Occupational exposure to vapors, gasses, dusts, and fumes in relation to causes of death during 24 years in Helsinki, Finland.

PURPOSE: Environmental particulate matter (PM) exposure has been shown to cause excess all-cause and disease-specific mortality. Our aim was to compare disease-specific mortality by estimated occupational exposure to vapors, gasses, dusts, and fumes (VGDF). METHODS: The data source is the Helsinki part of the population-based FinEsS study on chronic obstructive pulmonary diseases including information on age, education level, main occupation, sex, and tobacco smoking combined with death registry information. We compared estimated VGDF exposure to mortality using adjusted competing-risks regression for disease-specific survival analysis for a 24-year follow-up. RESULTS: Compared to the no-exposure group, the high occupational VGDF exposure group had sub-hazard ratios (sHR) of 1.7 (95% CI 1.3-2.2) for all cardiovascular-related and sHR 2.1 (1.5-3.9) for just coronary artery-related mortality. It also had sHR 1.7 (1.0-2.8) for Alzheimer's or vascular dementia-related mortality and sHR 1.7(1.2-2.4) for all respiratory disease-related mortality. CONCLUSION: Long-term occupational exposure to VGDF increased the hazard of mortality- to cardiovascular-, respiratory-, and dementia-related causes. This emphasizes the need for minimizing occupational long-term respiratory exposure to dust, gasses, and fumes.

Agreement between self-reported and registered age at asthma diagnosis in Finland.

INTRODUCTION: In epidemiological studies, the age at asthma onset is often defined by patients' self-reported age at diagnosis. The reliability of this report might be questioned. Our objective was to evaluate the agreement between self-reported and registered age at asthma diagnosis and assess features contributing to the agreement. METHODS: As part of the FinEsS respiratory survey in 2016, randomly selected population samples of 13,435 from Helsinki and 8000 from Western Finland were studied. Self-reported age at asthma diagnosis was compared to age at asthma diagnosis registered in the Finnish register on special reimbursement for asthma medication. The reimbursement right is based on lung function criteria according to GINA and Finnish guidelines. If the difference was less than 5 years, self-reported diagnosis was considered reliable. Features associated with the difference between self-reported and registered age at asthma diagnosis were evaluated. RESULTS: Altogether 197 subjects from Helsinki and 144 from Western Finland were included. Of these, 61.9% and 77.8%, respectively, reported age at diagnosis reliably. Median difference between self-reported and registered age at diagnoses was - 2.0 years (IQR - 9.0 to 0) in Helsinki and - 1.0 (IQR - 4.3 to 0) in Western Finland indicating earlier self-reported age at diagnosis. More reliable self-report was associated with non-allergic subjects and subjects who reported having asthma diagnosis more recently. CONCLUSIONS: Agreement between self-reported and registered age at asthma diagnosis was good especially with adult-onset asthma patients. Poor agreement in early-onset asthma could be related to delay in registration due to reimbursement criteria.

Exogenous female sex steroid hormones and new-onset asthma in women: a matched case-control study.

BACKGROUND: Evidence on the role of exogenous female sex steroid hormones in asthma development in women remains conflicting. We sought to quantify the potential causal role of hormonal contraceptives and menopausal hormone therapy (MHT) in the development of asthma in women. METHODS: We conducted a matched case-control study based on the West Sweden Asthma Study, nested in a representative cohort of 15,003 women aged 16-75 years, with 8-year follow-up (2008-2016). Data were analyzed using Frequentist and Bayesian conditional logistic regression models. RESULTS: We included 114 cases and 717 controls. In Frequentist analysis, the odds ratio (OR) for new-onset asthma with ever use of hormonal contraceptives was 2.13 (95% confidence interval [CI] 1.03-4.38). Subgroup analyses showed that the OR increased consistently with older baseline age. The OR for new-onset asthma with ever MHT use among menopausal women was 1.17 (95% CI 0.49-2.82). In Bayesian analysis, the ORs for ever use of hormonal contraceptives and MHT were, respectively, 1.11 (95% posterior interval [PI] 0.79-1.55) and 1.18 (95% PI 0.92-1.52). The respective probability of each OR being larger than 1 was 72.3% and 90.6%. CONCLUSIONS: Although use of hormonal contraceptives was associated with an increased risk of asthma, this may be explained by selection of women by baseline asthma status, given the upward trend in the effect estimate with older age. This indicates that use of hormonal contraceptives may in fact decrease asthma risk in women. Use of MHT may increase asthma risk in menopausal women.

