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Single nucleotide polymorphisms (SNPs) in various genes have been shown to associate with COPD, suggesting a role in disease pathogenesis. Sulfatase modifying factor (SUMF1) is a key modifier in connective tissue remodelling, and we have shown previously that several SNPs in

To determine how the presence of intravenous (IV) contrast-enhanced CT influences SUV measurements corrected for both attenuation and tissue fraction. Eighteen patients with different malignancies, free from lung disorders, lung cancer or metastasis, were prospectively recruited when referred for staging with combined There was no significant difference between low dose PET/CT and IV contrast-enhanced PET/CT when removing the impact of air fraction (p = 0.093 for the right lung and p = 0.085 for the left lung). When tissue fraction was not corrected for, there was a significant difference between low dose PET/CT and IV contrast enhanced PET/CT used for attenuation correction (p = 0.006 for the right lung and p = 0.015 for the left lung). There was only a marginal effect on the assessement of SUV in the lung tissue when using IV contrast enhanced CT for attenuation correction when the air fraction was accounted for.ZIEL: Bestimmung, inwiefern die intravenöse (IV) kontrastverstärkte CT Einfluss auf die SUV-Messungen mit Korrektur von beiden, der Schwächung und des Gewebeanteils, hat. Es wurden 18 Patienten mit verschiedenen Malignomen, ohne Lungenerkrankungen, Lungenkarzinome oder Metastasen, prospektiv rekrutiert, bei denen ein Staging mittels kombinierter 18F-FDG-PET/CT-Untersuchung durchgeführt wurde. Auf eine nicht-verstärkte Niedrigdosis-CT der Brust folgte unmittelbar darauf eine Ganzkörper IV kontrastverstärkte diagnostische CT und schließlich die PET-Akquisition. Die PET-Daten wurden mit Schwächungskorrektur auf Basis der beiden CT-Datensätze rekonstruiert. Die Lungen wurden in den CT-Aufnahmen segmentiert und die Lungendichte gemessen. Die Aufnahme von 18F-FDG in das Lungenparenchym wurde sowohl mit nicht-verstärkter als auch mit IV kontrastverstärkter CT sowie mit und ohne Kompensation der Lungenbelüftung erfasst. Die SUV-Werte der korrigierten und nicht-korrigierten PET-Bilder wurden verglichen. Es gab keinen signifikanten Unterschied zwischen Niedrigdosis PET/CT und IV kontrastverstärkter PET/CT wenn man den Einfluss der Luftfraktion entfernt (p = 0,093 für die rechte Lunge und p = 0,085 für die linke Lunge). Wenn nicht nach Gewebeanteil korrigiert wurde, gab es einen signifikanten Unterschied beim Einsatz von Niedigdosis PET/CT und IV kontrastverstärkter PET/CT zur Schwächungskorrektur (p = 0,006 für die rechte Lunge und p = 0,015 für die linke Lunge). Es gab es nur einen marginalen Effekt auf die Beurteilung des SUV im Lungengewebe bei Verwendung von IV kontrastverstärkter CT zur Schwächungskorrektur, wenn der Luftanteil berücksichtigt wurde.

BACKGROUND: The forced oscillation technique (FOT) provides detailed information about the mechanics of the respiratory system, while requiring minimal co-operation by the patient. FOT may be abnormal in subjects with normal spirometry and appears to be more closely related to airway symptoms. It is, therefore, attractive in epidemiological studies, where a large number of different examinations are made in each subjects in a short period of time. Current technical standards recommend the mean of three consecutive measurements to be used, but there is limited information regarding within-session variability of FOT measurements.OBJECTIVE: The purpose of this study was to examine the within-session variability in FOT measurements in a large, population-based sample.METHODS: We performed three consecutive FOT measurements in 700 subjects using the impulse oscillometry system. The first measurement was compared to the mean of three measurements for resistance at 5 and 20 Hz (R5 and R20, respectively), R5-R20, reactance at 5 Hz (X5) and resonant frequency (fres ).RESULTS: The differences between the first and the mean of three measurements (median, interquartile range) were minimal, for example 0.002, -0.008 to 0.014 kPa L-1 s for R5 and -0.001, -0.008 to 0.005 kPa L-1 s for X5. Findings were numerically similar for men and women as well as for subjects with and without airflow obstruction at spirometry.CONCLUSIONS: We conclude that, whereas in clinical situations, three FOT measurements are to be preferred, a single measurement may suffice in epidemiological studies. (Less)

Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are leading causes of global morbidity and mortality. There is a well-known comorbidity between COPD and CAD, which is only partly explained by smoking and other known common risk factors. In order to better understand the relationship between COPD and CAD, we analyzed myocardial perfusion, pulmonary function and novel cardiovascular biomarkers in patients with symptoms suggesting myocardial ischemia.A total of 396 subjects from the Swedish Biomarkers and Genetics CardioPulmonary Physiology Study (BiG CaPPS) were included, all of whom had been referred to myocardial perfusion imaging due to suspected myocardial ischemia. Subjects performed myocardial perfusion imaging (MPI), pulmonary function tests (PFT) and analysis of 92 proteomic biomarkers, previously associated with cardiovascular disease. Linear regression was used to study the relationship between MPI and PFT results and proteomic biomarkers.Subjects with CAD (n = 159) had lower diffusing capacity (DLCO) than patients without CAD (6.64 versus 7.17 mmol/(min*kPa*l); p = 0.004) in models adjusted for common covariates such as smoking, but also diabetes and brain natriuretic peptide (BNP). The association remained significant after additional adjustment for forced expiratory volume in one second (FEV1) (p = 0.009). Subjects with CAD, compared with subjects without CAD, had higher total airway resistance (0.37 vs 0.36 kPa/(l/s); p = 0.036). Among 92 protein biomarkers, nine were associated with a combined diagnosis of CAD and airflow obstruction: VSIG2, KIM1, FGF-23, REN, XCL1, GIF, ADM, TRAIL-R2 and PRSS8.Diffusing capacity for carbon monoxide is decreased in patients with CAD, independently of decreased FEV1, diabetes, and elevated BNP. Several cardiovascular biomarkers are associated with co-existent CAD and airflow obstruction, but none with airflow obstruction only. The current findings indicate that the interaction between CAD and lung function is complex, including mechanisms beyond the known association between CAD and reduced ventilation.

Impulse oscillometry (IOS) is regarded as a sensitive method to detect lung function impairment. Impaired IOS appears to relate better than spirometry to respiratory symptoms. However the evidence from large studies is scarce and therefore we studied if abnormal IOS relates to respiratory symptoms in individuals with normal spirometry from the SCAPIS. Normal values for postbronchodilatory IOS were defined in 3664 healthy, never-smoking individuals. Based on the upper limit of normal, we defined abnormal resistance (R) at 5 Hz (R5), at 20 Hz (R20), and area under reactance (AX). Similarly, lower limit of normal was used to define abnormal X5. We studied how abnormal IOS parameters related with respiratory symptoms in 8674 individuals, aged 50-65 years, with FEV1/VC-ratio >0.7 and FEV1>80% predicted. Higher prevalence of abnormal R5, R20, X5 and AX were found with regard to wheeze and dyspnea, analysed separately (all p-values In conclusion, abnormal IOS parameters are related with increased respiratory burden in individuals with normal spirometry. Reactance parameters appear to be stronger related to wheeze, while resistance is stronger related to dyspnea and cough.

