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Respiratory difficulties caused by exercise-induced laryngeal obstructions (EILOs) are reported with increasing frequency. The aim of this study was to assess the prevalence and symptoms of EILOs and their relation to airway hyperresponsiveness (AHR). In total, 556 randomly selected youths in Copenhagen aged 14-24 years were invited over a 2-year period. The study included a mailed questionnaire and two visits: day 1 (an interview-based questionnaire, methacholine bronchial provocation test and physical exertion test); and day 2 [an exercise test with continuous laryngoscopic recordings (CLE test)]. The diagnosis of EILOs was based on the CLE test. In total, 237 answered the mailed questionnaire and 150 participated on day 1 whereof 98 participated on day 2 also. AHR was verified in 23 (4.1% of invitees) and EILOs in 42 (7.5% of invitees). Co-morbidity was verified in 6 cases (26.1% of verified AHR cases). No symptoms were found specific for either AHR or EILOs. The minimum prevalence of EILOs in this cohort was 7.5%. EILOs were verified in 26.1% of participants with AHR. Questionnaires could not differentiate between AHR and EILOs. [ABSTRACT FROM AUTHOR]

Background Asthma is a complex disease characterized by symptoms of wheezing, shortness of breath, chest tightness, and cough. Objective To study the relative contribution of genetic and environmental factors in the liability to asthma in a large sample of twins. Methods Data on asthma in 21 135 twin pairs, 3–71 years of age, from the Danish Twin Registry were collected via a multidisciplinary questionnaire survey. Heritability estimates were calculated using variance components models. Results A monozygotic twin had an approximately sixfold increased risk of asthma whereas a dizygotic twin only had an approximately threefold increased risk relative to the general population if his or her co-twin was affected. The difference was more pronounced among males. Familial aggregation of asthma in children and adolescents was explained mainly by additive genetic factors, but common environment was also important. The heritability of asthma was also substantial in adults aged 20–49 years. In older adults (aged 50–71 years), additive genetic factors did not significantly influence the disease risk. Conclusion Genetic influences on asthma are substantial throughout the life span but the proportion of the disease liability explained by genetic factors is decreased in older adults. Cite this as: S. F. Thomsen, S. van der Sluis, K. O. Kyvik, A. Skytthe, V. Backer, Clinical & Experimental Allergy, 2010 (40) 1054–1061. [ABSTRACT FROM AUTHOR]

Background: The comprehensive consequences of atopic dermatitis (AD) include a negative influence on work life. However, data regarding use of social benefits in patients with AD are sparse., Objective: To examine the association between AD and use of social benefits, with a specific focus on paid sick leave and disability pension., Methods: The study cohort comprises citizens born in the period 1964-1999 with a diagnosis of AD registered in the Danish National Patient Registry (DNPR) and a 20-fold match control group from the background population. Cross-linkage of data from 1964 up to 2015 by four national registers (the DNPR; the Central Person Register; the Register of Medicinal Product Statistics; and the Danish Register for Evaluation of Marginalisation) enabled the comparison of AD patients and controls with respect to social benefits. Prescription of systemic medication served as a proxy for AD severity. Social benefits were analysed as a function of AD status using Cox regression., Results: A total of 28 156 AD patients were registered in the DNPR, and the control group comprised 473 836 individuals not registered with AD in the DNPR. AD was found to be associated with increased risk of receiving social benefits, paid sick leave in particular, and most pronounced for younger patients with severe AD (OR = 1.37, 95% CI: 1.25-1.52). The use of disability pension was increased for all groups of AD patients compared to controls and most pronounced for older patients with severe AD [HR 1.67 (95% CI: 1.45-1.93)]., Conclusion: Our data emphasize that AD significantly impacts work life negatively for the patients and is a financial burden for the society., (© 2019 European Academy of Dermatology and Venereology.)

