Allergic rhinoconjunctivitis doubles the risk for incident asthma – Results from a population study in Helsinki, Finland

SummaryObjectiveTo examine the incidence of allergic rhinoconjunctivitis and asthma, and to assess allergic rhinoconjunctivitis as a risk factor for incident asthma, we performed a 11-year follow-up postal survey.MethodsThe original study population was a random population sample of 8000 inhabitants of Helsinki aged 20–69 years in 1996. Participants in the first postal questionnaire survey, 6062 subjects, were invited to this follow-up study, and provided 4302 (78%) answers out of 5484 traced subjects in 2007.ResultsCumulative incidence of asthma from 1996 to 2007 was 4.0% corresponding to an annual incidence rate of 3.7/1000/year. After exclusion of those with asthma medication or physician-diagnosed chronic bronchitis or COPD at baseline in 1996, the cumulative incidence decreased to 3.5% (incidence rate 3.2/1000/year), and further to 2.7% (2.5/1000/year) when also those reporting recurrent wheeze or shortness of breath during the last year in 1996 were omitted from the population at risk. Remission of asthma occurred in 43 subjects and was 16.9% over 11 years. Cumulative 11-year incidence of allergic rhinoconjunctivitis was 16.9% corresponding to 16.8/1000/year, and cumulative remission was 18.1%. Incidence of allergic rhinoconjunctivitis was significantly lower among those who had lived in the countryside or on a farm during the first 5 years of life, but this was not true for asthma. In multivariate analysis, farm living during the first 5 years of life was protective for the development of allergic rhinoconjunctivitis, OR 0.75 (95%CI 0.57–0.99). Allergic rhinoconjunctivitis was a significant independent risk factor for incident asthma, OR 2.15 (95%CI 1.54–3.02). In the cohort, the prevalence of rhinoconjunctivitis increased from 38.0% in 1996 to 40.9% in 2007, physician-diagnosed asthma from 6.8% to 9.4%, while current smoking decreased from 31.3% to 23.3%.ConclusionIncidence of allergic rhinoconjunctivitis was higher than in earlier studies, while asthma incidence remained on similar level, both being significantly higher in women. Allergic rhinoconjunctivitis doubled the risk for incident asthma

State diagrams of the heart – a new approach to describing cardiac mechanics

<p>Abstract</p> <p>Background</p> <p>Cardiac time intervals have been described as a measure of cardiac performance, where prolongation, shortening and delay of the different time intervals have been evaluated as markers of cardiac dysfunction. A relatively recently developed method with improved ability to measure cardiac events is Tissue Doppler Imaging (TDI), allowing accurate measurement of myocardial movements.</p> <p>Methods</p> <p>We propose the state diagram of the heart as a new visualization tool for cardiac time intervals, presenting comparative, normalized data of systolic and diastolic performance, providing a more complete overview of cardiac function. This study aimed to test the feasibility of the state diagram method by presenting examples demonstrating its potential use in the clinical setting and by performing a clinical study, which included a comparison of the state diagram method with established echocardiography methods (E/E' ratio, LVEF and WMSI). The population in the clinical study consisted of seven patients with non ST-elevation myocardial infarction (NSTEMI) and seven control subjects, individually matched according to age and gender. The state diagram of the heart was generated from TDI curves from seven positions in the myocardium, visualizing the inter- and intraventricular function of the heart by displaying the cardiac phases.</p> <p>Results</p> <p>The clinical examples demonstrated that the state diagram allows for an intuitive visualization of pathological patterns as ischemia and dyssynchrony. Further, significant differences in percentage duration between the control group and the NSTEMI group were found in eight of the totally twenty phases (10 phases for each ventricle), e.g. in the transition phases (Pre-Ejection and Post-Ejection). These phases were significantly longer (> 2.18%) for the NSTEMI group than for the control group (p < 0.05). No significant differences between the groups were found for the established echocardiography methods.</p> <p>Conclusion</p> <p>The test results clearly indicate that the state diagram has potential to be an efficient tool for visualization of cardiac dysfunction and for detection of NSTEMI.</p