Background and aims The aim of the study was to determine potential associations between endothelial dysfunction and arterial stiffness, measured by peripheral arterial tonometry, and coronary artery calcium score (CACS) assessed by computed tomography (CT). Methods and results The BIG3 study is a prospective longitudinal, non-interventional, pulmonary-cardiovascular cohort study exploring the three major smoking-induced diseases: cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer, in a 45–75 aged cohort (mean 62 years), enriched in smokers. Computed tomography of the chest with assessment of CACS was performed in a selected subset of the participants (n = 2080). Peripheral arterial tonometry (EndoPAT) was used to assess endothelial function and arterial stiffness measured as reactive hyperaemia index (RHI) and augmentation index (AI), respectively. We observed significant associations of CACS, endothelial dysfunction, and arterial stiffness with several risk factors for coronary heart disease including age, sex, BMI, diabetes mellitus, and blood pressure. There was significant association of CACS, classified into three levels of severity, with RHI and AI (p = 0.0005 and p = 0.0009, respectively). For groups of increasing CACS (0, 1–400 and > 400 Agatston score), RHI decreased from median 1.89 (1.58–2.39), and 1.93 (1.62–2.41) to 1.77 (1.51–2.10). AI increased from median 14.3 (5.7–25.2), and 16.4 (8.1–27.6) to 18.0 (9.1–29.2). RHI, but not AI, remained significantly associated with CACS after risk factors adjustment. Conclusions In this large study of coronary artery calcium and vascular function, we found an association between CACS and both endothelial dysfunction and arterial stiffness, indicating that they may reflect similar mechanisms for development of cardiovascular disease.

Background Advanced glycation end-products (AGEs) have been implicated in the pathophysiology of chronic obstructive pulmonary disease (COPD). However, the association between AGE accumulation in the skin measured by skin autofluorescence (SAF) and lung function in healthy subjects has not been explored in detail. We use a population-based study of 50–64-year-olds to assess spirometry, diffusing capacity of the lung for carbon monoxide (DLCO) and impulse oscillometry (IOS) in relation to SAF. Methods Participants with information on SAF, lung function and potential confounding variables were included from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) cohort (spirometry, n=4111; DLCO, n=3889; IOS, n=3970). Linear regression was used to assess changes in lung function (as measured by spirometry (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC), DLCO and IOS (resistance measured at 5 (R5) and 20 Hz (R20), R5−R20, area of reactance, reactance measured at 5 Hz (X­5), and resonant frequency)) by a 1-sd increase in SAF. Results FEV1, FVC and DLCO were significantly and inversely associated with SAF after adjustment for potential confounding factors (per 1-sd increase in SAF: FEV1 −0.03 L (95% CI −0.04– −0.02 L), p, AGEs accumulation as measured by SAF is significantly associated with lung function decrements indicative of changes in the lung parenchyma http://bit.ly/2IRgSWz

The association between socioeconomic circumstances and incidence of chronic obstructive pulmonary disease (COPD) was investigated in an urban population in Sweden. The study included all 40–89 year-old inhabitants in Malmo, Sweden (N = 117,479) without previous hospitalization due to COPD, who were followed over 14 years for COPD related hospital admissions. The Malmo Preventive Project (MPP) cohort (n = 27,358) with information on biological and lifestyle factors was also used to study the association between socioeconomic circumstances and COPD. The Swedish hospital discharge register was used to record incidence of COPD hospitalizations. A total of 2,877 individuals (47.5% men) were discharged from hospital with COPD as the primary diagnosis during follow-up in Malmo. Low annual income (hazard ratio (HR): 2.23; 95%CI: 1.97–2.53, P < 0.001) and rented (vs. self-owned) housing (HR: 1.41; 1.30–1.52, P < 0.001) were associated with a higher risk for COPD. In addition, compared to married subjects, divorced (HR: 1.61; 1.46–1.78, P < 0.001) and widowed (HR: 1.30; 1.16–1.46, P < 0.001) individuals had an increased risk for hospitalization due to COPD. Low income, low occupation and being divorced or widowed were similarly associated with COPD in the MPP cohort, after adjustments for smoking, FEV 1 , BMI, age and sex. However, socioeconomic circumstances were not associated with COPD in analyses restricted to never smokers. Low socioeconomic circumstances were associated with an increased risk of COPD after adjustments for biological and lifestyle risk factors including smoking status. However, this relationship was not significant in those who never smoked.