Severe asthma trajectories in adults: findings from the NORDSTAR cohort.

BACKGROUND: There is limited evidence on the pathways leading to severe asthma and we are presently unable to effectively predict the progression of the disease. We aimed to describe the longitudinal trajectories leading to severe asthma and to describe clinical events preceding disease progression in a nationwide population of patients with severe asthma. METHODS: We conducted an observational study based on Swedish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform. We identified adult patients with severe asthma in 2018 according to the European Respiratory Society/American Thoracic Society definition and used latent class analysis to identify trajectories of asthma severity over a 10-year retrospective period from 2018. RESULTS: Among 169 128 asthma patients, we identified 4543 severe asthma patients. We identified four trajectories of severe asthma that were labelled as: trajectory 1 "consistently severe asthma" (n=389 (8.6%)), trajectory 2 "gradual onset severe asthma" (n=942 (20.7%)), trajectory 3 "intermittent severe asthma" (n=1685 (37.1%)) and trajectory 4 "sudden onset severe asthma" (n=1527 (33.6%)). "Consistently severe asthma" had a higher daily inhaled corticosteroid dose and more prevalent osteoporosis compared with the other trajectories. Patients with "gradual onset severe asthma" and "sudden onset severe asthma" developed type 2-related comorbidities concomitantly with development of severe asthma. In the latter group, this primarily occurred within 1-3 years preceding onset of severe asthma. CONCLUSIONS: Four distinct trajectories of severe asthma were identified illustrating different patterns of progression of asthma severity. This may eventually enable the development of better preventive management strategies in severe asthma.

Sensitization to molecular dog allergens in an adult population: Results from the West Sweden Asthma Study.

BACKGROUND: As the prevalence of dog allergy rises, component resolved diagnosis might improve the diagnosis, understanding of the clinical outcomes and the effectiveness of immunotherapy. Considering the paucity of data in adults, the current study characterized the patterns of sensitization to dog molecular allergens in an adult population. METHODS: Data were derived from the West Sweden Asthma Study, a population-based and representative sample of adults from western Sweden. Of the 2006 subjects clinically examined, 313 participants sensitized to whole dog allergen extract were measured for specific immunoglobulin E (sIgE) levels to Can f 1, Can f 2, Can f 3, Can f 4, Can f 5 and Can f 6 using ImmunoCAP™. Polysensitization was defined as sensitization to ≥3 components. Overlapping sensitization was defined as having concomitant sensitization to at least two dog molecular allergen families (lipocalin, albumin or prostatic kallikrein). RESULTS: Of 313, 218 (70%) subjects tested positive to at least one dog allergen component. Sensitization to Can f 1 (43%) was the most common, followed by Can f 5 (33%) among molecular allergens, while sensitization to lipocalins (56%) was the most common among component families. Polysensitization was found in 22% of all participants and was more common in participants with than in those without asthma. Subjects with asthma were less likely to be monosensitized to Can f 5 than those without asthma. Subjects with asthma had higher IgE levels of Can f 3, Can f 4 and Can f 6 than those without asthma. Overlapping sensitizations also differed between those with asthma and allergic rhinitis and those without. CONCLUSION: Increased knowledge about the sensitization patterns of dog allergen components can aid in defining their role in asthma and rhinitis. In complex clinical cases of dog allergy, a detailed analysis of dog allergen components can provide additional information on the nature of sensitization.

Comparison of clinician diagnosis of COVID-19 with real time polymerase chain reaction in an adult-representative population in Sweden.

