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1.  Postoperative outcome after coronary artery bypass grafting in chronic obstructive pulmonary disease 
It is uncertain if the presence and severity of airflow obstruction in chronic obstructive pulmonary disease (COPD) is predictive of surgical morbidity and mortality after coronary artery bypass grafting (CABG).
Retrospective study of patients who underwent CABG between 1998 and 2003 in a university-affiliated hospital for whom a preoperative spirometry was available. COPD was diagnosed in smokers or ex-smokers 50 years of age or older in the presence of irreversible airflow obstruction. Patients were divided into three groups depending on the spirometry: controls (forced expiratory volume in 1 s [FEV1] 80% or more, FEV1/forced vital capacity [FVC] greater than 0.7), mild to moderate COPD (FEV1 50% or more and FEV1/FVC 0.7 or less) and severe COPD (FEV1 less than 50% and FEV1/FVC 0.7 or less).
Among the 411 files studied, 322 (249 men, 68±8 years of age) were retained (controls, n=101; mild to moderate COPD, n=153; severe COPD, n=68). The mortality rate (3.0%, 2.6% and 0%, respectively) was comparable among the three groups. Patients with severe COPD had a slightly longer hospital stay than controls (mean difference 0.7±1.4 days, P<0.05). Pulmonary infections were more frequent in severe COPD (26.5%) compared with mild to moderate COPD (12.4%) and controls (12.9%), P<0.05. Atrial fibrillation tended to be more frequent in severe COPD than in the other two groups.
Mortality rate associated with CABG surgery is not influenced by the presence and severity of airflow obstruction in patients with COPD. The incidence of pulmonary infections and length of hospital stay were increased in patients with severe COPD.
PMCID: PMC2690441  PMID: 17315054
COPD; Coronary artery bypass; Heart surgery; Postoperative complications
2.  Lung function and blood markers of nutritional status in non-COPD aging men with smoking history: A cross-sectional study 
Cigarette smoking and advanced age are well known as risk factors for chronic obstructive pulmonary disease (COPD), and nutritional abnormalities are important in patients with COPD. However, little is known about the nutritional status in non-COPD aging men with smoking history. We therefore investigated whether reduced lung function is associated with lower blood markers of nutritional status in those men.
Subjects and methods:
This association was examined in a cross-sectional study of 65 Japanese male current or former smokers aged 50 to 80 years: 48 without COPD (non-COPD group), divided into tertiles according to forced expiratory volume in one second as percent of forced vital capacity (FEV1/FVC), and 17 with COPD (COPD group).
After adjustment for potential confounders, lower FEV1/FVC was significantly associated with lower red blood cell count (RBCc), hemoglobin, and total protein (TP); not with total energy intake. The difference in adjusted RBCc and TP among the non-COPD group tertiles was greater than that between the bottom tertile in the non-COPD group and the COPD group.
In non-COPD aging men with smoking history, trends toward reduced nutritional status and anemia may independently emerge in blood components along with decreased lung function even before COPD onset.
PMCID: PMC2921691  PMID: 20714377
anemia; chronic obstructive pulmonary disease; lung function; nutritional assessment; nutritional status; smoking
3.  Comparison of spirometry criteria for the diagnosis of COPD: results from the BOLD study 
The European respiratory journal  2009;34(3):588-597.
Published guidelines recommend spirometry to accurately diagnose chronic obstructive pulmonary disease (COPD). However, even spirometry-based COPD prevalence estimates can vary widely. We compared properties of several spirometry-based COPD definitions using data from the international Burden of Obstructive Lung Disease (BOLD)study.
14 sites recruited population-based samples of adults aged ≥40 yrs. Procedures included standardised questionnaires and post-bronchodilator spirometry. 10,001 individuals provided usable data.
Use of the lower limit of normal (LLN) forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio reduced the age-related increases in COPD prevalence that are seen among healthy never-smokers when using the fixed ratio criterion (FEV1/FVC <0.7) recommended by the Global Initiative for Chronic Obstructive Lung Disease. The added requirement of an FEV1 either <80% predicted or below the LLN further reduced age-related increases and also led to the least site-to-site variability in prevalence estimates after adjusting for potential confounders. Use of the FEV1/FEV6 ratio in place of the FEV1/FVC yielded similar prevalence estimates.
Use of the FEV1/FVC
PMCID: PMC3334278  PMID: 19460786
Adult; chronic obstructive pulmonary disease; epidemiology
Background:Metabolic syndrome (Mets) is reportedly associated with chronic obstructive pulmonary disease (COPD). However, the relationship between abdominal circumference (AC) and decline in FEV1 has not been elucidated. We aimed to investigate this relationship among male current smokers.
