Salmeterol/fluticasone Combination Research Articles

2019 Year in Review: Aerosol Therapy.

Relevant publications related to medicinal and toxic aerosols are discussed in this review. Treatment of COPD includes a combination of long-acting bronchodilators and long-acting muscarinic antagonists. A combination of aclidinium bromide and formoterol fumarate was approved in the United States. The combination was superior to its components alone, as well as tiotropium and a salmeterol-fluticasone combination. Increased risk of an asthma exacerbation was reported in children exposed to electronic nicotine delivery systems. A smart inhaler capable of recording inspiratory flow was approved in the United States. The use of as-needed budesonide-formoterol was reported to be superior to scheduled budesonide and as-needed terbutaline for the treatment of adults with mild-to-moderate asthma. A survey among teens with asthma and their caregivers revealed a disagreement in the number of inhaled controller medications the teen was taking. Treatment with inhaled hypertonic saline resulted in a decreased lung clearance index in infants and preschool children with cystic fibrosis. Surgical masks were well tolerated and significantly decreased the burden of aerosolized bacteria generated by coughing in adults with cystic fibrosis. Inhaled liposomal amikacin in addition to guideline-based therapy was reported to be superior to guideline-based therapy alone in achieving negative sputum cultures in adult subjects with Mycobacterium avium complex pulmonary disease. During 2019, lung injury associated to e-cigarette or vaping was reported, including 60 casualties.

Cost-effectiveness of indacaterol/glycopyrronium in comparison with salmeterol/fluticasone combination for patients with moderate-to-severe chronic obstructive pulmonary disease: a LANTERN population analysis from Singapore.

In light of the growing evidence base for better clinical results with the use of the dual bronchodilator indacaterol/glycopyrronium (IND/GLY) over inhaled corticosteroid-containing salmeterol/fluticasone combination (SFC), this study aimed to evaluate the cost-effectiveness of IND/GLY over SFC in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) who are at low risk of exacerbations, in the Singapore healthcare setting. A previously published patient-level simulation model was adapted for use in Singapore by applying local unit costs. The model was populated with clinical data from the LANTERN and ECLIPSE studies. Both costs and health outcomes were predicted for the lifetime horizon from a payer's perspective and were discounted at 3% per annum. Costs were expressed in 2015 USD exchange rates. Uncertainty was assessed through probabilistic sensitivity analysis. Compared to SFC, use of IND/GLY increased mean life expectancy by 0.316 years and mean quality-adjusted life years (QALYs) by 0.246 years, and decreased mean total treatment costs (drug costs and management of associated events) by USD 1,474 over the entire lifetime horizon. IND/GLY was considered to be 100% cost-effective at a threshold of 1 × gross domestic product per capita. The cost-effectiveness acceptability curve showed that IND/GLY was 100% cost-effective at a willingness-to-pay threshold of USD 0 (additional cost) when compared to SFC. IND/GLY was estimated to be highly cost-effective compared to SFC in patients with moderate-to-severe COPD who are not at high risk of exacerbations in the Singapore healthcare setting.

Comparison of the clinical effects of combined salmeterol/fluticasone delivered by dry powder or pressurized metered dose inhaler

The salmeterol/fluticasone combination (SFC) inhaler is currently the most widely used maintenance drug for asthmatics worldwide. Although the effectiveness of SFC as either a dry powder inhaler (DPI) or a pressurized metered dose inhaler (pMDI) is well documented, there is limited data comparing the clinical efficacies of the two devices. To address this issue, we carried out a randomized crossover trial in which asthmatic patients (n = 47; mean age, 62.5 ± 16.5 years old) received a 12-week treatment of SFC DPI (50/250 μg twice daily) or SFC pMDI (four puffs of 25/125 μg daily). After a 4-week washout period, patients received another crossover treatment for 12 weeks. Respiratory resistance and reactance were measured by forced oscillation technique (MostGraph-01), spirometry, fractional exhaled nitric oxide (FeNO), and an asthma control test (ACT) every 4 weeks. The mean forced expiratory volume1.0 at the baseline was 2.16 ± 0.86 (L). Respiratory system resistance at 5 Hz (R5), the difference between R5 and R at 20 Hz (R5 – R20), and FeNO improved in both treatment groups, while reactance at 5 Hz (X5) and ACT score improved only in the pMDI group. In patients >70 years old (n = 21), R5, R5 – R20, ΔX5, and FeNO improved only in the pMDI group. These results suggest that SFC by pMDI produces a stronger anti-inflammatory and bronchodilatory effect even in patients whose asthma is well controlled by SFC delivered by DPI.

