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The prostanoid DP receptor (PTGDR) is shown to be involved in the asthma patho-physiology and the results from the published genetic association studies are inconsistent. Four single nucleotide polymorphisms (SNPs) in PTGDR were genotyped in 342 and 294 families from UK and Denmark respectively. Asthma and asthma-related phenotypes were analyzed using family-based association analyses. In the UK families, a promoter polymorphism (−731A/G) showed significant associations with asthma (P=0.0022), atopic asthma (P=0.0044), bronchial hyperreactivity or BHR (P=0.00120) and strict asthma (P=0.0008). The P-values for asthma, BHR and strict asthma were significant even after the most stringent correction for the number of markers and the number of phenotypes analyzed (<0.0031). An intronic polymorphism (+6651C/T) also showed significant associations with asthma (P=0.0302), atopic asthma (P=0.0131), BHR (P=0.0249) and strict asthma (P=0.0261). In the Danish families, an intronic polymorphism (+6541C/T) showed significant associations with asthma (P=0.0071), atopic asthma (P=0.0348), BHR (P=0.0033) and strict asthma (P=0.0381). The results of haplotype analyses supported the ones of the single SNP analyses. Thus, we demonstrated significant evidence of association between polymorphisms in PTGDR with asthma phenotypes in the two Caucasian populations.Genes and Immunity (2007) 8, 398–403; doi:10.1038/sj.gene.6364399; published online 31 May 2007 [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests. NSH is chair of Action on Smoking and Health (UK). JG is chair of the European Respiratory Society’s tobacco control committee. AB is the European Respiratory Society’s guidelines director. The statements are personal and do not necessarily represent those of our employers.

Competing Interests: We have no competing interests.

Background: COPD is a major cause of morbidity and mortality in populations eligible for lung cancer screening. We investigated the role of spirometry in a community-based lung cancer screening programme., Methods: Ever smokers, age 55-74, resident in three deprived areas of Manchester were invited to a 'Lung Health Check' (LHC) based in convenient community locations. Spirometry was incorporated into the LHCs alongside lung cancer risk estimation (Prostate, Lung, Colorectal and Ovarian Study Risk Prediction Model, 2012 version (PLCO M2012 )), symptom assessment and smoking cessation advice. Those at high risk of lung cancer (PLCO M2012 ≥1.51%) were eligible for annual low-dose CT screening over two screening rounds. Airflow obstruction was defined as FEV 1 /FVC<0.7. Primary care databases were searched for any prior diagnosis of COPD., Results: 99.4% (n=2525) of LHC attendees successfully performed spirometry; mean age was 64.1±5.5, 51% were women, 35% were current smokers. 37.4% (n=944) had airflow obstruction of which 49.7% (n=469) had no previous diagnosis of COPD. 53.3% of those without a prior diagnosis were symptomatic (n=250/469). After multivariate analysis, the detection of airflow obstruction without a prior COPD diagnosis was associated with male sex ( adj OR 1.84, 95% CI 1.37 to 2.47; p<0.0001), younger age (p=0.015), lower smoking duration (p<0.0001), fewer cigarettes per day (p=0.035), higher FEV 1 /FVC ratio (<0.0001) and being asymptomatic ( adj OR 4.19, 95% CI 2.95 to 5.95; p<0.0001). The likelihood of screen detected lung cancer was significantly greater in those with evidence of airflow obstruction who had a previous diagnosis of COPD ( adj OR 2.80, 95% CI 1.60 to 8.42; p=0.002)., Conclusions: Incorporating spirometry into a community-based targeted lung cancer screening programme is feasible and identifies a significant number of individuals with airflow obstruction who do not have a prior diagnosis of COPD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The changes in grading of disease severity and treatment recommendations for patients with COPD in the 2017 GOLD strategy may present an opportunity for reducing treatment burden for the patients and costs to the health care system. The aim of this study was to assess the implications of the GOLD 2017 grading system in terms of change in distribution across GOLD groups A-D for existing patients in UK primary care and estimate the potential cost savings of implementing GOLD 2017 treatment recommendations in UK primary care., Patients and Methods: Using electronic health record data from the Clinical Practice Research Datalink (CPRD), patients aged ≥35 years with spirometry-confirmed COPD, receiving care during 2016, were included. The cohort was graded according to the GOLD 2017 groups (A-D), and treatment costs were calculated, according to corresponding recommendations, to observe the difference in actual vs predicted costs., Results: When applying GOLD 2013 criteria, less than half of the cohort (46%) was assigned to GOLD A or B, as compared to 86% when applying the GOLD 2017 grading. The actual mean annual maintenance treatment cost was £542 per patient vs a predicted £389 for treatment according to the 2017 GOLD strategy., Conclusion: There is a potential to make significant cost savings by implementing the grading and treatment recommendations from the 2017 GOLD strategy., Competing Interests: Disclosure AG, SD, KM and CP are employees of Boehringer Ingelheim Ltd. JV has received honoraria from AstraZeneca, Boehringer-Ingelheim, Chiesi and Novartis within the last 3 years for advising and presenting. AGM has received honoraria from Boehringer-Ingelheim and GlaxoSmithKline within the last 3 years. The authors report no other conflicts of interest in this work.

