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Sofia Eriksson,1 Maaike Giezeman,2,3 Mikael Hasselgren,2,3 Christer Janson,4 Marta A Kisiel,5 Scott Montgomery,2,6,7 Anna Nager,8 Hanna Sandelowsky,7,9 Björn Ställberg,10 Josefin Sundh,11 Karin Lisspers10 1Region Dalarna, Falun, Sweden; 2School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 3Centre for Clinical Research and Education, Region Värmland, Karlstad, Sweden; 4Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 5Department of Medical Sciences, Occupational and Environment Medicine, Uppsala University, Uppsala, Sweden; 6Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 7Department of Epidemiology and Public Health, University College, London, UK; 8NVS, Section for Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden; 9Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden; 10Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 11Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, SwedenCorrespondence: Karin Lisspers, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Box 564, Uppsala, SE-75122, Sweden, Tel +46703524721, Email Karin.lisspers@regiondalarna.se; Karin.lisspers@uu.sePurpose: To study risk factors for uncontrolled asthma and insufficient quality of life (QoL) in patients with mild asthma, ie those without preventer treatment.Patients and Methods: Patients aged 18– 75 years with a doctor’s diagnosis of asthma randomly selected from primary and secondary care in Sweden. Mild asthma was defined as self-reported current asthma and no preventer treatment. Data were collected from self-completed questionnaires in 2012 and 2015. Well-controlled asthma was defined as Asthma Control Test (ACT) ≥ 20 points and no exacerbation and uncontrolled asthma as ACT< 20 points and/or at least one exacerbation in the previous six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ), where a total mean score of ≥ 6 indicated sufficient and < 6 insufficient QoL. Multivariate logistic regression analyses were performed using asthma control and Mini-AQLQ as dependent variables. Asthma control was dichotomized as controlled and uncontrolled asthma and the Mini-AQLQ as sufficient QoL (mean score ≥ 6) and insufficient QoL (mean score < 6).Results: Among 298 patients, 26% had uncontrolled asthma, 40% insufficient QoL and 20% both uncontrolled asthma and insufficient QoL. Age ≥ 60 years, obesity, daily smoking, rhinitis and inadequate knowledge of asthma self-management were independently associated with poor asthma control. Factors independently associated with insufficient QoL were age ≥ 60 years, overweight, obesity, rhinitis, sinusitis and inadequate knowledge of asthma self-management. Age ≥ 60 years, obesity, rhinitis and inadequate knowledge of asthma self-management were independently associated with both uncontrolled asthma and insufficient QoL.Conclusion: Among asthma patients without preventer medication, 26% had uncontrolled asthma and 40% had insufficient asthma-related QoL. Older age, obesity, and rhinitis were risk factors for both poor asthma control and a reduced QoL, but having good knowledge of asthma self-management reduced this risk. Our findings suggest that this group of patients requires further attention and follow-up.Plain Language Summary: Many patients with little symptoms of asthma do not take asthma-preventer medication as their asthma is recognized as mild. Still, it is well-known that in this group there are patients with frequent and severe symptoms and acute attacks of asthma, defined as uncontrolled asthma. Quality of life (QoL) is less studied in these patients. Our aim was to study patient characteristics and factors with a higher risk for uncontrolled asthma and insufficient QoL in patients with mild asthma.We studied patients with asthma diagnosis 18– 75 of age in Sweden who reported asthma and no asthma preventer medication. They answered questionnaires about characteristics, knowledge of asthma, asthma symptoms, acute asthma attacks and QoL. A test for asthma symptom control, the Asthma Control Test (ACT), was answered, where 20 points or more meant good asthma symptom control. Patients were regarded as having uncontrolled asthma if they had less than 20 points and/or at least one acute asthma attack the last six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire. A mean score of 6 or more meant sufficient and less than 6 insufficient QoL.Of the 298 patients, 26% had uncontrolled asthma, 40% had insufficient QoL and 20% had both. Patients with risk for both uncontrolled asthma and insufficient QoL were 60 years and over, with obesity, rhinitis and those who reported insufficient knowledge of how to handle asthma. Our results suggest that patients with mild asthma need more attention, better management and follow-ups.Keywords: asthma, management, risk factors, asthma outcomes