BACKGROUND: Due to the high transmissibility of SARS-CoV-2, accurate diagnosis is essential for effective infection control, but the gold standard, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), is costly, slow, and test capacity has at times been insufficient. We compared the accuracy of clinician diagnosis of COVID-19 against RT-PCR in a general adult population. METHODS: COVID-19 diagnosis data by 30th September 2021 for participants in an ongoing population-based cohort study of adults in Western Sweden were retrieved from registers, based on positive RT-PCR and clinician diagnosis using recommended ICD-10 codes. We calculated accuracy measures of clinician diagnosis using RT-PCR as reference for all subjects and stratified by age, gender, BMI, and comorbidity collected pre-COVID-19. RESULTS: Of 42,621 subjects, 3,936 (9.2%) and 5705 (13.4%) had had COVID-19 identified by RT-PCR and clinician diagnosis, respectively. Sensitivity and specificity of clinician diagnosis against RT-PCR were 78% (95%CI 77-80%) and 93% (95%CI 93-93%), respectively. Positive predictive value (PPV) was 54% (95%CI 53-55%), while negative predictive value (NPV) was 98% (95%CI 98-98%) and Youden's index 71% (95%CI 70-72%). These estimates were similar between men and women, across age groups, BMI categories, and between patients with and without asthma. However, while specificity, NPV, and Youden's index were similar between patients with and without chronic obstructive pulmonary disease (COPD), sensitivity was slightly higher in patients with (84% [95%CI 74-90%]) than those without (78% [95%CI 77-79%]) COPD. CONCLUSIONS: The accuracy of clinician diagnosis for COVID-19 is adequate, regardless of gender, age, BMI, and asthma, and thus can be used for screening purposes to supplement RT-PCR.

Siblings and risk of allergic rhinitis: A systematic review and meta-analysis.

Following the "hygiene hypothesis" and the increase in the prevalence of atopic diseases such as allergic rhinitis, a plethora of studies have investigated the role of sibship composition as a protective factor, but findings are conflicting. The aim of this study was to synthesize the global literature linking birth order and sibship size (number of siblings) to the risk of allergic rhinitis. Fifteen databases were systematically searched, with no restrictions on publication date or language. Observational studies with defined sibship composition (birth order or sibship size) as exposure and allergic rhinitis or allergic rhinoconjunctivitis (self-reported or clinically diagnosed) as outcome were eligible. Study selection, data extraction, and quality assessment were performed independently in pairs. Relevant data were summarized in tables. Comparable numerical data were analyzed using meta-analysis with robust variance estimation (RVE). Seventy-six reports with >2 million subjects were identified. Being second- or later-born child was associated with protection against both current (pooled risk ratio [RR] 0.79, 95% CI 0.73-0.86) and ever (RR 0.77, 95% CI 0.68-0.88) allergic rhinitis. Having siblings, regardless of birth order, was associated with a decreased risk of current allergic rhinitis (RR 0.89, 95% CI 0.83-0.95) and allergic rhinoconjunctivitis (RR 0.92, 95% CI 0.86-0.98). These effects were unchanged across age, time period, and geographical regions. Our findings thus indicate that primarily, a higher birth order, and to a lesser extent the number of siblings, is associated with a lower risk of developing allergic rhinitis.

Level of education and asthma control in adult-onset asthma.