Impact of ABCB1 single-nucleotide polymorphisms on treatment outcomes with salmeterol/fluticasone combination therapy for stable chronic obstructive pulmonary disease.

To investigate the relationship between ABCB1 single-nucleotide polymorphisms and the efficacy of salmeterol/fluticasone combination (SFC) inhalation therapy for stable chronic obstructive pulmonary disease (COPD) in a Chinese Han population. A total of 362 patients with stable COPD were recruited between July 2012 and March 2014. Based on the therapeutic effects of lung function improvement and COPD Assessment Test (CAT) scores, all patients were either placed into the effective group (n = 138) or the ineffective group (n = 224). Three common polymorphisms (rs1045642C > T, rs1128503C > T, and rs1202184A > G) in the ABCB1 gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism in these patients. All data were analyzed by SPSS version 18.0 software. The genotype and allele frequencies of the ABCB1 rs1045642C > T polymorphic locus were significantly different between the effective group and the ineffective group under the codominant, recessive, and allele models (all p < 0.05). Haplotype analysis of ABCB1 indicated that CTA (rs1045642C-rs1128503T-rs1202184A) haplotype frequencies in the effective group were significantly lower than the ineffective group (p = 0.022), but TCG (rs1045642T-rs1128503C-rs1202184G) haplotype frequencies in the effective group were significantly higher than the ineffective group (p = 0.048). Logistic regression analysis showed that smoking history and rs1045642 CT + CC/TT may be correlated with the efficacy of SFC inhalation therapy in stable COPD patients. ABCB1 rs1045642C > T polymorphism and CTA/TCG haplotypes, as well as smoking history may influence the efficacy of SFC inhalation therapy in stable COPD patients in the Chinese Han population.

Salmeterol/fluticasone through breath-actuated inhaler versus pMDI: a randomized, double-blind, 12 weeks study

Objective: Salmeterol/fluticasone combination (SFC) formulated in a breath-actuated inhaler (BAI) overcomes the co-ordination problem associated with the pressurized-metered dose inhaler (pMDIs). Our aim was to compare the efficacy and the safety of SFC given through the BAI versus the conventional pMDI in moderate-to-severe asthmatics. Methods: In this randomized, double-blind, double-dummy, prospective, active-controlled, parallel group, multicenter, 12 weeks study, 150 asthmatics were randomized to receive SFC (25/125 mcg) through either BAI or pMDI. The primary efficacy endpoint was mean change in pre-dose morning PEFR value at 12 weeks and the secondary efficacy endpoints included, mean change in FEV1, pre-bronchodilator FVC, pre-dose morning and evening PEFR, symptom scores at 2, 4, 8, and 12 weeks. Patient preferences for device and safety were also assessed. Results: At 12 weeks, the mean change in pre-dose morning PEFR in BAI and pMDI groups was 50.72 L/min and 48.82 L/min, respectively (p < 0.0001; both groups) and the difference between the two groups was not significant. Both the treatment groups showed a statistically significant improvement in secondary endpoints at all-time points compared with baseline. The usability questionnaire assessment results showed that the BAI device was preferred by 75% of patients as compared with 25% preferring pMDI. SFC in both BAI and pMDI devices was found to be safe and well tolerated. Conclusion: This is the first study to demonstrate that SFC given through the BAI produces comparable efficacy and safety endpoints as pMDI. Additionally, BAI was the preferred inhaler by patients compared to conventional pMDI.

