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Madeleine Petersson-Sjögren,1,2 Jonas Jakobsson,3 H Laura Aaltonen,4,5 Hanna Nicklasson,6,7 Jenny Rissler,1,2,8 Gunnar Engström,9 Per Wollmer,6 Jakob Löndahl1,2 1Division of Ergonomics and Aerosol Technology, Department of Design Sciences, Lund University, Lund, Sweden; 2NanoLund, Lund University, Lund, Sweden; 3Division of Nuclear Physics, Department of Physics, Lund University, Lund, Sweden; 4Department of Translational Medicine, Medical Imaging and Physiology, Lund University, Malmö, Sweden; 5Department of Radiology, University of Washington, Seattle, WA, USA; 6Department of Translational Medicine, Clinical Physiology and Nuclear Medicine, Skåne University Hospital, Malmö, Sweden; 7MVIC Medicon Valley Inhalation Consortium AB, Lund, Sweden; 8Division of Bioeconomy and Health, RISE Research Institutes of Sweden, Borås, Sweden; 9Department of Clinical Sciences, Lund University, Malmö, SwedenCorrespondence: Jakob Löndahl, Division of Ergonomics and Aerosol Technology, Lund University, Box 118, Lund, SE-221 00, Sweden, Email jakob.londahl@design.lth.seBackground: 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.Keywords: aerosol nanoparticles, respiratory diagnostics with nanoparticles, distal airspaces, COPD diagnostics, airspace dimension assessment with nanoparticles

Georg Rüdiger Schramm,1 Behrouz Mostafavi,1 Eeva Piitulainen,1 Per Wollmer,2 Hanan A Tanash1 1Department of Respiratory Medicine and Allergology, Skåne University Hospital, Lund University, Malmö, Sweden; 2Department of Medical Imaging and Physiology, Skåne University Hospital, Lund University, Malmö, SwedenCorrespondence: Georg Rüdiger SchrammDepartment of Respiratory Medicine and Allergology, Skåne University Hospital, Jan Waldenströms Gata 24, Malmö, S – 205 02, SwedenTel +46 40 33 25 85Fax +46 40 33 74 90Email Georg.Schramm@med.lu.seBackground: Severe hereditary alpha-1-antitrypsin deficiency (AATD) is a known risk factor for the early development of pulmonary emphysema and COPD, especially in smokers. By the Swedish national screening programme carried out from 1972 to 1974, a cohort of individuals with severe (PiZZ) AATD was identified and has been followed up regularly. The aim of this study was to investigate health status, quality of life and lung function in this cohort at the age of 42 years compared with an age-matched control group randomly selected from the population registry.Methods: All study participants answered a questionnaire on smoking habits, symptoms, occupation, exposure to airway irritants and quality of life using Saint George’s Respiratory Questionnaire (SGRQ). They underwent complete pulmonary function tests (PFT) and forced oscillation technique (FOT) for the measurement of airway resistance and reactance. Blood samples were taken for allergies and IgG-subclasses as an indicator of increased risk of airway infections.Results: The residual volume (RV), total lung capacity (TLC) and RV/TLC ratio were significantly higher in the PiZZ ever-smokers compared to the PiMM ever-smokers and PiZZ never-smokers (p < 0.05). The resistance in the upper, small and total airways was significantly lower in PiZZ subjects compared to PiMM subjects (p < 0.05). A greater proportion of PiZZ never-smokers had an FEV1/VC ratio < 0.7 than PiMM never-smokers (p = 0.043). PiZZ subjects with occupational exposure to airway irritants showed a significantly lower FEV1, VC and higher RV/TLC ratio than PiMM individuals with exposure (p < 0.05).Conclusion: At the age of 42, ever-smoking PiZZ individuals have signs of COPD, and also PiZZ never-smokers have early, physiological signs of emphysema.Keywords: alpha-1-antitrypsin deficiency, COPD, lung function, quality of life

Abstract 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 (r AiDA). 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 (r AiDA) 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 r AiDA, as measured by the AiDA, can be used to better understand the individual variation in the dose to healthy and diseased lungs.

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.

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.

