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Background: A novel, once-daily, fixed-dose combination of mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY) delivered via Breezhaler® is the first inhaled corticosteroid/long-acting ꞵ2-agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) therapy approved for the maintenance treatment of asthma in adults inadequately controlled on ICS/LABA combination. In patients with asthma and persistent airflow limitation (PAL), maximal treatment, especially with combination is suggested. This post hoc analysis of data from the IRIDIUM study assessed the efficacy of MF/IND/GLY in asthma patients with and without PAL. Methods: Patients with post-bronchodilator FEV1 ≤80% of predicted and FEV1/FVC ratio of ≤0.7 were categorised as PAL subgroup and the remaining as the non-PAL subgroup. Lung function parameters (FEV1, PEF, and FEF25%–75%) and annualised asthma exacerbations rates were evaluated in both subgroups across the treatment arms: once-daily high-dose MF/IND/GLY (160/150/50 μg), high-dose MF/IND (320/150 μg) and twice-daily high-dose fluticasone/salmeterol (FLU/SAL; 500/50 μg). Results: Of the 3092 randomised patients, 64% (n = 1981) met the criteria for PAL. Overall, there was no evidence of treatment difference between PAL and non-PAL subgroups (interaction P-value for FEV1, FEF25%–75%, PEF, moderate or severe exacerbations, severe exacerbations and all exacerbations were 0.42, 0.08, 0.43 0.29, 0.35 and 0.12, respectively). In the PAL subgroup, high-dose MF/IND/GLY versus high-dose MF/IND and high-dose FLU/SAL improved trough FEV1 (mean difference: 102 mL [P < 0.0001] and 137 mL [P < 0.0001]) and reduced moderate or severe (16% and 32%), severe (25% and 39%) and all exacerbations (19% and 38%), respectively. Conclusions: Once-daily fixed-dose MF/IND/GLY was efficacious in asthma patients with and without persistent airflow limitation.

Kjell Larsson,1 Karin Lisspers,2 Björn Ställberg,2 Gunnar Johansson,2 Florian S Gutzwiller,3 Karen Mezzi,3 Bine Kjoeller Bjerregaard,4 Leif Jorgensen,4 Hyewon Koo,5 Christer Janson6 1Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 3Novartis Pharma AG, Basel, Switzerland; 4IQVIA Solutions, Copenhagen, Denmark; 5IQVIA Solutions, Solna, Sweden; 6Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, SwedenCorrespondence: Kjell Larsson, Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SE-171 77, Sweden, Tel +467 0582 0763, Email kjell.larsson@ki.seBackground: Patients with mild chronic obstructive pulmonary disease (COPD) account for more than half of the total COPD population but are often undiagnosed and sparsely studied. This real-world, longitudinal study compared the socioeconomic burden, clinical characteristics and treatment patterns in patients with mild COPD and age- and gender-matched controls.Patients and methods: Our population included mild COPD patients (forced expiratory volume in one second ≥ 80% of predicted value) and reference controls from 52 Swedish primary care centres over 15 years (2000– 2014). We linked electronic medical record (EMR) data to Sweden’s National Health Registries. The outcomes analyzed were socioeconomic status including annual income from work, presence of comorbidities and the use of medications.Results: 844 patients with mild COPD were included in this study and matched with 844 reference controls. Compared with the reference controls, mild COPD patients had a significantly lower annual income from work (mean difference, men: 12,559€ and women: 7143€) and were significantly less likely to be married or employed. The presence of comorbidities, including cardiovascular disease, anxiety and depression (only women) was significantly higher in mild COPD patients. The use of medications, such as proton pump inhibitors, antidepressants, central painkillers and sleep medications, was significantly higher in the mild COPD group.Conclusion: Mild COPD presents a considerable socioeconomic and clinical burden compared with reference controls The findings suggest that COPD constitutes a condition that influences health status even in mild disease clearly demanding an increased need for early detection and treatment.Keywords: chronic obstructive pulmonary disease, socioeconomic status, comorbidities, co-medications, annual income, exacerbation, Sweden