Dennis Bouhuis,1 Maaike Giezeman,1,2 Mikael Hasselgren,1,2 Christer Janson,3 Marta A Kisiel,4 Karin Lisspers,5 Scott Montgomery,6– 8 Anna Nager,9 Hanna Sandelowsky,7,9,10 Björn Ställberg,5 Josefin Sundh11 1School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 2Centre for Clinical Research and Education, Karlstad, Sweden; 3Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 4Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden; 5Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 6Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro, Sweden; 7Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; 8Department of Epidemiology and Public Health, University College, London, UK; 9Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden; 10Academic Primary Health Care Centre, Stockholm, Sweden; 11Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, SwedenCorrespondence: Josefin Sundh, Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden, Tel +46702349517, Email josefin.sundh@regionorebrolan.seBackground: Patients with chronic obstructive pulmonary disease (COPD) and no exacerbations may need less maintenance treatment and follow-up. The aim was to identify factors associated with a non-exacerbator COPD phenotype.Methods: Cross-sectional analysis of 1354 patients from primary and secondary care, with a doctor’s diagnosis of COPD. In 2014, data on demographics, exacerbation frequency and symptoms using COPD Assessment Test (CAT) were collected using questionnaires and on spirometry and comorbid conditions by record review. The non-exacerbator phenotype was defined as having reported no exacerbations the previous six months. Multivariable logistic regression with the non-exacerbator phenotype as dependent variable was performed, including stratification and interaction analyses by sex.Results: The non-exacerbator phenotype was found in 891 (66%) patients and was independently associated with COPD stage 1 (OR [95% CI] 5.72 [3.30– 9.92]), stage 2 (3.42 [2.13– 5.51]) and stage 3 (2.38 [1.46– 3.88]) compared with stage 4, and with CAT score < 10 (3.35 [2.34– 4.80]). Chronic bronchitis and underweight were inversely associated with the non-exacerbator phenotype (0.47 [0.28– 0.79]) and (0.68 [0.48– 0.97]), respectively. The proportion of non-exacerbators was higher among patients with no maintenance treatment or a single bronchodilator. The association of COPD stage 1 compared with stage 4 with the non-exacerbator phenotype was stronger in men (p for interaction 0.048). In women, underweight and obesity were both inversely associated with the non-exacerbator phenotype (p for interaction 0.033 and 0.046 respectively), and in men heart failure was inversely associated with the non-exacerbator phenotype (p for interaction 0.030).Conclusion: The non-exacerbator phenotype is common, especially in patients with no maintenance treatment or a single bronchodilator, and is characterized by preserved lung function, low symptom burden, and by absence of chronic bronchitis, underweight and obesity and heart failure. We suggest these patients may need less treatment and follow-up, but that management of comorbid conditions is important to avoid exacerbations.Keywords: COPD, exacerbations, lung function, CAT, body mass index, chronic bronchitis, sex, heart failure

Maaike Giezeman,1,2 Josefin Sundh,3 Åsa Athlin,1 Karin Lisspers,4 Björn Ställberg,4 Christer Janson,5 Scott Montgomery,6– 8 Marta A Kisiel,9 Anna Nager,10 Hanna Sandelowsky,7,10,11 Mikael Hasselgren1,2 1School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 2Centre for Clinical Research and Education, Karlstad, Sweden; 3Department of Respiratory Medicine, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 4Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 5Department of Medical Sciences, Respiratory, Allergy & Sleep Research, Uppsala University, Uppsala, Sweden; 6Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 7Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; 8Department of Epidemiology and Public Health, University College London, London, UK; 9Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden; 10Division of Family Medicine and Primary Care, Inst NVS, Karolinska Institutet, Stockholm, Sweden; 11Academic Primary Health Care Centre, Region Stockholm, SwedenCorrespondence: Maaike Giezeman, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden, Email Maaike.giezeman@oru.sePurpose: The aim of this study was to examine the association of comorbid heart disease, defined as chronic heart failure or ischemic heart disease, on all-cause and cause-specific hospitalization and mortality in patients with COPD over a period of nearly 15 years.Materials and Methods: The cohort study included patients with COPD from primary and secondary care in 2005 with data from questionnaires and medical record reviews. The Swedish Board of Health and Welfare provided hospitalization and mortality data from 2005 through 2019. Cox regression analyses, adjusted for sex, age, educational level, smoking status, BMI, exacerbations, dyspnea score and comorbid diabetes or hypertension, assessed the association of comorbid heart disease with all-cause and cause-specific time to first hospitalization and death. Linear regression analyses, adjusted for the same variables, assessed this association with hospitalization days per year for those patients that had been hospitalized.Results: Of the 1071 patients, 262 (25%) had heart disease at baseline. Cox regression analysis showed a higher risk of hospitalization for patients with heart disease for all-cause (HR (95% CI) 1.55; 1.32– 1.82), cardiovascular (2.14; 1.70– 2.70) and other causes (1.27; 1.06– 1.52). Patients with heart disease also had an increased risk of all-cause (1.77; 1.48– 2.12), cardiovascular (3.40; 2.41– 4.78) and other (1.50; 1.09– 2.06) mortality. Heart disease was significantly associated with more hospitalization days per year of all-cause (regression coefficient 0.37; 95% CI 0.15– 0.59), cardiovascular (0.57; 0.27– 0.86) and other (0.37; 0.12– 0.62) causes. No significant associations were found between heart disease and respiratory causes of hospitalization and death.Conclusion: Comorbid heart disease in patients with COPD is associated with an increased risk for all-cause hospitalization and mortality, mainly due to an increase of hospitalization and death of cardiovascular and other causes, but not because of respiratory disease. This finding advocates the need of a strong clinical focus on primary and secondary prevention of cardiovascular disease in patients with COPD.Keywords: chronic obstructive pulmonary disease, comorbidity, chronic heart failure, ischemic heart disease, hospitalization, mortality

