Concomitant Inhaled Corticosteroids Research Articles

Efficacy and Safety of Yukmijihwang-Tang in the Treatment of Cough-Variant Asthma: Study Protocol for a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Background: Cough-variant asthma (CVA), a precursor of typical asthma, is the main cause of chronic cough. We hypothesize that yukmijihwang-tang (YJT), which has been used for chronic cough in traditional medicine and has been reported to have an anti-inflammatory effect, could be an adjuvant to asthma treatment. Methods: We plan a randomized, double-blind, placebo-controlled, multicenter, phase 2 trial to investigate the efficacy and safety of YJT in CVA patients. A total of 60 patients with CVA will be recruited and randomly assigned to either a high-dose YJT group, standard-dose YJT group, or control group (placebo) in a 1:1:1 allocation ratio after a 2-week run-in period. For the run-in period, only inhaled corticosteroids (ICSs) will be used, and the investigational drug will be administered once a day with concomitant ICS for 6 weeks. Data will be collected at baseline, week 3, and week 6, and the primary outcome measure will be the mean cough symptom score (CSS) change before and after medication. The secondary outcome measures will include the Leicester cough questionnaire-Korean version (LCQ-K) score, eosinophil count and eosinophil cationic protein level, pulmonary function test, and the number of uses of rescue medication, and so on. Conclusion: This study aimed to evaluate the efficacy and safety of YJT in concomitant treatment with ICS in patients with CVA and to determine the optimal dosage of YJT. The results are expected to provide evidence for the use of YJT as an adjuvant treatment for CVA.

Short-Acting Beta-2-Agonist Exposure and Severe Asthma Exacerbations: SABINA Findings From Europe and North America

Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting beta-2 agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists. To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe. Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 y) from Canada, France, the Netherlands, Poland, Spain, the United Kingdom, and the United States. Negative binomial models (incidence rate ratio [IRR] [95% CI adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations. Across severities, 40.2% of patients were prescribed/possessed 3 or more SABA canisters/y. Per the Global Initiative for Asthma (GINA) 2018 definitions, steps 3 to 5-treated patients prescribed/possessing 3 or more versus 1 or 2 SABAs experienced more severe exacerbations (IRR 1.08 [95% CI 1.04‒1.13], U.S. Medicare; IRR 2.11 [95% CI 1.96‒2.27], Poland). This association was not observed in all step 1 or 2-treated patients (the Netherlands, IRR 1.25 [95% CI 0.91‒1.71]; U.S. commercial, IRR 0.92 [95% CI 0.91‒0.93]; U.S. Medicare, IRR 0.74 [95% CI 0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the U.S. datasets was attributable to the large patient population possessing fewer than 3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face health care provider encounters. In U.S. SABA monotherapy-treated patients, 3 or more SABAs were associated with more emergency/outpatient visits and hospitalizations (IRR 1.31 [95% CI 1.29‒1.34]). Most GINA 2 to 5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of 3 or more SABAs and severe exacerbations persisted (IRR 1.32 [95% CI 1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when U.K. SABA data were analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications. Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.

Anti-interleukin-13 and anti-interleukin-4 agents versus placebo, anti-interleukin-5 or anti-immunoglobulin-E agents, for people with asthma.

Anti-interleukin-13 and anti-interleukin-4 agents versus placebo, anti-interleukin-5 or anti-immunoglobulin-E agents, for people with asthma.

The prevalence and outcome of short-acting \u03b22-agonists overuse in asthma patients in Taiwan

This study aims to investigate the prevalence of short-acting β2-agonist (SABA) overuse in asthma and the associated risk of acute exacerbation and mortality in Taiwan. We used the Taiwanese pay-for-performance asthma program database, which included patients aged between 12 and 100 years who were enrolled in the program between 2001 and 2015. Among a total of 218,039 patients, 34,641 (15.9%) patients are classified as SABA over-users. Compared with patients who did not receive inhaled corticosteroids (ICS) and collected ≤2 canisters, SABA over-users had a higher risk of severe exacerbations. SABA over-users had a higher risk of all-cause mortality compared with patients who did not receive ICS and collected ≤2 canisters. The overall prevalence of SABA overuse in Taiwan is 15.9%, and this is even higher in concomitant ICS users. In addition, the overuse of SABA is associated with an increased risk of severe exacerbation and death.

Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate

Loss of bronchoprotection (LOBP) with a regularly used long-acting β2-adrenergic receptor agonist (LABA) is well documented. LOBP has been attributed to β2-adrenergic receptor (B2AR) downregulation, a process requiring farnesylation, which is inhibited by alendronate. We sought to determine whether alendronate can reduce LABA-associated LOBP in inhaled corticosteroid (ICS)-treated patients. We conducted a randomized, double-blind, placebo-controlled, parallel-design, proof-of-concept trial. Seventy-eight participants with persistent asthma receiving 250μg of fluticasone twice daily for 2weeks were randomized to receive alendronate or placebo while initiating salmeterol for 8weeks. Salmeterol-protected methacholine challenges (SPMChs) and PBMC B2AR numbers (radioligand binding assay) and signaling (cyclic AMP ELISA) were assessed before randomization and after 8weeks of ICS plus LABA treatment. LOBP was defined as a more than 1 doubling dose reduction in SPMCh PC20 value. The mean doubling dose reduction in SPMCh PC20 value was 0.50 and 0.27 with alendronate and placebo, respectively (P=.62). Thirty-eight percent of participants receiving alendronate and 33% receiving placebo had LOBP (P=.81). The after/before ICS plus LABA treatment ratio of B2AR number was 1.0 for alendronate (P=.86) and 0.8 for placebo (P=.15; P=.31 for difference between treatments). The B2AR signaling ratio was 0.89 for alendronate (P=.43) and 1.02 for placebo (P=.84; P=.44 for difference). Changes in lung function and B2AR number and signaling were similar between those who did and did not experience LOBP. This study did not find evidence that alendronate reduces LABA-associated LOBP, which relates to the occurrence of LOBP in only one third of participants. LOBP appears to be less common than presumed in concomitant ICS plus LABA-treated asthmatic patients. B2AR downregulation measured in PBMCs does not appear to reflect LOBP.

Prescribing of long-acting beta-2-agonists/inhaled corticosteroids after the SMART trial.

BackgroundAfter the SMART trial evaluating the safety of salmeterol (long-acting beta-2-agonist (LABA)) in asthma patients, regulatory actions were taken to promote a guideline-adherent prescribing of LABA only to patients receiving inhaled corticosteroids (ICS). We aim to analyse LABA- and ICS-related prescription patterns after the SMART trial in Germany.MethodsPatients documented in the Bavarian Association of Statutory Health Insurance Physicians database (approximately 10.5 million people) were included if they had a diagnosis of asthma and at least one prescription of LABA and/or ICS between 2004 and 2008. Annual period prevalence rates (PPRs) were estimated and Cochrane Armitage tests were used for time trend analyses.ResultsHighest annual PPRs were found for budesonide and the fixed combination of salmeterol/fluticasone. The proportion of “concomitant LABA and ICS users” increased from 52.0 to 57.6% within the study period, whereas for “LABA users without ICS” a slight decrease from 6.5 to 5.4% was found. In 2008, the proportion of patients with at least one quarter with a LABA prescription without concomitant ICS was highest in elderly, male patients (≈20%). In the majority of these patients, a concomitant diagnosis of COPD (i.e. asthma-COPD overlap syndrome [ACOS]) was present.ConclusionsBetween 2004 and 2008, we found a moderate increase in guideline-adherent LABA prescribing in a representative German population. Elderly men received a significant number of LABA prescriptions without concomitant ICS probably due to ACOS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-015-0051-x) contains supplementary material, which is available to authorized users.

