Factors most strongly associated with breathlessness in a population aged 50-64 years.

Background: Breathlessness is a troublesome and prevalent symptom in the population, but knowledge of related factors is scarce. The aim of this study was to identify the factors most strongly associated with breathlessness in the general population and to describe the shapes of the associations between the main factors and breathlessness. Methods: A cross-sectional analysis was carried out of the multicentre population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) of adults aged 50 to 64 years. Breathlessness was defined as a modified Medical Research Council breathlessness rating ≥2. The machine learning algorithm extreme gradient boosting (XGBoost) was used to classify participants as either breathless or nonbreathless using 449 factors, including physiological measurements, blood samples, computed tomography cardiac and lung measurements, lifestyle, health conditions and socioeconomics. The strength of the associations between the factors and breathlessness were measured by SHapley Additive exPlanations (SHAP), with higher scores reflecting stronger associations. Results: A total of 28 730 participants (52% women) were included in the study. The strongest associated factors for breathlessness were (in order of magnitude): body mass index ( SHAP score 0.39), forced expiratory volume in 1 s (0.32), physical activity measured by accelerometery (0.27), sleep apnoea (0.22), diffusing lung capacity for carbon monoxide (0.21), self-reported physical activity (0.17), chest pain when hurrying (0.17), high-sensitivity C-reactive protein (0.17), recent weight change (0.14) and cough (0.13). Conclusion: This large population-based study of men and women aged 50-64 years identified the main factors related to breathlessness that may be prevented or amenable to public health interventions.

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.

Inhomogeneity of ventilation in smokers and mild COPD assessed by the ratio of alveolar volume to total lung capacity.

BACKGROUND: Previous studies have shown that the ratio between alveolar volume (VA) and total lung capacity (TLC) reflects ventilation heterogeneity in subjects with chronic obstructive pulmonary disease (COPD). However, the ratio and its correlation to respiratory symptoms had to our knowledge not previously been investigated in subjects with mild chronic airflow obstruction or without airflow obstruction (normal ratio FEV1/VC). The purpose of this study was to investigate potential connection between VA/TLC and respiratory symptoms, smoking habits and lung function parameters in subjects with normal spirometry and with mild chronic airflow obstruction. METHODS: We examined 450 subjects (82 non-smokers with normal spirometry, 298 subjects who smoked or had smoked earlier but had a normal spirometry and 70 subjects with chronical airflow obstruction) with routine lung function tests and a questionnaire regarding respiratory symptoms. RESULTS: This study showed 31 out of 54 subjects with a low VA/TLC had a normal ratio FEV1/VC. Of these subjects, 58.1 % had respiratory symptoms, compared to the group with normal ratio for both VA/TLC and FEV1/VC where 35.8 % had respiratory symptoms (p-value 0.02). CONCLUSION: This study has shown that within the group of subjects with a normal ratio FEV1/VC, those with a decreased ratio VA/TLC had a higher prevalence of respiratory symptoms compared to subjects with a normal VA/TLC ratio. These findings indicate that including the ratio VA/TLC in the evaluation of a pulmonary function test assessment might increase the possibility to identify subjects with early or at risk of lung disease.

Factors important for health-related quality of life in men and women: The population based SCAPIS study.

INTRODUCTION: Health-related quality of life (HRQoL) is essential for human wellbeing, influenced by a complex interplay of factors, and is reported lower in women than men. We aimed to evaluate which factors were the most important for HRQoL in a middle-aged general population. METHODS: This was a cross-sectional, multi-centre study of 29,212 men (48%) and women (52%) aged 50-64 in the general population in Sweden. Physical and mental HRQoL (0-100) was assessed using the Short Form 12 questionnaire, and association was evaluated for 356 variables including demographics, lifestyle, symptoms, physiological measurements, and health conditions. Using machine learning, each variable´s importance for HRQoL was measured by an importance score, comparable to effect size, and summarised in 54 factors, in men and women separately. RESULTS: Men and women had similar mean and standard deviation (SD) scores for physical HRQoL (53.4 [SD 8.1] vs 51.4 [9.7]) and mental HRQoL (37.1 [5.0] vs 37.3 [5.4]). The most important factors for physical HRQoL were (importance score) physical activity (40), employment (36), pain (33), sleep (33), and sense of control (26). The most important factors for mental HRQoL were sense of control (18), physical activity (12), depression (12), pain (6), and employment (5). CONCLUSIONS: The factors important for HRQoL identified by this study are likely to be amenable to interventions, and our findings can support prioritising interventions. The identified factors need to be a target even before middle-age to lay the foundation for long and happy lives.

