Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry.

Rationale: Postbronchodilator spirometry is used for the diagnosis of chronic obstructive pulmonary disease. However, prebronchodilator reference values are used for spirometry interpretation. Objectives: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or postbronchodilator reference values generated within SCAPIS (Swedish CArdioPulmonary bioImage Study) when interpreting postbronchodilator spirometry in a general population. Methods: SCAPIS reference values for postbronchodilator and prebronchodilator spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or postbronchodilator reference values, with respiratory burden in the SCAPIS general population (28,851 individuals). Measurements and Main Results: Bronchodilation resulted in higher predicted medians and lower limits of normal (LLNs) for FEV1/FVC ratios. The prevalence of postbronchodilator FEV1/FVC ratio lower than the prebronchodilator LLN was 4.8%, and that of postbronchodilator FEV1/FVC lower than the postbronchodilator LLN was 9.9%, for the general population. An additional 5.1% were identified as having an abnormal postbronchodilator FEV1/FVC ratio, and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%; P < 0.001), and self-reported physician-diagnosed chronic obstructive pulmonary disease (2.8% vs. 0.5%, P < 0.001) than subjects with a postbronchodilator FEV1/FVC ratio greater than the LLN for both pre- and postbronchodilation. Conclusions: Pre- and postbronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of postbronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using postbronchodilator reference values when interpreting postbronchodilator spirometry might enable the identification of individuals with mild disease and be clinically relevant.

An experimental study on lung deposition of inhaled 2 µm particles in relation to lung characteristics and deposition models.

BACKGROUND: The understanding of inhaled particle respiratory tract deposition is a key link to understand the health effects of particles or the efficiency for medical drug delivery via the lung. However, there are few experimental data on particle respiratory tract deposition, and the existing data deviates considerably when comparing results for particles > 1 µm. METHODS: We designed an experimental set-up to measure deposition in the respiratory tract for particles > 1 µm, more specifically 2.3 µm, with careful consideration to minimise foreseen errors. We measured the deposition in seventeen healthy adults (21-68 years). The measurements were performed at tidal breathing, during three consecutive 5-minute periods while logging breathing patterns. Pulmonary function tests were performed, including the new airspace dimension assessment (AiDA) method measuring distal lung airspace radius (rAiDA). The lung characteristics and breathing variables were used in statistical models to investigate to what extent they can explain individual variations in measured deposited particle fraction. The measured particle deposition was compared to values predicted with whole lung models. Model calculations were made for each subject using measured variables as input (e.g., breathing pattern and functional residual capacity). RESULTS: The measured fractional deposition for 2.3 µm particles was 0.60 ± 0.14, which is significantly higher than predicted by any of the models tested, ranging from 0.37 ± 0.08 to 0.53 ± 0.09. The multiple-path particle dosimetry (MPPD) model most closely predicted the measured deposition when using the new PNNL lung model. The individual variability in measured particle deposition was best explained by breathing pattern and distal airspace radius (rAiDA) at half inflation from AiDA. All models underestimated inter-subject variability even though the individual breathing pattern and functional residual capacity for each participant was used in the model. CONCLUSIONS: Whole lung models need to be tuned and improved to predict the respiratory tract particle deposition of micron-sized particles, and to capture individual variations - a variation that is known to be higher for aged and diseased lungs. Further, the results support the hypothesis that the AiDA method measures dimensions in the peripheral lung and that rAiDA, as measured by the AiDA, can be used to better understand the individual variation in the dose to healthy and diseased lungs.

Lung function and self-rated symptoms in healthy volunteers after exposure to hydrotreated vegetable oil (HVO) exhaust with and without particles.