Abstract Previous studies have indicated that glabellar botulinum toxin (BTX) injections may lead to a sustained alleviation of depression. This may be accomplished by the disruption of a facial feedback loop, which potentially mitigates the experience of negative emotions. Accordingly, glabellar BTX injection can attenuate amygdala activity in response to emotional stimuli. A prototypic condition with an excess of negative emotionality and impulsivity accompanied by elevated amygdala reactivity to emotional stimuli is borderline personality disorder (BPD). In order to improve the understanding of how glabellar BTX may affect the processing of emotional stimuli and impulsivity, we conducted a functional magnetic resonance imaging (fMRI) study. Our hypotheses were (1) glabellar BTX leads to increased activation in prefrontal areas during inhibition performance and (2) BTX decreases amygdala activity during the processing of emotional stimuli in general. Using an emotional go-/no-go paradigm during fMRI, the interference of emotion processing and impulsivity in a sample of n = 45 women with BPD was assessed. Subjects were randomly assigned to BTX treatment or serial acupuncture (ACU) of the head. After 4 weeks, both treatments led to a reduction in the symptoms of BPD. However, BTX treatment was specifically associated with improved inhibition performance and increased activity in the motor cortex. In addition, the processing of negative emotional faces was accompanied by a reduction in right amygdala activity. This study provides the first evidence that glabellar BTX injections may modify central neurobiological and behavioural aspects of BPD. Since the control treatment produced similar clinical effects, these neurobiological findings may be specific to BTX and not a general correlate of symptomatic improvement.

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 (rAiDA) and zero-second recovery (R0), 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 rAiDA and R0 between firefighters (mean±sd rAiDA 0.301±0.024 mm; mean±sd R0 0.336±0.116 arbitrary units) and controls (mean±sd rAiDA 0.276±0.044 mm; mean±sd R0 0.5760.168 arbitrary units), p=0.03 and p

IntroductionHealth-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.MethodsThis 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.ResultsMen 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).ConclusionsThe 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.

Abstract 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

Abstract Randomized controlled trials (RCTs) have shown an antidepressant effect of glabellar botulinum toxin (BoNT) injections. In the FDA Adverse Event Reporting System (FAERS) database, BoNT injection is associated with reduced incidence rates of depression across various non-psychiatric indications, which confirms the previous findings independently of specific expectations to an antidepressant effect of BoNT. The rationale of using BoNT to treat depression is to interrupt proprioceptive body feedback that may reinforce negative emotions. Negative emotions also occur in other mental disorders, suggesting a transdiagnostic therapeutic potential of BoNT in psychiatry. Here we report an analysis of the FAERS database, in which we found that, compared to alternative treatments, BoNT injections were associated with lower incidence of anxiety symptoms and related disorders. Among seven indications/injection sites, we found this protective effect of BoNT in cosmetic use/facial muscles, migraine/facial and head muscles, spasms and spasticity/upper and lower limbs, torticollis and neck pain/neck muscles, and sialorrhea/parotid and submandibular glands (reporting odds ratios 0.79–0.27). These findings are encouraging for possible future RCTs on the use of BoNT as a treatment for anxiety and related disorders.

Inhibiting the facial expression of negative emotions via botulinum toxin A (BTX) has been shown to mitigate symptoms of clinical depression in randomized controlled trials. This retrospective case study sought to reproduce the beneficial effects of BTX in a naturalistic setting for major depressive disorder and collect casuistic data on its effect on other mental disorders. Moreover, we describe symptom development across multiple treatment cycles with BTX, and assess the implementation of additional injection targets in the lower face region. Participants were N = 51 adult psychiatric outpatients mainly seeking treatment for depression. Over 50% suffered from comorbid psychiatric conditions, predominantly generalized anxiety disorder (GAD) or borderline personality disorder (BPD). A pre–post case series design was adapted. All participants received BTX-injections in the glabellar region on at least one occasion. Some received additional injections in the mouth region and over multiple treatment cycles. Treatment response was followed up by self-rated scales at varying time intervals post treatment. The results showed that BTX may yield favorable outcomes across multiple and comorbid mental disorders, especially, however, for patients suffering from depression. It potentially prevents the recurrence of clinical symptoms if applied regularly. Adding additional regions of the face does not seem to be superior over applying it to the glabellar region alone. The results add to the growing evidence that BTX therapy is effective in alleviating symptoms of depression. Positive effects can be sustained and reinstated, when applied over multiple treatment cycles. Observed symptom reduction in other psychiatric disorders was less pronounced. Further research is needed to understand the mechanisms by which BTX therapy reduces psychiatric symptoms.

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 (DLCO) 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 DLCO, 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.

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.

Injection of botulinum toxin (BoNT) into the glabellar region of the face is a novel therapeutic approach in the treatment of depression. This treatment method has several advantages, including few side effects and a long-lasting, depot-like effect. Here we review the clinical and experimental evidence for the antidepressant effect of BoNT injections as well as the theoretical background and possible mechanisms of action. Moreover, we provide practical instructions for the safe and effective application of BoNT in the treatment of depression. Finally, we describe the current status of the clinical development of BoNT as an antidepressant and give an outlook on its potential future role in the management of mental disorders.

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.

