Early specialist palliative care on quality of life for malignant pleural mesothelioma: a randomised controlled trial.

PURPOSE: Malignant pleural mesothelioma (MPM) has a high symptom burden and poor survival. Evidence from other cancer types suggests some benefit in health-related quality of life (HRQoL) with early specialist palliative care (SPC) integrated with oncological services, but the certainty of evidence is low. METHODS: We performed a multicentre, randomised, parallel group controlled trial comparing early referral to SPC versus standard care across 19 hospital sites in the UK and one large site in Western Australia. Participants had newly diagnosed MPM; main carers were additionally recruited. INTERVENTION: review by SPC within 3 weeks of allocation and every 4 weeks throughout the study. HRQoL was assessed at baseline and every 4 weeks with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30. PRIMARY OUTCOME: change in EORTC C30 Global Health Status 12 weeks after randomisation. RESULTS: Between April 2014 and October 2016, 174 participants were randomised. There was no significant between group difference in HRQoL score at 12 weeks (mean difference 1.8 (95% CI -4.9 to 8.5; p=0.59)). HRQoL did not differ at 24 weeks (mean difference -2.0 (95% CI -8.6 to 4.6; p=0.54)). There was no difference in depression/anxiety scores at 12 weeks or 24 weeks. In carers, there was no difference in HRQoL or mood at 12 weeks or 24 weeks, although there was a consistent preference for care, favouring the intervention arm. CONCLUSION: There is no role for routine referral to SPC soon after diagnosis of MPM for patients who are cared for in centres with good access to SPC when required. TRIAL REGISTRATION NUMBER: ISRCTN18955704.

Respiratory Pathogens at Exacerbation in Chronic Bronchitis With Airway Bacterial Colonisation: A Cohort Study.

BACKGROUND AND OBJECTIVE: COPD and bronchiectasis are common causes of morbidity, particularly around exacerbation. Colonisation with respiratory pathogens can increase the frequency and severity of exacerbations. However, bacterial and viral presence at exacerbation in people with airway colonisation has not been well studied. METHODS: A 6-month cohort study of participants (n = 30) with chronic bronchitis due to bronchiectasis (n = 26) and/or COPD (n = 13) and colonisation with Pseudomonas aeruginosa or Haemophilus influenzae was proven on two sputum cultures at exacerbation in the previous 12 months. Participants were provided self-management education and collected sputum samples daily. Sputum samples at baseline (at least 14 days before or after an exacerbation) and at each exacerbation were examined for a panel of 34 respiratory pathogens using commercially available RT-PCR kits and compared to results obtained using culture methods for the detection of bacteria. RESULTS: Participants provided 29 baseline samples and 71 samples at exacerbation. In 17/29 baseline samples, RT-PCR analysis confirmed the organism demonstrated by culture, while 12 samples showed a discrepancy from culture results. Most exacerbations (57.7%) were not associated with acquiring new bacteria or viruses, while 19.8% showed new bacteria, 15.7% new viruses and 7% both new viruses and bacteria. CONCLUSION: Over half of exacerbations were not associated with new organisms in this cohort of participants with chronic bronchitis and colonisation. However, 26.8% demonstrated a new bacterial species in sputum, which is relevant for antibiotic therapy. Baseline RT-PCR and culture results were discordant in one-third of participants.

Predictive Value of Physiological Values and Symptom Scores for Exacerbations in Bronchiectasis and Chronic Obstructive Pulmonary Disease With Frequent Exacerbations: Longitudinal Observational Cohort Study.