Purpose Chronic obstructive pulmonary disease (COPD) and heart failure (HF) often occur concomitantly, presenting diagnostic and therapeutic challenges for clinicians. We examined the characteristics of patients prescribed adequate versus inadequate therapy within 3 months after newly diagnosed comorbid COPD or HF. Patients and methods Eligible patients in longitudinal UK electronic medical record databases had pre-existing HF and newly diagnosed COPD (2017 GOLD groups B/C/D) or pre-existing COPD and newly diagnosed HF. Adequate COPD therapy was defined as long-acting bronchodilator(s) with/without inhaled corticosteroid; adequate HF therapy was defined as beta-blocker plus angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker. Results Of 2439 patients with HF and newly diagnosed COPD (mean 75 years, 61% men), adequate COPD therapy was prescribed for 726 (30%) and inadequate for 1031 (42%); 682 (28%) remained untreated for COPD. Adequate (vs inadequate) COPD therapy was less likely for women (35%) than men (45%), smokers (36%) than ex-/non-smokers (45%), and non-obese (41%) than obese (47%); spirometry was recorded for 57% prescribed adequate versus 35% inadequate COPD therapy. Of 12,587 patients with COPD and newly diagnosed HF (mean 75 years, 60% men), adequate HF therapy was prescribed for 2251 (18%) and inadequate for 5332 (42%); 5004 (40%) remained untreated for HF. Adequate (vs inadequate) HF therapy was less likely for smokers (27%) than ex-/non-smokers (32%) and non-obese (30%) than obese (35%); spirometry was recorded for 65% prescribed adequate versus 39% inadequate HF therapy. Conclusion Many patients with comorbid COPD/HF receive inadequate therapy after new diagnosis. Improved equity of access to integrated care is needed for all patient subgroups.

The Breezhaler® dry powder inhaler (DPI) has a low carbon footprint compared with other inhalation therapies, consistent with the literature on other DPIs. This life-cycle assessment was conducted in France, Germany, the UK, and Japan using a “cradle-to-grave” technique to evaluate six environmental impact categories (global warming potential, acidification, ozone depletion, use of resource, minerals, and metals, eco-toxicity, and freshwater use) associated with the use of the Breezhaler®. Three variants of the Breezhaler® (30-day packs with and without the digital companion and a 90-day pack without the digital companion) were evaluated to identify major hotspots in the device life-cycle and to provide realistic solutions to reduce the environmental impact. Although no single life-cycle stage dominated the climate change impact of the 30-day device with the digital companion, the inhaler’s raw materials and packaging contributed to 96% of the resource depletion impact for the 30-day device without the digital companion. For the 90-day device without the digital companion, packaging contributed 42–62% of the impact across all categories. Overall, the Breezhaler® inhaler with the 90-day pack had the lowest environmental impact. The environmental impact of the device did not vary significantly among the considered markets. Further studies are needed to assess the impact of active pharmaceutical ingredients and improvement in clinical outcomes on the environment.

The concept of chronic obstructive pulmonary disease (COPD) control has been proposed to guide treatment decisions in COPD. In this study, we aimed to validate the prospective value of this concept in the SPARK study population. Control was assessed based on COPD stability and impact. Patients with low impact and stability during weeks 1–12 were classified as controlled, and exacerbations were measured during a 52-week follow-up. Of the 2044 patients included a majority were non-controlled (80%), frequently due to high impact. During the follow-up, the rate of moderate/severe exacerbations was significantly lower in controlled patients (rate ratio, 0.56, 95% CI 0.48 to 0.65 p

Respiratory inhalers have a substantial impact on the carbon footprint of the healthcare sector. Environmental factors, including carbon footprints, are gaining importance in choosing inhalers once medical considerations have been addressed. This paper provides a review of the carbon footprint (CFP) and life cycle assessment (LCA) environmental profile of dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs). Despite methodological challenges, our analysis reveals that the CFP varies between DPIs ranging from 359 gCO2e per inhaler (Enerzair Breezhaler® DPI without digital companion 30-day pack) to 1250 gCO2e per inhaler (Seretide Accuhaler® 50/500) and from 6.13 gCO2e per dose (Enerzair Breezhaler® without digital companion 90-day pack) to 27 gCO2e per dose (Relvar Elipta 92/22). The breakdown of inhaler CFP by life cycle stage reveals that, although the use and end-of-life stages together contribute to most of the CFP of the MDIs, the largest contributions to the CFP of the DPI/SMI are made by the API and manufacturing stages of the life cycle. Although from a climate perspective our review aligns with the findings of Jeswani and Azapagic that DPIs have a lower CFP than pMDIs, we conclude that the performance against other environment impact categories depends on the design, choice of material and manufacturing process of the DPIs. The challenge of comparing the CFP of different inhalers can be made easier by the standardization of study boundaries and methods.

