Search

RG Duenk,1 C Verhagen,1 EM Bronkhorst,2 PJWB van Mierlo,3,4 MEAC Broeders,5 SM Collard,6 PNR Dekhuijzen,7 KCP Vissers,1 Y Heijdra,7,* Y Engels1,* 1Department of Anesthesiology, Pain and Palliative Medicine, 2Department of Health Evidence, Radboud University Medical Center, Nijmegen, 3Department of Supportive and Palliative Medicine, 4Department of Geriatric Medicine, Rijnstate Hospital, Arnhem, 5Department of Pulmonary Diseases, Jeroen Bosch Hospital, ‘s-Hertogenbosch, 6Department of Pulmonary Diseases, Meander Medical Center, Amersfoort, 7Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, the Netherlands *These authors contributed equally to this work Background and aim: Patients with advanced chronic obstructive pulmonary disease (COPD) have poor quality of life. The aim of this study was to assess the effects of proactive palliative care on the well-being of these patients.Trial registration: This trial is registered with the Netherlands Trial Register, NTR4037.Patients and methods: A pragmatic cluster controlled trial (quasi-experimental design) was performed with hospitals as cluster (three intervention and three control) and a pretrial assessment was performed. Hospitals were selected for the intervention group based on the presence of a specialized palliative care team (SPCT). To control for confounders, a pretrial assessment was performed in which hospitals were compared on baseline characteristics. Patients with COPD with poor prognosis were recruited during hospitalization for acute exacerbation. All patients received usual care while patients in the intervention group received additional proactive palliative care in monthly meetings with an SPCT. Our primary outcome was change in quality of life score after 3 months, which was measured using the St George Respiratory Questionnaire (SGRQ). Secondary outcomes were, among others, quality of life at 6, 9 and 12 months; readmissions: survival; and having made advance care planning (ACP) choices. All analyses were performed following the principle of intention to treat.Results: During the year 2014, 228 patients (90 intervention and 138 control) were recruited and at 3 months, 163 patients (67 intervention and 96 control) completed the SGRQ. There was no significant difference in change scores of the SGRQ total at 3 months between groups (-0.79 [95% CI, -4.61 to 3.34], p=0.70). However, patients who received proactive palliative care experienced less impact of their COPD (SGRQ impact subscale) at 6 months (-6.22 [-11.73 to -0.71], p=0.04) and had more often made ACP choices (adjusted odds ratio 3.26 [1.49–7.14], p=0.003). Other secondary outcomes were not significantly different.Conclusion: Proactive palliative care did not improve the overall quality of life of patients with COPD. However, patients more often made ACP choices which may lead to better quality of care toward the end of life. Keywords: COPD, proactive palliative care, quality of life, advance care planning, readmission, survival

RG Duenk,1 C Verhagen,1 EM Bronkhorst,2 RS Djamin,3 GJ Bosman,4 E Lammers,5 PNR Dekhuijzen,6 KCP Vissers,1 Y Engels,1,* Y Heijdra6,* 1Department of Anesthesiology, Pain and Palliative Medicine, 2Department of Health Evidence, Radboud University Medical Center, Nijmegen, 3Department of Respiratory Medicine, Amphia Hospital, Breda, 4Department of Respiratory Medicine, Slingeland Hospital, Doetinchem, 5Department of Respiratory Medicine, Gelre Hospitals, Zutphen, 6Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, the Netherlands *These authors contributed equally to this work Background: Our objective was to develop a tool to identify patients with COPD for proactive palliative care. Since palliative care needs increase during the disease course of COPD, the prediction of mortality within 1 year, measured during hospitalizations for acute exacerbation COPD (AECOPD), was used as a proxy for the need of proactive palliative care.Patients and methods: Patients were recruited from three general hospitals in the Netherlands in 2014. Data of 11 potential predictors, a priori selected based on literature, were collected during hospitalization for AECOPD. After 1 year, the medical files were explored for the date of death. An optimal prediction model was assessed by Lasso logistic regression, with 20-fold cross-validation for optimal shrinkage. Missing data were handled using complete case analysis.Results: Of 174 patients, 155 patients were included; of those 30 (19.4%) died within 1 year. The optimal prediction model was internally validated and had good discriminating power (AUC =0.82, 95% CI 0.81–0.82). This model relied on the following seven predictors: the surprise question, Medical Research