis was conducted on 430 Chinese patients pooled from two 24-week, replicate phase 3 trials (NCT01172808 and NCT01172821), in which they received once-daily tiotropium 2.5 µg (Tio R2.5) or 5 µg (Tio R5) (n = 106 or 109, respectively), twice-daily salmeterol 50 µg (Sal 50) (n = 110), or placebo (n = 105), while maintaining inhaled corticosteroids (ICS). The co-primary endpoints assessed in week 24 were forced expiratory volume in 1 second (FEV1) peak0–3h response, trough FEV1 response, and responder rate as assessed using the Asthma Control Questionnaire (ACQ). RESULTS: For both FEV1 peak0–3h responses and trough FEV1 responses, the mean treatment differences were greater for Tio R2.5, Tio R5, and Sal 50 compared with placebo at 0.249 L, 0.234 L, and 0.284 L, and 0.172 L, 0.180 L, and 0.164 L, respectively (P< 0.001). The ACQ responder rate in placebo, Tio R2.5, Tio R5, and Sal 50 was 58.7%, 62.3%, 59.3%, and 69.1%, respectively. Furthermore, 11 (2.6%) of 430 patients had serious adverse events (Tio R5, n = 4; Tio R2.5, n = 1; Sal 50, n = 1; and placebo, n = 5). CONCLUSIONS: Once-daily tiotropium, as add-on to medium-dose ICS, was effective and well tolerated for Chinese patients with moderate symptomatic asthma, consistent with the main analysis.

Eficacia de la budesonida/formoterol comparado con la fluticasona/salmeterol en la mejoría de la capacidad pulmonar de personas mayores con Enfermedad Pulmonar Obstructiva Crónica: revisión sistemática de literatura / Effectiveness of budesonide/formoterol compared to fluticasone / salmeterol in improving the lung capacity of older people with Chronic Obstructive Pulmonary Disease: systematic literature review / Eficiência da budesonida/formoterol comparado com fluticasona/salmeterol na melhora da capacidade pulmonar de idosos com Doença Pulmonar Obstrutiva Crônica: revisão sistemática da literatura

Introducción. La Enfermedad Pulmonar Obstructiva Crónica (EPOC) es una patología no transmisible, caracterizada por una limitación de flujo de aire en las vías respiratorias debido a una respuesta inmunológica anormal frente a partículas. Objetivo. Conocer la eficacia que tiene la budesonida/formoterol comparado con la fluticasona/salmeterol en la mejoría de la capacidad pulmonar en personas mayores de 40 años con Enfermedad Pulmonar Obstructiva Crónica. Materiales y métodos. Se realizó una revisión sistemática de documentos producidos entre el año 2000 y 2018 en distintas bases de datos, donde se incluyeron ensayos clínicos. Se identificaron cuatro artículos para el análisis final. Resultados. Durante la evaluación comparativa de budesonida con formoterol, los artículos muestran un total de 709 personas evaluadas, con un promedio de edad de 53,5 años. El 65,4 % eran varones, el 21 % manifestaba no haber consumido tabaco, todos con diagnóstico de Enfermedad Pulmonar Obstructiva Crónica moderada-severa, según la escala GOLD (Global Initiative For Chronic Obstrutive Lung Disease). Los estudios determinaron que al administrar budesonida/formoterol de 400/12 mcg y 320/9 mcg, los pacientes tuvieron una leve mejoría en el Volumen Espiratorio Forzado del primer segundo (VEF1). Solo dos pacientes presentaron efectos adversos. No obstante, para los resultados mencionados anteriormente no se encontró diferencias significativas. Conclusiones. El uso de budesonida/formoterol es eficaz al mejorar la capacidad ventilatoria pulmonar, disminuye el número de exacerbaciones anuales y genera un adecuado control de los síntomas, sin embargo, es igual de efectivo a la fluticasona/salmeterol.