Chantal Raherison-Semjen,1 Karen Mezzi,2 Konstantinos Kostikas,2 Alexander J Mackay,3 Dave Singh4 1Department of Respiratory Diseases, University of Bordeaux, Bordeaux, France; 2Global Medical Affairs Department, Novartis Pharma AG, Basel, Switzerland; 3Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK; 4Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundations Trust, Manchester, UKCorrespondence: Chantal Raherison-SemjenCentre INSERM 1219 Equipe Epicene, BPH Bordeaux Population Health Research Center, Université de Bordeaux, ISPED Institut de Santé Publique d’épidémiologie et de Développement, 146 Rue Leo Saignat, Bordeaux, 33076, FranceTel +33 0 557571234Email chantal.raherison-semjen@u-bordeaux.frObjective: To evaluate the perception of physicians on gender-specific differences in the diagnosis of chronic obstructive pulmonary disease (COPD) using a qualitative and anonymous questionnaire-based survey.Methods: The survey was conducted amongst respiratory physicians attending a standalone educational conference (29– 30 September 2017) using the SpotMe® App. The 20-item standardized closed questionnaire had pre-coded responses to questions on physician’s profile, and perception of COPD diagnosis and existing comorbidities between genders. All the responses were recorded anonymously.Results: Of 368 physicians who downloaded the SpotMe® App and had access to the survey, 132 (35.9%) completed the survey. Respondents were predominantly hospital-based (57.3%), aged 30– 49 years (54.2%), male (56.5%), and from large cities (59.5%). 68.7% of physicians perceived the prevalence of COPD to be higher in men; over 50% of physicians perceived that women were more prone to the effects of smoking. More than 60% of physicians agreed that women experience more severe symptoms (anxiety and depression) and have reduced quality of life than men. Over 50% of physicians agreed that misdiagnosis/underdiagnosis of COPD in women was an important factor for gender-differences.Conclusion: Results from this survey indicate that the understanding of COPD burden in women varies among healthcare professionals.Keywords: comorbidity, COPD, gender difference, physician perception, gender bias

Kjell Larsson,1 Christer Janson,2 Karin Lisspers,3 Björn Ställberg,3 Gunnar Johansson,3 Florian S Gutzwiller,4 Karen Mezzi,4 Bine Kjoeller Bjerregaard,5 Leif Jorgensen5 1Integrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; 2Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 3Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 4Novartis Pharma AG, Global Patient Access, Basel, Switzerland; 5IQVIA Solutions, Real World Evidence Solutions, Copenhagen, DenmarkCorrespondence: Kjell LarssonIntegrative Toxicology, The National Institute of Environmental Medicine, Karolinska Institute, Stockholm, SE-171 77, SwedenTel +467 0582 0763Email kjell.larsson@ki.sePurpose: The aim of this study was to assess the association between exacerbation frequency and clinical and economic outcomes in patients with COPD.Patients and Methods: Electronic medical record data linked to National Health Registries were collected from COPD patients at 52 Swedish primary care centers (2000– 2014). The outcomes analyzed were exacerbation rate, mortality, COPD treatments, lung function and healthcare costs during the follow-up period. Based on the exacerbation rate two years before index date, the patients were initially classified into three groups, either 0, 1 or ≥ 2 exacerbations per year. After the index date, the classification into exacerbation groups was updated each year based on the exacerbation rate during the last year of follow-up. A sensitivity analysis was conducted excluding patients with asthma diagnosis from the analysis.Results: In total 18,586 COPD patients were analyzed. A majority of the patients (60– 70%) who either have had no exacerbation or frequent exacerbations (≥ 2/year) during the pre-index period remained in their group (ie, with 0 or ≥ 2 annual exacerbations) during up to 11 years of follow-up. Compared with having no exacerbation, mortality was higher in patients having 1 (HR; 2.06 [1.93– 2.20]) and ≥ 2 (4.58 [4.33– 4.84]) exacerbations at any time during the follow-up. Lung function decline was more rapid in patients with frequent exacerbations and there was an almost linear relationship between exacerbations frequency and mortality. Total healthcare costs were higher in the frequent exacerbation group (≥ 2/year) than in patients with no or one exacerbation annually (p< 0.0001 for both). The results did not differ from the main analysis after exclusion of patients with a concurrent asthma diagnosis.Conclusion: In addition to faster lung function decline and increased mortality, frequent exacerbations in COPD patients imply a significant economic burden.Keywords: chronic obstructive pulmonary disease, exacerbations, mortality, lung function, healthcare cost, Sweden

