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Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK

Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK
Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK

Background: Studies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use. Methods: We analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study. All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis. Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age (<16 years, 16–49 years, and ≥50 years). In-hospital mortality was measured by use of multilevel Cox proportional hazards, adjusting for demographics, comorbidities, and medications (inhaled corticosteroids, short-acting β-agonists [SABAs], and long-acting β-agonists [LABAs]). Patients with asthma who were taking an inhaled corticosteroid plus LABA plus another maintenance asthma medication were considered to have severe asthma. Findings: 75 463 patients from 258 participating health-care facilities were included in this analysis: 860 patients younger than 16 years (74 [8·6%] with asthma), 8950 patients aged 16–49 years (1867 [20·9%] with asthma), and 65 653 patients aged 50 years and older (5918 [9·0%] with asthma, 10 266 [15·6%] with chronic pulmonary disease, and 2071 [3·2%] with both asthma and chronic pulmonary disease). Patients with asthma were significantly more likely than those without asthma to receive critical care (patients aged 16–49 years: adjusted odds ratio [OR] 1·20 [95% CI 1·05–1·37]; p=0·0080; patients aged ≥50 years: adjusted OR 1·17 [1·08–1·27]; p<0·0001), and patients aged 50 years and older with chronic pulmonary disease (with or without asthma) were significantly less likely than those without a respiratory condition to receive critical care (adjusted OR 0·66 [0·60–0·72] for those without asthma and 0·74 [0·62–0·87] for those with asthma; p<0·0001 for both). In patients aged 16–49 years, only those with severe asthma had a significant increase in mortality compared to those with no asthma (adjusted hazard ratio [HR] 1·17 [95% CI 0·73–1·86] for those on no asthma therapy, 0·99 [0·61–1·58] for those on SABAs only, 0·94 [0·62–1·43] for those on inhaled corticosteroids only, 1·02 [0·67–1·54] for those on inhaled corticosteroids plus LABAs, and 1·96 [1·25–3·08] for those with severe asthma). Among patients aged 50 years and older, those with chronic pulmonary disease had a significantly increased mortality risk, regardless of inhaled corticosteroid use, compared to patients without an underlying respiratory condition (adjusted HR 1·16 [95% CI 1·12–1·22] for those not on inhaled corticosteroids, and 1·10 [1·04–1·16] for those on inhaled corticosteroids; p<0·0001). Patients aged 50 years and older with severe asthma also had an increased mortality risk compared to those not on asthma therapy (adjusted HR 1·24 [95% CI 1·04–1·49]). In patients aged 50 years and older, inhaled corticosteroid use within 2 weeks of hospital admission was associated with decreased mortality in those with asthma, compared to those without an underlying respiratory condition (adjusted HR 0·86 [95% CI 0·80−0·92]). Interpretation: Underlying respiratory conditions are common in patients admitted to hospital with COVID-19. Regardless of the severity of symptoms at admission and comorbidities, patients with asthma were more likely, and those with chronic pulmonary disease less likely, to receive critical care than patients without an underlying respiratory condition. In patients aged 16 years and older, severe asthma was associated with increased mortality compared to non-severe asthma. In patients aged 50 years and older, inhaled corticosteroid use in those with asthma was associated with lower mortality than in patients without an underlying respiratory condition; patients with chronic pulmonary disease had significantly increased mortality compared to those with no underlying respiratory condition, regardless of inhaled corticosteroid use. Our results suggest that the use of inhaled corticosteroids, within 2 weeks of admission, improves survival for patients aged 50 years and older with asthma, but not for those with chronic pulmonary disease. Funding: National Institute for Health Research, Medical Research Council, NIHR Health Protection Research Units in Emerging and Zoonotic Infections at the University of Liverpool and in Respiratory Infections at Imperial College London in partnership with Public Health England.

2213-2600
699-711
Bloom, Chloe I
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Drake, Thomas M
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Docherty, Annemarie B
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Lipworth, Brian J
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Johnston, Sebastian L
9635a9c8-cbd6-4470-8cde-cf8147dd9ddf
Nguyen-Van-Tam, Jonathan S
1aac2164-f614-4c82-87f9-e123817bf128
Carson, Gail
56178b9a-2f1e-4823-b6d0-0ee1b2eef830
Dunning, Jake
a311288a-ef83-4475-bf56-b36d9a3525b3
Harrison, Ewen M
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Baillie, J Kenneth
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Semple, Malcolm G
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Cullinan, Paul
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Openshaw, Peter J M
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Dushianthan, Ahilanandan
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ISARIC investigators
Bloom, Chloe I
0f60f176-8b02-489f-af4a-1dfe0932d29e
Drake, Thomas M
059a4d12-8b2d-449a-87d6-f59e00786557
Docherty, Annemarie B
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Lipworth, Brian J
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Johnston, Sebastian L
9635a9c8-cbd6-4470-8cde-cf8147dd9ddf
Nguyen-Van-Tam, Jonathan S
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Carson, Gail
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Dunning, Jake
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Harrison, Ewen M
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Baillie, J Kenneth
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Semple, Malcolm G
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Cullinan, Paul
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Openshaw, Peter J M
4e1ec99b-8f41-4740-be78-a57b2361d483
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751

