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To evaluate the relationship of cardiac function, including time-volume-curves, with lung volumes derived from pulmonary function tests (PFT) and MRI in subjects without cardiovascular diseases. 216 subjects underwent whole-body MRI and spirometry as part of the KORA-FF4 cohort study. Lung volumes derived semi-automatically using an in-house algorithm. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and residual volume were measured. Cardiac parameters derived from Cine-SSFP-sequence using cvi42, while left ventricle (LV) time-volume-curves were evaluated using pyHeart. Linear regression analyses assessed the relationships of cardiac parameters with PFT and MRI-based lung volumes. Mean age was 56.3 ± 9.2 years (57% males). LV and right ventricular (RV) end-diastolic-, end-systolic-, stroke volume, LV peak ejection- and early/late diastolic filling rate were associated with FEV1, FVC, and residual volume (excluding late diastolic filling rate with FEV1, LV end-systolic/stroke volume and RV end-diastolic/end-systolic volumes with residual volume). In contrast, LV end-diastolic volume (ß = − 0.14, p = 0.01), early diastolic filling rate (ß = − 0.11, p = 0.04), and LV/RV stroke volume (ß = − 0.14, p = 0.01; ß = − 0.11, p = 0.01) were inversely associated with MRI-based lung volume. Subclinical cardiac impairment was associated with reduced FEV1, FVC, and residual volume. Cardiac parameters decreased with increasing MRI-based lung volume contrasting the results of PFT.

Background Multiple effects of ultrafine particles (UFP) on human subjects are known but there is less knowledge of how relative exposure levels between ultrafine and fine particles as typically encountered in large cities affect lung function and cardiovascular parameters. Methods Four sites with high/low levels of ultrafine particles and/or fine particles were selected in the city of Munich, Germany: control area (woodland), urban environment, heavy traffic site, biomass combustion (beech wood). In a randomized cross-over design, 26 young, healthy individuals were exposed at each site over 75 min to atmospheric pollutants, which were monitored continuously, while performing intermittent (5 min per 15 min) light exercise. Parameters assessed pre and post exposure comprised symptoms, spirometry, lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), alveolar volume (AV), the fractional concentration of exhaled nitric oxide (FeNO), reactive hyperemia index (RHI), blood pressure, and heart rate. Outcomes were expressed as percent changes of parameters and analyses performed by either comparing the four sites or by multiple linear regression analyses using the measured pollutant levels. Results The sites showed the planned pattern of exposure levels but with large overlap. Outcomes showed no statistically significant differences between sites, except for symptoms which were elevated with heavy traffic site exposure and biomass combustion. In regression analyses, AV decreased by 0.92 (95% confidence interval (CI): 0.28 to 1.57) % per 10,000/cm 3 UFP; similarly, for LDSA (lung-deposited surface area), which was highly correlated with UFP. Overall, FeNO slightly increased after exposure, but this increase was attenuated by 5.4 (95% CI: 1.8 to 9.2) % per 10 ppb ambient NO 2 . Heart rate decreased after exposures overall; this decrease was enhanced by 2.1 (95% CI: 0.3 to 4.0) % per 10,000/cm 3 UFP. Conclusions Short-term exposures to UFP elicited a reduction in the lung volume (AV) accessible to gas transport by diffusion and convection. FeNO was slightly elevated after all exposures, but this increase was significantly smaller at higher ambient NO 2 concentrations. While these effects were too small to be clinically relevant, they demonstrated that typical levels of urban air pollution had measurable acute effects in young, healthy individuals.

