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Introduction: In Japan, patients with chronic obstructive pulmonary disease (COPD) can be escalated to treatment with inhaled triple therapy. Two single-inhaler triple therapies combining an inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β 2 -agonist (ICS/LAMA/LABA) are approved maintenance therapies for patients with COPD, and multiple-inhaler triple therapies (MITTs) are also available. There is limited evidence regarding real-life treatment patterns and characteristics of patients with COPD initiating triple therapies., Methods: This observational, retrospective cohort study identified patients with COPD in Japan from an administrative claims database (May 2018-December 2021). Demographics, clinical characteristics, and healthcare resource utilization (HCRU) were assessed in four cohorts initiating a triple therapy: budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) early adopters (initiated ≤ 12 months after market approval [September 1, 2019]), contemporary BGF users (initiated > 12 months after market approval), fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) users, and any MITT users., Results: A total of 636 patients were BGF early adopters, 2558 were contemporary BGF users, 11,187 used FF/UMEC/VI, and 5931 used MITT. The percentage of patients with concomitant asthma in each cohort was 73.0%, BGF early adopter; 74.2%, contemporary BGF; 75.7%, FF/UMEC/VI; and 84.5%, MITT. During the 12-month baseline period, the frequency of patients with ≥ 1 moderate/severe exacerbation was 18.2%, BGF early adopter; 14.3%, contemporary BGF; 13.1%, FF/UMEC/VI; and 14.0%, MITT. ICS/LABA treatment during baseline was the most frequent pathway to triple therapy, ranging from 38.2% to 51.7% across cohorts. HCRU was relatively high across cohorts (range of hospital outpatient visits/patient during the 12-month baseline period, 11.0-14.1). Multimorbidity was observed in > 80% of patients in all cohorts; cardiovascular diseases were among the most common., Conclusion: Many patients initiating triple therapy for COPD had concomitant asthma and had previously received ICS/LABA maintenance therapy. Patients prescribed BGF in the initial post-launch period were more likely to have a previous exacerbation history versus other cohorts, indicating more severe disease., (© 2024. The Author(s).)

Objectives: To evaluate the cost-effectiveness of budesonide/formoterol reliever and maintenance therapy compared with salmeterol/fluticasone plus salbutamol as reliever therapy for asthma patients ≥12 years from the societal perspective in China., Methods: A Markov model was developed with three health states (non-exacerbation, exacerbation, and death) with a lifetime horizon. The exacerbation rates were obtained from a prospective cohort study conducted in Chinese asthma patients. Healthcare resources utilization data were estimated based on current clinical asthma management guidelines. Asthma-related mortality, cost input and utility values were derived from public database and literature. Model robustness was assessed with one-way sensitivity and probabilistic sensitivity analyses., Results: Compared with salmeterol/fluticasone plus salbutamol, budesonide/formoterol reliever and maintenance therapy led to fewer exacerbation events (13.6 vs. 15.9) and 0.0077 quality-adjusted life years (QALY) gain at an additional cost of ¥196.38 over lifetime. The base case incremental cost-effectiveness ratio (ICER) was ¥25,409.98 per QALY gained. The variables that had most impact on the model output included drug costs and medication adherence. At a willingness-to-pay threshold of ¥257,094/QALY (3 times of gross domestic product per capita in China in 2022), the probability of budesonide/formoterol maintenance and reliever therapy being cost-effective versus salmeterol/fluticasone plus as-needed salbutamol was 83.00%., Conclusion: From the societal perspective, budesonide/formoterol reliever and maintenance therapy is likely to be a cost-effective option compared with salmeterol/fluticasone plus as-needed salbutamol for Chinese asthma patients ≥12 years.

Background: As-needed low-dose inhaled corticosteroid (ICS)-formoterol reliever is recommended in patients with asthma prescribed maintenance ICS-formoterol. Clinicians often ask whether ICS-formoterol reliever can be used with other maintenance ICS-long-acting β 2 -agonists., Objective: To evaluate the safety and effectiveness of as-needed formoterol in patients taking maintenance ICS-formoterol or ICS-salmeterol from the RELIEF study., Methods: RELIEF (SD-037-0699) was a 6-month, open-label study that randomized 18,124 patients with asthma to as-needed formoterol 4.5 μg or salbutamol 200 μg on top of maintenance therapy. This post hoc analysis included patients on maintenance ICS-formoterol or ICS-salmeterol (n = 5436). The primary safety outcome was a composite of serious adverse events (SAEs) and/or adverse events leading to discontinuation (DAEs); the primary effectiveness outcome was time-to-first exacerbation., Results: For both maintenance groups and both relievers, similar numbers of patients had ≥1 SAE and/or DAE. In patients taking maintenance ICS-salmeterol, but not ICS-formoterol, significantly more non-asthma-related and nonserious DAEs occurred with as-needed formoterol versus as-needed salbutamol (P = .0066 and P = .0034, respectively). In patients taking maintenance ICS-formoterol, there was a significantly lower risk in time-to-first exacerbation with as-needed formoterol versus as-needed salbutamol (hazard ratio [HR]: 0.82, 95% confidence interval [CI]: 0.70, 0.95; P = .007). In patients taking ICS-salmeterol maintenance, time-to-first exacerbation was not significantly different between treatment arms (HR: 0.95, 95% CI: 0.84, 1.06; P = .35)., Conclusions: As-needed formoterol significantly reduced exacerbation risk compared with as-needed salbutamol when added to maintenance ICS-formoterol, but not to maintenance ICS-salmeterol. More DAEs were seen with ICS-salmeterol maintenance therapy plus as-needed formoterol. Further research is needed to assess whether this is relevant to as-needed combination ICS-formoterol., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate and discuss the salbutamol combined with budesonide in treatment of pediatric bronchial asthma (BA) and its effect on eosinophils (EOS)., Methods: Ninety-eight BA children admitted and treated in our hospital from July 2016 to June 2017 were collected and divided into control group (N.=49) and observation group (N.=49) according to random number table. The children in control group were treated with budesonide and those in observation group were treated with salbutamol combined with budesonide. The clinical efficacy, pulmonary functions and levels of T-lymphocyte subsets (including cluster of differentiation 3 (CD3)+, CD4+, CD8+ and CD4+/CD8+) in the immune system between two groups were compared after the treatment; the levels of eosinophil cationic protein (ECP) and eotaxin in the children were compared before the treatment and at 1, 4 and 8 weeks after the treatment; the changes in EOS counts in blood and induced sputum of the children before and after the treatment were compared, and the EOS apoptosis rate was compared at 1, 4 and 8 weeks after the treatment., Results: The effective rate of treatment in observation group was significantly higher than that in control group (P<0.05). After the treatment, the indexes of pulmonary function in observation group were obviously better than those in control group (P<0.05). Compared with those in control group, the levels of CD3+, CD4+ and CD4+/CD8+ of the children in observation group were elevated remarkably, while the CD8+ level was lowered (P<0.05). The levels of ECP and eotaxin in the two groups were decreased after the treatment compared with those before the treatment, and the levels in observation group were superior to those in control group (P<0.05). After the treatment, the EOS counts of both groups of children were lower than those before the treatment, and the decrease in observation group was more notable than that in control group. At 1, 4 and 8 weeks after the treatment, the EOS apoptosis rate in observation group was obviously higher than that in control group (P<0.05)., Conclusions: The treatment of salbutamol combined with budesonide for pediatric BA has significant therapeutic effects; it can restore the pulmonary functions rapidly and improve the immunity of the lung, reduce the levels of eotaxin, ECP and EOS of the child patients and promote EOS apoptosis.

Objectives/hypothesis: It is not unequivocally proven whether a combination of an intranasal corticosteroids (INSs) and a cysteinyl leukotriene receptor antagonist has greater efficacy than INSs in the treatment of seasonal allergic rhinitis (SAR)., Study Design: Single-center, randomized, open-label study., Methods: Study subjects included 46 participants with SAR. Participants were randomized to receive budesonide (BD; 256 μg) plus montelukast (MNT; 10 mg) (BD + MNT) or BD alone (256 μg) for 2 weeks. Visual analog scale scores for five major symptoms of SAR, nasal cavity volume (NCV), nasal airway resistance (NAR), and fractional exhaled nitric oxide (FeNO) were assessed before and at the end of treatments., Results: Both treatments significantly improved the five main SAR symptoms from baseline; however, BD + MNT produced significantly greater improvements in nasal blockage and nasal itching compared to BD alone. At baseline, the nasal blockage score was significantly correlated with NCV and NAR (r = -0.473, P = .002 and r = -0.383, P = .013, respectively). After 2 weeks of treatment, BD + MNT significantly improved NCV, but not NAR, to a greater level than BD. The number of patients with FeNO concentration ≥ 30 ppb at baseline was significantly decreased after BD + MNT treatment, but not after BD treatment. Similarly, BD + MNT treatment led to a significantly greater decrease in FeNO concentration than BD treatment., Conclusions: BD + MNT treatment may have an overall superior efficacy than BD monotherapy for patients with SAR, especially in improvement of nasal blockage, itching, and subclinical lower airway inflammation. Also, NCV and NAR could be used to assess nasal blockage more accurately., Level of Evidence: 1b Laryngoscope, 131:E1054-E1061, 2021., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: The efficacy of inhaled budesonide for managing moderate-to-severe acute exacerbations in children is not clear. Therefore, this study aimed to evaluate hospital admission rates, need for use of systemic corticosteroids, length of hospital stay and adverse events when inhaled budesonide is added to standard pediatric emergency department management of moderate-to-severe acute exacerbations of asthma., Methods: A systematic search was conducted in PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar databases. Randomized controlled trials that evaluated the effect of nebulized budesonide in moderate-to-severe acute exacerbations of asthma in pediatric patients were included for this meta-analysis. Statistical analysis was done using STATA version 13.0., Results: A total of 16 RCTs were included. Children receiving nebulized budesonide had 43% lower risk of being hospitalized (RR 0.57; 95% CI, 0.39; 0.85) and 66% lower risk of requiring systemic corticosteroids (RR 0.34; 95 % CI, 0.21; 0.55) compared with those receiving placebo. There were no differences in the length of hospital stay (Hedges's g standardized mean difference - 1.53; 95% CI, - 3.64; 0.58) and risk of adverse events (RR 0.87, 95% CI; 0.65; 1.17) between the two groups. There was no evidence of publication bias for any of the outcomes considered., Conclusion: The findings of this meta-analysis support the use of inhaled budesonide in reducing risk of hospitalization and the need for systemic corticosteroids among children with acute moderate-to-severe asthma exacerbation.