Methods:Spirometry was performed on subjects (n = 3,257) ≥ 40 years of age, who participated in a community-based annual health check in Takahata, Japan, from 2004 through 2006 (visit 1). Spirometry was re-evaluated, and AC was assessed in 147 of the male current smokers in 2009 (visit 2). The diagnosis of Mets was based on the criteria used in the Hisayama Study.
Results:No significant relationships were observed between AC and spirometric parameters such as % predicted forced vital capacity (FVC), % predicted forced expiratory volume in 1 s (FEV1) and FEV1/FVC. However, decline in FEV1 was significantly correlated with AC. Multivariate logistic regression analysis showed that AC was a significant discriminating factor for decline in FEV1, independently of age, Brinkman index and change in body mass index from visit 1 to visit 2. At visit 2, there was a greater prevalence of decline in FEV1 among subjects with Mets (n=17) than among those without Mets. Although there were no differences in % predicted FVC, % predicted FEV1 or FEV1/FVC between subjects with or without Mets, the rate of decline in FEV1 was significantly greater in subjects with Mets than in those without.
Conclusions:This retrospective analysis suggested that measuring AC may be useful for discriminating male smokers who show a decline in FEV1.
PMCID: PMC3534871  PMID: 23288999
decline in FEV1; abdominal circumference; smoker; health check.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of severity of chronic obstructive pulmonary disease (COPD) is based solely on obstruction and does not capture physical functioning. The hypothesis that the Medical Research Council (MRC) dyspnoea scale would correlate better with quality of life than the level of airflow limitation was examined.
To study the associations between quality of life in smokers and limitations in physical functioning (MRC dyspnoea scale) and, quality of life and airflow limitation (GOLD COPD stages).
Cross-sectional study.
The city of IJsselstein, a small town in the centre of The Netherlands.
Male smokers aged 40–65 years without a prior diagnosis of COPD and enlisted with a general practice, participated in this study. Quality of life was assessed by means of a generic (SF–36) and a disease-specific, questionnaire (QOLRIQ).
A total of 395 subjects (mean age 55.4 years, pack years 27.1) performed adequate spirometry and completed the questionnaires. Limitations of physical functioning according to the MRC dyspnoea scale were found in 25.1 % (99/395) of the participants and airflow limitation in 40.2% (159/395). The correlations of limitations of physical functioning with all quality-of-life components were stronger than the correlations of all quality-of-life subscales with the severity of airflow limitation.
In middle-aged smokers the correlation of limitations of physical functioning (MRC dyspnoea scale) with quality of life was stronger than the correlation of the severity of airflow limitation with quality of life. Future staging systems of severity of COPD should capture this and not rely on forced expiratory volume in one second (FEV1) alone.
PMCID: PMC2078172  PMID: 17550673
dyspnoea; FEV1; middle-aged; FEV1; quality of life; smokers
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. However, much of the disease burden remains undiagnosed.
To compare the yield and cost effectiveness of two COPD case-finding approaches in primary care.
Design and setting
Pilot randomised controlled trial in two general practices in the West Midlands, UK.
A total of 1634 ever-smokers aged 35–79 years with no history of COPD or asthma were randomised into either a ‘targeted’ or ‘opportunistic’ case-finding arm. Respiratory questionnaires were posted to patients in the ‘targeted’ arm and provided to patients in the ‘opportunistic’ arm at routine GP appointments. Those reporting at least one chronic respiratory symptom were invited for spirometry. COPD was defined as pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC)<0.7 and FEV1<80% of predicted. Primary outcomes were the difference in the proportion of patients diagnosed with COPD and the cost per case detected.
Twenty-six per cent (212/815) in the ‘targeted’ and 13.6% (111/819) in the ‘opportunistic’ arm responded to the questionnaire and 78.3% (166/212) and 73.0% (81/111), respectively, reported symptoms; 1.2% (10/815) and 0.7% (6/819) of patients in the ‘targeted’ and ‘opportunistic’ arms were diagnosed with COPD (difference in proportions = 0.5% [95% confidence interval {CI} = –0.5% to 3.08%]). Over a 12-month period, the ‘opportunistic’ case-finding yield could be improved to 1.95% (95% CI = 1.0% to 2.9%). The cost-per case detected was £424.56 in the ‘targeted’ and £242.20 in the ‘opportunistic’ arm.
Opportunistic case finding may be more effective and cost effective than targeting patients with a postal questionnaire alone. A larger randomised controlled trial with adequate sample size is required to test this.
PMCID: PMC3529293  PMID: 23336474
chronic obstructive pulmonary disease; early detection of disease; primary care; randomised controlled trial; signs and symptoms; respiratory
Thorax  2003;58(5):388-393.
