Relevance of Coding Variation in FLG And DOCK8 in Finnish Pediatric Patients with Early-Onset Moderate-To-Severe Atopic Dermatitis.

Early-onset, persistent atopic dermatitis (AD) is proposed as a distinct subgroup that may have specific genotypic features. FLG gene loss-of-function variants are the best known genetic factors contributing to epidermal barrier impairment and eczema severity. In a cohort of 140 Finnish children with early-onset moderate-to-severe AD, we investigated the effect of coding variation in FLG and 13 other genes with epidermal barrier or immune function through the use of targeted amplicon sequencing and genotyping. A FLG loss-of-function variant (Arg501Ter, Ser761fs, Arg2447Ter, or Ser3247Ter) was identified in 20 of 140 patients showing higher transepidermal water loss values than patients without these variants. Total FLG loss-of-function variant frequency (7.14%) was significantly higher than in the general Finnish population (2.34%). When tested separately, only Arg2447Ter showed a significant association with AD (P = 0.003104). In addition, a modest association with moderate-to-severe pediatric AD was seen for rs12730241 and rs6587667 (FLG2:Gly137Glu). Loss-of-function variants, previously reported pathogenic variants, or statistically significant enrichment of nonsynonymous coding region variants were not found in the 13 candidate genes studied by amplicon sequencing. However, higher IgE and eosinophil counts were found in carriers of potentially pathogenic DOCK8 missense variants, suggesting that the role of DOCK8 variation in AD should be further investigated in larger cohorts.

Topical tacrolimus versus corticosteroids in childhood moderate-to-severe atopic dermatitis and the impact on airway inflammation: a long-term randomized open-label study.

BACKGROUND: Childhood atopic dermatitis (AD) is often followed by other atopic comorbidities such as asthma. AIM: To compare the effectiveness of topical tacrolimus (TAC) and topical corticosteroids (TCSs) and their impact on airway inflammation and bronchial hyperresponsiveness in patients with paediatric AD. METHODS: This was a 3-year randomized open-label comparative follow-up study of 152 1-3-year-old children with moderate-to-severe AD (trial registration: EudraCT2012-002412-95). Frequent study visits including clinical examinations, laboratory investigations (total IgE, specific IgEs, blood eosinophils), skin prick and respiratory function tests to assess airway inflammation and bronchial hyperresponsiveness (exhaled nitric oxide, airway responsiveness to exercise and methacholine) were performed. RESULTS: Changes in eczema parameters at 36 months were similar in the TCS and TAC groups for mean body surface area (BSA) difference 1.4 [95% confidence interval (CI) -1.48 to 4.19); P = 0.12], mean Eczema Area and Severity Index (EASI) difference 0.2 (95% CI -1.38 to 1.82; P = 0.2), mean Investigator's Global Assessment (IGA) difference, 0.3 (95% CI -0.12 to 0.67; P = 0.12) and mean transepidermal water loss (TEWL) difference at the eczema site, -0.3 (95% CI -4.93 to 4.30; P = 0.96) and at the control site, 1.4 (95% CI -0.96 to 3.60, P = 0.19). The control-site TEWL increased more towards the end of follow-up in the TCS vs. TAC group (mean change difference -4.2, 95% CI -8.14 to -0.29; P = 0.04). No significant impact on development of airway inflammation or bronchial hyperresponsiveness occurred in early effective eczema-treatment responders vs. others ('early' vs. 'other' response was defined as the difference in treatment response to airway outcomes in BSA, EASI or IGA at 3 months). CONCLUSION: Children with moderate-to-severe AD benefit from long-term treatment with TCS or TAC. There were no significant differences in treatment efficacy. No differences in the impact on airways occurred between early effective treatment responders vs. others.

Effective treatment of atopic dermatitis in small children significantly improves the quality of life of patients and their families.

