Interventional lifestyle and self-management trials: A double-edged sword. Is it time to mandate formal data and safety monitoring?

Worldwide, the number of individuals living with chronic respiratory disease is increasing, because of both new diagnoses but also because people are living longer with their condition.1 Irrespective of the cause of their underlying respiratory condition, those with advanced disease have common physical limitations, psychological comorbidities and complex care needs. Support and care at home is commonly provided by family members, often at significant personal cost,2 and the role these informal caregivers play in patient care is often overlooked. Traditional interventions focus on disease sufferers, however targeting those providing care is a potentially complementary treatment, particularly when trying to improve factors such as adherence to medication, smoking cessation and physical activity

Dupilumab in type 2 airway inflammation-a step forward in targeted therapy for COPD.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent symptoms and airflow limitation due to a combination of small airway obliteration and alveolar destruction.1 Underpinning its diverse nature and phenotypic heterogeneity is a complex interplay of genetics, lung development, dysanapsis, and environmental exposures, in particular cigarette smoking, over time.1 The adoption of precision medicine in fields such as asthma has spurred efforts in phenotyping and endotyping COPD to guide management. </p

Pulmonary Rehabilitation for individuals with persistent symptoms following COVID-19

Topic importance COVID-19 can cause ongoing and persistent symptoms (such as breathlessness and fatigue) that lead to reduced functional capacity. There are parallels in symptoms and functional limitations in adults with post-COVID symptoms and adults with chronic respiratory diseases. Pulmonary Rehabilitation is a key treatment for adults with chronic respiratory diseases with the aims to improve symptom management, increase functional capacity. Given the similarities in presentation and aims, a Pulmonary Rehabilitation programme may be optimally placed to meet the needs of those with ongoing symptoms following COVID-19. Review findings Aerobic and strength training has shown benefit for adults living with Long COVID though there is little evidence on structured education in this population. Breathing pattern disorder is common in adults with Long COVID and considerations to treatment prior to rehabilitation, or alongside rehabilitation are necessary. Considerations to Post Exertional Malaise is important in this population and evidence from the Chronic Fatigue Syndrome literature supports the need for individualisation of exercise programmes, and considerations for those that have an adverse reaction to activity and/or exercise. Summary This narrative review summarises the current evidence of Pulmonary Rehabilitation programmes in a long COVID population. Where the evidence is lacking in long COVID the supporting evidence of these programmes in chronic respiratory diseases has highlighted the importance of aerobic and strength training, considerations for fatigue, potential mechanism for immunology improvement and management of breathing pattern disorders in these programmes.</p

Pulmonary Rehabilitation for individuals with persistent symptoms following COVID-19.

Topic importanceCOVID-19 can cause ongoing and persistent symptoms (such as breathlessness and fatigue) that lead to reduced functional capacity. There are parallels in symptoms and functional limitations in adults with post-COVID symptoms and adults with chronic respiratory diseases. Pulmonary Rehabilitation is a key treatment for adults with chronic respiratory diseases with the aims to improve symptom management, increase functional capacity. Given the similarities in presentation and aims, a Pulmonary Rehabilitation programme may be optimally placed to meet the needs of those with ongoing symptoms following COVID-19.Review findingsAerobic and strength training has shown benefit for adults living with Long COVID though there is little evidence on structured education in this population. Breathing pattern disorder is common in adults with Long COVID and considerations to treatment prior to rehabilitation, or alongside rehabilitation are necessary. Considerations to Post Exertional Malaise is important in this population and evidence from the Chronic Fatigue Syndrome literature supports the need for individualisation of exercise programmes, and considerations for those that have an adverse reaction to activity and/or exercise.SummaryThis narrative review summarises the current evidence of Pulmonary Rehabilitation programmes in a long COVID population. Where the evidence is lacking in long COVID the supporting evidence of these programmes in chronic respiratory diseases has highlighted the importance of aerobic and strength training, considerations for fatigue, potential mechanism for immunology improvement and management of breathing pattern disorders in these programmes

Prognostication of co-morbidity clusters on hospitalisation and mortality in advanced COPD

RationaleAs the prevalence of multimorbidity increases, understanding the impact of isolated comorbidities in people COPD becomes increasingly challenging. A simplified model of common comorbidity patterns may improve outcome prediction and allow targeted therapy.ObjectivesTo assess whether comorbidity phenotypes derived from routinely collected clinical data in people with COPD show differences in risk of hospitalisation and mortality.MethodsTwelve clinical measures related to common comorbidities were collected during annual reviews for people with advanced COPD and k-means cluster analysis performed. Cox proportional hazards with adjustment for covariates was used to determine hospitalisation and mortality risk between clusters.Measurements and main resultsIn 203 participants (age 66 ± 9 years, 60 % male, FEV1%predicted 31 ± 10 %) no comorbidity in isolation was predictive of worse admission or mortality risk. Four clusters were described: cluster A (cardiometabolic and anaemia), cluster B (malnourished and low mood), cluster C (obese, metabolic and mood disturbance) and cluster D (less comorbid). FEV1%predicted did not significantly differ between clusters. Mortality risk was higher in cluster A (HR 3.73 [95%CI 1.09-12.82] p = 0.036) and B (HR 3.91 [95%CI 1.17-13.14] p = 0.027) compared to cluster D. Time to admission was highest in cluster A (HR 2.01 [95%CI 1.11-3.63] p = 0.020). Cluster C was not associated with increased risk of mortality or hospitalisation.ConclusionsDespite presence of advanced COPD, we report striking differences in prognosis for both mortality and hospital admissions for different co-morbidity phenotypes. Objectively assessing the multi-system nature of COPD could lead to improved prognostication and targeted therapy for patients

A proof of concept for continuous, non-invasive, free-living vital signs monitoring to predict readmission following an acute exacerbation of COPD: a prospective cohort study.