Introduction. Chronic Obstructive Pulmonary Disease (COPD) is a not transmissible disease, characterized by a limitation of airflow in the respiratory tract, due to an abnormal immune response to particles. Objective. This article aims to show that the application of budesonide / formoterol improves lung capacity in people over 40 years with Chronic Obstructive Pulmonary Disease. Materials and methods. A systematic review was conducted in the period between 2000 and 2018 in different databases where clinical trials were included. Four articles were identified for the final analysis. Results. During the comparative evaluation of budesonide with formoterol, a total of 709 people were evaluated, with an average age of 53.5 years, 65.4% were male, 21% reported not having used tobacco, all with a diagnosis of moderate-severe Chronic Obstructive Pulmonary Disease according to the GOLD scale (Global Initiative For Chronic Obstrutive Lung Disease). The studies determined that when budesonide / formoterol of 400/12 mcg and 320/9 mcg was administered, the patients had a slight improvement in the Forced Expiratory Volume of the first second (FEV1). Only two patients presented adverse effects. However, for the results mentioned above no significant differences were found. Conclusions. The use of budesonide / formoterol is effective in improving pulmonary ventilatory capacity, decreases the number of annual exacerbations and generates adequate control of symptoms, however, it is equally effective in fluticasone / salmeterol.

Introdução. A Doença Pulmonar Obstrutiva Crônica (DPOC) é uma patologia não transmissível, caraterizada por uma limitação do fluxo de ar nas vias aéreas devido a uma resposta imune anormal contra partículas. Objetivo. Conhecer a eficiência que apresenta a budesonida/formoterol comparado com fluticasona/salmeterol na melhora da capacidade pulmonar em pessoas com mais de 40 anos com Doença Pulmonar Obstrutiva Crônica. Materiais e métodos. Foi realizada uma revisão sistemática dos documentos produzidos entre 2000 e 2018 em diferentes bancos de dados, onde foram incluídos ensaios clínicos. Quatro artigos foram identificados para a análise final. Resultados. Durante a avaliação comparativa de budesonida com formoterol, os artículos mostram um total de 709 pessoas avaliadas, com uma idade média de 53,5 anos. O 65,4 % eram do sexo masculino, o 21 % disseram que não usavam tabaco, todos diagnosticados com Doença Pulmonar Obstrutiva Crônica moderada a grave, de acordo com a escala GOLD (Global Initiative For Chronic Obstrutive Lung Disease). Os estudos determinaram que administrar budesonida/formoterol de 400/12 mcg e 320/9 mcg, os pacientes apresentaram uma leve melhora no Volume Expiratório Forçado no primeiro segundo (VEF1). Apenas dois pacientes tiveram efeitos adversos. No entanto, não foram encontradas diferenças significativas para os resultados mencionados acima. Conclusões. O uso de budesonida/formoterol é eficaz na melhora da capacidade ventilatória pulmonar, diminui o numero de exacerbações anuais e gera controle adequado dos sintomas, no entanto, é igualmente eficaz para a fluticasona/salmeterol.

Pharmacokinetic characteristics of fluticasone, salmeterol and tiotropium after concurrent inhalation

Chronic obstructive pulmonary disease (COPD) is a type of progressive, obstructive lung disease characterized by long-term poor airflow. The symptoms of COPD may be relieved and its progression delayed by fluticasone (FTS), salmeterol (SM), and tiotropium (TTP). The aim of this study is to investigate pharmacokinetic (PK) characteristics of inhaled FTS, SM, and TTP after co-administration. An open-label, single-arm, three-period, simple ascending dose study was conducted in 10 healthy male subjects. A single dose of FTS/SM (250/50 µg) and TTP (18 µg) were concomitantly inhaled in period 1, and the dose of each drug was escalated to two- and three-fold in periods 2 and 3, respectively, with a 2-week washout between periods. Activated charcoal was co-administered before and after inhalation to block gastrointestinal absorption. Blood samples for PK analysis were collected up to 24 hours. PK parameters were obtained by non-compartmental analysis. FTS, SM, and TTP rapidly reached maximum plasma concentration after inhalation (0.08–3.00 h, 0.03–0.10 h and 0.03–0.10 h, respectively) and were eliminated with mean half-lives of 9.29–10.44 h, 6.09–12.39 h and 0.25–47.42 h, respectively. PK assessment of the lowest dose of TTP was limited due to relatively low systemic exposure compared to the lower limit of quantification. In conclusion, PK characteristics of FTS, SM, and TTP by pulmonary absorption were evaluated after concurrent inhalation. FTS and SM showed dose-proportional PK profiles between 250–750 µg and 50–150 µg, respectively, while TTP presented dose-proportionality in the early phase exposure between 18-54 µg.

