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This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the impact of interventions to improve inhaler technique on performance and clinical outcomes in people with COPD.

Background Airway clearance techniques (ACTs) are integral to cystic fibrosis (CF) management. However, there is no consensus as to which outcome measures (OMs) are best for assessing ACT efficacy. Objectives: To summarise OMs that have been assessed for their clinimetric properties (including validity, feasibility, reliability & reproducibility) within the context of ACT research. MethodsEligibility Criteria - Any parallel or cross-over randomised controlled trial (RCT) investigating outcome measures for ACT in the CF population. Information sources: Five medical databases; clinicaltrials.gov; abstracts from international CF conferences. Risk of Bias - The authors planned to independently assess study quality and risk of bias using the COSMIN risk of bias checklist with external validity assessment based upon study details (participants and study intervention).Synthesis of Results – Two review authors (GS and MJ) independently screened search results against inclusion criteria, further data extraction was planned but not required.ResultsIncluded studies - No completed RCTs from the 187 studies identified met inclusion criteria for the primary or post-hoc secondary objective. Two ongoing trials were identified.DiscussionLimitations of evidence: The search strategy may have missed some lesser-known terms for ACT or manuscripts reporting clinimetric properties solely within text. Studies validating outcome measures for use in other aspects of CF, which may be relevant to ACT, are not included.Interpretation - High-quality RCTs are urgently needed to investigate & validate the clinimetric properties of OMs used to assess ACT efficacy. With the changing demographics of CF combined with the introduction of CFTR modulator therapies, an accurate assessment of the current benefit of ACT or the effect of ACT withdrawal is a high priority for clinical practice and future research and OMs which have been validated for this purpose are essential.OtherFunding: NIHR/HEE Clinical Doctoral Fellowship grant for GS (reference CDRF-2014-05-055).Systematic review registration number - PROSPERO no.CRD42020206033

Introduction: Incorrect inhaler technique is one reason why the efficacies of inhaled asthma treatments in clinical trials and effectiveness in the real world differ. Inhaler technique is critical for drug delivery to the lungs; incorrect technique negatively impacts asthma control and long-term outcomes. Breath-triggered inhalers (BTIs) can simplify drug administration and are suitable for most patients, including those with reduced inspiratory flow. Until recently, no inhaled corticosteroid/long-acting β2-agonist combination BTI was available in Europe. The flutiform® (fluticasone propionate/formoterol fumarate [FP/FORM]) k-haler® is the first combination BTI now approved in Europe for asthma maintenance treatment.Areas covered: We review studies examining the challenges posed to patients by different inhaler types and explore evidence demonstrating the clinical efficacy of FP/FORM administered via a pressurized metered-dose inhaler. We also review the pharmacokinetic/pharmacodynamic studies supporting FP/FORM k-haler use, and consider data showing high lung deposition with the device. Finally, we review patient experiences using the BTI, device characteristics, and health economic aspects.Expert opinion: Despite the availability of therapies, asthma control levels remain low, and there is a clear need for easy-to-use inhalers. Research to increase our understanding of critical errors with each inhaler and how to overcome them is important for improving care.Abbreviations: AUCt: area under the plasma concentration-time curve from the time of dosing to the last measurable concentration; BDP: beclometasone dipropionate; BTI: breath-triggered inhaler; BUD: budesonide; CI: confidence interval; Cmax: maximum observed plasma concentration; DPI: dry powder inhaler; FDC: fixed-dose combination; FEV1: forced expiratory volume in 1 s; FORM: formoterol fumarate; FP: fluticasone propionate; HCP: health-care professional; ICS: inhaled corticosteroid; LABA: long-acting β2-agonist; OR: odds ratio; PIL: patient information leaflet; pMDI: pressurized metered-dose inhaler; SAL: salmeterol xinafoate.

Appropriate selection and correct use of inhalation devices is an integral component in the management of asthma and chronic obstructive pulmonary disease (COPD). It is well known that there are many challenges with the use of inhalers, and no one device suits all patients. Challenges can range from difficulties related to lung disease severity and pulmonary function to physical considerations, including manual dexterity and comorbidities such as arthritis. In terms of device selection and adherence, patient engagement and satisfaction are also important factors to consider. Furthermore, problems with inhaler use can be most evident in children and older patients. Here, we discuss aspects for consideration with commonly used devices, including nebulizers, pressurized metered-dose inhalers, dry powder inhalers, and the soft mist inhaler. As each inhaler offers varying technical properties, a tailored and personalized approach to the selection of the most appropriate device for the patient is highly recommended in order to increase the likelihood of achieving improved disease outcomes and enhance persistence with device adherence. Importantly, education and support is crucial, not only to enable patients to recognize the need for optimal disease management, but also to help them develop good inhaler technique. In addition, health care professionals should also aim to increase their knowledge of the devices they prescribe, and develop systems to ensure that they offer comprehensive support to patients in clinical practice. Considering these aspects, this review discusses potential strategies to help address the challenges of inhaler use in asthma and COPD.