Omalizumab: An update on efficacy and safety in moderate-to-severe allergic asthma

Omalizumab is an anti-immunoglobulin E (anti-IgE) monoclonal antibody approved in the United States since 2003 for treatment of moderate-to-severe allergic asthma in adults and adolescents (aged ≥12 years) inadequately controlled with inhaled corticosteroids (ICSs). Current treatment guidelines recommend considering the addition of omalizumab if allergic asthma symptoms are not adequately controlled with high-dose ICS + long-acting beta-agonist (LABA) therapy. This study was designed to review the clinical efficacy and safety of omalizumab as established in previously published pivotal clinical trials used to support registration in the United States, i.e., primarily including patients receiving only concomitant ICS therapy, as well as results from the recently completed additional study, which specifically enrolled patients who were poorly controlled despite high-dose ICS + LABA therapy ± additional controllers (including oral corticosteroids [OCSs]). Summary of published omalizumab pivotal trials and associated extension trials, plus key results from the additional study, were used. Pediatric data (i.e., <12 years) were outside the scope of this article. Treatment with omalizumab significantly reduced asthma exacerbations versus placebo when added to ICS therapy during both steroid-stable and steroid-reduction phases of two pivotal trials. In the additional study, omalizumab significantly reduced asthma exacerbation rates versus placebo when added to high-dose ICS + LABA therapy with or without other controller medications. Results from the additional clinical study further support current asthma guideline recommendations to consider omalizumab in steps 5 or 6 for persistent allergic asthma patients whose symptoms are not adequately controlled despite high-dose ICS + LABA therapy ± additional controllers (including OCS).

Long-Acting β-Agonists in Asthma Management

Large surveillance studies or phase IV clinical studies of long-acting β-agonists (LABA) compared with placebo in asthma patients using variable (from nil to regular) doses of inhaled corticosteroids (ICS) have raised the issue of mortality risk in patients with asthma taking regular LABA. There have been a number of meta-analyses and systematic reviews that have examined the risk of LABA in asthma patients, and the general conclusion is that LABA added to ICS reduces asthma-related hospitalizations compared with ICS alone and there is no statistical increase in mortality. However, LABA without ICS do increase mortality risk in asthma. All reviews and analyses show a greater number of LABA deaths, but not all are statistically significant. A recent meta-analysis found LABA with concomitant ICS had a higher mortality rate in asthma than ICS alone. The flaw in the study is the higher doses of ICS in the control arms, but the implicit message remains: the essential need for enough ICS to control airway inflammation. We suggest that the pragmatic solution is to have LABA only available in the same device as ICS for asthma treatment. We do not think that a study comparing the safety of LABA plus ICS versus ICS alone in asthma is necessary. If such a study is conducted, the measurement of morbidity from increased doses of ICS is an essential design consideration. Furthermore, the critical focus in asthma management should not be forgotten - education of health professionals and the community of the critical role of ICS, and the need for good communication between health professionals and the asthma patient to facilitate good asthma control. The same arguments apply to the asthma-with-chronic obstructive pulmonary disease overlap syndrome in older patients. There is an urgent need to provide medical practitioners with the capability to diagnose the overlap syndrome.

Age and Risks of FDA-Approved Long-Acting β2-Adrenergic Receptor Agonists

To determine the risk, by age group, of serious asthma-related events with long-acting β(2)-adrenergic receptor agonists marketed in the United States for asthma. The US Food and Drug Administration performed a meta-analysis of controlled clinical trials comparing the risk of LABA use with no LABA use for patients 4 to 11, 12 to 17, 18 to 64, and older than 64 years old. The effects of age on a composite of asthma-related deaths, intubations, and hospitalizations (asthma composite index) and the effects of concomitant inhaled corticosteroid (ICS) use were analyzed. One hundred ten trials with 60 954 patients were included in the meta-analysis. The composite event incidence difference for all ages was 6.3 events per 1000 patient-years (95% confidence interval [CI]: 2.2-10.3) for using LABAs compared with not using LABAs. The largest incidence difference was observed for the 4- to 11-year age group (30.4 events per 1000 patient-years [95% CI: 5.7-55.1]). Differences according to age were statistically significant (P = .020). Results for the subgroup of patients with concomitant ICS use (n = 36 210) were similar to the overall results; with assigned ICSs (n = 15 192), the incidence difference was 0.4 events per 1000 patient-years (95% CI: -3.8 to 4.6), and there was no statistically significant difference according to age group. The excess of serious asthma-related events attributable to LABAs was greatest among children. Additional data are needed to assess risks of LABA use for children with simultaneous ICS use.