Role of combined indacaterol and glycopyrronium bromide (QVA149) for the treatment of COPD in Japan.

Once-daily dual-bronchodilator therapy with combined indacaterol and glycopyrronium bromide in one device (Ultibro, Breezhaler), often called QVA149, was first approved in 2013 in Japan and Europe. As of November 2014, more than 40 countries had approved this medication except for the USA. This is the first dual bronchodilator in one device. Now, the Breezhaler is the only device that can provide long-acting muscarinic antagonist (glycopyrronium bromide), long-acting beta agonist (indacaterol), and a combination of the two medications (QVA149). The choice among the three medications allows a patient to use the same inhalation device even when the regimen is changed from single-bronchodilator therapy to dual-bronchodilator therapy. In addition, the quick bronchodilation effect and once-daily administration can improve patient adherence to medical treatment for chronic obstructive pulmonary disease (COPD). To our knowledge, as of November 2014, the safety and the efficacy of QVA149 have been evaluated in 14 randomized controlled trials. The 14 trials generally showed good safety profiles, and there were better or not-inferior bronchodilator effects of QVA149 when compared with placebo, or other inhaled medication. According to the Japanese Respiratory Society guidelines, QVA149 is a combination of the two first-line bronchodilators. Our meta-analysis indicated that QVA149 is superior to the salmeterol–fluticasone combination to treat COPD in respect of the frequency of adverse effects, exacerbation, pneumonia, and improvement of trough forced expiratory volume in 1 second (FEV1). Thus, we believe that QVA149 can be a key medication for COPD treatments.

Efficacy and Safety of Umeclidinium/Vilanterol (UMEC/VI) Once Daily (OD) vs Fluticasone/Salmeterol Combination (FSC) Twice Daily (BD) in Patients With Moderate-to-Severe COPD and Infrequent COPD Exacerbations

Efficacy and Safety of Umeclidinium/Vilanterol (UMEC/VI) Once Daily (OD) vs Fluticasone/Salmeterol Combination (FSC) Twice Daily (BD) in Patients With Moderate-to-Severe COPD and Infrequent COPD Exacerbations

P237 Comparison of COPD exacerbations with once-daily QVA149 versus twice-daily salmeterol/fluticasone combination: the ILLUMINATE study

IntroductionExacerbations are the most frequent cause of hospitalisation and death among patients with COPD. Combinations of long-acting bronchodilators maximise bronchodilation and may reduce the risk of exacerbations. QVA149, a once-daily...

Effect of fluticasone/salmeterol combination on dyspnea and respiratory mechanics in mild-to-moderate COPD

The purpose of this exploratory physiological study was to evaluate the effects of inhaled fluticasone/salmeterol combination (FSC) on sensory and physiological responses to exercise in subjects with mild-to-moderate COPD. In a randomized, double-blind, placebo-controlled, crossover study, subjects underwent 6-week treatments with FSC or placebo (PLA). Detailed pulmonary function and constant-work rate cycle exercise tests were performed following each treatment period. Fifteen subjects completed the study (mean±SD): age 64±10 years; smoking history 47±29 pack-years; post-bronchodilator forced expiratory volume in 1s 86±15 %predicted (10 mild and 5 moderate COPD); peak incremental oxygen uptake 71±16 %predicted. Compared with PLA, FSC treatment was associated with improved: FEV1 by 0.23±0.18L; inspiratory capacity by 0.18±0.23L; functional residual capacity by -0.28±0.30L; and specific airways resistance by -4.6±4.5cmH2Os (all p<0.01). There were no significant changes in dyspnea intensity throughout exercise and endurance time did not change significantly (1.2±3.0min, p=0.149). Following FSC, inspiratory capacity at rest and throughout exercise increased by 0.2-0.3L with concomitant increases in tidal volume and ventilation (p<0.05). Compared with PLA, the work of breathing and the ratio of respiratory muscle effort to tidal volume improved with FSC during exercise (p<0.05). In mild-to-moderate COPD, FSC was associated with significant improvements in airway function at rest and during exercise. Despite important mechanical improvements, there were no significant effects on dyspnea intensity and exercise endurance.