International audience; In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system for integrated care with organizational health literacy. MASK (Mobile Airways Sentinel NetworK) (1), a new development of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health) (2), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life integrated care pathways (ICPs) (3)-centred around the patient with rhinitis and using mHealth monitoring of environmental exposure (4).An expert meeting took place at the Pasteur Institute in Paris, December 3, 2018. The aim was to discuss next-generation care pathways: (I) Patient participation, health literacy and self-care through technology-assisted “patient activation”; (II) Implementation of care pathways by pharmacists and (III) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) assessed by mobile technology.The EU (5) and global political agendas are of great importance in supporting health care transformation. MASK has been recognized by DG Santé as a Good Practice (6) in the field of digitally-enabled, integrated, person-centred care.The one-day meeting objectives were clear (Figure 1). The meeting was followed by a workshop. The present paper reports the background of the two-day meeting.

David Price,1,2 Rupert Jones,3 Pascal Pfister,4 Hui Cao,5 Victoria Carter,6 Anu Kemppinen,6 Björn Holzhauer,4 Alan Kaplan,7 Allan Clark,8 David MG Halpin,9 Hilary Pinnock,10 James D Chalmers,11 Job FM van Boven,12 Kai M Beeh,13 Konstantinos Kostikas,14 Nicolas Roche,15 Omar Usmani,16 Paul Mastoridis5 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Faculty of Health, University of Plymouth, Plymouth, Devon, UK; 4Novartis Pharma AG, Basel, Switzerland; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 6Observational and Pragmatic Research International Ltd, Stubbs House Stubbs Green, London, Norwich, UK; 7Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada; 8Norwich Medical School, University of East Anglia, Norwich, UK; 9University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK; 10Allergy and Respiratory Research Group, Usher Institute, University of Edinburgh, Edinburgh, UK; 11College of Medicine, University of Dundee, Dundee, UK; 12Department of Clinical Pharmacy & Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 13Clinical Research, Insaf Respiratory Research Institute, Wiesbaden, Germany; 14Respiratory Medicine Department, University of Ioannina School of Medicine, Ioannina, Greece; 15Cochin Hospital and Institute, APHP Centre, University of Paris, Paris, France; 16National Heart & Lung Institute (NHLI), Imperial College London and Royal Brompton Hospital, London, UKCorrespondence: David PriceCentre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UKTel +44 65 6962 3627Email dprice@opri.sgBackground: Poor treatment adherence in COPD patients is associated with poor clinical outcomes and increased healthcare burden. Personalized approaches for adherence management, supported with technology-based interventions, may offer benefits to patients and providers but are currently unproven in terms of clinical outcomes as opposed to adherence outcomes.Methods: Maximizing Adherence and Gaining New Information For Your COPD (MAGNIFY COPD study), a pragmatic cluster randomized trial, aims to evaluate the impact of an adherence technology package (interventional package), comprising an adherence review, ongoing provision of a dual bronchodilator but with an add-on inhaler sensor device and a connected mobile application. This will compare time to treatment failure and other clinical outcomes in patients identified at high risk of exacerbations with historic poor treatment adherence as measured by prescription collection to mono/dual therapy over one year (1312 patients) versus usual care. Treatment failure is defined as the first occurrence of one of the following: (1) moderate/severe COPD exacerbation, (2) prescription of triple therapy (inhaled corticosteroid/long-acting β2-agonist/long-acting muscarinic antagonist [ICS/LABA/LAMA]), (3) prescription of additional chronic therapy for COPD, or (4) respiratory-related death. Adherence, moderate/severe exacerbations, respiratory-related healthcare resource utilization and costs, and intervention package acceptance rate will also be assessed. Eligible primary care practices (N=176) participating in the Optimum Patient Care Quality Improvement Program will be randomized (1:1) to either adherence support cluster arm (suitable patients already receiving or initiated Ultibro® Breezhaler® [indacaterol/glycopyrronium] will be offered interventional package) or the control cluster arm (suitable patients continue to receive usual clinical care). Patients will be identified and outcomes collected from anonymized electronic medical records within the Optimum Patient Care Research Database. On study completion, electronic medical record data will be re-extracted to analyze outcomes in both study groups.Registration Number: ISRCTN10567920.Conclusion: MAGNIFY will explore patient benefits of technology-based interventions for electronic adherence monitoring.Keywords: adherence monitoring, applications, chronic obstructive pulmonary disease, medication adherence, pragmatic randomized clinical trial, technology

175 years have elapsed since John Hutchinson introduced the world to his version of an apparatus that had been in development for nearly two centuries, the spirometer. Though he was not the first to build a device that sought to measure breathing and quantify the impact of disease and occupation on lung function, Hutchison coined the termsspirometerandvital capacitythat are still in use today, securing his place in medical history. As Hutchinson envisioned, spirometry would become crucial to our growing knowledge of respiratory pathophysiology, from Tiffeneau and Pinelli's work on forced expiratory volumes, to Fry and Hyatt's description of the flow–volume curve. In the 20th century, standardization of spirometry further broadened its reach and prognostic potential. Today, spirometry is recognized as essential to respiratory disease diagnosis, management and research. However, controversy exists in some of its applications, uptake in primary care remains sub-optimal and there are concerns related to the way in which race is factored into interpretation. Moving forward, these failings must be addressed, and innovations like Internet-enabled portable spirometers may present novel opportunities. We must also consider the physiologic and practical limitations inherent to spirometry and further investigate complementary technologies such as respiratory oscillometry and other emerging technologies that assess lung function. Through an exploration of the storied history of spirometry, we can better contextualize its current landscape and appreciate the trends that have repeatedly arisen over time. This may help to improve our current use of spirometry and may allow us to anticipate the obstacles confronting emerging pulmonary function technologies.

