Tailored, psychological intervention for anxiety or depression in people with chronic obstructive pulmonary disease (COPD), TANDEM (Tailored intervention for ANxiety and DEpression Management in COPD): protocol for a randomised controlled trial.

BACKGROUND: People with chronic obstructive pulmonary disease (COPD) are at increased risk of depression and anxiety, which greatly reduces their quality of life and is associated with worse outcomes; but these psychological co-morbidities are under-recognised and undertreated in COPD patients. Pulmonary rehabilitation (PR) improves mood for up to 6 months but health practitioners under-refer, and patients commonly fail to attend/complete PR. Research suggests that complex non-pharmacological interventions, including both psychological and exercise components, may reduce anxiety and depression in COPD. We have developed a tailored, cognitive behavioural approach (CBA) intervention for patients with COPD and co-morbid anxiety and/or depression ('TANDEM'), which precedes and optimises the benefits of currently offered PR. We hypothesise that such a psychological intervention, delivered by supervised, trained respiratory healthcare professionals, will improve mood in patients with mild to moderate anxiety and/or depression and encourage uptake and completion of PR. METHODS: We will conduct a multi-centre, pragmatic, randomised controlled trial of the TANDEM intervention compared to usual care across the Midlands, London, the South East and Bristol, UK. We will train healthcare professionals familiar with COPD to deliver the manualised, tailored, face-to-face, one-to-one intervention weekly for 6-8 weeks. We will recruit 430 participants from primary, community and secondary care with confirmed COPD and moderate to very severe airflow limitation, who are eligible for assessment for PR, and who screen positive for symptoms of mild/moderate depression and/or anxiety using the Hospital Anxiety and Depression scale (HADS). Participants will be randomised 1.25:1 (intervention: usual care). The co-primary outcomes are the HADS anxiety and depression subscale scores at 6 months; participants will be followed up to 12 months. Secondary outcomes include uptake and completion of PR and healthcare resource use. There will be a parallel process evaluation and a health economic evaluation. DISCUSSION: The TANDEM intervention has the potential to optimise the unrealised synergy between a psychological intervention and PR. The CBA sessions will precede PR and target individuals' cognitions, behaviours and symptoms associated with anxiety and depression to decrease psychological morbidity and increase effective self-management amongst patients with COPD. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN59537391. Registered on 20 March 2017. Protocol version 6.0, 22 April 2018.

Safety and tolerability of nintedanib for the treatment of idiopathic pulmonary fibrosis in routine UK clinical practice.

In IPF, commencement of antifibrotic therapy in patients with preserved lung volume may increase the duration of therapy http://ow.ly/4HeM30lFS67.

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.

Asthma and occupation in the 1958 birth cohort.

OBJECTIVE: To examine the association of adult onset asthma with lifetime exposure to occupations and occupational exposures. METHODS: We generated lifetime occupational histories for 9488 members of the British 1958 birth cohort up to age 42 years. Blind to asthma status, jobs were coded to the International Standard Classification of Occupations 1988 and an Asthma Specific Job Exposure Matrix (ASJEM) with an expert re-evaluation step. Associations of jobs and ASJEM exposures with adult onset asthma were assessed in logistic regression models adjusting for sex, smoking, social class at birth and childhood hay fever. RESULTS: Of the 7406 cohort members with no asthma or wheezy bronchitis in childhood, 639 (9%) reported asthma by age 42 years. Adult onset asthma was associated with 18 occupations, many previously identified as risks for asthma (eg, farmers: OR 4.26, 95% CI 2.06 to 8.80; hairdressers: OR 1.88, 95% CI 1.24 to 2.85; printing workers: OR 3.04, 95% CI 1.49 to 6.18). Four were cleaning occupations and a further three occupations were likely to use cleaning agents. Adult onset asthma was associated with five of the 18 high-risk specific ASJEM exposures (flour exposure: OR 2.12, 95% CI 1.17 to 3.85; enzyme exposure: OR 2.32, 95% CI 1.22 to 4.42; cleaning/disinfecting products: OR 1.67, 95% CI 1.26 to 2.22; metal and metal fumes: OR 1.45, 95% CI 1.02 to 2.07; textile production: OR 1.71, 95% CI 1.12 to 2.61). Approximately 16% (95% CI 3.8% to 27.1%) of adult onset asthma was associated with known asthmagenic occupational exposures. CONCLUSIONS: This study suggests that about 16% of adult onset asthma in British adults born in the late 1950s could be due to occupational exposures, mainly recognised high-risk exposures.