OBJECTIVE: Education in itself and as a proxy for socioeconomic status, may influence asthma control, but remains poorly studied in adult-onset asthma. Our aim was to study the association between the level of education and asthma control in adult-onset asthma. METHODS: Subjects with current asthma with onset >15 years were examined within the Obstructive Lung Disease in Northern Sweden study (OLIN, n = 593), Seinäjoki Adult Asthma Study (SAAS, n = 200), and West Sweden Asthma Study (WSAS, n = 301) in 2009-2014 in a cross-sectional setting. Educational level was classified as primary, secondary and tertiary. Uncontrolled asthma was defined as Asthma Control Test (ACT) score ≤19. Altogether, 896 subjects with complete data on ACT and education were included (OLIN n = 511, SAAS n = 200 and WSAS n = 185). RESULTS: In each cohort and in pooled data of all cohorts, median ACT score was lower among those with primary education than in those with secondary and tertiary education. Uncontrolled asthma was most common among those with primary education, especially among daily ICS users (42.6% primary, 28.6% secondary and 24.2% tertiary; p = 0.001). In adjusted analysis, primary education was associated with uncontrolled asthma in daily ICS users (OR 1.92, 95% CI 1.15-3.20). When stratified by atopy, the association between primary education and uncontrolled asthma was seen in non-atopic (OR 3.42, 95% CI 1.30-8.96) but not in atopic subjects. CONCLUSIONS: In high-income Nordic countries, lower educational level was a risk factor for uncontrolled asthma in subjects with adult-onset asthma. Educational level should be considered in the management of adult-onset asthma.

Participation in scheduled asthma follow-up contacts and adherence to treatment during 12-year follow-up in patients with adult-onset asthma.

BACKGROUND: Poor treatment compliance is a common problem in the treatment of asthma. To our knowledge, no previous long-term follow-up studies exist on how scheduled asthma follow-up contacts occur in primary health care (PHC) versus secondary care and how these contacts relate to adherence to medication and in participation to further scheduled asthma contacts. The aim of this study was to evaluate occurrence of scheduled asthma contacts and treatment compliance in PHC versus secondary care, and to identify the factors associated with non-participation to scheduled contacts. METHODS: Patients with new adult-onset asthma (n = 203) were followed for 12 years in a real-life asthma cohort of the Seinäjoki Adult Asthma Study (SAAS). The first contacts were mainly carried out in secondary care and therefore the actual follow-up time including PHC visits was 10 years. RESULTS: A majority (71%) of the patients had ≥ 2 scheduled asthma contacts during 10-year follow-up and most of them (79%) mainly in PHC. Patients with follow-up contacts mainly in PHC had better adherence to inhaled corticosteroid (ICS) medication during the whole 12-year period compared to patients in secondary care. In the study population, 29% of the patients had only 0-1 scheduled asthma contacts during the follow-up. Heavy alcohol consumption predicted poor participation in scheduled contacts. CONCLUSIONS: Patients with mainly PHC scheduled asthma contacts were more adherent to ICS medication than patients in the secondary care. Based on our results it is necessary to pay more attention to actualization of asthma follow-up visits and systematic assessment of asthma patients including evaluation of alcohol consumption. Trial registration Seinäjoki Adult Asthma Study is retrospectively registered at www.ClinicalTrials.gov with identifier number NCT02733016. Registered 11 April 2016.

Self-Reported Physician Diagnosed Asthma with COPD is Associated with Higher Mortality than Self-Reported Asthma or COPD Alone - A Prospective 24-Year Study in the Population of Helsinki, Finland.

Asthma and COPD are common chronic obstructive respiratory diseases. COPD is associated with increased mortality, but for asthma the results are varying. Their combination has been less investigated, and the results are contradictory. The aim of this prospective study was to observe the overall mortality in obstructive pulmonary diseases and how mortality was related to specific causes using postal questionnaire data. This study included data from 6,062 participants in the FinEsS Helsinki Study (1996) linked to mortality data during a 24-year follow-up. According to self-reported physician diagnosed asthma, COPD, or smoking status, the population was divided into five categories: combined asthma and COPD, COPD alone and asthma alone, ever-smokers without asthma or COPD and never-smokers without asthma or COPD (reference group). For the specific causes of death both the underlying and contributing causes of death were used. Participants with asthma and COPD had the highest hazard of mortality 2.4 (95% CI 1.7-3.5). Ever-smokers without asthma or COPD had a 9.5 (3.7-24.2) subhazard ratio (sHR) related to lower respiratory tract disease specific causes. For asthma, COPD and combined, the corresponding figures were 10.8 (3.4-34.1), 25.0 (8.1-77.4), and 56.1 (19.6-160), respectively. Ever-smokers without asthma or COPD sHR 1.7 (95% CI 1.3-2.5), and participants with combined asthma and COPD 3.5 (1.9-6.3) also featured mortality in association with coronary artery disease. Subjects with combined diseases had the highest hazard of overall mortality and combined diseases also showed the highest hazard of mortality associated with lower respiratory tract causes or coronary artery causes.Abbreviations: CigCigaretteCOPDChronic obstructive pulmonary diseaseCVDCardiovascular diseaseFEV1Forced Expiratory Volume in one secondFVCForced Vital CapacityFinEsSFinland, Estonia, and Sweden study on chronic obstructive pulmonary diseasesHRHazard RatiosHRSubhazard RatioICD-10International Statistical Classifications of Diseases and Related Health Problems (Version 10).