Council dyspnea questionnaire (MRC dyspnea), Clinical COPD Questionnaire (CCQ), FEV1% of predicted value, body mass index, previous hospitalizations for AECOPD and specific comorbidities. To ensure minimal miss out of patients in need of proactive palliative care, we proposed a cutoff in the model that prioritized sensitivity over specificity (0.90 over 0.73, respectively). Our model (ProPal-COPD tool) was a stronger predictor of mortality within 1 year than the CODEX (comorbidity, age, obstruction, dyspnea, and previous severe exacerbations) index.Conclusion: The ProPal-COPD tool is a promising multivariable prediction tool to identify patients with COPD for proactive palliative care. Keywords: COPD, exacerbation, proactive palliative care, prognosis, mortality

RG Duenk,1 C Verhagen,1 PNR Dekhuijzen,2 KCP Vissers,1 Y Engels,1,* Y Heijdra2,* 1Department of Anesthesiology, Pain and Palliative Medicine, 2Department of Lung Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands *These authors contributed equally to this work Introduction: Early palliative care is not a common practice for patients with COPD. Important barriers are the identification of patients for palliative care and the organization of such care in this patient group. Objective: Pulmonologists have a central role in providing good quality palliative care for patients with COPD. To guide future research and develop services, their view on palliative care for these patients was explored. Methods: A survey study was performed by the members of the Netherlands Association of Physicians for Lung Diseases and Tuberculosis. Results: The 256 respondents (31.8%) covered 85.9% of the hospital organizations in the Netherlands. Most pulmonologists (92.2%) indicated to distinguish a palliative phase in the COPD trajectory, but there was no consensus about the different criteria used for its identification. Aspects of palliative care in COPD considered important were advance care planning conversation (82%), communication between pulmonologist and general practitioner (77%), and identification of the palliative phase (75.8%), while the latter was considered the most important aspect for improvement (67.6%). Pulmonologists indicated to prefer organizing palliative care for hospitalized patients with COPD themselves (55.5%), while 30.9% indicated to prefer cooperation with a specialized palliative care team (SPCT). In the ambulatory setting, a multidisciplinary cooperation between pulmonologist, general practitioner, and a respiratory nurse specialist was preferred (71.1%). Conclusion: To encourage pulmonologists to timely initiate palliative care in COPD, we recommend to conduct further research into more specific identification criteria. Furthermore, pulmonologists should improve their skills of palliative care, and the members of the SPCT should be better informed about the management of COPD to improve care during hospitalization. Communication between pulmonologist and general practitioner should be emphasized in training to improve palliative care in the ambulatory setting. Keywords: proactive palliative care, pulmonologists, identification, organization, cooperation

Pieter Nicolaas Richard Dekhuijzen,1 Federico Lavorini,2 Omar S Usmani3 1Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, the Netherlands; 2Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy; 3National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, UK Abstract: Poor inhaler technique hampers the efficacy of drug therapy in asthma and chronic obstructive pulmonary disease. Not only does this affect individual patient care, but it also impacts on the wider health care economics associated with these conditions. Treatment guidelines recommend a systematic approach to drug class selection; however, standardization of inhaler selection is currently difficult owing to the complexity of the interaction between the inhaler device and the patient. Specifically, individual patient preference can influence how successful a treatment is overall. This article reviews inhaler devices from the patient perspective, with a particular focus on the dry powder inhaler HandiHaler® and Respimat® Soft Mist™ Inhaler. It discusses factors that influence device preference and treatment compliance and reviews tools that can aid health care professionals to better match inhaler devices to individual patients’ needs. Keywords: asthma, chronic obstructive pulmonary disease, inhaler technique, Soft Mist™ Inhaler, tiotropium Respimat®, tiotropium HandiHaler®