BACKGROUND: Atopic dermatitis (AD) has a severe impact on quality of life (QoL). OBJECTIVES: To analyze the impact of AD on QoL of small children with moderate-to-severe AD in a tertiary health care hospital in Helsinki, Finland. MATERIALS & METHODS: Based on interim analysis of this longitudinal follow-up study, we investigated treatment response (topical corticosteroids vs. tacrolimus) and QoL of 152 small children with moderate-to-severe AD. RESULTS: The tacrolimus group had a significantly better treatment response at 12 months visit, but thereafter no differences were observed (p = 0.029; Mann-Whitney U test). The odds ratio for group comparisons was 2.258 (CI: 1.151-4.431). There was a significant improvement in QoL during follow-up in both treatment groups. Our study showed substantial improvements in disease severity and QoL based on active management and effective treatments in small children with AD. The main improvement was seen during the first year in both treatment groups with a lasting response. CONCLUSION: Effective treatment has a significant positive impact on the QoL of small children with AD and their families.

Young children with moderate-to-severe atopic dermatitis can be treated safely and effectively with either topical tacrolimus or mild corticosteroids.

AIM: We collected evidence and safety data for topical tacrolimus in small children with atopic dermatitis (AD) and compared the usage with topical corticosteroid. METHODS: This was an interim analysis of 75 patients (55% female) at 1 year of an ongoing 3-year randomised open-label comparative follow-up study of topical tacrolimus vs corticosteroid treatment. One- to three-year-old children with moderate-to-severe eczema referred to the Skin and Allergy Hospital in Helsinki, Finland, were enrolled. RESULTS: Efficacy parameters, the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), transepidermal water loss (TEWL), eczema area, serum total immunoglobulin E (IgE) and the blood eosinophil count, showed improvement in both groups during the study. However, patients with signs of early sensitisation at baseline (elevated serum total IgE, elevated eosinophil count, positive prick tests or specific IgEs to aero or food allergens) had statistically significantly lower TEWL at the eczema site and a smaller eczema area at 12 months in the tacrolimus group. No severe adverse effects were seen during the treatment. CONCLUSION: Children with AD and signs of early sensitisation appeared to benefit more from early tacrolimus than corticosteroid treatment. Small children may need stronger but nevertheless safe ointment options when treating moderate-to-severe AD.

SO2 emission measurement with the European standard reference method, EN 14791, and alternative methods - observations from laboratory and field studies.

EN 14791 is a European Standard Reference method for the measurement of SO2 in emissions. This standard is based on a wet-chemical method in which SO2 present in flue gases is absorbed into an absorption solution containing hydrogen peroxide, and analyzed as sulfates after sampling. This study presents the results obtained when three portable automated measuring systems (P-AMS), based on Fourier-transform infrared (FTIR) spectroscopy, non-dispersive infrared (NDIR) and ultraviolet-fluorescence (UV) techniques, were compared to the Standard Reference Method for SO2 (EN 14791) in order to verify whether they could be used as alternative methods (AM) to EN 14791. In the case of FTIR, the measurements were performed from hot and wet gas, without any conditioning. UV-fluorescence analyzers were equipped with dilution probes and one NDIR applied a permeation dryer, whereas the other had a chiller. Tests were carried out at concentration ranges from 0 to 200 mg/m3(n) and from 0 to 800 mg/m3(n) for testing of equivalency according to CEN/TS 14793 using a test bench. Equivalency test criteria were met for all tested P-AMS except for NDIR at the lower range. The SO2 results measured with NDIR and the chiller were lower compared to the set-up with NDIR and permeation. This was most probably due to the chiller causing absorption of SO2 in the condensate. Tests were also carried out at field conditions, measuring the SO2 emissions from a boiler combusting mainly bark. The same phenomena were observed in these tests as during the test bench study, i.e. the measurement set-up with NDIR and the chiller gave the lowest results. These data demonstrated that the tested alternative methods (FTIR, UV-fluorescence, and NDIR) could be used instead of the standard reference method EN 14791, thus providing real-time calibration of automated measuring systems. It must however be emphasized that when measuring water-soluble gases, such as SO2, the choice of suitable conditioning technique is critical in order to minimize losses of the studied component in the condensate. Implications: Portable automated measuring systems (P-AMS) provide real-time information about emissions and their concentrations, thus offering significant advantages compared to wet-chemical methods. This study presents results which can be used as a validation protocol to show that the tested P-AMS techniques (FTIR, NDIR, UV-fluorescence) could be used instead of EN 14791 (CEN 2017a) as alternative methods (AM), when paying attention to the selection of an appropriate conditioning technique.