Background The use of vital signs monitoring in the early recognition of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) post-hospital discharge is limited. This study investigated whether continuous vital signs monitoring could predict an AECOPD and readmission. Methods 35 people were recruited at discharge following hospitalisation for an AECOPD. Participants were asked to wear an Equivital LifeMonitor during waking hours for 6 weeks and to complete the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a 14-item symptom diary, daily. The Equivital LifeMonitor recorded respiratory rate (RR), heart rate (HR), skin temperature (ST) and physical activity (PA) every 15-s. An AECOPD was classified as mild (by EXACT score), moderate (prescribed oral steroids/antibiotics) or severe (hospitalisation). Results Over the 6-week period, 31 participants provided vital signs and symptom data and 14 participants experienced an exacerbation, of which, 11 had sufficient data to predict an AECOPD. HR and PA were associated with EXACT score (p  Conclusions Increased heart rate and reduced physical activity were associated with worsening symptoms. Even with high-resolution data, the variation in vital signs data remains a challenge for predicting AECOPDs. Respiratory rate and heart rate should be further explored as potential predictors of an impending AECOPD.</p

A proof of concept for continuous, non-invasive, free-living vital signs monitoring to predict readmission following an acute exacerbation of COPD: a prospective cohort study

Background: The use of vital signs monitoring in the early recognition of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) post-hospital discharge is limited. This study investigated whether continuous vital signs monitoring could predict an AECOPD and readmission.  Methods: 35 people were recruited at discharge following hospitalisation for an AECOPD. Participants were asked to wear an Equivital LifeMonitor during waking hours for 6 weeks and to complete the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a 14-item symptom diary, daily. The Equivital LifeMonitor recorded respiratory rate (RR), heart rate (HR), skin temperature (ST) and physical activity (PA) every 15-s. An AECOPD was classified as mild (by EXACT score), moderate (prescribed oral steroids/antibiotics) or severe (hospitalisation).  Results: Over the 6-week period, 31 participants provided vital signs and symptom data and 14 participants experienced an exacerbation, of which, 11 had sufficient data to predict an AECOPD. HR and PA were associated with EXACT score (p Conclusions: Increased heart rate and reduced physical activity were associated with worsening symptoms. Even with high-resolution data, the variation in vital signs data remains a challenge for predicting AECOPDs. Respiratory rate and heart rate should be further explored as potential predictors of an impending AECOPD.  Trial registration: ISRCTN registry; ISRCTN12855961. Registered 07 November 2018—Retrospectively registered, https://www.isrctn.com/ISRCTN12855961</p

Gut-related metabolites are associated with respiratory symptoms in COVID-19: a proof-of-concept study

Gut-related metabolites have been linked with respiratory disease. The crosstalk between the gut and lung suggests that gut health may be compromised in COVID-19. The aims of the present study were to analyse a panel of gut-related metabolites (acetyl-L-carnitine, betaine, choline, L-carnitine, trimethylamine and TMAO) in COVID-19 patients, matched with healthy subjects, and non-COVID-19 respiratory patients. As results, metabolites from this panel are impaired in COVID-19, associated with symptoms (breathlessness and temperature) and able to differentiate between COVID-19 and asthma. Preliminary results show lower levels of betaine appear to be associated with poor outcomes in COVID-19 patients suggesting betaine as a marker of gut microbiome health

Characterisation of volatile organic compounds in hospital indoor air and exposure health risk determination

Several volatile organic compounds (VOCs) have impacts on human health, but little is known about the concentrations of VOCs in the hospital environment. This study characterised VOCs present in clinical assessment rooms. More than 600 samples of air were collected over 31 months (2017–2020) at two hospital sites in Leicester, United Kingdom, and analysed by comprehensive two-dimensional gas chromatography, making this the largest hospital environment database worldwide on VOCs and first such UK study. The most abundant VOCs found were 2-propanol, ethyl chloride, acetone and hexane, with respective mean concentrations of 696.6 μgm−3, 436.5 μgm−3, 83.9 μgm−3 and 58.5 μgm−3. Acetone, 2-propanol and hexane concentrations were 4, 9 and 30-fold higher respectively compared to similar studies performed in other hospitals. Our results showed that the most frequently detected VOCs, with the highest concentrations, were most likely released by healthcare activities, or related to ingress of vehicle emissions. Hazard quotient (HQ) and cancer risk (CR) were calculated to identify the potential risk of VOCs exposure to the health of healthcare workers. No HQs were measured above 1, compared to inhaled US EPA and OEHHA health guidelines for non-cancer chemicals. For both hospitals, trichloroethylene CR were calculated above 1E-06 by using inhaled US EPA cancer risk values, leading to possible risks to healthcare workers with long-term exposure. More studies of this type, including measurements of VOCs such as formaldehyde that we were unable to include in this study, are needed to better characterise exposures and risks, both to healthcare workers and patients.</p

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study

Background The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. Methods One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. Results Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. Conclusions Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.</p