BACKGROUND: Diesel engine exhaust causes adverse health effects. Meanwhile, the impact of renewable diesel exhaust, such as hydrotreated vegetable oil (HVO), on human health is less known. Nineteen healthy volunteers were exposed to HVO exhaust for 3 h in a chamber with a double-blind, randomized setup. Exposure scenarios comprised of HVO exhaust from two modern non-road vehicles with 1) no aftertreatment system ('HVOPM+NOx' PM1: 93 µg m-3, EC: 54 µg m-3, NO: 3.4 ppm, NO2: 0.6 ppm), 2) an aftertreatment system containing a diesel oxidation catalyst and a diesel particulate filter ('HVONOx' PM1: ~ 1 µg m-3, NO: 2.0 ppm, NO2: 0.7 ppm) and 3) filtered air (FA) as control. The exposure concentrations were in line with current EU occupational exposure limits (OELs) of NO, NO2, formaldehyde, polycyclic aromatic hydrocarbons (PAHs), and the future OEL (2023) of elemental carbon (EC). The effect on nasal patency, pulmonary function, and self-rated symptoms were assessed. Calculated predicted lung deposition of HVO exhaust particles was compared to data from an earlier diesel exhaust study. RESULTS: The average total respiratory tract deposition of PM1 during HVOPM+NOx was 27 µg h-1. The estimated deposition fraction of HVO PM1 was 40-50% higher compared to diesel exhaust PM1 from an older vehicle (earlier study), due to smaller particle sizes of the HVOPM+NOx exhaust. Compared to FA, exposure to HVOPM+NOx and HVONOx caused higher incidence of self-reported symptoms (78%, 63%, respectively, vs. 28% for FA, p < 0.03). Especially, exposure to HVOPM+NOx showed 40-50% higher eye and throat irritation symptoms. Compared to FA, a decrement in nasal patency was found for the HVONOx exposures (- 18.1, 95% CI: - 27.3 to - 8.8 L min-1, p < 0.001), and for the HVOPM+NOx (- 7.4 (- 15.6 to 0.8) L min-1, p = 0.08). Overall, no clinically significant change was indicated in the pulmonary function tests (spirometry, peak expiratory flow, forced oscillation technique). CONCLUSION: Short-term exposure to HVO exhaust concentrations corresponding to EU OELs for one workday did not cause adverse pulmonary function changes in healthy subjects. However, an increase in self-rated mild irritation symptoms, and mild decrease in nasal patency after both HVO exposures, may indicate irritative effects from exposure to HVO exhaust from modern non-road vehicles, with and without aftertreatment systems.

Airspace dimension assessment with nanoparticles as a proposed biomarker for emphysema.

Airspace dimension assessment with nanoparticles (AiDA) is a novel method to measure distal airspace radius non-invasively. In this study, AiDA radii were measured in 618 individuals from the population-based Swedish CArdiopulmonary BioImaging Study, SCAPIS. Subjects with emphysema detected by computed tomography were compared to non-emphysematous subjects. The 47 individuals with mainly mild-to-moderate visually detected emphysema had significantly larger AiDA radii, compared with non-emphysematous subjects (326±48 µm vs 291±36 µm); OR for emphysema per 10 µm: 1.22 (1.13-1.30, p<0.0001). Emphysema according to CT densitometry was similarly associated with larger radii compared with non-emphysematous CT examinations (316±41 µm vs 291 µm±26 µm); OR per 10 µm: 1.16 (1.08-1.24, p<0.0001). The results are in line with comparable studies. The results show that AiDA is a potential biomarker for emphysema in individuals in the general population.

Physical activity spectrum discriminant analysis-A method to compare detailed patterns between groups.

Investigating physical activity (PA) patterns as a detailed intensity spectrum instead of crude intensity categories have improved the ability to analyze the relationship between measured PA and health variables. The aim of this methodological study was to introduce and investigate the utility of using detailed PA intensity spectrum compared to crude PA intensity categories for comparison of PA between groups and between repeated measures. The study sample consisted of two groups of children, where one group was scheduled for extended physical education (PE) by daily classes while the other group followed usual PE schedule. Accelerometer data was processed into traditional crude PA intensity categories and into detailed PA intensity spectrum. Multivariate partial least squares regression for discriminant analysis (PLS-DA) was applied for PA intensity spectrum group comparison and compared to traditional univariate statistical analysis. Repeated measures were investigated using independent PLS-DA as well as multilevel PLS-DA for paired analysis. While traditional analysis of crude PA intensity categories was unable to find any group differences, multivariate analysis of the PA intensity spectrum identified statistically significant differences. By the extension of multilevel PLS-DA for paired comparison, a clear difference in the PA intensity spectrum was demonstrated between repeated measures. In conclusion, analysis of detailed PA intensity spectrum demonstrates utility for comparing detailed PA data between groups and between repeated measures in interventional and observational research.

