Comparing performance of primary care clinicians in the interpretation of SPIROmetry with or without Artificial Intelligence Decision support software (SPIRO-AID): a protocol for a randomised controlled trial.

INTRODUCTION: Spirometry is a point-of-care lung function test that helps support the diagnosis and monitoring of chronic lung disease. The quality and interpretation accuracy of spirometry is variable in primary care. This study aims to evaluate whether artificial intelligence (AI) decision support software improves the performance of primary care clinicians in the interpretation of spirometry, against reference standard (expert interpretation). METHODS AND ANALYSIS: A parallel, two-group, statistician-blinded, randomised controlled trial of primary care clinicians in the UK, who refer for, or interpret, spirometry. People with specialist training in respiratory medicine to consultant level were excluded. A minimum target of 228 primary care clinician participants will be randomised with a 1:1 allocation to assess fifty de-identified, real-world patient spirometry sessions through an online platform either with (intervention group) or without (control group) AI decision support software report. Outcomes will cover primary care clinicians' spirometry interpretation performance including measures of technical quality assessment, spirometry pattern recognition and diagnostic prediction, compared with reference standard. Clinicians' self-rated confidence in spirometry interpretation will also be evaluated. The primary outcome is the proportion of the 50 spirometry sessions where the participant's preferred diagnosis matches the reference diagnosis. Unpaired t-tests and analysis of covariance will be used to estimate the difference in primary outcome between intervention and control groups. ETHICS AND DISSEMINATION: This study has been reviewed and given favourable opinion by Health Research Authority Wales (reference: 22/HRA/5023). Results will be submitted for publication in peer-reviewed journals, presented at relevant national and international conferences, disseminated through social media, patient and public routes and directly shared with stakeholders. TRIAL REGISTRATION NUMBER: NCT05933694.

Spirometry services in England post-pandemic and the potential role of AI support software: a qualitative study of challenges and opportunities.

BACKGROUND: Spirometry services to diagnose and monitor lung disease in primary care were identified as a priority in the NHS Long Term Plan, and are restarting post-COVID-19 pandemic in England; however, evidence regarding best practice is limited. AIM: To explore perspectives on spirometry provision in primary care, and the potential for artificial intelligence (AI) decision support software to aid quality and interpretation. DESIGN AND SETTING: Semi-structured interviews with stakeholders in spirometry services across England. METHOD: Participants were recruited by snowball sampling. Interviews explored the pre- pandemic delivery of spirometry, restarting of services, and perceptions of the role of AI. Transcripts were analysed thematically. RESULTS: In total, 28 participants (mean years' clinical experience = 21.6 [standard deviation 9.4, range 3-40]) were interviewed between April and June 2022. Participants included clinicians (n = 25) and commissioners (n = 3); eight held regional and/or national respiratory network advisory roles. Four themes were identified: 1) historical challenges in provision of spirometry services; 2) inequity in post- pandemic spirometry provision and challenges to restarting spirometry in primary care; 3) future delivery closer to patients' homes by appropriately trained staff; and 4) the potential for AI to have supportive roles in spirometry. CONCLUSION: Stakeholders highlighted historic challenges and the damaging effects of the pandemic contributing to inequity in provision of spirometry, which must be addressed. Overall, stakeholders were positive about the potential of AI to support clinicians in quality assessment and interpretation of spirometry. However, it was evident that validation of the software must be sufficiently robust for clinicians and healthcare commissioners to have trust in the process.

Frailty and Mortality Risk in COPD: A Cohort Study Comparing the Fried Frailty Phenotype and Short Physical Performance Battery.

Background: Identifying frailty in people with chronic obstructive pulmonary disease (COPD) is deemed important, yet comparative characteristics of the most commonly used frailty measures in COPD are unknown. This study aimed to compare how the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB) characterise frailty in people with stable COPD, including prevalence of and overlap in identification of frailty, disease and health characteristics of those identified as living with frailty, and predictive value in relation to survival time. Methods: Cohort study of people with stable COPD attending outpatient clinics. Agreement between frailty classifications was described using Cohen's Kappa. Disease and health characteristics of frail versus not frail participants were compared using t-, Mann-Whitney U and Chi-Square tests. Predictive value for mortality was examined with multivariable Cox regression. Results: Of 714 participants, 421 (59%) were male, mean age 69.9 years (SD 9.7), mean survival time 2270 days (95% CI 2185-2355). Similar proportions were identified as frail using the FFP (26.2%) and SPPB (23.7%) measures; classifications as frail or not frail matched in 572 (80.1%) cases, showing moderate agreement (Kappa = 0.469, SE = 0.038, p < 0.001). Discrepancies seemed driven by FFP exhaustion and weight loss criteria and the SPPB balance component. People with frailty by either measure had worse exercise capacity, health-related quality of life, breathlessness, depression and dependence in activities of daily living. In multivariable analysis controlling for the Age Dyspnoea Obstruction index, sex, BMI, comorbidities and exercise capacity, both the FFP and SPPB had predictive value in relation to mortality (FFP aHR = 1.31 [95% CI 1.03-1.66]; SPPB aHR = 1.29 [95% CI 0.99-1.68]). Conclusion: In stable COPD, both the FFP and SPPB identify similar proportions of people living with/without frailty, the majority with matching classifications. Both measures can identify individuals with multidimensional health challenges and increased mortality risk and provide additional information alongside established prognostic variables.