Bloom, Chloe I, Drake, Thomas M, Docherty, Annemarie B, Lipworth, Brian J, Johnston, Sebastian L, Nguyen-Van-Tam, Jonathan S, Carson, Gail, Dunning, Jake, Harrison, Ewen M, Baillie, J Kenneth, Semple, Malcolm G, Cullinan, Paul and Openshaw, Peter J M , ISARIC investigators (2021) Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK. The Lancet Respiratory Medicine, 9 (7), 699-711. (doi:10.1016/S2213-2600(21)00013-8).

Record type: Article

Abstract

Background: Studies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use. Methods: We analysed data from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study. All patients admitted to hospital with COVID-19 across England, Scotland, and Wales between Jan 17 and Aug 3, 2020, were eligible for inclusion in this analysis. Patients with asthma, chronic pulmonary disease, or both, were identified and stratified by age (<16 years, 16–49 years, and ≥50 years). In-hospital mortality was measured by use of multilevel Cox proportional hazards, adjusting for demographics, comorbidities, and medications (inhaled corticosteroids, short-acting β-agonists [SABAs], and long-acting β-agonists [LABAs]). Patients with asthma who were taking an inhaled corticosteroid plus LABA plus another maintenance asthma medication were considered to have severe asthma. Findings: 75 463 patients from 258 participating health-care facilities were included in this analysis: 860 patients younger than 16 years (74 [8·6%] with asthma), 8950 patients aged 16–49 years (1867 [20·9%] with asthma), and 65 653 patients aged 50 years and older (5918 [9·0%] with asthma, 10 266 [15·6%] with chronic pulmonary disease, and 2071 [3·2%] with both asthma and chronic pulmonary disease). Patients with asthma were significantly more likely than those without asthma to receive critical care (patients aged 16–49 years: adjusted odds ratio [OR] 1·20 [95% CI 1·05–1·37]; p=0·0080; patients aged ≥50 years: adjusted OR 1·17 [1·08–1·27]; p<0·0001), and patients aged 50 years and older with chronic pulmonary disease (with or without asthma) were significantly less likely than those without a respiratory condition to receive critical care (adjusted OR 0·66 [0·60–0·72] for those without asthma and 0·74 [0·62–0·87] for those with asthma; p<0·0001 for both). In patients aged 16–49 years, only those with severe asthma had a significant increase in mortality compared to those with no asthma (adjusted hazard ratio [HR] 1·17 [95% CI 0·73–1·86] for those on no asthma therapy, 0·99 [0·61–1·58] for those on SABAs only, 0·94 [0·62–1·43] for those on inhaled corticosteroids only, 1·02 [0·67–1·54] for those on inhaled corticosteroids plus LABAs, and 1·96 [1·25–3·08] for those with severe asthma). Among patients aged 50 years and older, those with chronic pulmonary disease had a significantly increased mortality risk, regardless of inhaled corticosteroid use, compared to patients without an underlying respiratory condition (adjusted HR 1·16 [95% CI 1·12–1·22] for those not on inhaled corticosteroids, and 1·10 [1·04–1·16] for those on inhaled corticosteroids; p<0·0001). Patients aged 50 years and older with severe asthma also had an increased mortality risk compared to those not on asthma therapy (adjusted HR 1·24 [95% CI 1·04–1·49]). In patients aged 50 years and older, inhaled corticosteroid use within 2 weeks of hospital admission was associated with decreased mortality in those with asthma, compared to those without an underlying respiratory condition (adjusted HR 0·86 [95% CI 0·80−0·92]). Interpretation: Underlying respiratory conditions are common in patients admitted to hospital with COVID-19. Regardless of the severity of symptoms at admission and comorbidities, patients with asthma were more likely, and those with chronic pulmonary disease less likely, to receive critical care than patients without an underlying respiratory condition. In patients aged 16 years and older, severe asthma was associated with increased mortality compared to non-severe asthma. In patients aged 50 years and older, inhaled corticosteroid use in those with asthma was associated with lower mortality than in patients without an underlying respiratory condition; patients with chronic pulmonary disease had significantly increased mortality compared to those with no underlying respiratory condition, regardless of inhaled corticosteroid use. Our results suggest that the use of inhaled corticosteroids, within 2 weeks of admission, improves survival for patients aged 50 years and older with asthma, but not for those with chronic pulmonary disease. Funding: National Institute for Health Research, Medical Research Council, NIHR Health Protection Research Units in Emerging and Zoonotic Infections at the University of Liverpool and in Respiratory Infections at Imperial College London in partnership with Public Health England.