Síndrome de Cushing iatrogénico por corticoides inhalados en paciente VIH / Cushing syndrome in a HIV patient using inhaled steroids: report of one case

We report a 41-year-old man with HIV and a chronic obstructive pulmonary disease, treated for seven months with Fluticasone/Salmeterol and antiretroviral therapy (Lamivudine, Tenofovir, Atazanavir and Ritonavir). While using these medications, the patients developed a Cushing syndrome in a period of five months. After performing laboratory and imaging tests, it was concluded that the most probable cause of the syndrome was the interaction of inhaled steroids with Ritonavir. After discontinuing these medications the syndrome reverted in a period of 8 months.

Mesenchymal Stem Cells Combined with Budesonide, Almeterol and Azithromycin for the Treatment of Bronchiolitis Obliterans Syndrome after Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the safety and effectiveness of a novel therapeutic regimen for bronchiolitis obliterans sydrome (BOS) affter hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>Seven patients who had received HSCT and had been diagnosed as BOS were enrolled in this study. They received weekly intravenous injection of umbilical cord-derived mesenchymal stem cells (MSC) at a dose of 1 × 10(6)/kg for 4 weeks. Budesonide was given orally at a daily dose of 0.25 g, and salmeterol was inhaled at a dose of 4.5 µg for 3 times per day. Methylprednisolone was given at a dose of 1 mg/(kg·d) for 2 weeks when respiratory failure occured. The dose of methylprednisolone was tapered to 0.25 mg/(kg·d) after 4 weeks and was adjusted according to the occurrence and severity of chronic graft-versus-host disease (cGVHD).</p><p><b>RESULTS</b>The therapy was generally safe and no severe acute toxicity was observed. One patient died of heart failure during the treatment, the other 6 patients were alive and the pulmonary function parameters including FEV1, FEV1/FVC, PaO2 and AaDO2 were significantly improved after 6 months as compared with the baseline parameters (P < 0.05).</p><p><b>CONCLUSION</b>MSC combined with budesonide, almeterol and azithromycin has been confirmed to be generally safe and can reduce the dose of glucocorticoid in treatment of BOS after HSCT.</p>

Three-month Treatment Response and Exacerbation in Chronic Obstructive Pulmonary Disease

The aim of this study was to investigate relationships between acute exacerbation and Forced Expiratory Volume 1 second (FEV1) improvement after treatment with combined long-acting beta-agonist (LABA) and inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD). A total of 137 COPD patients were classified as responders or nonresponders according to FEV1 improvement after 3 months of LABA/ICS treatment in fourteen referral hospitals in Korea. Exacerbation occurrence in these two subgroups was compared over a period of 1 yr. Eighty of the 137 COPD patients (58.4%) were classified as responders and 57 (41.6%) as nonresponders. Acute exacerbations occurred in 25 patients (31.3%) in the responder group and in 26 patients (45.6%) in the nonresponder group (P=0.086). FEV1 improvement after LABA/ICS treatment was a significant prognostic factor for fewer acute exacerbations in a multivariate Cox proportional hazard model adjusted for age, sex, FEV1, smoking history, 6 min walk distance, body mass index, exacerbation history in the previous year, and dyspnea scale.Three-month treatment response to LABA/ICS might be a prognostic factor for the occurrence of acute exacerbation in COPD patients.

Efficacy on chronic obstructive pulmonary disease at stable stage treated with cutting method and western medication / 中国针灸