Menopausal hormone therapy and women's health: An umbrella review.

BACKGROUND: There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). CONCLUSIONS: MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.

Long-term prognosis of new adult-onset asthma in obese patients.

BACKGROUND: Obesity has been associated with poor outcomes of asthma in cross-sectional studies, but long-term effect of obesity on asthma remains unknown. AIMS: To study the effects of obesity, found at the time of diagnosis of adult-onset asthma, on 12-year prognosis by focusing on oral corticosteroid (OCS) use and respiratory-related hospital admissions. METHODS: Patients diagnosed with adult-onset asthma (n=203) were divided into three categories based on diagnostic body mass index (BMI) (<25 kg·m-2, 25-29.9 kg·m-2, ≥30 kg·m-2) and followed for 12 years as part of the Seinäjoki Adult Asthma Study. Self-reported and dispensed OCS were assessed for the 12-year period. Data on hospital admissions were analysed based on medical records. RESULTS: 12 years after diagnosis, 86% of the patients who were obese (BMI ≥30 kg·m-2) at diagnosis remained obese. During the follow-up, no difference was found in weight gain between the BMI categories. During the 12-year follow-up, patients obese at diagnosis reported more frequent use of OCS courses (46.9% versus 23.1%, p=0.028), were dispensed OCS more often (81.6% versus 56.9%, p=0.014) and at higher doses (median 1350 (interquartile range 280-3180) mg versus 600 (0-1650) mg prednisolone, p=0.010) compared to normal-weight patients. Furthermore, patients who were obese had more often one or more respiratory-related hospitalisations compared to normal-weight patients (38.8% versus 16.9%, p=0.033). In multivariate logistic regression analyses, obesity predicted OCS use and hospital admissions. CONCLUSIONS: In adult-onset asthma, patients obese at diagnosis mostly remained obese at long-term and had more exacerbations and respiratory-related hospital admissions compared to normal-weight patients during 12-year follow-up. Weight loss should be a priority in their treatment to prevent this outcome.

Differences in diagnostic patterns of obstructive airway disease between areas and sex in Sweden and Finland - the Nordic EpiLung study.

OBJECTIVE: To investigate the current prevalence of physician-diagnosed obstructive airway diseases by respiratory symptoms and by sex in Sweden and Finland. METHOD: In 2016, a postal questionnaire was answered by 34,072 randomly selected adults in four study areas: Västra Götaland and Norrbotten in Sweden, and Seinäjoki-Vaasa and Helsinki in Finland. RESULTS: The prevalence of asthma symptoms was higher in Norrbotten (13.2%), Seinäjoki-Vaasa (14.8%) and Helsinki (14.4%) than in Västra Götaland (10.7%), and physician-diagnosed asthma was highest in Norrbotten (13.0%) and least in Västra Götaland (10.1%). Chronic productive cough was most common in the Finnish areas (7.7-8.2% versus 6.3-6.7%) while the prevalence of physician-diagnosed chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) varied between 1.7 and 2.7% in the four areas. Among individuals with respiratory symptoms, the prevalence of asthma was most common in Norrbotten, while a diagnosis of COPD or CB was most common in Västra Götaland and Seinäjoki-Vaasa. More women than men with respiratory symptoms reported a diagnosis of asthma in Sweden and Seinäjoki-Vaasa but there were no sex differences in Helsinki. In Sweden, more women than men with symptoms of cough or phlegm reported a diagnosis of CB or COPD, while in Finland the opposite was found. CONCLUSION: The prevalence of respiratory symptoms and corresponding diagnoses varied between and within the countries. The proportion reporting a diagnosis of obstructive airway disease among individuals with respiratory symptoms varied, indicating differences in diagnostic patterns both between areas and by sex.

