Graham Burns

Effectiveness of cognitive behavioural therapy (CBT) interventions for anxiety in patients with chronic obstructive pulmonary disease (COPD) undertaken by respiratory nurses: the COPD CBT CARE study: (ISRCTN55206395)

BackgroundAnxiety and depression are common co-morbidities in patients with chronic obstructive pulmonary disease (COPD). Serious implications can result from psychological difficulties in COPD including reduced survival, lower quality of life, and reduced physical and social functioning, increased use of health care resources and are associated with unhealthy behaviours such as smoking. Cognitive behavioural therapy (CBT) is a psychological intervention which is recommended for the treatment of many mental health problems including anxiety and depression. Unfortunately access to trained CBT therapists is limited. The aim of this study is to test the hypothesis that CBT delivered by respiratory nurses is effective in the COPD population. In this paper the design of the Newcastle Chronic Obstructive Pulmonary Disease Cognitive Behavioural Therapy Study (Newcastle COPD CBT Care Study) is described.Methods/DesignThis is a prospective open randomised controlled trial comparing CBT with self-help leaflets. The primary outcome measure is the Hospital Anxiety & Depression Scale (HADS) – anxiety subscale. Secondary outcome measures include disease specific quality of life COPD Assessment Tool (CAT), generic quality of life (EQ5D) and HADS-depression subscale. Patients will be followed up at three, six and 12 months following randomisation.DiscussionThis is the first randomised controlled trial to evaluate the use of cognitive behavioural therapy undertaken by respiratory nurses. Recruitment has commenced and should be complete by February 2014.Trial registrationCurrent Controlled Trials, ISRCTN55206395

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial

BackgroundChronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that ‘low dose’ theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of ‘low dose’ theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD.Method/DesignTWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either ‘low dose’ theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1–5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period.DiscussionThe demonstration that ‘low dose’ theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally.Trial registrationCurrent Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014.

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Antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease: protocol of a randomised controlled proof-of-concept trial (APPLE COPD-ICON 2)

Introduction The antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease (APPLE COPD-ICON2) trial is a prospective 2×2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) at high risk of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the required response in platelet function measured using the Multiplate test in patients with COPD. Methods and analysis Patients with COPD are screened for eligibility using inclusion and exclusion criteria. Eligible patients are randomised and allocated into one of four groups to receive aspirin plus placebo, ticagrelor plus placebo, aspirin plus ticagrelor or placebo only. Markers of systemic inflammation, platelet reactivity, arterial stiffness, carotid intima-media thickness (CIMT), lung function and quality of life questionnaires are assessed. The primary outcome consists of inhibition (binary response) of aspirin and ADP-induced platelet function at 6 months. Secondary outcomes include changes in inflammatory markers, CIMT, non-invasive measures of vascular stiffness, quality of life using questionnaires (EuroQol–five dimensions–five levels of perceived problems (EQ5D-5L), St. George’s COPD questionnaire) and to record occurrence of repeat hospitalisation, angina, myocardial infarction or death from baseline to 6 months. Safety outcomes will be rates of major and minor bleeding, forced expiratory volume in 1 s, forced vital capacity and Medical Research Council dyspnoea scale. Ethics and dissemination The study was approved by the North East-Tyne and Wear South Research Ethics Committee (15/NE/0155). Findings of the study will be presented in scientific sessions and published in peer-reviewed journals. Trial registration number ISRCTN43245574; Pre-results.

Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is one of the commonest causes of death worldwide. It causes substantial disability which progresses over many years. Patients need a high level of treatment and supportive care throughout the course of the disease. A key goal of treatment is to improve patient-centered outcomes such as quality of life, symptom burden, and the impact of symptoms on the patient’s overall functioning. Palliative care of COPD is particularly complex because of the clinical course of the disease over many years, the unpredictable trajectory of the disease and the fact that patients often die from other causes. End of life issues and anticipatory care planning should be discussed in patients with advanced COPD but disease-specific therapies, emergency management of exacerbations, and palliative supportive care must run in parallel in an integrated manner. The dying phase is often short, over a few days, when the patient fails to recover from the final exacerbation.

Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD: A Randomized Clinical Trial

Importance Chronic obstructive pulmonary disease (COPD) is a major global health issue and theophylline is used extensively. Preclinical investigations have demonstrated that low plasma concentrations (1-5 mg/L) of theophylline enhance antiinflammatory effects of corticosteroids in COPD. Objective To investigate the effectiveness of adding low-dose theophylline to inhaled corticosteroids in COPD. Design, Setting, and Participants The TWICS (theophylline with inhaled corticosteroids) trial was a pragmatic, double-blind, placebo-controlled, randomized clinical trial that enrolled patients with COPD between February 6, 2014, and August 31, 2016. Final follow-up ended on August 31, 2017. Participants had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 0.7 with at least 2 exacerbations (treated with antibiotics, oral corticosteroids, or both) in the previous year and were using an inhaled corticosteroid. This study included 1578 participants in 121 UK primary and secondary care sites. Interventions Participants were randomized to receive low-dose theophylline (200 mg once or twice per day) to provide plasma concentrations of 1 to 5 mg/L (determined by ideal body weight and smoking status) (n = 791) or placebo (n = 787). Main Outcomes and Measures The number of participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids, or both over the 1-year treatment period. Results Of the 1567 participants analyzed, mean (SD) age was 68.4 (8.4) years and 54% (843) were men. Data for evaluation of the primary outcome were available for 1536 participants (98%) (772 in the theophylline group; 764 in the placebo group). In total, there were 3430 exacerbations: 1727 in the theophylline group (mean, 2.24 [95% CI, 2.10-2.38] exacerbations per year) vs 1703 in the placebo group (mean, 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference, 0.01 (95% CI, −0.19 to 0.21) and adjusted incidence rate ratio, 0.99 (95% CI, 0.91-1.08). Serious adverse events in the theophylline and placebo groups included cardiac, 2.4% vs 3.4%; gastrointestinal, 2.7% vs 1.3%; and adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%). Conclusions and Relevance Among adults with COPD at high risk of exacerbation treated with inhaled corticosteroids, the addition of low-dose theophylline, compared with placebo, did not reduce the number COPD exacerbations over a 1-year period. The findings do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations. Trial Registration isrctn.org Identifier: ISRCTN27066620

S4 A randomised controlled trial (rct) of cognitive behavioural therapy (cbt) for patients with chronic obstructive pulmonary disease

Background Anxiety and depression are common co-morbidities in COPD. We conducted a RCT comparing CBT delivered by respiratory nurses (RNs) and self-help leaflets in 279 patients with COPD and anxiety. The CBT intervention delivered by RNs achieved clinical and statistical improvements for anxiety, depression and improving quality of life.1 RNs with dual physical and psychological skills are rare. However there is an appetite for RNs to be trained to identify and treat psychological difficulties experienced by respiratory patients using CBT.2 Aims To evaluate the effectiveness of The Lung Manual Intervention used in The Newcastle COPD CBT Care study1 on patient outcomes when delivered by nurses who completed 3 day foundation training compared to advanced post-graduate education in CBT. Methods Following an educational course, four respiratory nurses delivered The Lung Manual Intervention.1 Four nurses were randomly allocated patients and delivered CBT. Nurses with Diploma training delivered CBT to 83 patients; foundation level delivered 32. CBT sessions were audio-recorded to explore delivery of the intervention in practice. The recordings were then assessed fidelity of intervention delivery by an independent CBT therapist. Unpaired t-tests were used to compare mean anxiety scores and at baseline and three months. Results The nurses competency was rated highly by an independent CBT therapist. The mean number of CBT sessions was 4 and this was similar for all nurses. Table 1 summarises the outcome from nurses delivering The Lung Manual CBT intervention. Conclusion Brief education in CBT was effective in improving patient symptoms of anxiety at three months. RNs with dual skills in physical and psychological well being may be an appropriate model to provide holistic care for patients with COPD. References Heslop-Marshall K, Stenton C, Newton J, Carrick-Sen D, Baker C, Burns G, De Soyza A. A RCT of CBT delivered by respiratory nurses to reduce anxiety in COPD`. ERJ 2016;48:OA289. doi:10.1183/13993003.congress-2016.OA289 Heslop-Marshall K, Knighting K, Pilkington M, Kelly C. A UK survey on the experiences and views of Respiratory Nurses (RNs) on their role in delivering Cognitive Behavioural Therapy (CBT) for patients with Chronic Obstructive Pulmonary Disease (COPD)2017. In press. Abstract S4 Table 1 Summary of outcome from RNs delivering the lung manual intervention based on level of training Level of Training Number of patients/(percent) Mean HADS-Anxiety/SD at baseline Mean HADS-Anxiety at Three months Mean Difference at threemonths p-value (95% CI) Diploma level 83 (72) 12.3 (3.11) 8.93 (4.36) 3.37 <0.001 2.43–4.34 Foundation level 32 (28) 12.2 (3.26) 8.8 (4.92) 3.41 <0.001 2.05–4.76

