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      What to consider before prescribing inhaled medications: a pragmatic approach for evaluating the current inhaler landscape

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          Abstract

          Inhaled therapies are the cornerstone of treatment in asthma and chronic obstructive pulmonary disease, and there are a multitude of devices available. There is, however, a distinct lack of evidence-based guidance for healthcare providers on how to choose an appropriate inhaler. This review aims to summarise recent updates on topics related to inhaler choice, and to offer practical considerations for healthcare providers regarding currently marketed devices. The importance of choosing the right inhaler for the right patient is discussed, and the relative merits of dry powder inhalers, pressurised metered dose inhalers, breath-actuated pressurised metered dose inhalers, spacers and soft mist inhalers are considered. Compiling the latest studies in the devices therapy area, this review focuses on the most common types of handling errors, as well as the comparative rates of incorrect inhalation technique between devices. The impact of device-specific handling errors on inhaler performance is also discussed, and the characteristics that can impair optimal drug delivery, such as inhalation flow rate, inhalation volume and particle size, are compared between devices. The impact of patient perceptions, behaviours and problems with inhalation technique is analysed, and the need for appropriate patient education is also highlighted. The continued development of technology in inhaler design and the need to standardise study assessment, endpoints and patient populations are identified as future research needs.

          The reviews of this paper are available via the supplemental material section .

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          Most cited references135

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          Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

          Summary Background Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide. Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study. The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year. Methods We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool. First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases. Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data. Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA. We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma. We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence. We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level. Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate. Findings In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990. There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population. From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9). In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0). The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9). Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply. Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI. The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum. Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke. Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD. Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma. Interpretation Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD. Deaths from COPD were eight times more common than deaths from asthma. In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs. Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD. Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions. Funding Bill & Melinda Gates Foundation.
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            What the pulmonary specialist should know about the new inhalation therapies.

            A collaboration of multidisciplinary experts on the delivery of pharmaceutical aerosols was facilitated by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM), in order to draw up a consensus statement with clear, up-to-date recommendations that enable the pulmonary physician to choose the type of aerosol delivery device that is most suitable for their patient. The focus of the consensus statement is the patient-use aspect of the aerosol delivery devices that are currently available. The subject was divided into different topics, which were in turn assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. To achieve consensus, draft reports and recommendations were reviewed and voted on by the entire panel. Specific recommendations for use of the devices can be found throughout the statement. Healthcare providers should ensure that their patients can and will use these devices correctly. This requires that the clinician: is aware of the devices that are currently available to deliver the prescribed drugs; knows the various techniques that are appropriate for each device; is able to evaluate the patient's inhalation technique to be sure they are using the devices properly; and ensures that the inhalation method is appropriate for each patient.
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              Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size.

              Aerosol particle size influences the extent, distribution, and site of inhaled drug deposition within the airways. We hypothesized that targeting albuterol to regional airways by altering aerosol particle size could optimize inhaled bronchodilator delivery. In a randomized, double-blind, placebo-controlled study, 12 subjects with asthma (FEV1, 76.8 +/- 11.4% predicted) inhaled technetium-99m-labeled monodisperse albuterol aerosols (30-microg dose) of 1.5-, 3-, and 6-microm mass median aerodynamic diameter, at slow (30-60 L/min) and fast (> 60 L/min) inspiratory flows. Lung and extrathoracic radioaerosol deposition were quantified using planar gamma-scintigraphy. Pulmonary function and tolerability measurements were simultaneously assessed. Clinical efficacy was also compared with unlabeled monodisperse albuterol (15-microg dose) and 200 microg metered-dose inhaler (MDI) albuterol. Smaller particles achieved greater total lung deposition (1.5 microm [56%], 3 microm [50%], and 6 microm [46%]), farther distal airways penetration (0.79, 0.60, and 0.36, respective penetration index), and more peripheral lung deposition (25, 17, and 10%, respectively). However, larger particles (30-microg dose) were more efficacious and achieved greater bronchodilation than 200 microg MDI albuterol (deltaFEV1 [ml]: 6 microm [551], 3 microm [457], 1.5 microm [347], MDI [494]). Small particles were exhaled more (1.5 microm [22%], 3 microm [8%], 6 microm [2%]), whereas greater oropharyngeal deposition occurred with large particles (15, 31, and 43%, respectively). Faster inspiratory flows decreased total lung deposition and increased oropharyngeal deposition for the larger particles, with less bronchodilation. A shift in aerosol distribution to the proximal airways was observed for all particles. Regional targeting of inhaled beta2-agonist to the proximal airways is more important than distal alveolar deposition for bronchodilation. Altering intrapulmonary deposition through aerosol particle size can appreciably enhance inhaled drug therapy and may have implications for developing future inhaled treatments.
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                Author and article information

                Contributors
                Journal
                Ther Adv Respir Dis
                Ther Adv Respir Dis
                TAR
                sptar
                Therapeutic Advances in Respiratory Disease
                SAGE Publications (Sage UK: London, England )
                1753-4658
                1753-4666
                6 December 2019
                Jan-Dec 2019
                : 13
                : 1753466619884532
                Affiliations
                [1-1753466619884532]Careggi University Hospital, Department of Experimental and Clinical Medicine, Largo Brambilla 3, 50134, Florence, Italy
                [2-1753466619884532]Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden
                [3-1753466619884532]Allergy and Respiratory Disease Clinic, DIMI-University of Genova, IRCCS AOU San Martino-IST, Genova, Italy
                [4-1753466619884532]Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden
                [5-1753466619884532]AstraZeneca Nordic-Baltic, Astraallén, Sødertälje, Sweden
                [6-1753466619884532]Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus C, Denmark
                Author notes
                Author information
                https://orcid.org/0000-0002-3293-2123
                Article
                10.1177_1753466619884532
                10.1177/1753466619884532
                6900625
                31805823
                e4c74939-b839-42b1-b7f8-6ff499242363
                © The Author(s), 2019

                This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 29 April 2019
                : 12 September 2019
                Funding
                Funded by: AstraZeneca, FundRef https://doi.org/10.13039/100004325;
                Award ID: N/A
                Categories
                Review
                Custom metadata
                January-December 2019

                asthma,copd,critical errors,dry powder inhaler,inhalation technique,metered dose inhaler

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