Concomitant Asthma Medication Use in Patients Receiving Omalizumab: Results from Three Large Insurance Claims Databases

Background. Omalizumab (Xolair®) is a monoclonal antibody indicated for moderate to severe persistent allergic asthma patients with symptoms that are inadequately controlled with inhaled corticosteroids (ICS). Objective. This study describes concomitant asthma medication use in patients treated with omalizumab. Methods. An analysis of health insurance claims from MarketScan (2002–2009), Medicaid (2002–2009), and the HealthCore Integrated Research Database (HIRD™) (2002–2010) was conducted. Medical charts were also extracted for a subset of HIRD patients. Patients aged ≥12 years and newly initiated on omalizumab with 12 months of continuous insurance coverage prior to the first omalizumab dispensing (baseline period) and ≥2 asthma claims were included. Concomitant asthma medication use was summarized in eight medication classes. Results. A total of 6038 patients were identified (Medicaid: 731; MarketScan: 3521; HIRD: 1786). A high proportion of new omalizumab users had an asthma-related emergency room visit (Medicaid: 34%; MarketScan: 17%; HIRD: 16%) or hospitalization (Medicaid: 36%; MarketScan: 14%; HIRD: 21%) within 12 months prior to initiating omalizumab. Most patients (Medicaid: 96%; MarketScan: 89%; HIRD: 86%) received three concomitant asthma medication classes or more during the baseline period. Concomitant ICS use was observed in 95%, 89%, and 86% of Medicaid, MarketScan, and HIRD patients, respectively. In HIRD patients without evidence of receiving other asthma medication prior to omalizumab, 17 out of 20 patients had a documented baseline history of asthma-related medication use in their medical charts. Conclusions. This large observational study using health insurance claims from three databases and confirming results from medical charts provides evidence that nearly all omalizumab users had received other asthma medications prior to initiating omalizumab.

Safety of formoterol in adults and children with asthma: a meta-analysis

The safety of long-acting β2 agonists (LABA) for the treatment of persistent asthma remains a topic of ongoing debate. To evaluate the risk of serious asthma-related events among patients treated with formoterol, a meta-analysis of all Novartis-sponsored controlled clinical trials was conducted. Forty-five randomized, placebo- and active-controlled, parallel-group or crossover studies with formoterol were included. Background inhaled corticosteroid (ICS) use was permitted in all studies; however, in only 2 studies was ICS randomized as study medication. Sub-analyses of the pooled data were performed according to age (5-12; 13-18; >18 years), baseline ICS use, and lung function. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated between formoterol (twice-daily), albuterol (salbutamol) 4 times per day (active control), and placebo. Patients were randomized to formoterol (n = 5,367), placebo (n = 2,026), and albuterol (n = 976). Two deaths were reported, 1 each in the formoterol (asthma exacerbation) and the placebo (hemorrhagic pancreatitis) groups. No statistically significant differences in serious asthma exacerbations were observed compared with placebo in adolescents and adults. In children, a higher frequency of hospitalizations was observed among patients treated with formoterol compared with placebo (OR 8.4; 95% CI: 1.1-65.3). A trend toward fewer exacerbations was observed among subjects reporting concomitant ICS use at baseline. This analysis supports current guideline recommendations for the use of LABAs only as add-on therapy to ICS.

Bronchodilator treatment and asthma death: A new analysis of a British case-control study

We investigated the relationship between asthma mortality and long-acting beta(2)-agonists (LABA), including interactions with age, inhaled corticosteroids (ICS) and social deprivation. We used a new, expanded dataset of recorded medication extracted blind from the anonymised primary care records of an earlier British case-control study. The cases were 532 asthma deaths aged < 65 occurring between 1994 and 1998 and the controls were 532 asthma admissions, matched for age, hospital, and index date (date of death/asthma admission). The exposure periods prior to the index date were current (≤ 2 months) or recent ( > 2-6 months). We found no evidence of an overall association with current (OR = 0.89 [95% confidence interval 0.61-1.30]) or recent (1.08 [0.76-1.53]) mention of LABA, but there was some evidence of a positive interaction with age. Among controls with mention of LABA, a concurrent mention of ICS (within 1 month) was common (85% and 93% for the two respective periods) which limited our power to investigate any interaction between LABA and ICS. There was no coherent evidence of effect modification by social deprivation. In a population based case-control study where prescription of LABA without concomitant ICS was uncommon there was no evidence of an overall association between LABA and asthma death.

