Residual Lung Abnormalities after COVID-19 Hospitalization: Interim Analysis of the UKILD Post-COVID-19 Study.

Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage. Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post-COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata. Methods: The PHOSP-COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP-COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up. Measurements and Main Results: The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83-155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05-1.40), percent predicted DlCO less than 80% (RR, 1.25; 95% CrI, 1.00-1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07-1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6-9.5), rising to 11.7% (95% CrI, 10.3-13.1) in the sensitivity analysis. Conclusions: Residual lung abnormalities were estimated in up to 11% of people discharged after COVID-19-related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications.

Lung volume reduction surgery versus endobronchial valves: a randomised controlled trial.

BACKGROUND: Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. METHODS: This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. RESULTS: 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 versus BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) versus BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm. CONCLUSION: Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.

Development and implementation of the lung volume reduction pulmonary rehabilitation tool to identify eligibility for lung volume reduction in people with chronic obstructive pulmonary disease during pulmonary rehabilitation.

BACKGROUND: Completion of pulmonary rehabilitation is recognised in chronic obstructive pulmonary disease (COPD) guidelines as a key opportunity to consider systematically whether a respiratory review to assess potential suitability for a lung volume reduction (LVR) procedure might be appropriate. We describe the development of a simple decision-support tool (the LVR-PR tool) to aid clinicians working in pulmonary rehabilitation, to operationalise this process. METHODS: We took an iterative mixed methods approach, which was partnership-based and involved an initial consensus survey, focus groups and an observational study cohort at multiple pulmonary rehabilitation centres. RESULTS: Diagnosis (97%), exercise capacity (84%), breathlessness (78%) and co-morbidities (76%) were acknowledged to be essential items for assessing basic LVR eligibility. Collating prior investigations and assessing patient understanding were considered useful but not essential. Clinician concerns included; streamlining the tool; access to clinical information and investigations; and care needed around introducing LVR therapies to patients in a PR setting. Access to clearer information about LVR procedures, the clinician's role in considering eligibility and how educational resources should be delivered were identified as important themes from patient group discussions. The LVR-PR tool was considered to be feasible and valid for implementation in a variety of PR services across the UK subject to the provision of appropriate health professional training. Clinicians working in specialist LVR centres across the UK who were not otherwise involved in the development process confirmed the tool's validity using the content validity index (CVI). INTERPRETATION: The LVR-PR tool appears to be an acceptable tool that can be feasibly implemented in PR services subject to good quality educational resources for both patients and healthcare professionals.

Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial.

RATIONALE: The long-acting ß2-agonist/long-acting muscarinic antagonist combination indacaterol/glycopyrronium (IND/GLY) elicits bronchodilation, improves symptoms, and reduces exacerbations in COPD. Magnetic resonance imaging (MRI) of the lung with hyperpolarized gas and gadolinium contrast enhancement enables assessment of whole lung functional responses to IND/GLY. OBJECTIVES: The primary objective was assessment of effect of IND/GLY on global ventilated lung volume (%VV) versus placebo in COPD. Lung function, regional ventilation and perfusion in response to IND/GLY were also measured. METHODS: This double-blind, randomized, placebo-controlled, crossover study assessed %VV and pulmonary perfusion in patients with moderate-to-severe COPD after 8 days of once-daily IND/GLY treatment (110/50 µg) followed by 8 days of placebo, or vice versa, using inhaled hyperpolarized 3He gas and gadolinium contrast-enhanced MRI, respectively. Lung function measures including spirometry were performed for each treatment after 8 days. MEASUREMENTS AND MAIN RESULTS: Of 31 patients randomized, 29 completed both treatment periods. IND/GLY increased global %VV versus placebo (61.73% vs. 56.73%, respectively, least squares means treatment difference: 5.00% [90% CI 1.40 to 8.60]; P = 0.025). IND/GLY improved whole lung index of ventilation volume to perfusion volume (V/Q) ratio versus placebo; 94% (90% CI 83 to 105) versus 86% (90% CI 75 to 97; P = 0.047), respectively. IND/GLY showed a trend to improve diffusing capacity for carbon monoxide (DLCO) (+ 0.66 mL/min/mmHg; P = 0.082). By Day 8, forced expiratory volume in 1 s (FEV1) was increased by 0.32 L versus placebo (90% CI 0.26 to 0.38; P < 0.0001), substantiating earlier findings and providing evidence of assay sensitivity for this trial. CONCLUSIONS: IND/GLY improved lung ventilation assessed by 3He MRI after 1 week of treatment. This observation may provide mechanistic support for the symptomatic clinical benefit shown with IND/GLY in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT02634983).