Integrating Home-Based Exercise Training with a Hospital at Home Service for Patients Hospitalised with Acute Exacerbations of COPD: Developing the Model Using Accelerated Experience-Based Co-Design.

BACKGROUND: Hospital at home (HaH) schemes allow early discharge of patients hospitalised with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Traditional outpatient pulmonary rehabilitation (PR) following an AECOPD has an established evidence-base, but there are issues with low referral, uptake and completion. One commonly cited barrier to PR post-hospitalisation relates to poor accessibility. To address this, the aim of this project was to enrol service users (patients with COPD and informal carers) and healthcare professionals to co-design a model of care that integrates home-based exercise training within a HaH scheme for patients discharged from hospital following AECOPD. METHODS: This accelerated experience-based co-design project included three audio-recorded stakeholder feedback events, using key "touchpoints" from previous qualitative interviews and a recent systematic review. Audio-recordings were inductively analysed using directed content analysis. An integrated model of care was then developed and finalised through two co-design groups, with the decision-making process facilitated by the tables of changes approach. RESULTS: Seven patients with COPD, two informal carers and nine healthcare professionals (from an existing outpatient PR service and HaH scheme) participated in the stakeholder feedback events. Four key themes were identified: 1) individualisation, 2) progression and transition, 3) continuity between services, and 4) communication between stakeholders. Two patients with COPD, one informal carer and three healthcare professionals participated in the first joint co-design group, with five healthcare professionals attending a second co-design group. These achieved a consensus on the integrated model of care. The agreed model comprised face-to-face supervised, individually tailored home-based exercise training one to three times a week, delivered during HaH scheme visits where possible by a healthcare professional competent to provide both home-based exercise training and usual HaH care. CONCLUSION: An integrated model of care has been co-designed by patients with COPD, informal carers and healthcare professionals to address low uptake and completion of PR following AECOPD. The co-designed model of care has now been integrated within a well-established HaH scheme.

Gait speed and adverse outcomes following hospitalised exacerbation of COPD.

BACKGROUND: The 4-m gait speed (4MGS) test is a simple physical performance measure and surrogate marker of frailty that is associated with adverse outcomes in older adults. We aimed to assess the ability of 4MGS to predict prognosis in patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). METHODS: 213 participants hospitalised with AECOPD (52% male, mean age 72 years and mean forced expiratory volume in 1 s (FEV1) 35% predicted) were enrolled. 4MGS and baseline demographics were recorded at hospital discharge. All-cause readmission and mortality were collected for 1 year after discharge and multivariable Cox proportional hazards regressions were performed. Kaplan-Meier and competing risks analyses were conducted comparing time to all-cause readmission and mortality between 4MGS quartiles. RESULTS: 111 participants (52%) were readmitted and 35 (16%) died during the follow-up period. 4MGS was associated with all-cause readmission, with an adjusted subdistribution hazard ratio of 0.868 (95% CI 0.797-0.945; p=0.001) per 0.1 m·s-1 increase in gait speed, and with all-cause mortality, with an adjusted subdistribution hazard ratio of 0.747 (95% CI 0.622-0.898; p=0.002) per 0.1 m·s-1 increase in gait speed. Readmission and mortality models incorporating 4MGS had higher discrimination than age or FEV1 % pred alone, with areas under the receiver operator characteristic curves of 0.73 and 0.80, respectively. Kaplan-Meier and competing risks curves demonstrated that those in slower gait speed quartiles had reduced time to readmission and mortality (log-rank, both p<0.001). CONCLUSIONS: 4MGS provides a simple means of identifying at-risk patients with COPD at hospital discharge. This provides valuable information to plan post-discharge care and support.

The Effects of a Video Intervention on Posthospitalization Pulmonary Rehabilitation Uptake. A Randomized Controlled Trial.

