Asthma and COVID-19: an update

As the world faces the coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, concerns have been raised that asthma patients could be at increased risk of SARS-CoV-2 infection and disease severity. However, it appears that asthma is not an independent risk factor for both. Furthermore, asthma is not over-represented in hospitalised patients with severe pneumonia due to SARS-CoV-2 infection and there was no increased risk of asthma exacerbations triggered by SARS-CoV-2. There is accumulating evidence that asthma phenotypes and comorbidities are important factors in evaluating the risk for SARS-CoV-2 infection and disease severity, as findings suggest that Th2-high inflammation may reduce the risk of SARS-Cov-2 infection and disease severity in contrast to increased risk in patients with Th2-low asthma. The use of inhaled corticosteroids (ICS) is safe in asthma patients with SARS-CoV-2 infection. Furthermore, it has been proposed that ICS may confer some degree of protection against SARS-CoV-2 infection and the development of severe disease by reducing the expression of angiotensin converting enzyme-2 and transmembrane protease serine in the lung. In contrast, chronic or recurrent use of systemic corticosteroids before SARS-CoV-2 infection is a major risk factor of poor outcomes and worst survival in asthma patients. Conversely, biological therapy for severe allergic and eosinophilic asthma does not increase the risk of being infected with SARS-CoV-2 or having worse COVID-19 severity. In the present review we will summarise the current literature regarding asthma and COVID-19.

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Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

BMC Infectious Diseases ◽

10.1186/s12879-021-05992-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

M. Flook ◽

C. Jackson ◽

E. Vasileiou ◽

C. R. Simpson ◽

M. D. Muckian ◽

...

Keyword(s):

Public Health ◽

Risk Factors ◽

Systematic Review ◽

At Risk ◽

Risk Factor ◽

Disease Severity ◽

Severe Disease ◽

Public Health Response ◽

Wide Range ◽

Multivariable Analyses

Abstract Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. Registration This review was registered on PROSPERO as CRD42020177714.

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Eosinopenie als Biomarker des Schweregrads einer COVID-19-Infektion

Karger Kompass Autoimmun ◽

10.1159/000520189 ◽

2021 ◽

pp. 1-2

Author(s):

Panagiota Xanthouli

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Disease Severity ◽

Respiratory Diseases ◽

Severe Disease ◽

Public Hospitals ◽

Chronic Respiratory Diseases ◽

Lack Of Information ◽

Obstructive Sleep ◽

Increased Risk

Background: Studies on the role of eosinophils in coronavirus disease 2019 (COVID-19) are scarce, though available findings suggest a possible association with disease severity. Our study analyzes the relationship between eosinophils and COVID-19, with a focus on disease severity and patients with underlying chronic respiratory diseases. Methods: We performed a retrospective analysis of 3,018 subjects attended at two public hospitals in Madrid (Spain) with PCR-confirmed SARS-CoV-2 infection from January 31 to April 17, 2020. Patients with eosinophil counts less than 0.02 × 109/L were considered to have eosinopenia. Individuals with chronic respiratory diseases (n = 384) were classified according to their particular underlying condition, i.e., asthma, chronic pulmonary obstructive disease, or obstructive sleep apnea. Results: Of the 3018 patients enrolled, 479 were excluded because of lack of information at the time of admission. Of 2539 subjects assessed, 1,396 patients presented an eosinophil count performed on admission, revealing eosinopenia in 376 cases (26.93%). Eosinopenia on admission was associated with a higher risk of intensive care unit (ICU) or respiratory intensive care unit (RICU) admission (OR:2.21; 95% CI:1.42–3.45; p < 0.001) but no increased risk of mortality (p > 0.05). Conclusion: Eosinopenia on admission conferred a higher risk of severe disease (requiring ICU/RICU care), but was not associated with increased mortality. In patients with chronic respiratory diseases who develop COVID-19, age seems to be the main risk factor for progression to severe disease or death.

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Adherence to corticosteroids and clinical outcomes in mepolizumab therapy for severe asthma

European Respiratory Journal ◽

10.1183/13993003.02259-2019 ◽

2020 ◽

Vol 55 (5) ◽

pp. 1902259 ◽

Cited By ~ 5

Author(s):

Gráinne d'Ancona ◽

Joanne Kavanagh ◽

Cris Roxas ◽

Linda Green ◽

Mariana Fernandes ◽

...