Inhaled corticosteroids have proven to be less effective in asthmatic patients who smoke; however, there is limited information on the efficacy of inhaled corticosteroid-containing regimens in COPD patients who continue smoking. We evaluate the differential efficacy of once-daily indacaterol/glycopyrronium 110/50 µg compared with twice-daily salmeterol/fluticasone 50/500 µg in current smokers and ex-smokers with COPD. A pooled analysis of data from ILLUMINATE, LANTERN and FLAME studies was conducted to assess the efficacy of indacaterol/glycopyrronium compared with salmeterol/fluticasone in current smokers and ex-smokers with COPD. Efficacy was assessed in terms of improvements in trough forced expiratory volume in 1 s (FEV1), transition dyspnoea index (TDI) focal score, St George's Respiratory Questionnaire (SGRQ) total score, reduced rescue medication use and exacerbation prevention at 26 weeks after the start of the therapy. In total, 1769 (38%) current smokers and 2848 (62%) ex-smokers were included. Patients treated with indacaterol/glycopyrronium experienced greater improvements in trough FEV1 versus salmeterol/fluticasone in both current and ex-smokers (least squares mean treatment difference, 105 mL and 78 mL, respectively). Improvements in TDI focal score, SGRQ total score and reduction in rescue medication use were also greater with indacaterol/glycopyrronium versus salmeterol/fluticasone in current and ex-smokers. Furthermore, indacaterol/glycopyrronium reduced all exacerbations (moderate/severe) compared with salmeterol/fluticasone, irrespective of smoking status. The difference in efficacy in favour of indacaterol/glycopyrronium was more prominent in current smokers in most cases. Indacaterol/glycopyrronium demonstrated greater efficacy versus salmeterol/fluticasone, and the differences were generally more prominent in current smokers suggesting smoking may reduce the effects of salmeterol/fluticasone., In both current smokers and ex-smokers with COPD, indacaterol/glycopyrronium demonstrates greater efficacy than salmeterol/fluticasone but the difference is more prominent in current smokers for most of the evaluated parameters https://bit.ly/2Ih8Hq3

This study reports the association of ICS use and the risk of type 2 diabetes mellitus (T2DM) in Swedish patients with COPD using data from real-world, primary care settings. A total of 7078 patients with COPD were included in this analysis and the 5-year cumulative incidence rate per 100,000 person years was 1506.9. The yearly incidence rate per 100,000 person years ranged from 850 to 1919. Use of ICS especially at a high dose in patients with COPD was related to an increased risk of T2DM.

The effect of inhaled corticosteroids (ICS) on the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. The aim of this study was to assess this risk in patients with COPD.Electronic medical record data linked to National Health Registries were collected from COPD patients and matched reference controls at 52 Swedish primary care centres from 2000 to 2014. The outcomes analysed were the effect of ICS on all fractures, fractures typically related to osteoporosis, recorded osteoporosis diagnosis, prescriptions of drugs for osteoporosis and a combined measure of any osteoporosis-related event. The COPD patients were stratified by the level of ICS exposure.A total of 9651 patients with COPD and 59 454 matched reference controls were analysed. During the follow-up, 19.9% of COPD patients had at least one osteoporosis-related event compared with 12.9% of reference controls (pWe conclude that patients with COPD have a greater risk of bone fractures and osteoporosis, and high-dose ICS use increased this risk further.

The present study aimed to generate real-world evidence regarding gender differences among chronic obstructive pulmonary disease (COPD) patients, especially as regards the diagnosis and outcomes in order to identify areas for improvement and management and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients and a matched reference population from 52 primary care centers in 2000–2014. The incidence of COPD, prevalence of asthma and other comorbidities, risk of exacerbations, mortality rate, COPD drug prescriptions, and healthcare resource utilization were analyzed. In total, 17,479 patients with COPD were included in the study. During the study period, COPD was more frequent among women (53.8%) and women with COPD experienced more exacerbations vs. men (6.66 vs. 4.66). However, the overall mortality rate was higher in men compared with women (45% vs. 38%), but no difference for mortality due to COPD was seen between genders over the study period. Women seemed to have a greater susceptibility to asthma, fractures, osteoporosis, rheumatoid arthritis, rhinitis, depression, and anxiety, but appeared less likely to have diabetes, kidney diseases, and cardiovascular diseases. Furthermore, women had a greater risk of COPD-related hospitalization and were likely to receive a significantly higher number of COPD drug prescriptions compared with men. These results support the need to reduce disease burden among women with COPD and highlight the role of healthcare professionals in primary care who should consider all these parameters in order to properly diagnose and treat women with COPD.

