Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. MethodsThe Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A posthoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5•9 months (IQR 4•9-6•5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity.Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments w...

Concurrent blockade of IL-13 and IL-17A may improve control of asthma.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection carries a substantial risk of severe and prolonged illness; treatment options are currently limited. We assessed the efficacy and safety of inhaled nebulised interferon beta-1a (SNG001) for the treatment of patients admitted to hospital with COVID-19. Methods We did a randomised, double-blind, placebo-controlled, phase 2 pilot trial at nine UK sites. Adults aged 18 years or older and admitted to hospital with COVID-19 symptoms, with a positive RT-PCR or point-of-care test, or both, were randomly assigned (1:1) to receive SNG001 (6 MIU) or placebo by inhalation via a mouthpiece daily for 14 days. The primary outcome was the change in clinical condition on the WHO Ordinal Scale for Clinical Improvement (OSCI) during the dosing period in the intention-to-treat population (all randomised patients who received at least one dose of the study drug). The OSCI is a 9-point scale, where 0 corresponds to no infection and 8 corresponds to death. Multiple analyses were done to identify the most suitable statistical method for future clinical trials. Safety was assessed by monitoring adverse events for 28 days. This trial is registered with Clinicaltrialsregister.eu (2020-001023-14) and ClinicalTrials.gov ( NCT04385095 ); the pilot trial of inpatients with COVID-19 is now completed. Findings Between March 30 and May 30, 2020, 101 patients were randomly assigned to SNG001 (n=50) or placebo (n=51). 48 received SNG001 and 50 received placebo and were included in the intention-to-treat population. 66 (67%) patients required oxygen supplementation at baseline: 29 in the placebo group and 37 in the SNG001 group. Patients receiving SNG001 had greater odds of improvement on the OSCI scale (odds ratio 2·32 [95% CI 1·07–5·04]; p=0·033) on day 15 or 16 and were more likely than those receiving placebo to recover to an OSCI score of 1 (no limitation of activities) during treatment (hazard ratio 2·19 [95% CI 1·03–4·69]; p=0·043). SNG001 was well tolerated. The most frequently reported treatment-emergent adverse event was headache (seven [15%] patients in the SNG001 group and five [10%] in the placebo group). There were three deaths in the placebo group and none in the SNG001 group. Interpretation Patients who received SNG001 had greater odds of improvement and recovered more rapidly from SARS-CoV-2 infection than patients who received placebo, providing a strong rationale for further trials. Funding Synairgen Research.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition (1). The identification of COPD phenotypes may allow stratified treatment approaches that modulate discrete disease mechanisms. Peripheral blood eosinophilia is both a common and repeatable finding in COPD (2). In addition, the presence of a blood/sputum eosinophilia is associated with a significant proportion of COPD exacerbations (3, 4) and a favorable response to systemic steroids (5). However, the role of blood eosinophils in stratifying treatment response to inhaled corticosteroid/long-acting b-agonist combinations is poorly understood.The FORWARD (Foster 48-Week Trial to Reduce Exacerbations in COPD) study was a randomized, double-blind, parallel group trial that compared 48 weeks of treatment with extrafine beclomethasone dipropionate plus formoterol fumarate (BDP/FF), 100/6 mg pressurized metered-dose inhaler, two inhalations twice a day, versus FF 12 mg pressurized metered-dose inhaler, one inhalation twice a day, in patients with severe COPD with a history of exacerbations (clinical trial registered with www.clinicaltrials.gov [NCT 00929851]). The results of the study have been reported (6) and showed a significant reduction in exacerbation rate (28%) and improvement in lung function with BDP/FF compared with FF treatment.Here we evaluate the hypothesis that these treatment differences differ according to the baseline blood eosinophil count by performing a post hoc analysis on the FORWARD study data. MethodsThe median (quartile 1; quartile 3) baseline blood eosinophil count was 181.6 (110.4; 279.8), and the distribution of counts is shown in Figure E1 in the online supplement. The patients (n = 1,184) were stratified into quartile groups on the basis of the baseline eosinophil count. The clinical characteristics of the study population across the quartiles of baseline blood eosinophils are reported in Table E1. The following endpoints were analyzed: COPD exacerbation rate over the course of 48 weeks, using a negative binomial model for adjusted exacerbation rates, Kaplan-Meier analysis, and Cox proportional hazard model for time to first exacerbation event; change from baseline in predose morning FEV 1 at 48 weeks, using a linear mixed model for repeated measurements; and change from baseline in St. George's Respiratory Questionnaire total score at 48 weeks, using an analysis of covariance model. Further details of the models are provided in the online supplement. Additional analyses using percentage eosinophil count thresholds and considering absolute counts as a continuous variable were also performed. A predictive model (see online supplement for details) for future COPD exacerbation rate was estimated, accounting for a variety of baseline factors that may influence exacerbations (7). The effect of baseline blood eosinophil count on adverse events, and in particular pneumonia, was also evaluated. ResultsThe adjusted exacerbation rate in patients receiving BDP/FF was similar across the quartiles, ranging from 0.75 to 0.87 event...