Assessment of Global Lung Function Initiative (GLI) reference equations for diffusing capacity in relation to respiratory burden in the Swedish CArdioPulmonary bioImage Study (SCAPIS).

The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (D LCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired D LCO We examined if the GLI LLN for D LCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, D LCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15 040 participants, aged 50-64 years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for D LCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of D LCO GLI LLN but GLI LLN but GLI LLN and >SCAPIS LLN). No differences were found with regard to physician-diagnosed asthma.The GLI LLN for D LCO is lower than the estimated LLN in healthy, never-smoking, middle-aged Swedish adults. Individuals with D LCO above the GLI LLN but below the SCAPIS LLN had, to a larger extent, an increased respiratory burden. This suggests clinical implications for choosing an adequate LLN for studied populations.

Low lung function and the risk of incident chronic kidney disease in the Malmö Preventive Project cohort.

BACKGROUND: Although the prevalence of kidney disease is higher in those with reduced lung function, the longitudinal relationship between low lung function and future risk of chronic kidney disease (CKD) has not been widely explored. METHODS: Baseline lung function was assessed in 20,700 men and 7325 women from 1974 to 1992. Mean age was 43.4 (±6.6) and 47.5 (±7.9) for men and women respectively. Sex-specific quartiles of FEV1 and FVC (L) were created (Q4: highest, reference) and the cohort was also divided by the FEV1/FVC ratio (≥ or < 0.70). Cox proportional hazards regression was used to determine the risk of incident CKD events (inpatient or outpatient hospital diagnosis of CKD) in relation to baseline lung function after adjustment for various confounding factors. RESULTS: Over 41 years of follow-up there were 710 and 165 incident CKD events (main diagnosis) in men and women respectively. Low FEV1 was strongly associated with future risk of CKD in men (Q1 vs Q4 adjusted HR: 1.46 (CI:1.14-1.89), p-trend 0.002). Similar findings were observed for FVC in men (1.51 (CI:1.16-1.95), p-trend 0.001). The adjusted risks were not found to be significant in women, for either FEV1 or FVC. FEV1/FVC < 0.70 was not associated with increased incidence of CKD in men or women. CONCLUSION: Low FEV1 and FVC levels at baseline are a risk factor for the development of future incident CKD in men. Monitoring kidney function in those with reduced vital capacity in early life could help with identifying those at increased risk of future CKD.

Relative and absolute lung function change in a general population aged 60-102†years.

Data on longitudinal lung function change in the elderly are scarce. Uncertainty remains about whether to use absolute or relative change and how it relates to subject demographics.We studied absolute and relative forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) change in a population-based geriatric sample using a repeated measurements model adjusted for age, sex, smoking habits, heart failure, hypertension, diabetes, coronary heart disease, educational level, occupation, alcohol consumption, C-reactive protein (CRP) and body mass index. 3736 participants aged 60-102 years completed between one and five spirometries during 13.5 years of follow-up. Lung volumes, FEV1 quotient (Q) and Global Lung Initiative (GLI)-2012 and National Health and Nutrition Examination Survey (NHANES) III z-scores were presented from 6932 spirometries.Adjusted absolute change per year (95% CI) was -51.7 (-63.7--39.9) mL for FEV1 and -56.2 (-73.6--38.8) mL for FVC. Adjusted relative change per year was -2.97 (-3.53--2.40)% for FEV1 and -2.46 (-3.07--1.85)% for FVC. Risk factors for increased relative FVC and FEV1 decline were female sex, higher age, current smoking habits, elevated CRP (nonsignificant for FEV1, p=0.057) and low educational level. For increased absolute decline the risk factors were male sex and being a current smoker for FEV1 and low education for FVC.Relative but not absolute change correlated significantly with clinically relevant markers of functional status and may be superior to absolute change in risk factor analysis. Cross-sectional reduction in terms of FEV1Q was ∼1 unit per 10 years for both sexes. Proportions of subjects with results below lower limit of normal using NHANES III were close to anticipated, but were two to four times higher than expected using GLI-2012.

Comparison of conventional and Si-photomultiplier-based PET systems for image quality and diagnostic performance.

