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This large trial involving children with asthma examined whether the addition of a long-acting beta-agonist to current therapy with inhaled glucocorticoids affected asthma control in children. The primary safety end point was within the prespecified noninferiority margin. The safety of inhaled beta-agonists in patients with asthma has been debated since the 1960s. 1 – 5 After the introduction of long-acting beta-agonists (LABAs) in the 1990s and the findings of two studies involving adults, attention focused on a potential association of LABAs with an increased risk of asthma-related death. 6 , 7 A 2008 meta-analysis conducted by the Food and Drug Administration (FDA) showed a higher risk of asthma-related events (death, intubation, or hospitalization) among patients receiving LABAs than among patients not receiving these medications. 8 In a subsequent meta-analysis, a higher risk of serious asthma-related events was observed with salmeterol than with . . .

Inhaled glucocorticoids may prevent a mild loss of asthma control from becoming a full exacerbation. In a randomized trial involving children, quintupling the daily dose at early signs of loss of asthma control did not result in a lower rate of severe asthma exacerbations. Increases in symptoms may occur before exacerbations fully develop. In two trials, when symptoms occurred, the dose of inhaled glucocorticoids was increased by a factor of 5 (pediatric trial) or 4 (adult trial). There was no benefit, and perhaps some harm, in children, and a modest benefit in adults.

Increases in symptoms may occur before exacerbations fully develop. In a trial involving adults and adolescents, quadrupling the dose of inhaled glucocorticoids when symptoms occurred resulted in fewer severe asthma exacerbations than not increasing the dose. Increases in symptoms may occur before exacerbations fully develop. In two trials, when symptoms occurred, the dose of inhaled glucocorticoids was increased by a factor of 5 (pediatric trial) or 4 (adult trial). There was no benefit, and perhaps some harm, in children, and a modest benefit in adults.

Patients with obstructive sleep apnea (OSA) often struggle with CPAP therapy adherence. The intranasal corticosteroids (INS) alone have not significantly improved CPAP adherence but the combination drugs that faster relieved symptoms were not well studied. This study aimed to assess the combined effectiveness of INS (fluticasone propionate) and intranasal antihistamines (azelastine hydrochloride) in enhancing CPAP adherence and mitigating CPAP-induced rhinitis symptoms in OSA patients. A double-blind, randomized controlled trial with stratified random sampling was conducted at Thammasat University Hospital from March 2022 to March 2023. Participants included OSA patients undergoing CPAP treatment. The patients completed questionnaires and interviews at the baseline, the second week, and one month after starting CPAP therapy, with CPAP usage electronic data collected. Among 116 enrolled patients, most had severe OSA (78.9%), with a majority being male (56.9%). The intervention group did not significantly differ from the placebo group in terms of CPAP usage, nasal symptoms, quality of life, or side effects. Subgroup analysis showed improved CPAP adherence in the treatment group when using pressure below 15 cm H 2 O (7.8% increase in CPAP usage days, P  = 0.04). This study marks the first evaluation of combination drugs for enhancing CPAP therapy adherence in OSA patients. Although these drugs did not significantly enhance overall CPAP adherence, there was a trend toward increasing CPAP adherence in patients using lower pressure levels. Thus, combining fluticasone and azelastine may benefit certain OSA patients. Further research is essential to comprehend and validate these benefits fully. Clinicaltrials.in.th number TCTR20220308003 (08/03/2022).

Whether an increase in the dose of inhaled glucocorticoids or the addition of long-acting beta-agonists will lead to better outcomes in black children with moderate asthma is not known. Surprisingly, the data showed that increased doses of an inhaled glucocorticoid were as effective as addition of a LABA.

Many patients with chronic obstructive pulmonary disease (COPD) have an accelerated loss of lung function. It is unclear whether drug treatment can modify this in patients with moderately severe disease. In a prespecified analysis of the key secondary outcome in SUMMIT (Study to Understand Mortality and Morbidity), we investigated whether the inhaled corticosteroid fluticasone furoate (FF; 100 μg), the long-acting β-agonist vilanterol (VI; 25 μg), or their combination (FF/VI) modified the rate of decline in FEV compared with placebo. We also investigated how baseline covariates affected this decline. Spirometry was measured every 12 weeks in this event-driven, randomized, placebo-controlled trial of 16,485 patients with moderate COPD and heightened cardiovascular risk. An average of seven spirometric assessments per subject among the 15,457 patients with at least one on-treatment measurement were used in the analysis of rate of FEV decline. All statistical comparisons are considered nominal. The adjusted rates of FEV decline were -46 ml/yr (-3.0% of baseline) with placebo, -47 ml/yr (-3.1%) with VI, -38 ml/yr (-2.5%) with FF, and -38 ml/yr (-2.3%) with FF/VI. FF-containing regimens had lower rates of decline than placebo (P < 0.03), and FF/VI had a lower rate of decline than VI alone (P < 0.005). The FEV decline was faster in current smokers, those with a lower body mass index, males, and patients with established cardiovascular disease. In patients with moderate COPD and heightened cardiovascular risk, FF alone or in combination with VI appears to reduce the rate of FEV decline. Clinical trial registered with www.clinicaltrials.gov (NCT01313676).