<p><b>OBJECTIVE</b>To compare the difference in clinical efficacy on chronic obstructive pulmonary disease (COPD) at stable stage in the patients among the combined therapy of cutting method and western medication (combined therapy), simple cutting method and simple western medication.</p><p><b>METHODS</b>One hundred and twenty cases of COPD were randomized into three groups, 40 cases in each one. In the cutting method group, for excessive phlegm pattern/syndrome, Feishu (BL 13), Danzhong (CV 17), Dingchuan (EX-B 1) and Yuji (LU 10) were selected as the main acupoints, and Lieque (LU 7) and Pianli (LI 6) were as the supplementary acupoints. For the pattern/syndrome of failure to consolidate kidney primary, Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4) and Yuji (LU 10) were selected as main acupoints, and Jueyinshu (BL 14) and Zusanli (ST 36) were as the supplementary acupoint. Three acupoints were selected alternatively in each treatment and the cutting method was applied once every 10 days. Three treatments made one session. Two sessions of treatment were required. In the western medication group, salbutamol sulfate aerosol, one press (200 μg/press) was used each night, as well as salmeterol xinafoate and fluticasone propionate powder for inhalation, one inhalation each night. The treatment of 1 month made one session. Two sessions were required. In the combined therapy group, the cutting method and western medication were applied in combination. The results of clinical symptom score, lung function test, arterial blood gas analysis, degree of inflation as well as clinical efficacy were observed before and after treatment in each group.</p><p><b>RESULTS</b>Except the degree of lung inflation, the clinical symptom score, indices of lung function test, partial pressure of arterial blood gas (PaO2) and partial pressure of carbon dioxide (PaCO2) were all obviously improved after treatment as compared with those before treatment in each group (all P<0.05). They were apparently improved after treatment in the combined therapy group and the cutting method group as compared with those in the western medication group (all P<0.05). The total effective rate was 77.5% (31/40) in the combined therapy group and was 75.0% (30/40) in the cutting method group, both better than 60.0% (24/40) in the western medication group (both P<0.05).</p><p><b>CONCLUSION</b>The simple cutting method based on syndrome differentiation and the combined therapy with western medication achieve the superior efficacy on COPD at stable stage as compared with the simple western medication. The effect mechanism is possibly related to the improvement of bronchial airway function through constant acupoint stimulation.</p>

Salmeterol/fluticasone treatment reduces circulating C-reactive protein level in patients with stable chronic obstructive pulmonary disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Evidence suggests that systemic inflammation may play an important role in the progression and morbidity of chronic obstructive pulmonary disease. It remains controversial whether inhaled corticosteroid in combination with a long-acting beta(2)-adrenoceptor agonist can attenuate systemic inflammation. We evaluated the effect of salmeterol/fluticasone propionate on circulating C-reactive protein level in stable chronic obstructive pulmonary disease patients.</p><p><b>METHODS</b>An open-label clinical trial was conducted to recruit 122 outpatients with stable moderate-to-severe chronic obstructive pulmonary disease from department of respiratory medicine in two teaching hospitals between June 2007 and March 2008. Patients were randomized into two groups (1:1) to receive either the combination of 50 microg salmeterol and 500 microg fluticasone twice daily (n = 61), or the combination of 206 microg albuterol and 36 microg ipratropium q.i.d (n = 61) over 6 months. Circulating C-reactive protein concentrations were measured before randomization and during the follow-up. The efficacy of treatment was also assessed by spirometry, as well as health status and dyspnea score at baseline and after 6-month treatment.</p><p><b>RESULTS</b>Baseline characteristics of two groups were similar. Compared with ipratropium/albuterol, the combination of salmeterol/fluticasone significantly reduced circulating level of C-reactive protein (-1.73 vs. 0.08 mg/L, respectively, P < 0.05) after 6-month treatment. Forced expiratory volume in one second (FEV(1)) and health status also improved significantly in salmeterol/fluticasone group compared with ipratropium/albuterol. Salmeterol/fluticasone treatment subjects who had a decrease of circulating C-reactive protein level had a significant improvement in FEV(1) and St George's Respiratory Questionnaire total scores compared with those who did not (185 vs. 83 ml and -5.71 vs. -1.79 units, respectively, both P < 0.01).</p><p><b>CONCLUSION</b>Salmeterol/fluticasone treatment reduced circulating C-reactive protein concentration in clinically stable moderate-to-severe chronic obstructive pulmonary disease patients after 6-month treatment.</p>

Comparison for the Effects of Triple Therapy with Salmeterol/Fluticasone Propionate and Tiotropium Bromide versus Individual Components in Patients of Severe COPD Combined with Bronchial Hyperresponsiveness / 결핵및호흡기질환