Marta A Kisiel,1,&ast; Martin Jacobsson,2,&ast; Susann Järhult,3 Linda Ekerljung,4 Kjell Alving,5 Roelinde Middelveld,6 Karl Franklin,7 Christer Janson2 1Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden; 2Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 3Department of Medical Sciences, Emergency Department, Uppsala University, Uppsala, Sweden; 4Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, University of Gothenburg, Gothenburg, Sweden; 5Department of Women’s and Children’s Health, Paediatric Research, Uppsala University, Uppsala, Sweden; 6Centre for Allergy Research and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 7Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden&ast;These authors contributed equally to this workCorrespondence: Marta A Kisiel, Dag Hammarskjölds väg 60, Uppsala, 751 85, Sweden, Tel +46704145919, Email marta.kisiel@medsci.uu.seBackground: Asthma is a common chronic disease presenting with airway symptoms such as wheezing, chest tightness and attacks of breathlessness. Underdiagnosis of asthma is common and correlates to negative outcomes such as a lower quality of life and reduced work capacity.Purpose: This study aims to identify factors for not being diagnosed with asthma if presenting with asthma symptoms.Patients and Methods: A questionnaire was sent to 45,000 subjects (age 16– 74 years) in Sweden. Subjects who reported both wheeze and breathlessness and wheeze when not having a cold were defined as having asthma-related symptoms. Data on demographics, educational level, smoking, physical activity, comorbidities, symptoms and asthma were collected. Logistic regression was used to identify risk factors for not being diagnosed with asthma.Results: Of the 25,391 who responded to the survey, 6.2% reported asthma-related symptoms. Of these, 946 had been diagnosed with asthma previously, while 632 had not. Independent risk factors for not being diagnosed with asthma were higher age (OR (95% CI) (2.17 (1.39– 3.40))), male sex (1.46 (1.17– 1.81)), current smoking (2.92 (2.22– 3.84)), low level of education (1.43 (1.01– 2.01)), low physical activity (1.36 (1.06– 1.74)), and hypertension (1.50 (1.06– 2.12)).Conclusion: Men, smokers, older subjects, and those with low educational level or low physical activity are less likely to be diagnosed with asthma despite presenting asthma-related symptoms.Keywords: asthma symptoms, no diagnosis despite symptoms of asthma

Abstract Background Myosin VI, encoded by jaguar (jar) in Drosophila melanogaster, is a unique member of the myosin superfamily of actin-based motor proteins. Myosin VI is the only myosin known to move towards the minus or pointed ends of actin filaments. Although Myosin VI has been implicated in numerous cellular processes as both an anchor and a transporter, little is known about the role of Myosin VI in the nervous system. We previously recovered jar in a screen for genes that modify neuromuscular junction (NMJ) development and here we report on the genetic analysis of Myosin VI in synaptic development and function using loss of function jar alleles. Results Our experiments on Drosophila third instar larvae revealed decreased locomotor activity, a decrease in NMJ length, a reduction in synaptic bouton number, and altered synaptic vesicle localization in jar mutants. Furthermore, our studies of synaptic transmission revealed alterations in both basal synaptic transmission and short-term plasticity at the jar mutant neuromuscular synapse. Conclusions Altogether these findings indicate that Myosin VI is important for proper synaptic function and morphology. Myosin VI may be functioning as an anchor to tether vesicles to the bouton periphery and, thereby, participating in the regulation of synaptic vesicle mobilization during synaptic transmission.

Introduction: The study aimed to compare prevalence of comorbid allergic manifestations and rhinitis, allergy testing and associations with patient-related outcomes in patients with asthma and COPD., Methods: Cross-sectional study of randomly selected Swedish patients with a doctor's diagnosis of asthma ( n  = 1291) or COPD ( n  = 1329). Self-completion questionnaires from 2014 provided data on demographics, rhinitis, allergic symptoms at exposure to pollen or furry pets, exacerbations, self-assessed severity of disease and scores from the Asthma Control Test (ACT) and the COPD Assessment Test (CAT), and records were reviewed for allergy tests., Results: Allergic manifestations were more common in asthma (75%) compared with COPD (38%). Rhinitis was reported in 70% of asthma and 58% of COPD patients. Allergy tests had been performed during the previous decade in 28% of patients with asthma and in 8% of patients with COPD.In patients with asthma; comorbid allergy and rhinitis were both independently associated with increased risk for poor asthma symptom control (ACT < 20) (OR [95% CI] 1.41 [1.05 to 1.87] and 2.13 [1.60 to 2.83]), exacerbations (1.58 [1.15 to 2.17] and 1.38 [1.02 to 1.86]), and self-assessed moderate/severe disease (1.64 [1.22 to 2.18] and 1.75 [1.33 to 2.30]). In patients with COPD, comorbid allergy and rhinitis were both independently associated with increased risk for low health status (CAT ≥ 10) (OR [95% CI] 1.46 [1.20 to 1.95] and 2.59 [1.97 to 3.41]) respectively, with exacerbations during the previous six months (1.91 [1.49 to 2.45] and 1.57 [1.23 to 2.01]), and with self-assessed moderate/severe disease (1.70 [1.31 to 2.22] and 2.13 [1.66 to 2.74])., Conclusion: Allergic manifestations and rhinitis are more common in asthma than COPD but associated with worse outcomes in both diseases. This highlights the importance of examining and treating comorbid allergy and rhinitis, not only in asthma but also in COPD., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