Relationship between age and bronchodilator response at diagnosis in adult-onset asthma.

BACKGROUND: Possible variation in bronchodilator response (BDR) according to age at the diagnosis of adult-onset asthma is unknown. Our aim was to assess if BDR in FEV1 is related to age at diagnosis of adult-onset asthma and how many subjects fulfill the 400 mL criterion of BDR, the suggested cut-off for asthma-like reversibility in asthma-COPD overlap (ACO). METHODS: A total of 1030 patients with adult-onset asthma were included; 245 from SAAS (Seinäjoki Adult Asthma Study, Finland) and 785 from COREA (Cohort for Reality and Evolution of Adult Asthma in Korea) cohorts. BDR in FEV1 at the diagnosis of asthma was assessed. Patients were divided into groups based on age at asthma diagnosis: < 40, 40-59.9, and ≥ 60 years. The cohorts were analyzed separately. RESULTS: BDR % in FEV1 did not differ between the groups of different age at asthma diagnosis and no correlation between BDR and age was found. Of patients aged ≥40 years, only 18% (SAAS-cohort) and 5% (COREA-cohort) reached the 400 mL BDR in FEV1. After exclusion of possible ACO patients, the results remained similar. CONCLUSION: By using two large cohorts of steroid-naive patients with asthma, we have shown that BDR at diagnosis of asthma is constant over large age span range, and the limit of 400 mL in BDR in FEV1 is rarely reached. TRIAL REGISTRATION: Seinäjoki Adult Asthma Study is registered at ClinicalTrials.gov with identifier number NCT02733016 .

Decreased COPD prevalence in Sweden after decades of decrease in smoking.

BACKGROUND: COPD has increased in prevalence worldwide over several decades until the first decade after the millennium shift. Evidence from a few recent population studies indicate that the prevalence may be levelling or even decreasing in some areas in Europe. Since the 1970s, a substantial and ongoing decrease in smoking prevalence has been observed in several European countries including Sweden. The aim of the current study was to estimate the prevalence, characteristics and risk factors for COPD in the Swedish general population. A further aim was to estimate the prevalence trend of COPD in Northern Sweden from 1994 to 2009. METHODS: Two large random population samples were invited to spirometry with bronchodilator testing and structured interviews in 2009-2012, one in south-western and one in northern Sweden, n = 1839 participants in total. The results from northern Sweden were compared to a study performed 15 years earlier in the same area and age-span. The diagnosis of COPD required both chronic airway obstruction (CAO) and the presence of respiratory symptoms, in line with the GOLD documents since 2017. CAO was defined as post-bronchodilator FEV1/FVC < 0.70, with sensitivity analyses based on the FEV1/FVC < lower limit of normal (LLN) criterion. RESULTS: Based on the fixed ratio definition, the prevalence of COPD was 7.0% (men 8.3%; women 5.8%) in 2009-2012. The prevalence of moderate to severe (GOLD ≥ 2) COPD was 3.5%. The LLN based results were about 30% lower. Smoking, occupational exposures, and older age were risk factors for COPD, whereof smoking was the most dominating risk factor. In northern Sweden the prevalence of COPD, particularly moderate to severe COPD, decreased significantly from 1994 to 2009, and the decrease followed a decrease in smoking. CONCLUSIONS: The prevalence of COPD has decreased in Sweden, and the prevalence of moderate to severe COPD was particularly low. The decrease follows a major decrease in smoking prevalence over several decades, but smoking remained the dominating risk factor for COPD.

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.