Rationale: In the phase III, 52-week ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial in chronic obstructive pulmonary disease (COPD) (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) significantly reduced all-cause mortality compared with glycopyrrolate/formoterol fumarate (GFF). However, 384 of 8,509 patients were missing vital status at Week 52 in the original analyses. Objectives: To assess the robustness of the ETHOS mortality findings after additional data retrieval for patients missing Week 52 vital status in the original analyses. Methods: Patients with moderate to very severe COPD and prior history of exacerbation received twice-daily dosing with 320/18/9.6 μg of BGF (BGF 320), 160/18/9.6 μg of BGF (BGF 160), 18/9.6 μg of GFF, or 320/9.6 μg of budesonide/formoterol fumarate (BFF) (all delivered via a single metered-dose Aerosphere inhaler). Time to death (all-cause) was a prespecified secondary endpoint. Measurements and Main Results: In the final retrieved dataset, which included Week 52 vital status for 99.6% of the intent-to-treat population, risk of death with BGF 320 was significantly lower than GFF (hazard ratio, 0.51; 95% confidence interval, 0.33-0.80; unadjusted P  = 0.0035). There were no significant differences in mortality when comparing BGF 320 with BFF (hazard ratio, 0.72; 95% confidence interval, 0.44-1.16; P  = 0.1721), nor were significant differences observed when comparing BGF 160 against either dual comparator. Results were similar when the first 30, 60, or 90 days of treatment were excluded from the analysis. Deaths from cardiovascular causes occurred in 0.5%, 0.8%, 1.4%, and 0.5% of patients in the BGF 320, BGF 160, GFF, and BFF groups, respectively. Conclusions: Using final retrieved vital status data, triple therapy with BGF 320 reduced the risk of death compared with GFF, but was not shown to significantly reduce the risk of death compared with BFF, in patients with COPD. Triple therapy containing a lower dose of inhaled corticosteroid (BGF 160) was not shown to significantly reduce the risk of death compared with the dual therapy comparators.

Background: In mild asthma, as-needed budesonide-formoterol reduces long-term exacerbation risk compared with as-needed short-acting β 2 -agonist (SABA), with a similar or increased reduction versus maintenance with budesonide plus as-needed SABA, despite a lower budesonide dose. In this post-hoc analysis of the SYmbicort Given as needed in Mild Asthma (SYGMA) 1 study, we investigated the short-term risk of severe exacerbations after a single day with various levels of reliever use., Methods: SYGMA 1 was a 52-week, double-blind, randomised, controlled, phase 3 trial, in which patients aged 12 years or older with mild asthma were randomly assigned (1:1:1) to placebo twice daily plus as-needed terbutaline 0·5 mg, placebo twice daily plus as-needed budesonide-formoterol 200-6 μg, or budesonide 200 μg twice daily plus as-needed terbutaline (ie, budesonide maintenance group). In this post-hoc analysis, we assessed the frequency of reliever use and the risk of a severe exacerbation in the 21 days after first use of more than two, four, six, or eight reliever inhalations in 24 h. SYGMA 1 is registered with ClinicalTrials.gov, NCT02149199, and is now complete., Findings: Of 5721 patients enrolled in SYGMA 1, 3849 were randomly assigned to as-needed terbutaline (n=1280), as-needed budesonide-formoterol (n=1279), or budesonide maintenance (n=1290), of whom 3836 had evaluable data (n=1277 as-needed terbutaline, n=1277 as needed budesonide-formoterol, and n=1282 budesonide maintenance). Median reliever use was 0·32 (IQR 0·08-0·91) inhalations per day for the as-needed terbutaline group, 0·29 (0·07-0·72) for the as-needed budesonide-formoterol group, and 0·16 (0·04-0·52) for the budesonide maintenance group. Compared with as-needed terbutaline, after adjustment for age, sex, randomly assigned treatment, pre-study treatment group, baseline % predicted post-bronchodilator FEV 1 , and severe exacerbation in the 12 months before enrolment in the study, the hazard ratio (HR) for severe exacerbation in the 21 days after a single day with more than two as-needed inhalations was 0·27 (95% CI 0·12-0·58; p=0·0008) with as-needed budesonide-formoterol and 0·39 (0·19-0·79; p=0·0091) with budesonide maintenance; after a single day of more than four as-needed inhalations the HR was 0·24 (0·10-0·62; p=0·0030) with as-needed budesonide-formoterol and 0·30 (0·13-0·72; p=0·0065) with budesonide maintenance; and after a single day of more than six as-needed inhalations the HR was 0·14 (0·02-1·06; p=0·057) with as-needed budesonide-formoterol and 0·43 (0·14-1·26; p=0·12) with budesonide maintenance. HRs were not calculated for more than eight as-needed inhalations due to the small number of events., Interpretation: In mild asthma, as-needed budesonide-formoterol reduces the short-term risk of severe exacerbations after a single day of higher use (more than two as-needed inhalations), even when overall use is infrequent. Use of an anti-inflammatory reliever might reduce the risk of short-term severe exacerbations by the timely provision of increased doses of as-needed inhaled corticosteroids and formoterol when symptoms occur. These findings should be further assessed in prospective randomised clinical trials., Funding: AstraZeneca., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Few studies have utilized 24-h serial spirometry to compare the effects of inhaled chronic obstructive pulmonary disease (COPD) therapies on lung function. The FULFIL study previously reported significant lung function improvements with once-daily single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus twice-daily single-inhaler budesonide/formoterol (BUD/FOR) in patients with symptomatic COPD at risk of exacerbations., Methods: This prespecified analysis evaluated 24-h serial spirometry data from a subgroup of 406 patients in FULFIL. BUD/FOR twice-daily dosing was maintained during 24-h spirometry. A post hoc analysis evaluated serial forced expiratory volume in 1 s (FEV 1 ) at day 1 and week 24 by disease severity at screening (FEV 1 < 50% predicted and no moderate or severe exacerbation in prior year, FEV 1 < 50% predicted and ≥ 1 moderate or severe exacerbation in prior year, and FEV 1 ≥ 50% and < 80% predicted and ≥ 2 moderate or ≥ 1 severe exacerbations in prior year)., Results: Odds of achieving a ≥ 100-mL increase from baseline in FEV 1 within the first 6 h post dose on day 1 were significantly greater with FF/UMEC/VI than BUD/FOR [odds ratio 2.79 (95% confidence interval 1.56-4.98); p < 0.001]. FF/UMEC/VI led to greater improvements in weighted mean FEV 1 over 0-6, 0-12, 0-24, and 12-24 h on day 1 and at week 24, with the greatest between-group differences at week 24 (range 196-210 mL; all p < 0.001). Significant between-treatment differences in FEV 1 and forced vital capacity (FVC) in favor of FF/UMEC/VI versus BUD/FOR were seen at all time points at week 24 (FEV 1 range 156-231 mL, all p < 0.001; FVC range 139-309 mL, all p ≤ 0.002). Serial FEV 1 results were consistent irrespective of disease severity at screening., Conclusion: These findings further demonstrate sustained lung function benefits with once-daily FF/UMEC/VI single-inhaler triple therapy in patients with symptomatic COPD at risk of exacerbations across a range of disease severities.

Hyperinflation contributes to dyspnea intensity in COPD. Little is known about the molecular mechanisms underlying hyperinflation and how inhaled corticosteroids (ICS) affect this important aspect of COPD pathophysiology. To investigate the effect of ICS/long-acting β 2 -agonist (LABA) treatment on both lung function measures of hyperinflation, and the nasal epithelial gene-expression profile in severe COPD. 117 patients were screened and 60 COPD patients entered a 1-month run-in period on low-dose ICS/LABA budesonide/formoterol (BUD/F) 200/6 one inhalation b.i.d. Patients were then randomly assigned to 3-month treatment with either a high dose BDP/F 100/6 two inhalations b.i.d. (n = 31) or BUD/F 200/6 two inhalations b.i.d. (n = 29). Lung function measurements and nasal epithelial gene-expression were assessed before and after 3-month treatment and validated in independent datasets. After 3-month ICS/LABA treatment, residual volume (RV)/total lung capacity (TLC)% predicted was reduced compared to baseline (p < 0.05). We identified a nasal gene-expression signature at screening that associated with higher RV/TLC% predicted values. This signature, decreased by ICS/LABA treatment was enriched for genes associated with increased p53 mediated apoptosis was replicated in bronchial biopsies of COPD patients. Finally, this signature was increased in COPD patients compared to controls in nasal, bronchial and small airways brushings. Short-term ICS/LABA treatment improves RV/TLC% predicted in severe COPD. Furthermore, it decreases the expression of genes involved in the signal transduction by the p53 class mediator, which is a replicable COPD gene expression signature in the upper and lower airways.Trial registration: ClinicalTrials.gov registration number NCT01351792 (registration date May 11, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 20, 2009), ClinicalTrials.gov registration number NCT00158847 (registration date September 12, 2005).

