Evaluating the impact of a pulse oximetry remote monitoring programme on mortality and healthcare utilisation in patients with COVID-19 assessed in emergency departments in England: a retrospective matched cohort study.

BACKGROUND: To identify the impact of enrolment onto a national pulse oximetry remote monitoring programme for COVID-19 (COVID-19 Oximetry @home; CO@h) on health service use and mortality in patients attending Emergency Departments (EDs). METHODS: We conducted a retrospective matched cohort study of patients enrolled onto the CO@h pathway from EDs in England. We included all patients with a positive COVID-19 test from 1 October 2020 to 3 May 2021 who attended ED from 3 days before to 10 days after the date of the test. All patients who were admitted or died on the same or following day to the first ED attendance within the time window were excluded. In the primary analysis, participants enrolled onto CO@h were matched using demographic and clinical criteria to participants who were not enrolled. Five outcome measures were examined within 28 days of first ED attendance: (1) Death from any cause; (2) Any subsequent ED attendance; (3) Any emergency hospital admission; (4) Critical care admission; and (5) Length of stay. RESULTS: 15 621 participants were included in the primary analysis, of whom 639 were enrolled onto CO@h and 14 982 were controls. Odds of death were 52% lower in those enrolled (95% CI 7% to 75%) compared with those not enrolled onto CO@h. Odds of any ED attendance or admission were 37% (95% CI 16% to 63%) and 59% (95% CI 32% to 91%) higher, respectively, in those enrolled. Of those admitted, those enrolled had 53% (95% CI 7% to 76%) lower odds of critical care admission. There was no significant impact on length of stay. CONCLUSIONS: These findings indicate that for patients assessed in ED, pulse oximetry remote monitoring may be a clinically effective and safe model for early detection of hypoxia and escalation. However, possible selection biases might limit the generalisability to other populations.

Educational opportunities for postgraduate medical trainees during the COVID-19 pandemic: deriving value from old, new and emerging ways of learning.

The COVID-19 pandemic has had a significant impact on postgraduate medical training across all specialties. Although some traditional learning opportunities have been curtailed, there have been numerous examples of highly valuable educational experiences that have arisen during this time. Here, from a trainee perspective, we consider the educational merits of the re-emergence of 'firm-based' teams, new online learning opportunities, use of digital technologies and the rise of telephone clinics and new COVID-19 clinical services. As health services continue to recover from surges in COVID-19 cases, it is important to reflect on and recognise the value of these educational experiences so that helpful elements can be retained and embedded into training programmes for the benefit of both trainees and patients.

Population-level impact of a pulse oximetry remote monitoring programme on mortality and healthcare utilisation in the people with COVID-19 in England: a national analysis using a stepped wedge design.

BACKGROUND: To identify the population-level impact of a national pulse oximetry remote monitoring programme for COVID-19 (COVID Oximetry @home (CO@h)) in England on mortality and health service use. METHODS: We conducted a retrospective cohort study using a stepped wedge pre-implementation and post-implementation design, including all 106 Clinical Commissioning Groups (CCGs) in England implementing a local CO@h programme. All symptomatic people with a positive COVID-19 PCR test result from 1 October 2020 to 3 May 2021, and who were aged ≥65 years or identified as clinically extremely vulnerable were included. Care home residents were excluded. A pre-intervention period before implementation of the CO@h programme in each CCG was compared with a post-intervention period after implementation. Five outcome measures within 28 days of a positive COVID-19 test: (i) death from any cause; (ii) any ED attendance; (iii) any emergency hospital admission; (iv) critical care admission and (v) total length of hospital stay. RESULTS: 217 650 people were eligible and included in the analysis. Total enrolment onto the programme was low, with enrolment data received for only 5527 (2.5%) of the eligible population. The period of implementation of the programme was not associated with mortality or length of hospital stay. The period of implementation was associated with increased health service utilisation with a 12% increase in the odds of ED attendance (95% CI: 6% to 18%) and emergency hospital admission (95% CI: 5% to 20%) and a 24% increase in the odds of critical care admission in those admitted (95% CI: 5% to 47%). In a secondary analysis of CO@h sites with at least 10% or 20% of eligible people enrolled, there was no significant association with any outcome measure. CONCLUSION: At a population level, there was no association with mortality before and after the implementation period of the CO@h programme, and small increases in health service utilisation were observed. However, lower than expected enrolment is likely to have diluted the effects of the programme at a population level.