Reproducibility of 19 F-MR ventilation imaging in healthy volunteers.

PURPOSE: To assess the reproducibility of percentage ventilated lung volume (%VV) measurements in healthy volunteers acquired by fluorine (19 F)-MRI of inhaled perfluoropropane, implemented at two research sites. METHODS: In this prospective, ethically approved study, 40 healthy participants were recruited (May 2018-June 2019) to one of two research sites. Participants underwent a single MRI scan session on a 3T scanner, involving periodic inhalation of a 79% perfluoropropane/21% oxygen gas mixture. Each gas inhalation session lasted about 30 seconds, consisting of three deep breaths of gas followed by a breath-hold. Four 19 F-MR ventilation images were acquired per participant, each separated by approximately 6 minutes. The value of %VV was determined by registering separately acquired 1 H images to ventilation images before semi-automated image segmentation, performed independently by two observers. Reproducibility of %VV measurements was assessed by components of variance, intraclass correlation coefficients, coefficients of variation (CoV), and the Dice similarity coefficient. RESULTS: The MRI scans were well tolerated throughout, with no adverse events. There was a high degree of consistency in %VV measurements for each participant (CoVobserver1 = 0.43%; CoVobserver2 = 0.63%), with overall precision of %VV measurements determined to be within ± 1.7% (95% confidence interval). Interobserver agreement in %VV measurements revealed a high mean Dice similarity coefficient (SD) of 0.97 (0.02), with only minor discrepancies between observers. CONCLUSION: We demonstrate good reproducibility of %VV measurements in a group of healthy participants using 19 F-MRI of inhaled perfluoropropane. Our methods have been successfully implemented across two different study sites, supporting the feasibility of performing larger multicenter clinical studies.

Comparison of 3 He and 129 Xe MRI for evaluation of lung microstructure and ventilation at 1.5T.

BACKGROUND: To support translational lung MRI research with hyperpolarized 129 Xe gas, comprehensive evaluation of derived quantitative lung function measures against established measures from 3 He MRI is required. Few comparative studies have been performed to date, only at 3T, and multisession repeatability of 129 Xe functional metrics have not been reported. PURPOSE/HYPOTHESIS: To compare hyperpolarized 129 Xe and 3 He MRI-derived quantitative metrics of lung ventilation and microstructure, and their repeatability, at 1.5T. STUDY TYPE: Retrospective. POPULATION: Fourteen healthy nonsmokers (HN), five exsmokers (ES), five patients with chronic obstructive pulmonary disease (COPD), and 16 patients with nonsmall-cell lung cancer (NSCLC). FIELD STRENGTH/SEQUENCE: 1.5T. NSCLC, COPD patients and selected HN subjects underwent 3D balanced steady-state free-precession lung ventilation MRI using both 3 He and 129 Xe. Selected HN, all ES, and COPD patients underwent 2D multislice spoiled gradient-echo diffusion-weighted lung MRI using both hyperpolarized gas nuclei. ASSESSMENT: Ventilated volume percentages (VV%) and mean apparent diffusion coefficients (ADC) were derived from imaging. COPD patients performed the whole MR protocol in four separate scan sessions to assess repeatability. Same-day pulmonary function tests were performed. STATISTICAL TESTS: Intermetric correlations: Spearman's coefficient. Intergroup/internuclei differences: analysis of variance / Wilcoxon's signed rank. Repeatability: coefficient of variation (CV), intraclass correlation (ICC) coefficient. RESULTS: A significant positive correlation between 3 He and 129 Xe VV% was observed (r = 0.860, P < 0.001). VV% was larger for 3 He than 129 Xe (P = 0.001); average bias, 8.79%. A strong correlation between mean 3 He and 129 Xe ADC was obtained (r = 0.922, P < 0.001). MR parameters exhibited good correlations with pulmonary function tests. In COPD patients, mean CV of 3 He and 129 Xe VV% was 4.08% and 13.01%, respectively, with ICC coefficients of 0.541 (P = 0.061) and 0.458 (P = 0.095). Mean 3 He and 129 Xe ADC values were highly repeatable (mean CV: 2.98%, 2.77%, respectively; ICC: 0.995, P < 0.001; 0.936, P < 0.001). DATA CONCLUSION: 129 Xe lung MRI provides near-equivalent information to 3 He for quantitative lung ventilation and microstructural MRI at 1.5T. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2018.