There is no general agreement on the spirometric definition of chronic obstructive pulmonary disease (COPD). The global initiative for obstructive lung disease recommends a fixed ratio between forced expiratory volume in one-second (FEV1 ) and forced vital capacity (FVC) of 0·7.

SummaryBackgroundStudies 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.MethodsThe 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.ResultsUsing 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

Background Levels of plasma brain natriuretic peptide (BNP) have been shown to be elevated in chronic obstructive pulmonary disease (COPD) especially in connection with cor pulmonale (CP) and the late stages of the disease. BNP is also raised in left sided heart failure which sometimes coincides with COPD. Whether BNP is elevated in subjects with mild–moderate stable COPD and normal left ventricular function is not clear. Objective To investigate BNP levels in subjects with mild–moderate COPD and normal left ventricular function. Methods This was a cross sectional study of 450 subjects from a population-based respiratory questionnaire survey. All subjects were examined with echocardiography and spirometry and blood samples were drawn for BNP measurements. Subjects with left sided heart disease (n = 26) or echocardiographic signs of elevated filling pressure (n = 75), COPD stages III and IV (n = 5) or missing data (n = 13) were excluded. Results In the final study population (n = 331) spirometry identified 86 subjects with COPD (GOLD stage I, n = 65 and GOLD stage II, n = 21). In comparison with the rest of the study population subjects with COPD were significantly older, longer and with a male predominance. In a multivariate linear regression analysis with log-normalized (lnBNP) as the dependent variable a significant correlation was found with age, left atrial volume, body surface area and haemoglobin, but not with any pulmonary variables. Even when comparing groups no significant difference could be found between the plasma levels of lnBNP in normal subjects (1.8 ± 0.7 mean ± SD, pmol/L) subjects and in COPD subjects (1.9 ± 0.7, P = 0.47). Conclusions In a population with normal left ventricular function no significant differences in BNP levels between stable mild–moderate COPD subjects and normal individuals could be found.

Background: Smoking is known to have many short- and long-term cardiovascular effects. Cardiac index (CI), which is cardiac output indexed to body surface area, is considered to be a valid measure of cardiac performance. We investigated whether there were any differences in CI or other echocardiographic variables between never smokers, ex-smokers, and current smokers in a cardiopulmonary healthy population. Methods: Subjects (n=355) from a previous population-based respiratory questionnaire survey (never smokers, ex-smokers, and current smokers without significant chronic obstructive lung disease) were examined with echocardiography, and CI (L/min/m2) was calculated. Results: Current smokers had a higher CI than never smokers 2.61±0.52 L/min/m2 vs. 2.42±0.49 L/min/m2 (P .05). Smoking status had no significant effect on other echocardiographic variables. Conclusion: We conclude that currents smokers without known cardiac disease or significant chronic obstructive lung disease show signs of slightly altered hemodynamics. (Less)

BACKGROUND: Spirometry is used to diagnose chronic obstructive pulmonary disease (COPD). The Impulse oscillometry system (IOS) allows determination of respiratory impedance indices, which might be of potential value in early COPD, although previous experience is limited. We examined pulmonary resistance and reactance measured by IOS in subjects with or without self-reported chronic bronchitis or emphysema or COPD (Q+ or Q-) and subjects with or without COPD diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (G+ or G-). METHODS: From a previous population-based study 450 subjects were examined with spirometry and IOS and answered a questionnaire on respiratory symptoms and diseases. RESULTS: Seventy-seven subjects were Q+, of whom 34 also were G+. Q+/G- subjects (n = 43) reported respiratory symptoms more frequently (35-40% vs 8-14%) but had higher FEV(1) (100% vs 87%) than Q-/G+ subjects (n = 90), p < 0.05 for both comparisons. Q+ subjects had higher pulmonary resistance and lower pulmonary reactance than Q- subjects (p < 0.01 for all comparisons). The same pattern was seen both in G+ subjects ((Q+/Q-) R5 0.39/0.32, R5-R20 0.10/0.07, X5 0.13/0.09, AX 0.55/0.27, p < 0.05 for all) and G- subjects ((Q+/Q-) R5 0.35/0.29, R5-R20 0.08/0.06, X5 0.10/0.08, AX 0.31/0.19 p < 0.05 for all) except for R20 (adjusted for gender and age). CONCLUSIONS: Self-reported chronic bronchitis or emphysema or COPD was associated with higher pulmonary resistance and lower pulmonary reactance measured by IOS, both among subjects with and without COPD according to GOLD criteria. IOS may have the potential to detect pathology associated with COPD earlier than spirometry.

