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      Clinical characteristics of patients newly diagnosed with COPD by the fixed ratio and lower limit of normal criteria: a cross-sectional analysis of the TargetCOPD trial

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          Consensus on the definition of airflow obstruction to diagnose COPD remains unresolved.


          We undertook systematic case finding for COPD in primary care using the fixed ratio (FR) criterion (forced expiratory volume in 1 s/forced vital capacity [FEV 1/FVC] <0.7) for defining airflow obstruction and also using the lower limit of normal (LLN). We then compared the clinical characteristics of those identified by the 2 criteria.


          A total of 3,721 individuals reporting respiratory symptoms were invited for spirometry. A total of 2,607 attended (mean age 60.4 years, 52.8% male, 29.8% current smokers) and 32.6% had airflow obstruction by FR (“FR+”) and 20.2% by LLN (“LLN+”). Compared with the LLN+/FR+ group, the LLN−/FR+ group (12.4%) was significantly older, had higher FEV 1 and FEV 1/FVC, lower COPD assessment test scores, and less cough, sputum, and wheeze, but was significantly more likely to report a diagnosis of heart disease (14.2% versus 6.9%, p<0.001). Compared with the LLN+/FR+ group, the LLN−/FR− group was younger, had a higher body mass index, fewer pack-years, a lower prevalence of respiratory symptoms except for dyspnea, and lower FVC and higher FEV 1. The probability of known heart disease was significantly lower in the LLN+/FR+ group compared with those with preserved lung function (LLN−/FR−) (adjusted odds ratio 0.62, 95% CI: 0.43–0.90) but this was not seen in the LLN−/FR+ group (adjusted odds ratio 0.90, 95% CI: 0.63–1.29).


          In symptomatic individuals, defining airflow obstruction by FR instead of LLN identifies a significant number of individuals who have less respiratory and more cardiac clinical characteristics.

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          Most cited references 14

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          Lung function testing: selection of reference values and interpretative strategies. American Thoracic Society.

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            Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD.

            Chronic obstructive pulmonary disease (COPD) is associated with important chronic comorbid diseases, including cardiovascular disease, diabetes and hypertension. The present study analysed data from 20,296 subjects aged > or =45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). The sample was stratified based on baseline lung function data, according to modified Global Initiative for Obstructive Lung Disease (GOLD) criteria. Comorbid disease at baseline and death and hospitalisations over a 5-yr follow-up were then searched for. Lung function impairment was found to be associated with more comorbid disease. In logistic regression models adjusting for age, sex, race, smoking, body mass index and education, subjects with GOLD stage 3 or 4 COPD had a higher prevalence of diabetes (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-1.9), hypertension (OR 1.6, 95% CI 1.3-1.9) and cardiovascular disease (OR 2.4, 95% CI 1.9-3.0). Comorbid disease was associated with a higher risk of hospitalisation and mortality that was worse in people with impaired lung function. Lung function impairment is associated with a higher risk of comorbid disease, which contributes to a higher risk of adverse outcomes of mortality and hospitalisations.
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              Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

              Inhaled anticholinergics (ipratropium bromide or tiotropium bromide) are widely used in patients with chronic obstructive pulmonary disease (COPD) but their effect on the risk of cardiovascular outcomes is unknown. To ascertain the cardiovascular risks of inhaled anticholinergics, including cardiovascular death, myocardial infarction (MI), and stroke. Systematic searches were conducted on March 19, 2008, of relevant articles in MEDLINE, the Cochrane Database of systematic reviews, regulatory authority Web sites in the United States and the United Kingdom, and manufacturers' trial registries with no date restrictions. Randomized controlled trials of any inhaled anticholinergic for treatment of COPD that had at least 30 days of treatment and reported on cardiovascular events. The primary outcome was a composite of cardiovascular death, MI, or stroke. The secondary outcome was all-cause mortality. Relative risks (RRs) were estimated using fixed-effects models and statistical heterogeneity was estimated with the I(2) statistic. After a detailed screening of 103 articles, 17 trials enrolling 13,645 [corrected] patients were analyzed. Follow-up duration ranged from 6 weeks to 5 years. Cardiovascular death, MI, or stroke occurred in 134 of 6984 [corrected] patients (1.9%) [corrected] receiving inhaled anticholinergics and 83 of 6661 [corrected] patients (1.2%) receiving control therapy (RR, 1.60 [corrected] [95% confidence interval {CI}, 1.22-2.10]; [corrected] P 6 months) confirmed the significantly increased risk of cardiovascular death, MI, or stroke (2.9% of patients treated with anticholinergics vs 1.8% of the control patients; RR, 1.73 [95% CI, 1.27-2.35]; [corrected] P < .001, I(2) = 0%). Inhaled anticholinergics are associated with a significantly increased risk of cardiovascular death, MI, or stroke among patients with COPD.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                21 June 2018
                : 13
                : 1979-1986
                [1 ]Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK
                [2 ]Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK
                Author notes
                Correspondence: Shamil Haroon, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK, Tel +44 121 414 5042, Email s.haroon@
                © 2018 Miller et al. This work is published by Dove Medical Press Limited, and licensed under a Creative Commons Attribution License

                The full terms of the License are available at The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Original Research

                Respiratory medicine

                lower limit of normal, diagnostic criteria, primary care


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