The Respimat® Soft Mist™ inhaler (SMI) has recently been improved, with a re-usable device replacing the disposable version. Certain countries are currently phasing out the disposable inhaler. This study aimed to assess patient satisfaction with and preference for the re-usable device. This 4–6-week, multicentre, open-label, prospective, real-world, non-interventional study was conducted across six European countries. Patients with chronic obstructive pulmonary disease were enrolled between October and December 2019, in three cohorts: (1) currently using the re-usable Respimat SMI; (2) switched from disposable Respimat SMI at study entry; and (3) naïve to any Respimat SMI. Patients were assessed using the Patient Satisfaction and Preference Questionnaire (PASAPQ) and Ease of Handling Questionnaire. In total, 262 patients were enrolled. At follow-up, the mean PASAPQ score was 83.3/100 overall, with similar results across all three patient cohorts. Most patients were ‘satisfied’ or ‘very satisfied’ with the re-usable device. The overall score for willingness to continue using the device was 87.8/100. In total, 13 adverse events were recorded, none of which was classified as serious. This study provides real-world evidence for practitioners to start patients on Respimat re-usable, irrespective of a patient’s prior experience with this inhaler. Plain language summary: Inhalers are often used to treat patients with chronic obstructive pulmonary disease (COPD). However, there are many available, which can lead to confusion and poor inhaler technique. It is important for a patient to be happy with their inhaler. This study looked at how patients liked the re-usable Respimat® Soft Mist™ inhaler vs. their previous inhaler. It also asked whether they would be willing to continue using the device at the end of the study period.After 4–6 weeks of using the re-usable device, patients reported that they were happy with the inhaler and most would be willing to carry on using it.Overall, these results show that doctors can prescribe Respimat re-usable to patients, even if the patient has not used the inhaler before.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes CoronaVirus Disease 2019 (COVID-19), has resulted in a worldwide pandemic and currently represents a major public health crisis. It has caused outbreaks of illness through person-to-person transmission of the virus mainly via close contacts, and droplets produced by an infected person's cough or sneeze. Aerosolised inhaled therapy is the mainstay for treating obstructive airway diseases at home and in healthcare settings, but there is heightened particular concern about the potential risk for transmission of SARS-CoV-2 in the form of aerosolised respiratory droplets during the nebulised treatment of patients with COVID-19. As a consequence of this concern, the use of hand-held inhalers, especially pressurised metered dose inhalers, has risen considerably as an alternative to nebulisers, and this switch has led to inadequate supplies of inhalers in some countries. However, there is no evidence supporting an increased risk of viral transmission during nebulisation in COVID-19 patients. Furthermore, some patients may be unable to adequately use their new device and may not benefit fully from the switch to treatment via hand-held inhalers. Thus, there is no compelling reason to alter aerosol delivery devices for patients with established nebuliser-based regimens. The purpose of this paper is to discuss the current evidence and understanding of the use of aerosolised inhaled therapies during the SARS-CoV-2 pandemic and to provide some guidance on the measures to be taken to minimise the risk of transmitting infection, if any, during aerosol therapies.

Patients’ peak inspiratory flow rate (PIFR) may help clinicians select a suitable inhaler device. The In-Check® device has gained some status as a simple tool to estimate PIFR (scale reflecting inhaler resistance from R0 to R5). It has been suggested that some patients with asthma may not be able to generate sufficient PIFR with high resistance devices (R5) to satisfy the minimum requirements of 30 L/min. We conducted a prospective service evaluation study to identify what proportion of patients with asthma are able to generate a correct PIFR at In-Check device R0-R5 resistance settings and what the phenotypical features of those patients are. As part of UK general practice asthma review service, sequential patients were recruited from 41 centres by 10 respiratory specialist nurses. Patients had PIFR checked at the resistance corresponding to their current preventer inhaler device, at R5 (high resistance dry powder inhaler (DPI) setting), and, at R0 (no resistance, pressurised metered dose inhaler (pMDI) setting. Correct PIFR (pass) was defined for R5 as 30–90 L/min, and, for R0 as 20–60 L/min. 994 adults (female 64.3%) were included, of whom 90.4% currently used a preventer inhaler (71.5% MDI (R0), 0% R1, 6.3% R2, 14.5% R3, 4.9% R4, 2.8% R5). 93.7% of patients passed at R5 resistance, compared to 70.5% at R0 (p 71 years) 90.2% passed at R5 compared to 71.0% at R0. Conclusion Patients with asthma can achieve adequate inspiratory flow 30–90 L/min with high resistance DPI (R5).

