Previously reported markers of small airway obstruction do not appear to be independently associated with asthma disease expression. In contrast, the IOS parameter R20, a marker of mean airway resistance of both large and small airways, appears to have independent clinical significance. These observations require confirmation in prospective longitudinal studies.

Background: Severe asthma is characterised by a variety of symptoms, which include chronic cough, however the mechanisms responsible for cough reflex hypersensitivity in asthma remain poorly elucidated. Current asthma patient-related outcome instruments such as the six-point Juniper Asthma Control Score (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ) were not primarily designed to capture cough and its related morbidity in asthma. The Leicester Cough Questionnaire (LCQ) is a patient-related outcome instrument designed to capture the health-related quality of life associated with cough. To date the LCQ has not been evaluated in a severe asthma population. Methods: We evaluated 262 extensively characterised adult patients with severe asthma attending the Leicester Severe Asthma Service. All patients had a clinician diagnosis of asthma and objective physiological evidence and met the ATS/ERS criterion for servere asthma. In all patients we evaluated a) the LCQ distribution and b) the relationships between the LCQ and ACQ-6, AQLQ, airway inflammation in sputum. Results: The LCQ demonstrated the following properties; mean: 15.0, standard deviation: 4.54, median: 15.48, and range: 11.6-19.2. We found a moderate correlation between LCQ and ACQ-6 (r = − 0.605, p < 0.0001) and a LCQ and AQLQ (r = 0.710, p < 0.0001). There was no relationship between LCQ and log 10 sputum percentage eosinophils (%). Conclusion: A proportion of patients with severe asthma have a significant degree of cough-related morbidity that appears independent of eosinophilic airway inflammation and is not captured fully by existing asthma patient-reported outcome instruments. Our preliminary findings suggest that further research is now required to validate the LCQ and its responsiveness in severe asthma populations to capture cough-related morbidity and response to specific interventions.

ObjectivesTo assess the applicability of risk factors for severe COVID-19 defined in the general population for patients on haemodialysis.SettingA retrospective cross-sectional study performed across thirty four haemodialysis units in midlands of the UK.ParticipantsAll 274 patients on maintenance haemodialysis who tested positive for SARS-CoV-2 on PCR testing between March and August 2020, in participating haemodialysis centres.ExposureThe utility of obesity, diabetes status, ethnicity, Charlson Comorbidity Index (CCI) and socioeconomic deprivation scores were investigated as risk factors for severe COVID-19.Main outcomes and measuresSevere COVID-19, defined as requiring supplemental oxygen or respiratory support, or a C reactive protein of ≥75 mg/dL (RECOVERY trial definitions), and its association with obesity, diabetes status, ethnicity, CCI, and socioeconomic deprivation.Results63.5% (174/274 patients) developed severe disease. Socioeconomic deprivation associated with severity, being most pronounced between the most and least deprived quartiles (OR 2.81, 95% CI 1.22 to 6.47, p=0.015), after adjusting for age, sex and ethnicity. There was no association between obesity, diabetes status, ethnicity or CCI with COVID-19 severity. We found no evidence of temporal evolution of cases (p=0.209) or clustering that would impact our findings.ConclusionThe incidence of severe COVID-19 is high among patients on haemodialysis; this cohort should be considered high risk. There was strong evidence of an association between socioeconomic deprivation and COVID-19 severity. Other risk factors that apply to the general population may not apply to this cohort.

BackgroundAsthma and COPD continue to cause considerable diagnostic and treatment stratification challenges. Volatile Organic Compounds (VOCs) have been proposed as feasible diagnostic and monitoring biomarkers in airways diseases.AimsTo conduct a systematic review evaluating (i) the diagnostic accuracy of VOCs in diagnosing airways diseases, (ii) understand the relationship between reported VOCs and biomarkers of type-2 inflammation, (iii) assess the standardisation of reporting according to STARD and TRIPOD criteria, (iv) review current methods of breath sampling and analysisMethodsA PRISMA-oriented systematic search was conducted (January 1997–December 2020). Search terms included: “asthma”, “volatile organic compound(s)”, “VOC”, and “COPD”. Two independent reviewers examined the extracted titles against review objectives.Results44 full-text papers were included. 40/44 studies were cross-sectional and 4 studies were interventional in design. 17/44 studies used sensor-array technologies (e.g. eNose). Cross-study comparison was not possible across identified studies due to the heterogeneity in design. The commonest airways diseases differentiating VOCs belonged to carbonyl-containing classes (i.e. Aldehydes, Esters, and Ketones) and hydrocarbons (i.e. Alkanes and Alkenes). Although individual markers that are associated with clinical biomarkers of type-2 inflammation were recognised (i.e. Ethane and 3,7–Dimethylnonane for asthma and α-Methylstyrene and Decane for COPD), these were not consistently identified across studies. Only (3/44) reported following STARD or TRIPOD criteria for diagnostic accuracy and multivariate reporting respectively.ConclusionsBreath VOCs show promise as diagnostic biomarkers of airways diseases and for type-2 inflammation profiling. However, future studies should focus on transparent reporting of diagnostic accuracy and multivariate models and continue to focus on chemical identification of volatile metabolites.