Targeted Retreatment of Incompletely Recovered Chronic Obstructive Pulmonary Disease Exacerbations with Ciprofloxacin. A Double-Blind, Randomized, Placebo-controlled, Multicenter, Phase III Clinical Trial.

Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are prone to nonrecovery, but there are no data about the effectiveness of retreatment for these prolonged events. We examined whether further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event.Objectives: To assess whether incompletely recovered COPD exacerbations benefit from additional treatment with ciprofloxacin, at Day 14.Methods: In a multicenter, randomized double-blind placebo-controlled trial, we studied retreatment with oral ciprofloxacin 500 mg or matched placebo twice daily for 7 days in patients with Global Initiative for Chronic Obstructive Lung Disease stage II-IV COPD and persistent symptoms and/or serum C-reactive protein ≥8 mg/L initiated 14 (±3) days after an index COPD exacerbation. The primary outcome was the time to the next exacerbation within a 90-day period.Measurements and Main Results: Among 826 patients screened at four centers, 144 eligible participants with incomplete recovery were randomized to receive ciprofloxacin (n = 72) or placebo (n = 72). Within 90 days of randomization, 57% of the patients in the ciprofloxacin group and 53% in the placebo group experienced one or more exacerbations. The median time to the next exacerbation was 32.5 days (interquartile range 13-50) in the placebo arm and 34 days (interquartile range 17-62) in the ciprofloxacin arm, which was not significantly different (adjusted hazard ratio, 1.07; 95% confidence interval, 0.68-1.68; P = 0.76). No significant differences were seen in quality-of-life scores or lung function between the treatment groups.Conclusions: In patients with persistent symptoms and/or raised C-reactive protein 14 days after a COPD exacerbation, an additional course of ciprofloxacin resulted in no additional benefit compared with placebo. This suggests that nonrecovered exacerbations are not driven by ongoing bacterial infection and may potentially be targeted with antiinflammatory therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02300220).

Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have increased susceptibility to respiratory tract infection, which contributes to disease progression and mortality, but mechanisms of increased susceptibility to infection remain unclear. OBJECTIVES: The aim of this study was to determine whether glucose concentrations were increased in airway samples (nasal lavage fluid, sputum, and bronchoalveolar lavage fluid) from patients with stable COPD and to determine the effects of viral infection on sputum glucose concentrations and how airway glucose concentrations relate to bacterial infection. METHODS: We measured glucose concentrations in airway samples collected from patients with stable COPD and smokers and nonsmokers with normal lung function. Glucose concentrations were measured in patients with experimentally induced COPD exacerbations, and these results were validated in patients with naturally acquired COPD exacerbations. Relationships between sputum glucose concentrations, inflammatory markers, and bacterial load were examined. RESULTS: Sputum glucose concentrations were significantly higher in patients with stable COPD compared with those in control subjects without COPD. In both experimental virus-induced and naturally acquired COPD exacerbations, sputum and nasal lavage fluid glucose concentrations were increased over baseline values. There were significant correlations between sputum glucose concentrations and sputum inflammatory markers, viral load, and bacterial load. Airway samples with higher glucose concentrations supported more Pseudomonas aeruginosa growth in vitro. CONCLUSIONS: Airway glucose concentrations are increased in patients with stable COPD and further increased during COPD exacerbations. Increased airway glucose concentrations might contribute to bacterial infections in both patients with stable and those with exacerbated COPD. This has important implications for the development of nonantibiotic therapeutic strategies for the prevention or treatment of bacterial infection in patients with COPD.