In this pooled analysis, we compared the effect of indacaterol/glycopyrronium (IND/GLY) by sex versus other commonly used chronic obstructive pulmonary disease (COPD) treatments and placebo. Male and female patients with moderate-to-very-severe COPD who had participated in six randomized controlled trials were included in the analysis. Baseline demographics and disease characteristics were analyzed by sex, and any differences noted. The effects of IND/GLY versus salmeterol/fluticasone (SFC), glycopyrronium, tiotropium and placebo, on lung function and the patient-reported outcomes (health status, dyspnea, rescue medication use and symptoms) were assessed by sex after 26 weeks treatment. The analysis population comprised 4719 men and 1389 women. Most baseline parameters differed significantly between men and women. Nonetheless, despite these differences in baseline characteristics, IND/GLY significantly improved lung function versus placebo (p < 0.0001) and all active comparators (p < 0.01) in men and women. Overall, IND/GLY showed better improvement in dyspnea and health status compared with all other treatments in both sex. Greater reduction of rescue medication use was observed with IND/GLY versus placebo and other treatments (all p < 0.01 expect IND/GLY versus SFC). Although some variability was observed, improvements in health status, dyspnea, rescue medication use and symptoms were generally larger in women than in men. Irrespective of sex, IND/GLY provided superior efficacy to monotherapy or SFC in both men and women. Small differences in efficacy response by sex were observed, which should be evaluated further in prospective clinical studies. Nevertheless, the benefits observed with IND/GLY confirm dual bronchodilator as the preferred therapy in patients with moderate-to-very-severe COPD regardless of sex.

Claus Vogelmeier,1 Nanshan Zhong,2 Michael J Humphries,3 Karen Mezzi,4 Robert Fogel,5 Giovanni Bader,4 Francesco Patalano,4 Donald Banerji5 1Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany; 2State Key Laboratory, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, 3Beijing Novartis Pharma Co. Ltd., Shanghai, People’s Republic of China; 4Novartis Pharma AG, Basel, Switzerland; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Background: Indacaterol/glycopyrronium (IND/GLY) is approved for maintenance treatment of adult patients with COPD. This post hoc analysis explored the efficacy and safety of IND/GLY versus salmeterol/fluticasone (SFC) in symptomatic (Global Initiative for Chronic Obstructive Lung Disease [GOLD] B and GOLD D) patients with moderate-to-severe COPD.Patients and methods: Data from LANTERN and ILLUMINATE studies were pooled and analyzed. In both studies, symptomatic COPD patients were randomized to once-daily IND/GLY 110 µg/50µg or twice-daily SFC 50 µg/500µg. End points were pre-dose trough forced expiratory volume in one second (FEV1), standardized area under the curve for FEV1 from 0 to 12hours (FEV1 AUC0–12hours), peak FEV1, peak forced vital capacity (FVC), pre-dose trough FVC, Transition Dyspnea Index (TDI) total score, St George’s Respiratory Questionnaire total score, rescue medication use and safety.Results: A total of 1,263 patients were classified as either GOLD B (n=809) or GOLD D (n=454). At week 26, IND/GLY demonstrated statistically significant improvement in all lung function parameters versus SFC in patients in both the GOLD B and GOLD D subgroups. TDI total score and rescue medication use were significantly improved with IND/GLY versus SFC in the overall population and in the GOLD B (TDI total score only) and GOLD D (rescue medication only) subgroups. IND/GLY also reduced the rate of exacerbations in the pooled population. Overall safety profile was comparable with a higher incidence of pneumonia in the SFC-treated group.Conclusion: In this pooled analysis, IND/GLY demonstrated superior efficacy compared with SFC in patients in the GOLD B and GOLD D subgroups and supported its use in symptomatic COPD patients. Keywords: COPD, exacerbation, LABA/LAMA, LABA/ICS, lung function

Introduction: The Global initiative for chronic Obstructive Lung Disease (GOLD) recommends treating patients with chronic obstructive pulmonary disease (COPD) based on a combined assessment of symptom severity and airflow limitation and/or exacerbation risk. According to GOLD, patients with mild-to-moderate airflow limitation and distressing symptoms such as dyspnea should be treated with a long-acting beta2-agonist (LABA) or a long-acting muscarinic antagonist (LAMA). If symptoms persist on monotherapy, GOLD recommends a combination of bronchodilators (LABA/LAMA). Methods: We performed a post-hoc analysis of data from two 26-week, prospective clinical trials to investigate the effect of treating patients with moderate-to-severe dyspnea with the once-daily LABA/LAMA combination indacaterol/glycopyrronium (IND/GLY) 110/50 µg compared with placebo, once-daily tiotropium 18 µg, and twice-daily salmeterol/fluticasone propionate (SFC) 50/500 µg. In this analysis, a Baseline Dyspnea Index (BDI) score ≤7 was used to identify dyspneic patients. Results: In dyspneic patients, IND/GLY significantly improved Transition Dyspnea Index (TDI) total scores compared with tiotropium (0.59 units; p