Rationale: Pulmonary rehabilitation (PR) after hospitalizations for exacerbations of chronic obstructive pulmonary disease (COPD) improves exercise capacity and health-related quality of life and reduces readmissions. However, posthospitalization PR uptake is low. To date, no trials of interventions to increase uptake have been conducted.Objectives: To study the effect of a codesigned education video as an adjunct to usual care on posthospitalization PR uptake.Methods: The present study was an assessor- and statistician-blinded randomized controlled trial with nested, qualitative interviews of participants in the intervention group. Participants hospitalized with COPD exacerbations were assigned 1:1 to receive either usual care (COPD discharge bundle including PR information leaflet) or usual care plus the codesigned education video delivered via a handheld tablet device at discharge. Randomization used minimization to balance age, sex, FEV1 % predicted, frailty, transport availability, and previous PR experience.Measurements and Main Results: The primary outcome was PR uptake within 28 days of hospital discharge. A total of 200 patients were recruited, and 196 were randomized (51% female, median FEV1% predicted, 36 [interquartile range, 27-48]). PR uptake was 41% and 34% in the usual care and intervention groups, respectively (P = 0.37), with no differences in secondary (PR referral and completion) or safety (readmissions and death) endpoints. A total of 6 of the 15 participants interviewed could not recall receiving the video.Conclusions: A codesigned education video delivered at hospital discharge did not improve posthospitalization PR uptake, referral, or completion.

The prognostic significance of weight loss in chronic obstructive pulmonary disease-related cachexia: a prospective cohort study.

BACKGROUND: Cachexia is an important extra-pulmonary manifestation of chronic obstructive pulmonary disease (COPD) presenting as unintentional weight loss and altered body composition. Previous studies have focused on the relative importance of body composition compared with body mass rather than the relative importance of dynamic compared with static measures. We aimed to determine the prevalence of cachexia and pre-cachexia phenotypes in COPD and examine the associations between cachexia and its component features with all-cause mortality. METHODS: We enrolled 1755 consecutive outpatients with stable COPD from two London centres between 2012 and 2017, stratified according to European Respiratory Society Task Force defined cachexia [unintentional weight loss >5% and low fat-free mass index (FFMI)], pre-cachexia (weight loss >5% but preserved FFMI), or no cachexia. The primary outcome was all-cause mortality. We calculated hazard ratios (HRs) using Cox proportional hazards regression for cachexia classifications (cachexia, pre-cachexia, and no cachexia) and component features (weight loss and FFMI) and mortality, adjusting for age, sex, body mass index, and disease-specific prognostic markers. RESULTS: The prevalence of cachexia was 4.6% [95% confidence interval (CI): 3.6-5.6] and pre-cachexia 1.6% (95% CI: 1.0-2.2). Prevalence was similar across sexes but increased with worsening Global Initiative for Chronic Obstructive Pulmonary Disease spirometric stage and Medical Research Council dyspnoea score (all P < 0.001). There were 313 (17.8%) deaths over a median (interquartile range) follow-up duration 1089 (547-1704) days. Both cachexia [HR 1.98 (95% CI: 1.31-2.99), P = 0.002] and pre-cachexia [HR 2.79 (95% CI: 1.48-5.29), P = 0.001] were associated with increased mortality. In multivariable analysis, the unintentional weight loss feature of cachexia was independently associated with mortality [HR 2.16 (95% CI: 1.31-3.08), P < 0.001], whereas low FFMI was not [HR 0.88 (95% CI: 0.64-1.20), P = 0.402]. Sensitivity analyses using body mass index-specific, age-specific, and gender-specific low FFMI values found consistent findings. CONCLUSIONS: Despite the low prevalence of cachexia and pre-cachexia, both confer increased mortality risk in COPD, driven by the unintentional weight loss component. Our data suggest that low FFMI without concurrent weight loss may not confer the poor prognosis as previously reported for this group. Weight loss should be regularly monitored in practice and may represent an important target in COPD management. We propose the incorporation of weight monitoring into national and international COPD guidance.

Gait speed and pedestrian crossings in COPD.

The assumed minimum walking speed at pedestrian crossings is 1.2 m/s. In this prospective cohort study, usual walking speed was measured over a 4 m course in 926 community-dwelling, ambulatory patients with stable COPD. Mean (SD) walking speed was 0.91 (0.24) m/s with only 10.7% walking at a speed equal or greater than 1.2 m/s. In order for 95% of this cohort to safely negotiate a pedestrian cross, traffic lights would have to assume a minimum walking speed of 0.50 m/s (2.4 times longer than current times). The current assumed normal walking speed for pedestrian crossings is inappropriate for patients with COPD.The studies were registered on clinicaltrials.gov and these data relate to the pre-results stage: NCT01649193, NCT01515709 and NCT01507415.