BACKGROUND: COPD (chronic obstructive pulmonary disease) and bronchiectasis are common, and exacerbations contribute to their morbidity and mortality. Predictive factors for the frequency of future exacerbations include previous exacerbation frequency and airway colonization. Earlier treatment of exacerbations is likely to reduce severity. OBJECTIVE: This study tested the hypothesis that, in a population with bronchiectasis, COPD, or both who have frequent exacerbations and airway colonization, changes in symptom scores or physiological variables within 10 days prior to an exacerbation would allow the prediction of the event. METHODS: We performed a 6-month, longitudinal, observational, cohort study among 30 participants with bronchiectasis, COPD, or both; at least 2 exacerbations per year; and colonization with Pseudomonas aeruginosa or Haemophilus influenzae. Daily symptom and physiological data were collected, comprising pulse rate, blood pressure, oxygen saturation, peak flow rate, step count, weight, and temperature. Exacerbations (defined as the onset of new antibiotic use for respiratory symptoms) were collected, and predictive values for abnormal values in the 10 days prior to an exacerbation were calculated. RESULTS: A total of 30 participants were recruited, collecting a total of 39,534 physiological and 25,334 symptom data points across 5358 participant-days; these included 78 exacerbations across 27 participants, with the remaining 3 participants not having exacerbations within the 6-month observation period. Peak flow rate, oxygen saturation, and weight were significantly different at the point of exacerbation (all P<.001), but no significant trends around exacerbation were noted and no clinically beneficial predictive value was found in the overall or individually adjusted model. Symptom scores tended to worsen for 10 days on either side of an exacerbation but were of insufficient magnitude for prediction, with area under the receiver operating characteristic curve values of ranging from 0.4 to 0.6. CONCLUSIONS: Within this small cohort with bronchiectasis, COPD, or both and airway colonization, physiological and symptom variables did not show sufficient predictive value for exacerbations to be of clinical utility. The self-management education provided as standard of care may be superior to either of these approaches, but benefit in another or larger cohort cannot be excluded. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/resprot.6636.

MISSION ABC: transforming respiratory care through one-stop multidisciplinary clinics - an observational study.

OBJECTIVES: The Modern Innovative Solutions to Improve Outcomes in Asthma, Breathlessness and Chronic Obstructive Pulmonary Disease (COPD) (MABC) service aimed to enhance disease management for chronic respiratory conditions through specialist multidisciplinary clinics, predominantly in the community. This study assesses the outcomes of these clinics. DESIGN: This study used a prospective, longitudinal, participatory action research approach. SETTING: The study was conducted in primary care practices across Hampshire, UK. PARTICIPANTS: Adults aged 16 years and above with poorly controlled asthma or COPD, as well as those with undifferentiated breathlessness not under specialist care, were included. INTERVENTIONS: Participants received care through the multidisciplinary, specialist-led MABC clinics. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes included disease activity, quality of life and healthcare utilisation. Secondary outcomes encompassed clinic attendance, diagnostic changes, patient activation, participant and healthcare professional experiences and cost-effectiveness. RESULTS: A total of 441 participants from 11 general practitioner practices were recruited. Ninety-six per cent of participants would recommend MABC clinics. MABC assessments led to diagnosis changes for 64 (17%) participants with asthma and COPD and treatment adjustments for 252 participants (57%). Exacerbations decreased significantly from 236 to 30 after attending the clinics (p<0.005), with a mean reduction of 0.53 exacerbation events per participant. Reductions were also seen in unscheduled and out-of-hours primary care attendance, emergency department visits and hospital admissions (all p<0.005). Cost savings from reduced exacerbations and healthcare utilisation offset increased medication costs and clinic expenses. CONCLUSIONS: Specialist-supported multidisciplinary teams in MABC clinics improved diagnosis accuracy and adherence to guidelines. High patient satisfaction, disease control improvements and reduced exacerbations resulted in decreased unscheduled healthcare use and cost savings. TRIAL REGISTRATION NUMBER: NCT03096509.

Capability, Opportunity, and Motivation Model for Behavior Change in People With Asthma: Protocol for a Cross-Sectional Study.

BACKGROUND: Asthma is a common lung condition that cannot be cured, but it can usually be effectively managed using available treatments. Despite this, it is widely acknowledged that 70% of patients do not adhere to their asthma treatment. Personalizing treatment by providing the most appropriate interventions based on the patient's psychological or behavioral needs produces successful behavior change. However, health care providers have limited available resources to deliver a patient-centered approach for their psychological or behavioral needs, resulting in a current one-size-fits-all strategy due to the nonfeasible nature of existing surveys. The solution would be to provide health care professionals with a clinically feasible questionnaire that identifies the patient's personal psychological and behavioral factors related to adherence. OBJECTIVE: We aim to apply the capability, opportunity, and motivation model of behavior change (COM-B) questionnaire to detect a patient's perceived psychological and behavioral barriers to adherence. Additionally, we aim to explore the key psychological and behavioral barriers indicated by the COM-B questionnaire and adherence to treatment in patients with confirmed asthma with heterogeneous severity. Exploratory objectives will include a focus on the associations between the COM-B questionnaire responses and asthma phenotype, including clinical, biological, psychosocial, and behavioral components. METHODS: In a single visit, participants visiting Portsmouth Hospital's asthma clinic with a diagnosis of asthma will be asked to complete a 20-minute questionnaire on an iPad about their psychological and behavioral barriers following the theoretical domains framework and capability, opportunity, and motivation model. Participants' data are routinely collected, including demographics, asthma characteristics, asthma control, asthma quality of life, and medication regime, which will be recorded on an electronic data capture form. RESULTS: The study is already underway, and it is anticipated that the results will be available by early 2023. CONCLUSIONS: The COM-B asthma study will investigate an easily accessible theory-based tool (a questionnaire) for identifying psychological and behavioral barriers in patients with asthma who are not adhering to their treatment. This will provide useful information on the behavioral barriers to asthma adherence and whether or not a questionnaire can be used to identify these needs. The highlighted barriers will improve health care professionals' knowledge of this important subject, and participants will benefit from the study by removing their barriers. Overall, this will enable health care professionals to use effective individualized interventions to support improved medication adherence while also recognizing and meeting the psychological needs of patients with asthma. TRIAL REGISTRATION: ClinicalTrials.gov NCT05643924; https://clinicaltrials.gov/ct2/show/NCT05643924. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44710.