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.

High prevalence of interstitial lung abnormalities in middle-aged never-smokers.

Background: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms. Methods: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing. Findings: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA. Interpretation: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.

Impulse oscillometry indices in relation to respiratory symptoms and spirometry in the Swedish Cardiopulmonary Bioimage Study.

Background: Impulse oscillometry (IOS) is sensitive in detecting lung function impairment. In small studies, impaired IOS relates better to respiratory symptoms than spirometry. We studied how IOS related to spirometry and respiratory symptoms in a large population of individuals (n=10 360) in a cross-sectional analysis. Methods: Normal values for IOS and spirometry were defined in healthy, never-smoking individuals, aged 50-64 years, from the Swedish CArdioPulmonary bioImage Study (n=3664 for IOS and 3608 for spirometry). For IOS, abnormal values for resistance at 5 Hz (R5) and at 20 Hz and area of reactance were defined using the 95th percentile. Abnormal reactance at 5 Hz for IOS and abnormal conventional spirometry indices (forced expiratory volume in 1 s (FEV1), forced and slow vital capacity and their ratios) were defined using the 5th percentile. Results: Abnormal IOS parameters were found in 16% of individuals and were associated with increased odds ratios for nearly all respiratory symptoms when adjusted for age, gender and smoking. In individuals with normal spirometry, abnormal IOS resistance was related to cough and dyspnoea, while abnormal reactance was related to wheeze. In these individuals, the combination of abnormal R5 with abnormal reactance resulted in approximately two-fold higher likelihood for having cough, chronic bronchitis and dyspnoea, even when further adjusting for FEV1, expressed as % predicted. Conclusions: Abnormal IOS is related to increased respiratory burden in middle-aged individuals with normal spirometry, especially when resistance and reactance parameters are combined. The different relationships between respiratory symptoms and reactance and resistance warrant further research.

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.

Airspace Dimension Assessment for early detection of lung function impairment in the peripheral airways of firefighters.

Introduction: Firefighters have increased risk of chronic respiratory disease. Standard clinical techniques used in medical checkups may not detect the earliest microstructural changes in peripheral airways. A new technique called Airspace Dimension Assessment (AiDA) has been shown to enable early detection of emphysema in COPD. This method may be useful in the occupational setting to detect early pulmonary changes and enable prevention. The aim of the present study was to evaluate whether AiDA detects changes in the most peripheral airways of firefighters. Methods: AiDA, measuring the effective airspace radius (r AiDA) and zero-second recovery (R 0), was used as a complement to other standardised lung function measures in 21 male firefighters and 16 age-matched male controls. Results: There were significant differences in r AiDA and R 0 between firefighters (mean±sd r AiDA 0.301±0.024 mm; mean±sd R 0 0.336±0.116 arbitrary units) and controls (mean±sd r AiDA 0.276±0.044 mm; mean±sd R 0 0.5760.168 arbitrary units), p=0.03 and p<0.001, respectively. Higher forced vital capacity was found in firefighters (mean 101% of predicted) than in controls (mean 93% of predicted; p=0.03). No significant differences were found with regard to either the ratio between forced expiratory volume in 1 s and forced vital capacity or forced expiratory volume in 1 s. The majority of firefighters had diffusing capacity of the lung for carbon monoxide, oscillometry and single-breath nitrogen washout values within the normal ranges. Conclusion: AiDA parameters can provide information on early pulmonary peripheral changes that may not be seen with standard techniques used in screening of pulmonary function.