Up-to-date on mortality in COPD - report from the OLIN COPD study

<p>Abstract</p> <p>Background</p> <p>The poor recognition and related underdiagnosis of COPD contributes to an underestimation of mortality in subjects with COPD. Data derived from population studies can advance our understanding of the true burden of COPD. The objective of this report was to evaluate the impact of COPD on mortality and its predictors in a cohort of subjects with and without COPD recruited during the twenty first century.</p> <p>Methods</p> <p>All subjects with COPD (n = 993) defined according to the GOLD spirometric criteria, FEV₁/FVC < 0.70, and gender- and age-matched subjects without airway obstruction, non-COPD (n = 993), were identified in a clinical follow-up survey of the Obstructive Lung Disease in Northern Sweden (OLIN) Studies cohorts in 2002-2004. Mortality was observed until the end of year 2007. Baseline data from examination at recruitment were used in the risk factor analyses; age, smoking status, lung function (FEV₁% predicted) and reported heart disease.</p> <p>Results</p> <p>The mortality was significantly higher among subjects with COPD, 10.9%, compared to subjects without COPD, 5.8% (p < 0.001). Mortality was associated with higher age, being a current smoker, male gender, and COPD. Replacing COPD with FEV₁% predicted in the multivariate model resulted in the decreasing level of FEV₁being a significant risk factor for death, while heart disease was not a significant risk factor for death in any of the models.</p> <p>Conclusions</p> <p>In this cohort COPD and decreased FEV₁were significant risk factors for death when adjusted for age, gender, smoking habits and reported heart disease.</p

In silico druggability assessment of the NUDIX hydrolase protein family as a workflow for target prioritization

Computational chemistry has now been widely accepted as a useful tool for shortening lead times in early drug discovery. When selecting new potential drug targets, it is important to assess the likelihood of finding suitable starting points for lead generation before pursuing costly high-throughput screening campaigns. By exploiting available high-resolution crystal structures, an in silico druggability assessment can facilitate the decision of whether, and in cases where several protein family members exist, which of these to pursue experimentally. Many of the algorithms and software suites commonly applied for in silico druggability assessment are complex, technically challenging and not always user-friendly. Here we applied the intuitive open access servers of DoGSite, FTMap and CryptoSite to comprehensively predict ligand binding pockets, druggability scores and conformationally active regions of the NUDIX protein family. In parallel we analyzed potential ligand binding sites, their druggability and pocket parameter using Schrödinger's SiteMap. Then an in silico docking cascade of a subset of the ZINC FragNow library using the Glide docking program was performed to assess identified pockets for large-scale small-molecule binding. Subsequently, this initial dual ranking of druggable sites within the NUDIX protein family was benchmarked against experimental hit rates obtained both in-house and by others from traditional biochemical and fragment screening campaigns. The observed correlation suggests that the presented user-friendly workflow of a dual parallel in silico druggability assessment is applicable as a standalone method for decision on target prioritization and exclusion in future screening campaigns

Expression of Concern: Redox modification of cysteine residues regulates the cytokine activity of high mobility group box-1 (HMGB1) (Molecular Medicine (2012) 18 (250-259) DOI: 10.2119/molmed.2011.00389)

© The Author(s). 2020. The Editors-in-Chief would like to alert readers that this article (Yang et al. 2012) is part of an investigation being conducted by the journal following the conclusions of an institutional enquiry at the University of Liverpool with respect to the quantitative mass spectrometrygenerated results regarding acetylated and redox-modified HMGB1. Appropriate editorial action will be taken once the investigation is concluded. Huan Yang, Peter Lundbäck, Lars Ottosson, Helena Erlandsson-Harris, Emilie Venereau, Marco E. Bianchi, Yousef Al-Abed, Ulf Andersson, and Kevin J. Tracey agree to this editorial expression of concern. Daniel J. Antoine has not responded to any correspondence from the editor/publisher about this editorial expression of concern

Multimorbidity in Finnish and Swedish speaking Finns; association with daily habits and socioeconomic status - Nordic EpiLung cross-sectional study

Multimorbidity is an emerging public health priority. This study aims to assess the role of lifestyle and socioeconomic status in the prevalence of multimorbidity and chronic diseases by using two language groups that are part of the same genetic subgroup but differ by daily habits. We conducted a cross-sectional survey in 2016 with randomly selected population sample with 4173 responders (52.3%) aged 20-69 years in Western Finland. We included 3864 Finnish participants with Swedish (28.1%) or Finnish (71.9%) as a native language. We used a questionnaire to assess participants' chronic diseases and lifestyle. We determined multimorbidity as a disease count >= 2. Finnish speakers were more likely to have a diagnosis of COPD, heart failure, diabetes, reflux disease, chronic kidney failure, and painful conditions than Swedish speakers. The prevalence of multimorbidity was higher for Finnish speakers in the age group of 60-69 years (41.0% vs. 32.0%, p = 0.018) than Swedish speakers. A higher proportion of Finnish speakers smoked, were obese, inactive, and had lower socioeconomic status compared to Swedish speakers. All these factors, in addition to age and female sex, were significant risk factors for multimorbidity. Prevalence of multimorbidity was different in two language groups living in the same area and was associated with differences in lifestyle factors such as smoking, physical inactivity and obesity.Peer reviewe

