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Asthma and chronic obstructive pulmonary disease (COPD) affect millions of people throughout Europe, being one of the leading causes of death in the continent. Both conditions also impose considerable morbidity on patients, adversely affecting individuals’ physical and psychological wellbeing, and their capacity to live and work normally. Asthma and COPD also impose a substantial economic burden on healthcare providers and wider society through both direct and indirect costs of care. Inhaler-delivered therapy has been central to the successful management of both conditions for several decades. Advances in device technology and understanding of the pathophysiology of both conditions (while theoretically introducing greater flexibility and responsiveness into the repertoire of inhalation therapies) have also added complexity and sometimes confusion into the task of identifying the precise combination of medication and delivery device best suited to the needs of individual patients. Recently published multinational consensus reports have set out best-practice frameworks for the management of both asthma and COPD. Presentations at the two symposia summarised in this report examined the implications of these guidelines for the treatment of both conditions. Special focus was on dry power inhalers (DPI) as a means of delivering effective treatment that combines ease of use and widespread acceptance among patients, with the potential to reduce medically-related emissions of greenhouses gases compared with pressurised metered-dose inhalers (pMDI). The authors emphasised the importance of patient partnership in determining the care plan, including the choice of both inhaler device and treatment; the benefits of regular monitoring of adherence to the treatment for both patients with asthma and COPD; and the benefits of simplicity, using one type of inhaler where possible to minimise critical errors in inhalation technique.

The 52-week, phase 3 LIBERTY ASTHMA QUEST study (NCT02414854) in patients aged above or equal to 12 years with uncontrolled, moderate-to-severe asthma demonstrated the efficacy and safety of dupilumab 200 mg and 300 mg every 2 weeks vs matched placebo.To assess whether dupilumab improves clinical outcomes in QUEST patients with persistent airflow obstruction (PAO) defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio less than 0.7 at baseline.End points were annualized rate of severe exacerbations, pre and post-bronchodilator forced expiratory volume in 1 second over time, proportion achieving reversal of PAO, and quality of life. Efficacy was evaluated in patients with or without PAO at baseline in subpopulations with eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 25 ppb or eosinophils ≥ 300 cells/µL and FeNO ≥ 25 ppb.Of 1902 patients enrolled in QUEST, 1039 (55%) had PAO at baseline. Dupilumab vs placebo rapidly and significantly improved lung function in patients with PAO and elevated type 2 inflammatory biomarkers at baseline. Dupilumab improved probability of reversing airflow obstruction (hazard ratio vs placebo 1.616 [95% confidence interval, 1.272-2.052] and 1.813 [1.291-2.546]; both P.001) and significantly reduced severe exacerbations by 69% (relative risk, 0.411; 95% confidence interval [0.327-0.516]; P.0001) and by 75% (0.252 [0.178-0.356]; P.0001) in patients with PAO with eosinophils ≥ 150 cells/µL or FeNO ≥ 25 ppb and eosinophils ≥ 300 cells/µL and FeNO ≥ 25 ppb, respectively. Similar results were observed in patient subgroups without PAO.In patients with uncontrolled moderate-to-severe asthma, treatment with dupilumab facilitates reversal of PAO status and improves clinical outcomes.ClinicalTrials.gov identifier: NCT02414854.

Background There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012. Methods A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC Results Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication. Conclusions False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.

Background: Despite significant reductions in mortality, preventable and treatable conditions remain leading causes of death and illness in children aged under five in South Africa. The PACK Child intervention, comprising a clinical decision support tool (guide), training strategy and health systems strengthening components, was developed to expand on WHO’s Integrated Management of Childhood Illness programme, and in 2017-2018 was piloted in 10 primary healthcare facilities in the Western Cape Province. Here we report findings from an investigation into the contextual features of South African primary care that shaped how clinicians delivered the PACK Child intervention within clinical consultations. Methods: Process evaluation using semi-structured interviews, focus groups, observation, audio-recorded consultations and documentary analysis. Linguistic ethnographic analysis of relationship between primary care contextual features and clinician-caregiver interactions.Results: Primary healthcare facilities demonstrated dominance of a risk minimisation approach upheld by provincial documentation, providing curative episodic care to children presenting with acute symptoms, and preventive care including immunisations, feeding and growth monitoring, all in children 5 years or younger. Children with chronic illnesses such as asthma rarely received routine care. These contextual features constrained the ability of clinicians to use the PACK Child intervention to facilitate diagnosis of long-term conditions, elicit and manage psychosocial issues, and navigate use of the guide alongside provincial documentation. Conclusion: Our findings provide evidence that PACK Child is catalysing a transition to an approach that strikes a balance between risk minimisation on the day of an acute presentation and a larger remit of care for the child over time. However, to optimise success of the intervention requires reviewing priorities for paediatric care which will facilitate enhanced skills, knowledge and deployment of clinical staff to better address acute illnesses and long-term health conditions of children of all ages, as well as complex psychosocial issues surrounding the child.