Effect of Combination Fluticasone Propionate and Salmeterol or Inhaled Corticosteroids on Asthma-Related Outcomes in a Medicare-Eligible Population

BackgroundNational asthma treatment guidelines recommend either the use of inhaled corticosteroids (ICS) or ICS in combination with a long-acting bronchodilator for the treatment of moderate to severe asthma. Even though asthma is common among older adults, few studies have assessed the differences in effectiveness between these two recommended therapies in patients over 65 years of age. ObjectiveThe aim of this study was to assess the association of the fluticasone-salmeterol combination (FSC) or ICS initiation on asthma-related events in Medicare-eligible asthma patients. MethodsThis was a retrospective observational study using a large health claims database (July 1, 2001 to June 30, 2008). Subjects 65 to 79 years of age with 12-month preindex and 3- to 12-month postindex eligibility, an asthma diagnosis (ICD-493.xx), and with 1 or more FSC or ICS claims at index were included. Subjects with an FSC or ICS claim in the preindex and any claim for chronic obstructive pulmonary disease were excluded. Subjects were observed until they had an event (emergency department [ED] inpatient hospitalization [IP], combined IP/ED or oral corticosteroid [OCS] use) or were no longer eligible in the database, whichever came first. Cox proportional hazards regression was used to assess risk of an asthma-related event (IP, ED, or IP/ED). Baseline characteristics (age, sex, region, index season, comorbidities, preindex use of short-acting β-agonists, OCS, other asthma controllers, and asthma-related ED/IP visits) were independent covariates in the model. ResultsA total of 10,837 met the criteria (4843 ICS and 5994 FSC). Age (70.4 and 70.5 years, respectively) and the percentage of female subjects (65.5% and 64.8%, respectively) were similar. Asthma-related events were also similar at baseline. Postindex unadjusted rates occurring after >30 days were ED (1.8% vs 1.5%, P = 0.18), IP (2.7% vs 1.7%, P < 0.001), and ED/IP (4.1% vs 2.8%, P < 0.001) for ICS and FSC, respectively. Subjects who received FSC were associated with a 32% (adjusted HR = 0.68; 95% CI, 0.51–0.91) lower risk of experiencing an IP visit and a 22% (HR = 0.78; 95% CI, 0.62–0.98) lower risk of experiencing an ED/IP visit. No differences were observed for ED visits (HR = 0.94; 95% CI, 0.68–1.29). ConclusionsIn Medicare-eligible asthma patients, FSC use was associated with lower rates of asthma-related serious exacerbations compared with ICS.

Observational Study on the Impact of Initiating Tiotropium Alone Versus Tiotropium with Fluticasone Propionate/Salmeterol Combination Therapy on Outcomes and Costs in Chronic Obstructive Pulmonary Disease