Ikarugamycin: A Natural Product Inhibitor of Clathrin-Mediated Endocytosis.

Ikarugamycin (IKA) is a previously discovered antibiotic, which has been shown to inhibit the uptake of oxidized low-density lipoproteins in macrophages. Furthermore, several groups have previously used IKA to inhibit clathrin-mediated endocytosis (CME) in plant cell lines. However, detailed characterization of IKA has yet to be performed. Consequently, we performed biochemistry and microscopy experiments to further characterize the effects of IKA on CME. We show that IKA has an IC50 of 2.7 µm in H1299 cells and acutely inhibits CME, but not other endocytic pathways, in a panel of cell lines. Although long-term incubation with IKA has cytotoxic effects, the short-term inhibitory effects on CME are reversible. Thus, IKA can be a useful tool for probing routes of endocytic trafficking.

Socioeconomic deprivation and the outcome of pulmonary rehabilitation in England and Wales.

BACKGROUND: Pulmonary rehabilitation (PR) improves exercise capacity and health status in patients with COPD, but many patients assessed for PR do not complete therapy. It is unknown whether socioeconomic deprivation associates with rates of completion of PR or the magnitude of clinical benefits bequeathed by PR. METHODS: PR services across England and Wales enrolled patients to the National PR audit in 2015. Deprivation was assessed using Index of Multiple Deprivation (IMD) derived from postcodes. Study outcomes were completion of therapy and change in measures of exercise performance and health status. Univariate and multivariate analyses investigated associations between IMD and these outcomes. RESULTS: 210 PR programmes enrolled 7413 patients. Compared with the general population, the PR sample lived in relatively deprived neighbourhoods. There was a statistically significant association between rates of completion of PR and quintile of deprivation (70% in the least and 50% in the most deprived quintiles). After baseline adjustments, the risk ratio (95% CI) for patients in the most deprived relative to the least deprived quintile was 0.79 (0.73 to 0.85), p<0.001. After baseline adjustments, IMD was not significantly associated with improvements in exercise performance and health status. CONCLUSIONS: In a large national dataset, we have shown that patients living in more deprived areas are less likely to complete PR. However, deprivation was not associated with clinical outcomes in patients who complete therapy. Interventions targeted at enhancing referral, uptake and completion of PR among patients living in deprived areas could reduce morbidity and healthcare costs in such hard-to-reach populations.

COPD Multidisciplinary Team Meetings in the United Kingdom: Health Care Professionals' Perceptions of Aims and Structure.

Over the last 10 years, community and hospital-based multidisciplinary teams (MDTs) have been set up for the management of patients with chronic obstructive pulmonary disease (COPD) in the UK. Meetings of the MDTs have become a regular occurrence, mostly on healthcare professionals' own initiatives. There are no standardized methods to conduct an MDT meeting, and although cancer MDT meetings are widely implemented, the value and purpose of COPD MDT meetings are less clear. Therefore, the aim of this study was to conduct a cross-sectional descriptive online survey to explore COPD MDT members' perceptions of the purpose and usefulness of MDT meetings, and to identify suggestions or requirements to improve the meetings. In total, we received 68 responses from 10 MDTs; six teams (n = 36 members) were located in London and four (n = 32 members) outside. Analysis of the replies by two independent researchers found that MDT meetings aim to optimise management and improve pathways for respiratory patients by improving communication between providers across settings and disciplines. Education of the MDT members also occurs with the aim of safer practice. Discussed patients are characterised by (multiple) co-morbidities, frequent exacerbations and admissions, social and mental health problems, unclear diagnosis and suboptimal responses to interventions. Members reported participating in a COPD MDT as very useful (74%) or useful (20%). Meetings could be improved by ensuring attendance through requirement in job plans, by clear documentation and sharing of derived plans with a wider audience including general practitioners and patients.

Endocytic pathways and endosomal trafficking: a primer.