This study aimed to determine whether the EQ-5D-5L tool captures the most common persistent symptoms, such as fatigue, memory/concentration problems and dyspnea, in patients with post-COVID-19 conditions while also investigating if adding these symptoms improves the explained variance of the health-related quality of life (HRQoL). In this exploratory cross-sectional study, two cohorts of Swedish patients (n = 177) with a history of COVID-19 infection answered a questionnaire covering sociodemographic characteristics and clinical factors, and their HRQoL was assessed using EQ-5D-5L with the Visual Analogue Scale (EQ-VAS). Spearman rank correlation and multiple regression analyses were employed to investigate the extent to which the most common persistent symptoms, such as fatigue, memory/concentration problems and dyspnea, were explained by the EQ-5D-5L. The explanatory power of EQ-5D-5L for EQ-VAS was also analyzed, both with and without including symptom(s). We found that the EQ-5D-5L dimensions partly captured fatigue and memory/concentration problems but performed poorly in regard to capturing dyspnea. Specifically, the EQ-5D-5L explained 55% of the variance in memory/concentration problems, 47% in regard to fatigue and only 14% in regard to dyspnea. Adding fatigue to the EQ-5D-5L increased the explained variance of the EQ-VAS by 5.7%, while adding memory/concentration problems and dyspnea had a comparatively smaller impact on the explained variance. Our study highlights the EQ-5D-5L's strength in capturing fatigue and memory/concentration problems in post-COVID-19 patients. However, it also underscores the challenges in assessing dyspnea in this group. Fatigue emerged as a notably influential symptom, significantly enhancing the EQ-5D-5L's predictive ability for these patients' EQ-VAS scores.

Objective: Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids (ICS) and overuse of short-acting β2-agonists (SABA). Our aim was to investigate longitudinal trends and associated factors in asthma treatment., Methods: Two separate cohorts of adults with physician-diagnosed asthma were randomly selected from 14 hospitals and 56 primary health centers in Sweden in 2005 ( n  = 1182) and 2015 ( n  = 1225). Information about symptoms, maintenance treatment, and use of rescue medication was collected by questionnaires. Associations between treatment and sex, age, smoking, education, body mass index (BMI), physical activity, allergic asthma, and symptom control were analyzed using Pearson's chi 2 -test. Odds ratios (ORs) were calculated using logistic regression., Results: Maintenance treatment with ICS together with long-acting β2-agonists (LABA) and/or montelukast increased from 39.2% to 44.2% ( p  = 0.012). The use of ICS + LABA as-needed increased (11.1-18.9%, p  < 0.001), while SABA use decreased (46.4- 41.8%, p  = 0.023). Regular treatment with ICS did not change notably (54.2-57.2%, p  = 0.14). Older age, former smoking, and poor symptom control were related to treatment with ICS + LABA/montelukast. In 2015, 22.7% reported daily use of SABA. A higher step of maintenance treatment, older age, obesity, shorter education, current smoking, allergic asthma, low or very high physical activity, and a history of exacerbations were associated with daily SABA use., Conclusions: The use of ICS + LABA both for maintenance treatment and symptom relief has increased over time. Despite this, the problem of low use of ICS and high use of SABA remains.

Background: This study aimed to estimate absenteeism costs and identify their predictors in non-hospitalized patients in Sweden., Methods: This cross-sectional study's data were derived from the longitudinal project conducted at Uppsala University Hospital. The mean absenteeism costs due to COVID-19 were calculated using the human capital approach, and a Poisson regression analysis was employed to determine predictors of these costs., Results: The findings showed that the average absenteeism cost due to COVID-19 was USD 1907.1, compared to USD 919.4 before the pandemic ( p < 0.001). Notably, the average absenteeism cost for females was significantly higher due to COVID-19 compared to before the pandemic (USD 1973.5 vs. USD 756.3, p = 0.001). Patients who had not fully recovered at the 12-month follow-up exhibited significantly higher costs than those without symptoms at that point (USD 3389.7 vs. USD 546.7, p < 0.001). The Poisson regression revealed that several socioeconomic factors, including age, marital status, country of birth, educational level, smoking status, BMI, and occupation, along with COVID-19-related factors such as severity at onset, pandemic wave, persistent symptoms at the follow-up, and newly introduced treatment for depression after the infection, were significant predictors of the absenteeism costs., Conclusions: Our study reveals that the mean absenteeism costs due to COVID-19 doubled compared to the year preceding the pandemic. This information is invaluable for decision-makers and contributes to a better understanding of the economic aspects of COVID-19., Competing Interests: All authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Striving to return to work is of great importance to many cancer survivors. The purpose of the study is to prospectively investigate the factors that hinder and facilitate return to work (RTW) at 3 and 12 months after the end of treatment in head and neck cancer (HNC) survivors and whether these factors influence the ability to continue working after treatment. Participants ( n = 227) aged ≤ 65 years at diagnosis with HNC were included. Data were collected before the start of treatment and at 3 and 12 months after the end of treatment. The Rubin causal model was used for statistical analysis. Within the 3-month follow-up period, 92 participants had RTW and 30 had retired. At the 12-month follow-up, 80 of these participants were still working, another 51 participants had RTW, and five participants working still suffered from cancer. The hindrance to RTW within 3 months was advanced tumour stage (stage III and IV) ( p = 0.0038). Hindrances to RTW at the 12-month follow-up were oral cancer ( p = 0.0210) and larynx cancer ( p = 0.0041), and facilitators were living in a relationship ( p = 0.0445) and a white-collar job ( p = 0.00267). Participants with early tumour stage (stage I and II) ( p = 0.0019) and a white-collar job ( p = 0.0185) had earlier RTW. The conclusion is that disease factors were the most important hindrances to RTW, and type of work and living with a spouse or partner were nonclinical factors influencing RTW.

