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      Asthma and Coronavirus Disease 2019 Risk: a systematic review and meta-analysis

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          Abstract

          Background

          Individual case series and cohort studies have reported conflicting results on the vulnerability to and risk of mortality of people with asthma from COVID-19.

          Research Question

          Are people with asthma at a higher risk of being infected, hospitalised or of poorer clinical outcomes from COVID-19?

          Methods

          A systematic review and meta-analysis based on five main databases including the WHO COVID-19 database between December 1, 2019 to July 11, 2021 on studies with a control (non-asthma) group was conducted. Prevalence and risk ratios were pooled using Sidik-Jonkman random effects meta-analyses.

          Findings

          Fifty-one studies with an 8.08% (95% CI 6.87–9.30) pooled prevalence of people with asthma among COVID-19 positive cases. The risk ratios were 0.83 (95% CI 0.73–0.95, p=0.01) for acquiring COVID-19; 1.18 (95% CI 0.98–1.42, p=0.08) for hospitalisation; 1.21 (95% CI 0.97–1.51, p=0.09) for ICU admission; 1.06 (95% CI 0.82–1.36, p=0.65) for ventilator use and 0.94 (95% CI 0.76–1.17; p=0.58) for mortality for people with asthma. Subgroup analyses by continent revealed a significant difference in risk of acquiring COVID-19, ICU admission, ventilator use and death between the continents.

          Interpretation

          The risk of being infected with SARS-CoV-2 was reduced compared to the non-asthma group. No statistically significant differences in hospitalisation, ICU admission and ventilator use were found between groups. Subgroup analyses showed significant differences in outcomes from COVID-19 between America, Europe and Asia. Additional studies are required to confirm this risk profile, particularly in Africa and South America where few studies originate.

          Abstract

          The risk of being infected with SARS-CoV-2 was reduced compared to the non-asthma group. No significant differences in hospitalisation, ICU admission, ventilator use and mortali were found between groups.

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          Rayyan—a web and mobile app for systematic reviews

          Mourad Ouzzani, Hossam Hammady, Zbys Fedorowicz … (2017)
          Background Synthesis of multiple randomized controlled trials (RCTs) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions. Filtering of searches is time consuming, and no single method fulfills the principal requirements of speed with accuracy. Automation of systematic reviews is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making. We developed Rayyan (http://rayyan.qcri.org), a free web and mobile app, that helps expedite the initial screening of abstracts and titles using a process of semi-automation while incorporating a high level of usability. For the beta testing phase, we used two published Cochrane reviews in which included studies had been selected manually. Their searches, with 1030 records and 273 records, were uploaded to Rayyan. Different features of Rayyan were tested using these two reviews. We also conducted a survey of Rayyan’s users and collected feedback through a built-in feature. Results Pilot testing of Rayyan focused on usability, accuracy against manual methods, and the added value of the prediction feature. The “taster” review (273 records) allowed a quick overview of Rayyan for early comments on usability. The second review (1030 records) required several iterations to identify the previously identified 11 trials. The “suggestions” and “hints,” based on the “prediction model,” appeared as testing progressed beyond five included studies. Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements. The survey respondents reported 40% average time savings when using Rayyan compared to others tools, with 34% of the respondents reporting more than 50% time savings. In addition, around 75% of the respondents mentioned that screening and labeling studies as well as collaborating on reviews to be the two most important features of Rayyan. As of November 2016, Rayyan users exceed 2000 from over 60 countries conducting hundreds of reviews totaling more than 1.6M citations. Feedback from users, obtained mostly through the app web site and a recent survey, has highlighted the ease in exploration of searches, the time saved, and simplicity in sharing and comparing include-exclude decisions. The strongest features of the app, identified and reported in user feedback, were its ability to help in screening and collaboration as well as the time savings it affords to users. Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of reviewers.
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            Epidemiology of Asthma in Children and Adults

            Shyamali Dharmage, Jennifer Perret, Adnan Custovic (2019)
            Asthma is a globally significant non-communicable disease with major public health consequences for both children and adults, including high morbidity, and mortality in severe cases. We have summarized the evidence on asthma trends, environmental determinants, and long-term impacts while comparing these epidemiological features across childhood asthma and adult asthma. While asthma incidence and prevalence are higher in children, morbidity, and mortality are higher in adults. Childhood asthma is more common in boys while adult asthma is more common in women, and the reversal of this sex difference in prevalence occurs around puberty suggesting sex hormones may play a role in the etiology of asthma. The global epidemic of asthma that has been observed in both children and adults is still continuing, especially in low to middle income countries, although it has subsided in some developed countries. As a heterogeneous disease, distinct asthma phenotypes, and endotypes need to be adequately characterized to develop more accurate and meaningful definitions for use in research and clinical settings. This may be facilitated by new clustering techniques such as latent class analysis, and computational phenotyping methods are being developed to retrieve information from electronic health records using natural language processing (NLP) algorithms to assist in the early diagnosis of asthma. While some important environmental determinants that trigger asthma are well-established, more work is needed to define the role of environmental exposures in the development of asthma in both children and adults. There is increasing evidence that investigation into possible gene-by-environment and environment-by-environment interactions may help to better uncover the determinants of asthma. Therefore, there is an urgent need to further investigate the interrelationship between environmental and genetic determinants to identify high risk groups and key modifiable exposures. For children, asthma may impair airway development and reduce maximally attained lung function, and these lung function deficits may persist into adulthood without additional progressive loss. Adult asthma may accelerate lung function decline and increase the risk of fixed airflow obstruction, with the effect of early onset asthma being greater than late onset asthma. Therefore, in managing asthma, our focus going forward should be firmly on improving not only short-term symptoms, but also the long-term respiratory and other health outcomes.
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              Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial

