Fibroblast growth factor 23 is an independent marker of COPD and is associated with impairment of pulmonary function and diffusing capacity.

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that in recent years has been reported to have significant effects on numerous tissues. Chronic obstructive pulmonary disease (COPD) is associated with hypophosphatemia but the evidence for elevated plasma levels of FGF23 in COPD subjects is ambiguous. Recently, FGF23 has even been shown to be involved in the inflammatory pathways activated in COPD, so FGF23 could be a novel biomarker for COPD and impairment of pulmonary function. The purpose was thus to explore the association of FGF23 with COPD and measures of pulmonary function. This was a cross sectional study of 450 subjects who underwent spirometry, body plethysmography, determination of diffusing capacity (DL,CO) and biomarker analysis of FGF23, interleukin (IL)-1 receptor antagonist, IL-6 and IL-8. Forty-four participants were excluded due to missing data or renal impairment (eGFR <45 mL/min/m2). Spirometry identified 123 subjects with COPD. FGF23 levels were elevated in COPD subjects compared to non COPD subjects, and this remained significant after adjustment for age, sex and smoking habits (OR = 1.6, p = 0.02). Linear regression showed significant relationships between FGF23 and FEV1 (ß = -0.15, p = 0.003), RV/TLC (ß = 0.09, p = 0.05) and DL, CO (ß = -0.24, p < 0.001). In conclusion we found that plasma levels of FGF23 are elevated in COPD subjects even when adjusting for traditional risk factors. Furthermore, FGF23 is associated with impairment in lung function as measured by FEV1 and DL,CO. Further studies are needed to establish whether FGF23 could serve as a novel biomarker of COPD and emphysema development.

Matrix Metalloproteinases in COPD and atherosclerosis with emphasis on the effects of smoking.

BACKGROUND: Matrix metalloproteinases (MMP´s) are known biomarkers of atherosclerosis. MMP´s are also involved in the pathophysiological processes underlying chronic obstructive pulmonary disease (COPD). Cigarette smoking plays an important role in both disease states and is also known to affect the concentration and activity of MMP´s systemically. Unfortunately, the epidemiological data concerning the value of MMP´s as biomarkers of COPD and atherosclerosis with special regards to smoking habits are limited. METHODS: 450 middle-aged subjects with records of smoking habits and tobacco consumption were examined with comprehensive spirometry, carotid ultrasound examination and biomarker analysis of MMP-1, -3, -7, -10 and -12. Due to missing data 33 subjects were excluded. RESULTS: The remaining 417 participants were divided into 4 different groups. Group I (n = 157, no plaque and no COPD), group II (n = 136, plaque but no COPD), group III (n = 43, COPD but no plaque) and group IV (n = 81, plaque and COPD). Serum levels of MMP-1,-7,-10-12 were significantly influenced by smoking, and MMP-1, -3, -7 and-12 were elevated in subjects with COPD and carotid plaque. This remained statistically significant for MMP-1 and-12 after adjusting for traditional risk factors. CONCLUSION: COPD and concomitant plaque in the carotid artery were associated with elevated levels of MMP-1 and -MMP-12 even when adjusting for risk factors. Further studies are needed to elucidate if these two MMP´s could be useful as biomarkers in a clinical setting. Smoking was associated with increased serum levels of MMP´s (except for MMP-3) and should be taken into account when interpreting serum MMP results.

Associations between lung function and alcohol consumption--assessed by both a questionnaire and a blood marker.

BACKGROUND: Studies on the influence of alcohol consumption on lung function have shown conflicting results. Self-reported alcohol consumption may be inaccurate. This study used both a validated alcohol questionnaire and a blood marker of heavy alcohol consumption, and examined potential associations with different lung physiological variables. METHODS: The study population (450 subjects) answered an alcohol questionnaire (AUDIT-C) and performed spirometry, body plethysmography and a test for diffusing capacity for CO (DL,CO). Carbohydrate deficient transferrin (CDT), a clinically used blood marker for identifying heavy alcohol consumption, and C-reactive protein (CRP), a marker of systemic inflammation were analysed. RESULTS: Using AUDIT-C, 407 subjects were alcohol drinkers and 29 non-drinkers. Of the alcohol drinkers, 224 subjects were "hazardous drinkers" and 183 "moderate drinkers". Thirty-four subjects had a CDT ≥2.0% (=heavy drinkers). There was no difference in lung function between hazardous and moderate drinkers. Heavy drinkers had lower DL,CO (74% vs 83% PN, p = 0.003), more symptoms of chronic bronchitis (p = 0.001) and higher AUDIT-C scores (p < 0.001) than non-heavy drinkers. After adjustments (pack years and CRP) the difference in DL,CO (p = 0.037) remained. Multiple regression showed an association between CDT and both FEV1 (p = 0.004) and DL,CO (p = 0.012) in all alcohol drinkers, but not in never-smokers. The AUDIT-C score was associated with CDT (also after adjustments, p < 0.001) but not with any lung function variable. CONCLUSION: The results from this study suggest that alcohol and particularly heavy drinking has an independent additive negative effect on lung function in smokers.

Preoperative spirometry results as a determinant for long-term mortality after EVAR for AAA.