Rationale: Studies show that the myosin content of the diaphragm in patients with mild to moderate chronic obstructive pulmonary disease (COPD) is reduced, compromising diaphragm contractile performance. The mechanisms for reduced contractile protein content are unknown. In the present study we hypothesized that the loss of contractile protein content is associated with activation of the ubiquitin-proteasome pathway in the diaphragm of patients with mild to moderate COPD. Methods: Proteolytic activity of isolated 20S proteasomes was determined in diaphragm biopsies from patients with and without COPD (predicted mean FEV1, 66 and 93%, respectively). In addition, we determined 20S proteasome subunit C8 protein levels by means of Western blotting, ubiquitin-ligase mRNA levels by means of real-time polymerase chain reaction, and caspase-3 activity by determining the hydrolysis of fluorogenic substrates. Results: The 20S proteasome activity was about threefold increased in the diaphragm of patients with COPD. C8 protein levels were not significantly different between COPD and non-COPD diaphragm, indicating increased specific activity of individual proteasomes, rather than an increased number of proteasomes. mRNA levels of the muscle-specific ubiquitin-ligase MAFbx were significantly higher in diaphragm from patients with COPD compared with patients without COPD. Caspase-3-mediated cleavage of actomyosin complexes is considered an initial step in muscle wasting, yielding fragments that can be degraded by the ubiquitin-proteasome pathway. In line with the increased ubiquitin-proteasome activity, caspase-3 activity was higher in diaphragm homogenates from patients with COPD. Conclusions: The present study is the first to demonstrate increased activity of the ubiquitin-proteasome pathway in COPD diaphragm. Importantly, these changes occur in patients with only mild to moderate COPD (Global Initiative for Chronic Obstructive Lung Disease stage I/II). [ABSTRACT FROM AUTHOR]

Rationale: Although oxygen therapy is of clear benefit in patients with severe chronic obstructive pulmonary disease (COPD), recent studies have shown that short-term supplementary oxygen may increase oxidative stress and inflammation within the airways. Objective: We investigated whether systemic inflammation and oxidative stress at rest and during exercise in patients with COPD are influenced by supplemental oxygen. Methods: Nine normoxemic, muscle-wasted patients with moderate to very severe COPD were studied. Plasma markers of systemic inflammation (leukocyte counts, interleukin 6 [IL-6]) and oxidative stress (lipid peroxidation, protein oxidation, antioxidant capacity) were measured after treatment with either supplemental oxygen (nasal, 4 L . min(-1)) or compressed air, both at rest (1 h treatment) and after submaximal exercise (40 W, constant work rate). In addition, free-radical production by neutrophils and ATP-degradation products were determined before and after exercise. Results: Short-term oxygen breathing at rest did not influence systemic low-grade inflammation and oxidative stress. The IL-6 response to exercise was attenuated during cycling with supplemental oxygen. Exercise-induced lipid and protein oxidation were prevented by treatment with supplemental oxygen. This was associated with both decreased free-radical production by neutrophils and reduced formation of (hypo)xanthine and uric acid. Conclusion: Short-term supplementary oxygen does not affect basal systemic inflammation and oxidative stress but prevents exercise-induced oxidative stress in normoxemic, muscle-wasted patients with COPD, and attenuates plasma IL-6 response. Inhibition of neutrophil activation and ATP degradation appears to be involved in this effect. [ABSTRACT FROM AUTHOR]

Rationale: Hypercapnic respiratory failure because of inspiratory muscle weakness is the most important cause of death in chronic obstructive pulmonary disease (COPD). However, the pathophysiology of failure of the diaphragm to generate force in COPD is in part unclear.Objectives: The present study investigated contractile function and myosin heavy chain content of diaphragm muscle single fibers from patients with COPD.Methods: Skinned muscle fibers were isolated from muscle biopsies from the diaphragm of eight patients with mild to moderate COPD and five patients without COPD (mean FEV(1) % predicted, 70 and 100%, respectively). Contractile function of single fibers was assessed, and afterwards, myosin heavy chain content was determined in these fibers. In diaphragm muscle homogenates, the level of ubiquitin-protein conjugation was determined.Results: Diaphragm muscle fibers from patients with COPD showed reduced force generation per cross-sectional area, and reduced myosin heavy chain content per half sarcomere. In addition, these fibers had decreased Ca2+ sensitivity of force generation, and slower cross-bridge cycling kinetics. Our observations were present in fibers expressing slow and 2A isoforms of myosin heavy chain. Ubiquitin-protein conjugation was increased in diaphragm muscle homogenates of patients with mild to moderate COPD.Conclusions: Early in the development of COPD, diaphragm fiber contractile function is impaired. Our data suggest that enhanced diaphragm protein degradation through the ubiquitin-proteasome pathway plays a role in loss of contractile protein and, consequently, failure of the diaphragm to generate force. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic obstructive pulmonary disease (COPD) may be prescribed multiple inhalers that require different techniques for optimal performance. Mixing devices has been associated with poorer COPD outcomes suggesting that it leads to inappropriate inhaler technique. However, empirical evidence is lacking., Aims: Compare the nature and frequency of dry powder inhaler (DPI) technique errors in patients with COPD using (1) a single DPI or (2) mixed-devices (a DPI and pressurised metered dose inhaler (pMDI))., Methods: Data from the PIFotal study-a cross-sectional study on Peak Inspiratory Flow in patients with COPD using a DPI as maintenance therapy, capturing data from 1434 patients on demographic characteristics, COPD health status and inhaler technique-were used to select 291 patients using mixed-devices. Frequency matching based on country of residence and DPI device type was used to select 291 patients using a DPI-only for comparison. Predetermined checklists were used for the evaluation of DPI video recordings and complemented with additional errors that were observed in ≥10%. Error proportions were calculated for the (1) individual and total number of errors, (2) number of critical errors and (3) number of pMDI-related errors., Results: The study sample contained 582 patients (mean (SD) age 69.6 (9.4) years, 47.1% female). DPI technique errors were common, but not significantly different between the groups. The majority of patients made at least one critical error (DPI-only: 90.7% vs mixed-devices: 92.8%). Proportions of total, 'pMDI-related' and critical errors did not significantly differ between the groups., Conclusion: The nature and frequency of inhaler technique errors did not substantially differ between patients prescribed with a single DPI and mixed-devices. Currently, 'pMDI-related errors' in DPI use are not accounted for in existing checklists., Trial Registration Number: ENCEPP/EUPAS48776., Competing Interests: Competing interests: LD, MK, MD, YG and ML were employed by the General Practitioners Research Institute (GPRI) at the time of the study. In the past 4 years (2019–2022), GPRI conducted investigator-initiated and sponsor-initiated research funded by non-commercial organisations, academic institutes and pharmaceutical companies (including AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Novartis and Teva). SB-A has received grants from TEVA, and personal fees from TEVA, Boehringer Ingelheim, AstraZeneca, GSK, Sanofi and Mylan. JC-d-S reports or personal fees from AstraZeneca, Bial, Boehringer Ingelheim, GSK, Medinfar, Mundipharma and Sanofi. PNRD has received grants and personal fees from TEVA, Boehringer Ingelheim, AstraZeneca, GSK, Chiesi, Focus Care, and Glenmark. HAMK has performed consultancies for, received unrestricted research and educational grants from, and has participated in clinical trials on a per patient fee basis for: AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Novartis. All renumerations were non personal and were received by his institution. DBP reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Theravance and Zentiva (Sanofi Generics); grants from the British Lung Foundation, Respiratory Effectiveness Group, UK National Health Service, and AKL Research and Development; personal fees from Cipla, GlaxoSmithKline, Kyorin, Merck, Mundipharma, Airway Vista Secretariat, EPG Communication Holdings, FIECON, Fieldwork International, OM Pharma SA, PeerVoice, Phadia AB, Spirosure, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, and WebMD Global; non-financial support from Efficacy and Mechanism Evaluation programme and Health Technology Assessment; stock/stock options from AKL Research and Development, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); and 5% shareholding in Timestamp, which develops adherence monitoring technology. IT reports grants and personal fees from GSK, AstraZeneca, Boehringer Ingelheim, Menarini, Novartis, Chiesi and Elpen. OU reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Edmond Pharma, Chiesi and GSK; grants from Edmond Pharma; and personal fees from