Chronic respiratory disease 18, (2021). doi:10.1177/1479973120986228, Published by Sage, London

Background: Functional respiratory imaging (FRI) is a computational fluid dynamics-based technique using three-dimensional models of human lungs and formulation profiles to simulate aerosol deposition. Methods: FRI was used to evaluate lung deposition of extrafine beclomethasone dipropionate (BDP)/formoterol fumarate (FF)/glycopyrronium bromide (GB) and extrafine BDP/FF delivered through pressurized metered dose inhalers and to compare results with reference gamma scintigraphy data. FRI combined high-resolution computed tomography scans of 20 patients with moderate-to-severe chronic obstructive pulmonary disease (mean forced expiratory volume in 1 second 42% predicted) with in silico computational flow simulations, and incorporated drug delivery parameters to calculate aerosol airway deposition. Inhalation was simulated using profiles obtained from real-life measurements. Results: Total lung deposition (proportion deposited in intrathoracic region) was similarly high for both products, with mean ± standard deviation (SD) values of 31.0% ± 5.7% and 28.1% ± 5.2% (relative to nominal dose) for BDP/FF/GB and BDP/FF, respectively. Pairwise comparison of the deposition of BDP and FF gave a mean intrathoracic BDP/FF/GB:BDP/FF deposition ratio of 1.10 (p = 0.0405). Mean intrathoracic, central and peripheral deposition ratios for BDP were 1.09 (95% confidence interval [CI]: 1.05–1.14), 0.92 (95% CI: 0.89–0.96), and 1.20 (95% CI: 1.15–1.26), respectively, and for FF were 1.11 (95% CI: 1.07–1.15), 0.94 (95% CI: 0.91–0.98), and 1.21 (95% CI: 1.15–1.27), within the bioequivalence range (0.80–1.25) for intrathoracic and central regions, and slightly exceeding the upper boundary in the peripheral region. Mean ± SD central:peripheral deposition (C:P) was 0.48 ± 0.13 for BDP/FF/GB and 0.62 ± 0.17 for BDP/FF, indicating a higher proportion of drug deposition in the small airways than in the large airways. Conclusion: FRI demonstrated similar deposition patterns for extrafine BDP/FF/GB and BDP/FF, with both having a high lung deposition. Moreover, the deposition patterns of BDP and FF were similar in both products. Furthermore, the C:P ratios of both products indicated a high peripheral deposition, supporting small airway targeting and delivery of these two extrafine fixed combinations, with a small difference in ratios potentially due to mass median aerodynamic diameters.

The pattern of deposition of inhaled aerosols in the lungs of man in health and disease, in vivo, is reliant on multiple factors. The disease being targeted has a major influence on the eventual site of deposition. Obstructive lung disease alters the flow dynamics within the airways and restrictive lung diseases alters the ‘stiffness’ of the lungs and ability to inhale large volumes. There are multiple methods used to assess the fate of an inhaled aerosol within the lungs and the consequent clinical effect. Imaging allows visualization of inhaled aerosols via the use of labeling with radio-isotopes combined with imaging techniques such as planar scintigraphy, single photon emission computed tomography (SPECT) and positron emission tomography (PET). Computed tomography (CT), and magnetic resonance imaging (MRI) allow visualization of the structure of the lung and can also offer information of physiological dysfunction. Data from imaging can be related to physiological measurements of lung function and to clinical outcome. The combination of lung CT images with Computational Fluid and Particle Dynamics (CFPD) simulations has led to the development of personalized functional modeling of the airways to investigate disease in the small and large airways. All of these methods have advantages, disadvantages and limitations. None of these methods are able to directly visualize the small airways which is frequently the area of interest in lung disease. There are emerging methods of interest that may offer further data on the effects of inhaled therapeutic agents including novel MRI methods and use of micro-CT to investigate changes in small airway function. This chapter will summarize developments relating to inhaled aerosols and emerging clinical methods used to assess efficacy.

Despite advances in the pathophysiology of chronic obstructive pulmonary disease (COPD), there is a distinct lack of biochemical markers to aid clinical management. Microvesicles (MVs) have been implicated in the pathophysiology of inflammatory diseases including COPD, but their association to COPD disease severity remains unknown. We analyzed different MV populations in plasma and bronchoalveolar lavage fluid (BALF) taken from 62 patients with mild to very severe COPD (51% male; mean age: 65.9 yr). These patients underwent comprehensive clinical evaluation (symptom scores, lung function, and exercise testing), and the capacity of MVs to be clinical markers of disease severity was assessed. We successfully identified various MV subtype populations within BALF [leukocyte, polymorphonuclear leukocyte (PMN; i.e., neutrophil), monocyte, epithelial, and platelet MVs] and plasma (leukocyte, PMN, monocyte, and endothelial MVs) and compared each MV population to disease severity. BALF neutrophil MVs were the only population to significantly correlate with the clinical evaluation scores including forced expiratory volume in 1 s, modified Medical Research Council dyspnea score, 6-min walk test, hyperinflation, and gas transfer. BALF neutrophil MVs, but not neutrophil cell numbers, also strongly correlated with BODE index. We have undertaken, for the first time, a comprehensive evaluation of MV profiles within BALF/plasma of COPD patients. We demonstrate that BALF levels of neutrophil-derived MVs are unique in correlating with a number of key functional and clinically relevant disease severity indexes. Our results show the potential of BALF neutrophil MVs for a COPD biomarker that tightly links a key pathophysiological mechanism of COPD (intra-alveolar neutrophil activation) with clinical severity/outcome.