Redefining Cut-Points for High Symptom Burden of the Global Initiative for Chronic Obstructive Lung Disease Classification in 18,577 Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference. METHODS: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores. MAIN OUTCOMES: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points. FINDINGS: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points. CONCLUSIONS: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed.

Validity, responsiveness and minimum clinically important difference of the incremental shuttle walk in idiopathic pulmonary fibrosis: a prospective study.

The incremental shuttle walk (ISW) is well validated in COPD but limited psychometric data restrict its use in idiopathic pulmonary fibrosis (IPF). Study 1: 50 patients performed the ISW and 6 min walk test (6MWT). Study 2: 72 patients completed the ISW before and after pulmonary rehabilitation (PR). The ISW correlated strongly with 6MWT distance (r=0.81,p<0.0001). Mean (95% confidence interval) improvement in ISW with PR was 54 (38 to 70) m with an effect size of 0.29. Distribution-based and anchor-based minimum clinically important difference (MCID) estimates ranged from 31 to 46 m. The ISW is valid and responsive in IPF, with an anchor-based MCID estimate similar to that observed in chronic obstructive pulmonary disease. TRIAL REGISTRATION NUMBER: Pre-results; NCT02530736, NCT02436278.

ACE and response to pulmonary rehabilitation in COPD: two observational studies.

INTRODUCTION: Skeletal muscle impairment is an important feature of chronic obstructive pulmonary disease (COPD). Renin-angiotensin system activity influences muscle phenotype, so we wished to investigate whether it affects the response to pulmonary rehabilitation. METHODS: Two studies are described; in the first, the response of 168 COPD patients (mean forced expiratory volume in one second 51.9% predicted) to pulmonary rehabilitation was compared between different ACE insertion/deletion polymorphism genotypes. In a second, independent COPD cohort (n=373), baseline characteristics and response to pulmonary rehabilitation were compared between COPD patients who were or were not taking ACE inhibitors or angiotensin receptor antagonists (ARB). RESULTS: In study 1, the incremental shuttle walk distance improved to a similar extent in all three genotypes; DD/ID/II (n=48/91/29) 69(67)m, 61 (76)m and 78 (78)m, respectively, (p>0.05). In study 2, fat free mass index was higher in those on ACE-I/ARB (n=130) than those who were not (n=243), 17.8 (16.0, 19.8) kg m-2 vs 16.5 (14.9, 18.4) kg/m2 (p<0.001). However change in fat free mass, walking distance or quality of life in response to pulmonary rehabilitation did not differ between groups. CONCLUSIONS: While these data support a positive association of ACE-I/ARB treatment and body composition in COPD, neither treatment to reduce ACE activity nor ACE (I/D) genotype influence response to pulmonary rehabilitation.

Pedometer Step Count Targets during Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial.

RATIONALE: Increasing physical activity is a key therapeutic aim in chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) improves exercise capacity, but there is conflicting evidence regarding its ability to improve physical activity levels. OBJECTIVES: To determine whether using pedometers as an adjunct to PR can enhance time spent in at least moderate-intensity physical activity (time expending ≥3 metabolic equivalents [METs]) by people with COPD. METHODS: In this single-blind randomized controlled trial, participants were assigned 1:1 to receive a control intervention (PR comprising 8 wk, two supervised sessions per week) or the trial intervention (PR plus pedometer-directed step targets, reviewed weekly for 8 wk). In the randomization process, we used minimization to balance groups for age, sex, FEV1 percent predicted, and baseline exercise capacity and physical activity levels. Outcome assessors and PR therapists were blinded to group allocation. The primary analysis was based on the intention-to-treat principle. MEASUREMENTS AND MAIN RESULTS: The primary outcome was change from baseline to 8 weeks in accelerometer-measured daily time expending at least 3 METs. A total of 152 participants (72% male; mean [SD] FEV1 percent predicted, 50.5% [21.2]; median [first quartile, third quartile] time expending ≥3 METs, 46 [21, 92] min) were enrolled and assigned to the intervention (n = 76) or control (n = 76) arm. There was no significant difference in change in time expending at least 3 METs between the intervention and control groups at 8 weeks (median [first quartile, third quartile] difference, 0.5 [-1.0, 31.0] min; P = 0.87) or at the 6-month follow-up (7.0 [-9, 27] min; P = 0.16). CONCLUSIONS: Pedometer-directed step-count targets during an outpatient PR program did not enhance moderate-intensity physical activity levels in people with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01719822).