Background: Management of moderate-to-severe atopic dermatitis (AD) frequently requires treatment with systemic therapies. Dupilumab is the first biological agent approved for treatment of moderate-to-severe AD. Although promising results have appeared in clinical trials, real-life data on efficacy and safety are lacking., Objectives: To assess effectiveness and safety of treatment with dupilumab in the real-life clinical setting at a Danish tertiary referral centre., Methods: All patients with AD treated with dupilumab from October 2017 to October 2018 at Bispebjerg Hospital, Denmark, were included in the study. Patients were evaluated three times: at treatment initiation and at 1 and 3 months after first dupilumab injection. At each visit, disease activity was assessed by severity score (Eczema Area and Severity Index, EASI), patient-reported outcomes (Dermatology Life Quality Index, DLQI, pruritus and sleep score) and serological markers [immunoglobulin (Ig)E, eosinophil count and lactate dehydrogenase (LDH)]., Results: A total of 43 patients were included in the study. The mean reduction in EASI score from baseline was 19.6 points (72.4%) at 1-month and 22.6 points (76.7%) at 3-month follow-up. EASI, DLQI, pruritus score, sleep score, IgE and LDH were all statistically significantly reduced between baseline and 1- and 3-month follow-up. Mean reductions in EASI score and LDH at 3-month follow-up were significantly correlated (P = 0.003). One patient (2.3%) discontinued treatment due to side-effects, and seven patients (18.4%) developed conjunctivitis during the study period., Conclusion: The effectiveness and safety of dupilumab treatment in a real-life clinical setting are comparable to that of phase 3 clinical trials. LDH is suggested as a potential serological marker predictive of treatment response., (© 2019 European Academy of Dermatology and Venereology.)

Background: There are limited data regarding causes of mortality in patients with psoriasis or psoriatic arthritis (PsA)., Objectives: This retrospective cohort study evaluated the risk and leading causes of mortality in patients with psoriasis or PsA., Methods: Individuals with a hospital-based diagnosis of PsA or psoriasis were identified using the Danish National Patient Registry. Matched control individuals were identified from the general population. The main outcome measures were risk of death and cause-specific mortality in patients with psoriasis or PsA., Results: Death rates per 1000 patient-years (with 95% confidence intervals) vs. controls were 22·3 (19·7-24·9) vs. 13·9 (11·8-16·0) for patients with psoriasis and 10·8 (8·9-12·8) vs. 11·6 (9·6-13·6) for patients with PsA. Survival, according to stratified hazard ratios (HRs), was significantly lower in patients with psoriasis than in controls (HR 1·74, P < 0·001), but not in patients with PsA (HR 1·06, P = 0·19). Significantly increased risk of death was observed in patients with psoriasis vs. controls due to a number of causes; the highest risks were observed for diseases of the digestive system; endocrine, nutritional and metabolic diseases; and certain infectious and parasitic diseases (HRs 3·61, 3·02 and 2·71, respectively). In patients with PsA, increased mortality was observed only for certain infectious and parasitic diseases (HR 2·80) and diseases of the respiratory system (HR 1·46). Patients with psoriasis died at a younger age than controls (mean age 71·0 vs. 74·5 years, P < 0·001)., Conclusions: Patients with severe psoriasis have increased mortality risk compared with matched controls, due to a number of causes. Evidence to support an increased risk for patients with PsA was less convincing., (© 2018 British Association of Dermatologists.)

Secukinumab (anti-IL17A) is effective as treatment for moderate to severe plaque psoriasis, but real-life data on effectiveness and safety lack. We aimed to present real-life data of all Danish patients treated with secukinumab (n = 69). At baseline, before initiation of treatment with secukinumab 300 mg (47.8%) or off-label treatment with secukinumab 150 mg (52.2%), the median PASI score was 7.1. A total of 66.7% (34/51) and 52.9% (27/51) of patients still on secukinumab at week 12 achieved a PASI (Psoriasis Area and Severity Index)-50 and PASI-75 of 66.7% and 52.9%, respectively. A total of 83.0% (44/53) and 60.4% (32/53) of the patients had a PASI-score < 5 and PASI-score < 2, respectively, after 12 weeks on treatment with secukinumab. A third of the patients had secukinumab discontinued due to limited clinical improvement or adverse events (n = 23) within a median of 92 days (interquartile range 51-212 days). Notably, the majority of the patients may represent a particularly difficult-to-treat group of patients, as 92.8% had been refractory to other biologic treatment. A total of 26.1% (n = 18) experienced adverse events. Secukinumab appears to be an effective treatment option with a favorable side effect profile in patients with plaque psoriasis who are refractory to or have side effects of traditional biologic drugs., (© 2017 Wiley Periodicals, Inc.)