Background: A study was undertaken to define the risk of death among a national cohort of US adults both with and without lung disease.
Methods: Participants in the first National Health and Nutrition Examination Survey (NHANES I) followed for up to 22 years were studied. Subjects were classified using a modification of the Global Initiative for Chronic Obstructive Lung Disease criteria for chronic obstructive pulmonary disease (COPD) into the following mutually exclusive categories using the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and the presence of respiratory symptoms: severe COPD, moderate COPD, mild COPD, respiratory symptoms only, restrictive lung disease, and no lung disease. Proportional hazard models were developed that controlled for age, race, sex, education, smoking status, pack years of smoking, years since quitting smoking, and body mass index.
Results: A total of 1301 deaths occurred in the 5542 adults in the cohort. In the adjusted proportional hazards model the presence of severe or moderate COPD was associated with a higher risk of death (hazard ratios (HR) 2.7 and 1.6, 95% confidence intervals (CI) 2.1 to 3.5 and 1.4 to 2.0), as was restrictive lung disease (HR 1.7, 95% CI 1.4 to 2.0).
Conclusions: The presence of both obstructive and restrictive lung disease is a significant predictor of earlier death in long term follow up.
PMCID: PMC1746680  PMID: 12728157
Pulmonary Medicine  2013;2013:782052.
Classification of COPD into different GOLD stages is based on forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) but has shown to be of limited value. The aim of the study was to relate spirometry values to more advanced measures of lung function in COPD patients compared to healthy smokers. The lung function of 65 COPD patients and 34 healthy smokers was investigated using flow-volume spirometry, body plethysmography, single breath helium dilution with CO-diffusion, and impulse oscillometry. All lung function parameters, measured by body plethysmography, CO-diffusion, and impulse oscillometry, were increasingly affected through increasing GOLD stage but did not correlate with FEV1 within any GOLD stage. In contrast, they correlated fairly well with FVC%p, FEV1/FVC, and inspiratory capacity. Residual volume (RV) measured by body plethysmography increased through GOLD stages, while RV measured by helium dilution decreased. The difference between these RV provided valuable additional information and correlated with most other lung function parameters measured by body plethysmography and CO-diffusion. Airway resistance measured by body plethysmography and impulse oscillometry correlated within COPD stages. Different lung function parameters are of importance in COPD, and a thorough patient characterization is important to understand the disease.
PMCID: PMC3697409  PMID: 23844288
Thorax  2009;64(11):944-949.
A study was undertaken to determine if quantitative CT estimates of lung parenchymal overinflation and airway dimensions in smokers with a normal forced expiratory volume in 1 s (FEV1) can predict the rapid decline in FEV1 that leads to chronic obstructive pulmonary disease (COPD).
Study participants (n = 143; age 45–72 years; 54% male) were part of a lung cancer screening trial, had a smoking history of >30 pack years and a normal FEV1 and FEV1/forced vital capacity (FVC) at baseline (mean (SD) FEV1 99.4 (12.8)%, range 80.2–140.7%; mean (SD) FEV1/FVC 77.9 (4.4), range 70.0–88.0%). An inspiratory multislice CT scan was acquired for each subject at baseline. Custom software was used to measure airway lumen and wall dimensions; the percentage of the lung inflated beyond a predicted maximal lung inflation, the low attenuation lung area with an x ray attenuation lower than −950 HU and the size distribution of the overinflated lung areas and the low attenuation area were described using a cluster analysis. Multiple regression analysis was used to test the hypothesis that these CT measurements combined with other baseline characteristics might identify those who would develop an excessive annual decline in FEV1.
The mean (SD) annual change in FEV1 was −2.3 (4.7)% predicted (range −23.0% to +8.3%). Multiple regression analysis revealed that the annual change in FEV1%predicted was significantly associated with baseline percentage overinflated lung area measured on quantitative CT, FEV1%predicted, FEV1/FVC and gender.
Quantitative CT scan evidence of overinflation of the lung predicts a rapid annual decline in FEV1 in smokers with normal FEV1.
PMCID: PMC3035577  PMID: 19734130
In China, the burden of chronic obstructive disease (COPD) is high in never-smokers but little is known about its causes in this group.
We analysed data on 287 000 female and 30 000 male never-smokers aged 30–79 years from 10 regions in China, who participated in the China Kadoorie Biobank baseline survey (2004–2008). Prevalence of airflow obstruction (AFO) (pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and below the lower limit of normal (LLN)) was estimated, by age and region. Cross-sectional associations of AFO (FEV1/FVC <0.7), adjusted for confounding, were examined.
