Patients' acceptance of outcome and experience measurements during hospitalisation for COPD exacerbations: a CICERO Clinical Research Collaboration-European Lung Foundation online patient survey.

Background: The lack of standardised outcome assessments during hospitalisation and follow-up for acute COPD exacerbations has hampered scientific progress and clinical proficiency. The objective of the present study was to evaluate patients' acceptance of selected outcome and experience measurements during hospitalisations for COPD exacerbations and follow-up. Methods: An online survey was held amongst COPD patients in France, Belgium, The Netherlands, Germany and the UK. The European Lung Foundation COPD Patient Advisory Group was involved in the conceptualisation, development and dissemination of the survey. The survey was complementary to a previously obtained expert consensus. We assessed patients' views and acceptance of selected patient-reported outcomes or experiences and corresponding measurement instruments (for dyspnoea, frequent productive cough, health status and hospitalisation experience), and of selected clinical investigations (blood draw, pulmonary function test, 6-min walk test, chest computed tomography, echocardiography). Findings: 200 patients completed the survey. All selected outcomes and experiences were deemed important, and acceptance of their methods of assessment was high. The modified Medical Research Council scale and a numerical rating scale to address dyspnoea, the COPD Assessment Test for quality of life and frequent productive cough, and the Hospital Consumer Assessment of Healthcare Providers and Systems for hospital experiences were the instruments preferred by patients. Consensus on importance of blood draw and spirometry was higher compared with the other investigations. Interpretation: The survey results endorse the use of the selected outcome and experience measurements during hospitalisations for COPD exacerbations. They can be used to optimise standardised and patient-centred care and facilitate multicentric data collection.

DEcancer: Machine learning framework tailored to liquid biopsy based cancer detection and biomarker signature selection.

Cancer is a leading cause of mortality worldwide. Over 50% of cancers are diagnosed late, rendering many treatments ineffective. Existing liquid biopsy studies demonstrate a minimally invasive and inexpensive approach for disease detection but lack parsimonious biomarker selection, exhibit poor cancer detection performance and lack appropriate validation and testing. We established a tailored machine learning pipeline, DEcancer, for liquid biopsy analysis that addresses these limitations and improved performance. In a test set from a published cohort of 1,005 patients including 8 cancer types and 812 cancer-free individuals, DEcancer increased stage 1 cancer detection sensitivity across cancer types from 48 to 90%. In addition, with a test set cohort of patients from a high dimensional proteomics dataset of 61 lung cancer patients and 80 cancer-free individuals, DEcancer's performance using a 14-43 protein panel was comparable to 1,000 original proteins. DEcancer is a promising tool which may facilitate improved cancer detection and management.

Predicting treatment outcomes following an exacerbation of airways disease.

BACKGROUND: COPD and asthma exacerbations result in many emergency department admissions. Not all treatments are successful, often leading to hospital readmissions. AIMS: We sought to develop predictive models for exacerbation treatment outcome in a cohort of exacerbating asthma and COPD patients presenting to the emergency department. METHODS: Treatment failure was defined as the need for additional systemic corticosteroids (SCS) and/or antibiotics, hospital readmissison or death within 30 days of initial emergency department visit. We performed univariate analysis comparing characteristics of patients either given or not given SCS at exacerbation and of patients who succeeded versus failed treatment. Patient demographics, medications and exacerbation symptoms, physiology and biology were available. We developed multivariate random forest models to identify predictors of SCS prescription and for predicting treatment failure. RESULTS: Data were available for 81 patients, 43 (53%) of whom failed treatment. 64 (79%) of patients were given SCS. A random forest model using presence of wheeze at exacerbation and blood eosinophil percentage predicted SCS prescription with area under receiver operating characteristic curve (AUC) 0.69. An 11 variable random forest model (which included medication, previous exacerbations, symptoms and quality of life scores) could predict treatment failure with AUC 0.81. A random forest model using just the two best predictors of treatment failure, namely, visual analogue scale for breathlessness and sputum purulence, predicted treatment failure with AUC 0.68. CONCLUSION: Prediction of exacerbation treatment outcome can be achieved via supervised machine learning combining different predictors at exacerbation. Validation of our predictive models in separate, larger patient cohorts is required.

Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial.

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 400 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 usual care group and one (1%) of 69 participants in the budesonide 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.

Standardisation of Clinical Assessment, Management and Follow-Up of Acute Hospitalised Exacerbation of COPD: A Europe-Wide Consensus.

BACKGROUND: Despite hospitalization for exacerbation being a high-risk event for morbidity and mortality, there is little consensus globally regarding the assessment and management of hospitalised exacerbations of COPD. We aimed to establish a consensus list of symptoms, physiological measures, clinical scores, patient questionnaires and investigations to be obtained at time of hospitalised COPD exacerbation and follow-up. METHODS: A modified Delphi online survey with pre-defined consensus of importance, feasibility and frequency of measures at hospitalisation and follow-up of a COPD exacerbation was undertaken. FINDINGS: A total of 25 COPD experts from 18 countries contributed to all 3 rounds of the survey. Experts agreed that a detailed history and examination were needed. Experts also agreed on which treatments are needed and how soon these should be delivered. Experts recommended that a full blood count, renal function, C-reactive protein and cardiac blood biomarkers (BNP and troponin) should be measured within 4 hours of admission and that the modified Medical Research Council dyspnoea scale (mMRC) and COPD assessment test (CAT) should be performed at time of exacerbation and follow-up. Experts encouraged COPD clinicians to strongly consider discussing palliative care, if indicated, at time of hospitalisation. INTERPRETATION: This Europe-wide consensus document is the first attempt to standardise the assessment and care of patients hospitalised for COPD exacerbations. This should be regarded as the starting point to build knowledge and evidence on patients hospitalised for COPD exacerbations.