Sensitive methods for assessment of lung health in welders and controls.

BACKGROUND: Welders are exposed to gas and particle emissions that can cause severe lung disease, such as chronic obstructive pulmonary disease (COPD), a leading cause of mortality and morbidity worldwide. It is difficult to detect COPD early and therefore mitigating measures may be delayed. The aim of this study was to investigate lung health in welders and evaluate new sensitive methods with potential to assess early onset pulmonary changes in occupational settings. METHODS: This study assessed the lung health and symptoms in active welders (n = 28) and controls (n = 17). Lung measurements were performed with standard spirometry and new methods: airspace dimension assessment (AiDA), oscillometry, blood serum biomarkers (club cell secretory protein 16, surfactant protein D, matrix metalloproteinases, fibroblast, hepatocyte growth factor, interleukins), and one urine biomarker (desmosine). RESULTS: According to spirometry measurements, all participants had normal lung function. However, prevalence of cough was significantly higher among welders compared with controls and lung changes were found in welders with the novel methods. Welders had significantly higher respiratory system resistance assessed with oscillometry, serum levels of metalloproteinases 9 and hepatocyte growth factor, compared with controls. Airspace dimensions were on average higher among welders compared with controls, but the difference was not significant. The number of welding years correlated with decreased respiratory system reactance and increased serum levels of matrix metalloproteinases 9, interleukin 6, and hepatocyte growth factor. Airspace dimension assessment indices were correlated with increasing levels of inflammatory markers and matrix metalloproteinases. CONCLUSIONS: This study indicated the potential to use new and more sensitive methods for identification of changes in lungs when standard spirometry failed to do so.

Functional and structural impairments of the pulmonary system in middle-aged people with cervical and upper thoracic spinal cord injuries.

OBJECTIVES: To describe functional and structural impairments of the pulmonary system in middle-aged people with cervical and upper thoracic spinal cord injuries (SCI), and compare findings to the general population. To determine if the neurological level of injury (NLI) is related to functional and structural impairments, and if age is related to structural impairments. DESIGN: Cross-sectional study with matched controls. Data from the Swedish SPinal Cord Injury Study on Cardiopulmonary and Autonomic Impairment (SPICA). Matched control data were obtained from the Swedish CArdioPulmonary bioImage Study (SCAPIS). SETTING: Outpatient SCI unit in southern Sweden. PARTICIPANTS: 25 people (20% women, mean age 58 years, mean time since injury 28 years, NLIs C2-T6, American Spinal Injury Association Impairment Scale A-C). INTERVENTIONS: Not applicable. OUTCOME MEASURES: Lung function was assessed with spirometry, diffusing capacity and impulse oscillometry. Structural assessments were performed with computed tomography. RESULTS: Pulmonary function was generally worse compared to the controls. Structural impairments were common (75% of the participants and 65% of the controls; P = 0.36, NS). NLI was significantly related to some of the functional and structural impairments. CONCLUSIONS: Middle-aged people with long-term cervical and upper thoracic SCI can have substantial pulmonary functional impairments, whereas structural impairments do not differ considerably from the general population. Further larger and longitudinal studies should focus on the clinical impact of these impairments over time.

Airspace Dimension Assessment with Nanoparticles (AiDA) in Comparison to Established Pulmonary Function Tests.

Background: Airspace Dimensions Assessment with nanoparticles (AiDA) is a new method for non-invasive measurement of pulmonary distal airspaces. The aim of this study was to compare AiDA measurements with other pulmonary function variables to better understand the potential of AiDA in a clinical context. Methods: AiDA measurements and pulmonary function tests were performed in 695 subjects as part of the Swedish CArdioPulmonary bioImage Study. The measurement protocol included spirometry, measurement of diffusing capacity of carbon monoxide, oscillometry and pulmonary computed tomography. AiDA indices were compared to all other pulmonary examination measurements using multivariate statistical analysis. Results: Our results show that AiDA measurements were significantly correlated with other pulmonary function examination indices, although covariance was low. We found that AiDA variables explained variance in the data that other lung function variables only influenced to a minor extent. Conclusion: We conclude that the AiDA method provides information about the lung that is inaccessible with more conventional lung function techniques.

