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Helena Backman,1,* Laxmi Bhatta,2,3,* Linnea Hedman,1 Ben Brumpton,2 Iida Vähätalo,4,5 Paul G Lassmann-Klee,6 Bright I Nwaru,7 Linda Ekerljung,7 Steinar Krokstad,8,9 Sigrid Anna Aalberg Vikjord,2 Anne Lindberg,10 Hannu Kankaanranta,7 Eva Rönmark,1,* Arnulf Langhammer8,* 1Section of Sustainable Health/ the OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden; 2K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology NTNU, Trondheim, Norway; 3Division of Mental Health Care, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; 4Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; 5Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 6Clinical Physiology and Nuclear Medicine Unit, Helsinki University Hospital’s Diagnostic Center and University of Helsinki, Helsinki, Finland; 7Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 8HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway; 9Nord-Trøndelag Hospital Trust, Levanger Hospital, Levanger, Norway; 10Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden*These authors contributed equally to this workCorrespondence: Helena Backman, Email helena.backman@norrbotten.seBackground and Aim: The relationship between socioeconomic status (SES), asthma and mortality is complex and multifaceted, and it is not established if educational level modifies the association between asthma and mortality. The aim was to study the association between asthma and mortality in Sweden and Norway and to what extent educational level modifies this association.Participants and Methods: Within the Nordic EpiLung Study, > 56,000 individuals aged 30– 69 years participated in population-based surveys on asthma and associated risk factors in Sweden and Norway during 2005– 2007. Data on educational level and 10-year all-cause mortality were linked by national authorities. The fraction of mortality risk attributable to asthma was calculated, and Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for mortality related to asthma, stratified by educational level.Results: In total, 5.5% of all deaths was attributed to asthma. When adjusted for potential confounders, the HR for mortality related to asthma was 1.71 (95% CI 1.52– 1.93). Those with primary level of education had higher hazard of all-cause death related to asthma than those with tertiary level (HR 1.80, 95% CI 1.48– 2.18, vs HR 1.39, 95% CI 0.99– 1.95).Conclusion: Asthma was associated with an overall 71% increased all-cause mortality and 5.5% of deaths can be attributed to asthma. Educational levels modified the risk of mortality associated with asthma, with the highest risk among those with primary education.Keywords: epidemiology, cohort, prognosis

Marta A Kisiel,1,* Martin Jacobsson,2,* 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*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

Lina Rönnebjerg,1 Malin Axelsson,2 Hannu Kankaanranta,1,3,4 Helena Backman,5 Madeleine Rådinger,1 Bo Lundbäck,1 Linda Ekerljung1 1Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 2Department of Care Science, Faculty of Health and Society, Malmö University, Malmö, Sweden; 3Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; 4Tampere University Respiratory Research Group, Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland; 5Department of Public Health and Clinical Medicine, Umeå University, Umeå, SwedenCorrespondence: Lina RönnebjergKrefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Box 424, 405 30, Gothenburg, SwedenTel +46 31 786 67 09Email lina.ronnebjerg@gu.sePurpose: Current guidelines primarily use medication levels to distinguish severe asthma from other types of asthma. In addition, severe asthma must also be uncontrolled at high-intensity treatment or become uncontrolled if treatment level is decreased. To date, only a few studies have used this definition to investigate the prevalence and clinical characteristics of severe asthma in population-based samples. Therefore, the aim of this study was to evaluate the prevalence and clinical characteristics of individuals with severe asthma in the population-representative West Sweden Asthma Study.Materials and Methods: In this cross-sectional population-based study, a randomly selected sample (n=1172) and a separate asthma sample (n=744) underwent clinical examinations, completed a structured interview and responded to questionnaires. Severe asthma was defined as at least one feature of uncontrolled asthma despite treatment in line with the Global Initiative for Asthma (GINA) steps 4/5. This treatment level required a minimum medium dose of inhaled corticosteroids (ICS) plus a second controller or oral corticosteroids.Results: The prevalence of severe asthma was 1.1% in the adult random sample and 9.5% within the asthma sample. Individuals with severe asthma were older and had more symptoms, activity limitations, heart disease and blood neutrophils compared to those with other asthma. They also had lower lung function and despite these impairments, 32% did not have annual contact with a healthcare provider.Conclusion: The prevalence of severe asthma was higher compared to previous studies, and many individuals with severe asthma did not have regular contact with healthcare providers. Due to the high burden of symptoms and impairments for individuals with severe asthma, it is important that the healthcare system implement strategies to improve follow-up and evaluate these patients according to existing guidelines.Keywords: asthma epidemiology, asthma control, asthma-medication, asthma severity symptoms, lung function