This brief overview of endocytic trafficking is written in honor of Renate Fuchs, who retires this year. In the mid-1980s, Renate pioneered studies on the ion-conducting properties of the recently discovered early and late endosomes and the mechanisms governing endosomal acidification. As described in this review, after uptake through one of many mechanistically distinct endocytic pathways, internalized proteins merge into a common early/sorting endosome. From there they again diverge along distinct sorting pathways, back to the cell surface, on to the trans-Golgi network or across polarized cells. Other transmembrane receptors are packaged into intraluminal vesicles of late endosomes/multivesicular bodies that eventually fuse with and deliver their content to lysosomes for degradation. Endosomal acidification, in part, determines sorting along this pathway. We describe other sorting machinery and mechanisms, as well as the rab proteins and phosphatidylinositol lipids that serve to dynamically define membrane compartments along the endocytic pathway.

Breath metabolite response to major upper gastrointestinal surgery.

BACKGROUND: Esophagectomy and gastrectomy are associated with profound metabolic changes and significant postoperative morbidity. The aim of this prospective clinical study was to determine whether breath analysis can offer novel insight into the surgical metabolic response and identify biomarkers of postoperative complications, including lung injury. METHODS: Breath samples were collected preoperatively and at 24, 48, 72, 96 and 168 h after esophagectomy (n = 25) and gastrectomy (n = 15). Targeted analysis of four prominent breath metabolites was performed by selected ion flow-tube mass spectrometry. Patients with nonsurgical lung injury (community-acquired pneumonia) were recruited as positive controls. RESULTS: Perioperative starvation and subsequent reintroduction of nutritional input were associated with significant changes in breath acetone levels. Breath acetone levels fell after esophagectomy (P = 0.008) and were significantly lower than in gastrectomy patients at postoperative time points 48 (P < 0.001) and 72 h (P < 0.001). In contrast, concentrations of isoprene increased significantly after esophagectomy (P = 0.014). Pneumonia was the most frequently observed postoperative complication (esophagectomy 36% and gastrectomy 7%). The concentration of hydrogen cyanide was significantly lower in the breath of patients who developed pneumonia, 72 h after surgery (P = 0.008). Exhaled hydrogen cyanide (P = 0.001) and isoprene (P = 0.014) were also reduced in patients with community-acquired pneumonia compared with healthy controls. CONCLUSIONS: Selected ion flow-tube mass spectrometry can be used as a totally noninvasive resource to monitor multiple aspects of metabolic alterations in the postoperative period. Exhaled concentrations of several prominent metabolites are significantly altered after major upper gastrointestinal surgery and in response to pneumonia.

Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease.

RATIONALE: Rhinovirus infection is followed by significantly increased frequencies of positive, potentially pathogenic sputum cultures in chronic obstructive pulmonary disease (COPD). However, it remains unclear whether these represent de novo infections or an increased load of organisms from the complex microbial communities (microbiome) in the lower airways. OBJECTIVES: To investigate the effect of rhinovirus infection on the airway bacterial microbiome. METHODS: Subjects with COPD (n = 14) and healthy control subjects with normal lung function (n = 17) were infected with rhinovirus. Induced sputum was collected at baseline before rhinovirus inoculation and again on Days 5, 15, and 42 after rhinovirus infection and DNA was extracted. The V3-V5 region of the bacterial 16S ribosomal RNA gene was amplified and pyrosequenced, resulting in 370,849 high-quality reads from 112 of the possible 124 time points. MEASUREMENTS AND MAIN RESULTS: At 15 days after rhinovirus infection, there was a sixfold increase in 16S copy number (P = 0.007) and a 16% rise in numbers of proteobacterial sequences, most notably in potentially pathogenic Haemophilus influenzae (P = 2.7 × 10(-20)), from a preexisting community. These changes occurred only in the sputum microbiome of subjects with COPD and were still evident 42 days after infection. This was in contrast to the temporal stability demonstrated in the microbiome of healthy smokers and nonsmokers. CONCLUSIONS: After rhinovirus infection, there is a rise in bacterial burden and a significant outgrowth of Haemophilus influenzae from the existing microbiota of subjects with COPD. This is not observed in healthy individuals. Our findings suggest that rhinovirus infection in COPD alters the respiratory microbiome and may precipitate secondary bacterial infections.