For more than 50 years, small airways disease has been considered a key feature of chronic obstructive pulmonary disease (COPD) and a major cause of airway obstruction. Both preventable and treatable, small airways disease has important clinical consequences if left unchecked. Small airways disease is associated with poor spirometry results, increased lung hyperinflation, and poor health status, making the small airways an important treatment target in COPD. The early detection of small airways disease remains the key barrier; if detected early, treatments designed to target small airways may help reduce symptoms and allow patients to maintain their activities. Studies are needed to evaluate the possible role of new drugs and novel drug formulations, inhalers, and inhalation devices for treating small airways disease. These developments will help to improve our management of small airways disease in patients with COPD.

Prescribers and asthma patients should know that ICS/LABA combination inhalers used as reliever therapy may expire under patient use sooner than the expiration shown on the inhaler, compromising effectiveness if not considered by the prescriber and patienthttps://bit.ly/3fhHMX2

Identification of pathologic changes in early and mild obstructive lung disease has shown the importance of the small airways and their contribution to symptoms. Indeed, significant small airways dysfunction has been found prior to any overt airway obstruction being detectable by conventional spirometry techniques. However, most therapies for the treatment of obstructive lung disease target the physiological changes and associated symptoms that result from chronic lung disease, rather than directly targeting the specific underlying causes of airflow disruption or the drivers of disease progression. In addition, although spirometry is the current standard for diagnosis and monitoring of response to therapy, the most widely used measure, FEV

IntroductionAirway clearance techniques (ACTs) are a gold standard of cystic fibrosis management; however, the majority of research evidence for their efficacy is of low standard; often attributed to the lack of sensitivity from outcome measures (OMs) used historically. This randomised controlled trial (RCT) investigates these standard OMs (sputum weight, forced expiratory volume in 1 s) and new OMs (electrical impedance tomography (EIT), multiple breath washout (MBW) and impulse oscillometry (IOS)) to determine the most useful measures of ACT.Methods and analysisThis is a single-centre RCT with crossover design. Participants perform MBW, IOS and spirometry, and then are randomised to either rest or supervised ACT lasting 30–60 min. MBW, IOS and spirometry are repeated immediately afterwards. EIT and sputum are collected during rest/ACT. On a separate day, the OMs are performed with the other intervention. Primary endpoint is difference in change in OMs before and after ACT/rest. Sample size was calculated with 80% power and significance of 5% for each OM (target n=64).Ethics and disseminationEthics approval was gained from the London–Chelsea Research Ethics Committee (reference 16/LO/0995, project ID 154635). Dissemination will involve scientific conference presentation and publication in a peer-reviewed journal.Trial registration numbersISRCTN11220163 and NCT02721498.

BACKGROUND: Patients' peak inspiratory flow rate (PIFR) may help clinicians select an inhaler device. OBJECTIVE: To determine the proportion of patients with asthma who could generate correct PIFRs at different inhaler resistance settings. METHODS: During a UK asthma review service, patients' PIFR was checked at resistance settings matching their current preventer inhaler device, at R5 (high resistance dry powder inhaler (DPI)) and at R0 (low resistance, pressurised metered dose inhaler (pMDI)). Correct PIFR ('pass') was defined for R5 as 30-90 L/min and for R0 as 20-60 L/min. A logistic regression model examined the independent predictors of incorrect PIFR ('fail') at R5 and R0. Asthma severity was assessed retrospectively from treatment level. RESULTS: A total of 994 adults (female 64.3%) were included, of whom 90.4% currently used a preventer inhaler (71.5% pMDI). PIFR pass rates were: 93.7% at R5 compared with 70.5% at R0 (p60 L/min), and 20% of patients currently using pMDI failed for this reason. Independent risk factors for failing R5 were: female gender, older age group and current preventer pMDI; and for failing R0 included: male gender, younger age group, current preventer DPI and mild versus severe asthma. CONCLUSIONS: This study demonstrates that most patients with asthma can achieve adequate inspiratory flow to activate high resistance DPIs, whereas approximately a third of patients breathe in too fast to achieve recommended inspiratory flows for correct pMDI use, including one fifth of patients who currently use a pMDI preventer.

Several countries have applied exemptions of respiratory patients on the compulsory use of face masks indoor and outdoor during the coronavirus disease 2019 (COVID-19) pandemic. It must be strongly stated that such exemption is not evidence-based, and it may carry increased risk of personal infection to the estimated 544·9 million people worldwide suffering a chronic respiratory disease [1]., Exemptions of respiratory patients on the compulsory use of face masks for COVID-19 pandemic are not evidence-based

