The Timed Up and Go test predicts frailty in patients with COPD.

The Timed Up and Go (TUG) is a global measure of mobility and has the ability to detect frail individuals. Frail patients with chronic obstructive pulmonary disease (COPD) are usually undiagnosed. We hypothesised that the TUG would identify frail patients with COPD. Frailty was assessed in 520 patients diagnosed with COPD and 150 controls using a Comprehensive Geriatric Assessment questionnaire and frailty index (FI) was derived. The TUG was used to assess physical mobility. All participants were assessed for lung function and body composition. A ROC curve was used to identify how well TUG discriminates between frail and non-frail patients with COPD. The patients with COPD and controls were similar in age, sex and BMI but the patients with COPD were more frail, mean ± SD FI 0.16 ± 0.08 than controls 0.05 ± 0.03, P < 0.001. Frail patients with COPD had a greater TUG time (11.55 ± 4.03 s) compared to non-frail patients (9.2 ± 1.6 sec), after controlling for age and lung function (F = 15.94, P < 0.001), and both were greater than the controls (8.3 ± 1.2 sec), P < 0.001. The TUG discriminated between frail and non-frail patients with COPD with an area under the curve of 72 (95% CI: 67-76), and a diagnostic odds ratio of 2.67 (95% CI:1.5-4.6), P < 0.001. The TUG showed the ability to discriminate between frail and non-frail patients with COPD, independent of age and severity of the airflow obstruction. The TUG is a simple, easy and quick measure that could be easily applied in restricted settings to screen for frailty in COPD.

Daily physical activity and related risk factors in COPD.

BACKGROUND: Factors associated with reduced daily physical activity (DPA) in patients with COPD are still controversial. Physical inactivity in COPD increases risk of cardiovascular disease, frequent exacerbations, reduced health status, and increased symptoms. We hypothesised that reduced DPA in patients with COPD is independent of traditional risk factors including age and spirometry. METHODS: In this cross-sectional study, DPA (over 7 days) was assessed on 88 community stable patients with COPD and 40 controls free from cardiorespiratory disease. Spirometry, body composition, number of exacerbations, handgrip strength (HGS), modified Medical Research Council (mMRC), arterial stiffness, 6-min walking distance (6MWD) and BODE index were also determined. Frequent exacerbation was defined as ≥2 and non-frequent exacerbation < 2. RESULTS: Patients with COPD had reduced DPA and exercise capacity compared with controls similar in age, BMI and gender, p < 0.001. Frequent exacerbators had less DPA than infrequent exacerbators and both less than controls, p < 0.001. Patients with higher BODE index were less active than those with lower index. Time spent on moderate activity was related to cardiovascular risk factors including arterial stiffness. The DPA in patients was independent of age, gender, spirometry, body composition and HGS, p > 0.05. The level of breathlessness was superior to lung function in predicting the level of DPA. CONCLUSION: The level of DPA in COPD was independent of traditional risk factors. Breathlessness score is a better predictor of the DPA than lung function and handgrip strength.

Aortic Pulse Wave Velocity as a Measure of Cardiovascular Risk in Chronic Obstructive Pulmonary Disease: Two-Year Follow-Up Data from the ARCADE Study.