AFO prevalence defined as FEV1/FVC <0.7 was 4.0% in females and 5.1% in males (mean ages 51 and 54 years, respectively). AFO prevalence defined as FEV1/FVC
AFO is prevalent in Chinese never-smokers, particularly among those with low socioeconomic status or prior tuberculosis, and in rural males.
Airflow obstruction is prevalent in Chinese never-smokers and particularly associated with low socioeconomic status
PMCID: PMC4076527  PMID: 24603814
Respiratory medicine  2010;104(8):1189-1196.
Among older persons, we previously endorsed a two-step spirometric definition of chronic obstructive pulmonary disease (COPD) that requires a ratio of forced expiratory volume in 1-second to forced vital capacity (FEV1/FVC) below .70, and an FEV1 below the 5th or 10th standardized-residual percentile (“SR-tile strategy”).
To evaluate the clinical validity of an SR-tile strategy, compared to a current definition of COPD, as published by the Global Initiative for Obstructive Lung Disease (GOLD-COPD), in older persons.
We assessed national data from 2,480 persons aged 65-to-80 years. In separate analyses, we evaluated the association of an SR-tile strategy with mortality and respiratory symptoms, relative to GOLD-COPD. As per convention, GOLD-COPD was defined solely by an FEV1/FVC<.70, with severity staged according to FEV1 cut-points at 80 and 50 percent-predicted (%Pred).
Among 831 participants with GOLD-COPD, the risk of death was elevated only in 179 (21.5%) of those who also had an FEV1 <5thSR-tile; and the odds of having respiratory symptoms was elevated only in 310 (37.4%) of those who also had an FEV1 <10thSR-tile. In contrast, GOLD-COPD staged at an FEV1 50-79%Pred led to misclassification (overestimation) in terms of 209 (66.4%) and 77 (24.6%) participants, respectively, not having an increased risk of death or likelihood of respiratory symptoms.
Relative to an SR-tile strategy, the majority of older persons with GOLD-COPD had neither an increased risk of death nor an increased likelihood of respiratory symptoms. These results raise concerns about the clinical validity of GOLD guidelines in older persons.
PMCID: PMC2890041  PMID: 20199857
COPD; spirometry; respiratory symptoms; mortality
Thorax  2006;62(3):237-241.
The Global Initiative on Obstructive Lung Disease stages for chronic obstructive pulmonary disease (COPD) uses a fixed ratio of the post‐bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of 0.70 as a threshold. Since the FEV1/FVC ratio declines with age, using the fixed ratio to define COPD may “overdiagnose” COPD in older populations.
To determine morbidity and mortality among older adults whose FEV1/FVC is less than 0.70 but more than the lower limit of normal (LLN).
The severity of COPD was classified in 4965 participants aged ⩾65 years in the Cardiovascular Health Study using these two methods and the age‐adjusted proportion of the population who had died or had a COPD‐related hospitalisation in up to 11 years of follow‐up was determined.
1621 (32.6%) subjects died and 935 (18.8%) had at least one COPD‐related hospitalisation during the follow‐up period. Subjects (n = 1134) whose FEV1/FVC fell between the LLN and the fixed ratio had an increased adjusted risk of death (hazard ratio (HR) 1.3, 95% CI 1.1 to 1.5) and COPD‐related hospitalisation (HR 2.6, 95% CI 2.0 to 3.3) during follow‐up compared with asymptomatic individuals with normal lung function.
In this cohort, subjects classified as “normal” using the LLN but abnormal using the fixed ratio were more likely to die and to have a COPD‐related hospitalisation during follow‐up. This suggests that a fixed FEV1/FVC ratio of <0.70 may identify at‐risk patients, even among older adults.
PMCID: PMC2117148  PMID: 17090573
Thorax  2000;55(3):189-193.
BACKGROUND—It has been suggested that oxidative stress is an important factor in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have shown that an oxidant/antioxidant imbalance occurs in the distal air spaces of smokers and in patients with COPD which is reflected systemically in the plasma. A study was undertaken to determine whether plasma antioxidant status correlated with lung function as assessed by forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in smokers and patients with COPD.
METHODS—Plasma antioxidant capacity, assessed by the Trolox equivalent antioxidant capacity (TEAC) as an index of overall systemic oxidative stress, and protein thiol levels were measured in 95patients with stable COPD, in 82 healthy smokers, and in 37 healthy non-smokers.
