Randomised controlled trial testing effectiveness of feedback about lung age or exhaled CO combined with very brief advice for smoking cessation compared to very brief advice alone in North Macedonia: findings from the Breathe Well group.

INTRODUCTION: In 2019, smoking prevalence in North Macedonia was one of the world's highest at around 46% in adults. However, access to smoking cessation treatment is limited and no co-ordinated smoking cessation programmes are provided in primary care. METHODS: We conducted a three parallel-armed randomised controlled trial (n = 1368) to investigate effectiveness and cost-effectiveness of lung age (LA) or exhaled carbon monoxide (CO) feedback combined with very brief advice (VBA) to prompt smoking cessation compared with VBA alone, delivered by GPs in primary care in North Macedonia. All participants who decided to attempt to quit smoking were advised about accessing smoking cessation medications and were also offered behavioural support as part of the "ACT" component of VBA. Participants were aged ≥ 35 years, smoked ≥ 10 cigarettes per day, were recruited from 31 GP practices regardless of motivation to quit and were randomised (1:1:1) using a sequence generated before the start of recruitment. The primary outcome was biochemically validated 7-day point prevalence abstinence at 4 weeks (wks). Participants and GPs were not blinded to allocation after randomisation, however outcome assessors were blind to treatment allocation. RESULTS: There was no evidence of a difference in biochemically confirmed quitting between intervention and control at 4wks (VBA + LA RR 0.90 (97.5%CI: 0.35, 2.27); VBA + CO RR 1.04 (97.5%CI: 0.44, 2.44)), however the absolute number of quitters was small (VBA + LA 1.6%, VBA + CO 1.8%, VBA 1.8%). A similar lack of effect was observed at 12 and 26wks, apart from in the VBA + LA arm where the point estimate was significant but the confidence intervals were very wide. In both treatment arms, a larger proportion reported a reduction in cigarettes smoked per day at 4wks (VBA + LA 1.30 (1.10, 1.54); VBA + CO 1.23 (1.03, 1.49)) compared with VBA. The point estimates indicated a similar direction of effect at 12wks and 26wks, but differences were not statistically significant. Quantitative process measures indicated high fidelity to the intervention delivery protocols, but low uptake of behavioural and pharmacological support. VBA was the dominant intervention in the health economic analyses. CONCLUSION: Overall, there was no evidence that adding LA or CO to VBA increased quit rates. However, a small effect cannot be ruled out as the proportion quitting was low and therefore estimates were imprecise. There was some evidence that participants in the intervention arms were more likely to reduce the amount smoked, at least in the short term. More research is needed to find effective ways to support quitting in settings like North Macedonia where a strong smoking culture persists. TRIAL REGISTRATION: The trial was registered at http://www.isrctn.com (ISRCTN54228638) on the 07/09/2018.

Community lung health service design for COPD patients in China by the Breathe Well group.

COPD is increasingly common in China but is poorly understood by patients, medications are not used as prescribed and there is no access to recommended non-pharmacological treatment. We explored COPD patients' and general practitioners' (GPs) knowledge of COPD, views on its management and the acceptability of a flexible lung health service (LHS) offering health education, exercise, self-management, smoking cessation and mental health support. Using a convergent mixed methods design, data were collected from patients and GPs using focus groups (FGs) in four Chinese cities, questionnaires were also used to collect data from patients. FGs were audio-recorded and transcribed. Quantitative data were analysed descriptively, thematic framework analysis was used for the qualitative data. Two-hundred fifty-one patients completed the questionnaire; 39 patients and 30 GPs participated in ten separate FGs. Three overarching themes were identified: patients' lack of knowledge/understanding of COPD, current management of COPD not meeting patients' needs and LHS design, which was well received by patients and GPs. Participants wanted COPD education, TaiChi, psychological support and WeChat for social support. 39% of survey responders did not know what to do when their breathing worsened and 24% did not know how to use their inhalers. 36% of survey respondents requested guided relaxation. Overall, participants did not fully understand the implications of COPD and current treatment was sub-optimal. There was support for developing a culturally appropriate intervention meeting Chinese patients' needs, health beliefs, and local healthcare delivery. Further research should explore the feasibility of such a service.

Case-finding for COPD in primary care: a qualitative study of patients' perspectives.

Background: COPD is a leading cause of morbidity and mortality, yet it remains largely under-diagnosed. Case-finding is encouraged by many professionals, but there is a lack of information on the patients' views and perspectives. Patients and methods: Semistructured interviews were conducted with adults, aged 40 years or older with a history of smoking, who were eligible and invited for case-finding for COPD as a part of a large UK primary care trial. Patients, including those who consented or declined participation and those with and without COPD after screening, were interviewed. Interviews were transcribed and analyzed using the framework method. Results: The 43 interviews revealed the following two main categories of themes: patients' views on COPD case-finding and barriers to case-finding. Overall, case-finding was deemed important and beneficial. Participants highlighted the need for screening activities to be convenient for patients but perceived that general practitioners (GPs) lacked the time and accessing appointments was difficult. Desire for a health check among symptomatic patients facilitated participation in case-finding. Psychological barriers to engagement included denial of ill health or failure to recognize symptoms, fear of the "test", and lung symptoms being low on the hierarchy of patient health complaints. Mechanical barriers included providing care for another person (and therefore being too busy), being unable to access GP appointments, and lacking feedback of spirometry results or communication of the diagnosis. Conclusion: Patient engagement with case-finding may be limited by denial or lack of recognition of symptoms and physical barriers to attendance. Increasing public awareness of COPD risk factors and early symptoms may enhance case-finding.

Targeted case finding for chronic obstructive pulmonary disease versus routine practice in primary care (TargetCOPD): a cluster-randomised controlled trial.