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More information

e-pub ahead of print date: 4 March 2021
Published date: July 2021
Additional Information: Funding Information: BJL has received funding from AstraZeneca, Chiesi, and Teva for research, consulting, advisory boards, and giving talks, from Novartis Glenmark, Cipla, and Vectura for consulting, and from Sanofi for research and consulting. SLJ reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, and Novartis, outside of the submitted work. SLJ is the Asthma UK clinical chair (grant CH11SJ) and an NIHR Emeritus senior investigator and is funded in part by European Research Council Advanced Grant 788575. JKB reports grants from the UK Medical Research Council. MGS reports grants from the Department of Health and Social Care, the National Institute for Health Research, the UK Medical Research Council, and the Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool, UK, during the conduct of the study, and from Integrum Scientific (Greensboro, NC, USA) outside of the submitted work. PJMO reports personal fees from Janssen and Pfizer, and collaborative grant funding from GSK within a UK Medical Research Council consortium and is an NIHR Senior Investigator. ABD reports grants from the Department of Health and Social Care during the conduct of the study; and grants from Wellcome Trust outside of the submitted work. JSN-V-T reports grants from the Department of Health and Social Care during the conduct of the study and is seconded to the Department of Health and Social Care. CIB, TMD, PC, JD, EMH, and GC report no competing interests. Funding Information: This work uses data provided by patients and collected by the UK National Health Service (NHS) as part of their care and supports #DataSavesLives. We are grateful to the 2648 front-line NHS clinical and research staff and volunteer medical students who collected these data in challenging circumstances; and grateful for the generosity of the participants and their families for their individual contributions in these difficult times. We also acknowledge the support of Jeremy J Farrar and Nahoko Shindo. This work is supported by grants from the National Institute for Health Research (NIHR award CO-CIN-01), the Medical Research Council (grant MC_PC_19059) and the NIHR Health Protection Research Units in Emerging and Zoonotic Infections at the University of Liverpool and in Respiratory Infections at Imperial College London in partnership with Public Health England. We acknowledge support from the Liverpool School of Tropical Medicine and the University of Oxford (NIHR award 200907), the NIHR Biomedical Research Centre at Imperial College London, the Wellcome Trust, and Department for International Development (215091/Z/18/Z), and the Bill and Melinda Gates Foundation (OPP1209135). We thank the Liverpool Experimental Cancer Medicine Centre for providing infrastructure support (grant reference: C18616/A25153). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Funding Information: This work uses data provided by patients and collected by the UK National Health Service (NHS) as part of their care and supports #DataSavesLives. We are grateful to the 2648 front-line NHS clinical and research staff and volunteer medical students who collected these data in challenging circumstances; and grateful for the generosity of the participants and their families for their individual contributions in these difficult times. We also acknowledge the support of Jeremy J Farrar and Nahoko Shindo. This work is supported by grants from the National Institute for Health Research (NIHR award CO-CIN-01), the Medical Research Council (grant MC_PC_19059) and the NIHR Health Protection Research Units in Emerging and Zoonotic Infections at the University of Liverpool and in Respiratory Infections at Imperial College London in partnership with Public Health England. We acknowledge support from the Liverpool School of Tropical Medicine and the University of Oxford (NIHR award 200907), the NIHR Biomedical Research Centre at Imperial College London, the Wellcome Trust, and Department for International Development (215091/Z/18/Z), and the Bill and Melinda Gates Foundation (OPP1209135). We thank the Liverpool Experimental Cancer Medicine Centre for providing infrastructure support (grant reference: C18616/A25153). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Publisher Copyright: © 2021 Elsevier Ltd

Identifiers

Local EPrints ID: 449174
URI: http://eprints.soton.ac.uk/id/eprint/449174
ISSN: 2213-2600
PURE UUID: d5fb5ad1-1777-413e-a815-9e01b2807c0d
ORCID for Ahilanandan Dushianthan: ORCID iD orcid.org/0000-0002-0165-3359

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Date deposited: 18 May 2021 16:38
Last modified: 17 Mar 2024 03:51

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Contributors

Author: Chloe I Bloom
Author: Thomas M Drake
Author: Annemarie B Docherty
Author: Brian J Lipworth
Author: Sebastian L Johnston
Author: Jonathan S Nguyen-Van-Tam
Author: Gail Carson
Author: Jake Dunning
Author: Ewen M Harrison
Author: J Kenneth Baillie
Author: Malcolm G Semple
Author: Paul Cullinan
Author: Peter J M Openshaw
Author: Ahilanandan Dushianthan ORCID iD
Corporate Author: ISARIC investigators

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