Immediate bronchodilator response in FEV1 as a diagnostic criterion for adult asthma.

Asthma is characterised by variable and reversible expiratory airflow limitations. Thus, it is logical to use the change in forced expiratory volume in 1 s (FEV1) in response to a bronchodilator (ΔFEV1BDR) as a diagnostic tool; increases of ≥12% and ≥200 mL from the baseline FEV1 are commonly used values. We aimed to evaluate the historical development of diagnostic cut-off levels for the ΔFEV1BDR for adults and the evidence behind these recommendations.We searched for studies from the reference lists of all the main statements, reports and guidelines concerning the interpretation of spirometry and diagnostics for asthma and conducted a literature search.A limited amount of evidence regarding the ΔFEV1BDR in healthy populations was found, and even fewer patient studies were found. In healthy persons, the upper 95th percentile for the absolute ΔFEV1BDR ranges between 240 mL and 320 mL, the relative ΔFEV1BDR calculated from the initial FEV1 ranges from 5.9% to 13.3% and the ΔFEV1BDR calculated from the predicted FEV1 ranges from 8.7% to 11.6%. However, the absolute and percentage ΔFEV1BDR values calculated from the initial FEV1 are dependent on age, sex, height and the degree of airway obstruction. Thus, the use of the ΔFEV1BDR calculated from the predicted FEV1 might be more appropriate.Not enough data exist to assess the sensitivity of any of the cut-off levels for the ΔFEV1BDR to differentiate asthma patients from healthy subjects. Further studies in newly diagnosed asthma patients are needed.

Transient Receptor Potential Ankyrin 1 Enhances Ovalbumin-Induced Acute Allergic Inflammation in Murine Models.

BACKGROUND: Transient receptor potential ankyrin 1 (TRPA1) is an ion channel known to mediate nociception and neurogenic inflammation, and to be activated by reactive oxygen and nitrogen species (ROS and RNS) produced at the sites of inflammation. Because neurogenic inflammation as well as the release of ROS and RNS are typical features of early stages of allergic responses, we hypothesized that TRPA1 may be involved in triggering and/or amplifying allergic inflammation. OBJECTIVE: This study aims at exploring the role of TRPA1 ion channel in acute ovalbumin-induced allergic inflammation in applicable murine models. METHODS: The effects of pharmacological blockade and genetic deletion of TRPA1 in ovalbumin-induced allergic conjunctivitis and acute paw inflammation were studied in mice sensitized to ovalbumin. RESULTS: Ovalbumin-induced allergic conjunctivitis was milder in TRPA1-deficient mice and alleviated in wild-type mice treated with the TRPA1 antagonist TCS 5861528. Subcutaneous challenge with ovalbumin caused a significant paw edema and interleukin (IL)-4 production in sensitized mice; these responses were attenuated in animals treated with the TRPA1 antagonist and in TRPA1-deficient mice. Interestingly, blockade of the major secondary effector of TRPA1, substance P, also resulted in attenuated ovalbumin-induced paw edema and IL-4 production. However, the splenocytes' responses to ovalbumin were similar in cells from wild-type and TRPA1-deficient mice sensitized to ovalbumin. CONCLUSION: These results introduce a novel concept that TRPA1 mediates early events in allergic inflammation, but does not seem to affect allergic sensitization, and could therefore be a novel drug target to treat conditions associated with allergic inflammation.

Chronic obstructive pulmonary disease guidelines in Europe: a look into the future.

Clinical practice guidelines are ubiquitous and are developed to provide recommendations for the management of many diseases, including chronic obstructive pulmonary disease. The development of these guidelines is burdensome, demanding a significant investment of time and money. In Europe, the majority of countries develop their own national guidelines, despite the potential for overlap or duplication of effort. A concerted effort and consolidation of resources between countries may alleviate the resource-intensity of maintaining individual national guidelines. Despite significant resource investment into the development and maintenance of clinical practice guidelines, their implementation is suboptimal. Effective strategies of guideline dissemination must be given more consideration, to ensure adequate implementation and improved patient care management in the future.