Background: Eosinophil cationic protein (ECP) is one of four basic proteins of the secretory granules of eosinophils. It has a variety of functions associated with inflammatory responses. Little is known about the causes for variation in serum ECP levels., Aim: To identify factors associated with variation in serum ECP and to determine the relative proportion of the variation in ECP due to genetic and non-genetic factors, in an adult twin sample., Methods: A sample of 575 twins, selected through a proband with self-reported asthma, had serum ECP, lung function, airway responsiveness to methacholine, exhaled nitric oxide, and skin test reactivity, measured. Linear regression analysis and variance component models were used to study factors associated with variation in ECP and the relative genetic influence on ECP levels., Results: Sex (regression coefficient = -0.107, P < 0.001), body mass index (BMI) (0.007, P = 0.028), and airway responsiveness to methacholine (0.074, P = 0.001) were significantly associated with ECP. Adjusted for these factors, ECP correlated 0.53 (P < 0.001) and 0.27 (P = 0.001) in monozygotic and dizygotic twins, respectively (P-value for difference = 0.05). According to the most parsimonious variance component model, genetic factors accounted for 57% (CI: 42-72%, P < 0.001) of the variance in ECP levels, whereas the remainder (43%) was ascribable to non-shared environmental factors. The genetic correlation between ECP and airway responsiveness to methacholine was statistically non-significant (r = -0.11, P = 0.50)., Conclusion: Around half of all variance in serum ECP is explained by genetic factors. Serum ECP is influenced by sex, BMI, and airway responsiveness. Serum ECP and airway responsiveness seem not to share genetic variance., (© 2014 John Wiley & Sons Ltd.)

Background: Skin diseases are the most frequently recognized occupational diseases in Denmark. The prognosis for occupational contact dermatitis is often poor., Objectives: To investigate the prognosis, assessed by eczema, job status and skin-related quality of life, among patients allergic to rubber chemicals and latex (ubiquitous allergens) and epoxy (nonubiquitous allergen), 2 years after recognition of occupational allergic contact dermatitis., Methods: From a cohort of all patients recognized as having occupational dermatitis by the Danish National Board of Industrial Injuries in 2010, 199 patients with relevant rubber allergy (contact allergy to rubber chemicals or contact urticaria from latex) or epoxy allergy were identified. Follow-up consisted of a questionnaire covering current severity of eczema, employment, exposure and quality of life., Results: The response rate was 75%. Clearance of eczema was reported by 11% of patients and 67% reported improvement. Overall 22% of patients with allergy to a nonubiquitous allergen had total clearance of eczema compared with 10% of cases allergic to ubiquitous allergens and 0% of those with contact urticaria (P = 0·116). Improvement was significantly more frequent in those who had changed jobs compared with those who had not (P = 0·01)., Conclusions: At follow-up, patients with contact urticaria had significantly poorer prognosis than those with contact allergy, and there was a trend towards a poorer prognosis for those with contact allergy to rubber chemicals than those with allergy to epoxy. A significant positive association between job change and improvement was found., (© 2013 British Association of Dermatologists.)

Background: Previous twin studies have shown greater concordance rates for psoriasis in MZ than in DZ twins, and heritability estimates between 66% and 90%. This supports a genetic influence on psoriasis, but also highlights the fact that genes are not the only explanation for the disease., Objectives: To study the concordance of psoriasis in a population-based twin sample., Methods: Data on psoriasis in 10 725 twin pairs, aged 20-71 years, from the Danish Twin Registry was collected via a questionnaire survey. The concordance and heritability of psoriasis were estimated., Results: In total, 4·1% of the men and 4·2% of the women had a lifetime history of psoriasis. The proband-wise concordance for psoriasis was larger in monozygotic than in dizygotic twins, 0·33 vs. 0·17. Genetic factors explained 68% (60-75%) of the variation in the susceptibility to psoriasis, whereas the rest of the variation was explained by nonshared environmental factors., Conclusion: The results confirm that psoriasis is a complex multifactorial disease controlled by both exogenous and endogenous factors., (© 2013 The Authors BJD © 2013 British Association of Dermatologists.)

Background: Sarcoidosis is a multiorgan granulomatous inflammatory disease of unknown aetiology. Familial clustering of cases and ethnic variation in the epidemiology suggests a genetic influence on susceptibility to the disease. This paper reports twin concordance and heritability estimates of sarcoidosis in order to assess the overall contribution of genetic factors to the disease susceptibility., Methods: Monozygotic and dizygotic twins enrolled in the Danish and the Finnish population-based national twin cohorts (61,662 pairs in total) were linked to diagnostic information on sarcoidosis obtained from the Danish National Patient Registry or the Social Insurance Institution, Finland registry of reimbursed medication using the 8th and 10th editions of the International Classification of Diseases. The Fisher exact test was used to compare probandwise concordance rates in different zygosity groups. Heritability was estimated based on a multifactorial threshold liability model., Results: A total of 210 twin pairs with at least one proband with a diagnosis of sarcoidosis were identified. The probandwise concordance rate was higher in monozygotic than in dizygotic twins (0.148 vs 0.012). Compared with the general population there was an 80-fold increased risk of developing sarcoidosis in co-twins of affected monozygotic brothers or sisters. The increased risk in dizygotic twins was only 7-fold. Aetiological model fitting gave a heritability of sarcoidosis of 0.66 (95% CI 0.45 to 0.80)., Conclusions: This study suggests that genetic factors play an important role in the susceptibility to sarcoidosis. This result should encourage the search for molecular genetic markers of susceptibility to the disease.