Omar S Usmani,1 Nicolas Roche,2 Martin Jenkins,3 Neda Stjepanovic,4 Peter Mack,5 Wilfried De Backer6 1National Heart and Lung Institute (NHLI), Imperial College London, and Royal Brompton Hospital, London, UK; 2Respiratory Medicine, Cochin Hospital, University Paris Descartes, Paris, France; 3AstraZeneca, Cambridge, UK; 4AstraZeneca, Gothenburg, Mölndal, Sweden; 5AstraZeneca, Durham, NC, USA; 6Department of Pulmonary Medicine, Faculty of Medicine, University of Antwerp, Antwerp, BelgiumCorrespondence: Wilfried De BackerDepartment of Pulmonary Medicine, Faculty of Medicine, University of Antwerp, Lange Lozanastraat 142, Antwerp 2018, BelgiumTel +32 468 195206Email wilfried.debacker@uantwerpen.beAbstract: Metered dose inhalers (MDIs) are one of the most common device types for delivering inhaled therapies. However, there are several technical challenges in development and drug delivery of these medications. In particular, suspension-based MDIs are susceptible to suspension heterogeneity, in vitro drug–drug interactions, and patient handling errors, which may all affect drug delivery. To overcome these challenges, new formulation approaches are required. The AerosphereTM inhaler, formulated using co-suspension delivery technology, combines drug crystals with porous phospholipid particles to create stable, homogenous suspensions that dissolve once they reach the airways. Two combination therapies using this technology have been developed for the treatment of COPD: glycopyrrolate/formoterol fumarate (GFF MDI; dual combination) and budesonide/glycopyrrolate/formoterol fumarate (BGF MDI; triple combination). Here, we review the evidence with a focus on studies assessing dose delivery, lung deposition, and effects on airway geometry. In vitro assessments have demonstrated that the Aerosphere inhaler provides consistent dose delivery, even in the presence of simulated patient handling errors. Combination therapies delivered with this technology also show a consistent fine particle fraction (FPF) and an optimal particle size distribution for delivery to the central and peripheral airways even when multiple drugs are delivered via the same inhaler. Studies using gamma scintigraphy and functional respiratory imaging have demonstrated that GFF MDI is effectively deposited in the central and peripheral airways, and provides clinically meaningful benefits on airway volume and resistance throughout the lung. Overall, studies suggest that the Aerosphere inhaler, formulated using co-suspension delivery technology, may offer advantages over traditional formulations, including consistent delivery of multiple components across patient handling conditions, optimal particle size and FPF, and effective delivery to the central and peripheral airways. Future studies may provide additional evidence to further characterize the clinical benefits of these technical improvements in MDI drug delivery.Keywords: Aerosphere, BGF MDI, co-suspension delivery technology, FRI, GFF MDI, metered dose inhaler

Patients with severe asthma experience a significant burden of symptoms, disease exacerbations and medication side-effects. Severe asthma interferes with the patients' quality of life and has high health-care costs. New targeted biologic therapies have improved the management of severe asthma by significantly reducing exacerbations and maintenance corticosteroid use, and also improving lung function and patient quality of life.Not all severe asthmatics are eligible for such therapies. Those with allergic and eosinophilic asthma, usually referred to as 'T2-high' asthma benefit from anti-IgE and anti-IL-5/5 R antibodies respectively, whereas some asthmatics are eligible for both: 'overlap' endotype. In this review, we present briefly the monoclonal antibodies that have been approved in the management of severe asthma and we focus on the 'overlap' endotype.Since these therapies are costly, it is extremely important to choose the right treatment for the right patient especially in the 'overlapping' one. The decision is mainly based on the judgment of the clinician and is often driven by the most easily obtainable biomarker, thus the blood eosinophil count. Comorbidities, patient's input and administration frequency may aid the decision of choosing one over another biologic.

Inhalation therapy is integral in the management of patients with chronic obstructive pulmonary disease (COPD). Specifically, intravenous augmentation therapy is available to patients with alpha-1 antitrypsin deficiency (AATD), although there is insufficient alpha-1 antitrypsin (AAT) delivery to the lungs to modify airways inflammation. In contrast, the inhaled route allows replacement therapy to reach the target site of action and with higher AAT levels. Patients certainly support the inhalation route as an alternative to intravenous injections, obviating repetitive needle insertion and allowing treatment empowerment rather than dependency on traveling to specialized units. The difficulty with inhalation has been the ability to target the formulation to the pathophysiological site of disease: the emphysematous lung parenchyma of the small alveolated airways. Recent advances have suggested nebulizers as being able to deliver an adequate dose, consistently and reproducibly, and, coupled with developments in formulation science, allowed replacement therapy to reach the epithelial lining fluid of the small airways. The bench science has been translated to the first randomized, placebo-controlled clinical trial to study the effects of nebulized AAT, which, although not meeting the primary endpoint of prolonging time to first exacerbation, showed this treatment modality was safe and achievable in a large patient cohort. Indeed, learning from this trial suggests the importance of choosing the right clinical endpoints, and recent key advances in lung physiology indices allow better assessment of the "silent zone" of small airways disease. Knowledge from other respiratory diseases will complement treating patients with AATD, where there is considerable innovation in aerosol science and inhalation medicine directed at utilizing the inhaled route. Indeed, it could be postulated that the inhaled route may not only achieve local pulmonary therapeutic benefit, but through systemic absorption and controlled pharmacokinetic profiling, the formulation may reach and treat liver disease.