BackgroundThis retrospective cohort study compared the risks of exacerbations and COPD-related healthcare costs between patients with chronic obstructive pulmonary disease (COPD) initiating tiotropium (TIO) alone and patients initiating triple therapy with fluticasone-salmeterol combination (FSC) added to TIO.MethodsManaged-care enrollees who had an index event of ≥ 1 pharmacy claim for TIO during the study period (January 1, 2003-April 30, 2008) and met other eligibility criteria were categorized into one of two cohorts depending on their medication use. Patients in the TIO+FSC cohort had combination therapy with TIO and FSC, defined as having an FSC claim on the same date as the TIO claim. Patients in the TIO cohort had no such FSC use. The risks of COPD exacerbations and healthcare costs were compared between cohorts during 1 year of follow-up.ResultsThe sample comprised 3333 patients (n = 852 TIO+FSC cohort, n = 2481 TIO cohort). Triple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation (hazard ratio 0.772; 95% confidence interval [CI] 0.641, 0.930) and any exacerbation (hazard ratio 0.763; 95% CI 0.646, 0.949) and a nonsignificant reduction in COPD-related adjusted monthly medical costs.ConclusionsTriple therapy with FSC added to TIO compared with TIO monotherapy was associated with significant reductions in the adjusted risks of moderate exacerbation and any exacerbation over a follow-up period of up to 1 year. These improvements were gained with triple therapy at roughly equal cost of that of TIO alone.

Effect of Switching from Salmeterol/Fluticasone to Formoterol/Budesonide Combinations in Patients with Uncontrolled Asthma

Combination therapy with an inhaled corticosteroid (ICS) and a long-acting β(2)-agonist (LABA) in a single inhaler is the mainstay of asthma management and salmeterol/fluticasone combination (SFC) and fixed-dose formoterol/budesonide combination (FBC) are currently available in Japan; however, there is nothing to choose between the two. The purpose of this study was to clarify the effect of switching from SFC to FBC in patients with asthma not adequately controlled under the former treatment regimen. This was a prospective, multicenter, open-label, uncontrolled longitudinal study in 87 adult patients with an Asthma Control Questionnaire, 5-item version (ACQ5) score of greater than 0.75 under treatment with SFC 50/250μg one inhalation twice daily (bid). SFC was switched to FBC 4.5/160μg two inhalations bid. Study outcomes included ACQ5 score, peak expiratory flow (PEF), FEV(1), and fractional exhaled nitric oxide (FeNO) at the end of treatment period. Eighty-three patients completed the study. ACQ5 scores improved and exceeded the clinically meaningful difference after 12 weeks of treatment and well-controlled asthma (ACQ5 score ≤0.75) was attained in 37 (44.6%) patients. Minimum and maximum PEF and FEV(1) values improved significantly, but not FeNO values, after switching from SFC to FBC. Switching ICS/LABA combination therapy is a useful option in the management of asthma that is not optimally controlled.

Effects of intranasal salmeterol and fluticasone given alone and in combination in persistent allergic rhinitis

Backgroundβ2-Agonists have previously been shown to be effective inhibitors of mediator release from airway mucosal mast cells. ObjectiveTo evaluate the effects of intranasal salmeterol and fluticasone propionate alone and in combination on the response to nasal adenosine monophosphate (AMP) challenge to assess mast cell activation. MethodsTwenty-three patients with persistent allergic rhinitis completed a randomized, double-blind, placebo-controlled, 4-way crossover trial. They received once daily treatment with placebo, salmeterol, 50 μg, fluticasone propionate, 500 μg, or fluticasone propionate and salmeterol combination, 500/50 μg, delivered via an antistatic spacer with nasal adapter for 1 week each, with trough measurements being made 12 hours after the first and last dose. The primary outcome was the maximum percentage decrease in peak nasal inspiratory flow after nasal AMP challenge. ResultsFor the primary outcome there was significant protection after single and long-term dosing with fluticasone alone and fluticasone-salmeterol combination, whereas salmeterol alone only afforded protection after the first dose. Fluticasone-salmeterol combination and fluticasone but not salmeterol conferred significant chronic dosing effects on secondary outcomes of nasal symptoms and disease-specific quality of life. There was no potentiation of the response to fluticasone by salmeterol on any outcomes when given in combination. ConclusionChronic dosing with fluticasone but not salmeterol confers anti-inflammatory activity against nasal AMP challenge, but there was no potentiation of fluticasone when given in combination with salmeterol. Thus, salmeterol may not be an effective treatment for use in allergic rhinitis. Trial Registrationclinicaltrials.gov Identifier: NCT01388595.