Improving Quality in Adult Long Covid Services: Findings from the LOCOMOTION Quality Improvement Collaborative.

The protracted form of COVID-19 known as 'long covid' was first described in 2020. Its symptoms, course and prognosis vary widely; some patients have a multi-system, disabling and prolonged illness. In 2021, ring-fenced funding was provided to establish 90 long covid clinics in England; some clinics were also established in Scotland and Wales. The NIHR-funded LOCOMOTION project implemented a UK-wide quality improvement collaborative involving ten of these clinics, which ran from 2021 to 2023. At regular online meetings held approximately 8-weekly, participants prioritized topics, discussed research evidence and guidelines, and presented exemplar case histories and clinic audits. A patient advisory group also held a priority-setting exercise, participated in quality meetings and undertook a service evaluation audit. The goal of successive quality improvement cycles aimed at changing practice to align with evidence was sometimes hard to achieve because definitive evidence did not yet exist in this new condition; many patients had comorbidities; and clinics were practically constrained in various ways. Nevertheless, much progress was made and a series of 'best practice' guides was produced, covering general assessment and management; breathing difficulties; orthostatic tachycardia and other autonomic symptoms; fatigue and cognitive impairment; and vocational rehabilitation. This paper summarises key findings with the front-line clinician in mind.

Singing for lung health in COPD: a multicentre randomised controlled trial of online delivery.

BACKGROUND: Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach. METHODS: We conducted an assessor-blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH sessions against usual care on health-related quality of life, assessed using the RAND 36-Item Short Form Health Survey (SF-36) Mental Health Composite (MHC) and Physical Health Composite (PHC) scores. RESULTS: We enrolled 115 people with stable chronic obstructive pulmonary disease (COPD), median (IQR) age 69 (62-74), 56.5% females, 80% prior pulmonary rehabilitation, Medical Research Council dyspnoea scale 4 (3-4), forced expiratory volume in 1 s % predicted 49 (35-63). 50 participants in each arm completed the study. The intervention arm experienced improvements in physical but not mental health components of RAND SF-36; PHC (regression coefficient (95% CI): 1.77 (95% CI 0.11 to 3.44); p=0.037), but not MHC (0.86 (95% CI -1.68 to 3.40); p=0.504). A prespecified responder analysis based on achieving a 10% improvement from baseline demonstrated a response rate for PHC of 32% in the SLH arm and 12.7% for usual care (p=0.024). A between-group difference in responder rate was not found in relation to the MHC (19.3% vs 25.9%; p=0.403). DISCUSSION AND CONCLUSION: A 12-week online SLH programme can improve the physical component of quality of life for people with COPD, but the overall effect is relatively modest compared with the impact seen in research using face-to-face group sessions. Further work on the content, duration and dose of online interventions may be useful. TRIAL REGISTRATION NUMBER: NCT04034212.

A broad specificity nucleoside kinase from Thermoplasma acidophilum.

The crystal structure of Ta0880, determined at 1.91 Å resolution, from Thermoplasma acidophilum revealed a dimer with each monomer composed of an α/ß/α sandwich domain and a smaller lid domain. The overall fold belongs to the PfkB family of carbohydrate kinases (a family member of the Ribokinase clan) which include ribokinases, 1-phosphofructokinases, 6-phosphofructo-2-kinase, inosine/guanosine kinases, fructokinases, adenosine kinases, and many more. Based on its general fold, Ta0880 had been annotated as a ribokinase-like protein. Using a coupled pyruvate kinase/lactate dehydrogenase assay, the activity of Ta0880 was assessed against a variety of ribokinase/pfkB-like family substrates; activity was not observed for ribose, fructose-1-phosphate, or fructose-6-phosphate. Based on structural similarity with nucleoside kinases (NK) from Methanocaldococcus jannaschii (MjNK, PDB 2C49, and 2C4E) and Burkholderia thailandensis (BtNK, PDB 3B1O), nucleoside kinase activity was investigated. Ta0880 (TaNK) was confirmed to have nucleoside kinase activity with an apparent KM for guanosine of 0.21 µM and catalytic efficiency of 345,000 M(-1) s(-1) . These three NKs have significantly different substrate, phosphate donor, and cation specificities and comparisons of specificity and structure identified residues likely responsible for the nucleoside substrate selectivity. Phylogenetic analysis identified three clusters within the PfkB family and indicates that TaNK is a member of a new sub-family with broad nucleoside specificities. Proteins 2013. © 2012 Wiley Periodicals, Inc.