Background: Hospitalization is a major cause of medical expenditure for asthma. Budesonide inhalation suspension (BIS) may assist in reducing asthma-related symptoms in severe asthma exacerbation. However, its effectiveness for hospitalized patients remains poorly known. The objective of this study is to determine associations of BIS with asthma hospitalization., Methods: We retrospectively analyzed 98 patients who were admitted to our hospital due to severe asthma exacerbation (24 treated with BIS in combination with procaterol) from April 2014 to January 2019. Length of stay, recovery time from symptoms (wheezes), and hospitalization costs were compared between the 2 groups according to clinical factors including the use of BIS and sings of respiratory infections (i.e. C-reactive protein, the presence of phlegm, and the use of antibiotics). Multivariate logistic regression analysis was performed to determine factors contributing to hospitalization outcomes., Results: The use of BIS was associated with shorter length of stay, faster recovery time from symptoms, and more reduced hospitalization costs (6.0 vs 8.5 days, 2.5 vs 5.0 days, and 258,260 vs 343,350 JPY). Signs of respiratory infection were also associated with hospitalization outcomes. On a multivariate regression analysis, the use of BIS was a determinant of shortened length of stay and reduced symptoms and medical costs for asthma hospitalization along with signs of respiratory infection., Conclusions: BIS may contribute to shorten length of hospital stay and to reduce symptoms and medical expenditure irrespective of the presence or absence of respiratory infection., (Copyright © 2020 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Whether blood eosinophil counts and exhaled nitric oxide (FeNO) are associated with important outcomes in mild asthma is unclear. In this prespecified subgroup analysis of a previously published open-label clinical trial, we aimed to assess associations between blood eosinophil counts and FeNO with outcomes and response to asthma treatment., Methods: In the previously reported 52-week, open-label, randomised controlled trial, people with mild asthma receiving only β agonist reliever inhalers were enrolled at one of 16 clinical trials units in New Zealand, the UK, Italy, or Australia. Eligible participants were randomly assigned (1:1:1, stratified by country), to receive inhalers to take as-needed salbutamol (two inhalations of 100 μg in a pressurised metered dose inhaler), maintenance budesonide (200 μg twice per day by inhaler) plus as-needed salbutamol (two inhalations of 100 μg), or as-needed budesonide-formoterol (one inhalation of 200 μg budesonide and 6μg formoterol by inhaler). The primary outcome was the annual rates of asthma exacerbations per patient, and in this prespecified subgroup analysis, we assessed whether annual exacerbation rates in each treatment group were significantly different depending on levels of blood eosinophil count, FeNO, or a composite score of both. Analyses were done for patients with available biomarker measurements The study was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12615000999538., Findings: 675 participants were enrolled between March 17, 2016, and Aug 29, 2017, of whom 656 had results for blood eosinophil analysis and 668 had results for FeNO. Of the patients who received as-needed salbutamol, the proportion of patients having a severe exacerbation increased progressively with increasing blood eosinophil count (two [4%] of 49 participants with <0·15 × 10 9 /L, six [6%] of 93 with 0·15 to <0·3 × 10 9 /L, and 15 [19%] of 77 with ≥0·3 × 10 9 /L; p=0·014). There were no significant interactions between blood eosinophil count or FeNO level and the effect of as-needed budesonide-formoterol compared with as-needed salbutamol for either exacerbations or severe exacerbations. However, there were significant interactions between blood eosinophil count subgroups and the effect of maintenance budesonide plus as-needed salbutamol compared with as-needed salbutamol, both for exacerbations (p=0·0006) and severe exacerbations (p=0·0007). Maintenance budesonide plus as-needed salbutamol was more effective than as-needed salbutamol in patients with blood eosinophil counts of 0·3 × 10 9 /L or more, both for exacerbations (rate ratio 0·13 [95% CI 0·05-0·33]) and severe exacerbations (risk odds ratio 0·11 [0·03-0·45]). This difference was not seen for blood eosinophil counts of less than 0·15 × 10 9 /L (1·15 [0·51-1·28] for exacerbations and 5·72 [0·97-33·60] for severe exacerbations). There was no consistent interaction between treatment response and FeNO or the composite score., Interpretation: In patients with mild asthma, the effects of as-needed budesonide-formoterol on exacerbations are independent of biomarker profile, whereas the benefits of maintenance inhaled budesonide are greater in patients with high blood eosinophil counts than in patients with low counts., Funding: AstraZeneca, Health Research Council of New Zealand., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Triple inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β 2 -agonist (ICS/LAMA/LABA) combination therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience further exacerbations/symptoms on dual LAMA/LABA or ICS/LABA therapy. The relative efficacy of budesonide/glycopyrronium/formoterol fumarate metered dose inhaler 320/18/9.6 µg (BGF MDI) in COPD was compared with other ICS/LAMA/LABA fixed-dose and open combination therapies in a network meta-analysis (NMA)., Methods: A systematic literature review was conducted to identify randomized controlled trials of at least 10-week duration, including at least one fixed-dose or open combination triple therapy arm, in patients with moderate to very severe COPD. Studies were assessed for methodological quality and risk of bias. A three-level hierarchical Bayesian NMA model was used to determine the exacerbation rate per patient per year as well as the following outcomes at week 24: changes from baseline in pre-dose trough forced expiratory volume in 1 s (FEV 1 ), post-dose peak FEV 1 , and St. George's Respiratory Questionnaire (SGRQ) total score; proportion of SGRQ responders; and Transition Dyspnea Index focal score. Change from baseline in rescue medication use over weeks 12-24 was also analyzed. Meta-regression and sensitivity analyses were used to assess heterogeneity across studies., Results: Eighteen studies (n = 29,232 patients) contributed to the NMA. ICS/LABA dual combinations were combined as a single treatment group to create a connected network. Across all outcomes, there were no statistically significant differences between BGF MDI and other triple ICS/LAMA/LABA fixed-dose (fluticasone furoate/umeclidinium/vilanterol and beclomethasone dipropionate/glycopyrronium/formoterol fumarate) and open combinations with data available within the network. Results from sensitivity analyses and meta-regression were consistent with the base-case scenario., Conclusion: This NMA suggested that BGF MDI has comparable efficacy to other ICS/LAMA/LABA fixed-dose and open triple combination therapies in reducing exacerbations and improving lung function and symptoms in patients with moderate to very severe COPD. Further research is warranted as additional evidence regarding triple therapies, especially fixed-dose combinations, becomes available.

Background: There is no strict correlation between early bronchopulmonary dysplasia and long-term respiratory disease. Early inhaled corticosteroids seem to reduce the incidence of bronchopulmonary dysplasia, but the long-term outcome remains unknown., Research Question: The aim of this study was to evaluate the effect of early inhaled corticosteroids on chronic respiratory morbidity., Methods: Fifty-nine survivors from the Prague cohort included in Neonatal European Study of Inhaled Steroids underwent further follow-up comprising of respiratory morbidity monitoring during the first 2 years of life followed by objective lung function testing performed at the age of 5.9 years (range 5-7 years). Both outcomes were pursued and finalized before the unblinding of budesonide subgroups., Results: Fifty randomized (budesonide vs placebo group, 56% vs 44%) survivors were included in the study. Spirometry was successfully performed in 48 children. No statistically significant differences were found in the lung function test (forced expiratory flow [FEF] - FEF 75 , FEF 50, FEF 25 , and FEF 25-75; FEV 1 , forced vital capacity [FVC], FEV 1 /FVC) although mild trend to the improvement of expiratory flow pattern was observed in the budesonide group (median z-score of FEV 1 /FVC -0.376 vs -0.983, P = .13; median z-score of FEF 25-75 -1.004 vs -1.458, P = .13; median z-score of FEF 75 -0.527 vs -0.996, P = .17). Children assigned to budesonide had a significantly lower rate of symptoms of chronic lung disease (34.6% vs 68.2%; P = .04) than children assigned to placebo., Interpretation: Our study suggests that early inhaled budesonide was associated with the trend to the improvement of functional lung parameters and with a lower rate of symptoms of chronic lung disease within the first 2 years of life., (© 2020 Wiley Periodicals, Inc.)

Introduction : Inhaled therapies are likely to continue to dominate asthma and chronic obstructive pulmonary disease treatment. Dry powder inhalers (DPIs) have several advantages over pressurized metered-dose inhaler (pMDIs), that are most frequently marketed world-wide, but often difficult to use. This literature search focus on DPI features, with respect to Easyhaler, that may affect their use and patients' clinical benefit. Areas covered : DPIs are breath-actuated, easy to use, convenient to use, and more environmentally friendly. During inhalation, the formulation in a DPI is disaggregated by a turbulent airflow energy to generate particles with the greatest likelihood of deposition into the airways. The resistance among DPIs varies from low to high and those with high resistance are wrongly considered as difficult to use. Multidose reservoir-type DPIs have been developed to efficiently deliver a wide range of medications, including the fixed-dose combination of budesonide and formoterol. Easyhaler® shares a similar shape with pMDIs and, as other DPIs, its performance is unaffected by environmental and storage conditions. Due to Easyhaler internal design, dose emission is consistent irrespective of the inhalation flow used by each patient. Expert opinion : Easyhaler® may be considered one of the most convenient inhalers, for daily use, in patients with asthma or COPD.