Background: Obesity is linked to asthma in a yet poorly understood manner. We examined the relationship between obesity and asthma in a population-based sample of twins., Methods: From the cohorts born between 1953 and 1982, who were enrolled in The Danish Twin Registry, a total of 29 183 twin individuals participated in a nationwide questionnaire study, where data on height, weight and asthma were collected. Latent factor models of genetic and environmental effects were fitted using maximum likelihood methods., Results: The age-adjusted risk of asthma was increased both in obese females, OR = 1.96 (1.45-2.64), P < or = 0.001 and in obese males, OR = 1.59 (1.08-2.33), P = 0.02. According to best-fitting models, the heritability for obesity was 81% in males and 92% in females, whereas the heritability for asthma was 78% and 68% in males and females respectively. The age-adjusted genetic liabilities to obesity and asthma were significantly correlated only in females, r = 0.28 (0.16-0.38)., Conclusions: Obese subjects have an increased risk for asthma, which in females seems partly because of common genes.

Background: The aim of this study was to describe differences between allergic rhinitis (AR) and nonallergic rhinitis (NAR) in a large community-based sample of Danish adolescents and adults., Methods: A total of 1,186 subjects, 14-44 years of age, who in a screening questionnaire had reported a history of airway symptoms suggestive of asthma and/or allergy, or who were taking any medication for these conditions were clinically examined. All participants were interviewed about respiratory symptoms and furthermore skin test reactivity, lung function and airway responsiveness were measured using standard techniques., Results: A total of 77% of the subjects with rhinitis had AR, whereas 23% had NAR. Subjects with NAR were more likely to be females, OR = 2.05 (1.31-3.20), P = 0.002, to have persistent symptoms within the last 4 weeks, OR = 1.88 (1.23-2.89), P = 0.003, and to have recurring headaches, OR = 1.94, (1.12-3.37), P = 0.019. On the other hand, subjects with NAR were less likely to have airway hyperresponsiveness, OR = 0.40, (0.24-0.66), P < 0.001, food allergy, OR = 0.40, (0.19-0.36), P = 0.009 and to have been treated with antihistamines in the last 4 weeks, OR = 0.22, (0.13-0.38), P < 0.001 compared with subjects with AR. Subjects with AR were symptomatically worse within their season in terms of sneezing (P < 0.001) and itchy eyes (P < 0.001), compared to subjects with NAR, whereas nasal congestion and rhinorrhea were equally frequent in the two groups (P = 0.901 and P = 0.278, respectively)., Conclusions: The proportion of subjects with NAR in an adolescent and adult population with rhinitis is around one-fourth. Women have NAR twice as often as men. In general, subjects with NAR have more persistent but equally severe symptoms compared to subjects with AR. However, subjects with AR have more sneezing and itchy eyes within their particular season of allergy compared to subjects with NAR.

Objective: To estimate to what extent the same genetic and environmental risk factors influence asthma, hay fever and eczema., Design: From the nationwide Danish Twin Registry, twin cohorts born between 1953 and 1982 were contacted for a questionnaire survey, and a total of 29 183 twin individuals (86%) responded. Subjects were classified as cases when responding affirmatively to three questions about the lifetime occurrence of asthma, hay fever and eczema. Variance components twin analysis was conducted using maximum likelihood methods., Results: The phenotypic (within-subject) correlations in liability between the different diseases were 0.57 (95% CI 0.54-0.59) for asthma and hay fever, 0.40 (95% CI 0.36-0.42) for asthma and eczema, and 0.33 (95% CI 0.29-0.36) for hay fever and eczema. Decomposition of these correlations into their genetic and environmental contributions showed that shared genes explained between 70% and 85% of the correlation between the different diseases. The remaining parts were explained by environmental factors shared between the diseases., Conclusion: To a large extent, atopic diseases share a common genetic background, although disease-specific genes also play a considerable role. These results can prove informative when counselling families with atopy, and may furthermore be used to guide the search for pleiotropic genes of importance for these diseases.