Napp, Mundipharma, Sandoz, Takeda, Cipla, COVIS, Novartis, Mereobiopharma, Orion and Menarini. JWHK reports grants, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from Boehringer Ingelheim, grants and personal fees from Chiesi, grants, personal fees and non-financial support from GSK, non-financial support from Mundi Pharma, grants and personal fees from Teva, personal fees from MSD, personal fees from COVIS Pharma, grants from Valneva outside the submitted work; and JWHK holds <5% shares of Lothar Medtec and 72.5% of shares in the General Practitioners Research Institute., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Inhaled medications are central to treating asthma and chronic obstructive pulmonary disease (COPD), yet critical inhaler technique errors are made by up to 90% of patients. In the clinical research setting, recruitment of subjects with poor inhaler technique may give a false impression of both the benefits and the necessity of add-on treatments such as biologic therapies., Objective: To assess the frequency with which inhaler technique is assessed and reliably optimized before and during patient enrollment into randomized controlled trials (RCTs) addressing the efficacy of topical therapy, and the escalation of therapy for asthma and COPD., Methods: Systematic searches were conducted of PubMed and Embase for RCTs published in the past 10 years involving patients with a diagnosis of asthma or COPD undergoing escalation of baseline inhaled therapy (stepping up, changing, adding, switching, increasing, etc) or the introduction of biologic agents., Results: Searches highlighted 1,014 studies, 118 of which were eligible after the removal of duplicates as well as screening and full text review. Of these, only 14 (11.9%) included accessible information in the methods section or referred to such information in online supplements or protocols concerning assessment of participants' inhaler technique. We therefore developed the proposed Best Practice Inhaler Technique Assessment and Reporting Checklist., Conclusions: Our study identifies a concerning lack of checking and correcting inhaler technique, or at least reporting that this was undertaken, before enrollment in asthma and COPD RCTs, which may affect the conclusions drawn. Mandating the use of a standardized checklist in RCT protocols and ensuring all published RCTs report checking and correcting inhaler technique before enrollment are important next steps., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Inhaler selection is important when managing respiratory conditions; a patient's inhalation technique should be appropriate for the selected device, and patients should ideally be able to use a device successfully regardless of disease severity. The NEXThaler is a multidose dry-powder inhaler with a breath-actuated mechanism (BAM) and dose counter that activates only following inhalation, so effectively an 'inhalation counter'. We assessed inspiratory flow through the NEXThaler in two studies and examined whether inhalation triggered the BAM., Methods: The two studies were open-label, single-arm, and single visit. One study recruited patients with asthma aged ≥ 18 years; the other recruited patients with chronic obstructive pulmonary disease (COPD) aged ≥ 40 years. All patients inhaled twice through a placebo NEXThaler. The inspiratory profile through the device was assessed for each inhalation using acoustic monitoring, with flow at and time to BAM firing, peak inspiratory flow (PIF), and total inhalation time assessed., Results: A total of 40 patients were enrolled in the asthma study: 20 with controlled asthma and 20 with partly controlled/uncontrolled asthma. All patients were able to trigger the BAM, as evidenced by the inhalation counter activating on closing the device. Mean flow at BAM firing following first inhalation was 35.0 (range 16.3-52.3) L/min; mean PIF was 64.6 (35.0-123.9) L/min. A total of 72 patients were enrolled in the COPD study, with data analysed for 69 (mean forced expiratory volume in 1 s 48.7% predicted [17-92%]). As with the asthma study, all patients, regardless of airflow limitation, were able to trigger the BAM. Mean flow at BAM firing following first inhalation was 41.9 (26.6-57.1) L/min; mean PIF was 68.0 (31.5-125.4) L/min. Device usability was rated highly in both studies, with 5 min sufficient to train the patients, and a click heard shortly after inhalation in all cases (providing feedback on BAM firing)., Conclusions: Inhalation flows triggering the BAM in the NEXThaler were similar between patients with controlled and partly controlled/uncontrolled asthma, and were similar across COPD airflow limitation. All enrolled patients were able to activate the device.

