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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.

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.

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.

The World Health Organization estimates the number of people suffering from depression to be over 264 million. Current monoamine transmission modulating therapeutics, even with proper adherence and acceptable tolerability, are not effective for nearly one third of the patients, leading clinicians to explore other therapeutic options such as electroconvulsive therapy, transcranial magnetic stimulation, ketamine infusions, and, more recently, glabellar botulinum toxin, BoNT, injections. The scale and mechanism of antidepressant action of BoNT is unclear and maybe hypothetically attributed to the disruption of proprioceptive facial feedback reinforcing negative emotions. Here we verify the antidepressant effect of botulinum toxin by analysis of over 40 thousand BoNT treatment reports out of thirteen million postmarketing safety reports in the FDA Adverse Event Reporting System, FAERS. The results of the analysis indicate that patients who received BoNT injections to treat hyperhidrosis, facial wrinkles, migraine prophylaxis, spasticity, and spasms, had a significantly lower number of depression reports when compared to patients undergoing different treatments for the same conditions. These findings suggest that the antidepressant effect of BoNT is significant, and, surprisingly, is observed for a broad range of injection sites.

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.

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

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

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

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.

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 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.

Abstract Background Studies investigating postural orientation in uninjured youth athletes are scarce. Understanding how postural orientation during functional performance tests change with age in uninjured athletes has the potential to enhance awareness of changes in performance after injury and to set realistic goals for injured athletes. Thus, the aim of this study was to explore postural orientation during functional tasks at early adolescence, and changes in postural orientation from early to middle adolescence and relate this to sex, type of sport and right leg lean body mass (RLLBM). Methods In this cohort study 144 (38% female) youth athletes (mean age 13.5 years, SD 0.3) were included at baseline and 86 of these at follow up 2 years later. Four functional performance tests were visually evaluated for Postural Orientation Errors (POEs) with an ordinal scale, ranging from 0 (good) to 2 (poor), yielding a maximum total POE score of 51, and RLLBM by dual energy X-ray absorptiometry. Results Improvements were observed in the total POE score from baseline to follow-up, median difference − 10 and − 7 (p