RESULTS—Mean (SE) plasma TEAC levels were significantly decreased in patients with COPD (0.81 (0.03) mmol/l, p<0.001) and in healthy smokers (0.87 (0.04) mmol/l, p<0.001) compared with healthy non-smokers (1.31 (0.11) mmol/l). The mean differences in plasma antioxidant capacity (mM) were (0.81, 95% confidence interval (CI) 0.22 to 1.48), (0.87, 95% CI 0.2 to 1.46), and (1.31, 95% CI 1.09 to 1.58) in patients with COPD, healthy smokers, and healthy non-smokers, respectively. This reduction was associated with a 29% (95% CI 18 to 38) and a 30% (95% CI 19 to 40) decrease in plasma protein thiol levels in COPD patients and smokers, respectively. Current smoking was not the main contributor to the reduction in antioxidant capacity in patients with COPD as those patients who were still smokers had similar TEAC levels (mean (SE) 0.78 (0.05); n = 25) to those who had stopped smoking (0.84 (0.02); n = 70). No significant correlations were found between spirometric data measured as FEV1 % predicted or FEV1/FVC % predicted and the plasma levels of TEAC in patients with COPD, healthy smokers, or healthy non-smokers. Similarly, there was no significant correlation between FEV1 %predicted or FEV1/FVC % predicted and the levels of plasma protein thiols in the three groups.
CONCLUSIONS—These data confirm decreased antioxidant capacity in smokers and patients with COPD, indicating the presence of systemic oxidative stress. However, no relationship was found between protein thiols or TEAC levels and measurements of airflow limitation in either smokers or in patients with COPD.

PMCID: PMC1745692  PMID: 10679536
Respiratory Research  2012;13(1):13.
The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis.
In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography.
Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN.
GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.
PMCID: PMC3299632  PMID: 22309369
COPD diagnosis; lower limit of normal; GOLD; validation
Aclidinium bromide is a long-acting muscarinic antagonistic used in maintenance treatment of chronic obstructive pulmonary disease (COPD). A model-based health economic study evaluated the cost-effectiveness of aclidinium 400 μg bid as an alternative to tiotropium 18 μg od for this indication in the US.
Patients and methods
Patient characteristics in this model reflect those in the aclidinium clinical studies: age >40 years, stable moderate-to-severe COPD, current or ex-smokers (>10 pack-years), post-salbutamol forced expiratory volume in 1 second (FEV1) ≥30% and <80% of predicted normal value, and FEV1/forced vital capacity <70%. The model consists of five main health states indicating severity of COPD and the level of utility, resource use, and costs. Treatment efficacy over 5 years was modeled using FEV1% predicted; a network meta-analysis comparing aclidinium and tiotropium was used to estimate disease progression during the first 24 weeks, and results from the UPLIFT trial were used for time points after 24 weeks. Quality of life was assessed using utility scores in US patients from the UPLIFT trial. Cost-effectiveness was assessed as the incremental cost per quality-adjusted life year (QALY) gained.
Over 5 years, QALYs were 3.50 for aclidinium versus 3.49 for tiotropium; life years accumulated were 4.52 for both. In this economic model, aclidinium versus tiotropium showed marginally fewer exacerbations (3.364 versus 3.390, respectively) and mean total health care costs (US$126,274 versus US$128,591, respectively). In all scenario analyses performed (discount factors of 0% and 6% for benefits and costs; time horizon of 1 year; mapping St George’s Respiratory Questionnaire to European Quality of Life–5 Dimensions; excluding pharmacy costs, COPD-related cost only; cost of exacerbations; including ACCORD II trial in the network meta-analysis), aclidinium was associated with lower costs and marginally greater QALYs versus tiotropium.
Aclidinium is potentially cost-effective compared with tiotropium for maintenance treatment of moderate-to-severe COPD.
PMCID: PMC3984059  PMID: 24741321
chronic obstructive pulmonary disease; cost-effectiveness; model; tiotropium
Respiratory Research  2006;7(1):52.
Recent reports indicate that over the next decade rates of chronic obstructive pulmonary disease (COPD) in women will exceed those in men in the western world, though in most jurisdictions, women continue to smoke less compared with men. Whether female adult smokers are biologically more susceptible to COPD is unknown. This study reviewed the available evidence to determine whether female adult smokers have a faster decline in forced expiratory volume in one second (FEV1) compared with male adult smokers and whether age modifies the relationship between cigarette smoke and lung function decline.
A systematic review and a meta-analysis was performed of population-based cohort studies that had a follow-up period of at least 3 years, measured FEV1 on at least two different time points, and presented FEV1 data stratified by gender and smoking status in adults.
Of the 646 potentially relevant articles, 11 studies met these criteria and were included in the analyses (N = 55 709 participants). There was heterogeneity in gender-related results across the studies. However, on average current smokers had a faster annual decline rate in FEV1% predicted compared with never and former smokers. Female current smokers had with increasing age a significantly faster annual decline in FEV1% predicted than male current smokers (linear regression analysis, R2 = 0.56; p = 0.008). Age did not materially affect the rate of decline in FEV1% predicted in male and female former and never smokers (p = 0.775 and p = 0.326, respectively).