Background: The efficacy and safety of fluticasone propionate/formoterol fumarate pressurized metered-dose inhaler (pMDI) (fluticasone/formoterol; Flutiform®; 100/10 µg b.i.d.) was compared with fluticasone propionate (Flixotide® Evohaler® pMDI; 100 µg b.i.d.) and fluticasone/salmeterol (Seretide® Evohaler® pMDI; 100/50 µg b.i.d.) in a pediatric asthma population (EudraCT number: 2010-024635-16). Methods: A double-blind, double-dummy, parallel group, multicenter study. Patients, aged 5–<12 years with persistent asthma ⩾ 6 months and forced expiratory volume in 1 s (FEV1) ⩽ 90% predicted were randomized 1:1:1 to 12 weeks’ treatment. The study objectives were to demonstrate superiority of fluticasone/formoterol to fluticasone and non-inferiority to fluticasone/salmeterol. Results: A total of 512 patients were randomized: fluticasone/formoterol, 169; fluticasone, 173; fluticasone/salmeterol, 170. Fluticasone/formoterol was superior to fluticasone for the primary endpoint: change from predose FEV1 at baseline to 2 h postdose FEV1 over 12 weeks [least squares (LS) mean difference 0.07 l; 95% confidence interval (CI) 0.03, 0.11; p < 0.001] and the first key secondary endpoint, FEV1 area under the curve over 4 hours (AUC0–4 h) at week 12 (LS mean difference 0.09 l; 95% CI: 0.04, 0.13; p < 0.001). Per a prespecified non-inferiority margin of −0.1 l, fluticasone/formoterol was non-inferior to fluticasone/salmeterol for the primary endpoint (LS mean difference 0.00 l; 95% CI −0.04, 0.04; p < 0.001) and first key secondary endpoint (LS mean difference 0.01; 95% CI −0.03, 0.06; p < 0.001). Fluticasone/formoterol was non-inferior to fluticasone/salmeterol for the second key secondary endpoint, change from predose FEV1 over 12 weeks (treatment difference −0.02 l; 95% CI −0.06, 0.02; p < 0.001), but was not superior to fluticasone for this endpoint (LS mean difference 0.03 l; 95% CI −0.01, 0.07; p = 0.091). All treatments elicited large improvements from baseline to week 12 for the Pediatric Asthma Quality of Life Questionnaire (LS mean change 0.76 to 0.85 units) and Asthma Control Questionnaire (LS mean change −1.03 to −1.13 units). Few severe exacerbations were seen (fluticasone/formoterol: two; fluticasone/salmeterol: two). All treatments were well tolerated. Conclusions: This study supports the efficacy and safety of fluticasone/formoterol in a pediatric asthma population and its superiority to fluticasone.

Abstract Background: Easyhaler® dry powder inhaler (DPI) containing salmeterol and fluticasone propionate was developed for the treatment of asthma and chronic obstructive pulmonary disease. Three different Salmeterol/fluticasone Easyhaler test products (Orion Pharma, Finland) were compared against the reference product Seretide® Diskus® DPI (GlaxoSmithKline, United Kingdom) to study whether any of the test products are bioequivalent with the reference. Methods: Open and randomized pharmacokinetic four-period crossover study on 65 healthy volunteers was performed in a single center to compare the lung deposition and total systemic exposure of salmeterol and fluticasone propionate after administration of single doses (two inhalations of 50/500 μg/inhalation strength) in fasting conditions. Blood samples were drawn before dosing and at frequent time points between 2 minutes and 34 hours after dosing for determination of drug concentrations. The primary variables for total systemic exposure and lung deposition of fluticasone propionate were maximum concentration of the concentration–time curve (Cmax) and area under the concentration–time curve from time zero to the last sample with quantifiable concentration (AUCt). For salmeterol, the primary variables for total systemic exposure were Cmax and AUCt and for lung deposition Cmax and AUC up to 30 minutes after study treatment administration (AUC30min). Results: One of the Easyhaler test products met all the criteria for bioequivalence with the reference. The 96.7% confidence intervals (CIs) for the test/reference ratios of fluticasone propionate Cmax and AUCt were 0.9901–1.1336 and 0.9448–1.0542, respectively. Ninety percent CIs for salmeterol Cmax, AUC30min, and AUCt ratios were 1.0567–1.2012, 1.0989–1.2255, and 1.0769–1.1829, respectively. Median salmeterol time to maximum concentration (tmax) was 4.0 minutes. Median fluticasone propionate tmax was from 1.5 to 2.0 hours. Terminal elimination half-life was 11 hours for salmeterol and 9–10 hours for fluticasone propionate. Conclusions: Salmeterol/fluticasone Easyhaler was shown to be bioequivalent with the reference product.