The burden of chronic obstructive lung disease (COPD) is increasing in women, with recent evidence suggesting gender differences in disease characteristics and potentially in treatment outcomes. FLAME was a 52-week randomized controlled trial in patients with severe-to-very-severe COPD and a history of exacerbations. In this post-hoc analysis, gender-based baseline differences and treatment outcomes between indacaterol/glycopyrronium 110/50 μg once daily (IND/GLY) and salmeterol/fluticasone 50/500 twice daily (SFC) were assessed in terms of rate of exacerbations, time-to-first exacerbation, lung function, health status, and rescue medication use. This post-hoc analysis included 2557 men and 805 women. Baseline characteristics differed between genders, with women being younger, having better lung function and more often experiencing ≥2 exacerbations in the previous year. Compared with SFC, IND/GLY treatment was associated with reductions in the annualized rates of moderate/severe exacerbations (rate ratio [95% CI]: 0.81 [0.73–0.91], 0.89 [0.74–1.07] in men and women, respectively). Similarly, time-to-first moderate/severe exacerbation was also delayed (hazard ratio [95% CI]: 0.79 [0.70–0.89] and 0.76 [0.63–0.91] in men and women, respectively). Results were similar for all (mild/moderate/severe) exacerbations. Improvements in lung function, health status and rescue medication use with IND/GLY vs SFC were comparable between men and women. The smaller sample size for women may account for some observed discrepancies in treatment responses. Although there were gender differences in baseline characteristics, IND/GLY demonstrated similar trends for exacerbation prevention and lung function improvement in men and women with moderate-to-very-severe COPD and a history of exacerbations compared with SFC. Small differences in the effects seen between genders may be attributed to the different sizes of the two groups and need to be further evaluated in randomized trials that are appropriately powered for gender analysis. Post hoc analysis of the FLAME study. ClinicalTrials.gov number: NCT01782326 . Registered 1 February 2013.

Background Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening. This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study. Methods CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St. George’s Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation. Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID−) at Week 12. Results IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67–0.78]; P

Background: Prevalence of chronic obstructive pulmonary disease (COPD) in women is increasing and the disease may present with a different course of progression and comorbidity pattern compared to men. Objective: To assess gender differences in exacerbations, prevalence of comorbidities and health related costs in COPD patients treated with standard of care. Methods: Electronic medical record data collected from COPD patients in 52 Swedish primary care centres were linked to patient socio-economics, prescriptions and hospital care data from mandatory national registries between 2000 and 2014. Outcomes were analysed 2 years after COPD diagnosis. Results: 17,479 COPD patients (mean age: 65.01 yrs; women: 54.4%) were analysed. Time to first exacerbation analysis showed a 12% higher risk for women compared to men (HR 1.12; p Conclusion: Women with COPD have more exacerbations and are more likely to have osteoporosis than men. However, HCRU costs were slightly higher for men than women and the largest differences were driven by non-COPD related hospitalisations.

Antonio R Anzueto,1,2 Claus F Vogelmeier,3 Konstantinos Kostikas,4 Karen Mezzi,4 Sebastian Fucile,5 Giovanni Bader,4 Steven Shen,5 Donald Banerji,5 Robert Fogel5 1University of Texas Health Science Center, 2South Texas Veterans Healthcare System, University of Texas, San Antonio, TX, United States; 3Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany; 4Novartis Pharma AG, Basel, Switzerland; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States Background: Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD. In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.Methods: Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC). Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD. Definition 1 (D1) comprised a ≥100 mL decrease in forced expiratory volume in 1second (FEV1), a ≥4-unit increase in St George’s Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation. In Definition2 (D2), a ≥1-unit decrease in transition dyspnea index replaced FEV1.Results: Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P