Background: Asthma and inflammatory bowel disease (IBD) are common inflammatory diseases. The aim of this study was to investigate the associations of IBD with asthma and respiratory symptoms., Methods: This study is based on 13,499 participants from seven northern European countries that filled in a postal questionnaire on asthma, respiratory symptoms, IBD including ulcerative colitis and Crohn's disease and various lifestyle variables., Results: There were 195 participants with IBD. The prevalence of asthma (14.5 vs 8.1%, p = 0.001), different respiratory symptoms (range 11.9-36.8% vs range 6.0-18.6%, p < 0.005), non-infectious rhinitis (52.1 vs. 41.6%, p = 0.004) and chronic rhinosinusitis (11.6 vs 6.0%, p = 0.001) were higher in subjects with IBD than in those without IBD. In multivariable regression analysis, the association between IBD and asthma was statistically significant (OR 1.95 (95% CI 1.28-2.96)) after adjusting for confounders such as sex, BMI, smoking history, educational level and physical activity. There was a significant association between asthma and ulcerative colitis (adjusted OR 2.02 (95% CI 1.27-2.19)), and asthma but not Crohn's disease (adjusted OR 1.66 (95% CI 0.69-3.95)). A significant gender interaction was found with a significant association between IBD and asthma in women but not in men ((OR 2.72 (95% CI 1.67-4.46) vs OR 0.87 (95% CI 0.35-2.19), p = 0.038)., Conclusions: Patients with IBD, particularly those with ulcerative colitis and female, have a higher prevalence of asthma and respiratory symptoms. Our findings indicate that it is important to consider respiratory symptoms and disorders when examining patients with manifest or suspected IBD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Molecular hydrogen (H 2 ) has shown therapeutic potential in several oxidative stress-related conditions in humans, is well-tolerated, and is easily administered via inhalation.The aim of this preclinical in vivo study was to investigate whether impulse noise trauma can be prevented by H 2 when inhaled immediately after impulse noise exposure., Methods: Guinea pigs (n = 26) were subjected to impulse noise (n = 400; 156 dB SPL; 0.33/s; n = 11; the Noise group), to impulse noise immediately followed by H 2 inhalation (2 mol%; 500 ml/min; 1 hour; n = 10; the Noise + H 2 group), or to H 2 inhalation (n = 5; the H 2 group). The acoustically evoked ABR threshold at 3.15, 6.30, 12.5, 20.0, and 30.0 kHz was assessed before and 4 days after impulse noise and/or H 2 exposure. The cochleae were harvested after the final ABR assessment for quantification of hair cells., Results: Noise exposure caused ABR threshold elevations at all frequencies (median 35, 35, 30, 35, and 35 dB SPL, the Noise group; 20, 25, 10, 13, and 20 dB SPL, the Noise + H 2 group; P  < .05) but significantly less so in the Noise + H 2 group ( P  < .05). Outer hair cell (OHC) loss was in the apical, mid, and basal regions 8.8%, 53%, and 14% in the Noise group and 3.5%, 22%, and 1.2% in the Noise + H 2 group. The corresponding inner hair cell (IHC) loss was 0.1%, 14%, and 3.5% in the Noise group and 0%, 2.8%, and 0% in the Noise + H 2 group. The difference between the groups was significant in the basal region for OHCs ( P  = .003) and apical ( P  = .033) and basal ( P  = .048) regions for IHCs., Conclusions: Acute acoustic trauma can be reduced by H 2 when inhaled immediately after impulse noise exposure.

Background/aim: This study aimed to distinguish different phenotypes of long COVID through the post-COVID syndrome (PCS) score based on long-term persistent symptoms following COVID-19 and evaluate whether these symptoms affect general health and work ability. In addition, the study identified predictors for severe long COVID., Method: This cluster analysis included cross-sectional data from three cohorts of patients after COVID-19: non-hospitalized (n = 401), hospitalized (n = 98) and those enrolled at the post-COVID outpatient's clinic (n = 85). All the subjects responded to the survey on persistent long-term symptoms and sociodemographic and clinical factors. K-Means cluster analysis and ordinal logistic regression were used to create PCS scores that were used to distinguish patients' phenotypes., Results: 506 patients with complete data on persistent symptoms were divided into three distinct phenotypes: none/mild (59%), moderate (22%) and severe (19%). The patients with severe phenotype, with the predominating symptoms were fatigue, cognitive impairment and depression, had the most reduced general health status and work ability. Smoking, snuff, body mass index (BMI), diabetes, chronic pain and symptom severity at COVID-19 onset were factors predicting severe phenotype., Conclusion: This study suggested three phenotypes of long COVID, where the most severe was associated with the highest impact on general health status and working ability. This knowledge on long COVID phenotypes could be used by clinicians to support their medical decisions regarding prioritizing and more detailed follow-up of some patient groups.