Introduction: This pre-specified subgroup analysis evaluated the efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) triple therapy versus corresponding dual therapies in the China subgroup of the phase III, double-blind KRONOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD)., Methods: Patients were randomized 2:2:1:1 to BGF MDI 320/18/9.6 μg, glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6 μg, budesonide/formoterol fumarate (BFF) MDI 320/9.6 μg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice daily for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV 1 ) over weeks 12-24. Secondary endpoints included symptoms, health-related quality of life, and safety. Rate of moderate/severe COPD exacerbations was an additional efficacy endpoint., Results: In the China subgroup (n = 432; 22.7% of the KRONOS population), BGF MDI demonstrated nominally significant improvements in the primary endpoint versus BFF MDI (least squares mean (LSM) difference 68 mL; P = 0.0035) and BUD/FORM DPI (LSM difference 78 mL; P = 0.0010) but not GFF MDI (LSM difference - 4 mL; P = 0.8316). BGF MDI demonstrated at least numerical improvements versus comparators in secondary lung function and symptom endpoints. BGF MDI reduced the rate of moderate/severe COPD exacerbations versus GFF MDI (rate ratio 0.41; P = 0.0030), with numerical benefits versus BFF MDI and BUD/FORM DPI. All treatments were well tolerated., Conclusions: Results demonstrated that BGF MDI showed benefits on lung function (vs inhaled corticosteroid/long-acting β 2 -agonist), as well as symptoms and exacerbations relative to dual therapies. Findings support BGF MDI use in Chinese patients with moderate to very severe COPD., Clinical Trial Registration: ClinicalTrials.gov NCT02497001.

Aim: Quality, real-world comparative effectiveness (CE) studies of asthma and chronic obstructive pulmonary disease therapy efficacy are scarce. We identified and evaluated peer-reviewed CE and appropriate-use evaluations of budesonide/formoterol combination (BFC) maintenance therapy. Materials & methods: Analyses were limited to retrospective, real-world utilization studies of BFC delivered by pressurized metered-dose inhalers. Results: In a CE study of BFC versus fluticasone/salmeterol combinations (FSC) in asthma, BFC users had fewer total exacerbations. In appropriate-use studies of asthma treatment, BFC patients were consistently more likely to meet treatment escalation recommendations. BFC comparisons with FSC or tiotropium for chronic obstructive pulmonary disease found differences in exacerbation rates and rescue inhaler use. Conclusion: We found available, good quality BFC CE and appropriate-use articles; however, all had limitations.

Introduction : Inhaled corticosteroid (ICS) plus long-acting β 2 -agonist (LABA) combinations are commonly used in the treatment of patients with chronic obstructive pulmonary disease (COPD). At least four fixed-dose ICS/LABA combinations are available, including budesonide/formoterol, beclomethasone/formoterol, fluticasone/vilanterol and fluticasone/salmeterol, but there is little guidance for clinicians on which of these combinations to prescribe. Areas covered : The aim of this in-depth review was to identify studies that compared budesonide/formoterol with the other ICS/LABA combinations and assess the data on exacerbations, safety, and patient quality of life. PubMed and Ovid databases were searched, and 14 studies were identified. Our findings highlight the lack of prospective, randomized, controlled trials comparing LABA/ICS combinations in the treatment of COPD as only two such studies were identified. However, current evidence suggests that the effects of budesonide/formoterol on reducing exacerbations and improving quality of life may be similar to, or more marked than, those of other LABA/ICS combinations in COPD and, compared with the other LABA/ICS combinations, budesonide/formoterol may be associated with a lower incidence of serious pneumonia events and oral candidiasis. Expert opinion : To better guide clinicians in selecting between the available ICS/LABA, robust meta-analyses and well-designed head-to-head clinical trials are urgently needed.

Background: The aim of this study is to estimate the budget impact of budesonide/formoterol fixed dose combination (FDC) vs salbutamol, both used as needed, in mild asthma patients, from the perspective of the Health Insurance Organization (HIO). Methods: A static budget impact model was developed to assess the impact of budesonide/formoterol FDC entry on HIO budget over a 3-year period in Egyptian settings. Direct medical costs, including the costs of asthma medications, exacerbations, and management of side-effects, were obtained from HIO cost data. Population data were obtained from the World Bank and supplemented with local studies, and the rates of exacerbations, adverse effects, and number of sick leave days were elicited from the SYGMA 1 trial. Scenario analyses from a societal perspective and deterministic sensitivity analyses were conducted. Results: The total costs (drug and non-drug costs) for managing mild asthma patients from the HIO perspective were estimated to be EGP8.563 billion before budesonide/formoterol entry compared to EGP5.525 billion post-entry, leading to a total budget savings of EGP3.038 billion after 3 years. This total budget saving included an increase in drug costs (EGP104 million) and a decrease in non-drug costs (EGP3.143 billion). Drug costs were higher in the budesonide/formoterol group than in the salbutamol group, but this cost was offset by reductions in non-drug costs, resulting in a reduction in the total costs of healthcare resources. At the societal level, the total budget savings after including the indirect costs was expected to be EGP5.976 billion after 3 years of budesonide/formoterol entry. Conclusion: Budesonide/formoterol in mild asthma instead of salbutamol produces better patient outcomes and decreases total costs, with increases in drug cost offset by reductions in non-drug costs due to fewer exacerbations. Budesonide/formoterol is a budget saving option for guideline-directed treatment, from the economic perspective of the payer and the health perspective of the patient.

Introduction: In real-life practice, asthma remains poorly controlled, with a considerable burden on patients' quality of life. Budesonide/formoterol (B/F) Easyhaler ® has demonstrated similar dose consistency, therapeutic equivalence, and equivalent bronchodilator efficacy to B/F Turbuhaler ® , but no real-life comparisons are yet available in patients switching from B/F Turbuhaler ® to B/F Easyhaler ® ., Methods: The primary objective of this real-life, non-interventional, observational study was to show non-inferiority of asthma control when adult patients in Swedish primary care with persistent asthma switched from B/F Turbuhaler ® to B/F Easyhaler ® . At visit 1, baseline demographic and endpoint data were recorded, and eligible patients switched to B/F Easyhaler ® . The study comprised a control visit (visit 2) and a concluding examination (visit 3) after 12 weeks. Asthma control was assessed using the Asthma Control Test (ACT). The mini-Asthma Quality of Life Questionnaire (AQLQ) and lung function test were performed, and participants and investigators answered questionnaires about ease-of-use and teaching., Results: A total of 117 patients were enrolled in the on-treatment population; 81 (64.8%) were female. At visit 3, B/F Easyhaler ® demonstrated non-inferiority to B/F Turbuhaler ® ; the mean difference in change from baseline ACT was statistically significant (18.9 vs. 20.7, respectively; p < 0.0001) and met the non-inferiority criteria of B/F Easyhaler ® being greater than - 1.5 points versus the reference product. Asthma was well controlled in 62 (53.0%) patients at baseline, increasing to 83 patients (70.9%) at visit 3. Patients experienced statistically significant improvements in mini-AQLQ score after B/F Easyhaler ® treatment and lung function remained stable across the treatment period. B/F Easyhaler ® was easy to learn and prepare for use., Conclusion: This real-life, non-interventional, non-inferiority study in adults with persist asthma demonstrates equivalent or better disease control when patients switch from B/F Turbuhaler ® to B/F Easyhaler ® . A further study with direct comparison between treatments could add to the understanding of inhaler switch., Funding: Orion Corporation, Orion Pharma.