Rationale: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure., Objectives: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population., Methods: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7., Results: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCO

Rationale: Knowledge regarding prevalence and shared and unique characteristics of Restrictive spirometric pattern (RSP) and Preserved ratio impaired spirometry (PRISm) is lacking for a general population investigated with post-bronchodilator spirometry and computed tomography of the lungs., Objectives: To investigate shared and unique features for RSP and PRISm., Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), a general population sample of 28,555 people aged 50 - 64 years (including 14,558 never-smokers) was assessed. The participants answered a questionnaire and underwent computed tomography of the lungs, post-bronchodilator spirometry, and coronary artery calcification score (CACS). Odds ratios (OR) with 95% confidence intervals (CI) were calculated using adjusted logistic regression. RSP was defined as FEV 1 /FVC≥0.70 and FVC<80%. PRISm was defined as FEV 1 /FVC≥0.70 and FEV 1 <80%. A local reference equation was applied., Measurements and Results: The prevalence of RSP and PRISm were 5.1% (95% CI 4.9 - 5.4) and 5.1% (95% CI 4.8 - 5.3), respectively, with similar values seen in never-smokers. For RSP and PRISm, shared features were current smoking, dyspnea, chronic bronchitis, rheumatic disease, diabetes, ischemic heart disease (IHD), bronchial wall thickening, interstitial lung abnormalities (ILA), and bronchiectasis. Emphysema was uniquely linked to PRISm (OR 1.69, 1.36-2.10) vs 1.10 (0.84-1.43) for RSP. CACS≥300 was related to PRISm, but not among among never-smokers., Conclusions: PRISm and RSP have respiratory, cardiovascular, and metabolic conditions as shared features. Emphysema is only associated with PRISm. Coronary atherosclerosis may be associated with PRISm. Our results indicate that RSP and PRISm may share more features than not. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

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., Competing Interests: Conflict of interest: M. Olsson, A.J. Björkelund, J. Sandberg, A. Blomberg, A. Malinovschi, M. Börjesson, M. Sköld, P. Wollmer, K. Torén, C.J. Östgren, G. Engström and Magnus Ekström report no conflict of interest related to this work. Conflict of interest: D. Currow reports receiving consulting fees from Helsinn Pharmaceuticals, Mayne Pharma International Pty Ltd, Nous Group Pty Ltd, Icare Dust Diseases Board, Chris O'Brien Lifehouse and IHMRI, outside the submitted work; and received payment for intellectual property from Mayne Pharma International Pty Ltd., (Copyright ©The authors 2024.)

Background: Previous studies have shown that the ratio between alveolar volume (V A ) 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 FEV 1 /VC). The purpose of this study was to investigate potential connection between V A /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 V A /TLC had a normal ratio FEV 1 /VC. Of these subjects, 58.1 % had respiratory symptoms, compared to the group with normal ratio for both V A /TLC and FEV 1/ 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 FEV 1 /VC, those with a decreased ratio V A /TLC had a higher prevalence of respiratory symptoms compared to subjects with a normal V A /TLC ratio. These findings indicate that including the ratio V A /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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/ personal relationships which may be considered as potential competing interests: P Wollmer reports a relationship with Chiesi Pharma that includes consulting or advisory. P Wollmer has patent issued to Method and device for pulmonary function measurement., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: AB, AJB, AM, CJÖ, GE, JS, MB, ME, MO, MS, and KT declare no competing interest in relation to this work. DC reports being an unpaid advisory board member for Helsinn Pharmaceuticals; being a paid consultant for and receiving payment for intellectual property from Mayne Pharma; being a consultant with Specialised Therapeutics Australia Pty. Ltd.; being a subcontractor to Nous Group Pty Ltd; and being a paid board member for icare Dust Diseases Care NSW. DC also reports an unpaid board member/Director for Chris O’Brien Lifehouse and being on the Board of IHMRI. PW reports grants from the Swedish Heart and Lung Foundation and personal fees from Chiesi Pharma unrelated to the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Olsson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: Conflict of interest: I. Pesonen reports fees from Boehringer Ingelheim for lectures and participation on advisory boards. Conflict of interest: A. Egeston reports consulting fees from BioCryst, payment/honoraria from AstraZeneca and an unrestricted research grant from CSL-Behring. Conflict of interest: Ö.I. Emilsson reports payment from study work from Boehringer Ingelheim, unrelated to this publication. Conflict of interest: E. Hagström reports payments to institution from Pfizer and Amgen, small personal fees from Amgen, NovoNordisk, Bayer and AstraZeneca, and a small personal fee from Amarin AB for participation on an advisory board. He is the co-chair of the Swedish secondary prevention registry and the national coordinator for the trials DalCore DAL301 DalGne, Regeneron R1500-CL-1643 and Aegis II/Perfuse. Conflict of interest: L.E.G.W. Vanfleteren reports grants paid to his institution from the Swedish Heart and Lung Foundation and the family Kamprad foundation, and payments/honoraria from AstraZeneca, GSK, Boehringer, Novartis, Chiesi, Pulmonx for lectures and presentations. He also reports personal payments for participation on a data safety monitoring board or advisory board for AstraZeneca. He was member of the board for the Swedish National Airway registry. He is as associate editor of this journal. Conflict of interest: P. Wollmer received fees for lectures from Chiesi Pharma outside the scope of the study. He also has a patent issued for a device and method for pulmonary function measurement outside the scope of the study. Conflict of interest: S. Zaigham reports a research project grant from Magnus Bergvalls Stiftelse, and support for meeting attendance from the Swedish Heart and Lung Foundation and Bror Hjerpstedts Stiftelse. Conflict of interest: C.M. Sköld reports research grants from Boehringer Ingelheim for pulmonary fibrosis research, payments for lectures and educational activities related to pulmonary fibrosis, and participation on advisory boards related to pulmonary fibrosis. Conflict of interest: All other authors declare no conflicts of interest., (Copyright ©The authors 2023.)