Nigeria, in its quest to strengthen its primary healthcare system, is faced with a number of challenges including a shortage of clinicians and skills. Methods are being sought to better equip primary healthcare clinicians for the clinical demands that they face. Using a mentorship model between developers in South Africa and Nigerian clinicians, the Practical Approach to Care Kit (PACK) for adult patients, a health systems strengthening programme, has been localised and piloted in 51 primary healthcare facilities in three Nigerian states. Lessons learnt from this experience include the value of this remote model of localisation for rapid localisation, the importance of early, continuous stakeholder engagement, the need expressed by Nigeria’s primary healthcare clinicians for clinical guidance that is user friendly and up-to-date, a preference for the tablet version of the PACK Adult guide over hard copies and the added value of WhatsApp groups to complement the programme of face-to-face continuous learning. Introduction of the PACK programme in Nigeria prompted uptake of evidence-informed recommendations within primary healthcare services.

One of the biggest problems in global health is the lack of well trained and supported health workers in less developed settings. In many rural areas there are no physicians, and it is important to find ways to support and empower nurses and other health workers. The Knowledge Translation Unit of the University of Cape Town Lung Institute has spent 14 years developing a series of innovative packages to support and empower nurses and other health workers. PACK (Practical Approach to Care Kit) Adult comprises policy-based and evidence-informed guidelines; onsite, team and case-based training; non-physician prescribing; and a cascade system of scaling up. A series of randomised trials has shown the effectiveness of the packages, and methods are now being developed to respond cost-effectively and sustainably to global demand for implementing PACK Adult. Global health would probably benefit from less time and money spent developing new innovations and more spent on finding ways to spread those we already have.

Effectively tackling the growing noncommunicable disease (NCD) burden in low- and middle-income countries (LMIC) is a major challenge. To address research needs in this setting for NCDs, in 2009, National Heart, Lung, and Blood Institute (NHLBI) and UnitedHealth Group (UHG) engaged in a public-private partnership that supported a network of 11 LMIC-based research centers and created the NHLBI-UnitedHealth Global Health Centers of Excellence (COE) Program. The Program’s overall goal was to contribute to reducing the cardiovascular and lung disease burdens by catalyzing in-country research institutions to develop a global network of biomedical research centers. Key elements of the Program included team science and collaborative approaches, developing research and training platforms for future investigators, and creating a data commons. This Program embraced a strategic approach for tackling NCDs in LMICs and will provide capacity for locally driven research efforts that can identify and address priority health issues in specific countries’ settings.HighlightsA public-private partnership created the Program.Forming the Program captured all the elements of team science.The Program used best practices of collaborative science.Research training for future investigators was a high priority.

GSK233705 is a recently developed inhaled anticholinergic being investigated for the potential treatment of chronic obstructive pulmonary disease (COPD).This dose-ranging, parallel-group, double-blind study compared the bronchodilator efficacy, safety and pharmacokinetics of GSK233705 with placebo in patients with moderate-to-severe COPD.Patients were randomised to receive 12.5 µg, 25 µg, 50 µg, 100 µg or 200 µg of GSK233705 or placebo once daily for 28 days. The primary endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV(1)) on day 29.The intent-to-treat population consisted of 576 patients (mean predicted FEV(1) 51%; mean age 62 years). Treatment with GSK233705 produced statistically significant improvements in pulmonary function compared with placebo. Only the 200 µg dose exceeded the predefined target threshold of 130-mL difference compared with placebo for the primary endpoint of change from baseline in trough FEV(1) on day 29. No clear pattern of dose response was observed for the other doses. Serial FEV(1) (0-24 h) showed a peak effect around 2 h postdose and tended to decline to clinically insignificant levels compared with placebo at 23 and 24 h. Each dose of GSK233705 was well tolerated. The incidence of adverse events was low and similar across all treatment groups. There were no clinically significant effects on laboratory parameters, vital signs or electrocardiograms.All doses of GSK233705 demonstrated bronchodilatory activity and were well tolerated. Although the onset of bronchodilation was rapid, it was not sustained over 24 h making it unsuitable for once-daily dosing.

Introduction and Objectives The Phase III ATTAIN study investigated the effect of two twice daily doses of aclidinium bromide, a second-generation, long-acting muscarinic antagonist with low systemic activity, in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Methods In this 24-week, double-blind study, patients were randomised (1:1:1) to receive aclidinium (200 μg, 400 μg) or placebo, twice daily. The primary endpoint was change from baseline in trough forced expiratory volume in 1 second (FEV 1 ) at Week 24. Other study assessments at 24 weeks included: change from baseline in peak FEV 1 ; percentage of patients achieving a clinically meaningful improvement in St George9s Respiratory Questionnaire total score and Transition Dyspnoea Index; COPD symptoms as assessed by the EXACT Respiratory Symptoms score; exacerbation rate based on two definitions (healthcare resource utilisation and EXAcerbations of Chronic pulmonary disease Tool). Adverse events (AEs), clinical laboratory measures, vital signs and ECGs were also assessed. Results A total of 819 patients were included in intention-to-treat (ITT) and safety populations. At Week 24, aclidinium 200 μg and 400 μg significantly improved trough FEV 1 from baseline compared with placebo (by 99 ml and 128 ml, respectively; both p Conclusion Aclidinium 200 μg and 400 μg twice daily provided clinically meaningful improvements in bronchodilation, health status, symptoms, breathlessness and exacerbation rate. Aclidinium was well tolerated with a similar safety profile for both doses; the incidence of AEs was similar to placebo.