BACKGROUND: A new generation of positron emission tomography with computed tomography (PET-CT) was recently introduced using silicon (Si) photomultiplier (PM)-based technology. Our aim was to compare the image quality and diagnostic performance of a SiPM-based PET-CT (Discovery MI; GE Healthcare, Milwaukee, WI, USA) with a time-of-flight PET-CT scanner with a conventional PM detector (Gemini TF; Philips Healthcare, Cleveland, OH, USA), including reconstruction algorithms per vendor's recommendations. METHODS: Imaging of the National Electrical Manufacturers Association IEC body phantom and 16 patients was carried out using 1.5 min/bed for the Discovery MI PET-CT and 2 min/bed for the Gemini TF PET-CT. Images were analysed for recovery coefficients for the phantom, signal-to-noise ratio in the liver, standardized uptake values (SUV) in lesions, number of lesions and metabolic TNM classifications in patients. RESULTS: In phantom, the correct (> 90%) activity level was measured for spheres ≥17 mm for Discovery MI, whereas the Gemini TF reached a correct measured activity level for the 37-mm sphere. In patient studies, metabolic TNM classification was worse using images obtained from the Discovery MI compared those obtained from the Gemini TF in 4 of 15 patients. A trend toward more malignant, inflammatory and unclear lesions was found using images acquired with the Discovery MI compared with the Gemini TF, but this was not statistically significant. Lesion-to-blood-pool SUV ratios were significantly higher in images from the Discovery MI compared with the Gemini TF for lesions smaller than 1 cm (p < 0.001), but this was not the case for larger lesions (p = 0.053). The signal-to-noise ratio in the liver was similar between platforms (p = 0.52). Also, shorter acquisition times were possible using the Discovery MI, with preserved signal-to-noise ratio in the liver. CONCLUSIONS: Image quality was better with Discovery MI compared to conventional Gemini TF. Although no gold standard was available, the results indicate that the new PET-CT generation will provide potentially better diagnostic performance.

Markers of cardiovascular autonomic dysfunction predict COPD in middle-aged subjects.

Autonomic dysfunction is commonly observed in chronic obstructive pulmonary disease (COPD) and may relate to the known comorbidity with coronary artery disease (CAD). We hypothesised that clinical markers of cardiovascular autonomic dysfunction predict COPD in the population, independently of CAD.In a population-based cohort of 24 768 subjects (mean age 45 years) without baseline airflow obstruction, we analysed the cross-sectional relationship of one-minute orthostatic systolic (SBP) and diastolic (DBP) blood pressure changes, and resting heart rate with forced vital capacity (FVC) and forced expiratory volume (FEV1). Cox-regression-models were used to analyse the association of orthostatic SBP and DBP changes (SBP/DBP-decrease) and resting heart rate with incident COPD over 32-year follow-up.Baseline orthostatic SBP-decrease (p=0.020) and DBP-decrease (p=0.001) associated with reduced FVC, whereas resting heart rate associated with reduced FVC and FEV1 (p<0.001). After adjustment for smoking and baseline lung function, SBP-decrease predicted COPD (Hazard ratio [HR] 1.10 per 10 mmHg; 95% confidence interval [CI]:1.03-1.18). Resting heart rate predicted COPD among smokers (HR 1.11 per 10 beats-per-minute increase; 95%CI:1.05-1.18). Results were similar in subjects without CAD.Subtle signs of cardiovascular autonomic dysfunction may precede development of COPD in middle-aged subjects. This association is independent of the relationship between cardiovascular autonomic dysfunction and CAD.

ST segment depression on 24-hour electrocardiography predicts incident atrial fibrillation in two population-based cohorts.