ObjectiveTo assess the effectiveness of a potent topical corticosteroid (TCS) as an initial treatment in primary care for children with moderate flare-ups of atopic dermatitis (AD), compared to starting on a mild TCS.DesignAn observational prospective cohort study with an embedded pragmatic multicentre open-label randomised controlled trial.SettingA total of 53 general practices in the southwest of the Netherlands took part in the study.Participants209 children aged 3 months to 17 years diagnosed with AD (International Classification of Primary Care codes S87 or S88) who visited their general practitioner (GP) for AD or received repeat prescriptions for AD in the previous 12 months were included in the cohort study through the general practices. Finally, 32 patients (15%) were randomised and assigned to the trial (13 girls; 19 boys; median age 4.0 years).InterventionsIf cohort participants experienced a moderate flare-up (ie, need to intensify topical treatment from the child’s and/or parents’ point of view of AD and a three-item severity score from three to<6 scored by their GP) during cohort follow-up, they were randomised to either the intervention group, a strong TCS (class III, fluticasone propionate 0.05%), or the control group, a mild TCS (class I, hydrocortisone acetate 1%).Primary and secondary outcome measuresWe measured outcomes at baseline and at 1, 4 and 24 weeks. The primary outcome was AD-related symptoms (Patient-Oriented Eczema Measure (POEM) score) measured over 24 weeks of follow-up. Secondary outcomes included the Eczema Area and Severity Index, the Investigators Global Assessment, quality of life (QoL), Patient Global Assessment, Numeric Itch Intensity Score and TCS use.ResultsThe primary outcome showed a significant difference in the POEM scores over 24 weeks of follow-up between the intervention group (n=17) and the control group (n=15) (3.3 vs 9.4, p=0.023). The potent TCS also significantly improved the POEM at 1 week (5.5 vs 12.0, p=0.042) and 4 weeks (4.3 vs 12.7, p=0.030). Improvement in the QoL was significant at 4 weeks (1.0 vs 4.5, p=0.014) and 24 weeks (0.0 vs 2.0, p=<0.000).ConclusionDespite the small sample size, the data suggests a clinical benefit from starting with a potent TCS rather than a mild TCS when a flare-up of AD is moderate.Trial registrationThe Netherlands National Trial Register: NTR6679.

Blood eosinophil counts have been documented as a good biomarker for patients with chronic obstructive pulmonary disease (COPD) using inhaled corticosteroid (ICS) therapy. However, the effectiveness and safety of prescribing high or medium dose of ICS for patients with different eosinophil counts are unknown. A post hoc analysis of a previous prospective randomized study was performed for COPD patients using higher dose (HD: Fluticasone 1,000 μg/day) or medium dose (MD: Fluticasone 500 μg/day) of ICS combined with Salmeterol (100 μg/day). Patients were classified into two groups: those with high eosinophil counts (HE ≥3%) and those with low eosinophil counts (LE <3%). Lung function was evaluated with forced expiratory volume in 1 second, forced vital capacity, and COPD assessment test. Frequencies of acute exacerbation and pneumonia were also measured. Two hundred and forty-eight patients were studied and classified into higher eosinophil (HE) (n=85, 34.3%) and lower eosinophil (LE) groups (n=163, 65.7%). The levels of forced expiratory volume in 1 second were significantly increased in patients of HE group treated with HD therapy, compared with the other groups (HE/HD: 125.9±27.2 mL vs HE/MD: 94.3±23.7 mL, vs LE/HD: 70.4±20.5 mL, vs LE/MD: 49.8±16.7 mL; <0.05) at the end of the study. Quality of life (COPD assessment test) markedly improved in HE/HD group than in MD/LE group (HE/HD: 9±5 vs LE/MD: 16±7, =0.02). The frequency of acute exacerbation was more decreased in HE/HD group patients, compared with that in LE/MD group (HE/HD: 13.5% vs LE/MD: 28.7%, <0.01). Pneumonia incidence was similar in the treatment groups (HE/HD: 3.2%, HE/MD: 2.6%, LE/HD: 3.5%, LE/MD 2.8%; =0.38). The study results support using blood eosinophil counts as a biomarker of ICS response and show the benefits of greater improvement of lung function, quality of life, and decreased exacerbation frequency in COPD patients with blood eosinophil counts higher than 3%, especially treated with higher dose of ICS.