Individuals with severe asthma often report poor Health-related quality of life (HRQoL) and more research is essential to increase understanding of how they may be helped to improve HRQoL. The main aim of the current paper is to evaluate HRQoL, and possible factors influencing HRQoL, in individuals with severe asthma. The aim is also to explore associations among anxiety, depression, beliefs of medication, self-efficacy, and HRQoL among individuals with severe and other asthma as well as those with no asthma. Participants with severe asthma (n = 59), other asthma (n = 526), and no asthma (n = 902) were recruited from West Sweden Asthma Study, a population-based study, which includes both questionnaire surveys and clinical examinations. Individuals with severe asthma had worse physical HRQoL (measured with SF-8) than those with other and no asthma (median 48.4, 51.9, and 54.3, respectively). They also had worse mental HRQoL (median 46.7) and reported higher anxiety and depression scores (measured using HADS, median 5.0 and 3.5, respectively) compared to no asthma (median 4.0 and 2.0, respectively). HRQoL was particularly affected among women with severe asthma. Individuals with severe asthma believed that their asthma medication was more necessary than those with other asthma, but they reported more concern for the medication. Asthma control and packyears predicted physical HRQoL and anxiety predicted mental HRQoL among individuals with severe asthma. Efforts to improve asthma control and to reduce anxiety may improve HRQoL in individuals with severe asthma. Especially, women with severe asthma seem to need support to improve their HRQoL. Reducing concerns with asthma medication is most likely essential as high concerns may lead to poor adherence, which in turn may negatively affect asthma control and HRQoL. [ABSTRACT FROM AUTHOR]

Background Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population-based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied. Objective To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics. Material and Methods Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA2 LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire-assessed. Results Male gender ( P < 0.001), greater height ( P < 0.001) and sensitization to both perennial allergens and pollen ( P < 0.001) are related to higher FeNO levels. Current smoking ( P < 0.001) and having both parents smoking during childhood, vs. having neither ( P < 0.001) or only one parent smoking ( P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age ( P = 0.03) or 15 and 17 years of age ( P = 0.003). Conclusions and Clinical relevance Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies. [ABSTRACT FROM AUTHOR]

Background Asthma and chronic rhinosinusitis ( CRS) both impair quality of life, but the quality-of-life impact of comorbid asthma and CRS is poorly known. The aim of this study was to evaluate the impact of CRS and other relevant factors on quality of life in asthmatic subjects. Methods This Swedish cohort (age 17-76 years) consists of 605 well-characterized asthmatics with and without CRS, 110 individuals with CRS only, and 226 controls and is part of the Global Allergy and Asthma European Network ( GA2 LEN) survey. The Mini Asthma Quality of Life Questionnaire ( mAQLQ), the Euro Quality of Life ( EQ-5 D) health questionnaire, spirometry, skin prick test (SPT), exhaled nitric oxide ( Fe NO), smell test, and peak nasal inspiratory flow were used. Results Subjects having both asthma and CRS have lower mAQLQ scores in all domains ( P < 0.001) and a lower EQ-5 D index value and EQ-5 D VAS value ( P < 0.001) compared to those with asthma only. Asthmatics with CRS have significantly lower FEV1%pred and FVC%pred (88.4 [85.1-91.7] and 99.9 [96.7-103.0], respectively) compared with asthma only (91.9 [90.3-93.4] and 104.0 [102.5-105.5], respectively P < 0.05). Multiple regression analysis shows that low asthma quality of life is associated with having CRS ( P < 0.0001), lower lung function ( P = 0.008), current smoking ( P = 0.01), BMI > 30 kg/m2 ( P = 0.04), high age ( P = 0.03), and a negative SPT ( P = 0.04). Conclusions Comorbid CRS was a significant and independent negative predictor of quality of life in asthmatics. Other negative factors were lower lung function, current smoking, obesity, advanced age, and having nonatopic asthma. [ABSTRACT FROM AUTHOR]