Aims: ST-depression at 24hECG has not been studied in relation to atrial fibrillation (AF) risk. We aimed to determine whether ST-depression at 24hECG was associated with incident AF in two Swedish population-based cohorts - a sub-cohort of the Malmö Diet and Cancer study (MDCS), and the cohort 'Men born in 1914', and to determine whether 24hECG could be used to predict AF development. Methods and results: There were 378 acceptable 24hECG recordings in the MDCS (mean age 64.5 years, 43% men) and 394 acceptable recordings in 'Men born in 1914' (mean age 68.8 years). Incidence of AF was monitored using national registers of hospitalizations and outpatient visits in Sweden. Mean follow-up ± SD (cumulative incidence) was 10.4 ± 2 years (11.3%) in MDCS, and 10.9 ± 4 years (7.3%) in 'Men born in 1914'. ST-depressions were independently associated with incident AF; hazard ratio (HR) (95% CI) 2.41 (1.29-4.50, P = 0.006) and 2.28 (1.05-4.95, P = 0.038) after adjustment [age, sex, height, weight, systolic blood pressure, smoking, anti-hypertensive drugs, LDL/total cholesterol, and HOMA-IR (in MDCS)]. AF incidence was substantially lower in individuals who had neither ST-depressions or high supraventricular activity (SVA, negative predictive value 0.97 and 0.94, in MDCS and 'Men born in 1914', respectively), and similar in men and women. Conclusion: ST-depression at 24h-ECG is independently associated with incident AF, and incidence is substantially lower in individuals with neither ST-depression or high SVA. 24hECG can be used not only to diagnose AF but also to identify individuals at high and low AF risk.

Galectin-3 levels relate in children to total body fat, abdominal fat, body fat distribution, and cardiac size.

Galectin-3 has recently been proposed as a novel biomarker for cardiovascular disease in adults. The purpose of this investigation was to assess relationships between galectin-3 levels and total body fat, abdominal fat, body fat distribution, aerobic fitness, blood pressure, left ventricular mass, left atrial size, and increase in body fat over a 2-year period in a population-based sample of children. Our study included 170 children aged 8-11 years. Total fat mass and abdominal fat were measured by dual-energy x-ray absorptiometry (DXA). Body fat distribution was expressed as abdominal fat/total fat mass. Maximal oxygen uptake was assessed by indirect calorimetry during a maximal exercise test and scaled to body mass. Systolic and diastolic blood pressure and pulse pressure were measured. Left atrial size, left ventricular mass, and relative wall thickness were measured by echocardiography. Frozen serum samples were analyzed for galectin-3 by the Proximity Extension Assay technique. A follow-up DXA scan was performed in 152 children 2 years after the baseline exam. Partial correlations, with adjustment for sex and age, between galectin-3 versus body fat measurements indicated weak to moderate relationships. Moreover, left atrial size, left ventricular mass, and relative wall thickness and pulse pressure were also correlated with galectin-3. Neither systolic blood pressure nor maximal oxygen uptake was correlated with galectin-3. There was also a correlation between galectin-3 and increase in total body fat over 2 years, while no such correlations were found for the other fat measurements. CONCLUSION: More body fat and abdominal fat, more abdominal body fat distribution, more left ventricular mass, and increased left atrial size were all associated with higher levels of galectin-3. Increase in total body fat over 2 years was also associated with higher levels of galectin-3. What is Known: • Galectin-3 has been linked to obesity and been proposed to be a novel biomarker for cardiovascular disease in adults. • Information on this subject in children is very scarce. What is New: • The present study demonstrates a relationship between galectin-3 levels and total body fat, abdominal fat, body fat distribution, cardiac size and geometry, and increase in total body fat over 2 years in young children.

A prospective study to evaluate the intra-individual reproducibility of bone scans for quantitative assessment in patients with metastatic prostate cancer.

BACKGROUND: The Bone Scan Index (BSI) is used to quantitatively assess the total tumour burden in bone scans of patients with metastatic prostate cancer. The clinical utility of BSI has recently been validated as a prognostic imaging biomarker. However, the clinical utility of the on-treatment change in BSI is dependent on the reproducibility of bone scans. The objective of this prospective study is to evaluate the intra-patient reproducibility of two bone scan procedures performed at a one-week interval. METHODS: We prospectively studied prostate cancer patients who were referred for bone scintigraphy at our centres according to clinical routine. All patients underwent two whole-body bone scans: one for clinical routine purposes and a second one as a repeated scan after approximately one week. BSI values were obtained for each bone scintigraph using EXINI boneBSI software. RESULTS: A total of 20 patients were enrolled. There was no statistical difference between the BSI values of the first (median = 0.66, range 0-40.77) and second (median = 0.63, range 0-22.98) bone scans (p = 0.41). The median difference in BSI between the clinical routine and repeated scans was - 0.005 (range - 17.79 to 0). The 95% confidence interval for the median value was - 0.1 to 0. A separate analysis was performed for patients with BSI ≤ 10 (n = 17). Differences in BSI were smaller for patients with BSI ≤ 10 compared to the whole cohort (median - 0.1, range - 2.2-0, 95% confidence interval - 0.1 to 0). CONCLUSIONS: The automated BSI demonstrated high intra-individual reproducibility for BSI ≤ 10 in the two repeated bone scans of patients with prostate cancer. The study supports the use of BSI as a quantitative parameter to evaluate the change in total tumour burden in bone scans.

