COVID-19 住院患者伴有基础呼吸系统疾病的不良结局风险:一项全国性、多中心前瞻性队列研究,使用 ISARIC WHO 临床特征化方案 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.

机构信息

National Heart and Lung Institute, Imperial College London, London, UK.

Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK.

出版信息

Lancet Respir Med. 2021 Jul;9(7):699-711. doi: 10.1016/S2213-2600(21)00013-8. Epub 2021 Mar 4.

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.

摘要

背景

对因 COVID-19 住院的患者进行的研究发现,与基础呼吸系统疾病和吸入性皮质类固醇的使用相关的死亡率存在差异。本研究使用来自一个全国性、多中心、前瞻性队列的数据,旨在描述因基础呼吸系统疾病住院的 COVID-19 患者,评估所接受的护理水平,测量院内死亡率,并研究吸入性皮质类固醇使用的影响。

方法

我们分析了国际严重急性呼吸和新兴感染联盟(ISARIC)世界卫生组织临床特征化方案英国(CCP-UK)研究的数据。2020 年 1 月 17 日至 8 月 3 日期间,英格兰、苏格兰和威尔士所有因 COVID-19 住院的患者均有资格纳入本分析。有哮喘、慢性肺部疾病或两者并存的患者被识别出来,并按年龄(<16 岁、16-49 岁和≥50 岁)进行分层。使用多水平 Cox 比例风险模型测量院内死亡率,调整了人口统计学、合并症和药物(吸入性皮质类固醇、短效 β-激动剂[SABA]和长效 β-激动剂[LABA])。使用吸入性皮质类固醇联合 LABA 加另一种维持性哮喘药物的哮喘患者被认为患有严重哮喘。

结果

来自 258 个参与医疗保健机构的 75463 名患者被纳入本分析:860 名年龄<16 岁的患者(74 名[8.6%]患有哮喘)、8950 名年龄 16-49 岁的患者(1867 名[20.9%]患有哮喘)和 65653 名年龄≥50 岁的患者(5918 名[9.0%]患有哮喘、10266 名[15.6%]患有慢性肺部疾病和 2071 名[3.2%]患有哮喘和慢性肺部疾病)。与没有哮喘的患者相比,有哮喘的患者更有可能接受重症护理(年龄 16-49 岁的患者:调整后的优势比[OR]1.20[95%CI 1.05-1.37];p=0.0080;年龄≥50 岁的患者:调整后的 OR 1.17[1.08-1.27];p<0.0001),年龄≥50 岁且患有慢性肺部疾病(无论是否患有哮喘)的患者接受重症护理的可能性明显低于没有呼吸系统疾病的患者(调整后的 OR 0.66[0.60-0.72],无哮喘患者;0.74[0.62-0.87],有哮喘患者;p<0.0001)。在年龄 16-49 岁的患者中,只有严重哮喘患者的死亡率与无哮喘患者相比显著增加(未接受哮喘治疗的患者的调整后的危险比[HR]1.17[95%CI 0.73-1.86],仅使用 SABA 的患者 0.99[0.61-1.58],仅使用吸入性皮质类固醇的患者 0.94[0.62-1.43],使用吸入性皮质类固醇联合 LABA 的患者 1.02[0.67-1.54],严重哮喘患者 1.96[1.25-3.08])。在年龄≥50 岁的患者中,无论是否使用吸入性皮质类固醇,患有慢性肺部疾病的患者的死亡风险均显著增加,与无基础呼吸系统疾病的患者相比(未使用吸入性皮质类固醇的患者的调整后的 HR 1.16[95%CI 1.12-1.22],使用吸入性皮质类固醇的患者 1.10[1.04-1.16];p<0.0001)。年龄≥50 岁且患有严重哮喘的患者的死亡风险也高于未接受哮喘治疗的患者(调整后的 HR 1.24[95%CI 1.04-1.49])。在年龄≥50 岁的患者中,与无基础呼吸系统疾病的患者相比,入院后 2 周内使用吸入性皮质类固醇与降低哮喘患者的死亡率相关(调整后的 HR 0.86[95%CI 0.80-0.92])。

结论

基础呼吸系统疾病在因 COVID-19 住院的患者中很常见。无论入院时的症状严重程度和合并症如何,与无基础呼吸系统疾病的患者相比,哮喘患者更有可能,而慢性肺部疾病患者则更不可能接受重症护理。在 16 岁及以上的患者中,与非严重哮喘相比,严重哮喘与死亡率增加相关。在年龄≥50 岁的患者中,与无基础呼吸系统疾病的患者相比,使用吸入性皮质类固醇的哮喘患者的死亡率降低,而无论是否使用吸入性皮质类固醇,患有慢性肺部疾病的患者的死亡率均显著增加。我们的结果表明,在入院后 2 周内使用吸入性皮质类固醇可提高哮喘患者的生存率,但不能提高慢性肺部疾病患者的生存率。

资助

英国国民健康保险制度、医学研究理事会、利物浦大学新兴和人畜共患病感染以及帝国理工学院呼吸感染的国民健康保险制度健康保护研究单位与英国公共卫生署合作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/245b/8241313/78733a65ca5d/gr1_lrg.jpg

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