Down-titration from high-dose combination therapy in asthma: Removal of long-acting β 2-agonist

Asthma guidelines recommend reducing inhaled corticosteroids (ICS) to the minimum effective dose, but the timing of long-acting beta(2)-agonist (LABA) withdrawal is unclear. Recent FDA guidelines recommend LABA withdrawal once asthma is well-controlled. This 13-month double-blind study of patients taking high-dose combination therapy investigated the effect of discontinuation of LABA before ICS down-titration. Adults using salmeterol/fluticasone combination (SFC) 50/500 microg bd were randomized to SFC 50/500 microg bd or fluticasone propionate (FP) 500 microg bd, with subsequent ICS down-titration 8-weekly using a clinical algorithm. The primary outcome was mean daily FP dose, including ICS for exacerbations. 82 subjects were randomized. Asthma was well-controlled at baseline, with mean FEV(1) 84.8% predicted and Asthma Control Questionnaire (ACQ) score 0.9. There was no significant difference in mean daily FP dose (SFC: 721 microg, FP:816 microg, p = 0.3), but final dose was lower with SFC (534 microg cf. 724 microg, p = 0.005). ICS dose was reduced by >or=80% in 41% SFC and 15% FP patients. Ambulatory lung function was significantly higher with SFC, but there were no differences between groups in rescue beta(2)-agonist use, clinic spirometry, airway responsiveness, ACQ, sputum eosinophils or FeNO. Baseline airway responsiveness, and pre-reduction blood eosinophils, were significant predictors of mean daily FP dose and dose reduction failure respectively. Many patients prescribed high-dose combination therapy may be over-treated. Substantial reductions in dose can be achieved with a clinical algorithm, reaching lower FP doses with SFC than FP without losing asthma control or increasing disease activity. This study was commenced before mandatory registration of clinical trials.

喘息の治療と管理におけるサルメテロール／フルチカゾン製剤の費用対効果―プロピオン酸フルチカゾンとの比較検討―

We commenced to estimate the economic impact of salmeterol/fluticasone combination (SFC) therapy compared to fluticasone propionate (FP) therapy for asthma control in Japanese patients. A Markov model with five health states, developed by Price in 2002, was used. 1-week transition probabilities among status of asthma management were obtained from literature and epidemiological data from public data base. Direct cost for treatment was estimated from Japan medical fee schedule. Cost and effectiveness were not discounted due to 12-week simulation by the model. Univariate sensitivity analyses were undertaken to examine the main variables affecting cost-effectiveness. Probabilistic analysis was also undertaken to discuss statistical argument and to provide information for decision-making. In this analysis, the model was run over a 12-week period of time using transition probabilities. The results showed that treatment with SFC resulted in a higher proportion of totally controlled weeks per patient than treatment with FP (65.0 vs. 49.5%; incremental effectiveness by 15.5%), and lower mean direct asthma management costs ( yen168 702 vs. yen227 820). Probabilistic sensitivity analysis, conducted to assess robustness of the above base case result, showed that in the 95% of cases SFC was dominant (more effective and less costly) to FP. It suggested that SFC will be the most cost-effective therapy for asthma control. It would, however, be required to further evaluate cost-effectiveness of SFC in long-term observation.

Additional effects of pranlukast in salmeterol/fluticasone combination therapy for the asthmatic distal airway in a randomized crossover study

