Objectives: Work package 1: to evaluate alternative methods of screening for undiagnosed chronic obstructive pulmonary disease in primary care, with clinical effectiveness and cost-effectiveness analyses and an economic model of a routine screening programme. Work package 2: to recruit a primary care chronic obstructive pulmonary disease cohort, develop a prognostic model [Birmingham Lung Improvement StudieS (BLISS)] to predict risk of respiratory hospital admissions, validate an existing model to predict mortality risk, address some uncertainties about natural history and explore the potential for a home exercise intervention. Work package 3: to identify which factors are associated with employment, absenteeism, presenteeism (working while unwell) and evaluate the feasibility of offering formal occupational health assessment to improve work performance.
Design: Work package 1: a cluster randomised controlled trial with household-level randomised comparison of two alternative case-finding approaches in the intervention arm. Work package 2: cohort study – focus groups. Work package 3: subcohort – feasibility study.
Setting: Primary care settings in West Midlands, UK.
Participants: Work package 1: 74,818 people who have smoked aged 40–79 years without a previous chronic obstructive pulmonary disease diagnosis from 54 general practices. Work package 2: 741 patients with previously diagnosed chronic obstructive pulmonary disease from 71 practices and participants from the work package 1 randomised controlled trial. Twenty-six patients took part in focus groups. Work package 3: occupational subcohort with 248 patients in paid employment at baseline. Thirty-five patients took part in an occupational health intervention feasibility study.
Interventions: Work package 1: targeted case-finding – symptom screening questionnaire, administered opportunistically or additionally by post, followed by diagnostic post-bronchodilator spirometry. The comparator was routine care. Work package 2: twenty-three candidate variables selected from literature and expert reviews. Work package 3: sociodemographic, clinical and occupational characteristics; occupational health assessment and recommendations.
Main outcome measures: Work package 1: yield (screen-detected chronic obstructive pulmonary disease) and cost-effectiveness of case-finding; effectiveness of screening on respiratory hospitalisation and mortality after approximately 4 years. Work package 2: respiratory hospitalisation within 2 years, and barriers to and facilitators of physical activity. Work package 3: work performance – feasibility and acceptability of the occupational health intervention and study processes.
Results: Work package 1: targeted case-finding resulted in greater yield of previously undiagnosed chronic obstructive pulmonary disease than routine care at 1 year [n = 1278 (4%) vs. n = 337 (1%), respectively; adjusted odds ratio 7.45, 95% confidence interval 4.80 to 11.55], and a model-based estimate of a regular screening programme suggested an incremental cost-effectiveness ratio of £16,596 per additional quality-adjusted life-year gained. However, long-term follow-up of the trial showed that at ≈4 years there was no clear evidence that case-finding, compared with routine practice, was effective in reducing respiratory admissions (adjusted hazard ratio 1.04, 95% confidence interval 0.73 to1.47) or mortality (hazard ratio 1.15, 95% confidence interval 0.82 to 1.61). Work package 2: 2305 patients, comprising 1564 with previously diagnosed chronic obstructive pulmonary disease and 741 work package 1 participants (330 with and 411 without obstruction), were recruited. The BLISS prognostic model among cohort participants with confirmed airflow obstruction (n = 1894) included 6 of 23 candidate variables (i.e. age, Chronic Obstructive Pulmonary Disease Assessment Test score, 12-month respiratory admissions, body mass index, diabetes and forced expiratory volume in 1 second percentage predicted). After internal validation and adjustment (uniform shrinkage factor 0.87, 95% confidence interval 0.72 to 1.02), the model discriminated well in predicting 2-year respiratory hospital admissions (c-statistic 0.75, 95% confidence interval 0.72 to 0.79). In focus groups, physical activity engagement was related to self-efficacy and symptom severity. Work package 3: in the occupational subcohort, increasing dyspnoea and exposure to inhaled irritants were associated with lower work productivity at baseline. Longitudinally, increasing exacerbations and worsening symptoms, but not a decline in airflow obstruction, were associated with absenteeism and presenteeism. The acceptability of the occupational health intervention was low, leading to low uptake and low implementation of recommendations and making a full trial unfeasible.
Limitations: Work package 1: even with the most intensive approach, only 38% of patients responded to the case-finding invitation. Management of case-found patients with chronic obstructive pulmonary disease in primary care was generally poor, limiting interpretation of the long-term effectiveness of case-finding on clinical outcomes. Work package 2: the components of the BLISS model may not always be routinely available and calculation of the score requires a computerised system. Work package 3: relatively few cohort participants were in paid employment at baseline, limiting the interpretation of predictors of lower work productivity.
Conclusions: This programme has addressed some of the major uncertainties around screening for undiagnosed chronic obstructive pulmonary disease and has resulted in the development of a novel, accurate model for predicting respiratory hospitalisation in people with chronic obstructive pulmonary disease and the inception of a primary care chronic obstructive pulmonary disease cohort for longer-term follow-up. We have also identified factors that may affect work productivity in people with chronic obstructive pulmonary disease as potential targets for future intervention.
Future work: We plan to obtain data for longer-term follow-up of trial participants at 10 years. The BLISS model needs to be externally validated. Our primary care chronic obstructive pulmonary disease cohort is a unique resource for addressing further questions to better understand the prognosis of chronic obstructive pulmonary disease.
Trial registration: Current Controlled Trials ISRCTN14930255.
Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 13. See the NIHR Journals Library website for further project information.