Background: The Asthma Salford Lung Study demonstrated the effectiveness and safety of initiating once-daily inhaled fluticasone furoate/vilanterol (FF/VI) versus continuing usual care (UC) in asthma patients in UK primary care [1]. Here, we report a detailed analysis of patient-reported outcome (PRO) endpoints., Methods: Adults with symptomatic asthma maintained on inhaled corticosteroids (ICS) ± long-acting beta 2 -agonists (LABA) were randomized 1:1 to initiate FF/VI (100 [200]/25 μg) or continue UC. PROs were measured using the Asthma Control Test (ACT), Standardized Asthma Quality of Life Questionnaire (AQLQ [S]), Work Productivity and Activity Impairment: asthma questionnaire, and EQ-5D-3L (EuroQol 5-Dimensions 3-Levels) questionnaire, at timepoints across the 12-month study period., Results: The individual components of ACT response (total score ≥20 or improvement from baseline ≥3) both contributed to the composite primary effectiveness endpoint at Week 24, with odds ratios favoring FF/VI over UC in both cases. Patients initiating FF/VI versus continuing UC were more likely to maintain/improve asthma control, regardless of baseline control status. The odds of patients being responders on AQLQ (S) total score and on individual AQLQ domains at Week 52 were significantly higher for FF/VI versus UC (all p < .001). FF/VI was associated with significantly greater reductions in overall work and activity impairment due to asthma (both p < .001), and a significantly greater change from baseline in EQ visual analogue scale score (p = .007), versus UC at Week 52. PRO findings were consistent across baseline ICS and ICS/LABA subsets., Conclusions: Initiation of FF/VI versus continuing UC was associated with consistent improvements in PROs., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Guidelines for chronic obstructive pulmonary disease (COPD) management are based largely on results from double-blind randomised controlled trials (RCTs) of efficacy. These trials have high internal validity and test whether a drug is efficacious, but they are conducted in highly selected populations that may differ significantly from patients with COPD seen in routine practice.We compared the baseline characteristics, healthcare use and outcomes between the Salford Lung Study (SLS), an open-label effectiveness RCT, with six recent large-scale efficacy RCTs. We also calculated the proportion of SLS patients who would have been eligible for inclusion in an efficacy RCT by applying the inclusion criteria used in efficacy trials of combination treatments.SLS patients were older, included more females and more current smokers, had more comorbidities (including asthma), and had more often experienced exacerbations prior to inclusion. In the SLS, rates of moderate or severe exacerbations, incidence of overall serious adverse events (SAEs), and SAEs of pneumonia were more frequent. A maximum of 30% of patients enrolled in the SLS would have been eligible for a phase IIIa regulatory exacerbation study.Patients in large COPD efficacy RCTs have limited representativeness compared with an effectiveness trial. This should be considered when interpreting efficacy RCT outcomes and their inclusion into guidelines., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2018.)

Aim: Early morning symptoms (EMS) in people with COPD are associated with poor health, impaired activities and increased exacerbation risk. We describe the development and preliminary validation of the Manchester Early Morning Symptom Index (MEMSI) to quantify EMS in COPD., Methods: Focus groups and cognitive debriefing with patients with COPD were used to develop the potential item list, followed by a cross-sectional study to finalise the items for inclusion. In addition to test-retest reliability, comparisons with the St George's Respiratory Questionnaire-C (SGRQ-C), modified Medical Research Council Dyspnoea Scale, Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) and Hospital Anxiety and Depression Scale (HADS) evaluated construct validity. Hierarchical methods informed item deletion and Rasch analysis was applied to assess scale unidimensionality., Results: 23 items were identified from the focus groups and debriefings. The cross-sectional study involved 203 patients with COPD (mean age 64.7 SD 7.5 years, male 63%, Global Initiative for Chronic Obstructive Lung Disease (GOLD): 1:14% 2:41% 3:25% 4: 7%). 13 items were removed during item reduction. MEMSI contains 10 items, demonstrates good overall fit to the Rasch model (χ(2) p=0.26) and item score distribution; excellent reliability (Person Separation Index: 0.91) and good test-retest repeatability (r=0.82). It correlates with the SGRQ-C (r=0.73), FACIT-F (r=-0.65) and HADS (r=0.53-0.54) indicating good construct validity., Conclusions: MEMSI is a reliable and valid unidimensional measure of EMS for patients with COPD. It is simple to use and score supporting its suitability for research and clinical use. Work is underway to determine the minimal clinical important difference and cross-cultural validity., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)