Background and objectives: Cardiovascular (CV) disease is a major cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD). Patients with COPD have increased arterial stiffness, which may predict future CV risk. However, the development of arterial stiffness in COPD has not yet been studied prospectively. The Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE) is a longitudinal study of CV risk and other comorbidities in COPD. The aims of this analysis were to explore factors associated with aortic pulse wave velocity (aPWV) at baseline and to describe the progression of aPWV in patients with COPD and comparators over two years. Materials and methods: At baseline, 520 patients with COPD (confirmed by spirometry) and 150 comparators free from respiratory disease were assessed for body composition, blood pressure, aPWV, noninvasive measures of cardiac output, inflammatory biomarkers, and exercise capacity. This was repeated after two years, and mortality cases and causes were also recorded. Results: At baseline, aPWV was greater in COPD patients 9.8 (95% confidence interval (CI) 9.7-10.0) versus comparators 8.7 (8.5-9.1) m/s (p < 0.01) after adjustments for age, mean arterial pressure (MAP), and heart rate. Mean blood pressure was 98 ± 11 in COPD patients and 95 ± 10 mmHg in comparators at baseline (p = 0.004). After two years, 301 patients and 105 comparators were fully reassessed. The mean (95% CI) aPWV increased similarly in patients 0.44 (0.25-0.63) and comparators 0.46 (0.23-0.69) m/s, without a change in blood pressure. At the two-year follow-up, there were 29 (6%) deaths in COPD patients, with the majority due to respiratory causes, with an overall dropout of 43% of patients with COPD and 30% of comparators. Conclusions: This was the first large longitudinal study of CV risk in COPD patients, and we confirmed greater aPWV in COPD patients than comparators after adjustments for confounding factors. After two years, patients and comparators had a similar increase of almost 0.5 m/s aPWV.

Frailty: A global measure of the multisystem impact of COPD.

Chronic obstructive pulmonary disease (COPD) is a multisystem disease that resembles the accumulation of multiple impairments seen in aging. A comprehensive geriatric assessment (CGA) captures multisystem deficits, from which a frailty index (FI) can be derived. We hypothesized that patients with COPD would be frailer than a comparator group free from respiratory disease. In this cross-sectional analysis, the CGA questionnaire was completed and used to derive an FI in 520 patients diagnosed with COPD and 150 comparators. All subjects were assessed for lung function, body composition, 6-minute walking distance (6MWD), and handgrip strength. Patients completed validated questionnaires on health-related quality of life and respiratory symptoms. Patients and comparators were similar in age, gender, and body mass index, but patients had a greater mean ± SD FI 0.16 ± 0.08 than comparators 0.05 ± 0.03. In patients, a stepwise linear regression 6MWD ( ß = -0.43), number of comorbidities ( ß = -0.38), handgrip ( ß = -0.11), and number of exacerbations ( ß = 0.11) were predictors of frailty (all p < 0.01). This large study suggests patients with COPD are frailer than comparators. The FI derived from the CGA captures the deterioration of multiple systems in COPD and provides an overview of impairments, which may identify individuals at increased risk of morbidity and mortality in COPD.

Autoantibodies of IgM and IgG classes show differences in recognition of multiple autoantigens in chronic obstructive pulmonary disease.

Autoimmunity occurs in chronic obstructive pulmonary disease (COPD). We describe an antigen microarray for detecting serum autoantibodies (AAbs) to determine how IgM, as well as IgG, AAbs distinguish patients with COPD from controls with a history of smoking without COPD. All COPD patients' sera contained elevated levels of AAbs to some of 30 autoantigens. There were significant differences in the autoantigenic specificities of IgM AAbs compared to IgG AAbs in the COPD sera: for example, AAbs to histone and scl-70 were mainly IgG, whereas AAbs to CENP-B and La/ssB were mainly IgM; by contrast, IgM and IgG AAbs to collagen-V were equally prevalent. Thus, a combination of IgM and IgG AAbs specific for multiple autoantigens are detected in all cases of COPD at a level at which all non-COPD controls are negative for AAbs. This highlights the importance of different classes of AAbs to a range of autoantigens in COPD.

A simple and rapid test of physical performance inchronic obstructive pulmonary disease.

Impaired physical performance is common in chronic obstructive pulmonary disease (COPD), but its assessment can be difficult in routine clinical practice. We compared the timed up and go (TUG) test and other easily applied assessments of physical performance with the 6-minute walk distance (6MWD). In a longitudinal study of comorbidities in COPD, submaximal physical performance was determined in 520 patients and 150 controls using the TUG test and 6MWD. Spirometry, body composition, handgrip strength, the COPD assessment test, St George's Respiratory Questionnaire (SGRQ), and the modified Medical Research Council dyspnoea scale were also determined. Patients and controls were similar in age, body mass index, and sex proportions. The TUG in the patients was greater than that in the control group, P=0.001, and was inversely related to 6MWD (r=-0.71, P<0.001) and forced expiratory volume in one second predicted (r=-0.19, P<0.01) and was directly related to the SGRQ activity (r=0.39, P<0.001), SGRQ total (r=0.37, P<0.001), and total COPD assessment test scores (r=0.37, P<0.001). The TUG identified the difference in physical performance between patients and controls. The TUG test and validated questionnaires provide a measure of physical performance, which is rapid and could be used in clinical practice.

Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial.

BACKGROUND: There is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease. Aortic stiffness, an independent predictor of cardiovascular risk, and systemic and airway inflammation are increased in patients with the disease. Statins modulate aortic stiffness and have anti-inflammatory properties. A proof-of-principle, double-blind, randomized trial determined if 6 weeks of simvastatin 20 mg once daily reduced aortic stiffness and systemic and airway inflammation in patients with chronic obstructive pulmonary disease. METHODS: Stable patients (n=70) were randomized to simvastatin (active) or placebo. Pre-treatment and post-treatment aortic stiffness, blood pressure, spirometry, and circulating and airway inflammatory mediators and lipids were measured. A predefined subgroup analysis was performed where baseline aortic pulse wave velocity (PWV) was >10 m/sec. RESULTS: Total cholesterol dropped in the active group. There was no significant change in aortic PWV between the active group and the placebo group (-0.7 m/sec, P=0.24). In those with aortic stiffness >10 m/sec (n=22), aortic PWV improved in the active group compared with the placebo group (-2.8 m/sec, P=0.03). Neither systemic nor airway inflammatory markers changed. CONCLUSION: There was a nonsignificant improvement in aortic PWV in those taking simvastatin 20 mg compared with placebo, but in those with higher baseline aortic stiffness (a higher risk group) a significant and clinically relevant reduction in PWV was shown.

Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE): Protocol and preliminary data.

Chronic obstructive pulmonary disease (COPD) is a multisystem disease. Established comorbidities include cardiovascular disease, osteoporosis, loss of muscle mass and function, depression, and impaired quality of life. The natural history is not well understood. The Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE) is a longitudinal study of comorbidities in COPD. The primary aims are to delineate the progression and interrelationships of cardiovascular disease and associated comorbidities. Each year ARCADE aims to recruit 250 patients diagnosed with COPD and 50 comparators (free from respiratory disease). Assessments include spirometry, body composition, blood pressure, aortic stiffness (pulse wave velocity (PWV)), noninvasive measures of cardiac output, systemic inflammatory mediators, blood and urine biochemistry, and physical and health outcomes. These will be repeated at 2 and 5 years. In the first year of recruitment, 350 patients and 100 comparators were recruited. The reproducibility of aortic PWV, cardiac output, stroke volume, and cardiac index was evaluated and accepted in 30 patients free from overt cardiovascular disease. The preliminary data from ARCADE have demonstrated acceptable reproducibility of hemodynamic outcome measures. Further longitudinal data collection will increase knowledge of the progression and interactions between cardiovascular risk factors and other comorbidities in COPD.

Evaluating the role of inflammation in chronic airways disease: the ERICA study.

Extrapulmonary manifestations are recognized to be of increasing clinical importance in Chronic Obstructive Pulmonary disease. To investigate cardiovascular and skeletal muscle manifestations of COPD, we developed a unique UK consortium funded by the Technology Strategy Board and Medical Research Council comprising industry in partnership with 5 academic centres. ERICA (Evaluating the Role of Inflammation in Chronic Airways disease) is a prospective, longitudinal, observational study investigating the prevalence and significance of cardiovascular and skeletal muscle manifestations of COPD in 800 subjects. Six monthly follow up will assess the predictive value of plasma fibrinogen, cardiovascular abnormalities and skeletal muscle weakness for death or hospitalization. As ERICA is a multicentre study, to ensure data quality we sought to minimise systematic observer error due to variations in investigator skill, or adherence to operating procedures, by staff training followed by assessment of inter- and intra-observer reliability of the four key measurements used in the study: pulse wave velocity (PWV), carotid intima media thickness (CIMT), quadriceps maximal voluntary contraction force (QMVC) and 6-minute walk distance (6MWT). This report describes the objectives and methods of the ERICA trial, as well as the inter- and intra-observer reliability of these measurements.