Background Salmeterol/fluticasone combination (SFC) therapy is used to control inflammation in the distal airway of patients with well-controlled asthma, but the efficacy of this approach is unclear. Objectives The goal of the study was to evaluate the effect of pranlukast, a leukotriene receptor antagonist (LTRA), on distal airway inflammation and pulmonary resistance in patients with asthma that was well-controlled using SFC therapy alone. Methods The subjects were 32 patients with well-controlled asthma (age 61.1 ± 17.8 years old, Step 3 in the GINA guidelines, Asthma Control Test score 23.2 ± 1.8 points) based on use of SFC therapy alone for more than 3 months. These subjects were randomly assigned to groups receiving SFC alone or SFC + LTRA (pranlukast 450 mg daily) and then switched to the opposite group after 4 weeks in a crossover manner. Eosinophilic inflammation in induced sputum samples was assessed after each treatment period. Sputum was induced by inhalation of 10% hypertonic saline for 15 min. Impulse oscillometry parameters (R5, R20, X5 and AX) and spirometry were examined during each period. The Asthma-related Quality of Life Questionnaire (AQLQ) was also administered in each period. Results The ECP levels in late-phase sputum were significantly higher than those in early-phase sputum with SFC therapy alone (178.3 ± 166.0 vs. 65.5 ± 68.9 μg/l, p < 0.001), whereas these values did not differ significantly with SFC + LTRA treatment (70.9 ± 95.1 vs. 54.6 ± 65.7, p = 0.554). ECP levels in late-phase sputum with SFC therapy were also significantly higher than those with SFC + LTRA ( p = 0.045). The values of R5, R20, R5–R20 (kPa/(L/s)), and AX (kPa/L) all significantly improved during with SFC + LTRA treatment compared with SFC alone (median (25–75 percentile)): 0.350 (0.283–0.440) vs. 0.340 (0.280–0.378), p = 0.036; 0.280 (0.233–0.365) vs. 0.270 (0.240–0.318), p = 0.019; 0.050 (0.030–0.110) vs. 0.500 (0.030–0.073), p = 0.032; and 0.570 (0.308–1.045) vs. 0.410 (0.263–0.820), p = 0.014; respectively. Pulmonary function indexes did not differ significantly between the two treatments, but the symptom and activity limitation domains of the AQLQ were significantly improved by SFC + LTRA treatment. Conclusion This study suggests that the combination of SFC and LTRA may give better control of residual eosinophilic inflammation in the distal airway compared with SFC therapy alone.

The response to combination therapy treatment regimens in severe/difficult-to-treat asthma

The aim of the present study was to assess the response of high-dose salmeterol/fluticasone combination (SFC) and low-dose SFC compared with regimens without inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA) in a large cohort with severe or difficult-to-treat asthma. Subjects were administered low-dose SFC (100/50 or 250/50 microg) or high-dose SFC (500/50 microg), and a control group received medications that could include ICS or LABA but not both. The present authors calculated unadjusted and propensity score-adjusted differences in outcomes consistent with components of asthma control, comparing high-dose and low-dose SFC cohorts with controls. The low-dose SFC cohort had higher asthma-related quality of life and fewer asthma control problems compared with controls. The high-dose SFC cohort had higher forced expiratory volume in one second but higher odds of having severe asthma compared with controls. The present results support the evidence that some asthmatics achieve better outcomes while receiving a low-dose salmeterol/fluticasone combination, but also suggest that those on a high-dose salmeterol/fluticasone combination fail to achieve significant improvement in many control-related health outcomes as compared with similar patients not receiving salmeterol/fluticasone combination. These findings suggest a limited value of high-dose salmeterol/fluticasone combination compared with the alternatives. While additional studies are needed, the present findings call for alternative therapeutic approaches in severe/difficult-to-treat asthma for those unable to attain asthma control with or without salmeterol/fluticasone combination.