Introduction: Previous studies on the association between abdominal and general obesity and respiratory disease have provided conflicting results., Aims and Objectives: We aimed to explore the associations of abdominal obesity with respiratory symptoms, asthma, and chronic obstructive pulmonary disease independently from general obesity in women and men., Methods: This cross-sectional study was based on the Respiratory Health in Northern Europe (RHINE) III questionnaire (n = 12 290) conducted in 2010-2012. Abdominal obesity was self-measured waist circumference using a sex-specific standard cut-off point: ≥102 cm in males and ≥88 cm in females. General obesity was defined as self-reported BMI ≥30.0 kg/m 2 ., Results: There were 4261 subjects (63% women) with abdominal obesity and 1837 subjects (50% women) with general obesity. Both abdominal and general obesity was independent of each other and associated with respiratory symptoms (odds ratio (OR) from 1.25 to 2.00)). Asthma was significantly associated with abdominal and general obesity in women, OR (95% CI) 1.56 (1.30-1.87) and 1.95 (1.56-2.43), respectively, but not in men, OR 1.22 (0.97-3.17) and 1.28 (0.97-1.68) respectively. A similar sex difference was found for self-reported chronic obstructive pulmonary disease., Conclusions: General and abdominal obesity were independent factors associated with respiratory symptoms in adults. Asthma and chronic obstructive pulmonary disease were independently linked to abdominal and general obesity in women but not men., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (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 0.301±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., 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.)

The aim of this study was to describe factors associated with having COPD regularly reviewed in primary care by a nurse or physician and assess whether there was de-prioritisation for COPD in multimorbid patients. We defined de-prioritisation as not having at least one check-up by a physician during a two-year period. Among 713 COPD patients in the Swedish PRAXIS study, 473 (66%) had at least one check-up during the study period (ending in 2014). Patients with check-ups were more likely to have three or more comorbid conditions (31.9% vs. 24.6%) and exacerbations (35.1% vs. 21.7%) than those without. Compared with those without comorbidity, those with three or more diagnoses had increased relative risk ratios (and 95% CI) for consultations discussing COPD with only a physician (5.63 (2.68-11.79)), COPD-nurse only (1.67 (0.83-3.37)) or both (2.11 (1.09-4.06)). COPD patients received more frequent check-ups considering COPD if they had comorbidity or a history of exacerbations. We found no evidence of de-prioritisation for COPD in multimorbid patients., (© 2023. The Author(s).)

Objectives: The aim was to investigate if menstruation and use of exogenous sex hormones influence self-reported asthma related quality of life (QoL) and asthma control., Methods: The study is based on two asthma cohorts randomly selected in primary and secondary care. A total of 622 female patients 18-65 years were included and classified as premenopausal ≤ 46 years ( n  = 338) and peri/postmenopausal 47-65 years ( n  = 284). Questionnaire data from 2012 and 2014 with demographics, asthma related issues and sex hormone status. Outcome measures were Mini Asthma Quality of Life Questionnaire (Mini-AQLQ) and asthma control including Asthma Control Test (ACT) and exacerbations last six months., Results: Premenopausal women with menstruation related asthma worsening, perimenstrual asthma (PMA) (9%), had a clinically relevant lower Mini-AQLQ mean score 4.9 vs. 5.8 ( p  < 0.001), lower asthma control with ACT score < 20, 72% vs. 28% ( p  < 0.001) and higher exacerbation frequency 44% vs. 20% ( p  = 0.004) compared with women without PMA. Women with irregular menstruation had higher exacerbation frequency than women with regular menstruation ( p  = 0.023). Hormonal contraceptives had no impact on QoL and asthma control. Peri/postmenopausal women with menopausal hormone therapy (MHT) had a clinically relevant lower Mini-AQLQ mean score compared to those without MHT, 4.9 vs 5.4 ( p  < 0.001), but no differences in asthma control., Conclusion: Women with PMA had lower QoL and more uncontrolled asthma than women without PMA. Peri/postmenopausal women with MHT had lower QoL than women without MHT. Individual clinical management of women with asthma may benefit from information about their sex hormone status.

Background: Better knowledge of long-term symptoms following coronavirus disease 2019 (COVID-19), the so-called post-COVID-19, in non-hospitalized patients is needed. The aim of this study was to study persisent symptoms up to 12 months after COVID-19 in non-hospitalized patients and their impact on work ability. We also investigated predictors of persistent symptoms., Methods: This study encompassed non-hospitalized adult subjects with a COVID-19 infection confirmed via positive nasopharyngeal swab polymerase chain reaction test during the first wave of the pandemic in Uppsala, Sweden. In total, 566 subjects were sent a survey via e-mail or post with an invitation to participate in the survey 12 months post-diagnosis. The majority of subjects were healthcare workers, as this group was prioritized for testing., Results: A total of 366 subjects responded, with 47% reporting persistent symptoms 12 months after their COVID-19 diagnosis. The most commonly reported symptoms at this time were impaired sense of smell and/or taste and fatigue. Among the predictors of persistent symptoms were being born abroad, lower physical fitness compared with peers before COVID-19, body mass index >25 kg/m 2 , cooccurrence of hypertension and chronic pain, and having more than seven of the general COVID-19 symptoms at the onset. Respondents with symptoms after 12 months self-reported negatively about their general health and work ability., Conclusions: This study indicated that many people who had mild COVID-19 might have a variety of long-term symptoms. It highlights the importance of considering work ability after mild COVID-19., Competing Interests: The authors report no conflicts of interest., (© 2022 The Author(s). Published by Upsala Medical Society.)