Dynamic vascular changes following intravenous antibiotics in patients with cystic fibrosis.

BACKGROUND: Adults with cystic fibrosis (CF) have altered large artery haemodynamics which is associated with a persisting systemic inflammatory state. We hypothesized that a short-term intervention favorably influencing the inflammatory status may modify their haemodynamic state. METHODS: Adult patients with CF were studied immediately preceding and following 2 weeks of intravenous antibiotics. Large artery haemodynamics, principally heart rate-adjusted augmentation index (AIx) were obtained. Blood pressure (BP), spirometry and CRP were also measured. RESULTS: Complete data was available for 15 patients; mean (SD) age 28 (6)years. CRP was reduced while FEV1% predicted improved. Following treatment AIx was lower: 10.9 (10.9)% to 8.1 (10.9)% (p<0.05) while BP was similar and a trend toward lower heart rate (p=0.06). Change in AIx was related to baseline FEV1% predicted (r=0.77) and BMI (r=0.71) (both P<0.01). CONCLUSION: The abnormal central haemodynamics evident in adults with CF is modulated with a short intervention of intravenous antibiotics.

Systemic comorbidities in bronchiectasis.

Bronchiectasis is a chronic inflammatory lung disease, which has similarities to chronic obstructive pulmonary disease (COPD). Comorbidities of COPD include increased risk of cardiovascular (CV) disease, loss of bone mineral density (BMD) and loss of skeletal muscle mass and function, all linked to systemic inflammation. The potential for such comorbidities has not been explored in bronchiectasis. We hypothesised that patients with bronchiectasis would have similar increased comorbidities. A total of 20 patients with noncystic fibrosis bronchiectasis were compared to 20 controls similar in age, gender and smoking exposure. Assessments included aortic pulse wave velocity (PWV; (a measure of arterial stiffness and an independent predictor of CV risk), blood pressure (BP) as well as levels of interleukin-6 (IL-6), albumin, fasting glucose and lipids. Body composition (fat free mass index (FFMI)), BMD, the 6-min walk distance (6MWD) and self-reported physical activity were also determined. Patients with bronchiectasis had increased aortic PWV, 10.5 (3.0) m/second, when compared with controls, 8.8 (1.6) m/second (p < 0.05), despite similar central and peripheral BP and lipid profile. Patients also had increased IL-6 and reduced albumin and glucose. Although mean body mass index, FFMI and BMD were similar in patients and controls, only 20% of patients had a healthy BMD compared with 50% of controls. Patients had reduced 6MWD and reported less physical activity (p < 0.05). Patients with bronchiectasis had increased arterial stiffness (an indicator of increased CV risk), increased inflammation, reduced exercise capacity and bone thinning. These additional comorbidities require further evaluation for their management in these patients.

Low bone mineral density in men with chronic obstructive pulmonary disease.

BACKGROUND: Osteoporosis is common in patients with COPD but the likely multi-factorial causes contributing to this condition (e.g. sex, age, smoking, therapy) mask the potential contribution from elements related to COPD. In order to study osteoporosis and bone mineral density (BMD) related to COPD, we studied a well-defined group of patients and controls. METHODS: BMD, forced expiratory volume in one second (FEV1), circulating bone biomarkers and biochemistry were determined in 30 clinically stable male ex-smokers with confirmed COPD and 15 age matched "ex-smoker" male controls. None of the patients were on inhaled corticosteroids or received more than one short course of steroids. RESULTS: Mean (SD) FEV1% predicted of patients was 64(6)%, the majority having Global Initiative for Chronic Obstructive Lung Disease (GOLD) II airflow obstruction. There were 5/30 patients and 1/15 controls who were osteoporotic, while a further 17 patients and 5 controls were osteopenic. The BMD at the hip was lower in patients than controls, but not at the lumbar spine. Mean values of procollagen type 1 amino-terminal propeptide and osteocalcin, both markers of bone formation, and Type 1 collagen ß C-telopeptide, a marker of bone resorption, were similar between patients and controls. However, all bone biomarkers were inversely related to hip BMD in patients (r = -0.51, r = -0.67, r = -0.57, p < 0.05) but did not relate to lumbar spine BMD. 25-OH Vitamin D was lower in patients. CONCLUSIONS: Men with COPD had a greater prevalence of osteoporosis and osteopenia than age matched male controls, with a marked difference in BMD at the hip. Bone biomarkers suggest increased bone turnover.