Abstract Background Proteomic studies of respiratory disorders have the potential to identify protein biomarkers for diagnosis and disease monitoring. Utilisation of sensitive quantitative proteomic methods creates opportunities to determine individual patient proteomes. The aim of the current study was to determine if quantitative proteomics of bronchial biopsies from asthmatics can distinguish relevant biological functions and whether inhaled glucocorticoid treatment affects these functions. Methods Endobronchial biopsies were taken from untreated asthmatic patients (n = 12) and healthy controls (n = 3). Asthmatic patients were randomised to double blind treatment with either placebo or budesonide (800 μg daily for 3 months) and new biopsies were obtained. Proteins extracted from the biopsies were digested and analysed using isobaric tags for relative and absolute quantitation combined with a nanoLC-LTQ Orbitrap mass spectrometer. Spectra obtained were used to identify and quantify proteins. Pathways analysis was performed using Ingenuity Pathway Analysis to identify significant biological pathways in asthma and determine how the expression of these pathways was changed by treatment. Results More than 1800 proteins were identified and quantified in the bronchial biopsies of subjects. The pathway analysis revealed acute phase response signalling, cell-to-cell signalling and tissue development associations with proteins expressed in asthmatics compared to controls. The functions and pathways associated with placebo and budesonide treatment showed distinct differences, including the decreased association with acute phase proteins as a result of budesonide treatment compared to placebo. Conclusions Proteomic analysis of bronchial biopsy material can be used to identify and quantify proteins using highly sensitive technologies, without the need for pooling of samples from several patients. Distinct pathophysiological features of asthma can be identified using this approach and the expression of these features is changed by inhaled glucocorticoid treatment. Quantitative proteomics may be applied to identify mechanisms of disease that may assist in the accurate and timely diagnosis of asthma. Trial registration ClinicalTrials.gov registration NCT01378039

Abstract Background Little is known about prevalence and risk factors of allergic rhinitis and chronic nasal symptoms among adults in Vietnam. We aimed to estimate the prevalence, risk factor patterns and co-morbidities of allergic rhinitis and chronic nasal symptoms in one urban and one rural area in northern Vietnam. Methods A cross-sectional questionnaire survey was conducted from August 2007 to January 2008 in urban Hoankiem and rural Bavi in Hanoi among adults aged 21-70 years. Of 7008 randomly selected subjects, 91.7% participated in Bavi and 70.3% in Hoankiem. Results Allergic rhinitis ever or chronic nasal symptoms were reported by 50.2%. The prevalence of allergic rhinitis ever was considerably higher in Hoankiem compared to Bavi, 29.6% vs 10.0% (p < 0.001). Allergic rhinitis ever and chronic nasal symptoms were both significantly associated with asthma and respiratory symptoms, respectively (p < 0.001). Exposure to gas, dust or fumes at work was significantly associated with allergic rhinitis ever, OR 1.57 (95% CI 1.34 - 1.84), nasal blocking, OR 1.90 (95% CI 1.68 - 2.15) and runny nose, OR 1.32 (95% CI 1.17 - 1.49), while somewhat surprisingly no association with smoking was found. Female sex was a significant risk factor for both nasal blocking and runny nose. Conclusions Allergic rhinitis ever was considerably more common in the urban area. Nasal blocking and runny nose was each reported by about one third of the studied sample with no major urban-rural difference. Further, exposure to air pollution at work was significantly associated with allergic rhinitis ever, nasal blocking and runny nose.

Abstract Background We have previously shown that approximately 25% of those with asthma in West Sweden have multiple asthma symptoms, which may describe a group of patients with more severe disease. Furthermore, asthma is associated with several co-morbid diseases, including rhinitis and chronic rhinosinusitis. The aim of this study was to determine whether multi-symptom asthma is related to signs of severe asthma, and to investigate the association between multi-symptom asthma and different symptoms of allergic and chronic rhinosinusitis. Methods This study analyzed data on asthma symptoms, rhinitis, and chronic rhinosinusitis from the 2008 West Sweden Asthma Study, which is an epidemiologically based study using the OLIN and GA2LEN respiratory and allergy focused questionnaires. Results Multi-symptom asthma was present in 2.1% of the general population. Subjects with multi-symptom asthma had more than double the risk of having night-time awakenings caused by asthma compared with those with fewer asthma symptoms (P < 0.001). The prevalence of allergic rhinitis was similar in the fewer- and multi-symptom asthma groups, but nasal blockage and rhinorrhea were significantly increased in those with multi- versus fewer-symptom asthma (odds ratio 2.21; 95% confidence interval 1.64-2.97, versus 1.49; 1.10-2.02, respectively). Having any, or one to four symptoms of chronic rhinosinusitis significantly increased the risk of having multi- versus fewer-symptom asthma (P < 0.01). Conclusion An epidemiologically identified group of individuals with multiple asthma symptoms harbour to greater extent those with signs of severe asthma. The degree of rhinitis, described by the presence of symptoms of nasal blockage or rhinorrhea, as well as the presence of any or several signs of chronic rhinosinusitis, significantly increases the risk of having multi-symptom asthma.