BACKGROUND: A combination of salmeterol and fluticasone propionate (SFC) and tiotropium bromide (TIO) is commonly prescribed for COPD patients but there is little data on their effectiveness, particularly in COPD patients with bronchial hyperresponsiveness. This study compared the spirometric improvement based on the change in FEV1, FEV1/FVC, and IC as well as the clinical outcomes of the therapeutic strategies with SFC and TIO versus the individual components in patients with severe COPD and bronchial hyperresponsiveness. METHODS: This study examined the spirometric data and clinical outcomes of 214 patients with COPD and hyperresponsiveness, who were divided into three groups according to the therapeutic regimen (TIO only, SFC only, and a triple therapy regimen). RESULTS: All regimen groups showed early improvement in the FEV1 and IC (at 3- and 6 months after treatment). However, long-term beneficial effects were observed only in the SFC group (at 24 months after treatment). However, these beneficial effects decreased after a 36-month follow up. In all spirometric results, the 12-, 24-, and 36-months data showed a similar degree of improvement in the three groups. The triple therapy group showed higher St. George's Respiratory Questionnaire scores and lower acute exacerbations and hospitalization. CONCLUSION: SFC can be a more important component in the pharmacological treatment of severe COPD patients with hyperresponsiveness than TIO, particularly in the spirometric and clinical outcomes.

Successful pharmacotherapy for asthma exacerbation in an asthmatic patient with long QT syndrome / 대한내과학회지

beta -Blockers can cause bronchospasm in asthma. beta 2-agonists prolong the QT interval and alter the clinical course of long QT syndrome (LQTS). We report a case of asthma exacerbation treated cautiously with beta 2-agonists in a patient with LQTS, while LQTS was controlled with low-dose beta 1-antagonists. A 31-year-old woman with LQTS visited the emergency room for asthma exacerbation. FEV1 was 0.5 L (18%) and QTc interval was 520 ms. Low doses of salbutamol or salmeterol were used and gradually increased, while monitoring the QT interval. Simultaneously, a low dose of atenolol was maintained. FEV1 was increased to 2.2 L (83%) without further QT prolongation or cardiac events. The case suggests that lower doses of beta 1-antagonists can be tried for cardiac diseases, even in the presence of asthma exacerbations. beta 2-Agonists may be initiated at lower doses and, if tolerated, the dose can be increased in asthmatic patients with a risk for QT prolongation.

Influence of education level on self-evaluation and control of patients with bronchial asthma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of education on self-evaluation and control level in patients with bronchial asthma.</p><p><b>METHODS</b>Seventy-five asthmatic patients with the initial diagnosis in line with the American Thoracic Society criteria, including 46 with junior high school education or below (group A) and 29 with senior high school education or above (group B), were asked to complete a survey to assess their symptoms and asthma attacks. Asthma control test (ACT) and peak expiratory flow rate (PEFR) evaluation were performed 8, 12 and 24 weeks after salmeterol/fluticasone therapy. Step-down treatment was administered according to GINA guidelines. The self-evaluation of the patients was assessed according to ACT score, physical signs and pulmonary function. An ACT score over 19 indicate well controlled condition. The effect of education on the self-evaluation and control level of bronchial asthma was assessed.</p><p><b>RESULTS</b>The two groups had similar basal level of pulmonary function (FEV1). Eight weeks after the therapy, 29 patients in group A had ACT score over 19, including 11 with high control level; in group B, 17 had ACT score over 19, of whom 4 showed high control level. There was no significant difference between the two groups in control levels and self-evaluation (P>0.05). At 12 weeks, 37 patients in group A had ACT score over 19, with 17 having high control level; 22 patients in group B had ACT score over 19, 4 showing high control level; the two groups were similar in the control levels (P>0.05) but showed significant difference in self-evaluation (P<0.05). At the time of 24 weeks, 42 and 26 patients had ACT score over 19 in the two groups, with 19 and 5 having high control level, respectively. The two groups differed significantly in the control levels (P<0.05) and self-evaluation (P<0.05).</p><p><b>CONCLUSION</b>The patients' education level may play a role in self-evaluation and control level of bronchial asthma, but its impact differs in the course of the treatment.</p>

Determination of liposome/water partition coefficients of salmeterol and budesonide and study on their influencing factors / 药学学报

<p><b>AIM</b>The liposome/water partition coefficients of salmeterol and budesonide between aqueous phase and liposomes were determined and the factors that influence their partition coefficients were studied, the mechanism of interaction between the two drugs and phospholipid bilayer was elucidated.</p><p><b>METHODS</b>The liposome/water partition coefficients of the two drugs were determined by equilibrium dialysis technique. The change of the partition coefficients of the two drugs along with liposome composition and medium was also studied.</p><p><b>RESULTS</b>The partition coefficients of the two drugs decreased with the increase of cholesterol content and saturation of phospholipid used. The liposome/water partition coefficient of salmeterol increased with the increase of liposome surface negative charge, medium pH and ionic strength, while the liposome surface charge, medium pH and ionic strength had no distinct effect on the liposome/water partition coefficient of budesonide.</p><p><b>CONCLUSION</b>The liposome/water partition coefficient of drug was affected by the type, saturation of phospholipid used in liposome preparation, the cholesterol content and surface charge of liposome, as well as the pH and ionic strength of medium also have effect on the liposome/water partition coefficient of drug. Accordingly, in order to reflect the actual partition of drug in biological membrane, the determination condition including liposome composition and medium should be similar to the biological membrane.</p>