Does pulmonary rehabilitation address cardiovascular risk factors in patients with COPD?

BACKGROUND: Patients with COPD have an increased risk of cardiovascular disease. Whilst pulmonary rehabilitation has proven benefit for exercise tolerance and quality of life, any effect on cardiovascular risk has not been fully investigated. We hypothesised that pulmonary rehabilitation, through the exercise and nutritional intervention, would address these factors. METHODS: Thirty-two stable patients with COPD commenced rehabilitation, and were compared with 20 age and gender matched controls at baseline assessment. In all subjects, aortic pulse wave velocity (PWV) an independent non-invasive predictor of cardiovascular risk, blood pressure (BP), interleukin-6 (IL-6) and fasting glucose and lipids were determined. These measures, and the incremental shuttle walk test (ISWT) were repeated in the patients who completed pulmonary rehabilitation. RESULTS: On commencement of rehabilitation aortic PWV was increased in patients compared with controls (p<0.05), despite mean BP, age and gender being similar. The IL-6 was also increased (p<0.05). Twenty-two patients completed study assessments. In these subjects, rehabilitation reduced mean (SD) aortic PWV (9.8 (3.0) to 9.3 (2.7) m/s (p<0.05)), and systolic and diastolic BP by 10 mmHg and 5 mmHg respectively (p<0.01). Total cholesterol and ISWT also improved (p<0.05). On linear regression analysis, the reduction in aortic PWV was attributed to reducing the BP. CONCLUSION: Cardiovascular risk factors including blood pressure and thereby aortic stiffness were improved following a course of standard multidisciplinary pulmonary rehabilitation in patients with COPD.

The effect of exercise on large artery haemodynamics in cystic fibrosis.

BACKGROUND: Adult patients with cystic fibrosis (CF) have resting abnormal large artery haemodynamics. Here, we obtain further insight in patients with CF by evaluating haemodynamic response to physiological stress. METHODS: Thirty-six stable CF patients mean (SD) age 28.9 (9.0)years and 25 controls matched for age, gender and body mass index were studied. Central haemodynamic parameters; including augmentation index (AIx) and wasted left ventricular pressure energy (∆E(W)) were determined pre, during and post light intensity cycle ergometry. RESULTS: During exercise, despite a similar heart rate and blood pressure, patients had comparatively greater ∆E(W) (P=0.03) and trend towards greater AIx (P=0.07) than controls. Exercise ∆E(W) was greatest in patients with CF related diabetes (n=11). In all subjects, exercise ∆E(W) was related to age (r=0.54, P<0.001) and FEV(1)% predicted (r=-0.32, P=0.01). CONCLUSIONS: Adults with CF have an abnormal haemodynamic response to exercise. This finding has deleterious implications for myocardial performance.

The CRP genotype, serum levels and lung function in men: the Caerphilly Prospective Study.

Systemic CRP (C-reactive protein) has been associated with impaired lung function. A causal relationship would increase the value of CRP as both a diagnostic and therapeutic tool. We assessed the association between lung function parameters, circulating CRP and CRP polymorphisms using Mendelian randomization in efforts to attribute causality to known associations. Spirometric parameters of FEV1 (forced expiratory volume in 1 s) and FVC (forced vital capacity) were determined in 2173 men participating in the Caerphilly Prospective Study. Lung function measures on 1021 participants were available at follow-up (mean, 16.8 years later). Serum CRP levels were measured at baseline, and three CRP polymorphisms were analysed. Haplotype analysis was performed. Serum CRP levels at baseline were inversely associated with contemporaneous FEV1 and FVC as well as at follow-up (P<0.001) even after adjustment for conventional confounders. Serum CRP was associated with FEV1 decline (P=0.04). All three CRP polymorphisms (rs1800947, rs1130864 and rs1205) predicted serum CRP; however, there were no clear associations of the polymorphisms or haplotypes with lung function or with lung function decline. In conclusion, serum CRP was associated with lung function cross-sectionally; however, CRP polymorphisms were not associated with lung function or decline, suggesting that the CRP-lung function relationship is due to reverse causality, an unmeasured confounding factor or only has a modest causal effect.