Measurement of Vital Signs by Lifelight Software in Comparison to Standard of Care Multisite Development (VISION-MD): Protocol for an Observational Study.

BACKGROUND: Measuring vital signs (VS) is an important aspect of clinical care but is time-consuming and requires multiple pieces of equipment and trained staff. Interest in the contactless measurement of VS has grown since the COVID-19 pandemic, including in nonclinical situations. Lifelight is an app being developed as a medical device for the contactless measurement of VS using remote photoplethysmography (rPPG) via the camera on smart devices. The VISION-D (Measurement of Vital Signs by Lifelight Software in Comparison to the Standard of Care-Development) and VISION-V (Validation) studies demonstrated the accuracy of Lifelight compared with standard-of-care measurement of blood pressure, pulse rate, and respiratory rate, supporting the certification of Lifelight as a class I Conformité Européenne (CE) medical device. OBJECTIVE: To support further development of the Lifelight app, the observational VISION Multisite Development (VISION-MD) study is collecting high-quality data from a broad range of patients, including those with VS measurements outside the normal healthy range and patients who are critically ill. METHODS: The study is recruiting adults (aged ≥16 years) who are inpatients (some critically ill), outpatients, and healthy volunteers, aiming to cover a broad range of normal and clinically relevant VS values; there are no exclusion criteria. High-resolution 60-second videos of the face are recorded by the Lifelight app while simultaneously measuring VS using standard-of-care methods (automated sphygmomanometer for blood pressure; finger clip sensor for pulse rate and oxygen saturation; manual counting of respiratory rate). Feedback from patients and nurses who use Lifelight is collected via a questionnaire. Data to estimate the cost-effectiveness of Lifelight compared with standard-of-care VS measurement are also being collected. A new method for rPPG signal processing is currently being developed, based on the identification of small areas of high-quality signals in each individual. Anticipated recruitment is 1950 participants, with the expectation that data from approximately 1700 will be used for software development. Data from 250 participants will be retained to test the performance of Lifelight against predefined performance targets. RESULTS: Recruitment began in May 2021 but was hindered by the restrictions instigated during the COVID-19 pandemic. The development of data processing methodology is in progress. The data for analysis will become available from September 2022, and the algorithms will be refined continuously to improve clinical accuracy. The performance of Lifelight compared with that of the standard-of-care measurement of VS will then be tested. Recruitment will resume if further data are required. The analyses are expected to be completed in early 2023. CONCLUSIONS: This study will support the refinement of data collection and processing toward the development of a robust app that is suitable for routine clinical use. TRIAL REGISTRATION: ClinicalTrials.gov NCT04763746; https://clinicaltrials.gov/ct2/show/NCT04763746. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41533.

Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning.