Abstract Asthma prevalence has increased over the last fifty years, but the more recent changes have not been conclusively determined. Studies in children indicate that a plateau in the prevalence of asthma may have been reached, but this has not yet been confirmed in adults. Epidemiological studies have suggested that the prevalence of asthma in adults is approximately 7-10% in different parts of the western world. We have now performed a large-scale epidemiological evaluation of the prevalence of asthma and respiratory symptoms in adults between the ages of 16-75 in West Sweden. Thirty thousand randomly chosen individuals were sent a detailed questionnaire focusing on asthma and respiratory symptoms, as well possible risk factors. Sixty-two percent of the contacted individuals responded to the questionnaire. Asthma prevalence, defined as asthma diagnosed by a physician, was 8.3%. Moreover, the prevalence of respiratory symptoms was lower compared to previous studies. The most common respiratory symptom was any wheeze (16.6%) followed by sputum production (13.3%). In comparison with studies performed 18 years ago, the prevalence of asthma has not increased, and the prevalence of most respiratory symptoms has decreased. Therefore, our data argues that the continued increase in asthma prevalence that has been observed over the last half century is over.

Conclusion: Education, but not occupation, was differentially associated with adult asthma phenotypes in the general population. Further research into socioeconomic status variation in various asthma phenotypes is warranted., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Background/objectives: Quantification of diamine oxidase (DAO) concentrations in serum has been proposed as an adjunctive diagnostic modality for the evaluation of histamine intolerance (HIT). Limited empirical data exist concerning the influence of dietary patterns on DAO levels., Subjects/methods: In the context of a prospective study employing a crossover design, 18 individuals diagnosed with HIT were randomized to initiate either a low histamine diet (LHD) or a conventional mixed diet (MXD). Serum DAO concentrations were measured at the commencement of the study and following each dietary phase. A control group underwent analogous DAO assessments without imposition of dietary constraints., Results: During the time when a diet restricted in histamine was implemented, noticeable differences in changes in DAO levels did not become apparent when compared to the changes observed during the mixed (MXD) phase. Specifically, among the group, 10 of the 18 patients exhibited elevated DAO values subsequent to the LHD regimen, while the remaining eight displayed either reduced or unchanging DAO levels. The prevalence of elevated DAO levels in the LHD group did not differ significantly from that observed in the control group during the MXD phase. Additionally, during the LHD phase, patients reported a significant reduction in gastrointestinal and cutaneous symptoms., Conclusions: This prospective investigation underscores the enduring utility of a histamine-restricted diet, coupled with structured dietary reintroduction, as an efficacious diagnostic approach for individuals presenting with suspected food-related histamine hypersensitivity. Notably, the measurement of DAO levels appears to furnish only a limited capacity to discern dietary-induced fluctuations. Notwithstanding, the dynamics of DAO alteration do not appear to exhibit a discernible association with specific dietary patterns, a finding consistent across both patient and control groups., (© 2024. The Author(s).)

Background: Rhinitis encompasses diverse forms. Each form has distinct pathophysiology and clinical manifestations and may be influenced by differential risk factors. The association between socioeconomic status (SES) and different forms of rhinitis remains poorly understood. Our aim was to examine SES variations in allergic rhinitis, chronic rhinitis, and chronic rhinosinusitis in adults., Methods: Based on a 2016 postal questionnaire survey within the West Sweden Asthma Study, we analyzed data from 36,213 subjects aged 16-75 years. The measures of SES were levels of education and occupation. Adjusted logistic regression was used to examine associations between SES and the rhinitis outcomes., Results: Attaining a secondary school and tertiary education, compared to a primary school, were associated with increased risk of allergic rhinitis (secondary OR 1.33, 95% CI 1.22-1.45; tertiary 1.54, 1.41-1.69) and chronic rhinitis (secondary 1.18, 1.08-1.29; tertiary 1.17, 1.06-1.28). The influence of occupation was consistent with respect to allergic rhinitis. For instance, compared to the lowest occupational skill level, the highest level (OR 1.24, 95% CI 1.04-1.48) and the lower high occupation levels (1.24, 1.04-1.49) were associated with an increased risk of allergic rhinitis. No significant link was found between education and chronic rhinosinusitis or between occupation levels and risk of either chronic rhinitis or chronic rhinosinusitis., Conclusion: Individuals with higher education and those at higher occupational levels may be at higher risk of having different forms of rhinitis than those at lower education and occupation levels. Assessment of rhinitis burden via SES can be one strategy to develop preventive strategies., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)