Neutrophil adhesion molecules in experimental rhinovirus infection in COPD.

BACKGROUND: COPD exacerbations are associated with neutrophilic airway inflammation. Adhesion molecules on the surface of neutrophils may play a key role in their movement from blood to the airways. We analysed adhesion molecule expression on blood and sputum neutrophils from COPD subjects and non-obstructed smokers during experimental rhinovirus infections. METHODS: Blood and sputum were collected from 9 COPD subjects and 10 smoking and age-matched control subjects at baseline, and neutrophil expression of the adhesion molecules and activation markers measured using flow cytometry. The markers examined were CD62L and CD162 (mediating initial steps of neutrophil rolling and capture), CD11a and CD11b (required for firm neutrophil adhesion), CD31 and CD54 (involved in neutrophil transmigration through the endothelial monolayer) and CD63 and CD66b (neutrophil activation markers). Subjects were then experimentally infected with rhinovirus-16 and repeat samples collected for neutrophil analysis at post-infection time points. RESULTS: At baseline there were no differences in adhesion molecule expression between the COPD and non-COPD subjects. Expression of CD11a, CD31, CD62L and CD162 was reduced on sputum neutrophils compared to blood neutrophils. Following rhinovirus infection expression of CD11a expression on blood neutrophils was significantly reduced in both subject groups. CD11b, CD62L and CD162 expression was significantly reduced only in the COPD subjects. Blood neutrophil CD11b expression correlated inversely with inflammatory markers and symptom scores in COPD subjects. CONCLUSION: Following rhinovirus infection neutrophils with higher surface expression of adhesion molecules are likely preferentially recruited to the lungs. CD11b may be a key molecule involved in neutrophil trafficking in COPD exacerbations.

Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with virus (mostly rhinovirus) and bacterial infections, but it is not known whether rhinovirus infections precipitate secondary bacterial infections. OBJECTIVES: To investigate relationships between rhinovirus infection and bacterial infection and the role of antimicrobial peptides in COPD exacerbations. METHODS: We infected subjects with moderate COPD and smokers and nonsmokers with normal lung function with rhinovirus. Induced sputum was collected before and repeatedly after rhinovirus infection and virus and bacterial loads measured with quantitative polymerase chain reaction and culture. The antimicrobial peptides secretory leukoprotease inhibitor (SLPI), elafin, pentraxin, LL-37, α-defensins and ß-defensin-2, and the protease neutrophil elastase were measured in sputum supernatants. MEASUREMENTS AND MAIN RESULTS: After rhinovirus infection, secondary bacterial infection was detected in 60% of subjects with COPD, 9.5% of smokers, and 10% of nonsmokers (P < 0.001). Sputum virus load peaked on Days 5-9 and bacterial load on Day 15. Sputum neutrophil elastase was significantly increased and SLPI and elafin significantly reduced after rhinovirus infection exclusively in subjects with COPD with secondary bacterial infections, and SLPI and elafin levels correlated inversely with bacterial load. CONCLUSIONS: Rhinovirus infections are frequently followed by secondary bacterial infections in COPD and cleavage of the antimicrobial peptides SLPI and elafin by virus-induced neutrophil elastase may precipitate these secondary bacterial infections. Therapy targeting neutrophil elastase or enhancing innate immunity may be useful novel therapies for prevention of secondary bacterial infections in virus-induced COPD exacerbations.