Altered deposition of inhaled nanoparticles in subjects with chronic obstructive pulmonary disease.

BACKGROUND: Respiratory tract deposition of airborne particles is a key link to understand their health impact. Experimental data are limited for vulnerable groups such as individuals with respiratory diseases. The aim of this study is to investigate the differences in lung deposition of nanoparticles in the distal lung for healthy subjects and subjects with respiratory disease. METHODS: Lung deposition of nanoparticles (50 and 100 nm) was measured after a 10 s breath-hold for three groups: healthy never-smoking subjects (n = 17), asymptomatic (active and former) smokers (n = 15) and subjects with chronic obstructive pulmonary disease (n = 16). Measurements were made at 1300 mL and 1800 mL volumetric lung depth. Each subject also underwent conventional lung function tests, including post bronchodilator FEV1, VC, and diffusing capacity for carbon monoxide, DL,CO. Patients with previously diagnosed respiratory disease underwent a CT-scan of the lungs. Particle lung deposition fraction, was compared between the groups and with conventional lung function tests. RESULTS: We found that the deposition fraction was significantly lower for subjects with emphysema compared to the other subjects (p = 0.001-0.01), but no significant differences were found between healthy never-smokers and smokers. Furthermore, the particle deposition correlated with pulmonary function tests, FEV1%Pred (p < 0.05), FEV1/VC%Pred (p < 0.01) and DL,CO (p < 0.0005) when all subjects were included. Furthermore, for subjects with emphysema, deposition fraction correlated strongly with DL,CO (Pearson's r = 0.80-0.85, p < 0.002) while this correlation was not found within the other groups. CONCLUSIONS: Lower deposition fraction was observed for emphysematous subjects and this can be explained by enlarged distal airspaces in the lungs. As expected, deposition increases for smaller particles and deeper inhalation. The observed results have implications for exposure assessment of air pollution and dosimetry of aerosol-based drug delivery of nanoparticles.

School-based study found that physical activity and aerobic fitness predicted increases in total body fat and abdominal fat at a mean age of 9.8 years.

AIM: We assessed whether baseline measurements of physical activity, aerobic fitness, body fat and abdominal fat were predictors of changes in body fat measurements over a two-year period. METHODS: The study comprised of 204 children aged 9.8 ± 0.6 years with a normal body mass distribution, who recruited from four schools in middle-class areas of Malmö, Sweden, from 2001 to 2004. Peak oxygen uptake and physical activity were measured at baseline. Body fat was measured by dual-energy X-ray absorptiometry at baseline and two years later. RESULTS: Physical activity, aerobic fitness and total body fat or abdominal fat were predictors of change in total body fat or abdominal fat over a period of two years. Changes in the percentage of body fat were not related to any of the baseline measurements. CONCLUSION: Our two-year follow-up of children with a mean age of 9.8 years at baseline showed that physical activity, aerobic fitness and body fat or abdominal fat predicted changes in total body fat or abdominal fat, but not the percentage of body fat.

Serum Potassium Is Positively Associated With Stroke and Mortality in the Large, Population-Based Malmö Preventive Project Cohort.