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 ( R 5 ) 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 (FEV 1 ), 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 R 5 with abnormal reactance resulted in approximately two-fold higher likelihood for having cough, chronic bronchitis and dyspnoea, even when further adjusting for FEV 1 , 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., Competing Interests: Conflict of interest: J. Sundström reports stock or stock options in Anagram Kommunikation AB and Symptoms Europe AB, not related to the present work. Conflict of interest: P. Wollmer reports personal fees from Chiesi Pharmaceuticals outside the submitted work, has a patent for a device and method for pulmonary capacity measurements issued, not related to the present work. Conflict of interest: All other authors declare no conflicts of interest with regard to the present study., (Copyright ©The authors 2023.)

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 FEV 1 /FVC ratios. The prevalence of postbronchodilator FEV 1 /FVC ratio lower than the prebronchodilator LLN was 4.8%, and that of postbronchodilator FEV 1 /FVC lower than the postbronchodilator LLN was 9.9%, for the general population. An additional 5.1% were identified as having an abnormal postbronchodilator FEV 1 /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 FEV 1 /FVC ratio greater than the LLN for both pre- and postbronchodilation. Conclusions: Pre- and postbronchodilator spirometry reference values differ with regard to FEV 1 /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.

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., Competing Interests: Declaration of competing interest Professor Per Wollmer and Associate Professor Jakob Löndahl have a patent for “Device and Method for pulmonary function measurements” issued. The other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 0.5760.168 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.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., Competing Interests: Competing interests: P. Wollmer and J. Löndahl have a patent issued for a “Device and method for pulmonary function measurements”. The other authors declare no competing interests., (Copyright ©The authors 2023.)

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., (© 2022 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

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 (FEV 1 ) 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 FEV 1 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 FEV 1 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., Competing Interests: Declaration of competing interest Dr. Occhipinti reports grants from Fondazione Menarini, personal fees from Novartis, outside the submitted work; Dr. Wollmer reports grants from Swedish Heart and Lung Foundation, grants from Lund University, grants from Skåne Region, during the conduct of the study; personal fees from Chiesi Pharma, outside the submitted work; In addition, Dr. Wollmer has a patent Device and method for pulmonary function measurement issued.. Dr. Luoto reports grants from Skåne County, during the conduct of the study., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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 (FEV 1 ) and FEV 1 /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 FEV 1 /FVC, FEV 1 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., Competing Interests: Conflict of interest: P. Wollmer reports receiving support for the present manuscript from the Swedish Heart and Lung Foundation; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Chiesi Pharma, outside the submitted work: and a patent issued for a device and method for pulmonary function measurement (no licence). The remaining authors have nothing to disclose., (Copyright ©The authors 2022.)

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.

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., Competing Interests: The authors have declared that no competing interests exist.

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., (© 2021 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

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., Competing Interests: Competing interests: PW and JL have a patent issued for the device used in the measurements. PW reports personal fees from AstraZeneca and Chiesi Pharma, outside the submitted work, SZ reports grants from Allmänna sjukhuset i Malmös stiftelse för bekämpande av cancer (Translation: Malmö general hospital’s foundation for defeating cancer), and grants from Stiftelsen för cancerforskning vid onkologiska kliniken vid Universitetssjukhuset Malmö (Translation: Foundation for cancer research within the department of oncology in Malmö University Hospital) outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

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 (f res )., 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., (© 2021 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

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 (FEV 1 ) was more strongly associated with SCD than non-fatal CE even after full adjustment (FEV 1 : 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 FEV 1 /FVC. The results remained significant even in life-long never smokers (FEV 1 : 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 FEV 1 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., Competing Interests: Competing interests: PW reports grants from Swedish Heart and Lung Foundation during the conduct of the study, and personal fees from Chiesi Pharma, personal fees from GlaxoSmithKline, outside the submitted work. PW has a patent device and method for pulmonary function measurement issued., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)