Background In lung disease, physical activity (PA) yields beneficial health effects, but its association with the function of healthy lungs has rarely been studied. We investigated the association of accelerometer-based PA with spirometric indices, maximal inspiratory mouth pressure (PI max ) and lung diffusion capacity in lung-healthy adults. Methods In total, 341 apparently lung-healthy participants from the population-based KORA (Cooperative Health Research in the Region of Augsburg) FF4 cohort study (45% male, aged 48-68 years, 47% never smokers) completed lung function testing and wore ActiGraph accelerometers over a one week period at the hip. In adjusted regression analyses, moderate to vigorous PA (MVPA) was characterized as: sex-specific activity quartiles, achieving ≥ 10 consecutive minutes (yes vs. no), and meeting the WHO PA recommendations (yes vs. no). Results Positive associations of MVPA-quartiles with forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), and corresponding Global Lung Function Initiative z-scores were found. Subjects in the most active quartile (> 47 or > 50 min/day for females and males, respectively) had 142 ml [95% CI: 23, 260] higher FEV 1 and 155 ml [95% CI: 10, 301] higher FVC than those in the least active quartile (< 17 or < 21 min/day for females and males, respectively); however these associations were stronger among ex−/current smokers. Achieving at least once 10 consecutive minutes of MVPA was only associated with higher PI max [β-estimate: 0.57 kPa; 95% CI: 0.04, 1.10], remaining significant among never smokers. No associations were found with diffusion capacity or for reaching the WHO-recommended 150 min of MVPA/week in 10-min bouts. Conclusions Although the effects were small, active subjects showed higher spirometric results. The observed associations were more pronounced among ever smokers suggesting a higher benefit of PA for subjects being at a higher risk for chronic lung diseases.

Right (RV) and left ventricular (LV) volumetric measurements by cardiac magnetic resonance imaging (MRI) are established for assessing systolic and diastolic function, but the role of MRI-derived lung volumes in LV function remains unclear. This study investigated the relationship between RV and LV function, considering lung volumes. In the KORA-MRI cohort, 361 subjects underwent 3 T whole-body MRI. Cardiac functional parameters were measured from cine-steady-state free precession sequences using cvi42. Lung volumes were derived semi-automatically with an in-house algorithm. Linear regression analyses assessed RV-LV relationships, adjusted for age, sex, cardiovascular risk factors, and lung volumes. Among 361 subjects (mean age 56.1 ± 9.1 years; 43% women), RV end-diastolic volume was positively associated with LV end-diastolic (β = 28.1, p < 0.001), end-systolic (β = 11.0, p < 0.001), and stroke volume (β = 17.0, p < 0.001), but inversely with ejection fraction (β = -1.4, p = 0.001). RV end-systole was positively associated with LV end-diastolic (β = 21.2, p < 0.001), end-systolic (β = 11.5, p < 0.001), stroke volume (β = 9.7, p < 0.001), and inversely with ejection fraction (β = -3.3, p < 0.001). Adjusting for lung volumes did not alter RV-LV associations, and no effect modification by sex was observed despite lung volume differences. In individuals without cardiovascular disease, RV and LV volumetric parameters were strongly associated, supporting the critical role of RV function in LV function, independent of lung volumes.

Background Muscle dysfunction in chronic obstructive pulmonary disease (COPD) represents a significant extrapulmonary manifestation. Yet, the role of muscle fat infiltration (myosteatosis) in paraspinal muscles remains incompletely characterized. This study investigated whether paraspinal myosteatosis and its distribution patterns are associated with COPD and pulmonary function. Methods Within the population-based KORA cohort, 214 participants underwent whole-body magnetic resonance imaging and pulmonary function testing. Paraspinal myosteatosis was quantified by chemical shift-encoded MRI at lumbar vertebra 3 (L3), from which proton density fat fraction (PDFF, in %) maps were derived. Intramyocellular (IMCL) and extramyocellular lipids (EMCL) were determined through voxel-based analysis using validated PDFF thresholds. COPD was defined spirometrically as FEV1/FVC below the lower limit of normal. Associations were examined using multivariable regression models adjusted for age, sex, smoking status, physical activity, and body mass index. Results Among participants (mean age 58.5 ± 5.8 years, 56.1% male), 24 (11.2%) had spirometrically defined COPD. Participants with COPD showed higher paraspinal PDFF (19.9 ± 7.0% vs. 18.3 ± 7.6%) and lower IMCL/EMCL ratios (1.0 ± 0.4 vs. 1.2 ± 0.6) compared to those without COPD. After adjustment, higher PDFF was independently associated with increased odds of COPD (OR 1.69, 95% CI: 1.01–2.84, p  = 0.046), while a higher IMCL to EMCL ratio showed protective associations (OR 0.49, 95% CI: 0.24-1.00, p  = 0.050). Both total paraspinal PDFF and EMCL were negatively associated with pulmonary gas exchange capacity (TLCO/VA: β=-0.19, 95% CI: -0.35–0.04, p  = 0.016 and β=-0.18, 95% CI: -0.33–0.03, p  = 0.022, respectively). Conversely, higher IMCL/EMCL ratios were associated with better gas exchange (TLCO/VA: β = 0.15, 95% CI: 0.01–0.29, p  = 0.031). Conclusions This population-based study demonstrates that while increased total paraspinal muscle fat content is associated with higher COPD risk, its compartmental distribution reveals distinct patterns: A higher proportion of IMCL relative to EMCL shows protective associations, potentially reflecting preserved type I oxidative muscle fiber characteristics. These findings suggest that muscle fat distribution patterns may serve as imaging markers of metabolic adaptation in COPD, offering new perspectives for disease monitoring and therapeutic approaches.