Background: Cardiopulmonary bypass can result in lung injury. This prospective, double-blinded, randomized trial aimed to evaluate the protective effect of inhaled budesonide on lung injury after cardiopulmonary bypass., Methods: Sixty patients, aged 25 to 65 years, requiring cardiopulmonary bypass were randomized to groups treated with saline or budesonide inhalation preoperatively. The respiratory mechanics were recorded. Bronchoalveolar lavage fluid was collected before cardiopulmonary bypass and after sternal closure. Serum and bronchoalveolar lavage fluid levels of proinflammatory and anti-inflammatory factors were analyzed. The primary end point was the lowest ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen after cardiopulmonary bypass. The durations of ventilation and postoperative recovery time were noted., Results: Budesonide significantly improved respiratory mechanics after cardiopulmonary bypass. Budesonide improved the partial pressure of arterial oxygen to the fraction of inspired oxygen ratio from 8 to 48 hours after the operation. Budesonide shortened the durations of mechanical ventilation and postoperative recovery time. Budesonide decreased the levels of proinflammatory factors while increasing the levels of anti-inflammatory factors in bronchoalveolar lavage fluid and serum (all P < .05). The macrophage and neutrophil counts, and protein and elastase concentrations were decreased by budesonide treatment., Conclusions: Budesonide treatment shortened the durations of mechanical ventilation, inhibited local and systemic inflammation, and improved respiratory function after cardiopulmonary bypass., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Budesonide (BUD)/formoterol (FM) dry powder inhaler has a feature that the fine particle fraction output is dependent on users' inspiratory flow rate. The aim of this study was to assess the amount of nasally exhaled BUD/FM inhaled in the different inspiratory flow rate. We also examined the effect of nasal exhalation of BUD/FM dry powder inhaled on radiographic evidence of sinonasal inflammation in asthmatic patients with eosinophilic chronic rhinosinusitis (ECRS)., Materials and Methods: The quantitative amount of nasally exhaled BUD/FM was analyzed by high-performance liquid chromatography in 3 healthy subjects. We retrospectively evaluated the effect of nasal exhalation of BUD/FM dry powder inhaled at &gt; 60 L/min on radiographic evidence of sinonasal inflammation, which was assessed according to the Lund-Mackay staging (LMS) system, in 7 consecutive patients with asthma and ECRS., Results: The amount of nasally exhaled BUD in the setting of inhaling BUD/FM dry powder inhaler at 60 L/min (subject 1: 25.8 ng/mL; subject 2: 37.3 ng/mL; subject 3: 30.0 ng/mL) was high compared to at 30 L/min (subject 1: 9.3 ng/mL; subject 2: 4.1 ng/mL; subject 3: 9.2 ng/mL) in each healthy subject. Nasal exhalation of BUD/FM dry powder significantly reduced total (p = 0.018) and ethmoid LMS scores (p = 0.0077)., Conclusion: Nasal exhalation technique of BUD/FM dry powder inhaled at "fast" inspiratory flow has a potential of simultaneously treating asthma and ECRS.
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Terbutaline aerosol and budesonide suspension are commonly used in the treatment of bronchial asthma, and budesonide suspension has local high efficiency and anti-inflammatory effects. In this paper, we selected 240 patients with bronchial asthma and randomly divided them into two groups. The experimental group was treated with atomization inhalation of terbutaline, after 5 minutes interval, nebulized inhalation of budesonide was performed. The control group was treated with atomized inhalation of mixed liquid as terbutaline and budesonide. After treatment, the cough scores of the two groups decreased, and the dyspnea score improved significantly compared with that before treatment (P<0.05).After treatment, the levels of IL-6, BNP and CRP were decreased in the two groups. There was a significant difference between the two groups after treatment (P<0.05). The incidence of adverse drug reactions was low. There were 2 cases of panic disorder and 8 cases of pharyngeal discomfort in the experimental group. The results show that the interval medication of terbutaline and budesonide in the treatment of bronchial asthma can achieve better clinical efficacy and can provide reference for clinical treatment. In addition, this method can effectively reduce the level of inflammatory factors in acute asthma patients, thereby reducing the damage of inflammatory factors to the body.

Berger, Marc Moritz, Franziska Macholz, Peter Schmidt, Sebastian Fried, Tabea Perz, Daniel Dankl, Josef Niebauer, Peter Bärtsch, Heimo Mairbäurl, and Mahdi Sareban. Inhaled budesonide does not affect hypoxic pulmonary vasoconstriction at 4559 meters of altitude. High Alt Med Biol 19:52-59, 2018.-Oral intake of the corticosteroid dexamethasone has been shown to lower pulmonary artery pressure (PAP) and to prevent high-altitude pulmonary edema. This study tested whether inhalation of the corticosteroid budesonide attenuates PAP and right ventricular (RV) function after rapid ascent to 4559 m. In this prospective, randomized, double-blind, and placebo-controlled trial, 50 subjects were randomized into three groups to receive budesonide at 200 or 800 μg twice/day (n = 16 and 17, respectively) or placebo (n = 17). Inhalation was started 1 day before ascending from 1130 to 4559 m within 20 hours. Systolic PAP (SPAP) and RV function were assessed by transthoracic echocardiography at low altitude (423 m) and after 7, 20, 32, and 44 hours at 4559 m. Ascent to high altitude increased SPAP about 1.7-fold (p < 0.001), whereas RV function was preserved. There was no difference in SPAP and RV function between groups at low and high altitude (all p values >0.10). Capillary partial pressure of oxygen (PO 2 ) and carbon dioxide as well as the alveolar to arterial PO 2 difference were decreased at high altitude but not affected by budesonide. Prophylactic inhalation of budesonide does not attenuate high-altitude-induced pulmonary vasoconstriction and RV function after rapid ascent to 4559 m.

Background: The peripheral blood eosinophil count might help identify those patients with chronic obstructive pulmonary disease (COPD) who will experience fewer exacerbations when taking inhaled corticosteroids (ICS). Previous post-hoc analyses have proposed eosinophil cutoffs that are both arbitrary and limited in evaluating complex interactions of treatment response. We modelled eosinophil count as a continuous variable to determine the characteristics that determine both exacerbation risk and clinical response to ICS in patients with COPD., Methods: We analysed data from three AstraZeneca randomised controlled trials of budesonide-formoterol in patients with COPD with a history of exacerbations and available blood eosinophil counts. Patients with any history of asthma were excluded. Negative binomial regression analysis was done using splines for modelling of continuous variables to study the primary outcome of annual exacerbation rate adjusted for exposure time and study design. The trials are registered with ClinicalTrials.gov, NCT00206167, NCT00206154, and NCT00419744., Findings: 4528 patients were studied. A non-linear increase in exacerbations occurred with increasing eosinophil count in patients who received formoterol alone. At eosinophil counts of 0·10 × 10 9 cells per L or more, a significant treatment effect was recorded for exacerbation reduction with budesonide-formoterol compared with formoterol alone (rate ratio 0·75, 95% CI 0·57-0·99; p interaction =0·015). Interactions were observed between eosinophil count and the treatment effects of budesonide-formoterol over formoterol on St George's Respiratory Questionnaire (p interaction =0·0043) and pre-bronchodilator FEV 1 (linear effect p<0·0001, p interaction =0·067). Only eosinophil count and smoking history were independent predictors of response to budesonide-formoterol in reducing exacerbations (eosinophil count, p interaction =0·013; smoking history, p interaction =0·015)., Interpretation: In patients with COPD treated with formoterol, blood eosinophil count predicts exacerbation risk and the clinical response to ICS., Funding: AstraZeneca., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: This study aimed to compare the therapeutic effects of different drugs on obstructive sleep apnea/hypopnea syndrome (OSAHS) in children by using a network meta-analysis approach., Methods: PubMed, Embase and Cochrane Library were searched from the inception of each database to November 2015. Randomized controlled trials (RCTs) concerning the comparisons in the therapeutic effects of eight placebo-controlled drugs on OSAHS in children were included in this study. Network meta-analysis combined direct evidence and indirect evidence to evaluate the weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRA) of therapeutic effects of eight drugs on OSAHS in children., Results: A total of seven RCTs were finally incorporated into our network meta-analysis. Pairwise meta-analysis results revealed that therapeutic effect of placebo was significantly poorer than that of intranasal mometasone furoate, montelukast, budesonide and fluticasone concerning apnea hypopnea index (AHI) value [WMD=1.40, 95% confidence interval (CI)=1.17-1.63; WMD=2.80, 95% CI=1.01-4.59; WMD=3.50, 95% CI=3.34-3.66; WMD=7.20, 95% CI=5.26-9.14, respectively], and fluticasone is better than placebo concerning sleep efficiency (WMD=3.50, 95% CI=2.42-4.58); regarding visual analogue scale, the therapeutic effect of placebo was poorer compared with sucralfate and clindamycin (WMD=1.94, 95% CI=1.13-2.75; WMD=1.06, 95% CI=0.22-1.90), and sucralfate is better than clindamycin (WMD=-0.88, 95% CI=-1.65 to -0.11). However, network meta-analysis results showed no obvious difference in the therapeutic effects of different drugs on OSAHS regarding AHI and sleep efficiency. Furthermore, the best SUCRA value was very high for fluticasone concerning AHI (86.6%) and budesonide concerning sleep efficiency (94.0%) for OSAHS treatment., Conclusions: Fluticasone and budesonide have relatively good effects in the treatment of OSAHS in children, thus providing an important guiding significance for the treatment of OSAHS in children.

Introduction: The effectiveness of single-inhaler budesonide/formoterol fumarate combination therapy for asthma has been previously shown for the original product. The aim of this nonrandomized, open-label, postauthorization efficacy study (PAES) real-life clinical assessment was to evaluate the clinical effectiveness of a second product (Bufomix Easyhaler ® ) in the daily clinical practice of asthma therapy., Methods: This multicenter PAES was conducted by 220 unselected allergologists and pulmonologists who enrolled 2200 adult outpatients (age 49.8 ± 17.9 years) with asthma treated with Bufomix Easyhaler ® for at least 14 days before enrolment. Asthma control was assessed during three subsequent visits with 8-12-week intervals on the basis of the Asthma Control Test (ACT). Adherence was assessed with the Medication Adherence Questionnaire. In addition, patient satisfaction with Bufomix Easyhaler ® was scored, and adverse drug reactions were recorded., Results: The percentage of patients with well-controlled asthma or total control of asthma (ACT score 20-25 points) increased from 46.6% at the first visit to 90.8% at the third visit (p < 0.001). In addition, the percentage of patients with poor control of asthma (ACT score less than 15 points) decreased from 14.9% to 1.2% (p < 0.001). The adherence rate increased from 88% at the first visit to 95.3% at the third visit. Patient satisfaction with the use of this dry powder inhaler increased with the duration of its use. Only one adverse drug reaction was reported., Conclusion: The results obtained confirm the effectiveness of Bufomix Easyhaler ® in the treatment of asthma in outpatient adults in daily clinical practice., Funding: Orion Corporation.