As female smokers age, they appear to experience an accelerated decline in FEV1% predicted compared with male smokers. Future research powered specifically on gender-related changes in lung function is needed to confirm these early findings.
PMCID: PMC1435894  PMID: 16571126
Journal of Thoracic Disease  2012;4(Suppl 1):AB20.
In patients with COPD, there is an evidence of platelet activation due to chronic hypoxia and systemic inflammation. Aim of the study was to evaluate Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW), markers of platelet activation, in patients with Chronic Obstructive Pulmonary Disease (COPD), and to investigate possible associations with pulmonary function testing [Forced expiratory volume in 1 second (FEV1) and Forced vital capacity (FVC)].
Patients and methods
Current smokers with stable COPD (n=85) and smokers without airflow limitation (n=35) were included. To all of them pulmonary function testing was performed and count of white blood cells (WBC) platelets, as well as MPV and PDW were measured.
In smokers with COPD, MPV was significantly higher (mean value 10.563±1.531 vs. 9.956±1.046 fl, P<0.05) than in control group. WBC was also significantly higher in patients with COPD than in controls (9045.53±2664.34/μL vs. 7018.79±1989.74/μL, P<0.001). A significant correlation between MPV and WBC in COPD patients was revealed, especially in those at GOLD Stage III (r=0.475, P=0.012) and IV (r=0.367, P=0.033). WBC count was correlated with FEV1/FVC values (P=0.044). MPV did not correlate with any indices of COPD severity.
In patients with COPD, MPV and WBC levels are significantly correlated and are elevated in comparison to smokers with normal pulmonary function. WBC count was negatively correlated with FEV1/FVC values.
PMCID: PMC3537346
People with known risk factors for chronic obstructive pulmonary disease (COPD) are important targets for screening and early intervention. We sought to measure the prevalence of COPD among such individuals visiting a primary care practitioner for any reason. We also evaluated the accuracy of prior diagnosis or nondiagnosis of COPD and identified associated clinical characteristics.
We recruited patients from three primary care sites who were 40 years or older and had a smoking history of at least 20 pack-years. Participants were asked about respiratory symptoms and underwent postbronchodilator spirometry. COPD was defined as a ratio of forced expiratory volume in the first second of expiration to forced vital capacity (FEV1/FVC) of less than 0.7 and an FEV1 of less than 80% predicted.
Of the 1459 patients who met the study criteria, 1003 (68.7%) completed spirometry testing. Of these, 208 were found to have COPD, for a prevalence of 20.7% (95% confidence interval 18.3%–23.4%). Of the 205 participants with COPD who completed the interview about respiratory symptoms before spirometry, only 67 (32.7%) were aware of their diagnosis before the study. Compared with patients in whom COPD had been correctly diagnosed before the study, those in whom COPD had been over-diagnosed or undiagnosed were similar in terms of age, sex, current smoking status and number of visits to a primary care practitioner because of a respiratory problem.
Among adult patients visiting a primary care practitioner, as many as one in five with known risk factors met spirometric criteria for COPD. Underdiagnosis of COPD was frequent, which suggests a need for greater screening of at-risk individuals. Knowledge of the prevalence of COPD will help plan strategies for disease management.
PMCID: PMC2855915  PMID: 20371646
Yonsei Medical Journal  2009;50(5):672-676.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease (COPD) uses the post-bronchodilator spirometry for diagnosis and severity staging. We evaluated differences in the severity classification of COPD, based on pre- and post-bronchodilator spirometry.
Materials and Methods
From 2000 to 2004, 207 COPD patients who underwent spirometry before and after inhalation of 400 µg of fenoterol were analyzed. A responder to the bronchodilator test (BDT) was defined by the American Thoracic Society (ATS) as an increase in forced expiratory volume in one second (FEV1) or forced vital capacity ≥ 12% and ≥ 200 mL, and by the European Respiratory Society (ERS) as an increase in FEV1 ≥ 10% of the predicted value. COPD severity was classified according to the 2008 GOLD guidelines.
For the entire study population, the FEV1 increased by 11.8 ± 12.5% of baseline after BDT and 41.1% and 27.1% of subjects were classified as responders using the ATS and ERS criteria, respectively. Based on pre-BDT spirometry, 55, 85, 58, and 9 patients were classified as Stage I-IV COPD, respectively. Sixty-seven (32.4%) patients changed severity staging after BDT, including 20.0%, 28.2%, 44.8%, and 66.7% of pre-BDT patients Stages I through IV, respectively. More ATS or ERS BDT-responders had a change in severity staging than non-responders (52.9% vs. 18.9% and 62.5% vs. 21.2%, both p < 0.001).