Safety of formoterol in children and adolescents: experience from asthma clinical trials

BackgroundThe safety of long-acting β2 agonist (LABA) therapy in asthma remains controversial but no large scale analyses have been published of LABA safety in children.MethodsThe frequency of asthma-related deaths and...

An update on the safety of long-acting β-agonists in asthma patients using inhaled corticosteroids

Importance of the field: Pooled trial data have shown that long-acting β-agonists increase the risk for asthma hospitalizations and deaths by two to fourfold compared with placebo. Until recently, it was unclear whether concomitant inhaled corticosteroids (ICSs) could eliminate this risk.Areas covered in this review: This review summarizes the available data on the safety of long-acting β-agonist use in asthma, with and without concomitant ICSs. The results from an updated meta-analysis are presented, with data through December 2008.What the reader will gain: In pooled trial data, catastrophic asthma events (defined as asthma-related intubation or death) were increased fourfold for concomitant treatment with long-acting β-agonists and ICSs compared with corticosteroids alone (odds ratio 3.7; 95% CI 1.4 – 9.6). It is estimated that the addition of long-acting β-agonists to ICS therapy is associated with an absolute increase of one catastrophic event per 1500 patient-years.Take home message: When the available trial data are pooled together, it is clear that long-acting β-agonists significantly increase the risk for asthma-related intubations and deaths, even when used in a controlled fashion with concomitant ICSs. Clinical guidelines should readdress the role long-acting β-agonists have in the management of asthma.

Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy

Background:There is concern that long-acting β agonist (LABA) drugs may increase the risk of asthma mortality.Methods:A meta-analysis was conducted of asthma deaths in randomised controlled clinical trials from the GlaxoSmithKline...

Safety of Long-Acting β-Agonists: Are New Data Really Required?

Safety of Long-Acting β-Agonists: Are New Data Really Required?

The pattern of risk of myocardial infarction in patients taking asthma medication: a study with the General Practice Research Database

To describe the patterns of risks of acute myocardial infarction (MI) during exposure to long-acting beta2-agonists (LABA). The study population consisted of patients aged 18+ years prescribed LABA or short-acting beta2-agonists (SABA) in the UK General Practice Research Database (GPRD). The outcomes included acute MI as recorded in GPRD and hospitalization for acute MI as obtained from the national registry of hospital admissions in England. The patterns of the hazard rates over time (i.e. absolute risks) were evaluated. The study population included 507,966 patients, who received a total of 5.5 million inhaled SABA, 4.0 million inhaled corticosteroids (ICS) and 1.3 million LABA prescriptions. In patients who recently started asthma medication, there were substantial changes in the hazard rates of MI over time: hazard rates were increased shortly following the prescription and then decreased. The hazard rates of MI in GPRD and of MI hospitalizations were proportional over time between inhaled SABA, LABA and ICS. Heavy long-term users (13+ Rx of the same asthma drug in the 1 year before) had increased risks of MI both with inhaled SABA and ICS. The relative rate in the heavy long-term users was 1.6 with inhaled SABA, 1.1 with LABA and 1.7 with ICS. The pattern of risk was similar between LABA with and without concomitant ICS use. The patterns of risks of MI were broadly similar between inhaled SABA, LABA and ICS, suggesting that there were no major differences between these drugs.

Use of salmeterol with and without concurrent use of inhaled corticosteroids and the risk of asthma-related hospitalization among patients with asthma

ABSTRACTRationale: Studies evaluating the safety of salmeterol are inconclusive, which might be the result from not taking into account the impact of concomitant inhaled corti­costeroids (ICS).Objective: To study whether salmeterol use with and without concomitant ICS, respectively, was associated with an increased risk of asthma-related hospitalizations among patients with asthma.Methods: A case-control study nested within a cohort of patients with asthma, identified in the year 2000, over a 2-year period was conducted. Cases were subjects who had a first-time hospitalization for asthma in the year 2001, and were matched with up to five controls by age (± 5 years), sex, and number of asthma-related outpatient visits.Measurements: Hospitalizations and medication use were extracted from the MEDSTAT's MarketScan database.Main results: There were 333 cases of asthma-related hospitalizations and 1607 matched control subjects. Any use of salmeterol with concomitant ICS use during the prior year was associated with a 32% risk reduction for being hospitalized due to asthma (OR = 0.68; 95% CI = 0.48, 0.96). In the presence of concomitant ICS use, patients who either used salmeterol currently or used seven or more canisters of salmeterol during the prior year had 46% (OR = 0.54, 95% CI = 0.32, 0.92), and 59% (OR = 0.41, 95% CI = 0.21, 0.79) reductions in the risk of hospital admissions for asthma, respectively.Limitations: Though indirect measure of asthma severity was adjusted during the analyses, the lack of information on lung function might result in a selection bias. Additionally, only a small sample size of patients was found to use salmeterol without concomitant ICS use, and this introduced the issue of lack of power.Conclusions: Use of salmeterol in conjunction with ICS is associated with a decreased risk of hospital admission for asthma.