Objective: We investigated the effects of ventilator mask atomization inhalation of ipratropium bromide and budesonide suspension liquid in the treatment of acute exacerbation COPD (AECOPD) on circulating levels of inflammatory factors and prognosis., Patients and Methods: A total of 86 cases of patients on ventilator support were randomly divided into control group and observation group with 43 cases each. The control group was administered routine treatment including basic disease treatment, anti-infection, maintenance of a stable internal environment, nutritional support, oxygen inhalation and so on. The control group was administered saline through a ventilator mask. The observation group was treated with atomized inhalation of ipratropium bromide and budesonide suspension and oxygen flow 3-5 L/min, 15-20 min/time and twice a day for 1 week. The treatment effects were compared., Results: Serum TNF-α, IL-6, and CRP levels were decreased in both groups after treatment, but levels in the observation group were significantly lower than those of the control group; differences were statistically significant (p < 0.05). Forced vital capacity (FVC), forced expiratory volume (FEV1), FEV1/FVC and maximal expiratory flow rate in the observation group were significantly higher than those in the control group after treatment (p < 0.05). After treatment, the PaO2, SpO2 and respiratory failure index (RFI) of the observation group were significantly higher than those of the control group. The PaCO2 levels of the observation group were lower than those of the control group. The differences were statistically significant (p < 0.05). The clinical efficacy of the observation group was better than that of the control group; the ventilation time and total treatment time was significantly shorter and the differences were statistically significant (p < 0.05)., Conclusions: The ventilator mask atomizing inhalation of ipratropium bromide and budesonide suspension liquid in the treatment of AECOPD can significantly improve circulating inflammatory reaction, improve lung function and blood gas levels, increase the treatment efficiency, and shorten the treatment time.

Introduction: Chronic obstructive pulmonary disease is associated with a high healthcare resource and cost burden. Healthcare resource utilization was analyzed in patients with symptomatic chronic obstructive pulmonary disease at risk of exacerbations in the FULFIL study. Patients received either once-daily, single inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol) 100 µg/62.5 µg/25 µg or twice-daily dual inhaled corticosteroid/long-acting beta agonist therapy (budesonide/formoterol) 400 µg/12 µg., Methods: FULFIL was a phase III, randomized, double-blind, double-dummy, multicenter study. Unscheduled contacts with healthcare providers were recorded by patients in a daily electronic diary; the costs of healthcare resource utilization were calculated post hoc using UK reference costs., Results: Over 24 weeks, slightly fewer patients who received fluticasone furoate/umeclidinium/vilanterol (169/911; 18.6%) required contacts with healthcare providers compared with budesonide/formoterol (180/899; 20.0%). Over 52 weeks in an extension population, fewer patients who received fluticasone furoate/umeclidinium/vilanterol required unscheduled contacts with healthcare providers compared with budesonide/formoterol (25.2% vs. 32.7%). Non-drug costs per treated patient per year were lower in the fluticasone furoate/umeclidinium/vilanterol group than the budesonide/formoterol group over 24 and 52 weeks (£653.80 vs. £763.32 and £749.22 vs. £988.03, respectively), with the total annualized cost over 24 weeks being slightly greater for fluticasone furoate/umeclidinium/vilanterol than budesonide/formoterol (£1,289.35 vs. £1,267.45)., Conclusions: This healthcare resource utilization evidence suggests that, in a clinical trial setting over a 24- or 52-week timeframe, non-drug costs associated with management of a single inhaler fluticasone furoate/umeclidinium/vilanterol are lower compared with twice-daily budesonide/formoterol., Trial Registration: ClinicalTrials.gov number: NCT02345161., Funding: GSK.

Background: The systemic inflammation is associated with clinical outcome and mortality in chronic obstructive pulmonary disease (COPD) patients. To investigate the effects of tiotropium (Tio) and/or budesonide/formoterol (Bud/Form) on systemic inflammation biomarkers in stable COPD patients of group D, a randomized, open-label clinical trial was conducted., Methods: Eligible participants (n = 324) were randomized and received either Tio 18ug once daily (group I), Bud/Form 160/4.5ug twice daily (group II), Bud/Form 320/9ug twice daily (group III), or Tio 18ug once daily with Bud/Form 160/4.5ug twice daily (group IV) for 6 months. Systemic inflammation biomarkers were measured before randomization and during the treatment, including C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), serum amyloid A (SAA), tumor necrosis factor-α (TNF-α), fibrinogen (Fib), and white blood cell (WBC)., Results: After 6-month treatment, CRP levels in group II, group III and group IV changed by a median (interquartile range) of -1.25 (-3.29, 1.18) mg/L, -1.13 (-2.55, 0.77) mg/L, and -1.56 (-4.64, 0.22) mg/L respectively, all of which with statistical differences compared with group I. In addition, there were no treatment differences in terms of IL-8, SAA, TNF-α, Fib and WBC levels., Conclusions: A long-term treatment with Bud/Form alone or together with Tio can attenuate circulating CRP levels in COPD patients of group D, compared with Tio alone.

Objective: Prenatal corticosteroids were shown to reduce the respiratory complication in late preterm infants. Our objective was to determine if early inhaled corticosteroids could alleviate the respiratory distress and morbidity in late preterm and term neonates with transient tachypnea of the newborn (TTN)., Study Design: Double-blind, randomized placebo-controlled, multicenter pilot study. Infants born at >34 weeks gestational age with TTN at 4 h of age were randomized to two doses, 12 h apart, of inhaled Budesonide 1000 μg/dose or placebo within 6 h from delivery. Analysis was done by intention to treat., Results: The study (n = 24) and control (n = 25) groups were comparable in birth characteristics (gestational age: 36.8 ± 1.9 vs 36.4 ± 1.8 weeks) and clinical condition at the time of recruitment (vital signs, clinical score, ventilation support, and blood gases). There was no difference between the study and control groups in clinical score (based on grunting, retractions, ala nasi, and respiratory rate) at recruitment and at 12, 24, and 48 h after the first inhalation (4.3 ± 1.6 vs 4.1 ± 2.1; 1.9 ± 1.8 vs 1.5 ± 1.7; 1.1 ± 1.4 vs 1.3 ± 1.6; 0.5 ± 0.8 vs 0.6 ± 1.0; respectively). Respiratory support at each time point, time to spontaneous unsupported breathing (67.4 ± 74.1 vs 75.2 ± 95.2 h), time to full feeds (86.7 ± 68.7 vs 84.3 ± 66.6 h) and length of stay (9.9 ± 5.5 vs 12.4 ± 8.0 days) did not differ between the groups. We did not detect any side effects., Conclusions: Our pilot study was unable to detect a beneficial effect of early administration of inhaled steroids on the clinical course of TTN in late preterm and term infants., (© 2017 Wiley Periodicals, Inc.)

Background: The object of this study was to determine whether high doses of inhaled budesonide provide additional benefits to a standardized treatment regimen that includes systemic steroids and salbutamol in preschool patients presented to the emergency department (ED) with acute wheezing attacks. Methods This randomized, double-blind, placebo-controlled, parallel group trial was conducted in children, 6 months-6 years with moderate or severe acute wheezing epizode, as determined based on a pulmonary index score (PIS) of 7-13 points. We compared the addition of budesonide 3 mg versus placebo to standard acute asthma treatment, which included salbutamol and a single 1 mg/kg dose of methylprednisolone given at the beginning of therapy. The primary outcome was differences in hospitalization rates within 4 hr. Secondary outcome was difference in median PIS between treatment groups at 2 hr. Results One hundred patients were enrolled. Cumulative hospitalization rate at 120, 180, and 240 min were 0.72, 0.62, and 0.58 in placebo group; and 0.44, 0.30, and 0.24 in budesonide group. Discharged rate in budesonide group was significantly higher than the placebo group (log-rank = 12.407 ve P < 0.001). Expected mean discharged times were 200.4 (95%CI = 185.3-215.5) min in placebo group and 164.4 (95%CI = 149.4-179.4) min in budesonide group. Median (25-75%) PIS at the 120th min was significantly lower in budesonide group than the placebo group (5 [4-8] vs. 8 [5-9] respectively, P = 0.006). Conclusions The addition of budesonide nebulization may decrease the admission rate of preschool children who have moderate to severe acute wheezing epizodes. Pediatr Pulmonol. 2017;52:720-728. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Bronchodilator therapy is the backbone of the management of chronic obstructive pulmonary disease. In some patients, inhaled corticosteroids can be prescribed in combination with bronchodilators. Through a subgroup analysis of pooled data from two large phase III clinical trials of bronchodilator therapy according to concomitant inhaled corticosteroid use (user vs. non-user), we sought to evaluate the clinical benefit of adding inhaled corticosteroids to dual bronchodilator therapy in chronic obstructive pulmonary disease. The primary focus of this analysis of pooled data from the phase III ACLIFORM and AUGMENT studies was to evaluate the efficacy of aclidinium/formoterol on lung function stratified by inhaled corticosteroid use. We found that lung-function end points were significantly improved regardless of concomitant inhaled corticosteroid use among patients treated with the dual bronchodilator aclidinium/formoterol 400/12 µg twice daily compared with placebo and both monotherapies. Together with the previously reported observations that aclidinium/formoterol 400/12 µg reduces exacerbations vs. placebo in inhaled corticosteroid users and improves dyspnoea compared to monotherapy in inhaled corticosteroid non-users, these data suggest that both groups achieve lung function improvements, which translates to different clinical benefits depending on whether or not a patient is receiving concomitant inhaled corticosteroids.CHRONIC LUNG DISEASE: 'TRIPLE' THERAPY COULD PROVE BENEFICIAL: A dual bronchodilator therapy taken together with corticosteroid inhalers may benefit patients with severe chronic lung disease. Bronchodilator drugs relax the lungs and widen airways in patients with chronic obstructive pulmonary disease (COPD). While recent studies have shown that a dual bronchodilator therapy containing aclidinium and formoterol significantly improves lung function in COPD, little is known about combining the dual therapy with inhaled corticosteroids (ICSs). Anthony D'Urzo at the University of Toronto, Canada, and co-workers analysed data from 3394 patients with COPD undergoing dual therapy trials. Of these, 1180 were already taking ICSs. The team compared symptoms in the ICS group with those not taking ICSs. The dual therapy improved lung function across both groups regardless of ICS use, though patients gained different clinical benefits depending on ICS use and disease severity.

