Update on the Safety of Long-acting Beta2-agonists / 대한내과학회지

A recent meta-analysis of clinical trials found that long-acting beta2-agonists (LABA) increased life-threatening asthma exacerbations and deaths, which led to warnings concerning regular use of LABA by U.S. Food and Drug Administration (FDA). It is now obvious that LABA monotherapy in asthma increases the risk of serious adverse events. However, the risk is reduced with concomitant use of inhaled corticosteroid (ICS). Hence the FDA's recommendations that LABA should not be used in patients whose asthma is well controlled with a medium dose of ICS, or LABA should be withdrawn once asthma control is achieved, remain still controversial. It seems reasonable to follow current guidelines which recommend the use of LABA when asthma is not controlled with ICS, although more well-designed research on the safety of LABA, especially when combined with ICS, is required.

Effect of beta2-Adrenergic Receptor Polymorphism in Asthma Control of Patients Receiving Combination Treatment

PURPOSE: Combination treatment of inhaled corticosteroid (ICS) plus long-acting beta2-agonist (LABA) is widely used as a maintenance regimen for the management of asthma. This study evaluated the effect of the beta2-adrenergic receptor (ADRB2) polymorphism on lung function and asthma control with regular use of combination treatment of an inhaled ICS plus LABA. MATERIALS AND METHODS: 43 Korean asthmatics who were symptomatic despite regular ICS use for at least 3 months were enrolled. For a 2-week run-in period, they received ICS (budesonide 800 microgram/day) plus terbutaline (5 microgram prn). as needed. During the 24-week active treatment period, they received budesonide 160 microgram and formoterol 4.5 microgram b.i.d. as maintenance and rescue medication. Pulmonary function and quality of life scores were monitored every 8 weeks; morning/evening peak expiratory flow meter (PEFR) was recorded daily. Patients were genotyped for ADRB2 Arg16Gly using single base extension methodology. RESULTS: During the run-in period, there were no significant between-group differences in lung function; after 8 weeks of active treatment, Arg/Arg patients had significantly higher forced expiratory volume in 1 secord (FEV1) and maximal mid-expiratory flow (MMEF) (p = 0.023 and p = 0.021, respectively), and better asthma control and quality of life after 24 weeks (p = 0.016 and p = 0.028, respectively). During treatment, there was a greater improvement in morning/evening PEFR in Arg/Arg patients. CONCLUSION: Asthmatic patients with the Arg/Arg genotype at codon 16 of ADRB2 achieve better asthma control with long-term regular use of combined budesonide and formoterol treatment, suggesting that the ADRB2 genotype may dictate choice of treatment strategy.

Interpretation and application of recent large clinical studies in COPD / 대한내과학회지

Chronic obstructive pulmonary disease (COPD) shows a high mortality as well as a high prevalence around the world. Recent large-scale clinical studies showed that inhaled long-acting anticholinergics, inhaled long-acting beta2-agonists, and inhaled corticosteroid have beneficial effects on patients suffered from COPD. In addition, the combination of the two or three inhalers above shows more beneficial effects. The beneficial effects are the improvement of symptom, lung function, and quality of life as well as the reduction of exacerbation and possibly death. These beneficial effects are true not only for the patients with severe and very severe COPD but also for the patients with moderate COPD. Clinical studies also showed that mucolytics and roflumilast, a new anti-inflammatory drug have beneficial effects on the patients with COPD. According to these beneficial results proven by the recent clinical studies, the guidelines for the management of COPD might be revised to promote the usage of the beneficial drugs for the patients with COPD. The promoted usage of the COPD drugs would help the COPD patients to overcome their symptom, limitation of airflow and frequent exacerbation and also to improve their quality of life.

The effect of Combination Therapy of Inhaled Corticosteroids and Long-acting Beta2-agonists on Acute Exacerbation in Moderate to Severe COPD Patients / 결핵및호흡기질환

BACKGROUND: The role of combination therapy of inhaled corticosteroid (ICS) plus long-acting beta2-agonist (LABA) in asthma is well established, but nor much is known about this treatment in COPD. Recent studies have revealed that combining therapy is associated with fewer acute exacerbations in COPD, but in most of the studies, high-dose combination therapies have been employed. The current study assessed the effect of moderate or high-dose combination therapy of ICS plus LABA on the frequency of acute exacerbations in COPD. METHODS: Between January 1, 2001 and August 31, 2004, 46 patients with COPD (moderate, severe, very severe) were enrolled who received either fluticasone/salmeterol (flu/sal) 250 microgram/50 microgram twice a day (group A) or flu/sal 500 microgram/50 microgram twice a day (group B) for more than a year. We divided them into two groups depending on the dosage of ICS plus LABA. Effect of drugs was compared based on the factors such as symptom aggravation, number of admission, and time to first exacerbation during a year after use. RESULTS: Eleven of twenty-six patients in group A (42.3%) experienced acute exacerbation and eleven of twenty patients in group B (55%) experienced acute exacerbation during 1 year. Mean exacerbation rate of Group A was 0.96 and Group B was 1.05. Mean admission rate was 0.15 and 0.30, respectively. There was no statistically significant difference of aggravation rate, number of administration and time to first exacerbation between the two treatment groups. CONCLUSION: There was no significant difference between moderate and high dose combined inhaler therapy to reduce acute exacerbation in COPD patients (moderate, severe, very severe). Hence, the effective dose of combination therapy needs further study in patients with COPD.