Objective: Clinical triage in coronavirus disease 2019 (COVID-19) places a heavy burden on senior clinicians during a pandemic situation. However, risk stratification based on serum biomarker bioprofiling could be implemented by a larger, nonspecialist workforce. Method: Measures of Complement Activation and inflammation in patientS with CoronAvirus DisEase 2019 (CASCADE) patients (n = 72), (clinicaltrials.gov: NCT04453527), classified as mild, moderate, or severe (by support needed to maintain SpO2 > 93%), and healthy controls (HC, n = 20), were bioprofiled using 76 immunological biomarkers and compared using ANOVA. Spearman correlation analysis on biomarker pairs was visualised via heatmaps. Linear Discriminant Analysis (LDA) models were generated to identify patients likely to deteriorate. An X-Gradient-boost (XGB) model trained on CASCADE data to triage patients as mild, moderate, and severe was retrospectively employed to classify COROnavirus Nomacopan Emergency Treatment for covid 19 infected patients with early signs of respiratory distress (CORONET) patients (n = 7) treated with nomacopan. Results: The LDA models distinctly discriminated between deteriorators, nondeteriorators, and HC, with IL-27, IP-10, MDC, ferritin, C5, and sC5b-9 among the key predictor variables during deterioration. C3a and C5 were elevated in all severity classes vs. HC (p < 0.05). sC5b-9 was elevated in the "moderate" and "severe" categories vs. HC (p < 0.001). Heatmap analysis shows a pairwise increase of negatively correlated pairs with IL-27. The XGB model indicated sC5b-9, IL-8, MCP1, and prothrombin F1 and F2 were key discriminators in nomacopan-treated patients (CORONET study). Conclusion: Distinct immunological fingerprints from serum biomarkers exist within different severity classes of COVID-19, and harnessing them using machine learning enabled the development of clinically useful triage and prognostic tools. Complement-mediated lung injury plays a key role in COVID-19 pneumonia, and preliminary results hint at the usefulness of a C5 inhibitor in COVID-19 recovery.

Combining viral genomics and clinical data to assess risk factors for severe COVID-19 (mortality, ICU admission, or intubation) amongst hospital patients in a large acute UK NHS hospital Trust.

Throughout the COVID-19 pandemic, valuable datasets have been collected on the effects of the virus SARS-CoV-2. In this study, we combined whole genome sequencing data with clinical data (including clinical outcomes, demographics, comorbidity, treatment information) for 929 patient cases seen at a large UK hospital Trust between March 2020 and May 2021. We identified associations between acute physiological status and three measures of disease severity; admission to the intensive care unit (ICU), requirement for intubation, and mortality. Whilst the maximum National Early Warning Score (NEWS2) was moderately associated with severe COVID-19 (A = 0.48), the admission NEWS2 was only weakly associated (A = 0.17), suggesting it is ineffective as an early predictor of severity. Patient outcome was weakly associated with myriad factors linked to acute physiological status and human genetics, including age, sex and pre-existing conditions. Overall, we found no significant links between viral genomics and severe outcomes, but saw evidence that variant subtype may impact relative risk for certain sub-populations. Specific mutations of SARS-CoV-2 appear to have little impact on overall severity risk in these data, suggesting that emerging SARS-CoV-2 variants do not result in more severe patient outcomes. However, our results show that determining a causal relationship between mutations and severe COVID-19 in the viral genome is challenging. Whilst improved understanding of the evolution of SARS-CoV-2 has been achieved through genomics, few studies on how these evolutionary changes impact on clinical outcomes have been seen due to complexities associated with data linkage. By combining viral genomics with patient records in a large acute UK hospital, this study represents a significant resource for understanding risk factors associated with COVID-19 severity. However, further understanding will likely arise from studies of the role of host genetics on disease progression.

Multiple pathways of SARS-CoV-2 nosocomial transmission uncovered by integrated genomic and epidemiological analyses during the second wave of the COVID-19 pandemic in the UK.

Introduction: Throughout the global COVID-19 pandemic, nosocomial transmission has represented a major concern for healthcare settings and has accounted for many infections diagnosed within hospitals. As restrictions ease and novel variants continue to spread, it is important to uncover the specific pathways by which nosocomial outbreaks occur to understand the most suitable transmission control strategies for the future. Methods: In this investigation, SARS-CoV-2 genome sequences obtained from 694 healthcare workers and 1,181 patients were analyzed at a large acute NHS hospital in the UK between September 2020 and May 2021. These viral genomic data were combined with epidemiological data to uncover transmission routes within the hospital. We also investigated the effects of the introduction of the highly transmissible variant of concern (VOC), Alpha, over this period, as well as the effects of the national vaccination program on SARS-CoV-2 infection in the hospital. Results: Our results show that infections of all variants within the hospital increased as community prevalence of Alpha increased, resulting in several outbreaks and super-spreader events. Nosocomial infections were enriched amongst older and more vulnerable patients more likely to be in hospital for longer periods but had no impact on disease severity. Infections appeared to be transmitted most regularly from patient to patient and from patients to HCWs. In contrast, infections from HCWs to patients appeared rare, highlighting the benefits of PPE in infection control. The introduction of the vaccine at this time also reduced infections amongst HCWs by over four-times. Discussion: These analyses have highlighted the importance of control measures such as regular testing, rapid lateral flow testing alongside polymerase chain reaction (PCR) testing, isolation of positive patients in the emergency department (where possible), and physical distancing of patient beds on hospital wards to minimize nosocomial transmission of infectious diseases such as COVID-19.