Background: Previous studies on associations between reduced lung function and cardiovascular disease (CVD) have mainly been based on forced expiratory volume in 1-s (FEV(1) ) and vital capacity (VC). This study examined potential associations between five different lung function variables and plaques in the internal carotid artery (ICA). Methods: Subjects (n = 450) from a previous population-based respiratory questionnaire survey [current smokers without lower respiratory symptoms, subjects with a self-reported diagnosis of chronic obstructive pulmonary disease (COPD) and never-smokers without lower respiratory symptoms] were examined using spirometry, body plethysmography and measurements of diffusing capacity for CO (D(L,CO) ). Plaques in the ICA were assessed by ultrasonography. Results: Two hundred and twenty subjects were current smokers, 139 ex-smokers and 89 never-smokers. COPD was diagnosed in 130 subjects (GOLD criteria). Plaques in the ICA were present in 231 subjects (52%). General linear analysis with adjustment for established risk factors for atherosclerosis, including C-reactive protein, showed that D(L,CO) was lower [77·4% versus 83·7% of predicted normal (PN), P = 0·014] and residual volume (RV) was higher (110·3% versus 104·8% of PN, P = 0·020) in subjects with than without plaques in the ICA. This analysis did not show any statistically significant association between plaques and FEV(1) or VC. Conclusion: The occurrence of plaques in the ICA was associated with low D(L,CO) and high RV, but not significantly with FEV(1) or COPD status. The results suggest that the relationships between reduced lung function, COPD and CVD are complex and not only linked to bronchial obstruction and low-grade systemic inflammation. (Less)

BackgroundMatrix 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.Methods450 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.ResultsThe 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.ConclusionCOPD 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.

Previous studies on associations between reduced lung function and cardiovascular disease (CVD) have mainly been based on forced expiratory volume in 1-s (FEV(1) ) and vital capacity (VC). This study examined potential associations between five different lung function variables and plaques in the internal carotid artery (ICA).Subjects (n = 450) from a previous population-based respiratory questionnaire survey [current smokers without lower respiratory symptoms, subjects with a self-reported diagnosis of chronic obstructive pulmonary disease (COPD) and never-smokers without lower respiratory symptoms] were examined using spirometry, body plethysmography and measurements of diffusing capacity for CO (D(L,CO) ). Plaques in the ICA were assessed by ultrasonography.Two hundred and twenty subjects were current smokers, 139 ex-smokers and 89 never-smokers. COPD was diagnosed in 130 subjects (GOLD criteria). Plaques in the ICA were present in 231 subjects (52%). General linear analysis with adjustment for established risk factors for atherosclerosis, including C-reactive protein, showed that D(L,CO) was lower [77.4% versus 83.7% of predicted normal (PN), P = 0.014] and residual volume (RV) was higher (110.3% versus 104.8% of PN, P = 0.020) in subjects with than without plaques in the ICA. This analysis did not show any statistically significant association between plaques and FEV(1) or VC.The occurrence of plaques in the ICA was associated with low D(L,CO) and high RV, but not significantly with FEV(1) or COPD status. The results suggest that the relationships between reduced lung function, COPD and CVD are complex and not only linked to bronchial obstruction and low-grade systemic inflammation.