DNA methylation biomarkers offer improved diagnostic efficiency in lung cancer.

The exceptional high mortality of lung cancer can be instigated to a high degree by late diagnosis. Despite the plethora of studies on potential molecular biomarkers for lung cancer diagnosis, very few have reached clinical implementation. In this study, we developed a panel of DNA methylation biomarkers and validated their diagnostic efficiency in bronchial washings from a large retrospective cohort. Candidate targets from previous high-throughput approaches were examined by pyrosequencing in an independent set of 48 lung tumor/normal paired. Ten promoters were selected and quantitative methylation-specific PCR (qMSP) assays were developed and used to screen 655 bronchial washings from the Liverpool Lung Project (LLP) subjects divided into training (194 cases and 214 controls) and validation (139 cases and 109 controls) sets. Three statistical models were used to select the optimal panel of markers and to evaluate the performance of the discriminatory algorithms. The final logit regression model incorporated hypermethylation at p16, TERT, WT1, and RASSF1. The performance of this 4-gene methylation signature in the validation set showed 82% sensitivity and 91% specificity. In comparison, cytology alone in this set provided 43% sensitivity at 100% specificity. The diagnostic efficiency of the panel did not show any biases with age, gender, smoking, and the presence of a nonlung neoplasm. However, sensitivity was predictably higher in central (squamous and small cell) than peripheral (adenocarcinomas) tumors, as well as in stage 2 or greater tumors. These findings clearly show the impact of DNA methylation-based assays in the diagnosis of cytologically occult lung neoplasms. A prospective trial is currently imminent in the LLP study to provide data on the enhancement of diagnostic accuracy in a clinical setting, including by additional markers.

Correlation between perceived asthma control and thoraco-abdominal asynchrony in primary care patients diagnosed with asthma.

OBJECTIVE: Thoraco-abdominal asynchrony (TAA), the discordant movement of the abdomen and thorax, may impact upon health-related variables. Here, we investigated the extent to which TAA is associated with health-related variables, particularly perceived asthma control and quality of life. METHODS: Ambulatory respiratory data from 43 patients diagnosed with asthma and 43 healthy age and sex-matched controls were recorded over 4 hours. Phase relation (Ph Rel Total), the percentage of time that the effects of rib cage (RC) and diaphragmatic movement result in opposite effects on intra-thoracic volume, quantified TAA. Subjects completed the Mini Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ), Nijmegen questionnaire (NQ), Hospital Anxiety and Depression Scale (HADS), Spielberger State-Trait Anxiety Inventory (STAI), and General Health Perception (GHP) subscale of the short form 36 questionnaire'. Capnography profiling, breath-hold time (BHT), and standard spirometry were performed. RESULTS: The time in asynchrony was significantly greater in the asthma than in the healthy control group (Ph Rel Total = 14% (interquartile range (IQR) 8.5-20.7%) versus 10.4% (IQR 7.1-14.5%), p = .012). In patients with asthma, Ph Rel Total was weakly associated with poorer ACQ scores (r = 0.33, p = .03), and in the healthy control group with GHP (r = 0.319, p = .037). Post-hoc exploratory analysis revealed a moderate relationship in the female asthma subgroup between Ph Rel Total and AQLQ (r = -0.56, p = .003). CONCLUSIONS: TAA may be associated with decreased perceived asthma control. In healthy individuals, asynchrony may be associated with low perception of general health. Further studies are required to investigate if the reduction of TAA improves these health-related variables.

Performance evaluation of the DNA methylation biomarker SHOX2 for the aid in diagnosis of lung cancer based on the analysis of bronchial aspirates.