Evaluation of telehealth support in an integrated respiratory clinic.

Supporting self-management is key in improving disease control, with technology increasingly utilised. We hypothesised the addition of telehealth support following assessment in an integrated respiratory clinic could reduce unscheduled healthcare visits in patients with asthma and COPD. Following treatment optimisation, exacerbation-prone participants or those with difficulty in self-management were offered telehealth support. This comprised automated twice-weekly telephone calls, with a specialist nurse triaging alerts. We performed a matched cohort study assessing additional benefits of the telehealth service, matching by: confirmed diagnosis, age, sex, FEV1 percent predicted, smoking status and ≥1 exacerbation in the last year. Thirty-four telehealth participants were matched to twenty-nine control participants. The telehealth cohort generated 165 alerts, with 29 participants raising at least one alert; 88 (53.5%) alerts received a call discussing self-management, of which 35 (21%) received definitive advice that may otherwise have required an unscheduled healthcare visit. There was a greater reduction in median exacerbation rate across both telehealth groups at 6 months post-intervention (1 to 0, p < 0.001) but not in control groups (0.5 to 0.0, p = 0.121). Similarly, there was a significant reduction in unscheduled GP visits across the telehealth groups (1.5 to 0.0, p < 0.001), but not the control groups (0.5 to 0.0, p = 0.115). These reductions led to cost-savings across all groups, but greater in the telehealth cohorts. The addition of telehealth support to exacerbation-prone patients with asthma or COPD, following comprehensive assessment and treatment optimisation, proved beneficial in reducing exacerbation frequency and unscheduled healthcare visits and thus leads to significant cost-savings for the NHS.Clinical Trial Registration: ClinicalTrials.gov: NCT03096509.

Routine laboratory tests can predict in-hospital mortality in acute exacerbations of COPD.

Chronic obstructive pulmonary disease (COPD) has a rising global incidence and acute exacerbation of COPD (AECOPD) carries a high health-care economic burden. Classification and regression tree (CART) analysis is able to create decision trees to classify risk groups. We analysed routinely collected laboratory data to identify prognostic factors for inpatient mortality with AECOPD from our large district hospital. Data from 5,985 patients with 9,915 admissions for AECOPD over a 7-year period were examined. Randomly allocated training (n = 4,986) or validation (n = 4,929) data sets were developed and CART analysis was used to model the risk of all-cause death during admission. Inpatient mortality was 15.5%, mean age was 71.5 (±11.5) years, 56.2% were male, and mean length of stay was 9.2 (±12.2) days. Of 29 variables used, CART analysis identified three (serum albumin, urea, and arterial pCO(2)) to predict in-hospital mortality in five risk groups, with mortality ranging from 3.0 to 23.4%. C statistic indices were 0.734 and 0.701 on the training and validation sets, respectively, indicating good model performance. The highest-risk group (23.4% mortality) had serum urea >7.35 mmol/l, arterial pCO(2) >6.45 kPa, and normal serum albumin (>36.5 g/l). It is possible to develop clinically useful risk prediction models for mortality using laboratory data from the first 24 h of admission in AECOPD.

The VICTORY (Investigation of Inflammacheck to Measure Exhaled Breath Condensate Hydrogen Peroxide in Respiratory Conditions) Study: Protocol for a Cross-sectional Observational Study.