BACKGROUND: Many individuals with chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. Health-care organisations are implementing case-finding programmes without good evidence of which are the most effective and cost-effective approaches. We assessed the effectiveness and cost-effectiveness of two alternative approaches to targeted case finding for COPD compared with routine practice. METHODS: In this cluster-randomised controlled trial, participating general practices in the West Midlands, UK, were randomly assigned (1:1), via a computer-generated block randomisation sequence, to either a targeted case-finding group or a routine care group. Eligible patients were ever-smokers aged 40-79 years without a previously recorded diagnosis of COPD. Patients in the targeted case-finding group were further randomly assigned (1:1) via their household to receive either a screening questionnaire at the general practitioner (GP) consultation (opportunistic) or a screening questionnaire at the GP consultation plus a mailed questionnaire (active). Respondents reporting relevant respiratory symptoms were invited for post-bronchodilator spirometry. Patients, clinicians, and investigators were not masked to allocation, but group allocation was concealed from the researchers who performed the spirometry assessments. Primary outcomes were the percentage of the eligible population diagnosed with COPD within 1 year (defined as post-bronchodilator forced expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] ratio <0·7 in patients with symptoms or a new diagnosis on their GP record) and cost per new COPD diagnosis. Multiple logistic and Poisson regression were used to estimate effect sizes. Costs were obtained from the trial. This trial is registered with ISRCTN, number ISRCTN14930255. FINDINGS: From Aug 10, 2012, to June 22, 2014, 74 818 eligible patients from 54 diverse general practices were randomly assigned and completed the trial. At 1 year, 1278 (4%) cases of COPD were newly detected in 32 789 eligible patients in the targeted case-finding group compared with 337 (1%) cases in 42 029 patients in the routine care group (adjusted odds ratio [OR] 7·45 [95% CI 4·80-11·55], p<0·0001). The percentage of newly detected COPD cases was higher in the active case-finding group (822 [5%] of 15 378) than in the opportunistic case-finding group (370 [2%] of 15 387; adjusted OR 2·34 [2·06-2·66], p<0·0001; adjusted risk difference 2·9 per 100 patients [95% CI 2·3-3·6], p<0·0001). Active case finding was more cost-effective than opportunistic case finding (£333 vs £376 per case detected, respectively). INTERPRETATION: In this well established primary care system, routine practice identified few new cases of COPD. An active targeted approach to case finding including mailed screening questionnaires before spirometry is a cost-effective way to identify undiagnosed patients and has the potential to improve their health. FUNDING: National Institute for Health Research.

TargetCOPD: a pragmatic randomised controlled trial of targeted case finding for COPD versus routine practice in primary care: protocol.

BACKGROUND: Many people with clinically significant chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. There are a number of small studies which have examined possible methods of case finding through primary care, but no large RCTs that have adequately assessed the most cost-effective approach. METHODS/DESIGN: In this study, using a cluster randomised controlled trial (RCT) in 56 general practices in the West Midlands, we plan to investigate the effectiveness and cost-effectiveness of a Targeted approach to case finding for COPD compared with routine practice. Using an individual patient RCT nested in the Targeted arm, we plan also to compare the effectiveness and cost-effectiveness of Active case finding using a postal questionnaire (with supplementary opportunistic questionnaires), and Opportunistic-only case finding during routine surgery consultations.All ever-smoking patients aged 40-79 years, without a current diagnosis of COPD and registered with participating practices will be eligible. Patients in the Targeted arm who report positive respiratory symptoms (chronic cough or phlegm, wheeze or dyspnoea) using a brief questionnaire will be invited for further spirometric assessment to ascertain whether they have COPD or not. Post-bronchodilator spirometry will be conducted to ATS standards using an Easy One spirometer by trained research assistants.The primary outcomes will be new cases of COPD and cost per new case identified, comparing targeted case finding with routine care, and two types of targeted case finding (active versus opportunistic). A multilevel logistic regression model will be used to model the probability of detecting a new case of COPD for each treatment arm, with clustering of patients (by practice and household) accounted for using a multi-level structure.A trial-based analysis will be undertaken using costs and outcomes collected during the trial. Secondary outcomes include the feasibility, efficiency, long-term cost-effectiveness, patient and primary care staff views of each approach. DISCUSSION: This will be the largest RCT of its kind, and should inform how best to identify undiagnosed patients with COPD in the UK and other similar healthcare systems. Sensitivity analyses will help local policy-makers decide which sub-groups of the population to target first. TRIAL REGISTRATION: Current controlled trials ISRCTN14930255.

The acute impact of a hematopoietic allograft on lung function and inflammation: a prospective observational study.

BACKGROUND: No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT) on pulmonary inflammation or lung function. METHODS: Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant. RESULTS: Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94%) were included in the study. Compared to baseline, pulmonary inflammation as measured by exhaled nitric oxide increased after receiving a HSCT with the largest increment seen at three months (+6.0 ppb, 95%CI: +0.4 to +11.5), and this was sustained at six months. Percent predicted forced expiratory volume in one second decreased over the same period, with the largest decrease observed at six weeks (-5.9%, 95% CI: -8.9 to -2.9), and this was also sustained over a six month period. Similar associations were observed for FVC. A larger increase in exhaled nitric oxide from baseline at six weeks and three months may be associated with decreased mortality (p=0.06, p=0.04 respectively). CONCLUSION: Our data demonstrate that recipients of an allogeneic HSCT experience an increase in biomarkers of pulmonary inflammation and a decrease in lung function in the first six months after the procedure. If independently validated in other study populations, these observations could have potential as a prognostic biomarker for this patient group.