Keyword(s):

Clinical Outcomes ◽

Biologic Therapy ◽

Inhaled Corticosteroids ◽

Final Analysis ◽

Good Adherence ◽

Eosinophilic Asthma ◽

Exacerbation Rate ◽

Asthmatic Patients ◽

Severe Eosinophilic Asthma ◽

Asthma Patients

IntroductionInhaled corticosteroids (ICS) achieve disease control in the majority of asthmatic patients, although adherence to prescribed ICS is often poor. Patients with severe eosinophilic asthma may require treatment with oral corticosteroids (OCS) and/or biologic agents such as mepolizumab. It is unknown if ICS adherence changes on, or alters clinical response to, biologic therapy.MethodsWe examined ICS adherence and clinical outcomes in OCS-dependent severe eosinophilic asthma patients who completed 1 year of mepolizumab therapy. The ICS medicines possession ratio (MPR) was calculated (the number of doses of ICS issued on prescription/expected number) for the year before and the year after biologic initiation. Good adherence was defined as MPR >0.75, intermediate 0.74–0.51 and poor <0.5. We examined outcomes after 12 months of biologic therapy, including OCS reduction and annualised exacerbation rate (AER), stratified by adherence to ICS on mepolizumab.ResultsOut of 109 patients commencing mepolizumab, 91 who had completed 12 months of treatment were included in the final analysis. While receiving mepolizumab, 68% had good ICS adherence, with 16 (18%) having poor ICS adherence. ICS use within the cohort remained similar before (MPR 0.81±0.32) and during mepolizumab treatment (0.82±0.32; p=0.78). Patients with good adherence had greater reductions in OCS dose (median (interquartile range) OCS reduction 100 (74–100)% versus 60 (27–100)%; p=0.031) and exacerbations (AER change −2.1±3.1 versus 0.3±2.5; p=0.011) than those with poor adherence. Good ICS adherence predicted the likelihood of stopping maintenance OCS (adjusted OR 3.19, 95% CI 1.02–9.94; p=0.045).ConclusionICS nonadherence is common in severe eosinophilic asthma patients receiving mepolizumab, and is associated with a lesser reduction in OCS requirements and AER.

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Diagnosis and Management of Severe Asthma

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0037-1607391 ◽

2018 ◽

Vol 39 (01) ◽

pp. 091-099 ◽

Cited By ~ 5

Author(s):

Kian Fan Chung

Keyword(s):

Severe Asthma ◽

Inhaled Corticosteroids ◽

Immunoglobulin E ◽

High Dose ◽

Blood Eosinophil ◽

Exhaled Breath ◽

Eosinophilic Asthma ◽

Severe Eosinophilic Asthma ◽

Asthma Patients ◽

Long Acting

AbstractSevere therapy-resistant asthma has been defined as “asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy”. Patients who usually present with ‘difficult-to-treat asthma’ should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.

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Management of the patient with eosinophilic asthma: a new era begins

ERJ Open Research ◽

10.1183/23120541.00024-2015 ◽

2015 ◽

Vol 1 (1) ◽

pp. 00024-2015 ◽

Cited By ~ 55

Author(s):

Jantina C. de Groot ◽

Anneke ten Brinke ◽

Elisabeth H.D. Bel

Keyword(s):

Inhaled Corticosteroids ◽

Late Onset ◽

Airflow Obstruction ◽

Poor Quality ◽

Eosinophilic Asthma ◽

New Era ◽

Systemic Corticosteroids ◽

Asthma Patients ◽

Oral Corticosteroids ◽

Bronchial Biopsies

Now that it is generally accepted that asthma is a heterogeneous condition, phenotyping of asthma patients has become a mandatory part of the diagnostic workup of all patients who do not respond satisfactorily to standard therapy with inhaled corticosteroids. Late-onset eosinophilic asthma is currently one of the most well-defined asthma phenotypes and seems to have a different underlying pathobiology to classical childhood-onset, allergic asthma. Patients with this phenotype can be identified in the clinic by typical symptoms (few allergies and dyspnoea on exertion), typical lung function abnormalities (“fixed” airflow obstruction, reduced forced vital capacity and increased residual volume), typical comorbidities (nasal polyposis) and a good response to systemic corticosteroids. The definitive diagnosis is based on evidence of eosinophilia in bronchial biopsies or induced sputum, which can be estimated with reasonable accuracy by eosinophilia in peripheral blood. Until recently, patients with eosinophilic asthma had a very poor quality of life and many suffered from frequent severe exacerbations or were dependent on oral corticosteroids. Now, for the first time, novel biologicals targeting the eosinophil have become available that have been shown to be able to provide full control of this type of refractory asthma, and to become a safe and efficacious substitute for oral corticosteroids.