This gamma scintigraphy imaging study assessed pulmonary, extrathoracic and regional lung deposition patterns of a radiolabelled inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist triple fixed-dose combination budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF 320/14.4/10 μg), delivered by pressurised metered dose inhaler (pMDI) using innovative co-suspension delivery technology (Aerosphere™). In this Phase I, randomised, single-centre, single-dose, two-period, crossover study (NCT03740373), 10 healthy male adults received two actuations of BGF MDI (160/7.2/4.8 μg per actuation) radiolabelled with 99mTc, not exceeding 5 MBq per actuation. Immediately following each inhalation, subjects performed a 10- or 3-second breath-hold, then exhaled into an exhalation filter. The primary objective was to assess the pulmonary deposition of BGF MDI following the 10-second breath-hold. The secondary objectives were to assess deposition after the 3-second breath-hold and lung regional and extrathoracic deposition after each breath-hold length. Imaging of the lungs, stomach, head and neck was recorded by gamma scintigraphy immediately after exhalation. The mean BGF MDI emitted dose deposited in the lungs was 37.7% for the 10-second breath-hold and 34.5% for the 3-second breath-hold. Emitted dose detected in the exhalation filter was ≤0.4% for both breath-hold lengths. The mean normalised peripheral/central ratio was 0.65 and 0.75 for the 10- and 3-second breath-holds, respectively, while the standardised central/peripheral ratios were 1.79 and 1.40, respectively. There were no new or unexpected safety findings. In conclusion, BGF MDI was efficiently deposited in the central and the peripheral regions of the lungs, with similar regional deposition patterns following a 10- and 3-second breath-hold.

We examined associations between blood eosinophil counts (BEC) and risk of treatment failure or hospital readmission following acute oral corticosteroid (OCS)-treated COPD exacerbations. We conducted studies from the Optimum Patient Care Research Database (OPCRD) (www.optimumpatientcare.org/opcrd) and Clinical Practice Research Datalink (CPRD) (www.cprd.com/home/), validated databases for medical research, with linked Hospital Episode Statistics (HES) data for ∼20 000 COPD patients aged ≥40 years. For patients with OCS-treated COPD exacerbations treated in primary care, with BECs recorded on first day of OCS treatment (Cohort 1), we assessed treatment failure (COPD-related hospitalisations and OCS prescriptions beyond index OCS course). For patients hospitalised for COPD exacerbations, with BEC measured over an exacerbation-free period during the year prior to admission (Cohort 2), we assessed readmission rate. Cox proportional hazards regression analysis was adjusted for confounders to estimate the association between BEC and treatment outcomes. Of patients treated with OCS for COPD exacerbations in primary care (Cohort 1), 44% experienced treatment failure following single OCS courses, and 10% (255/2482) were hospitalised for ≤6 weeks. Greater BEC was associated with reduced hospital-admission risk (hazard ratio [HR]=0.26; 95% CI: 0.12–0.56, per 100 cells·µL−1 increase). BEC increases of ≥200 cells·µL−1 from exacerbation-free periods to exacerbations were associated with least hospitalisation risk (HR=0.32; 95% CI: 0.15–0.71) versus no BEC change. For patients hospitalised for COPD exacerbations (Cohort 2), 4-week hospital readmission was 12% (1189/10 245). BEC increases during an exacerbation-free period within the past year were associated with reduced risk of short-term readmission (HR=0.78; 95% CI: 0.63–0.96). Greater BEC predicted better outcomes for patients with OCS-treated COPD exacerbations, whether community or hospital managed. Eosinopenia predicted worse outcomes., Patients who have greater blood eosinophil counts during #AECOPD in the last year have lesser hospitalisation risk, enhanced OCS response and better response to OCS upon hospitalisation, as reflected by reduced readmissions https://bit.ly/2ZQIV1n

The European Respiratory Society (ERS) International Congress 2019 in Madrid, Spain, was a platform for scientific discussion of the highest quality scientific research, cutting-edge techniques and innovative new therapies within the respiratory field. This article discusses some of the high-quality research studies presented at that Congress, with a focus on airway diseases, including asthma, COPD, small airways, bronchiectasis and cough, presented through the Airway Diseases, Asthma and COPD Assembly (Assembly 5) of the ERS. The authors establish the key take-home messages of these studies, compare their findings and place them into context of current understanding., This article discusses some of the high-quality research studies presented at #ERSCongress in Madrid, with a particular focus on airway diseases, presented through the Airway Diseases, Asthma and COPD Assembly (Assembly 5) http://bit.ly/2RpDVvv

Regular physical activity is strongly recommended to prevent chronic respiratory diseases, including asthma. On the other hand, vigorous physical training may trigger airway symptoms and bronchoconstriction. The transient airway narrowing occurring because of exercise is named exercise-induced bronchoconstriction (EIB). Despite management according to guidelines, a significant proportion of patients experiences uncontrolled EIB, which thus represents a relevant unmet medical need. In particular, although prevention and treatment of EIB are effectively based on the use of beta-2 bronchodilator drugs, high heterogeneity in individual responses has been reported. Furthermore, even though beta-2 adrenergic drugs remain the mainstay of EIB management, occurrence of tolerance and side effects, as well as doping concerns have been reported with their use. In regard to this, inhaled antimuscarinics could represent an alternative or additional effective and safe bronchodilator therapeutic option for achieving optimal EIB control and minimize adverse events. The present systematic review aims to collect and provide the most updated and evidence-based literature findings on the efficacy and safety of short- and long-acting inhaled anti-muscarinic drugs for the preventive treatment of EIB in both children and adults. Take-Home Message: Anti-muscarinic drugs are effective and safe in preventing EIB, despite response variability is reported. Further studies should focus on long-acting molecules, chronic administration and phenotype-driven effects.