Reproducibility of quantitative indices of lung function and microstructure from 129 Xe chemical shift saturation recovery (CSSR) MR spectroscopy.

PURPOSE: To evaluate the reproducibility of indices of lung microstructure and function derived from 129 Xe chemical shift saturation recovery (CSSR) spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD), and to study the sensitivity of CSSR-derived parameters to pulse sequence design and lung inflation level. METHODS: Preliminary data were collected from five volunteers on three occasions, using two implementations of the CSSR sequence. Separately, three volunteers each underwent CSSR at three different lung inflation levels. After analysis of these preliminary data, five COPD patients were scanned on three separate days, and nine age-matched volunteers were scanned three times on one day, to assess reproducibility. RESULTS: CSSR-derived alveolar septal thickness (ST) and surface-area-to-volume (S/V) ratio values decreased with lung inflation level (P < 0.001; P = 0.057, respectively). Intra-subject standard deviations of ST were lower than the previously measured differences between volunteers and subjects with interstitial lung disease. The mean coefficient of variation (CV) values of ST were 3.9 ± 1.9% and 6.0 ± 4.5% in volunteers and COPD patients, respectively, similar to CV values for whole-lung carbon monoxide diffusing capacity. The mean CV of S/V in volunteers and patients was 14.1 ± 8.0% and 18.0 ± 19.3%, respectively. CONCLUSION: 129 Xe CSSR presents a reproducible method for estimation of alveolar septal thickness. Magn Reson Med 77:2107-2113, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Fractional exhaled nitric oxide for the management of asthma in adults: a systematic review.

The aim of this review was to evaluate the clinical effectiveness of fractional exhaled nitric oxide (FeNO) measured in a clinical setting for the management of asthma in adults.13 electronic databases were searched and studies were selected against predefined inclusion criteria. Quality assessment was conducted using QUADAS-2. Class effect meta-analyses were performed.Six studies were included. Despite high levels of heterogeneity in multiple study characteristics, exploratory class effect meta-analyses were conducted. Four studies reported a wider definition of exacerbation rates (major or severe exacerbation) with a pooled rate ratio of 0.80 (95% CI 0.63-1.02). Two studies reported rates of severe exacerbations (requiring oral corticosteroid use) with a pooled rate ratio of 0.89 (95% CI 0.43-1.72). Inhaled corticosteroid use was reported by four studies, with a pooled standardised mean difference of -0.24 (95% CI -0.56-0.07). No statistically significant differences for health-related quality of life or asthma control were found.FeNO guided management showed no statistically significant benefit in terms of severe exacerbations or inhaled corticosteroid use, but showed a statistically significant reduction in exacerbations of any severity. However, further research is warranted to clearly define which management protocols (including cut-off points) offer best efficacy and which patient groups would benefit the most.

Redesigning a home oxygen assessment and review service.

The Sheffield home oxygen assessment and review service was developed as a nurse-led, protocol-driven service, offering high standards of care to a limited number of patients. In line with national changes to oxygen provision in 2011, the service team was approached to address inconsistencies and inequalities in the existing care pathway, with a view to becoming a fully commissioned service. This required a complete redesign of the service, using a collaborative approach to include relevant interested parties in planning and decision making. Additional support was gained through participation in the NHS Improvement lung national improvement project. This article outlines the process of service redesign, including some of the major challenges as well as the main learning points. It has led to the provision of an equitable and efficient service for all oxygen patients across the city, offering more community clinics and robust cost controls, while maintaining quality of care.

(3)He pO2 mapping is limited by delayed-ventilation and diffusion in chronic obstructive pulmonary disease.

PURPOSE: Lung pO2 mapping with (3)He MRI assumes that the sources of signal decay with time during a breath-hold are radiofrequency depolarization and oxygen-dependent T1 relaxation, but the method is sensitive to other sources of spatio-temporal signal change such as diffusion. The purpose of this work was to assess the use of (3)He pO2 mapping in patients with chronic obstructive pulmonary disease. METHODS: Ten patients with moderate to severe chronic obstructive pulmonary disease were scanned with a 3D single breath-hold pO2 mapping sequence. RESULTS: Images showed signal increasing over time in some lung regions due to delayed ventilation during breath-hold. Regions of physically unrealistic negative pO2 values were seen in all patients, and regional mean pO2 values of -0.3 bar were measured in the two patients most affected by delayed ventilation (where mean time to signal onset was 3-4 s). CONCLUSIONS: Movement of gas within the lungs during breath-hold causes regional changes in signal over time that are not related to oxygen concentration, leading to erroneous pO2 measurements using the linear oxygen-dependent signal decay model. These spatio-temporal sources of signal change cannot be reliably separated at present, making pO2 mapping using this methodology unreliable in chronic obstructive pulmonary disease patients with significant bullous emphysema or delayed ventilation.