Our data suggest that the severity staging of COPD using pre-BDT spirometry might lead to significant differences as compared to staging, based on post-BDT spirometry, as recommended by the current GOLD guidelines.
PMCID: PMC2768242  PMID: 19881971
Bronchodilator test; chronic obstructive pulmonary disease; severity staging
Archives of osteoporosis  2013;8(0):115.
There is limited information available regarding the association between lung function and bone mineral density among healthy elderly subjects. We addressed this issue in the Hertfordshire Cohort Study.
985 subjects (496 men and 489 women) aged 60-72 years were recruited from the above cohort. All subjects underwent bone density measurements using dual energy X-ray absorptiometry (DXA), and lung function tests using standardised spirometry. Chronic obstructive pulmonary disease (COPD) was defined as a Forced Expiratory Volume in 1 second (FEV1)/ Forced Vital Capacity (FVC) ratio < lower limit of normal (LLN), calculated using separate equations for men and women.
Measures of lung function (FEV1, FVC, FEV1/FVC) were not associated with bone mineral density at the lumbar spine, femoral neck and total hip in men or women; associations with bone mineral content and bone area were removed by adjustment for body size and lifestyle confounders. In this cohort, there were no associations observed between COPD and any measure of bone mass.
There was no association between lung function and bone mass in this community dwelling cohort after adjustment for body size and other confounders.
PMCID: PMC3622903  PMID: 23322029
Bone disease; chronic bronchitis; epidemiology; osteoporosis; spirometry
Rationale: A significant proportion of smokers have lung function impairment characterized by a reduced FEV1 with a preserved FEV1/FVC ratio. These smokers are a poorly characterized group due to their systematic exclusion from chronic obstructive pulmonary disease (COPD) studies.
Objectives: To characterize the clinical, functional, and radiographic features of Global Initiative for Chronic Obstructive Lung Disease (GOLD)-Unclassified (FEV1/FVC ≥ 0.7 and FEV1 < 80% predicted) and lower limits of normal (LLN)-unclassified (FEV1/FVC ≥ LLN and FEV1 < LLN) subjects compared to smokers with normal lung function and subjects with COPD.
Methods: Data from the first 2,500 subjects enrolled in the COPDGene study were analyzed. All subjects had 10 or more pack-years of smoking and were between the ages of 45 and 80 years. Multivariate regression models were constructed to determine the clinical and radiological variables associated with GOLD-Unclassified (GOLD-U) and LLN-Unclassified status. Separate multivariate regressions were performed in the subgroups of subjects with complete radiologic measurement variables available.
Measurements and Main Results: GOLD-U smokers account for 9% of smokers in COPDGene and have increased body mass index (BMI), a disproportionately reduced total lung capacity, and a higher proportion of nonwhite subjects and subjects with diabetes. GOLD-U subjects exhibit increased airway wall thickness compared to smoking control subjects and decreased gas trapping and bronchodilator responsiveness compared to subjects with COPD. When LLN criteria were used to define the “unclassified” group, African American subjects were no longer overrepresented. Both GOLD-U and LLN-Unclassified subjects demonstrated a wide range of lung function impairment, BMI, and percentage of total lung emphysema.
Conclusions: Subjects with reduced FEV1 and a preserved FEV1/FVC ratio are a heterogeneous group with significant symptoms and functional limitation who likely have a variety of underlying etiologies beyond increased BMI.
Clinical trial registered with (NCT000608764).
PMCID: PMC3172890  PMID: 21493737
lung diseases, classification; lung diseases, diagnosis; lung diseases, epidemiology
Respiratory care  2008;53(7):892-896.
To examine whether change in slow vital capacity (SVC) correlates to dyspnea improvement during emergency department (ED) treatment of chronic obstructive pulmonary disease (COPD) exacerbation.
We performed a prospective cohort study and enrolled consecutive patients during a 3-week period. ED patients ≥ 55 years old with COPD exacerbation were asked to perform bedside spirometry shortly after ED arrival and again at discharge. SVC was measured first, then forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF), and forced vital capacity (FVC). Concurrent with spirometry, patients rated their dyspnea on a 10-cm visual analogue scale.
Thirty-six patients were enrolled. The median ED stay was 271 min (interquartile range 219–370 min). Seventy-one percent of the patients reported dyspnea improvement during their ED stay. Change in SVC was significantly higher among the patients whose dyspnea improved than among those whose did not (median increase of 0.15 L vs median decrease of 0.25 L, respectively, p < 0.01). By contrast, the change in spirometry values were similar for FEV1, PEF, and FVC (all p > 0.30). Spearman correlation supported these findings: SVC r = 0.45 (p = 0.02) versus nonsignificant correlation with FEV1 (r = 0.33), PEF (r = −0.22), and FVC (r = 0.35).