© 2020 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/), Spacers are pressurized metered-dose inhaler (pMDI) accessory devices developed to reduce problems of poor inhaler technique with pMDIs. Spacers that feature a 1-way inspiratory valve are termed valved holding chambers (VHCs); they act as aerosol reservoirs, allowing the user to actuate the pMDI device and then inhale the medication in a 2-step process that helps users overcome challenges in coordinating pMDI actuation with inhalation. Both spacers and VHCs have been shown to increase fine particle delivery to the lungs, decrease oropharyngeal deposition, and reduce corticosteroid-related side effects such as throat irritation, dysphonia, and oral candidiasis commonly seen with the use of pMDIs alone. Spacers and VHCs are not all the same, and also are not interchangeable: the performance may vary according to their size, shape, material of manufacture and propensity to become electrostatically charged, their mode of interface with the patient, and the presence or otherwise of valves and feedback devices. Thus, pairing of a pMDI plus a spacer or a VHC should be considered as a unique delivery system. In this Rostrum we discuss the risk potential for a patient getting switched to a spacer or VHC that delivers a reduced dose medication.

Introduction: Patients with severe asthma experience a significant burden of symptoms, disease exacerbations and medication side-effects. Severe asthma interferes with the patients’ quality of life and has high health-care costs. New targeted biologic therapies have improved the management of severe asthma by significantly reducing exacerbations and maintenance corticosteroid use, and also improving lung function and patient quality of life. Areas covered: Not all severe asthmatics are eligible for such therapies. Those with allergic and eosinophilic asthma, usually referred to as ‘T2-high’ asthma benefit from anti-IgE and anti-IL-5/5 R antibodies respectively, whereas some asthmatics are eligible for both: ‘overlap’ endotype. In this review, we present briefly the monoclonal antibodies that have been approved in the management of severe asthma and we focus on the ‘overlap’ endotype. Expert opinion: Since these therapies are costly, it is extremely important to choose the right treatment for the right patient especially in the ‘overlapping’ one. The decision is mainly based on the judgment of the clinician and is often driven by the most easily obtainable biomarker, thus the blood eosinophil count. Comorbidities, patient’s input and administration frequency may aid the decision of choosing one over another biologic. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Artículo con numerosos autores sólo se mencionan el primero y el de la UAM, Open access funding enabled and organized by Projekt DEAL

It is currently a very exciting time in airway disease. With recent pivotal changes in the global directives in the management for both asthma and COPD, new approved treatments and drugs, and innovative approaches in characterising the diseases, the time was right for assembly 5 (airway diseases, asthma and COPD) to undertake a masterclass this year in keeping with the new European Respiratory Society (ERS) continuing professional development initiatives from the Educational Council., Participants attending the recent ERS course on airways disease share their experiences http://bit.ly/2lojSl3

Optimal delivery of medication via dry powder inhalers, the most commonly prescribed inhaler type, is dependent on a patient achieving a minimum level of inspiratory flow during inhalation. However, measurement of peak inspiratory flow (PIF) against the simulated resistance of a dry powder inhaler is not frequently performed in clinical practice due to time or equipment limitations. Therefore, defining which patient characteristics are associated with lower PIF is critically important to help clinicians optimize their inhaler choice through a more personalized approach to prescribing. The objective of this scoping review was to systematically evaluate patient and disease characteristics determining PIF in patients with chronic obstructive pulmonary disease (COPD). Medline, Cochrane and Embase databases were systematically searched for relevant studies on PIF in patients with COPD published in English between January 2000 and May 2021. The quality of evidence was assessed using a modified Grading of Recommendations Assessment, Development and Evaluation checklist. Of 3382 citations retrieved, 35 publications were included in the review (nine scored as high quality, 13 as moderate, nine as low, and four as very low). Factors correlating with PIF in >70% of papers included both patient characteristics (lower PIF correlated with increased age, female gender, shorter height, decreased handgrip and inspiratory muscle strength, and certain comorbidities) and disease characteristics (lower PIF correlated with markers of lung hyperinflation, lower peak expiratory flow [PEF] and increased disease severity). Other factors correlating with adequate/optimal or improved PIF included education/counseling and exercise/inspiratory muscle training; impaired physical function and errors in inhalation technique/non-adherence were associated with low/suboptimal PIF. In conclusion, clinicians should measure PIF against the simulated resistance of a particular device wherever possible. However, as this often cannot be done due to lack of resources or time, the patient and disease characteristics that influence PIF, as identified in this review, can help clinicians to choose the most appropriate inhaler type for their patients.

Addressing the global morbidity associated with asthma, chronic obstructive pulmonary disease (COPD) and chronic cough is a major unmet need for the respiratory community. Reducing exacerbations and improving lung function have remained important primary endpoints in clinical studies in asthma and COPD, however, there is also a growing momentum to show efficacy and improvements in patient reported outcomes in real-world pragmatic studies.