BACKGROUND AND PURPOSE: Low serum potassium is associated with stroke in populations with cardiovascular disease, hypertension, and diabetes mellitus but has not been studied in a mainly healthy population. We aimed to study the relation between serum potassium and incident stroke and mortality in the Malmö Preventive Project, a large cohort with screening in early mid-life and follow-up >25 years. METHODS: Serum potassium measurements and covariates were available in 21 353 individuals (79% men, mean age 44 years). Mean follow-up time was 26.9 years for stroke analyses and 29.3 years for mortality analyses. There were 2061 incident stroke events and 8709 deaths. Cox regression analyses adjusted for multiple stroke risk factors (age, sex, height, weight, systolic blood pressure, fasting blood glucose, serum sodium, current smoking, prevalent diabetes mellitus, prevalent coronary artery disease, and treatment for hypertension) were fitted. RESULTS: There was an independent, linear association between serum potassium, per mmol/L increase, and both stroke (hazard ratio, 1.33; 95% confidence interval, 1.17-1.52; P<0.0001) and mortality (hazard ratio, 1.20; 95% confidence interval, 1.13-1.28; P<0.0001). This was significant in subjects both older and younger than the median age (46.5 years), and there was evidence of an interaction with serum sodium. The association was positive and significant for both ischemic stroke and intracerebral hemorrhage and in both hypertensive and normotensive subjects. CONCLUSIONS: Serum potassium, measured in early mid-life, was linearly associated with both incidence of ischemic stroke and intracerebral hemorrhage and all-cause mortality. An interaction with serum sodium implies that factors related to electrolyte balance and incident hypertension may be mediating factors.

Deposition efficiency of inhaled particles (15-5000 nm) related to breathing pattern and lung function: an experimental study in healthy children and adults.

BACKGROUND: Exposure to airborne particles has a major impact on global health. The probability of these particles to deposit in the respiratory tract during breathing is essential for their toxic effects. Observations have shown that there is a substantial variability in deposition between subjects, not only due to respiratory diseases, but also among individuals with healthy lungs. The factors determining this variability are, however, not fully understood. METHOD: In this study we experimentally investigate factors that determine individual differences in the respiratory tract depositions of inhaled particles for healthy subjects at relaxed breathing. The study covers particles of diameters 15-5000 nm and includes 67 subjects aged 7-70 years. A comprehensive examination of lung function was performed for all subjects. Principal component analyses and multiple regression analyses were used to explore the relationships between subject characteristics and particle deposition. RESULTS: A large individual variability in respiratory tract deposition efficiency was found. Individuals with high deposition of a certain particle size generally had high deposition for all particles <3500 nm. The individual variability was explained by two factors: breathing pattern, and lung structural and functional properties. The most important predictors were found to be breathing frequency and anatomical airway dead space. We also present a linear regression model describing the deposition based on four variables: tidal volume, breathing frequency, anatomical dead space and resistance of the respiratory system (the latter measured with impulse oscillometry). CONCLUSIONS: To understand why some individuals are more susceptible to airborne particles we must understand, and take into account, the individual variability in the probability of particles to deposit in the respiratory tract by considering not only breathing patterns but also adequate measures of relevant structural and functional properties.

Respiratory symptoms are poor predictors of concomitant chronic obstructive pulmonary disease in patients with primary Sjögren's syndrome.

Involvement of the respiratory system, in particular dry airways and chronic obstructive pulmonary disease (COPD), is common in patients with primary Sjögren's syndrome (pSS). As respiratory symptoms are also common in pSS patients and may have different etiologies, we wanted to evaluate the amount and impact of respiratory symptoms in out-patients with pSS and to assess if such symptoms are related to concomitant COPD. The St George's Respiratory Questionnaire (SGRQ) was used to assess respiratory symptoms. SGRQ scores were compared between 51 consecutive pSS patients, in an out-patient setting, and 80 population-based controls. The patients were also studied by pulmonary function tests and CT scans of the lungs to assess signs of obstructive airway disease, including COPD, as well as to assess signs of interstitial lung disease (ILD). 41 and 18% of pSS patients were found to have COPD and radiographic signs of ILD, respectively. pSS patients had significantly higher SGRQ scores compared to controls, but no significant differences in SGRQ scores were found between patients with and without COPD. Neither did the small group of pSS patients with ILD significantly differ in SGRQ scores in comparison to patients without ILD. Respiratory symptoms were common in pSS, but were not more common in patients with concomitant COPD. Since pulmonary involvement in pSS is associated with an increased mortality and respiratory symptoms is a poor marker for pulmonary involvement, we suggest that pulmonary function tests should be performed liberally in all pSS patients regardless of symptoms.