Detection of lymph node metastases in patients with prostate cancer: Comparing conventional and digital [18 F]-fluorocholine PET-CT using histopathology as a reference.

BACKGROUND: Positron emission tomography-computed tomography (PET-CT) with [18 F]-fluorocholine (FCH) is used to detect and stage metastatic lymph nodes in patients with prostate cancer. Improvements to hardware and software have recently been made. We compared the capability of detecting regional lymph node metastases using conventional and digital silicon photomultiplier (SiPM)-based PET-CT technology for FCH. Extended pelvic lymph node dissection (ePLND) histopathology was used as a reference method. METHODS: The study retrospectively examined 177 patients with intermediate or high-risk prostate cancer who had undergone staging with FCH PET-CT before ePLND. Images were obtained with either the conventional Philips Gemini PET-CT (n = 93) or the digital SiPM-based GE Discovery MI PET-CT (n = 84) and compared. RESULTS: Images that were obtained using the Philips Gemini PET-CT system showed 19 patients (20%) with suspected lymph node metastases, whereas the GE Discovery MI PET-CT revealed 36 such patients (43%). The sensitivity, specificity, and positive and negative predictive values were 0.3, 0.84, 0.47, and 0.72 for the Philips Gemini, while they were 0.58, 0.62, 0.31, and 0.83 for the GE Discovery MI, respectively. The areas under the curves in a receiver operating characteristic curve analysis were similar between the two PET-CT systems (0.57 for Philips Gemini and 0.58 for GE Discovery MI, p = 0.89). CONCLUSIONS: Marked differences in sensitivity and specificity were found for the different PET-CT systems, although the overall diagnostic performance was similar. These differences are probably due to differences in both hardware and software, including reconstruction algorithms, and should be considered when new technology is introduced.

Emphysema severity index (ESI) associated with respiratory death in a large Swedish general population.

Recently, it has been shown and validated that presence and severity of emphysema on computed tomography could be estimated by a novel spirometry based index, the emphysema severity index (ESI). However, the clinical relevance of the index has not been established. We conducted cox-regression analyses with adjustment for age, smoking, sex, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) to study whether ESI was associated with all-cause, respiratory and non-respiratory 10-year mortality. Study population was all participants with acceptable spirometry from the Gott Åldrande i Skåne study, a Swedish general population aged 65-102 years old. ESI is expressed as a continuous numeric parameter on a scale ranging from 0 to 10. Out of the 4453 participants in the main study, 3974 was included in the final analysis. Higher age, higher ESI, lower FEV1 and male sex increased hazard of respiratory death. ESI was significantly correlated to respiratory death but not non-respiratory death, while high age, male sex and low FEV1 was associated with non-respiratory as well as respiratory death. Current smoking habits increased the hazard of respiratory death but did not reach significance (p 0.066) One unit increase in ESI increased hazard of all-cause death by 20% (p 0.0002) and hazard of respiratory death by 57% (p < 0.0001). The ESI is a novel clinical marker of emphysema severity that is associated with respiratory death specifically. Since it can be derived from standard spirometry there are potential benefits for clinical practice in terms of more individualised prognosis and treatment alternatives.

Changes in Athletic Performance in Children Attending a Secondary School with a Physical Activity Profile.