Increase in SVC significantly correlated with dyspnea improvement among ED patients with moderate-to-severe COPD exacerbation. Change in SVC merits consideration when evaluating therapeutic response during COPD exacerbation.
PMCID: PMC3523353  PMID: 18593490
chronic obstructive pulmonary disease; COPD; dyspnea; emergency department; exacerbation; slow vital capacity; spirometry
BMC Research Notes  2012;5:209.
The aim of this study was to evaluate the effects of increasing doses of inhaled histamine on the forced expiratory volume in one second (FEV1), inspiratory lung function parameters (ILPs) and dyspnea in subjects with mild to moderate chronic obstructive pulmonary disease (COPD)
Thirty-nine (27 males and 12 females) stable COPD patients (GOLD stages I and II) inhaled a maximum of six sequential doses of histamine according to ERS standards until one of these provocative doses produced a 20% decrease in FEV1 (PD20). The effects on the FEV1, the forced inspiratory volume in one second (FIV1), inspiratory capacity (IC), forced inspiratory flow at 50% of the vital capacity (FIF50), peak inspiratory flow (PIF) and dyspnea score by a visual analogue scale (VAS) were measured and investigated after each dose step
After each dose of histamine, declines in all of the lung function parameters were detected; the largest decrease was observed in the FEV1. At the PD20 endpoint, more FEV1 responders than ILP responders were found. Among the ILPs, the FIV1 and IC best predicted which patients would reach the PD20 endpoint. No significant correlations were found between any of the lung function parameters and the VAS results
In COPD patients, the FEV1 and ILPs declined after each dose of inhaled histamine. FEV1 was more sensitive to histamine than the ILPs. Of the ILPs, FIV1 and IC were the best predictors of reaching the PD20 endpoint. No statistically significant correlations were found between the lung function parameters and the degree of dyspnea
PMCID: PMC3416583  PMID: 22546153
Chronic obstructive pulmonary disease; Forced expiratory volume 1 second; Inspiratory lung functions parameters; Visual analogue scale
Chest  2011;139(4):752-763.
Never smokers comprise a substantial proportion of patients with COPD. Their characteristics and possible risk factors in this population are not yet well defined.
We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study. Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines. In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio.
Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD. Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD. This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio. Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations.
This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD. Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers.
PMCID: PMC3168866  PMID: 20884729
To determine the accuracy of the history and selected elements of the physical examination in the diagnosis of chronic obstructive pulmonary disease (COPD).
Independent blind comparison of the standard clinical examination (evaluating the accuracy of history, wheezing, and forced expiratory time [FET]) with spirometry. The gold standard for diagnosis of COPD was a forced expiratory volume at 1 second (FEV1) below the fifth percentile (adjusted for patient height and age).
Seven sites in 6 countries, including investigators from primary care and secondary care settings.
One hundred sixty-one consecutive patients with varying severity of disease (known COPD, suspected COPD, or no COPD) participated in the study.
One hundred sixty-one patients (mean age 65 years, 39% female, 41% with known COPD, 27% with suspected COPD, and 32% normal) were recruited. Mean (±SD) FEV1 and forced vital capacity were 1,720 (±830) mL and 2,520 (±970) mL. The likelihood ratios (LR) for the tested elements of the clinical examination (and their P values on χ2 testing) were: self-reported history of COPD, 5.6 (P < .001); FET greater than 9 seconds, 6.7 (P < 0.01); smoked longer than 40 pack years, 3.3 (P = .001); wheezing, 4.0 (P < .001); male gender, 1.6 (P < .001); and age over 65 years, 1.6 (P = .025). The accuracy of these elements was not appreciably different when reference standards other than FEV1 below the 5th percentile were applied. Only 3 elements of the clinical examination were significantly associated with the diagnosis of COPD on multivariate analysis: self-reported history of COPD (adjusted LR 4.4), wheezing (adjusted LR 2.9), and FET greater than 9 seconds (adjusted LR 4.6). Area under the receiver operating characteristic curve for the model incorporating these 3 factors was 0.86.
Less emphasis should be placed on the presence of isolated symptoms or signs in the diagnosis of COPD. While numerous elements of the clinical examination are associated with the diagnosis of COPD, only 3 are significant on multivariate analysis. Patients having all 3 of these findings have an LR of 33 (ruling in COPD); those with none have an LR of 0.18 (ruling out COPD).
PMCID: PMC1495102  PMID: 12220364
chronic obstructive pulmonary disease; clinical examination; spirometry; diagnosis

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