BACKGROUND: More than 7% of the world's population is living with a chronic respiratory condition. In the United Kingdom, lung disease affects approximately 1 in 5 people, resulting in over 700,000 hospital admissions each year. People with respiratory conditions have several symptoms and can require multiple health care visits and investigations before a diagnosis is made. The tests available can be difficult to perform, especially if a person is symptomatic, leading to poor quality results. A new, easy-to-perform, point-of-care test that can be performed in any health care setting and that can differentiate between various respiratory conditions would have a significant, beneficial impact on the ability to diagnose respiratory diseases. OBJECTIVE: The objective of this study is to use a new handheld device (Inflammacheck) in different respiratory conditions to measure the exhaled breath condensate hydrogen peroxide (EBC H2O2) and compare these results with those of healthy controls and with each other. This study also aims to determine whether the device can measure other parameters, including breath humidity, breath temperature, breath flow dynamics, and end tidal carbon dioxide. METHODS: We will perform a single-visit, cross-sectional observational study of EBC H2O2 levels, as measured by Inflammacheck, in people with respiratory disease and volunteers with no known lung disease. Participants with a confirmed diagnosis of asthma, chronic obstructive pulmonary disease, lung cancer, bronchiectasis, pneumonia, breathing pattern disorder, and interstitial lung disease as well as volunteers with no history of lung disease will be asked to breathe into the Inflammacheck device to record their breath sample. RESULTS: The results from this study will be available in 2022, in anticipation of COVID-19-related delays. CONCLUSIONS: This study will investigate the EBC H2O2, as well as other exhaled breath parameters, for use as a future diagnostic tool.

Developing the Accuracy of Vital Sign Measurements Using the Lifelight Software Application in Comparison to Standard of Care Methods: Observational Study Protocol.

BACKGROUND: Vital sign measurements are an integral component of clinical care, but current challenges with the accuracy and timeliness of patient observations can impact appropriate clinical decision making. Advanced technologies using techniques such as photoplethysmography have the potential to automate noncontact physiological monitoring and recording, improving the quality and accessibility of this essential clinical information. OBJECTIVE: In this study, we aim to develop the algorithm used in the Lifelight software application and improve the accuracy of its estimated heart rate, respiratory rate, oxygen saturation, and blood pressure measurements. METHODS: This preliminary study will compare measurements predicted by the Lifelight software with standard of care measurements for an estimated population sample of 2000 inpatients, outpatients, and healthy people attending a large acute hospital. Both training datasets and validation datasets will be analyzed to assess the degree of correspondence between the vital sign measurements predicted by the Lifelight software and the direct physiological measurements taken using standard of care methods. Subgroup analyses will explore how the performance of the algorithm varies with particular patient characteristics, including age, sex, health condition, and medication. RESULTS: Recruitment of participants to this study began in July 2018, and data collection will continue for a planned study period of 12 months. CONCLUSIONS: Digital health technology is a rapidly evolving area for health and social care. Following this initial exploratory study to develop and refine the Lifelight software application, subsequent work will evaluate its performance across a range of health characteristics, and extended validation trials will support its pathway to registration as a medical device. Innovations in health technology such as this may provide valuable opportunities for increasing the efficiency and accessibility of vital sign measurements and improve health care services on a large scale across multiple health and care settings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14326.

A Study to Investigate the Prevalence of Device-Specific Errors in Inhaler Technique in Adults With Airway Disease (The SCORES Study): Protocol for a Single Visit Prevalence Study.

BACKGROUND: It is a recurring theme in clinical practice that patients using inhaled medications via an inhaler do not use their device to a standard that allows for optimum therapeutic effect, and some studies have shown that up to 90% of people do not use their inhalers properly. Observation and correction of the inhaler technique by health care professionals is advised by both national and international guidelines and should be performed at every opportunity to ensure that the optimum inhaler technique is achieved by the user. This study will provide a greater understanding of the most frequent technique errors made by people using 13 different inhaler types. OBJECTIVE: This study aims to identify and compare inhaler technique errors and their prevalence in adults, using device-specific checklists in accordance with manufacturers' guidelines, for 13 specific inhaler types across all lung conditions and to correlate these errors with possible determinants of poor technique. It also aims to assess the error frequency at each step in the device-specific questionnaires and compare the error rates among device types. METHODS: In a single visit, participants using an inhaler included in the inclusion criteria will have their inhaler technique observed using an identical placebo device, which will be recorded using device-specific checklists, and technique-optimized, or switched to a suitable inhaler. RESULTS: The study is already underway, and it is anticipated that the results will be available by 2022. CONCLUSIONS: The SCORES (Study to Investigate the Prevalence of Device-Specific Errors in Inhaler Technique in Adults With Airway Disease) study will ascertain the prevalence of device-specific inhaler technique errors at each step in the device-specific checklists, compare error rates among 13 device types, and correlate these errors with possible determinants of poor technique. Future work will involve the clarification and classification of these errors into critical and noncritical categories. TRIAL REGISTRATION: ClinicalTrials.gov NCT04262271; https://clinicaltrials.gov/ct2/show/NCT04262271. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26350.

Up-regulation of the extrinsic coagulation pathway in acute asthma--a case study.

