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A global pandemic of a new highly contagious disease called COVID-19 resulting from coronavirus (severe acute respiratory syndrome (SARS)-Cov-2) infection was declared in February 2020. Though primarily transmitted through the respiratory system, other organ systems in the body can be affected. Twenty percent of those affected require hospitalization with mechanical ventilation in severe cases. About half of the disease survivors have residual functional deficits that require multidisciplinary specialist rehabilitation. The workforce to deliver the required rehabilitation input is beyond the capacity of existing community services. Strict medical follow-up guidelines to monitor these patients mandate scheduled reviews within 12 weeks post discharge. Due to the restricted timeframe for these events to occur, existing care pathway are unlikely to be able to meet the demand. An innovative integrated post-discharge care pathway to facilitate follow up by acute medical teams (respiratory and intensive care) and a specialist multidisciplinary rehabilitation team is hereby proposed. Such a pathway will enable the monitoring and provision of comprehensive medical assessments and multidisciplinary rehabilitation. This paper proposes that a model of tele-rehabilitation is integrated within the pathway by using digital communication technology to offer quick remote assessment and efficient therapy delivery to these patients. Tele-rehabilitation offers a quick and effective option to respond to the specialist rehabilitation needs of COVID-19 survivors following hospital discharge.

Long COVID (LC), the persistent symptoms ≥12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace. This is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an integrated care pathway (Coverscan™, a multi-organ MRI, and Living with COVID Recovery™, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that integrated care pathway interventions are delivered as \"standard of care\" in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6-10 LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes at 3 months. The trial also includes an economic evaluation which will be described separately. The protocol was reviewed by South Central-Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan™ has UK certification (UKCA 752965). All participants will provide written consent to take part in the trial. The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations. ISRCTN10665760.

Coughing is a symptom of many respiratory diseases. An increased amount of coughs may signal an (upcoming) health issue, while a decreasing amount of coughs may indicate an improved health status. The presence of a cough can be identified by a cough classifier. The cough density fluctuates considerably over the course of a day with a pattern that is highly subject-dependent. This paper provides a case study of cough patterns from Chronic Obstructive Pulmonary Disease (COPD) patients as determined by a stationary semi-automated cough monitor. It clearly demonstrates the variability of cough density over the observation time, its patient specificity and dependence on health status. Furthermore, an earlier established empirical finding of a linear relation between mean and standard deviation of a session’s cough count is validated. An alert mechanism incorporating these findings is described.

The importance of integrated care for complex, multiple long term conditions was acknowledged before the COVID pandemic but remained a challenge. The pandemic and consequent development of Long COVID required rapid adaptation of health services to address the population’s needs, requiring service redesigns including integrated care. This Delphi consensus study was conducted in the UK and found similar integrated care priorities for Long COVID and complex, multiple long term conditions, provided by 480 patients and health care providers, with an 80% consensus rate. The resultant recommendations were based on more than 1400 responses from survey participants and were supported by patients, health care professionals, and by patient charities. Participants identified the need to allocate resources to: support integrated care, provide access to care and treatments that work, provide diagnostic procedures that support the personalization of treatment in an integrated care environment, and enable structural consultation between primary and specialist care settings including physical and mental health care. Based on the findings we propose a model for delivering integrated care by a multidisciplinary team to people with complex multisystem conditions. These recommendations can inform improvements to integrated care for complex, multiple long term conditions and Long COVID at international level.

Background Respiratory viral infections are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon-β is naturally produced in response to viral infection, limiting replication. This exploratory study aimed to demonstrate proof-of-mechanism, and evaluate the efficacy and safety of inhaled recombinant interferon-β1a (SNG001) in COPD. Part 1 assessed the effects of SNG001 on induced sputum antiviral interferon-stimulated gene expression, sputum differential cell count, and respiratory function. Part 2 compared SNG001 and placebo on clinical efficacy, sputum and serum biomarkers, and viral clearance. Methods In Part 1, patients ( N  = 13) with stable COPD were randomised 4:1 to SNG001 or placebo once-daily for three days. In Part 2, patients ( N  = 109) with worsening symptoms and a positive respiratory viral test were randomised 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B (moderate COPD exacerbation [i.e., acute worsening of respiratory symptoms treated with antibiotics and/or oral corticosteroids]). Results In Part 1, SNG001 upregulated sputum interferon gene expression. In Part 2, there were minimal SNG001–placebo differences in the efficacy endpoints; however, whereas gene expression was initially upregulated by viral infection, then declined on placebo, levels were maintained with SNG001. Furthermore, the proportion of patients with detectable rhinovirus (the most common virus) on Day 7 was lower with SNG001. In Group B, serum C-reactive protein and the proportion of patients with purulent sputum increased with placebo (suggesting bacterial infection), but not with SNG001. The overall adverse event incidence was similar with both treatments. Conclusions Overall, SNG001 was well-tolerated in patients with COPD, and upregulated lung antiviral defences to accelerate viral clearance. These findings warrant further investigation in a larger study. Trial registration EU clinical trials register (2017-003679-75), 6 October 2017.

The enduring impact of COVID-19 on patients has been examined in recent studies, leading to the description of Long-COVID. We report the lasting symptom burden of COVID-19 patients from the first wave of the pandemic. All patients with COVID-19 pneumonia discharged from a large teaching hospital trust were offered follow-up. We assessed symptom burden at follow-up using a standardised data collection technique during virtual outpatient clinic appointments. Eighty-six percent of patients reported at least one residual symptom at follow-up. No patients had persistent radiographic abnormalities. The presence of symptoms at follow-up was not associated with the severity of the acute COVID-19 illness. Females were significantly more likely to report residual symptoms including anxiety ( p  = 0.001), fatigue ( p  = 0.004), and myalgia ( p  = 0.022). The presence of long-lasting symptoms is common in COVID-19 patients. We suggest that the phenomenon of Long-COVID may not be directly attributable to the effect of SARS-CoV-2, and believe the biopsychosocial effects of COVID-19 may play a greater role in its aetiology.