Introduction Deterioration in lung function, health status and exacerbations are predictors of COPD worsening. A composite endpoint, CID of above parameters can be an indicator of treatment effect on disease progression. We report effects of IND/GLY vs. TIO on time to first CID in patients (pts) with moderate-severe COPD. Methods Data from 2 randomised trials were analysed. CID was defined, based on minimum clinically important differences, in two ways. Definition 1 [D1]: ≥100mL decrease in FEV 1 or ≥4U increase in SGRQ total score or moderate-severe exacerbation; sustained CID defined as ≥100mL decrease in FEV 1 or ≥4U increase in SGRQ total score on 2 consecutive visits ≥4 weeks apart or ≥50% of all subsequent visits or exacerbation. In Definition 2 (D2, assessed only in SHINE), FEV 1 was replaced with ≥1U decrease in TDI. Time to first CID was also assessed in subgroups based on age, gender, smoking status, disease severity and serum eosinophils. Results Data of 2429 pts (SHINE, n=954; SPARK, n=1475) were analysed. In D1, time to first CID was significantly delayed by IND/GLY vs. TIO in SHINE (HR, 0.72; p=0.0003) and SPARK (HR, 0.87; p=0.0229. IND/GLY also significantly delayed sustained CID vs. TIO in SHINE (HR, 0.73; p=0.0013) and SPARK (HR, 0.88; p=0.0397). In D2, IND/GLY showed significant delay in time to first CID (HR, 0.74; p=0.0022) and sustained CID (HR, 0.77; p=0.0184) vs. TIO. Subgroup analysis results were consistent with overall results. Conclusion IND/GLY significantly reduced risk of CID and provided sustained efficacy in patients with moderate-severe COPD vs. TIO.

Introduction In the past years, there is evidence of increasing prevalence and mortality rates in women diagnosed with COPD. Data on response to long-acting bronchodilators for COPD management are needed in order to identify optimal treatment according to gender variances. Here we report improvement in lung function with IND/GLY in men and women from randomised trials of IGNITE program. Methods Data were pooled from 6 trials of ≥6 months duration (SHINE [n=2144], SPARK [n=2224], ILLUMINATE [n=523], ENLIGHTEN [n=339], ARISE [n=160], and LANTERN [n=744]). Efficacy of IND/GLY was assessed in terms of improvement in FEV 1 and FVC vs. placebo (PBO), tiotropium (TIO), and salmeterol/fluticasone (SFC) in men and women with moderate to very severe COPD (FEV 1 Results Data of 6108 patients were pooled and analysed (men [n=4719] and women [n=1389]). There were significant differences in COPD baseline characteristics, with women being younger and more likely to have prior exacerbation. At Week 26, change from baseline in trough FEV 1 and FVC with IND/GLY was significantly better vs. all comparators in both men and women (Table). Conclusion Irrespective of gender differences in baseline characteristics, improvement in lung function with IND/GLY versus PBO, TIO and SFC was significantly better and comparable in both men and women with COPD.

Introduction FLAME was the first study to show superiority of IND/GLY (LABA/LAMA) in reducing risk of exacerbations vs. SFC (LABA/ICS) in COPD patients (pts) with history of exacerbations. We report results regarding effect of IND/GLY vs. SFC on COPD exacerbations in pts with or without prior ICS/LABA/LAMA triple therapy. Methods FLAME, a 52-week, randomised, double-blind study, compared once-daily IND/GLY 110/50µg vs. twice-daily SFC 50/500μg in pts with moderate-to-very severe COPD with ≥1 exacerbation in previous year. In this post-hoc analysis, time to first COPD exacerbation (mild, moderate or severe) and moderate/severe COPD exacerbation with IND/GLY vs. SFC were analysed. Additionally, treatment effects on rates of exacerbations were assessed in these pts. Results Of 3354 pts included in this analysis, 1148 (34.2%) were on prior triple therapy. IND/GLY significantly reduced the risk of any exacerbation and moderate/severe exacerbation vs. SFC in pts, irrespective of prior triple therapy (table). IND/GLY numerically reduced the rate of any and moderate/severe COPD exacerbations vs. SFC in pts with/without prior triple therapy (table). Conclusion IND/GLY significantly reduces risk of exacerbations versus SFC, irrespective of prior triple therapy in exacerbating patients with moderate-to-very severe COPD.

Introduction COPD is marked by progressive decline in lung function and quality of life, and exacerbations. A composite endpoint like CID can be an indicator of the treatment effect on COPD worsening. This was a post hoc analysis of IND/GLY vs. SFC on CID in symptomatic moderate-to-severe COPD patients (pts) without frequent exacerbations from the LANTERN and ILLUMINATE studies. Methods Data was pooled from two 26-week studies in symptomatic COPD pts randomised to IND/GLY 110/50μg o.d. or SFC 50/500μg b.i.d. We assessed risk of CID and sustained CID using 2 definitions based on minimum clinically important differences. Definition 1 (D1): CID defined as ≥100mL decrease in FEV 1 or ≥4unit increase in SGRQ total score or a moderate-severe COPD exacerbation; sustained CID defined as ≥100mL decrease in FEV 1 or ≥4unit increase in SGRQ total score on 2 consecutive visits ≥4weeks apart or ≥50% of all subsequent visits or a moderate-severe COPD exacerbation. Definition 2 (D2): same as D1 except FEV 1 criteria replaced with ≥1unit decrease in TDI. A subgroup analysis was done by gender, COPD severity, age, smoking status and serum eosinophil count. Results In total, 1263 pts (IND/GLY n=630, SFC n=633) were included. IND/GLY significantly delayed time to first and sustained CID vs. SFC in D1 [HR(95%CI):0.67(0.57–0.80), 0.63(0.52–0.77), respectively; p Conclusion IND/GLY reduced the risk of CID versus SFC, supporting its use over SFC in symptomatic COPD patients.