Background: Long-acting muscarinic antagonist (LAMA)/long-acting β 2 -agonist (LABA) combinations are a treatment option for patients with COPD who continue to have symptoms despite treatment with a LAMA or a LABA alone. The Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-Very Severe COPD (PINNACLE-1) (NCT01854645) and the Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-Very Severe COPD (PINNACLE-2) (NCT01854658) trials investigated the efficacy and safety of a novel glycopyrrolate [GP]/formoterol [FF] 18/9.6-μg (GFF) metered dose inhaler (MDI) formulated using the Co-Suspension Delivery Technology in patients with moderate-to-very severe COPD., Methods: These two phase III trials took place over 24 weeks and were randomized, double blind, and placebo controlled; 2,103 and 1,615 patients (40-80 years of age), respectively, were randomized. Patients received GFF MDI, GP MDI 18 μg, FF MDI 9.6 μg, or placebo MDI (all twice daily), or tiotropium 18 μg dry powder inhaler (once daily in PINNACLE-1 only [open-label active comparator]). Efficacy and safety were assessed., Results: At week 24, differences in change from baseline in the morning predose trough FEV 1 for GFF MDI vs placebo MDI, GP MDI, and FF MDI were 150 mL, 59 mL, and 64 mL in PINNACLE-1 (all P < .0001) and 103 mL, 54 mL, and 56 mL in PINNACLE-2 (all P < .001), respectively. There were no significant safety findings (incidence of adverse events was similar between treatment arms)., Conclusions: We conclude that GFF MDI 18/9.6 μg demonstrated superiority over placebo and monocomponent MDIs and was well tolerated, thus providing an additional treatment option for patients with moderate-to-very severe COPD., Trial Registry: ClinicalTrials.gov; No.: NCT01854645 and No. NCT01854658; URL: www.clinicaltrials.gov., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Low-dose inhaled corticosteroids (ICS) are highly effective for reducing asthma exacerbations and mortality. Conventionally, ICS treatment is recommended for patients with symptoms on more than 2 days per week, but this criterion has scant evidence. We aimed to assess the validity of the previous symptom-based cutoff for starting ICS by establishing whether there was a differential response to budesonide versus placebo for severe asthma exacerbations, lung function, and asthma symptom control across subgroups identified by baseline asthma symptom frequency., Methods: We did a post-hoc analysis of the 3 year inhaled Steroid Treatment As Regular Therapy (START) study, done in 32 countries, with clinic visits every 3 months. Patients (aged 4-66 years) with mild asthma diagnosed within the previous 2 years and no previous regular corticosteroids were randomised to receive once daily, inhaled budesonide 400 μg (those aged <11 years 200 μg) or placebo. Coprimary outcomes for this analysis were time to first severe asthma-related event (SARE; hospital admission, emergency treatment, or death) and change from baseline in lung function after bronchodilator. Interaction with baseline symptom frequency was investigated, with patients grouped by more than two symptom days per week and two or fewer symptom days per week (divided into no days to 1 day, and more than 1 day to 2 days). Analysis was done by intention to treat., Findings: Of 7138 patients (n=3577 budesonide; n=3561 placebo), baseline symptom frequency was 0-1 days per week for 2184 (31%) participants, more than 1 and less than or equal to 2 symptom days per week for 1914 (27%) participants, and more than 2 symptom days per week for 3040 (43%) participants. For budesonide versus placebo, time to first SARE was longer across symptom frequency subgroups (hazard ratios 0·54 [95% CI 0·34-0·86] for 0-1 symptom days per week, 0·60 [0·39-0·93] for >1 to ≤2 symptom days per week, 0·57 [0·41-0·79] >2 symptom days per week, p interaction =0·94), and the decline in postbronchodilator lung function was less at 3 years' follow-up (p interaction =0·32). For budesonide versus placebo, severe exacerbations requiring oral or systemic corticosteroids were reduced (rate ratio 0·48 [0·38-0·61] 0-1 symptom days per week, 0·56 [0·44-0·71] >1 to ≤2 symptom days per week, and 0·66 [0·55-0·80] >2 symptom days per week, p interaction =0·11), prebronchodilator lung function was higher, and symptom-free days were more frequent (p<0·0001 for all three subgroups), with no interaction by symptom frequency (prebronchodilator p interaction =0·43; symptom-free days p interaction =0·53). Similar results were noted when participants were classified by any guidelines criterion as so-called persistent versus so-called intermittent asthma., Interpretation: In mild recent-onset asthma, once daily, low-dose budesonide decreases SARE risk, reduces lung function decline, and improves symptom control similarly across all symptom subgroups. The results do not support restriction of inhaled corticosteroids to patients with symptoms on more than 2 days per week and suggest that treatment recommendations for mild asthma should consider both risk reduction and symptoms., Funding: AstraZeneca., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Almost all international guidelines recommend corticosteroids for management of exacerbations of chronic obstructive pulmonary disease (COPD), because it leads to improved outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Nevertheless, due to its side effects, there are still concerns regarding the use of systemic corticosteroid (SC). Inhaled corticosteroids (IC) can be used as an alternative to SC, while reducing the risk of occurrence of side effects., Purpose: To measure the clinical efficacy and side effects of nebulized budesonide and systemic methylprednisolone in AECOPD., Methods: Valid data from 410 AECOPD patients in 10 hospitals was collected. Patients were randomly divided into 2 groups; budesonide group, treated with nebulized budesonide (2 mg 3 times/day); and methylprednisolone group, treated with intravenously injected methylprednisolone (40 mg/day). COPD assessment test (CAT), arterial blood gas analysis, hospitalization days, adverse effects, fasting blood glucose, serum creatinine, alanine aminotransferase levels, and blood drug were measured and analyzed in both groups., Results: Symptoms, pulmonary function and arterial blood gas analysis were significantly improved after treatment in both groups (P < 0.05), with no significant differences between them (P > 0.05), while incidence of adverse events in the budesonide group was lower (P < 0.05). No significant differences in CAT score, days of admission, blood gas analysis results and physiological and biochemical indexes were found between the two groups. Patients treated with methylprednisolone showed a higher degree of PaO 2 level improvement., Conclusion: Results show that inhalation of budesonide (2 mg 3 times/day) and systemic methylprednisolone (40 mg/day) had similar clinical outcome in AECOPD. In conclusion, inhaled budesonide is an alternative to systemic corticosteroids in AECOPD treatment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterised by largely irreversible changes in air flow due to irritants such as tobacco smoke. Patients with COPD experience acute exacerbations. Severe disease may progress to chronic respiratory failure. We reviewed the literature on basic medications available for COPD, using the standard Prescrire methodology. There are few clinical data on treatment of mild COPD. Regular medication is not necessary for patients who do not have recurrent symptoms. Eliminating exposure to cigarette smoke and other irritants such as workplace irritants, is the only measure known to improve the outcome of COPD. Evaluation of inhaled short-acting beta-2 agonists is based mainly on short-term trials. These drugs have been shown to improve dyspnoea. Salmeterol and formoterol, two long-acting beta-2 agonists, have been extensively evaluated in symptomatic patients. Compared with no treatment, these drugs reduce breathlessness and acute exacerbations, preventing about two hospital admissions per 100 patients with moderate to severe COPD treated for 7 months. Indacaterol and olodateroldo not have a better harm-benefit balance. Inhaled beta-2 agonists occasionally provoke cardiovascular disorders. No excess mortality has been reported among the thousands of COPD patients included in clinical trials. There Is little evidence that ipratropium, an inhaled short-acting anti-muscarinic bronchodilator, improves COPD symptoms. A risk of Increased mortality among COPD patients treated with ipratroplum cannot be ruled out. Tiotroplum, an inhaled long-acting antimuscarinic bronchodilator, has been extensively evaluated In COPD. Tiotroplum has symptomatic efficacy in COPD, reducing dyspnoea and acute exacerbations. Tiotroplum had no tangible advantages over long-acting beta-2 agonists in seven randomised trials including more than 12 000 patients. Glycopyrronium and aclidinium, two other Inhaled long-acting antimuscarinics, do not appear to be more effective. Tiotroplum, like other inhaled anti-muscarinics, has antimuscarinic adverse effects including cardiac, visual and buccal disorders. Glycopyronium may carry a higher risk of serious cardiovascular effects. Combination of an antimuscarinic with an inhaled beta-2 agonist improves symptoms in 7% to 10% of patients. In patients with one or two COPD exacerbations per year, adding an Inhaled corticosterold (beclometa- sone, budesonide or fluticasone) to a long-acting beta-2 agonist prevents about 1 exacerbation during 3 to 4 years of treatment. Inhaled corticosteroids can cause pneumonia, candidiasis, dysphonia and adrenal Insufficiency. Fluticasone seems to have more adverse effects than other inhaled corticosterolds. Theophylline has uncertain efficacy on symptoms of COPD. This drug has a narrow therapeutic index and carries a risk of serious adverse effects. It should not be used in COPD. Long-term treatment with roflumilast or oral corticosteroids has an unfavourable harm-benefit balance in COPD. In practice, in 2016, the first measure in COPD is to eliminate exposure to the irritant, most often tobacco. Drugs used in COPD have only modest, mainly symptomatic efficacy. Treatment should be adapted to symptoms and the frequency of exacerbations: a short-acting beta-2 agonist should be tried first, then replaced by an inhaled long-acting bronchodilator, or possibly tiotropium, when its effect is too short-lived. An inhaled corticosteroid can be added if symptoms persist or exacerbations are frequent.