Cardiovascular and musculskeletal co-morbidities in patients with alpha 1 antitrypsin deficiency.

BACKGROUND: Determining the presence and extent of co-morbidities is fundamental in assessing patients with chronic respiratory disease, where increased cardiovascular risk, presence of osteoporosis and low muscle mass have been recognised in several disease states. We hypothesised that the systemic consequences are evident in a further group of subjects with COPD due to Alpha-1 Antitrypsin Deficiency (A1ATD), yet are currently under-recognised. METHODS: We studied 19 patients with PiZZ A1ATD COPD and 20 age, sex and smoking matched controls, all subjects free from known cardiovascular disease. They underwent spirometry, haemodynamic measurements including aortic pulse wave velocity (aPWV), an independent predictor or cardiovascular risk, dual energy X-ray absorptiometry to determine body composition and bone mineral density. RESULTS: The aPWV was greater in patients: 9.9(2.1) m/s than controls: 8.5(1.6) m/s, p = 0.03, despite similar mean arterial pressure (MAP). The strongest predictors of aPWV were age, FEV1% predicted and MAP (all p < 0.01). Osteoporosis was present in 8/19 patients (2/20 controls) and was previously unsuspected in 7 patients. The fat free mass and bone mineral density were lower in patients than controls (p < 0.001). CONCLUSIONS: Patients with A1ATD related COPD have increased aortic stiffness suggesting increased risk of cardiovascular disease and evidence of occult musculoskeletal changes, all likely to contribute hugely to overall morbidity and mortality.

Excessive aortic inflammation in chronic obstructive pulmonary disease: an 18F-FDG PET pilot study.

UNLABELLED: Chronic obstructive pulmonary disease (COPD) patients exhibit increased cardiovascular risk, even after controlling for smoking. Inflammation may underlie this observation. METHODS: We measured vascular inflammation in both COPD patients and controls using (18)F-FDG PET/CT. Aortic inflammation was expressed as the target-to-background ratio (TBR) of the standardized uptake value in 7 COPD patients, 5 metabolic syndrome patients, and 7 ex-smokers. RESULTS: Abdominal aortic mean TBR (+/-SD) was greater in COPD patients than in ex-smoker controls (1.60 +/- 0.13 vs. 1.34 +/- 0.15, P = 0.0001). Aortic arch and abdominal aorta mean TBRs were higher in metabolic syndrome patients than in COPD patients (aortic arch, 1.80 +/- 0.18 vs. 1.53 +/- 0.18, P = 0.001, and abdominal aorta, 1.71 +/- 0.14 vs. 1.60 +/- 0.13, P = 0.001). CONCLUSION: COPD patients exhibited aortic inflammation that fell between the aortic inflammation exhibited by ex-smokers and that by metabolic syndrome patients. This may in part explain the increased risk of cardiovascular disease in COPD patients.

Sub-clinical left and right ventricular dysfunction in patients with COPD.