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Is Rheumatoid Arthritis a Risk Factor for Fractures: A Systematic Review of Observational Studies

Current Rheumatology Reviews ◽

10.2174/1573397115666190723160312 ◽

2020 ◽

Vol 16 (1) ◽

pp. 29-37

Author(s):

Ambika Gupta ◽

Stephanie G. Pipe ◽

Tanveer Towheed ◽

Tassos Anastassiades

Keyword(s):

Risk Factor ◽

General Population ◽

Disease Severity ◽

Functional Impairment ◽

Primary Objective ◽

Control Group ◽

Cross Sectional ◽

Risk Of Fracture ◽

Increased Risk ◽

Study Heterogeneity

Aim: The primary objective was to assess the risk of fractures in adults with RA compared with controls from the general population. The review also assessed an increased risk of fractures in RA patients when accounting for steroid use, RA disease severity or functional impairment. Method: Citations were screened from MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and CINAHL. Included citations were written in English, including adult patients at least 18 years of age and compared fracture incidence or prevalence between RA patients and a control group. Case-control, cohort and cross-sectional studies were included. Results: There were a total of 3451 citations; after application of the inclusion criteria, 17 studies were selected. In 14 of the 17 studies, there was an increase in the risk of fracture in RA patients compared to controls. In studies that evaluated for glucocorticoid use, four of 13 demonstrated an increased risk of fracture with glucocorticoid use, however, only two of these four studies specifically assessed glucocorticoid use amongst patients with RA. In studies that analyzed RA severity or functional impairment, two of seven demonstrated disease severity or impairment as a risk factor for fracture. There was marked study heterogeneity in terms of patient and fracture characteristics, which was a limitation of the analysis that impeded the ability to make direct comparisons. Conclusion: The risk of fracture in RA patients is elevated when compared to the general population, although the etiology of the increased risk remains to be elucidated.

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IS ASTHMA AND USE OF INHALED CORTICOSTEROIDS A RISK FACTOR FOR COVID-19 INFECTION?A CLINICAL REVIEW

10.36106/1818181 ◽

2021 ◽

pp. 1-3

Author(s):

Ajeet Subramaniam ◽

Aktham Ghazal

Keyword(s):

Risk Factor ◽

Lung Disease ◽

Clinical Review ◽

Inhaled Corticosteroids ◽

Respiratory Infections ◽

Acute Respiratory Infections ◽

Increased Risk ◽

Lower Airways

Asthma is the most common chronic inammatory lung disease worldwide and SARS-CoV-2 primarily affects the upper and lower airways leading to marked inammation, the question arises about the possible clinical and pathophysiological association between asthma and SARS-CoV-2/COVID-19. Other questions include whether use of Inhaled Corticosteroids (ICS) affects the outcomes of acute respiratory infections due to coronavirus, whether patients with asthma are at increased risk of developing COVID-19? This clinical review aims to answer some of these questions based on latest research on asthma and COVID-19.

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Proton pump inhibitors as a risk factor for norovirus infection

Epidemiology and Infection ◽

10.1017/s0950268817000528 ◽

2017 ◽

Vol 145 (8) ◽

pp. 1617-1623 ◽

Cited By ~ 9

Author(s):

C. PRAG ◽

M. PRAG ◽

H. FREDLUND

Keyword(s):

Risk Factor ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Viral Gastroenteritis ◽