              Sanjay Ramakrishnan, Dan V. Nicolau, Beverly Langford … (2021)
              Background Multiple early reports of patients admitted to hospital with COVID-19 showed that patients with chronic respiratory disease were significantly under-represented in these cohorts. We hypothesised that the widespread use of inhaled glucocorticoids among these patients was responsible for this finding, and tested if inhaled glucocorticoids would be an effective treatment for early COVID-19. Methods We performed an open-label, parallel-group, phase 2, randomised controlled trial (Steroids in COVID-19; STOIC) of inhaled budesonide, compared with usual care, in adults within 7 days of the onset of mild COVID-19 symptoms. The trial was done in the community in Oxfordshire, UK. Participants were randomly assigned to inhaled budsonide or usual care stratified for age (≤40 years or >40 years), sex (male or female), and number of comorbidities (≤1 and ≥2). Randomisation was done using random sequence generation in block randomisation in a 1:1 ratio. Budesonide dry powder was delivered using a turbohaler at a dose of 800 μg per actuation. Participants were asked to take two inhalations twice a day until symptom resolution. The primary endpoint was COVID-19-related urgent care visit, including emergency department assessment or hospitalisation, analysed for both the per-protocol and intention-to-treat (ITT) populations. The secondary outcomes were self-reported clinical recovery (symptom resolution), viral symptoms measured using the Common Cold Questionnare (CCQ) and the InFLUenza Patient Reported Outcome Questionnaire (FLUPro), body temperature, blood oxygen saturations, and SARS-CoV-2 viral load. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. This trial is registered with ClinicalTrials.gov, NCT04416399. Findings From July 16 to Dec 9, 2020, 167 participants were recruited and assessed for eligibility. 21 did not meet eligibility criteria and were excluded. 146 participants were randomly assigned—73 to usual care and 73 to budesonide. For the per-protocol population (n=139), the primary outcome occurred in ten (14%) of 70 participants in the budesonide group and one (1%) of 69 participant in the usual care group (difference in proportions 0·131, 95% CI 0·043 to 0·218; p=0·004). For the ITT population, the primary outcome occurred in 11 (15%) participants in the usual care group and two (3%) participants in the budesonide group (difference in proportions 0·123, 95% CI 0·033 to 0·213; p=0·009). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was eight. Clinical recovery was 1 day shorter in the budesonide group compared with the usual care group (median 7 days [95% CI 6 to 9] in the budesonide group vs 8 days [7 to 11] in the usual care group; log-rank test p=0·007). The mean proportion of days with a fever in the first 14 days was lower in the budesonide group (2%, SD 6) than the usual care group (8%, SD 18; Wilcoxon test p=0·051) and the proportion of participants with at least 1 day of fever was lower in the budesonide group when compared with the usual care group. As-needed antipyretic medication was required for fewer proportion of days in the budesonide group compared with the usual care group (27% [IQR 0–50] vs 50% [15–71]; p=0·025) Fewer participants randomly assigned to budesonide had persistent symptoms at days 14 and 28 compared with participants receiving usual care (difference in proportions 0·204, 95% CI 0·075 to 0·334; p=0·003). The mean total score change in the CCQ and FLUPro over 14 days was significantly better in the budesonide group compared with the usual care group (CCQ mean difference −0·12, 95% CI −0·21 to −0·02 [p=0·016]; FLUPro mean difference −0·10, 95% CI −0·21 to −0·00 [p=0·044]). Blood oxygen saturations and SARS-CoV-2 load, measured by cycle threshold, were not different between the groups. Budesonide was safe, with only five (7%) participants reporting self-limiting adverse events. Interpretation Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery after early COVID-19. Funding National Institute for Health Research Biomedical Research Centre and AstraZeneca.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Eur Respir J
                Journal ID (iso-abbrev): Eur Respir J
                Journal ID (publisher-id): ERJ
                Journal ID (hwp): erj
                Title: The European Respiratory Journal
                Publisher: European Respiratory Society
                ISSN (Print): 0903-1936
                ISSN (Electronic): 1399-3003
                Publication date (Electronic): 12 August 2021
                Publication date PMC-release: 12 August 2021
                Electronic Location Identifier: 2101209
                Affiliations
                [1 ]The George Institute for Global Health, Newtown, New South Wales, Australia
                [2 ]The University of New South Wales, Sydney, New South Wales, Australia
                [3 ]Concord Clinical School, Medical Education Centre, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
                Author notes
                Author information
                https://orcid.org/0000-0003-2257-4374
                https://orcid.org/0000-0002-5470-3567
                https://orcid.org/0000-0003-2717-5647
                Article
                Publisher ID: ERJ-01209-2021
                DOI: 10.1183/13993003.01209-2021
                PMC ID: 8361304
                PubMed ID: 34385278
                SO-VID: 18b7e20e-4e9f-4e93-b1f6-a852d29394b9
                Copyright © Copyright ©The authors 2021.
                License:

                This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org

                History
                Date received : 27 April 2021
                Date accepted : 2 August 2021
                Categories
                Subject: Original Research Article

                ScienceOpen disciplines: Respiratory medicine
                Data availability:
                ScienceOpen disciplines: Respiratory medicine

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