INTRODUCTION: In the normal airway, the hemostatic balance is antithrombotic and favors fibrinolysis. Acute asthma is associated with inflammatory cell infiltrate and plasma exudation in the airways. Postmortem specimens following status asthmaticus suggest a role for the activation of the extrinsic coagulation cascade and intraluminal fibrin formation. The authors report a chance observation of fibrin formation in the airways of a patient with moderate asthma 5 days before a severe exacerbation requiring hospital admission. METHODS: Alpha-2 macroglobulin, an index of plasma leakage, coagulation factors, and D-dimers were measured by enzyme-linked immunosorbent assay (ELISA) in hypertonic saline-induced sputum, as part of a study into airway repair in stable asthma. All subjects were required to have stable symptoms and measures of asthma prior to sampling. RESULTS: The subject's baseline forced expiratory volume in one second (FEV(1)) was 94% predicted and fraction of exhaled nitric oxide (FeNO) level was 30 ppb prior to sputum induction. Differential sputum cell count revealed an airways neutrophilia (neutrophils 81.1%, eosinophils 0.19%). D-dimers were 70-fold and 22-fold higher than the median value for patients with stable moderate and severe asthma, respectively. Plasma exudation was 42-fold higher than in stable moderate asthma, but on a par with levels found in severe stable asthma, and locally produced coagulation factors may therefore be involved. Levels of fibrinogen, plasminogen, plasminogen activator inhibitor (PAI)-1 and thrombin-activatable fibrinolysis inhibitor (TAFI) were all at least an order of magnitude higher than those seen in stable moderate or severe asthma. CONCLUSIONS: Acute exacerbation of moderate asthma appears to be associated with a shift to a profibrinogenic, possibly antifibrinolytic, environment in the airways.

COVID-19: A collision of complement, coagulation and inflammatory pathways.

COVID-19 is frequently accompanied by a hypercoagulable inflammatory state with microangiopathic pulmonary changes that can precede the diffuse alveolar damage characteristic of typical acute respiratory distress syndrome (ARDS) seen in other severe pathogenic infections. Parallels with systemic inflammatory disorders such as atypical hemolytic uremic syndrome (aHUS) have implicated the complement pathway in the pathogenesis of COVID-19, and particularly the anaphylatoxins C3a and C5a released from cleavage of C3 and C5, respectively. C5a is a potent cell signalling protein that activates a cytokine storm-a hyper-inflammatory phenomenon-within hours of infection and the innate immune response. However, excess C5a can result in a pro-inflammatory environment orchestrated through a plethora of mechanisms that propagate lung injury, lymphocyte exhaustion, and an immune paresis. Furthermore, disruption of the homeostatic interactions between complement and extrinsic and intrinsic coagulation pathways contributes to a net pro-coagulant state in the microvasculature of critical organs. Fatal COVID-19 has been associated with a systemic inflammatory response accompanied by a pro-coagulant state and organ damage, particularly microvascular thrombi in the lungs and kidneys. Pathologic studies report strong evidence of complement activation. C5 blockade reduces inflammatory cytokines and their manifestations in animal studies, and has shown benefits in patients with aHUS, prompting investigation of this approach in the treatment of COVID-19. This review describes the role of the complement pathway and particularly C5a and its aberrations in highly pathogenic virus infections, and therefore its potential as a therapeutic target in COVID-19.

A randomised controlled feasibility trial of E-health application supported care vs usual care after exacerbation of COPD: the RESCUE trial.

Exacerbations of COPD are one of the commonest causes of admission and readmission to hospital. The role of digital interventions to support self-management in improving outcomes is uncertain. We conducted an open, randomised controlled trial of a digital health platform application (app) in 41 COPD patients recruited following hospital admission with an acute exacerbation. Subjects were randomised to either receive usual care, including a written self-management plan (n = 21), or the myCOPD app (n = 20) for 90 days. The primary efficacy outcome was recovery rate of symptoms measured by COPD assessment test (CAT) score. Exacerbations, readmission, inhaler technique quality of life and patient activation (PAM) scores were also captured by a blinded team. The app was acceptable in this care setting and was used by 17 of the 20 patients with sustained use over the study period. The treatment effect on the CAT score was 4.49 (95% CI: -8.41, -0.58) points lower in the myCOPD arm. Patients' inhaler technique improved in the digital intervention arm (101 improving to 20 critical errors) compared to usual care (100 to 72 critical errors). Exacerbations tended to be less frequent in the digital arm compared to usual care; 34 vs 18 events. Hospital readmissions risk was numerically lower in the digital intervention arm: OR for readmission 0.383 (95% CI: 0.074, 1.987; n = 35). In this feasibility study of the digital self-management platform myCOPD, the app has proven acceptable to patients to use and use has improved exacerbation recovery rates, with strong signals of lower re-exacerbation and readmission rates over 90 days. myCOPD reduced the number of critical errors in inhaler technique compared to usual care with written self-management. This provides a strong basis for further exploration of the use of app interventions in the context of recently hospitalised patients with COPD and informs the potential design of a large multi-centre trial.