Age-specific incidence of allergic and non-allergic asthma

Background Onset of allergic asthma has a strong association with childhood but only a few studies have analyzed incidence of asthma from childhood to late adulthood in relation to allergy. The purpose of the study was to assess age-specific incidence of allergic and non-allergic asthma. Methods Questionnaires were sent to 8000 randomly selected recipients aged 20-69 years in Finland in 2016. The response rate was 52.3% (n = 4173). The questionnaire included questions on e.g. atopic status, asthma and age at asthma diagnosis. Asthma was classified allergic if also a physician-diagnosed allergic rhinitis was reported. Results The prevalence of physician-diagnosed asthma and allergic rhinitis were 11.2 and 17.8%, respectively. Of the 445 responders with physician-diagnosed asthma, 52% were classified as allergic and 48% as non-allergic. Median ages at diagnosis of allergic and non-allergic asthma were 19 and 35 years, respectively. Among subjects with asthma diagnosis at ages 0-9, 10-19, 20-29, 30-39, 40-49, 50-59 and 60-69 years, 70, 62, 58, 53, 38, 19 and 33%, respectively, were allergic. For non-allergic asthma, the incidence rate was lowest in children and young adults (0.7/1000/year). It increased after middle age and was highest in older age groups (2.4/1000/year in 50-59 years old). Conclusions The incidence of allergic asthma is highest in early childhood and steadily decreases with advancing age, while the incidence of non-allergic asthma is low until it peaks in late adulthood. After approximately 40 years of age, most of the new cases of asthma are non-allergic.Peer reviewe

Age- and gender-specific incidence of new asthma diagnosis from childhood to late adulthood

Background: Asthma is currently divided into different phenotypes, with age at onset as a relevant differentiating factor. In addition, asthma with onset in adulthood seems to have a poorer prognosis, but studies investigating age-specific incidence of asthma with a wide age span are scarce. Objective: To evaluate incidence of asthma diagnosis at different ages and differences between child- and adult-diagnosed asthma in a large population-based study, with gender-specific analyzes included. Methods: In 2016, a respiratory questionnaire was sent to 8000 randomly selected subjects aged 20-69 years in western Finland. After two reminders, 4173 (52.3%) subjects responded. Incidence rate of asthma was retrospectively estimated based on the reported age of asthma onset. Adult-diagnosed asthma was defined as a physician-diagnosis of asthma made at >= 18 years of age. Results: Among those with physician-diagnosed asthma, altogether, 63.7% of subjects, 58.4% of men and 67.8% of women, reported adult-diagnosed asthma. Incidence of asthma diagnosis was calculated in 10-year age groups and it peaked in young boys (0-9 years) and middle-aged women (40-49 years) and the average incidence rate during the examined period between 1946 and 2015 was 2.2/1000/year. Adult-diagnosed asthma became the dominant phenotype among those with physician-diagnosed asthma by age of 50 years and 38 years in men and women, respectively. Conclusions: Asthma is mainly diagnosed during adulthood and the incidence of asthma diagnosis peaks in middle-aged women. Asthma diagnosed in adulthood should be considered more in clinical practice and management guidelines.Peer reviewe

Asthma Remission by Age at Diagnosis and Gender in a Population-Based Study

BACKGROUND: Child-onset asthma is known to remit with high probability, but remission in adult-onset asthma is seem-ingly less frequent. Reports of the association between remission and asthma age of onset up to late adulthood are scarce. OBJECTIVE: To evaluate the association between asthma remission, age at diagnosis and gender, and assess risk factors of nonremission. METHODS: In 2016, a random sample of 16,000 subjects aged 20 to 69 years from Helsinki and Western Finland were sent a FinEsS questionnaire. Physician-diagnosed asthma was catego-rized by age at diagnosis to early-(0-11 years), intermediate-(12-39 years), and late-diagnosed (40-69 years) asthma. Asthma remission was defined by not having had asthma symptoms and not having used asthma medication in the past 12 months. RESULTS: Totally, 8199 (51.5%) responded, and 879 reported physician-diagnosed asthma. Remission was most common in early-diagnosed (30.2%), followed by intermediate-diagnosed (17.9%), and least common in late-diagnosed asthma (5.0%) (P < .001), and the median times from diagnosis were 27, 18.5, and 10 years, respectively. In males, the corresponding remission rates were 36.7%, 20.0%, and 3.4%, and in females, 20.4%, 16.6%, and 5.9% (gender difference P < .001). In multivariable binary logistic regression analysis, signifi-cant risk factors of asthma nonremission were intermediate (odds ratio [OR] = 2.15, 95% confidence interval: 1.373.36) and late diagnosis (OR = 11.06, 4.82-25.37) compared with early diagnosis, chronic obstructive pulmonary disease (COPD) (OR = 5.56, 1.26-24.49), allergic rhinitis (OR = 2.28, 1.50-3.46), and family history of asthma (OR = 1.86, 1.22-2.85). Results were similar after excluding COPD. CONCLUSION: Remission was rare in adults diagnosed with asthma after age 40 years in both genders. Late-diagnosed asthma was the most significant independent risk factor for nonremission. (C) 2020 American Academy of Allergy, Asthma & ImmunologyPeer reviewe