Rationale: Integrated care models have the potential to improve outcomes for patients with COPD. We therefore designed the COPDnet integrated care model and implemented it in two hospitals and affiliated primary care regions in the Netherlands. The COPDnet model consists of a comprehensive diagnostic trajectory ran in secondary care followed by a non-pharmacological intervention program of both monodisciplinary and multidisciplinary components., Objective: To assess the clinical effectiveness of the COPDnet integrated care model on health status change in patients with COPD., Methods: A total of 402 patients with COPD were offered care according to the COPDnet model. At baseline and between 7- and 9-months later health status was measured with the Clinical COPD Questionnaire (CCQ). Primary analysis was carried out for the sample at large. In addition, subgroup analyses were performed after stratification for the type of non-pharmacological intervention where patients had been referred to., Results: The CCQ total score improved statistically significantly from 1.94 ± 1.04 to 1.73 ± 0.96 (P < 0.01) in the 154 patients with valid follow-up measurements. Subgroup analyses revealed significant improvements in the patients receiving pulmonary rehabilitation only. No change in health status was found in patients receiving pharmacotherapy only, carried out self-treatment or who participated in mono-disciplinary primary care offered by allied healthcare professionals., Conclusions: An improved health status was found in patients with COPD who received care according to the COPDnet integrated care model. Subgroups participating in an interdisciplinary pulmonary rehabilitation program predominantly accounted for this effect., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The daily impact of chronic obstructive pulmonary disease (COPD) on younger patients is often underappreciated. To assess this, we investigated the disease burden experienced by younger and older patients. A panel of questions was developed in conjunction with the European Federation of Allergy and Airways Diseases Patients' Associations and Boehringer Ingelheim. The online survey was conducted by Instar Research. Data were collected from eight countries in Europe, plus China, Japan and the United States. All patients were receiving COPD maintenance therapy. Patients were stratified by age (45-54, 55-64, ≥65 years). Data were analyzed from 1,375 patients from Europe (925), China (150), Japan (100) and the US (200); 365 were aged 45-54, 440 aged 55-64, and 570 aged ≥65 years. Mean age was 61.8 years; 771 (56%) were male. A significantly higher proportion of patients aged 45-54 years reported "poor" or "very poor" wellbeing (35% vs. 28%; p  < 0.05) and "high impact" on 8 of the 11 daily activities and requirements for adjusting activities assessed (all p  < 0.05), compared with patients aged ≥65 years. Significantly more patients aged 45-54 versus ≥65 years associated their COPD with feeling "anxious", "stressed", "sad", or "overwhelmed" (all p  < 0.05). Younger patients with COPD reported a higher impact on their daily activities, wellbeing and requirement for adjusting their activities due to their symptoms than older patients. Our findings highlight the importance of optimizing treatment for younger patients with COPD and suggest that clinicians should not overlook the burden of disease in these patients.