A case of Churg-Strauss syndrome associated with zafirlukast / 천식및알레르기

Churg-Strauss syndrome (CSS) is an eosinophil associated disease, characterized by vaculitis and granulomatosis on small vessel, asthma and eosinophil tissue infiltration. Several cases of CSS have been reported in patients treated with cysteinyl leukotriene receptor antagonist and weaned-off systemic or inhaled corticosteroids. A 39-year-old man with a history of childhood allergic rhinitis was diagnosed with bronchial asthma and his symptoms were well controlled with fluticasone propinate, salmeterol and zafirlukast. However four months later, he was admitted again with prominent skin lesions, tingling sensation on both extremities and fever. We diagnosed CSS with a history of sinusitis and bronchial asthma, marked peripheral eosinophilia, vasculitis and neuropathy. His symptoms and laboratory findings promptly improved after ten days of intravenous corticosteroid and cessation of zafirlukast without recurrence for six months during the follow-up period. We conclude that zafirlukast may cause CSS and attention should be taken when using zafirlukast.

Clinical studies of salmeterol / 알레르기

Salmeterol is a long acting, highly selective, beta2-adrenergic agonist. It prevents asthma symptoms in patients with mild or moderate disease and improves nocturnal asthma and sleep quality. We evaluated the bronchodilator and bronchoprotective effect and duration of action of inhaled salmeterol in patients wlth asthma. We compared the bronchodilator and bronchoprotective effects of salmeterol with salbutamol in 34 patients with asthma. Diagnosis of asthma was confirmed with methacholine challenge test or airway reversibility test. We performed the symptom index questionnaire, peak expiratory flow rate, pulmonary function test and methacholine challenge test. Symptom scores were more improved with salmeterol treatment than salbutamol treatment. After salmeterol inhalation, mean FEV1 increased from 1.95L(pre-treatment) to 2.04L(early stage in the treatment), 2.06L(late stage), 2.03L(follow up). There was no difference in FEV1 between early stage and late stage after salmeterol treatment. With salmeterol, there was a significant increases in PC30 on methacholine challenge test ( PC20 4.96 : 16.42). Salmeterol is a potent, long-acting bronchodilator, with a slower onset and longer duration of bronchodilation than salbutamol. It also has bronchoprotective effect and shows low incidence of adverse effects.

A Comparison of Salmeterol with Salbutamol Inhalation in Treatment of Mild to Moderate Asthma / 결핵

BACKGROUND: Salmeterol, a new beta2-adrenergic receptor agonist is a long-acting bronchodilator and benefits patients -with asthma who have nocturnal symptoms. We wished to assess the efficacy of inhaled salmeterol (50 microgram bid) compared to inhaled salbutamol (200 microgram qid) for the treatment of bronchial asthma, particular. ly nocturnal asthma. METHOD: We randomly assigned 35 patents (25 female and 0 male patients, 15 to 50 years old) to one of two treatment groups one group received 50 microgram of salmeterol twice daily and another did 200 microgram salbutamol four times per day. And this study was performed as an open-label and the 6 weeks inhalation period. RESULTS: Analysis of symptom scare; Day and night time symptom score showed significant difference between salmeterol and salbutamol Group (p<0.05). Number of days for additional bronchodilator requirements The number of days and puffs for additional bronchodilator were lower in the salbutamol group in either day and night time (p<0.05). Pulmonary function test; FEV1 showed significant increase in salbutamol group compared to salbutamol group after 2 and 4 weeks inhalation period. Adverse effects, We found no evidence of tolerance to the bronchodilating effects of salmeterol, and adverse reactions to all the treatments were infrequent and mild. CONCLUSION: For the management of bronchial asthma, salmeterol given twice daily is superior to salbutamol given four times daily.