In recent years, cases involving terbinafine-resistant Trichophyton isolates have been reported increasingly, particularly in India. We present 14 cases of terbinafine treatment failure in Trichophyton-infected Danish patients due to acquired resistance. Patients infected with Trichophyton rubrum (n = 12) or Trichophyton interdigitale (n = 2) with elevated terbinafine MICs during 2013–2018 were included. Antifungal susceptibility testing (AFST) was performed following a modified EUCAST E.Def 9.3.1 method (5 days of incubation) with or without cycloheximide and chloramphenicol (CC) supplementation of the growth medium. The squalene epoxidase (SE) target gene was sequenced, and 3-dimensional enzyme homology modeling was performed. Most patients (12/14 [86%]) were male. The mean age was 53.5 years (range, 11 to 77 years). The mean duration of infections was 4.8 years at the time of resistance detection. Prior systemic terbinafine treatment was documented for all patients, and topical therapy for 62% (information was missing in one case). Overall, nine isolates (64%) displayed high terbinafine resistance (MICs, 4 to >8 mg/liter), while two (14%) displayed moderate (MICs, 1 to 2 mg/liter) and three (21%) displayed low (MICs, 0.125 to 0.25 mg/liter) terbinafine resistance compared with control isolates. MICs generated with or without CC supplementation were similar, but CC prevented contamination. Known and novel SE amino acid substitutions (F397L, L393F, L393S, F415S, H440Y F484Y, and I121M V237I) were detected in resistant but not control isolates. Three-dimensional homology modeling suggested a role of the novel I121M and V237I alterations. Terbinafine resistance has been detected in Denmark using a modified EUCAST method, which facilitated susceptibility testing of dermatophytes. Action is needed for this emerging public health problem.

Coexistence of infertility and asthma has been observed clinically. Therefore, we investigated the association between asthma and delayed pregnancy in a nationwide population-based cohort of twins.A cohort of 15 250 twins living in Denmark (aged 12-41 years) participated in a questionnaire study including questions about the presence of asthma and fertility. Differences in time to pregnancy and pregnancy outcome were analysed in subjects with asthma, allergy and in healthy individuals using multiple regression analysis.Asthma was associated with an increased time to pregnancy, the percentage of asthmatics with a time to pregnancy .1 year was 27% versus 21.6% for non-asthmatics (OR (95% CI) 1.31 (1.1-1.6); p50.009). The association remained significant after adjustment for age, age at menarche, body mass index and socioeconomic status (OR (95% CI) 1.25 (1.0-1.6); p50.05), and was more pronounced in those .30 years of age (32.2% versus 24.9%, OR (95% CI) 1.44 (1.1-1.9); p50.04). Untreated asthmatics had a significant increased risk of prolonged time to pregnancy compared to healthy individuals (OR (95% CI) 1.79 (1.20-2.66); p50.004), while asthmatics receiving any kind of treatment for asthma tended to have a shorter time to pregnancy than untreated asthmatics (OR 1.40; p50.134).Asthma prolongs time to pregnancy. The negative effect of asthma on fertility increases with age and with disease intensity, indicating that a systemic disease characterised by systemic inflammation also can involve reproductive processes. @ERSpublications Asthma prolongs time to pregnancy: the negative effect of asthma on fertility increases with age and disease intensity

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The susceptibility to develop atopic dermatitis can be attributed both to genetic and environmental causes. We estimated the relative impact of genetic and environmental factors in the etiology of atopic dermatitis in a population-based sample of twins. From the birth cohorts of 1953-1982 who were enrolled in The Danish Twin Registry, a total of 11,515 twin pairs were identified in a nationwide questionnaire survey. Subjects were classified as atopic dermatitis cases when responding affirmatively to the question, "Do you have, or have you ever had, eczema in the folds of your elbows or knees?" Latent factor models of genetic and environmental influences were fitted to the observed data using maximum likelihood methods. The overall lifetime prevalence of atopic dermatitis was 7.3%. A cotwin of an affected identical twin had a sevenfold increased risk of atopic dermatitis compared with a threefold increased risk among cotwins of an affected fraternal twin, relative to the general population. Genes accounted for 82% and nonshared environmental factors accounted for 18% of the individual susceptibility to develop atopic dermatitis. The same genes contributed to the susceptibility to atopic dermatitis both in male and female patients (p = 0.98). The estimates were adjusted for age. The susceptibility to develop atopic dermatitis is attributable to mainly genetic differences between people. However, differences in environmental exposures also are of importance.

Different atopic conditions share, to a large extent, a common genetic background. In particular, upper and lower respiratory symptoms seem to be different phenotypic expressions of a common set of genes. These results add new insight into the origins of clinical heterogeneity within atopy and should stimulate the search for pleiotropic genes of importance for these conditions.

The susceptibility to develop severe COPD, as defined by hospitalizations, is strongly influenced by genetic factors. Approximately 60% of the individual susceptibility can be explained by genetic factors.

The prevalence of atopic dermatitis (AD) has increased during the last decades. Whether the prevalence is still increasing or has reached a stable level during the 1990s is still not certain. The purpose of this study was to compare the prevalence of AD in two different random samples of Danish children studied in 1986 and 2001 and to examine the associations between AD and other atopic outcomes. Two samples of children and adolescents living in urban Copenhagen were drawn at random from the civil registration list in 1986 and 2001. A total of 527 and 480 subjects participated in 1986 and 2001, respectively. Subjects were classified as AD cases when responding affirmatively to the question "Do you have, or have you ever had, significant and recurrent episodes of eczema in the folds of your elbows or knees?" Immunoglobulin E (IgE) measurements, skin-prick tests, and airway responsiveness tests were performed. The prevalence of AD increased from 17.3% in 1986 to 27.3% in 2001. For male subjects, the prevalence of AD was 16.4% in 1986 compared with 25.7% in 2001. For female subjects, the prevalence of AD was 18.1% in 1986 compared with 28.7% in 2001. Elevated levels of IgE, airway hyperresponsiveness (AHR), and rhinitis were statistically significant predictors of AD. The prevalence of AD has increased significantly from 1986 to 2001 in urban Copenhagen, Denmark. In addition, we found that AD was significantly associated with AHR, rhinitis, and elevated levels of IgE, supporting the idea of the atopic triad.

Ingenol mebutate gel was associated with a high number of AEs and withdrawals due to painful local and adjacent skin reactions. Furthermore, it showed promising efficacy in reducing AGW despite a difficult-to-treat population. Optimization of the formulation is warranted to improve the safety profile of the treatment.