M24 Prevalence of anxiety and patient characteristics from a randomised controlled trial (RCT) to identify if cognitive behavioural therapy (CBT) by respiratory nurses reduces anxiety in COPD

Introduction Anxiety and depression are common co-morbidities in COPD. Anxiety is associated with increased breathlessness, lower levels of self-efficacy, impaired health status, poorer treatment outcomes and reduced survival, increased risk of hospitalisation, longer in-patient stay, readmissions and unhealthy behaviours such as smoking and lack of exercise. The aim of this abstract is to present prevalence data, engagement and baseline patient characteristics from the largest RCT on CBT in COPD. Study design A multicentre RCT with follow up at 3, 6 and 12 months (ISCRCTN55206395). Outcome measures include mean HADS-A (anxiety) and HADS-D (depression) score,1 EuroQol -5D Questionnaire,2 COPD Clinical Assessment Tool3 and admission prevention at three, six and 12 months post intervention. Approach 1,518 patients were screened for symptoms of anxiety using the Hospital Anxiety and Depression Scale (HADS). Two thirds, 705 (59%) patients scored ≥8 for anxiety and were approached. Intervention Up to 6 CBT sessions provided by one of four respiratory nurses were offered. Self-help leaflets on anxiety and depression were provided as standard care. Usual care Self- help leaflets only. Results 42% of eligible patients consented to take part. Groups were well matched at baseline (Table 1) with no correlation between FEV1 and anxiety. A median of 4 CBT sessions (range 2–6) was delivered. Retention was high: 85% at 3 months and 72% at 6 months.Abstract M24 Table 1 Baseline characteristics CBT Group (n = 139) Control Group (n = 140) p-value (95% CI) Mean (SD) Mean (SD) Age 66 67 66.5 Gender Male 61 (44) 67 (48) 128 (46) Female 78 (56) 73 (52) 151 (54) Severity of COPD Mild 16 (11) 13 (9) 29 (10) Moderate 44 (32) 47 (34) 91 (33) Severe 50 (36) 49 (35) 99 (35) Very Severe 29 (21) 31 (22) 60 (22) Educational Level No educational qualifications 100 (75) 103 (77) 203 (73) HADS-Anxiety Score 12.3 (3.19) 12.0 (2.94) 0.47 (-0.456–0.988) HADS-Depression Score 9.4 (4.01) 9.0 (3.68) 0.34 (-0.470–1.347) CAT (Health Status) 28.2 (6.45) 28.7 (5.99) 0.52 (-1.944–0.990) EQ5D 0.41 (0.29) 0.41 (0.30) 0.95 (-0.07–0.07) Married or Co-habiting 68 (49) 63p (45) 132 (47) Current smoker 39 (28) 40 (29) 79 (28) Mean pack years 46 49 47 BMI 26 27 26.5 Conclusion The prevalence of anxiety and depression is high in patients with COPD and screening is therefore recommended. Affected patients were willing to engage in CBT in this large study. Results from 3, 6 and 12 months data will be will be available in November 2015 and will be reported. Results will include the cost effectiveness of CBT in COPD delivered by respiratory nurses. Funding NIHR fellowship. References 1 Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–370 2 EQ-5D. www.euroqol.org/about-eq5d/how-to-use-eq-5d.html. Accessed 11.4.2015 3 Jone PW, Harding G, Berry P, Wiklund I, Chen WH, Kline LN. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009;34(3):648–654