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      Short-course systemic corticosteroids in asthma: striking the balance between efficacy and safety

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          Abstract

          Short courses of systemic corticosteroids (SCS), both oral and injectable, are very effective for the resolution of acute asthma symptoms, including exacerbations. However, the benefits of SCS, even short courses, must be balanced against the impact of their side-effects. While the adverse consequences of long-term use are widely recognised, there appears to be a perception in the medical community that short courses of SCS are safe. Limited but growing evidence in the literature suggests that even very brief dosing periods (3–7 days) of SCS are enough to cause significantly negative outcomes for patients. Short courses of SCS are associated with increased risk of adverse events including loss of bone density, hypertension and gastrointestinal ulcers/bleeds, in addition to serious impacts on mental health. Strategies to improve asthma control are recommended, including: 1) as-needed combination therapies in mild asthma; 2) risk factor reduction; 3) improving adherence/inhaler technique; 4) earlier initiation of add-on therapies; 5) use of biologics in appropriate patients; 6) development of new therapies to better control the disease; and 7) widespread education of the medical community. We propose that patients and primary care physicians should consider a cumulative SCS dose of 1 g per year as a highly relevant and easy-to-recall threshold.

          Abstract

          Inappropriate use of systemic corticosteroids in asthma may add to disease burden. Even short-term, intermittent use is associated with health risks. Strategies to improve asthma control and reduce inappropriate use of systemic corticosteroids are needed. https://bit.ly/3bdieam

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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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            Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update from the American College of Physicians.

            This guideline updates the 2008 American College of Physicians (ACP) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women. This guideline is endorsed by the American Academy of Family Physicians.
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              Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study

              Objective To determine the frequency of prescriptions for short term use of oral corticosteroids, and adverse events (sepsis, venous thromboembolism, fractures) associated with their use. Design Retrospective cohort study and self controlled case series. Setting Nationwide dataset of private insurance claims. Participants Adults aged 18 to 64 years who were continuously enrolled from 2012 to 2014. Main outcome measures Rates of short term use of oral corticosteroids defined as less than 30 days duration. Incidence rates of adverse events in corticosteroid users and non-users. Incidence rate ratios for adverse events within 30 day and 31-90 day risk periods after drug initiation. Results Of 1 548 945 adults, 327 452 (21.1%) received at least one outpatient prescription for short term use of oral corticosteroids over the three year period. Use was more frequent among older patients, women, and white adults, with significant regional variation (all P<0.001). The most common indications for use were upper respiratory tract infections, spinal conditions, and allergies. Prescriptions were provided by a diverse range of specialties. Within 30 days of drug initiation, there was an increase in rates of sepsis (incidence rate ratio 5.30, 95% confidence interval 3.80 to 7.41), venous thromboembolism (3.33, 2.78 to 3.99), and fracture (1.87, 1.69 to 2.07), which diminished over the subsequent 31-90 days. The increased risk persisted at prednisone equivalent doses of less than 20 mg/day (incidence rate ratio 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P<0.001). Conclusion One in five American adults in a commercially insured plan were given prescriptions for short term use of oral corticosteroids during a three year period, with an associated increased risk of adverse events.
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                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                31 March 2020
                03 April 2020
                : 29
                : 155
                : 190151
                Affiliations
                [1 ]Observational and Pragmatic Research Institute, Singapore, Singapore
                [2 ]Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
                [3 ]Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, MO, USA
                [4 ]Dept of Respiratory Diseases, Université de Montpellier, PhyMedExp, INSERM, CNRS, CHU de Montpellier, Montpellier, France
                [5 ]Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
                Author notes
                David Price, Observational and Pragmatic Research Institute (OPRI) Pte Ltd, 883 North Bridge Rd, #02-05 Southbank, Singapore 198785. E-mail: dprice@ 123456opri.sg
                Author information
                https://orcid.org/0000-0002-9728-9992
                Article
                ERR-0151-2019
                10.1183/16000617.0151-2019
                9488828
                32245768
                65570d9a-df15-4471-890e-927a32124393
                Copyright ©ERS 2020.

                This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

                History
                : 11 November 2019
                : 20 March 2020
                Funding
                Funded by: Novartis Pharma, doi 10.13039/100008792;
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