Retrospective Case ◽

Hospitalised Patients ◽

Increased Risk ◽

Seriously Ill Patients ◽

Hospitalised Patient ◽

Significant Health

SUMMARYNorovirus causes viral gastroenteritis, which is a major problem in health care. The disease causes death in elderly and seriously ill patients, and results in significant health costs each year. Proton pump inhibitors (PPIs) reduce gastric acidity, which is an important protection against microorganisms. We hypothesised that treatment with PPIs increases the risk of contracting norovirus infection. This has not previously been studied. The study was a retrospective case–control study, in which 192 hospitalised patients positive for norovirus in Örebro County, Sweden, were identified as cases. For each case, a hospitalised patient who did not have the infection was selected as a control, and matched with respect to ward, gender, admission date and age. Details of exposure, i.e. treatment with PPIs, were retrieved from the patient records. Odds ratio (OR) with confidence intervals (CIs) and P-values were calculated using McNemar's test. There was a significantly increased risk of norovirus infection in patients treated with PPIs compared with patients without PPI treatment (OR 1·73, 95% CI 1·07–2·81; P = 0·02). PPIs appear to be a risk factor for norovirus infection, and our results motivate future studies to further examine this association.

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Immune profiles provide insights into respiratory syncytial virus disease severity in young children

Science Translational Medicine ◽

10.1126/scitranslmed.aaw0268 ◽

2020 ◽

Vol 12 (540) ◽

pp. eaaw0268 ◽

Cited By ~ 7

Author(s):

Santtu Heinonen ◽

Victoria M. Velazquez ◽

Fang Ye ◽

Sara Mertz ◽

Santiago Acero-Bedoya ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Disease Severity ◽

Virus Disease ◽

Severe Disease ◽

Mild Disease ◽

Hla Dr ◽

Increased Risk ◽

Determining Factors ◽

Rsv Infection ◽

Syncytial Virus

Respiratory syncytial virus (RSV) is associated with major morbidity in infants, although most cases result in mild disease. The pathogenesis of the disease is incompletely understood, especially the determining factors of disease severity. A better characterization of these factors may help with development of RSV vaccines and antivirals. Hence, identification of a “safe and protective” immunoprofile induced by natural RSV infection could be used as a as a surrogate of ideal vaccine-elicited responses in future clinical trials. In this study, we integrated blood transcriptional and cell immune profiling, RSV loads, and clinical data to identify factors associated with a mild disease phenotype in a cohort of 190 children <2 years of age. Children with mild disease (outpatients) showed higher RSV loads, greater induction of interferon (IFN) and plasma cell genes, and decreased expression of inflammation and neutrophil genes versus children with severe disease (inpatients). Additionally, only infants with severe disease had increased numbers of HLA-DRlow monocytes, not present in outpatients. Multivariable analyses confirmed that IFN overexpression was associated with decreased odds of hospitalization, whereas increased numbers of HLA-DRlow monocytes were associated with increased risk of hospitalization. These findings suggest that robust innate immune responses are associated with mild RSV infection in infants.

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Risk factors for recurrent wheezing after bronchiolitis in infants: 2-year follow up in China

BMC Infectious Diseases ◽

10.1186/s12879-021-05937-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sainan Chen ◽

Wenjing Gu ◽

Min Wu ◽

Chuangli Hao ◽

Canhong Zhu ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Independent Risk Factor ◽

Severe Disease ◽

Recurrent Wheezing ◽

Increased Risk ◽

Tnf Α ◽

History Of ◽

Outpatient Appointments

Abstract Background Infants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the risk factors for the development of recurrent wheezing after bronchiolitis remains controversial. Our study was to investigate risk factors of post-bronchiolitis recurrent wheezing. Methods Infants with bronchiolitis were enrolled from November 2016 through March 2017. Nasopharyngeal aspirates were obtained for detection of respiratory viruses which were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and direct immunofluorescent assay. Serum cytokines including TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α were measured by flow cytometry. Patients were followed up every 3 months for a duration of 2 years by telephone or at outpatient appointments. Results We enrolled 89 infants, of which 81 patients were successfully followed up. In total, 22.2% of patients experienced recurrent wheezing episodes. The proportion of patients with history of eczema, systemic glucocorticoid use and patients with moderate-to-severe disease were significantly higher in the recurrent wheezing group than the non-recurrent wheezing group (83.3% vs 52.4%; 66.7% vs 36.5%; 61.1% vs 33.3%, respectively, all P < 0.05); There were no significant differences between patients with and without recurrent wheezing episodes in the levels of TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α (P > 0.05). Logistic regression analysis showed that history of eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR] = 5.622; 95% confidence interval [CI], 1.3–24.9; P = 0.023). Conclusion The incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. History of eczema was the only independent risk factor identified and no correlation was found between the specific virus and disease severity in children with post-bronchiolitis recurrent wheezing.

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