The longitudinal and multidisciplinary research project Malmö Youth Sport Study measured the sports results achieved by two cohorts of pupils using a variable named ACHIEVE, dividing the pupils into three categories (an elite group competing at the national or international level, a group competing at the district level, and a third group either not competing at all or below district level). This was assessed three and six years after baseline at age 13. An additional hypothetical measure, based on information from the athletes' trainers, predicted the category the pupils were expected to belong to after twelve years (age 25). Social variables related to the ACHIEVE variable are sex, socio-economic position of the parents, ethnicity, completed secondary sports school, sports capital, and quartile of birth. After three years, 28% of the pupils belonged to the elite group and after six years, 26%. Thirty-two and 48%, respectively, had abandoned their elite efforts. The elite group remained fairly stable over time but fewer girls than boys advanced to the elite group. The pupils at the school have a homogenous middle-class background. We found little evidence that socio-economic factors affected ACHIEVE. Nearly all parents had been engaged in sports, either competing or as coaches. On admission to the school, there was a pronounced relative age effect (RAE). This remained after three years as the age was significantly different between the three groups but was reduced after six years. According to the prognosis made by the coaches, the elite group would be considerably smaller when the subjects reached the age of 25. The RAE was again significant in the prognosis. A further follow-up when the subjects are 25 years old will reveal not only what proportion of subjects are actively competing, but also if they are engaged in recreational sports, to what extent the RAE is present, and how accurately coaches can predict success.

Single-nucleotide polymorphisms in the sulfatase-modifying factor 1 gene are associated with lung function and COPD.

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 SUMF1 are associated with COPD. The aim of this study was to investigate the association between SUMF1 SNPs and advanced lung function characteristics. Never-, former and current smokers with (n=154) or without (n=405) COPD were genotyped for 21 SNPs in SUMF1 and underwent spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (D LCO) measurement and impulse oscillometry. Four SNPs (rs793391, rs12634248, rs2819590 and rs304092) showed a significantly decreased odds ratio of having COPD when heterozygous for the variance allele, together with a lower forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) ratio and an impaired peripheral resistance and reactance. Moreover, individuals homozygous for the variance allele of rs3864051 exhibited a strong association to COPD, a lower FEV1/FVC, FEV1 and D LCO, and an impaired peripheral resistance and reactance. Other SNPs (rs4685744, rs2819562, rs2819561 and rs11915920) were instead associated with impaired lung volumes and exhibited a lower FVC, total lung capacity and alveolar volume, in individuals having the variance allele. Several SNPs in the SUMF1 gene are shown to be associated with COPD and impaired lung function. These genetic variants of SUMF1 may cause a deficient sulfation balance in the extracellular matrix of the lung tissue, thereby contributing to the development of COPD.

Common physiologic and proteomic biomarkers in pulmonary and coronary artery disease.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. SIGNIFICANCE: 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.

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.

Low lung function, sudden cardiac death and non-fatal coronary events in the general population.

BACKGROUND: Many of those who suffer from a first acute coronary event (CE) die suddenly during the day of the event, most of them die outside hospital. Poor lung function is a strong predictor of future cardiac events; however, it is unknown whether the pattern of lung function impairment differs for the prediction of sudden cardiac death (SCD) versus non-fatal CEs. We examined measures of lung function in relation to future SCD and non-fatal CE in a population-based study. METHODS: Baseline spirometry was assessed in 28 584 middle-aged subjects, without previous history of CE, from the Malmö Preventive Project. The cohort was followed prospectively for incidence of SCD (death on the day of a first CE, inside or outside hospital) or non-fatal CE (survived the first day). A modified version of the Lunn McNeil's competing risk method for Cox regression was used to run models for both SCD and non-fatal CE simultaneously. RESULTS: A 1-SD reduction in forced expiratory volume in 1 s (FEV1) was more strongly associated with SCD than non-fatal CE even after full adjustment (FEV1: HR for SCD: 1.23 (1.15 to 1.31), HR for non-fatal CE 1.08 (1.04 to 1.13), p value for equal associations=0.002). Similar associations were found for forced vital capacity (FVC) but not FEV1/FVC. The results remained significant even in life-long never smokers (FEV1: HR for SCD: 1.34 (1.15 to 1.55), HR for non-fatal CE: 1.11 (1.02 to 1.21), p value for equal associations=0.038). Similar associations were seen when % predicted values of lung function measures were used. CONCLUSIONS: Low FEV1 is associated with both SCD and non-fatal CE, but consistently more strongly associated with future SCD. Measurement with spirometry in early life could aid in the risk stratification of future SCD. The results support the use of spirometry for a global assessment of cardiovascular risk.