Tiotropium and salmeterol/fluticasone combination do not cause oxygen desaturation in COPD

It has been documented that tiotropium is less likely to induce oxygen desaturation in stable COPD patients compared to long-acting beta2-agonists (LABAs) and combined administration of a LABA and an inhaled corticosteroid (ICS) reduces the potential for acute effects of LABA on blood-gas tensions. In this study, we have compared the acute effects of tiotropium 18 microg and salmeterol/fluticasone combination (SFC) 50/250 microg on arterial blood gases in 20 patients with stable COPD. Each subject was studied on 2 days, separated from one another by at least 4 days. Blood specimens were taken just before the inhalation and at 15, 30, 60, 180 and 360 min after inhalation of each treatment, and spirometry was performed at the same time points. As expected, both treatments significantly improved FEV1 (greatest changes were 0.20 L, 95% CI: 0.13-0.27 at 360 min after tiotropium; and 0.13 L, 95% CI: 0.06-0.19 at 180 min after SFC). The greatest mean changes from baseline in PaO2 were -1.7 (95% CI: -4.0 to 0.6)mmHg, p=0.134, after tiotropium; -0.8 (95% CI: -2.2 to 0.6)mmHg, after SFC. Both changes were observed after 15 min. Both drugs caused a small decrease in PaCO2 (greater changes: -1.9 (95% CI -3.2 to -0.6)mmHg, p=0.005 at 60 min after tiotropium; and -2.4 (95% CI: -3.5 to -1.3) mmHg, p=0.0002 at 180 min after SFC). These results indicate that both tiotropium and SFC are able to induce a significant long-last bronchodilation without affecting arterial blood gases. Moreover, they confirm that the impact of tiotropium on PaO2 is small and without clinical significance and the addition of a LABA to an ICS can reduce the potentially dangerous acute effect of the LABA on blood gases.

The long-acting beta-agonist controversy: A clinical dilemma

The Food and Drug Administration approved new safety labeling on March 2, 2006 for medication containing salmeterol, a long-acting beta-agonist (LABA), because of data suggesting an increased risk of fatal or potentially fatal asthma episodes. The "black box" warning, public health advisory, and label change for salmeterol, salmeterol-fluticasone combination, and formoterol has heightened public and physician concern over the risk-to-benefit ratio and the medicolegal implications of prescribing these agents for patients with asthma. A problem-based learning (PBL) case was presented to several breakout groups at the Eastern Allergy Conference, May 6, 2006, in Naples, FL, focusing on the LABA controversy in the context of an actual patient. The consensus of opinion during the interactive group sessions among approximately 100 allergists was that (1) the patient had poorly controlled asthma on inhaled corticosteroid (ICS) monotherapy and that warranted a change of therapy; (2) each physician must choose which option presents the best benefit-to-risk ratio after a thorough and open discussion with the patient; (3) of the several choices for step-up therapy when a patient is not well controlled on an ICS alone, the best choice based on current evidence is combined ICS plus LABA. After the PBL case discussion, a didactic lecture was presented describing the evidence pertaining to the LABA controversy, which is detailed in this article.

Duration of action of the salmeterol/fluticasone combination inhaler administered in the evening: A randomized controlled trial in childhood asthma

To investigate the duration of bronchodilator action of a salmeterol/fluticasone combination (SFC) inhaler when administered in the evening to children with asthma. A double-blind, placebo-controlled, cross-over study. Hospital inpatient. Fourteen children aged between 4 and 11 years with mild to moderate asthma (FEV(1) > 60% predicted) who exhibited a 15% increase in FEV(1) with bronchodilator. SUBJECTS inhaled, in random order, either SFC (100/50 microg) or placebo, via accuhaler, at 20.00 hours on two separate occasions with at least 3 days between study days. Lung function measurements including FEV(1), PEF, specific airways conductance (sGaw) and maximum expiratory flow at 25-75% of vital capacity were measured at baseline, 2, 12, 16, 20 and 24 h. For all lung function parameters SFC resulted in significantly greater bronchodilation than placebo for at least 20 h after inhalation. At 24 h, the increase in FEV(1) and PEF compared with placebo was 0.08 L (95% confidence interval: -0.18 to 0.02, P = 0.16) and 27 L/min (95% confidence interval: -47 to -6, P = 0.004), respectively. The single administration of SFC via an accuhaler in the evening resulted in significant bronchodilation for at least 20 h in children with asthma.