Background: The consistency of fixed airflow limitation status during treatment in patients with asthma is unknown., Objective: The objective of this study was to determine the consistency of fixed airflow obstruction (FAO) status during treatment and effects on treatment response., Methods: This post hoc analysis from a 12-week study (NCT00652002) assessed patients aged 12 years or more with moderate-to-severe asthma randomized to twice-daily budesonide/formoterol (BUD/FM) via pressurized metered-dose inhaler (pMDI) 320/9 μg, BUD pMDI 320 μg, FM 9 μg via dry-powder inhaler, or placebo. FAO status was assessed postbronchodilator at screening and after study drug administration at weeks 2, 6, and 12 via the forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) ratio < lower limit of normal (LLN) (FAO+) or ≥ LLN (FAO-). Patients with persistent FAO- and FAO+ retained their screening FAO status at all visits. Patients with inconsistent FAO changed categories at least once during the study. Assessments included early withdrawal due to predefined worsening asthma events (PAEs), lung function, and symptoms., Results: Of 386 patients, 29% had persistent FAO+, 31% inconsistent FAO, and 40% persistent FAO-. PAEs were lowest in the FAO- group overall and with BUD/FM treatment in patients with FAO+ and inconsistent FAO. Baseline demographics and treatment responses of the inconsistent FAO group were most similar to the FAO+ group. The greatest improvements in asthma control days and use of rescue medications were seen with BUD/FM treatment, regardless of FAO status., Conclusions: Approximately one third of patients with moderate-to-severe asthma in this study had inconsistent FAO, and their treatment responses were most similar to patients with FAO+. Regardless of FAO status, patients treated with BUD/FM experienced the most improved treatment responses and fewest withdrawals due to PAEs., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the impact of nebulized budesonide inhalation suspension (BIS) on guardian-reported symptoms in Chinese pediatric patients with cough variant asthma (CVA)., Methods: This was a secondary analysis of a prospective, non-interventional study conducted at 39 Chinese sites. Patients with CVA aged ≤5 years were classified according to the severity of baseline symptoms: mild (symptom score ≤3) or severe (symptom score >3). Daytime and night-time symptom scores, disease control, use of bronchodilators, and improvements in symptoms control were compared after 1, 3, 5 and 7 weeks of treatment between groups., Results: Among 914 patients, 821 (89.8%) completed the 7-week treatment. Among all patients, 368 (40.3%) were classified as mild CVA and 529 (57.9%), as severe CVA. Symptom scores in the severe group were higher than those in the mild group at weeks 1, 3, and 5 (p < 0.05), but not at week 7 (p > 0.05). Further, more patients in the mild group achieved disease control at any time point (98.6% at 3 weeks and 99.7% at 7 weeks), compared with the patients in the severe group (p < 0.001). The proportion of patients requiring bronchodilators differed between the groups until week 5 (p < 0.001). No severe or drug-related adverse events were reported., Conclusions: Individualized BIS treatment should be formulated according to the severity of baseline symptoms in CVA patients. Patients with mild CVA showed improvement after a shorter treatment time, while patients with severe CVA might require a longer time to respond to the treatment.

Maintenance treatment with an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) is recommended for patients whose asthma is not controlled with a low-to-moderate dose of ICS alone; a separate reliever medication is used on an as-needed basis. The Gaining Optimal Asthma ControL (GOAL) study demonstrated that salmeterol/fluticasone maintenance treatment can improve asthma control and reduce future risk compared with fluticasone alone, although the dose escalation design of this study meant that most patients treated with salmeterol/fluticasone were receiving the highest dose of ICS at the end of the study. Similarly, budesonide/formoterol maintenance therapy improved asthma control and reduced future risk compared with budesonide alone in the Formoterol and Corticosteroids Establishing Therapy (FACET) study. An alternative approach to asthma management is to use an ICS/LABA for both maintenance and reliever therapy. A large body of clinical evidence has shown that the use of budesonide/formoterol in this way improves both current control and reduces future risk compared with ICS/LABA plus as-needed short-acting β2-agonist (SABA), even when patients receive lower maintenance doses of ICS as part of the maintenance and reliever therapy regimen. In addition, one study has shown that beclometasone/formoterol maintenance and reliever therapy reduces exacerbations more effectively than beclometasone/formoterol plus as-needed SABA. The use of ICS/LABA as both maintenance and reliever therapy ensures that an increase in reliever use in response to worsening symptoms is automatically matched by an increase in ICS., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Budesonide is approved for delivery using a nebulized solution and dry-powder inhaler, but its use through a pressurized metered-dose inhaler (pMDI) in pediatric patients with asthma has not been determined., Objective: To examine the efficacy and safety of 160 μg twice daily of budesonide through a pMDI vs placebo in children 6 to younger than 12 years with asthma and a demonstrated need for inhaled corticosteroids., Methods: A 6-week, international, multicenter, double-blinded, parallel-group, phase 2 study randomized 304 pediatric patients (mean age, 9 years; 21.7% <8 years) 1:1 to 160 μg (80 μg × 2 inhalations) twice daily of budesonide through a pMDI or placebo after a 7- to 21-day run-in period. The primary efficacy end point was change from baseline in morning peak expiratory flow (PEF); safety end points included adverse events, vital signs, and discontinuations., Results: Budesonide treatment significantly improved morning PEF vs placebo; mean treatment effect (budesonide vs placebo) was 13.6 L/min (P < .0001). Budesonide also showed significant improvements vs placebo for forced expiratory volume in 1 second, evening PEF, forced expiratory flow at 25% to 75% of pulmonary volume, reliever medication use, nighttime awakenings, awakenings with reliever use, and percentage of patients with at least 15- and at least 30-L/min increase in morning PEF from baseline. The numbers of patients experiencing adverse events and discontinuations were smaller in the budesonide than in the placebo group. No serious adverse events were reported., Conclusion: Budesonide at 160 μg twice daily through a pMDI was generally well tolerated and significantly improved lung function, symptoms, rescue medication use, and nighttime awakenings vs placebo in children 6 to younger than 12 years with asthma and a demonstrated need for inhaled corticosteroids., (Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Increasing evidence suggests pharmacological treatments may impact on overall survival in Chronic Obstructive Pulmonary Disease (COPD) patients. Individual clinical trials are rarely powered to detect mortality differences between treatments and may not include all treatment options relevant to healthcare decision makers., Methods: A systematic review was conducted to identify RCTs of COPD treatments reporting mortality; evidence was synthesised using network meta-analysis (NMA). The analysis included 40 RCTs; a quantitative indirect comparison between 14 treatments using data from 55,220 patients was conducted., Results: The analysis reported two treatments reducing all-cause mortality; salmeterol/fluticasone propionate combination (SFC) was associated with a reduction in mortality versus placebo in the fixed effects (HR 0.79; 95 % Crl 0.67, 0.94) but not the random effects model (0.79; 0.56, 1.09). Indacaterol was associated with a reduction in mortality versus placebo in fixed (0.28; 0.08 to 0.85) and random effects (0.29; 0.08, 0.89) models. Mean estimates and credible intervals for hazard ratios for indacaterol versus placebo are based on a small number of events; estimates may change when the results of future studies are included. These results were maintained across a variety of assumptions and provide evidence that SFC and indacaterol may lead to improved survival in COPD patients., Conclusion: Results of an NMA of COPD treatments suggest that SFC and indacaterol may reduce mortality. Further research is warranted to strengthen this conclusion.

Rationale: Age and sex are associated with differences in asthma prevalence and morbidity., Objectives: To determine if age and sex associate with distinct phenotypes and a variable response to therapy in subjects with mild to moderate asthma., Methods: We used Asthma Clinical Research Network data to determine the impact of age and sex on phenotypes and treatment failures among subjects participating in 10 trials from 1993 to 2003., Measurements and Main Results: A total of 1,200 subjects were identified (median age, 30.4 yr; male, 520 [43.3%]; female, 680 [56.7%]) and analyzed. A higher proportion of subjects greater than or equal to 30 years old experienced treatment failures (17.3% vs. 10.3%; odds ratio [OR], 1.82; confidence interval [CI], 1.30-2.54; P < 0.001), and rates increased proportionally with increasing age older than 30 across the cohort (OR per yr, 1.02 [CI, 1.01-1.04]; OR per 5 yr, 1.13 [CI, 1.04-1.22]; P < 0.001). Lower lung function and longer duration of asthma were associated with a higher risk of treatment failures. A higher proportion of subjects greater than or equal to 30 years old receiving controller therapy experienced treatment failures. When stratified by specific therapy, treatment failures increased consistently for every year older than age 30 in subjects on inhaled corticosteroids (OR per year, 1.03; CI, 1.01-1.07). Females had a slightly higher FEV1 % predicted (84.5% vs. 81.1%; P < 0.001) but similar asthma control measures. There was not a statistically significant difference in treatment failures between females and males (15.2% vs. 11.7%; P = 0.088)., Conclusions: Older age is associated with an increased risk of treatment failure, particularly in subjects taking inhaled corticosteroids. There was no significant difference in treatment failures between sexes.