Breathlessness and skeletal muscle weakness in patients undergoing lung health screening in primary care.

Earlier diagnosis of COPD is a major public health challenge as symptoms may be attributed to the normal consequences of aging. The optimum strategy for identifying patients with COPD remains to be determined. People aged 35 and over (n = 1896) on a GP practice register were randomised to either invitation or an opportunistic lung health check which included spirometry, quadriceps strength and MRC dyspnoea score. Then, 101 participants subsequently completed the General Practice Physical Activity Questionnaire. A total of 335 attended over a 15-week period; 156 were in the invitation group and 179 from the opportunist group. In 25 persons, spirometry was unsatisfactory or contraindicated. Spirometry was normal in 204(65.8%) and restrictive in 36(11.6%). 70(22.6%) had airflow obstruction, corresponding to Global Initiative for Chronic Lung Disease (GOLD) stages I-IV in 18(5.8%), 35(11.3%), 14(4.5%) and 3(1.0%), respectively. The opportunist group were significantly more likely to have airflow obstruction 30.1% vs 14.3% (p = 0.001). Breathlessness was reported commonly (40.5%) and quadriceps strength correlated significantly with MRC dyspnoea score independent of age, sex, pack-years smoked, fat-free mass and FEV(1) percent predicted. This relationship was also present in the subgroup of healthy participants (n = 143). 51.5% of participants screened were classified as "inactive" and this group were weaker and more breathless than those who were more active. Airflow obstruction was more common in those screened opportunistically. Breathlessness and inactivity are common in patients taking part in spirometry screening. Breathlessness is significantly associated with leg strength independent of spirometry and should be amenable to interventions to increase physical activity.

Finding the missing millions - the impact of a locally enhanced service for COPD on current and projected rates of diagnosis: a population-based prevalence study using interrupted time series analysis.

BACKGROUND: Many patients with chronic obstructive pulmonary disease (COPD) are not identified until their condition is relatively advanced and there is a considerable gap between the modelled and diagnosed prevalence of the disease. We have previously shown that, in the first year after the introduction of a locally enhanced service (LES) for COPD in 2008, there was a significant step-up in the diagnosed prevalence. AIMS: To investigate whether this initial increase in prevalence was sustained, and the impact of this increase on future projected rates of COPD diagnosis. METHODS: Using data from 2005-2011, we compared the prevalence of diagnosed COPD in the LES Primary Care Trust (LES-PCT) before and after it was introduced. Data were compared with a neighbouring PCT, the London Strategic Health Authority, and England. The true prevalence of COPD was estimated based on data from the Health Survey for England. Trends were extrapolated to estimate the proportion of patients that would be diagnosed in 2017. RESULTS: The introduction of the LES was associated with a significant acceleration in the annual increase in diagnosed COPD (p<0.0001). By 2011 the prevalence was 1.17% in the LES-PCT compared with a predicted value of 0.91% (95% CI 0.86% to 0.95%) based on the pre-LES trend. There was no change in the rate of increase in COPD prevalence for the neighbouring PCT or for London as a whole. The LES-PCT would be expected to diagnose 55.6% of COPD patients by 2017 compared with only 27.3% without the LES, and only 33.3% would be diagnosed in the neighbouring PCT. CONCLUSIONS: These data suggest that, with appropriate incentives, it is possible to achieve a sustained improvement in COPD case-finding in primary care and that such policies need to be implemented systematically.

Factors associated with enrolment into a national COVID-19 pulse oximetry remote monitoring programme in England: a retrospective observational study.