BACKGROUND: Cardiovascular manifestations in COPD include increased arterial stiffness, ischaemic heart disease, chronic heart failure and cor pulmonale. We hypothesised that sub-clinical right (RV) and left ventricular (LV) dysfunction occurs in patients with COPD, related to the severity of airflow obstruction, arterial stiffness and systemic inflammation. METHODS: Thirty six patients and 14 controls, all free of overt cardiovascular disease underwent tissue Doppler echocardiography, spirometry, measurement of aortic pulse wave velocity (PWV) and venous sampling for inflammatory markers. RESULTS: Mean LV myocardial strain and strain rate were less in patients than controls, p<0.05. LV isovolumic relaxation time (IVRT) was prolonged in patients (125+/-15.2ms) compared with controls (98.2+/-21.1ms), p<0.01, indicating LV diastolic dysfunction. The RV free wall strain and strain rate were less in patients than controls, both p<0.05, indicating RV systolic dysfunction. Patients had sub-clinical pulmonary arterial hypertension with a greater RV myocardial relaxation time and Tei index, both p<0.01. Patients with mild airways obstruction had LV and RV dysfunction and evidence of increased RV afterload compared with controls. In multivariate analyses aortic PWV predicted LV IVRT, p<0.01, while FEV(1) predicted RV Tei index and myocardial relaxation time, both p<0.01. CONCLUSIONS: Patients with COPD have sub-clinical left ventricular dysfunction related to arterial stiffness, and right ventricular dysfunction related to airways obstruction. Both right and left ventricular dysfunction are present in patients with mild airways obstruction suggesting that cardiac co-morbidities commence early in the development of COPD.

The effects of hypoxia on markers of coagulation and systemic inflammation in patients with COPD.

BACKGROUND: It has been demonstrated that there is an increased risk of venous thromboembolism (VTE) during air travel on flights of long duration. Patients with COPD are also at increased risk of VTE, particularly during exacerbations, possibly because of a hypercoagulable state secondary to hypoxia and/or heightened systemic inflammation. We investigated the effects of hypoxia on indices of coagulation and systemic inflammation in patients with COPD. METHODS: Twenty clinically stable patients with mild COPD were recruited. Patients were randomized to receive either medical air or 100% nitrogen through a 40% venturi mask at a flow rate of 10 L/min for 2 h. Blood was sampled for thrombin-antithrombin complex (TAT), prothrombin activation fragments 1 + 2 (F(1 + 2)), von Willebrand factor antigen (VWF:Ag), D-dimer, and interleukin-6 (IL-6) at baseline and after 2 h. RESULTS: Patients in the hypoxia and control groups were similar in terms of age, sex, pack-years smoked, and severity of airflow obstruction. There was no difference in baseline TAT, F(1 + 2), VWF:Ag, D-dimer, or IL-6 levels between groups. In the control group, there was no change in markers of coagulation or systemic inflammation over the 2-h study. In patients who underwent hypoxic challenge, there was an increase in TAT (P < .001), F(1 + 2) (P < .01), and IL-6 (P < .01), whereas D-dimer and VWF:Ag levels were unchanged. CONCLUSIONS: This study demonstrates that a 2-h hypoxic challenge in patients with COPD results in coagulation activation in conjunction with an increase in systemic inflammation.

Lung function in mid-life compared with later life is a stronger predictor of arterial stiffness in men: the Caerphilly Prospective Study.

BACKGROUND: Increased arterial stiffness predicts future cardiovascular disease and in some cross-sectional studies it is related to worse lung function and obstructive pulmonary disease. We assessed the predictive value of lung function measured in mid-life as compared with later life on arterial stiffness in the Caerphilly Prospective Study (CaPS). METHODS: Men aged 47-67 years had lung function measured between 1984 and 1988 and repeated between 2002 and 2004 (n = 827) as well as having carotid-femoral pulse wave velocity (PWV) measured. RESULTS: Both forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) in mid-life and later life were inversely associated with PWV (P < 0.0001) but mid-life measures were stronger predictors. Only mid-life measures remained predictors after mutual adjustment (FEV(1) mid-life beta coeff. -0.65, 95% CI -1.04, -0.26, P < 0.0001; FVC mid-life beta coeff. -0.52, 95% CI -0.82, -0.23, P < 0.0001). Adjustment for smoking status, early life, inflammatory and metabolic factors in sub-groups did not markedly change the associations. CONCLUSIONS: Mid-life lung function is a stronger risk factor than in later life for arterial stiffness in men. It is possible that developmental factors influence both lung function and arterial stiffness. Lung function assessment in mid-life may identify individuals at greater risk of their future cardiovascular disease.