We present an extensive review of the literature to date pertaining to the rationale for using a spacer/valved holding chamber (VHC) to deliver inhaled therapy from a pressurised, metered-dose inhaler, a discussion of how the properties of individual devices may vary according to their physical characteristics and materials of manufacture, the potential risks and benefits of ancillaries such as valves, and the evidence that they contribute tangibly to the delivery of therapy. We also reiterate practical recommendations for the correct usage and maintenance of spacers/VHCs, which we trust offer practical help and advice to patients and healthcare professionals alike., Competing Interests: Conflict of interest: M.L. Levy reports receiving consultancy fees from Clement Clarke International, and personal fees for lectures and conference accommodation from Teva and AstraZeneca, is a board member of the Global Initiative for Asthma (GINA), and has received reimbursement for travel and accommodation expenses from GINA, has received funding from Chiesi for the DSMB, Triple, Forward, Trigger and Trimeran studies, and accommodation support from Chiesis to attend the ERS International Congress in 2017, has received an education grant from Consorzio Futuro in Ricerca for the ADMIT group, attended advisory board meetings with AstraZeneca in January 2018 and with Boehringer Ingelheim in November 2017, and has received lecture fees from Soar Beyond outside the submitted work. Conflict of interest: J. Scullion reports receiving honoraria for attending meetings from AstraZeneca, Chiesi, Teva, Boehringher Ingelheim, Pfizer, Mylan, Trudell, Nutricia and Sandoz, and support for a meeting from Roche, outside the submitted work. Conflict of interest: C.J. Corrigan reports attending an open day at GlaxoSmithKline headquarters, outside the submitted work.

Objective: Healthcare professionals (HCPs) are required to assess and train patients in the correct use of inhalers but are often unable to demonstrate correct technique themselves. We sought to assess the level of training required for HCPs to master and maintain device mastery when using two different dry powder inhalers (DPIs)., Methods: We conducted a randomized, un-blinded, crossover study in undergraduate HCPs who undertook a six-step training procedure (intuitive use, patient information leaflet, instructional video, individual tuition from expert, then two repeats of individual tuition) for the use of Turbuhaler® (an established device) and Spiromax® (a newer device, reportedly easier to use). Device mastery (absence of errors) was evaluated by expert assessors at each training step. Maintenance of mastery was assessed 4 ± 1 week (visit 2) and 8 ± 2 weeks (visit 3) after initial training (visit 1)., Results: Of 516 eligible participants, 113 (22%) demonstrated device mastery prior to training on Spiromax® compared with 20 (4%) on Turbuhaler® (p < 0.001). The median number of training steps required to achieve mastery was 2 (interquartile range [IQR] 2-4) for Spiromax® and 3 (IQR 2-4) for Turbuhaler® (p < 0.001). A higher number of participants maintained mastery with Spiromax® compared with Turbuhaler®, at visits 2 and 3 (64% vs 41% and 79% vs 65%, respectively; p < 0.001)., Conclusions: There are significant differences in the nature and extent of training required to achieve and maintain mastery for Spiromax® and Turbuhaler® devices. The implications on clinical practice, device education delivery, and patient outcomes require further evaluation.