Background: Asthma severity can be estimated as the level of medication needed to achieve asthma control or by the patient's subjective assessment. Factors associated with self-assessed asthma severity are still incompletely explored., Aim: The aim was to study factors associated with self-assessed moderate or severe asthma., Method: In total, 1828 randomly selected asthma patients from primary (69%) and secondary (31%) care, completed a questionnaire including items about patient characteristics, comorbidity, the Asthma Control Test (ACT), emergency care visits and a scale for self-assessed asthma severity. Logistic regression was used to analyze associations with the dependent variable, self-assessed moderate or severe asthma in the entire study population and stratified by sex., Results: Of the patients, 883 (45%) reported having moderate or severe asthma. Factors independently associated with self-assessed moderate or severe asthma were age >60 years (OR [95% CI] 1.98 [1.37-2.85]), allergic rhino-conjunctivitis (1.43 [1.05-1.95]), sinusitis (1.45 [1.09-1.93]), poor asthma control as measured by ACT <20 (5.64 [4.45-7.16]) and emergency care visits the previous year (2.52 [1.90-3.34]). Lower level of education was associated with self-assessed moderate/severe asthma in women (1.16 [1.05-2.43]) but not in men (0.90 [0.65-1.25]), p for interaction = .012., Conclusion: Poor asthma control, allergic rhino-conjunctivitis, recent sinusitis and older age were independently associated with self-assessed moderate or severe asthma. Important implications are that comorbid conditions of the upper airways should always be considered as part of asthma management, and that elderly patients may need extra attention.

The immune system has a crucial role in skin wound healing and the application of specific cell-laden immunomodulating biomaterials emerged as a possible treatment option to drive skin tissue regeneration. Cell-laden tissue-engineered skin substitutes have the ability to activate immune pathways, even in the absence of other immune-stimulating signals. In particular, mesenchymal stem cells with their immunomodulatory properties can create a specific immune microenvironment to reduce inflammation, scarring, and support skin regeneration. This review presents an overview of current wound care techniques including skin tissue engineering and biomaterials as a novel and promising approach. We highlight the plasticity and different roles of immune cells, in particular macrophages during various stages of skin wound healing. These aspects are pivotal to promote the regeneration of nonhealing wounds such as ulcers in diabetic patients. We believe that a better understanding of the intrinsic immunomodulatory features of stem cells in implantable skin substitutes will lead to new translational opportunities. This, in turn, will improve skin tissue engineering and regenerative medicine applications.

Healthcare and residential care workers represent two occupational groups that have, in particular, been at risk of Covid-19, its long-term consequences, and related sick leave. In this study, we investigated the predictors of prolonged sick leave among healthcare and residential workers due to non-hospitalized Covid-19 in the early period of the pandemic. This study is based on a patient register (n = 3209) and included non-hospitalized healthcare or residential care service workers with a positive RT- PCR for SARS-CoV-2 (n = 433) between March and August 2020. Data such as socio-demographics, clinical characteristics, and the length of sick leave because of Covid-19 and prior to the pandemic were extracted from the patient's electronic health records. Prolonged sick leave was defined as sick leave ≥ 3 weeks, based on the Swedish pandemic policy. A generalized linear model was used with a binary distribution, adjusted for age, gender, and comorbidity in order to predict prolonged sick leave. Of 433 (77% women) healthcare and residential care workers included in this study, 14.8% needed longer sick leave (> 3 weeks) due to Covid-19. Only 1.4% of the subjects were on sick leave because of long Covid. The risk of sick leave was increased two-fold among residential care workers (adjusted RR 2.14 [95% CI 1.31-3.51]). Depression/anxiety (adjusted RR 2.09 [95% CI 1.31-3.34]), obesity (adjusted RR 1.96 [95% CI 1.01-3.81]) and dyspnea at symptom onset (adjusted RR 2.47 [95% CI 1.55-3.92]), sick leave prior to the pandemic (3-12 weeks) (adjusted RR 2.23 [95% CI 1.21-4.10]) were associated with longer sick leave. From a public health perspective, considering occupational category, comorbidity, symptoms at onset, and sick leave prior to the pandemic as potential predictors of sick leave in healthcare may help prevent staff shortage., Competing Interests: The authors have declared that no competing interests exist.

Aim: The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals., Method: This study included 15 842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25-54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations., Results: In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53-3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18-4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood., Conclusion: In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma., Competing Interests: Conflict of interest: M.A. Kisiel has nothing to disclose. Conflict of interest: X. Zhou has nothing to disclose. Conflict of interest: E. Björnsson has nothing to disclose. Conflict of interest: M. Holm has nothing to disclose. Conflict of interest: A. Dahlman-Höglund has nothing to disclose. Conflict of interest: J. Wang has nothing to disclose. Conflict of interest: C. Svanes has nothing to disclose. Conflict of interest: D. Norbäck has nothing to disclose. Conflict of interest: K.A. Franklin has nothing to disclose. Conflict of interest: A. Malinovschi has nothing to disclose. Conflict of interest: A. Johannessen has nothing to disclose. Conflict of interest: V. Schlünssen has nothing to disclose. Conflict of interest: C. Janson has nothing to disclose., (Copyright ©The authors 2021.)