Efficacy and safety of formoterol fumarate delivered by nebulization to COPD patients

Nebulized solutions of long-acting bronchodilators provide an alternative to DPI and MDI delivery, particularly for COPD patients unable to use hand-held devices easily or correctly. The long-acting beta2-agonist, formoterol fumarate, is differentiated by its onset of significant bronchodilation within 5 min of administration. In a randomized, double-blind, double-dummy trial, COPD subjects (n=351, mean forced expiratory volume FEV1=1.3 L, 44% predicted) received nebulized formoterol fumarate (Perforomist inhalation solution; FFIS 20 microg) or DPI (Foradil Aerolizer; FA 12 microg), or placebo twice daily for 12 weeks. Efficacy was assessed with 12-h pulmonary function tests, and quality of life was assessed before and after treatment with the St. George's Respiratory Questionnaire (SGRQ). At the 12-week endpoint, FFIS significantly increased FEV1 AUC0-12h relative to placebo (p<0.0001). No evidence of tachyphylaxis was observed as indicated by maintained FEV1 AUC and reduced rescue albuterol use throughout treatment. FFIS also significantly increased peak FEV1, trough FEV1, and standardized FVC AUC0-12h compared with placebo. SGRQ assessment at Week 12 demonstrated significant and clinically meaningful improvements in total score (FFIS vs placebo, -4.9, p=0.0067), symptom, and impact scores. No significant differences in efficacy were observed between the two active treatments. Drug related AEs in the FFIS arm with a frequency > or = 1% and exceeding placebo were dry mouth, nausea, and insomnia. Nebulized FFIS provided significant improvement in respiratory status and quality of life in subjects with COPD relative to placebo and was well tolerated. The efficacy and safety profile of FFIS was comparable to FA DPI.

Drug Compliance in Patients with Bronchial Asthma: Relation among Compliance with Different Types of Antiasthmatic Drug and Association with Daily Administration Frequency

ABSTRACT Background Not only monotherapy with inhaled corticosteroids (ICS) but also the concurrent use of other antiasthmatic agents, including leukotriene receptor antagonists (LTRA), play an important role in the management of asthma. However, few studies have focused on compliance with these drugs and on the relation between drug compliance and drug usage. Methods Data were derived from a survey of pharmacists dispensing antiasthmatic drugs to adults with asthma who visited participating pharmacies from October through November 2002. The patients were limited to regular users of ICS whose medication had not been changed for at least 6 months before the survey. Drug compliance and the daily administration frequency of antiasthmatic agents were evaluated on the basis of pharmaceutical records. Results Completed data were received for 322 patients. ICS compliance was lower than compliance with oral sustained-released theophylline (OSRT) and compliance with LTRA. ICS compliance significantly correlated with OSRT compliance and with LTRA compliance. There were no significant differences of ICS compliance among ICS alone, ICS + LTRA, ICS + OSRT and ICS + LTRA + OSRT group, while the daily inhalation frequency in ICS + OSRT or ICS + OSRT + LTRA group were higher than those in ICS alone group. Although there was a significant negative correlation between ICS compliance and daily inhalation frequency, neither OSRT compliance nor LTRA compliance significantly correlated with the tablet or capsule numbers per day. These findings indicate that OSRT may increase the compliance of concomitant ICS, and that the compliance of OSRT or LTRA is independent of the numbers of tablets taken per day. Conclusions These unique characteristics should be considered in the treatment and guidance of patients with bronchial asthma.