An Evaluation of Agreement of Breathing Rates Measured by a Novel Device, Manual Counting, and Other Techniques Used in Clinical Practice: Protocol for the Observational VENTILATE Study.

BACKGROUND: Respiratory rate (RR) is the most sensitive physiological observation to predict clinical deterioration on hospital wards, and poor clinical monitoring has been highlighted as a primary contributor to avoidable mortality. Patients in intensive care have their RR monitored continuously, but this equipment is rarely available on general hospital wards. OBJECTIVE: The primary objective is to assess the accuracy of the RespiraSense device in comparison with other methods currently used in clinical practice. The secondary objective is to assess the accuracy of the RespiraSense device in participants in different positions and when reading aloud. METHODS: A single-center, prospective observational study will investigate the agreement of the RespiraSense device as compared with other device measurements (capnography, electrocardiogram) and the current standard measurement of RR (manual counting by a trained health care professional). The different methods will be employed concurrently on the same participant as part of a single study visit. RESULTS: Recruitment to this study has not yet started as funding decisions are still pending. Therefore, results are not available at this stage. It is anticipated that the data required could be collected within 2 months of first recruitment to the study and data analysis completed within 6 months of the study start date. CONCLUSIONS: The Evaluation of Agreement of Breathing Rates Measured by a Novel Device, Manual Counting, and Other Techniques Used in Clinical Practice (VENTILATE) study will provide further validation of the use of the RespiraSense device in subjects with abnormal respiratory rates. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/15437.

Measurement of FeNO in asthma: what the hospital doctor needs to know.

Asthma is the commonest chronic lung disease. Airway inflammation is a central component of asthma but clinical symptoms of asthma and standard spirometry are insensitive in reflecting the underlying inflammatory processes. Measurement of the fractional nitric oxide concentration in exhaled breath (FeNO) is a quantitative, non-invasive and safe method of measuring airway inflammation. Advances in technology and standardization have made FeNO measurements simple, enabling their use as a biomarker alongside traditional clinical tools in the assessment and management of asthma. Specifically, it can predict responsiveness to steroids and also newer biological therapy, predict future risk of exacerbation and help highlight treatment non-adherence, making it a useful asset to personalized medicine.

Modern Innovative Solutions to Improve Outcomes in Severe Asthma: Protocol for a Mixed Methods Observational Comparison of Clinical Outcomes in MISSION Versus Current Care Delivery.

BACKGROUND: Asthma that is poorly controlled and undertreated can progress to more severe disease that is associated with high levels of unscheduled care that requires high-cost therapy, leading to a significant health economic burden. The identification and appropriate referral to a specialist asthma service is also often delayed by several months or years because of poor recognition and understanding of symptom severity. Current severe asthma services may take several months to provide a comprehensive multidisciplinary assessment, often necessitating multiple hospital visits and costing up to £5000 per patient. OBJECTIVE: This study aims to evaluate whether a new service model could identify poorly controlled and potentially severe asthma much earlier in the patient pathway, and then compare clinical outcomes between this new care model with standard care. METHODS: Modern Innovative Solutions to Improve Outcomes in (MISSION) Severe Asthma is a novel service model developed by asthma specialists from Portsmouth and Southampton severe asthma services. MISSION Severe Asthma identified patients with poorly controlled disease from general practice databases who had not been under secondary outpatient care in the last 12 months or who were not known to secondary care. In 1- or 2-stop assessments, a thorough review of diagnosis, disease phenotype, and control is undertaken, and clinical outcomes collected at baseline. RESULTS: A variety of clinical outcomes will be collected to assess the service model. The results will be reported in February 2020. CONCLUSIONS: This protocol outlines a mixed methods study to assess the impact on disease control, unscheduled health care usage, and quality of life in patients seen in the MISSION clinic compared with a closely matched cohort who declined to attend. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/9585.