Pulmonary hypertension in COPD: results from the ASPIRE registry.

The phenotype and outcome of severe pulmonary hypertension in chronic obstructive pulmonary disease (COPD) is described in small numbers, and predictors of survival are unknown. Data was retrieved for 101 consecutive, treatment-naïve cases of pulmonary hypertension in COPD. Mean ± SD follow-up was 2.3 ± 1.9 years. 59 patients with COPD and severe pulmonary hypertension, defined by catheter mean pulmonary artery pressure ≥40 mmHg, had significantly lower carbon monoxide diffusion, less severe airflow obstruction but not significantly different emphysema scores on computed tomography compared to 42 patients with mild-moderate pulmonary hypertension. 1- and 3-year survival for severe pulmonary hypertension, at 70% and 33%, respectively, was inferior to 83% and 55%, respectively, for mild-moderate pulmonary hypertension. Mixed venous oxygen saturation, carbon monoxide diffusion, World Health Organization functional class and age, but not severity of airflow obstruction, were independent predictors of outcome. Compassionate treatment with targeted therapies in 43 patients with severe pulmonary hypertension was not associated with a survival benefit, although improvement in functional class and/or fall in pulmonary vascular resistance >20% following treatment identified patients with improved survival. Standard prognostic markers in COPD have limited value in patients with pulmonary hypertension. This study identifies variables that predict outcome in this phenotype. Despite poor prognosis, our data suggest that further evaluation of targeted therapies is warranted.

Is a large scale community programme as effective as a community rehabilitation programme delivered in the setting of a clinical trial?

BACKGROUND: The rationale for commissioning community pulmonary rehabilitation programmes is based on evidence from randomised clinical trials. However, there are a number of reasons why similar programmes might be less effective outside the environment of a clinical trial. These include a less highly selected patient group and less control over the fidelity of intervention delivery. The main objective of this study was therefore to test the hypothesis that the real-world programme would have similar outcomes to an intervention delivered in the context of a clinical trial. METHODS: As part of the evaluation of an innovative community-based pulmonary rehabilitation programme ("BreathingSpace"), clinical and quality of life measures were collected before and after delivery of a rehabilitation programme. Baseline characteristics of participants and the change in symptoms and quality of life after the BreathingSpace programme were compared to measures collected in the community-based arm of a separate randomised trial of pulmonary rehabilitation. RESULTS: Despite differences between the BreathingSpace participants and research participants in clinical status at baseline, patient reported symptoms and quality of life measures were similar. Improvements in both symptoms and quality of life were of the same order of magnitude despite the different contexts, setting and scale of the two intervention programmes. Whilst 73% (326/448) of those considered suitable for community rehabilitation in the trial and 80% (393/491) assessed as suitable for the BreathingSpace programme agreed to participate, less than half of participants completed rehabilitation, whether in a research or "real world" setting (47% and 45% respectively). CONCLUSION: The before-after changes in outcomes seen in a "real world" community rehabilitation programme are similar in magnitude to those seen in the intervention arm of a clinical trial. However suboptimal uptake and high dropout rates from rehabilitation amongst eligible participants occurs in both clinical trials and community based programmes and must be addressed if the benefits of rehabilitation for people with chronic lung disease are to be maximised.

COPD causation and workplace exposures: an assessment of agreement among expert clinical raters.

BACKGROUND: Although occupational exposure is a known risk factor for Chronic Obstructive Pulmonary Disease (COPD), it is difficult to identify specific occupational contributors to COPD at the individual level to guide COPD prevention or for compensation. The aim of this study was to gain an understanding of how different expert clinicians attribute likely causation in COPD. METHODS: Ten COPD experts and nine occupational lung disease experts assigned occupational contribution ratings to fifteen hypothetical cases of COPD with varying combinations of occupational and smoking exposures. Participants rated the cause of COPD as the percentage contribution to the overall attribution of disease for smoking, occupational exposures and other causes. RESULTS: Increasing pack-years of tobacco smoking was associated with significantly decreased proportional occupational causation ratings. Increasing weighted occupational exposure was associated with increased occupational causation ratings by 0.28% per unit change. Expert background also contributed significantly to the proportion of occupational causation rated, with COPD experts rating on average a 9.4% greater proportion of occupational causation per case. CONCLUSION: Our findings support the notion that respiratory physicians are able to assign attribution to different sources of causation in COPD, taking into account both smoking and occupational histories. The recommendations on whether to continue to work in the same job also differ, the COPD experts being more likely to recommend change of work rather than change of work practice.