Cough is an important symptom of asthma. The objective assessment of chronic cough has been enhanced by the development of ambulatory cough monitoring systems. Mepolizumab has been demonstrated to reduce exacerbations in eosinophilic asthmatics long-term. We evaluate the utility of objective cough count as an outcome measure in severe eosinophilic asthma treated with mepolizumab. Consecutive, consenting patients initiated on treatment with mepolizumab had a 24-h cough count recorded at baseline; this was repeated at 1, 3 and 6 months. Asthma control questionnaire (ACQ) scores and exacerbation frequency were also recorded. The mean 24-h cough count in 11 subjects (8 females, mean age 53.6 years) was 172.4 at baseline; at 1, 3 and 6 months following initiation of treatment this decreased to 101.4, 92 and 70.8, respectively ( p  < 0.02). Significant improvements were also observed in mean ACQ score (3–1.6, p  < 0.01) and exacerbation frequency (5.5 per year – 1.3, p  < 0.01). Objective cough measurement could be used as an early, precise and clinically relevant endpoint in assessing response to asthma therapy.

Background: The role of the gut-lung axis in respiratory disease is increasingly recognised. Much emphasis has been placed on gastro-oesophageal reflux disease; however, oesophageal dysmotility may also play a significant role. Azithromycin, a known prokinetic, has been shown to be of major benefit in a number of respiratory diseases, but the relationship between oesophageal function and the lung has not been examined. Objectives: We assessed the feasibility of performing continuous cough monitoring and repeated high-resolution oesophageal manometry (HROM) in patients with chronic respiratory disease. Design: We conducted an open-label, single-arm, feasibility trial. Methods: Azithromycin 250 mg once daily was given to patients with chronic respiratory disease who reported a chronic cough. All participants were monitored continually for at least 1 week prior to and 4 weeks after azithromycin with the Hyfe Cough Tracker. Participants also had HROM performed at two time-points, immediately before and 4 weeks after initiation of azithromycin. Feasibility outcomes pertaining to recruitment, data quality, and acceptability of trial processes were assessed. Exploratory outcome data for metrics of oesophageal function were also analysed. Results: A total of 30 participants (57% female, mean age 65.2 (SD = 11.3)) were recruited over a 10-month period, giving a recruitment rate of three patients per month in a single centre. A total of 87% (n = 26) of participants completed all three study visits. All pre-specified data quality outcomes met their ‘green’ traffic light stop-go criteria. HROM demonstrated that the majority (52%) of participants had abnormal oesophageal function, as defined by the Chicago Classification, at baseline. Changes in oesophageal function were not significantly associated with changes in objective or subjective cough measures, except for a weakly negative correlation with the Hull Airway Reflux Questionnaire score. Conclusion: A large-scale trial examining the effect of azithromycin on the relationship between oesophageal function and cough in respiratory disease is feasible and acceptable to patients. Trial registration: This trial was prospectively registered ClinicalTrials.gov ID: NCT05469555. Plain language summary Azithromycin and it’s effect on the gut-lung axis in respiratory disease: a feasibility study This study explores the connection between gullet function and cough, particularly in patients with chronic respiratory diseases. It focuses on azithromycin, a medication known to improve many different respiratory conditions. The researchers conducted a trial involving 30 patients who experienced chronic cough. They monitored patients’ coughs continuously and assessed their oesophageal function using a specialized test both before and after starting azithromycin. As oesophageal testing is known to be an invasive procedure, it was vital that the acceptability to patients of this procedure was tested. The trial showed that it is feasible to conduct this type of research, as most participants completed the study and reported that they were not put off by the investigation. The results of this study suggest that a larger clinical trial is required.

Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to age-matched controls. Whole blood flow cytometry was used to measure platelet-monocyte aggregate formation, platelet P-selectin expression and platelet fibrinogen binding at basal levels and following stimulation with platelet agonists. A plasma swap approach was used to assess the effect of IPF plasma on control platelets. Subjects with IPF showed greater platelet reactivity than controls. Platelet P-selectin expression was significantly greater in IPF patients than controls following stimulation with 0.1 µM ADP (1.9% positive ±0.5 (mean ± SEM) versus 0.7%±0.1; p = 0.03), 1 µM ADP (9.8%±1.3 versus 3.3%±0.8; p<0.01) and 10 µM ADP (41.3%±4.2 versus 22.5%±2.6; p<0.01). Platelet fibrinogen binding was also increased, and platelet activation resulted in increased platelet-monocyte aggregate formation in IPF patients. Re-suspension of control platelets in plasma taken from subjects with IPF resulted in increased platelet activation compared to control plasma. IPF patients exhibit increased platelet reactivity compared with controls. This hyperactivity may result from the plasma environment since control platelets exhibit increased activation when exposed to IPF plasma.

For management of chronic respiratory diseases, unobtrusive longitudinal monitoring of cough has been proposed. Such a monitoring system was developed using a classifier trained on an initial observation period. After this initial period, a personalized system is available being optimized for the patient and the particular acoustic environment. Long-term deployment of the system requires that the extracted features and learned model characterizing the coughs (and its environment) are time-invariant. This is studied by an example using annotation of two largely different epochs. The results suggest that time-invariance of the cough sound is sufficiently guaranteed for practical deployment, but that changing acoustic environmental conditions may be a factor to reckon with. Cues for detecting changing situations are discussed.