Background:Asthma and COPD are characterized by airway dysfunction and inflammation. Neutrophilic airway inflammation is a common feature of COPD and is recognized in asthma, particularly in severe disease. The T helper (Th) 17 cytokines IL-17A and IL-17F have been implicated in the development of neutrophilic airway inflammation, but their expression in asthma and COPD is uncertain.Methods:We assessed IL-17A and IL-17F expression in the bronchial submucosa from 30 subjects with asthma, 10 ex-smokers with mild to moderate COPD, and 27 nonsmoking and 14 smoking control subjects. Sputum IL-17 concentration was measured in 165 subjects with asthma and 27 with COPD.Results:The median (interquartile range) IL-17A cells/mm2 submucosa was increased in mild to moderate asthma (2.1 [2.4]) compared with healthy control subjects (0.4 [2.8]) but not in severe asthma (P = .04). In COPD, IL-17A+ cells/mm2 submucosa were increased (0.5 [3.7]) compared with nonsmoking control subjects (0 [0]) but not compared with smoking control subjects (P = .046). IL-17F+ cells/mm2 submucosa were increased in severe asthma (2.7 [3.6]) and mild to moderate asthma (1.6 [1.0]) compared with healthy controls subjects (0.7 [1.4]) (P = .001) but was not increased in subjects with COPD. IL-17A and IL-17F were not associated with increased neutrophilic inflammation, but IL-17F was correlated with the submucosal eosinophil count (rs = 0.5, P = .005). The sputum IL-17 concentration in COPD was increased compared with asthma (2 [0-7] pg/mL vs 0 [0-2] pg/mL, P < .0001) and was correlated with post-bronchodilator FEV1% predicted (r = −0.5, P = .008) and FEV1/FVC (r = −0.4, P = .04).Conclusions:Our findings support a potential role for the Th17 cytokines IL-17A and IL-17F in asthma and COPD, but do not demonstrate a relationship with neutrophilic inflammation.

Link to full study: https://clinicaltrials.gov/ct2/show/NCT02123667?term=NCT02123667&rank=1 relevance of SAD, which is present across all severity stages of asthma. It is particularly present in severe disease, likely reflecting structural lung changes that are not responsive toe the use of oral corticosteroids and/or high dose inhaled corticosteroids. Moreover, SAD relates to asthma stability, severity, quality of life, exacerbation rates and health care utilization and can be delineated by easyto-conduct, clinically applicable measures such as IOS and spirometry. Therefore, this aspect of asthma needs further consideration in the management of the disease.

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Background-Airway smooth muscle (ASM) hyperplasia is a hallmark of asthma that is associated with disease severity and persistent airflow obstruction.