Longitudinal Lung Function Assessment of Patients Hospitalized With COVID-19 Using 1H and 129Xe Lung MRI.

BACKGROUND: Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes in these patients remains unclear. RESEARCH QUESTION: Do patients hospitalized with COVID-19 without evidence of architectural distortion on structural imaging exhibit longitudinal improvements in lung function measured by using 1H and 129Xe MRI between 6 and 52 weeks following hospitalization? STUDY DESIGN AND METHODS: Patients who were hospitalized with COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25, and 51 weeks following hospital admission in a prospective cohort study between November 2020 and February 2022. The imaging protocol was as follows: 1H ultra-short echo time, contrast-enhanced lung perfusion, 129Xe ventilation, 129Xe diffusion-weighted, and 129Xe spectroscopic imaging of gas exchange. RESULTS: Nine patients were recruited (age 57 ± 14 [median ± interquartile range] years; six of nine patients were male). Patients underwent MRI at 6 (n = 9), 12 (n = 9), 25 (n = 6), and 51 (n = 8) weeks following hospital admission. Patients with signs of interstitial lung damage were excluded. At 6 weeks, patients exhibited impaired 129Xe gas transfer (RBC to membrane fraction), but lung microstructure was not increased (apparent diffusion coefficient and mean acinar airway dimensions). Minor ventilation abnormalities present in four patients were largely resolved in the 6- to 25-week period. At 12 weeks, all patients with lung perfusion data (n = 6) showed an increase in both pulmonary blood volume and flow compared with 6 weeks, although this was not statistically significant. At 12 weeks, significant improvements in 129Xe gas transfer were observed compared with 6-week examinations; however, 129Xe gas transfer remained abnormally low at weeks 12, 25, and 51. INTERPRETATION: 129Xe gas transfer was impaired up to 1 year following hospitalization in patients who were hospitalized with COVID-19 pneumonia, without evidence of architectural distortion on structural imaging, whereas lung ventilation was normal at 52 weeks.

Direct visualisation of collateral ventilation in COPD with hyperpolarised gas MRI.

BACKGROUND: Collateral ventilation has been proposed as a mechanism of compensation of respiratory function in obstructive lung diseases but observations of it in vivo are limited. The assessment of collateral ventilation with an imaging technique might help to gain insight into lung physiology and assist the planning of new bronchoscopic techniques for treating emphysema. OBJECTIVE: To obtain images of delayed ventilation that might be related to collateral ventilation over the period of a single breath-hold in patients with chronic obstructive pulmonary disease (COPD). METHODS: Time-resolved breath-hold hyperpolarised (3)He MRI was used to obtain images of the progressive influx of polarised gas into initially non-ventilated defects. RESULTS: A time-series of images showed that (3)He moves into lung regions which were initially non-ventilated. Ventilation defects with delayed filling were observed in 8 of the 10 patients scanned. CONCLUSIONS: A method for direct imaging of delayed ventilation within a single breath-hold has been demonstrated in patients with COPD. Images of what is believed to be collateral ventilation and slow filling of peripheral airspaces due to increased flow resistance are presented. The technique provides 3D whole-lung coverage with sensitivity to regional information, and is non-invasive and non-ionising.

Lung MRI with hyperpolarised gases: current & future clinical perspectives.

The use of pulmonary MRI in a clinical setting has historically been limited. Whilst CT remains the gold-standard for structural lung imaging in many clinical indications, technical developments in ultrashort and zero echo time MRI techniques are beginning to help realise non-ionising structural imaging in certain lung disorders. In this invited review, we discuss a complementary technique - hyperpolarised (HP) gas MRI with inhaled 3He and 129Xe - a method for functional and microstructural imaging of the lung that has great potential as a clinical tool for early detection and improved understanding of pathophysiology in many lung diseases. HP gas MRI now has the potential to make an impact on clinical management by enabling safe, sensitive monitoring of disease progression and response to therapy. With reference to the significant evidence base gathered over the last two decades, we review HP gas MRI studies in patients with a range of pulmonary disorders, including COPD/emphysema, asthma, cystic fibrosis, and interstitial lung disease. We provide several examples of our experience in Sheffield of using these techniques in a diagnostic clinical setting in challenging adult and paediatric lung diseases.

Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID).

INTRODUCTION: The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD). METHODS AND ANALYSIS: The UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment. ETHICS AND DISSEMINATION: All contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals. CONCLUSION: This study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.

Is inspiratory muscle training (IMT) an acceptable treatment option for people with chronic obstructive pulmonary disease (COPD) who have declined pulmonary rehabilitation (PR) and can IMT enhance PR uptake? A single-group prepost feasibility study in a home-based setting.

OBJECTIVES: This feasibility study aimed to assess the acceptability of inspiratory muscle training (IMT) in people with chronic obstructive pulmonary disease (COPD) who declined pulmonary rehabilitation (PR) as a potential treatment option or precursor to PR. Objectives were to assess attitudes to IMT, PR and alternatives to PR; factors influencing adherence with IMT and acceptability of outcome measures, research tools and study protocol. DESIGN: A pragmatic, mixed methods, prepost feasibility study was conducted. Recruitment took place over a 4-month period. Participants were followed up for a period of 6 months. SETTINGS: IMT sessions and assessments were conducted in the domiciliary setting. PARTICIPANTS: Inclusion criteria: people over the age of 35, stable COPD, Medical Research Council Dyspnoea scale of 3 or above, declined PR. EXCLUSION CRITERIA: history of spontaneous pneumothorax, incomplete recovery from a traumatic pneumothorax, asthma, known recently perforated eardrum, unstable angina, ventricular dysrhythmias, cerebrovascular event or myocardial infarction within the last 2 months. Participants were selected from a purposive sample. Of the 22 potential participants screened, 11 were recruited and interviewed. Ten participants commenced IMT. Seven participants completed the follow-up assessment. INTERVENTION: Eight weeks of IMT twice a day, 5 days a week with visits once weekly by a physiotherapist. Unsupervised IMT twice a day three times a week until follow-up at 6 months. OUTCOMES: Acceptability of IMT and the study process was explored via semi-structured interviews. Adherence with IMT was assessed by the Powerbreathe K3 device and participant diaries. Uptake of PR was identified. RESULTS: IMT was found to be acceptable. Adherence was explored. Four people went on to participate in PR. CONCLUSIONS: Feasibility was established. A randomised controlled trial is warranted to establish efficacy and cost-effectiveness of IMT in those who decline PR and IMT as an intervention to promote uptake of PR. TRIAL REGISTRATION NUMBER: NCT01956565; Post-results.

Using a multi-method, user centred, prospective hazard analysis to assess care quality and patient safety in a care pathway.

BACKGROUND: Care pathways can be complex, often involving multiple care providers and as such are recognised as containing multiple opportunities for error. Prospective hazard analysis methods may be useful for evaluating care provided across primary and secondary care pathway boundaries. These methods take into account the views of users (staff and patients) when determining where potential hazards may lie. The aim of this study is to evaluate the feasibility of prospective hazard analysis methods when assessing quality and safety in care pathways that lie across primary and secondary care boundaries. METHODS: Development of a process map of the care pathway for patients entering into a Chronic Obstructive Pulmonary Disease (COPD) supported discharge programme. Triangulation of information from: care process mapping, semi-structured interviews with COPD patients, semi-structured interviews with COPD staff, two round modified Delphi study and review of prioritised quality and safety challenges by health care staff. RESULTS: Interview themes emerged under the headings of quality of care and patient safety. Quality and safety concerns were mostly raised in relation to communication, for example, communication with other hospital teams. The three highest ranked safety concerns from the modified Delphi review were: difficulties in accessing hospital records, information transfer to primary care and failure to communicate medication changes to primary care. CONCLUSION: This study has demonstrated the feasibility of using mixed methods to review the quality and safety of care in a care pathway. By using multiple research methods it was possible to get a clear picture of service quality variations and also to demonstrate which points in the care pathway had real potential for patient safety incidents or system failures to occur. By using these methods to analyse one condition specific care pathway it was possible to uncover a number of hospital level problems. A number of safety challenges were systems related; these were therefore difficult to improve at care team level. Study results were used by National Health Service (NHS) stakeholders to implement solutions to problems identified in the review.