BACKGROUND: Hypoxaemia is an important predictor of severity in individuals with COVID-19 and can present without symptoms. The COVID Oximetry @home (CO@h) programme was implemented across England in November, 2020, providing pulse oximeters to higher-risk people with COVID-19 to enable early detection of deterioration and the need for escalation of care. We aimed to describe the clinical and demographic characteristics of individuals enrolled onto the programme and to assess whether there were any inequalities in enrolment. METHODS: This retrospective observational study was based on data from a cohort of people resident in England recorded as having a positive COVID-19 test between Oct 1, 2020, and May 3, 2021. The proportion of participants enrolled onto the CO@h programmes in the 7 days before and 28 days after a positive COVID-19 test was calculated for each clinical commissioning group (CCG) in England. Two-level hierarchical multivariable logistic regression with random intercepts for each CCG was run to identify factors predictive of being enrolled onto the CO@h programme. FINDINGS: CO@h programme sites were reported by NHS England as becoming operational between Nov 21 and Dec 31, 2020. 1 227 405 people resident in 72 CCGs had a positive COVID-19 test between the date of programme implementation and May 3, 2021, of whom 19 932 (1·6%) were enrolled onto the CO@h programme. Of those enrolled, 14 441 (72·5%) were aged 50 years or older or were identified as clinically extremely vulnerable (ie, having a high-risk medical condition). Higher odds of enrolment onto the CO@h programme were found in older individuals (adjusted odds ratio 2·21 [95% CI 2·19-2·23], p<0·001, for those aged 50-64 years; 3·48 [3·33-3·63], p<0·001, for those aged 65-79 years; and 2·50 [2·34-2·68], p<0·001, for those aged ≥80 years), in individuals of non-White ethnicity (1·35 [1·28-1·43], p<0·001, for Asian individuals; 1·13 [1·04-1·22], p=0·005, for Black individuals; and 1·17 [1·03-1·32], p=0·015, for those of mixed ethnicity), in those who were overweight (1·31 [1·26-1·37], p<0·001) or obese (1·69 [1·63-1·77], p<0·001), or in those identified as clinically extremely vulnerable (1·58 [1·51-1·65], p<0·001), and lower odds were reported in those from the least socioeconomically deprived areas compared with those from the most socioeconomically deprived areas (0·75 [0·69-0·81]; p<0·001). INTERPRETATION: Nationally, uptake of the CO@h programme was low, with clinical judgment used to determine eligibility. Preferential enrolment onto the pulse oximetry monitoring programme was observed in people known to be at the highest risk of developing severe COVID-19. FUNDING: NHS England, National Institute for Health Research, and The Wellcome Trust.

Chest CT features and functional correlates of COVID-19 at 3 months and 12 months follow-up.

Long-term pulmonary sequelae of Coronavirus 2019 (COVID-19) remain unclear. Thus, we aimed to establish post-COVID-19 temporal changes in chest computed tomography (CT) features of pulmonary fibrosis and to investigate associations with respiratory symptoms and physiological parameters at 3 and 12 months' follow-up. Adult patients who attended our initial COVID-19 follow-up service and developed chest CT features of interstitial lung disease, in addition to cases identified using British Society of Thoracic Imaging codes, were evaluated retrospectively. Clinical data were gathered on respiratory symptoms and physiological parameters at baseline, 3 months, and 12 months. Corresponding chest CT scans were reviewed by two thoracic radiologists. Associations between CT features and functional correlates were estimated using random effects logistic or linear regression adjusted for age, sex and body mass index. In total, 58 patients were assessed. No changes in reticular pattern, honeycombing, traction bronchiectasis/bronchiolectasis index or pulmonary distortion were observed. Subpleural curvilinear lines were associated with lower odds of breathlessness over time. Parenchymal bands were not associated with breathlessness or impaired lung function overall. Based on our results, we conclude that post-COVID-19 chest CT features of irreversible pulmonary fibrosis remain static over time; other features either resolve or remain unchanged. Subpleural curvilinear lines do not correlate with breathlessness. Parenchymal bands are not functionally significant. An awareness of the different potential functional implications of post-COVID-19 chest CT changes is important in the assessment of patients who present with multi-systemic sequelae of COVID-19 infection.