The best delivery of a drug in ventilated neonates is obtained when using a small particle diameter solution administered via a spacer. Lung deposition of hydrofluoroalkane beclomethasone dipropionate (QVAR, 1.3 microm particles), delivered via an Aerochamber-MV15, was measured in piglets under conditions mimicking ventilated severely ill neonates (uncuffed 2.5 mm endotracheal tube; peak pressure 16 cm H2O; respiratory rate 40/min). After determining the mass and particle size distribution of the 99mTc-labeled and unlabeled drug, three lung deposition studies were performed: after 1 h of ventilation (controls, n = 18), after 48 h aggressive ventilation inducing an acute lung injury (nine piglets out of the controls), and after increasing the pressure to 24 cm H2O during drug delivery (five piglets out of the nine with acute lung injury). All piglets were then killed for lung histology. Results (median, range), expressed as a percentage of the delivered dose, were compared using an inferential or the Friedman test. While lung deposition was low, it was greater (p = 0.003) in controls (2.66%, 0.50-7.70) than in piglets with histologically confirmed acute lung injury (0.26%, 0.06-1.28) or under a high-pressure ventilation (1.01%, 0.30-2.15). Lung deposition of QVAR in an animal model of ventilated neonates is low, variable, and dramatically affected by lung injury.

Introduction: This pooled analysis compared the incidence of moderate or severe COPD exacerbations with QVA149 vs SFC. We also investigated if baseline blood eosinophil (EOS) count was a predictor of exacerbation risk, and magnitude of treatment effect on this risk. Methods: All patients (pts) from two 26-week double-blind studies were included in this analysis. 1263 moderate-to-severe COPD pts with ≤1 exacerbation in the previous year were randomised (1:1) to QVA149 or SFC. Results: In the overall pool, the rate of moderate or severe exacerbations was significantly lower with QVA149 vs SFC (RR [95% CI]: 0.67 [0.48-0.94]; p=0.021). There was a trend (p=0.08) towards increased exacerbation rate with increased baseline blood EOS count. In pts with baseline blood EOS count of 3 and 150-300/mm 3 , QVA149 showed 45% and 43% reduction in the risk of exacerbations, respectively compared to SFC (Figure 1). In pts with >300/mm 3 blood EOS at baseline (12% of study population), risk of exacerbations was lower with SFC. Conclusion: QVA 149 was more effective in reducing exacerbation risk in pts with baseline blood eosinophil 3 (88% of pool) and SFC in pts with >300/mm 3 (12% of pool). These data suggest that baseline blood eosinophil count may be a useful biomarker in assessing potential benefit of QVA149 over SFC in reducing exacerbations in COPD patients.

Introduction: QVA149 is an approved once-daily dual bronchodilator for maintenance treatment of patients with COPD. Here, we assessed the efficacy of QVA149 in improving dyspnoea, health status and lung function in COPD patients with moderate-to-severe baseline dyspnoea (GOLD Group B) from SHINE and ILLUMINATE studies. Methods: Symptomatic patients from SHINE (N=2144) and ILLUMINATE (N=523) studies with baseline dyspnoea index (BDI) ≤7 (moderate-to-severe dyspnoea equivalent to GOLD Group B) were included in this subgroup analysis. QVA149 was compared to placebo (PBO), open-label tiotropium (TIO), and SFC; TDI, SGRQ and lung function (trough and pre-dose FEV 1 ) were assessed at Week 26. Results: Mean BDI was comparable in both SHINE [QVA149 (n=305): 5.44, TIO (n=313): 5.57, PBO (n=131): 5.47] and ILLUMINATE [QVA149 (n=166): 5.78, SFC (n=179): 5.85] studies. QVA149 provided significant improvement in dyspnoea and lung function, compared with PBO, TIO and SFC (Table). QVA149 also improved (not significant) SGRQ total score versus SFC. Conclusion: In patients with moderate-to-severe baseline dyspnoea (comparable to GOLD Group B), QVA149 was more efficacious than TIO and SFC in improving patient-reported outcomes and lung function.