Background: Gender discrimination (GD) and sexual harassment (SH) occur at all academic institutions worldwide. Medical students report high prevalence of GD and SH, which may negatively affect their education and health. There are indications that policies and reforms on reducing GD/SH are insufficient. Swedish medical students' experiences of GD/SH are monitored by course-evaluations and bi-annual student union evaluations; however, the response rate is usually low. The aim of this study was to compare the exposure to and context of self-reported GD/SH over an 11-year period amongst medical students at a Swedish university., Methods: In 2002, a questionnaire (n = 622) was mailed to medical students' home addresses. It was repeated in 2013 and then distributed during mandatory lectures (n = 856). The questions used a behavioristic approach and asked about specific GH/SH experiences. Participation was voluntary and anonymous. The changes in prevalence over time were calculated by sampling weights in order to obtain comparable estimates, representative of both cohorts., Results: The response frequency was 55% (62% women) in 2002 and 81% (59% women) in 2013. The prevalence of GD tended to decrease for male and clinical students in comparison to female and pre-clinical peers. However, the prevalence of SH increased for female compared to male students. The ratio of SH for female pre-clinical students doubled in many instances; most often, the mistreatment occurred in the clinic. Medical doctors were indicated as perpetrators up to five times more often by all students in 2013., Conclusion: Our results show a disproportional change in exposure to GD/SH between female and male medical students, resulting in a widening of the gender gap regarding prevalence of GD and SH between 2002 and 2013. In particular, personal experiences of SH increased for both sexes. It is proof that institutional efforts to fight mistreatment might be ineffective.

The aim of this study was to identify asthma phenotypes through cluster analysis. Cluster analysis was performed using self-reported characteristics from a cohort of 1291 Swedish asthma patients. Disease burden was measured using the Asthma Control Test (ACT), the mini Asthma Quality of Life Questionnaire (mini-AQLQ), exacerbation frequency and asthma severity. Validation was performed in 748 individuals from the same geographical region. Three clusters; early onset predominantly female, adult onset predominantly female and adult onset predominantly male, were identified. Early onset predominantly female asthma had a higher burden of disease, the highest exacerbation frequency and use of inhaled corticosteroids. Adult onset predominantly male asthma had the highest mean score of ACT and mini-AQLQ, the lowest exacerbation frequency and higher proportion of subjects with mild asthma. These clusters, based on information from clinical questionnaire data, might be useful in primary care settings where the access to spirometry and biomarkers is limited.

Teratoma is a germ cell neoplasm composed of tissue derived from at least two of three blastodermic embryonic layers (ectoderm, mesoderm and endoderm). The incidence of teratoma in the head and neck region is rare, in particularly in adults., A Case Report: We reported an uncommon case of teratoma in a 30 years male with a mass in the right fronto-temporal region of the face. Magnetic resonance imaging revealed a well encapsulated heterogenous mass with solid-cystic component extending from the fissure zygomatofrontal and the fissure zygomato-temporal. Serum alfa-fetoprotein levels were not elevated. Surgery was performed, the mass was completely removed, and microscopical analysis confirmed a diagnosis of mature benign teratoma. The patients showed no clinical signs of recurrence in 10 years follow-up. This case of teratoma is extraordinary due to three reasons: the location, the age of patient and benign nature of the tumor in patient at this age. Because such tumors occur exceptionally, each case should be studied with a long-term follow-up and reported., (© 2019 MEDPRESS.)

Background: Middle ear (intratympanic, IT) administration is a promising therapeutic method as it offers the possibility of achieving high inner ear drug concentrations with low systemic levels, thus minimizing the risk of systemic side effects and drug-drug interactions. Premature elimination through the Eustachian tube may be reduced by stabilizing drug solutions with a hydrogel, but this raises the secondary issue of conductive hearing loss., Aim: This study aimed to investigate the properties of a chitosan-based particulate hydrogel formulation when used as a drug carrier for IT administration in an in vivo model of ototoxicity., Materials and Methods: Two particulate chitosan-based IT delivery systems, Thio-25 and Thio-40, were investigated in albino guinea pigs ( n = 94). Both contained the hearing protecting drug candidate sodium thiosulfate with different concentrations of chitosan gel particles (25% vs. 40%). The safety of the two systems was explored in vivo . The most promising system was then tested in guinea pigs subjected to a single intravenous injection with the anticancer drug cisplatin (8 mg/kg b.w.), which has ototoxic side effects. Hearing status was evaluated with acoustically evoked frequency-specific auditory brainstem response (ABR) and hair cell counting. Finally, in vivo magnetic resonance imaging was used to study the distribution and elimination of the chitosan-based system from the middle ear cavity in comparison to a hyaluronan-based system., Results: Both chitosan-based IT delivery systems caused ABR threshold elevations ( p < 0.05) that remained after 10 days ( p < 0.05) without evidence of hair cell loss, although the elevation induced by Thio-25 was significantly lower than for Thio-40 ( p < 0.05). Thio-25 significantly reduced cisplatin-induced ABR threshold elevations ( p < 0.05) and outer hair cell loss ( p < 0.05). IT injection of the chitosan- and hyaluronan-based systems filled up most of the middle ear space. There were no significant differences between the systems in terms of distribution and elimination., Conclusion: Particulate chitosan is a promising drug carrier for IT administration. Future studies should assess whether the physical properties of this technique allow for a smaller injection volume that would reduce conductive hearing loss.

Dermal fibroblasts are the main cell type present in skin connective tissue (dermis). Fibroblasts interact with epidermal cells during hair development and in interfollicular skin. Moreover, they play an essential role during cutaneous wound healing and in bioengineering of skin. Hence, culture of primary fibroblast is gaining in importance. In addition, fibroblasts established from skin biopsies provide a powerful tool for investigating normal skin physiology or specific disease states. In this chapter, detailed procedures for establishing and maintaining primary cultures of adult human dermal fibroblasts are described.