Left atrial (LA) physiology and hemodynamics are intimately connected to cardiac and lung function in health and disease. This study examined the relationship between MRI-based left atrial (LA) size and function with MRI-based lung volume and pulmonary function testing (PFT) parameters in the population-based KORA study cohort of 400 participants without overt cardiovascular disease. MRI quantification assessed LA size/function in sequences with and without ECG synchronization, alongside lung volume. Regression analysis explored the relationship of LA with MRI lung volume and PFT parameters. Among 378 participants (average age 56.3 ± 9.2 years; 42.3% women), non-gated LA size averaged 16.8 cm 2 , while maximal and minimal LA size from gated measurements were 19.6 cm 2 and 11.9 cm 2 respectively. The average MRI-derived lung volume was 4.0 L, with PFT showing a total lung capacity of 6.2 L, residual lung volume of 2.1 L, and forced vital capacity of 4.1 L. Multivariate regression analysis, adjusted for age, gender, and cardiovascular risk factors, revealed an inverse association between maximum LA size, non-gated LA, and LA area fraction with lung volume (ß = − 0.03, p = 0.006; ß = − 0.03, p = 0.021; ß = − 0.01, p = 0.012), with no significant association with PFT parameters. This suggests that MRI-based assessment may offer greater sensitivity in detecting subclinical LA impairment than PFT.

In light of overall increasing healthcare expenditures, it is mandatory to study determinants of future costs in chronic diseases. This study reports the first longitudinal results on healthcare utilization and associated costs from the German chronic obstructive pulmonary disease (COPD) cohort COSYCONET. Based on self-reported data of 1904 patients with COPD who attended the baseline and 18-month follow-up visits, direct costs were calculated for the 12 months preceding both examinations. Direct costs at follow-up were regressed on baseline disease severity and other co-variables to identify determinants of future costs. Change score models were developed to identify predictors of cost increases over 18 months. As possible predictors, models included GOLD grade, age, sex, education, smoking status, body mass index, comorbidity, years since COPD diagnosis, presence of symptoms, and exacerbation history. Inflation-adjusted mean annual direct costs increased by 5% (n.s., €6,739 to €7,091) between the two visits. Annual future costs were significantly higher in baseline GOLD grades 2, 3, and 4 (factors 1.24, 95%-confidence interval [1.07-1.43], 1.27 [1.09-1.48], 1.57 [1.27-1.93]). A history of moderate or severe exacerbations within 12 months, a comorbidity count >3, and the presence of dyspnea and underweight were significant predictors of cost increase (estimates ranging between + €887 and + €3,679, all <0.05). Higher GOLD grade, comorbidity burden, dyspnea and moderate or severe exacerbations were determinants of elevated future costs and cost increases in COPD. In addition we identified underweight as independent risk factor for an increase in direct healthcare costs over time.