In the identification of subjects with lung cancer, increased DNA methylation of the SHOX2 gene locus in bronchial aspirates has previously been proven to be a clinically valuable biomarker. This is particularly true in cases where the cytological and histological results following bronchoscopy are undetermined. This previous case control study was conducted using research assay components and a complex work flow. To facilitate the use in a diagnostic setting, a CE marked in vitro diagnostic test kit to quantify SHOX2 DNA methylation in bronchial aspirates was developed and characterized. The presented assay for measuring SHOX2 DNA methylation in bronchial aspirates is based on two major steps: generation of bisulfite converted template DNA from patient samples followed by subsequent determination of SHOX2 biomarker methylation by real-time PCR. Individual kits for DNA preparation, real-time PCR analysis and work flow control were developed. This study describes the analytical performance (reproducibility, accuracy, interfering substances, cross-reactivity) of the in vitro diagnostic (IVD) test kit 'Epi proLung BL Reflex Assay'. In addition, the intended use of the test was validated in a clinical performance evaluation (case control) study comprised of 250 patients (125 cases, 125 controls). The results describe the test as a robust and reliable diagnostic tool for identifying patients with lung cancer using Saccomanno-fixed bronchial lavage specimens (AUC [95% confidence intervals] = 0.94 [0.91-0.98], sensitivity 78% [69-86]/specificity 96% [90-99]). This test may be used as a diagnostic adjunct to existing clinical and pathological investigations in lung cancer.

Guidelines on the radical management of patients with lung cancer.

A joint initiative by the British Thoracic Society and the Society for Cardiothoracic Surgery in Great Britain and Ireland was undertaken to update the 2001 guidelines for the selection and assessment of patients with lung cancer who can potentially be managed by radical treatment.

Are we failing workers with symptoms suggestive of occupational asthma?

AIMS: To assess the route to secondary care for patients with possible occupational asthma, and to document the duration of workrelated symptoms and referral times. METHODS: Consecutive patients with suspected occupational asthma were recruited to a case series from six secondary care clinics with an interest in occupational asthma. Semi-structured interviews were performed and hospital case notes were reviewed to summarise relevant investigations and diagnosis. RESULTS: 97 patients were recruited, with a mean age of 44.2 years (range 24-64), 51 of whom (53%) had occupational asthma confirmed as a diagnosis. Most (96%) had consulted their general practitioner (GP) at least once with work-related respiratory symptoms, although these had been present for a mean of 44.6 months (range 0-320 months) on presentation to secondary care. Patients experienced a mean delay for assessment in secondary care of 4 years (range 1-27 years) following presentation in primary care. CONCLUSIONS: Significant diagnostic delay currently occurs for patients with occupational asthma in the UK.

Occupational asthma: an assessment of diagnostic agreement between physicians.

OBJECTIVES: To investigate the levels of agreement between expert respiratory physicians when making a diagnosis of occupational asthma. METHODS: 19 cases of possible occupational asthma were identified as part of a larger national observational cohort. A case summary for each case was then circulated to 12 physicians, asking for a percentage likelihood, from the supplied information, that this case represented occupational asthma. The resulting probabilities were then compared between physicians using Spearman's rank correlation and Cohen's kappa coefficients. RESULTS: Agreement between the 12 physicians for all 19 cases was generally good as assessed by Spearman's rank correlation. For all 66 physician-physician interactions, 45 were found to correlate significantly at the 5% level. The agreement assessed by kappa analysis was more variable, with a median kappa value of 0.26, (range -0.2 to +0.76), although 7 of the physicians agreed significantly (p<0.05) with >or=5 of their colleagues. Only in one case did the responses for probability of occupational asthma all exceed the "on balance" 50% threshold, although 12 of the 19 cases had an interquartile range of probabilities not including 50%, implying "on balance" agreement. The median probability values for each physician (all assessing the identical 19 cases) varied from 20% to 70%. Factors associated with a high probability rating were the presence of a positive serial peak expiratory flow Occupation Asthma SYStem (OASYS)-2 chart, and both the presence of bronchial hyper-reactivity and significant change in reactivity between periods of work and rest. CONCLUSIONS: Despite the importance of the diagnosis of occupational asthma and reasonable physician agreement, certain variations in diagnostic assessment were seen between UK expert centres when assessing paper cases of possible occupational asthma. Although this may in part reflect the absence of a normal clinical consultation, a more unified national approach to these patients is required.