OBJECTIVES: The aim of this study was to analyse lung function test determinants for long-term mortality after standard endovascular aneurysm repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA). DESIGN: Retrospective analysis. MATERIALS: Three-hundred and four consecutive patients treated electively with EVAR (Zenith(®) stent grafts, Cook) between May 1998 and February 2006 were prospectively enrolled in a computerised database. METHODS: The Global Initiative for Chronic Obstructive Lung Diseases (GOLD) guideline was used to grade the severity of obstructive lung disease. Mortality was checked until 1 December 2010. Median follow-up time was 68 (interquartile range (IQR) 40-94) months. RESULTS: The percentage of patients with mild, moderate or severe (grade 3) chronic obstructive pulmonary disease (COPD) was 9.9%, 23.2% and 7.7%, respectively. In a combined medical severity assessment, arterial partial pressure of oxygen (PaO(2)) < 8.0 kPa or COPD, grade ≥3 (hazard ratio (HR) 2.06; 95% confidence interval (CI) (1.24-3.42)), anaemia (HR 1.72; 95% CI (1.21-2.44)), chronic kidney disease, stage ≥3 (HR 1.55; 95% CI (1.08-2.24)) and age ≥80 years (HR 1.55; 95% CI (1.04-2.31)) were independently associated with long-term mortality. Lower forced expiratory volume in 1 s (FEV(1)) (p = 0.002) and lower forced vital capacity (FVC) (p = 0.003) were independently associated with long-term mortality. CONCLUSIONS: Our findings strengthen the need for formal evaluation of lung function with spirometry prior to proceeding to AAA repair.

Comparison between transcranial Doppler and Coulter counter for detection of lipid micro embolization from mediastinal shed blood reinfusion during cardiac surgery.

INTRODUCTION: Lipid micro embolization (LME) from re-transfused shed blood has been postulated to be a potential reason for short- and long-term cognitive dysfunction after cardiac surgery. The purpose of this investigation was to evaluate if transcranial Doppler (TCD) has the capacity to detect LME. METHODS: Thirteen patients undergoing cardiopulmonary bypass surgery were investigated. Each patient's cerebral circulation was monitored with transcranial Doppler during the first two minutes after re-transfusion of shed blood and blood was simultaneously sampled and characterised by a Coulter counter. RESULTS: Strong correlation was found between embolic loads, as measured by transcranial Doppler and Coulter counter (r=0.79, P<0.005). CONCLUSIONS: This pilot study shows that non-invasive monitoring by transcranial Doppler could be a potential tool to monitor LME during cardiopulmonary bypass surgery.

Parametric quantification of myocardial ischaemia using real-time perfusion adenosine stress echocardiography images, with SPECT as reference method.

SUMMARY BACKGROUND: Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique, provides images for off-line parametric perfusion quantification using Qontrast software. From replenishment curves, this generates parametric images of peak signal intensity (A), myocardial blood flow velocity (beta) and myocardial blood flow (Axbeta) at rest and stress. This may be a tool for objective myocardial ischaemia evaluation. We assessed myocardial ischaemia by RTP-ASE Qontrast((R))-generated images, using 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) as reference. METHODS: Sixty-seven patients admitted to SPECT underwent RTP-ASE (SONOS 5500) during Sonovue infusion, before and throughout adenosine stress, also used for SPECT. Quantitative off-line analyses of myocardial perfusion by RTP-ASE Qontrast-generated A, beta and Axbeta images, at different time points during rest and stress, were blindly compared to SPECT. RESULTS: We analysed 201 coronary territories [corresponding to the left anterior descendent (LAD), left circumflex (LCx) and right coronary (RCA) arteries] from 67 patients. SPECT showed ischaemia in 18 patients. Receiver operator characteristics and kappa values showed that A, beta and Axbeta image interpretation significantly identified ischaemia in all territories (area under the curve 0.66-0.80, P = 0.001-0.05). Combined A, beta and Axbeta image interpretation gave the best results and the closest agreement was seen in the LAD territory: 89% accuracy; kappa 0.63; P<0.001. CONCLUSION: Myocardial isachemia can be evaluated in the LAD territory using RTP-ASE Qontrast-generated images, especially by combined A, beta and Axbeta image interpretation. However, the technique needs improvements regarding the LCx and RCA territories.

Real-time perfusion adenosine stress echocardiography versus myocardial perfusion adenosine scintigraphy for the detection of myocardial ischaemia in patients with stable coronary artery disease.

BACKGROUND: Real-time perfusion (RTP) contrast echocardiography using low mechanical index power modulation technique allows for simultaneous myocardial perfusion and wall motion analysis. RTP-adenosine stress echocardiography (ASE) could be an alternative to dobutamine-atropine stress echocardiography; more tolerable for the patients and possibly similarly accurate. We aimed to evaluate RTP-ASE for the detection of myocardial ischaemia, compared to 99mTc-sestamibi single-photon emission computed tomography (SPECT). METHODS: Patients with suspected coronary artery disease, admitted to SPECT evaluation, were prospectively invited to participate. Patients underwent RTP imaging (SONOS 5500) using infusion of Sonovue (Bracco, Milano, Italy) before and during ASE. Two separate readers performed off-line analysis of myocardial perfusion and wall motion by RTP-ASE. A perfusion defect was the principal marker of ischaemia. Wall motion assessment was used to evaluate ischaemia in segments with perfusion artefacts. Each segment was attributed to one of the three main coronary vessel areas of interest: the left anterior descending (LAD); the left circumflex (LCx) and the right posterior descending (RPD). Normal SPECT at stress was judged normal at rest. RESULTS: In 33 patients, 99 coronary territories were analysed by SPECT and RTP-ASE. SPECT showed evidence of ischaemia in 9 of 33 patients. For the detection of ischaemia, the overall level of agreement between RTP-ASE and SPECT was 92% in all segments. The level of agreement was 88% in LAD, 97% in LCx and 91% in RPD segments. CONCLUSION: Real-time perfusion-adenosine stress echocardiography using power modulation could be an accurate and feasible tool for evaluation of ischaemia in patients with suspected coronary artery disease. The results from this study need confirmation by a study of a larger patient sample.