Background: Fixed-dose combinations of inhaled corticosteroids and long-acting β 2 agonists are commonly used for the treatment of asthma and COPD. However, the most frequently prescribed dry powder inhaler delivering this medicine - Symbicort ® (budesonide and formoterol, BF) Turbuhaler ® - is associated with poor inhalation technique, which can lead to poor disease control and high disease management costs. A recent study showed that patients make fewer inhaler errors when using the novel DuoResp ® (BF) Spiromax ® inhaler, compared with BF Turbuhaler ® . Therefore switching patients from BF Turbuhaler ® to BF Spiromax ® could improve inhalation technique, and potentially lead to better disease control and healthcare cost savings., Methods: A model was developed to estimate the budget impact of reducing poor inhalation technique by switching asthma and COPD patients from BF Turbuhaler ® to BF Spiromax ® over three years in Germany, Italy, Sweden and the UK. The model estimated changes to the number, and associated cost, of unscheduled healthcare events. The model considered two scenarios: in Scenario 1, all patients were immediately switched from BF Turbuhaler ® to BF Spiromax ® ; in Scenario 2, 4%, 8% and 12% of patients were switched in years 1, 2 and 3 of the model, respectively., Results: In Scenario 1, per patient cost savings amounted to €60.10, €49.67, €94.14 and €38.20 in Germany, Italy, Sweden and the UK, respectively. Total cost savings in each country were €100.86 million, €19.42 million, €36.65 million and €15.44 million over three years, respectively, with an estimated 597,754, 151,480, 228,986 and 122,368 healthcare events avoided. In Scenario 2, cost savings totalled €8.07 million, €1.55 million, €2.93 million and €1.23 million over three years, respectively, with 47,850, 12,118, 18,319, and 9789 healthcare events avoided. Savings per patient were €4.81, €3.97, €7.53 and €3.06., Conclusions: We demonstrated that reductions in poor inhalation technique by switching patients from BF Turbuhaler ® to BF Spiromax ® are likely to improve patients' disease control and generate considerable cost savings through healthcare events avoided., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Little information is available on real-life occurrence of oral thrush in COPD patients treated with ICS. We investigated oral thrush incidence in COPD patients prescribed FDC ICS/LABA therapies and assessed whether it is modulated by the ICS type, dose, and delivery device., Methods: We conducted a historical, observational, matched cohort study (one baseline year before and one outcome year after initiation of therapy) using data from the UK Optimum Patient Care Research Database. We assessed oral thrush incidence in patients initiating long-acting bronchodilators or FDC ICS/LABA therapy. We then compared different combination therapies (budesonide/formoterol fumarate dihydrate [BUD/FOR] and fluticasone propionate/salmeterol xinafoate [FP/SAL]) and devices (DPI and pMDI)., Results: Patients prescribed FDC ICS/LABA had significantly greater odds of experiencing oral thrush than those prescribed long-acting bronchodilators alone (adjusted OR 2.18 [95% CI 1.84-2.59]). Significantly fewer patients prescribed BUD/FOR DPI developed oral thrush compared with FP/SAL DPI (OR 0.77 [0.63-0.94]) when allowing for differences in prescribed doses between the drugs. A significantly smaller proportion of patients developed oral thrush in the FP/SAL pMDI arm than in the FP/SAL DPI arm (OR 0.67 [0.55-0.82]). Additionally, in the FP/SAL cohort (both DPI and pMDI), increased risk of oral thrush was significantly associated with high ICS daily dose (OR 1.97 [1.22-3.17] vs low daily dose)., Conclusions: ICS use increases oral thrush incidence in COPD and this effect is dose-dependent for FP/SAL therapies. Of the therapies assessed, FP/SAL pMDI and BUD/FOR DPI may be more protective against oral thrush., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In this study, nonchromogenic mycobacteria were isolated from pulmonary samples of three patients in the Netherlands. All isolates had identical, unique 16S rRNA gene and 16S-23S ITS sequences, which were closely related to those of Mycobacterium chimaera and Mycobacterium marseillense. The biochemical features of the isolates differed slightly from those of M. chimaera, suggesting that the isolates may represent a possible separate species within the Mycobacterium avium complex (MAC). However, the cell-wall mycolic acid pattern, analysed by HPLC, and the partial sequences of the hsp65 and rpoB genes were identical to those of M. chimaera. We concluded that the isolates represent a novel variant of M. chimaera. The results of this analysis have led us to question the currently used methods of species definition for members of the genus Mycobacterium, which are based largely on 16S rRNA or rpoB gene sequencing. Definitions based on a single genetic target are likely to be insufficient. Genetic divergence, especially in the MAC, yields strains that cannot be confidently assigned to a specific species based on the analysis of a single genetic target.