Background Fighter aircraft pilots are regularly exposed to physiological challenges from high acceleration (G z ) forces, as well as increased breathing pressure and oxygen supply in the support systems. We studied whether effects on the lung and systemic oxidative stress were detectable after real training flights comprising of a wide variety of exposure conditions, and their combinations. Methods Thirty-five pilots of the German Air Force performed 145 flights with the Eurofighter Typhoon. Prior to and after flight lung diffusing capacity for carbon monoxide (DL CO ) and nitric oxide (DL NO ), alveolar volume (V A ), and diffusing capacities per volume (K CO , K NO ) were assessed. In addition, the fractional concentration of exhaled nitric oxide (FeNO) was determined, and urine samples for the analysis of molecular species related to 8-hydroxy-2’-deoxyguanosine (8-OHdG) were taken. For statistical analysis, mixed ANOVA models were used. Results DL NO , DL CO , K NO , K CO and V A were reduced ( p  < 0.001) after flights, mean ± SD changes being 2.9 ± 5.0, 3.2 ± 5.2, 1.5 ± 3.7, 1.9 ± 3.7 and 1.4 ± 3.1%, respectively, while FeNO decreased by 11.1% and the ratio of 8-OHdG to creatinine increased by 15.7 ± 37.8%. The reductions of DL NO (DL CO ) were smaller ( p  < 0.001) than those of K NO (K CO ). In repeated flights on different days, baseline values were restored. Amongst various flight parameters comprising G z -forces and/or being indicative of positive pressure breathing and oxygenation support, the combination of long flight duration and high altitude appeared to be linked to greater changes in DL NO and DL CO . Conclusions The pattern of reductions in diffusing capacities suggests effects arising from atelectasis and increased diffusion barrier, without changes in capillary blood volume. The decrease in exhaled endogenous NO suggests bronchial mucosal irritation and/or local oxidative stress, and the increase in urinary oxidized guanosine species suggests systemic oxidative stress. Although changes were small and not clinically relevant, their presence demonstrated physiological effects of real training flights in a modern 4th generation fighter jet.

Although hyperlipidemia is common in COPD, its relationship to comorbidities, risk factors and lung function in COPD has not been studied in detail. Using the baseline data of the COSYCONET cohort we addressed this question. Data from 1746 COPD patients (GOLD stage 1-4; mean age 64.6 y, mean FEV1%pred 57%) were evaluated, focusing on the comorbidities hyperlipidemia, diabetes and cardiovascular complex (CVC; including arterial hypertension, cardiac failure, ischemic heart disease). Risk factors comprised age, gender, BMI, and packyears of smoking. The results of linear and logistic regression analyses were implemented into a path analysis model describing the multiple relationships between parameters. Hyperlipidemia (prevalence 42.9%) was associated with lower intrathoracic gas volume (ITGV) and higher forced expiratory volume in 1 second (FEV1) when adjusting for its multiple relationships to risk factors and other comorbidities. These findings were robust in various statistical analyses. The associations between comorbidities and risk factors were in accordance with previous findings, thereby underlining the validity of our data. In conclusion, hyperlipidemia was associated with less hyperinflation and airway obstruction in patients with COPD. This surprising result might be due to different COPD phenotypes in these patients or related to effects of medication.

Impulse oscillometry (IOS) is a non-demanding lung function test. Its diagnostic use may be particularly useful in patients of advanced age with physical or mental limitations unable to perform spirometry. Only few reference equations are available for Caucasians, none of them covering the old age. Here, we provide reference equations up to advanced age and compare them with currently available equations. IOS was performed in a population-based sample of 1990 subjects, aged 45-91 years, from KORA cohorts (Augsburg, Germany). From those, 397 never-smoking, lung healthy subjects with normal spirometry were identified and sex-specific quantile regression models with age, height and body weight as predictors for respiratory system impedance, resistance, reactance, and other parameters of IOS applied. Women (n = 243) showed higher resistance values than men (n = 154), while reactance at low frequencies (up to 20 Hz) was lower (p<0.05). A significant age dependency was observed for the difference between resistance values at 5 Hz and 20 Hz (R5-R20), the integrated area of low-frequency reactance (AX), and resonant frequency (Fres) in both sexes whereas reactance at 5 Hz (X5) was age dependent only in females. In the healthy subjects (n = 397), mean differences between observed values and predictions for resistance (5 Hz and 20 Hz) and reactance (5 Hz) ranged between -1% and 5% when using the present model. In contrast, differences based on the currently applied equations (Vogel & Smidt 1994) ranged between -34% and 76%. Regarding our equations the indices were beyond the limits of normal in 8.1% to 18.6% of the entire KORA cohort (n = 1990), and in 0.7% to 9.4% with the currently applied equations. Our study provides up-to-date reference equations for IOS in Caucasians aged 45 to 85 years. We suggest the use of the present equations particularly in advanced age in order to detect airway dysfunction.