Doris Staab

Age related, structured educational programmes for the management of atopic dermatitis in children and adolescents: multicentre, randomised controlled trial

Abstract Objective To determine the effects of age related, structured educational programmes on the management of moderate to severe atopic dermatitis in childhood and adolescence. Design Multicentre, randomised controlled trial. Setting Seven hospitals in Germany. Participants Parents of children with atopic dermatitis aged 3 months to 7 years (n = 274) and 8-12 years (n = 102), adolescents with atopic dermatitis aged 13-18 years (n = 70), and controls (n = 244, n = 83, and n = 50, respectively). Interventions Group sessions of standardised intervention programmes for atopic dermatitis once weekly for six weeks or no education (control group). Main outcome measures Severity of eczema (scoring of atopic dermatitis scale), subjective severity (standardised questionnaires), and quality of life for parents of affected children aged less than 13 years, over 12 months. Results Significant improvements in severity of eczema and subjective severity were seen in all intervention groups compared with control groups (total score for severity: age 3 months to 7 years - 17.5, 95% confidence intervals - 19.6 to - 15.3 v - 12.2, - 14.3 to - 10.1; age 8-12 years - 16.0, - 20.0 to - 12.0 v - 7.8, - 11.4; - 4.3; and age 13-18 years - 19.7, - 23.7 to - 15.7 v - 5.2, - 10.5 to 0.1). Parents of affected children aged less than 7 years experienced significantly better improvement in all five quality of life subscales, whereas parents of affected children aged 8-12 years experienced significantly better improvement in three of five quality of life subscales. Conclusion Age related educational programmes for the control of atopic dermatitis in children and adolescents are effective in the long term management of the disease.

Evaluation of a parental training program for the management of childhood atopic dermatitis

Atopic dermatitis (AD) in childhood is a common disease with prevalence rates as high as 20%. Its early onset in infancy and its chronic relapsing course puts a special burden on families. Supporting parents in dealing with the management of AD presents a challenge for physicians. The objective of this study was to determine the effect of a structured parental training program on managing AD in children. Two‐hundred and four families participated in a prospective, randomized controlled trial. Children (5 months to 12 years in age) had suffered from moderate‐to‐severe AD for at least 4 months. They were randomly assigned to either the intervention group or a waiting, control group who could participate in the training program 1 year later. The intervention was an inter‐disciplinary, structured educational program which covered medical, nutritional, and psychological issues in six group sessions of 2 h each. The families were assessed at the beginning of the study and 1 year later. Main outcome measures were: severity of eczema (SCORAD); treatment habits; treatment costs; quality of life; and coping strategies. Significant effects were shown regarding treatment behavior, such as regular use of emollients, use of antiseptics and topical steroids in the event of exacerbation, and a reduction in the use of unconventional therapies. Satisfaction with medical treatment was improved, and rumination as an ineffective coping strategy was reduced. Finally, significant reduction of treatment costs was achieved. We conclude that structured training programs for parents of children with AD is a helpful adjunct to dermatological treatment.

Neutrophil Elastase Enhances Sputum Solubilization in Cystic Fibrosis Patients Receiving DNase Therapy

Cystic fibrosis patients suffer from chronic lung infection and inflammation due to the secretion of viscous sputum. Sputum viscosity is caused by extracellular DNA, some of which originates from the release of neutrophil extracellular traps (NETs). During NET formation neutrophil elastase (NE) partially processes histones to decondense chromatin. NE is abundant in CF sputum and is thought to contribute to tissue damage. Exogenous nucleases are a palliative treatment in CF as they promote sputum solubilization. We show that in a process reminiscent of NET formation, NE enhances sputum solubilization by cleaving histones to enhance the access of exogenous nucleases to DNA. In addition, we find that in Cf sputum NE is predominantly bound to DNA, which is known to downregulate its proteolytic activity and may restrict host tissue damage. The beneficial role of NE in CF sputum solubilization may have important implications for the development of CF therapies targeting NE.

Levofloxacin Inhalation Solution (MP-376) in Patients with Cystic Fibrosis with Pseudomonas aeruginosa

RATIONALE Lower respiratory tract infection with Pseudomonas aeruginosa (PA) is associated with increased morbidity in patients with cystic fibrosis (CF). Current treatment guidelines for inhaled antibiotics are not universally followed due to the perception of decreased efficacy, increasing resistance, drug intolerance, and high treatment burden with current aerosol antibiotics. New treatment options for CF pulmonary infections are needed. OBJECTIVES This study assessed the efficacy and safety of a novel aerosol formulation of levofloxacin (MP-376, Aeroquin) in a heavily treated CF population with PA infection. METHODS This study randomized 151 patients with CF with chronic PA infection to one of three doses of MP-376 (120 mg every day, 240 mg every day, 240 mg twice a day) or placebo for 28 days. The primary efficacy endpoint was the change in sputum PA density. Secondary endpoints included changes in pulmonary function, the need for other anti-PA antimicrobials, changes in patient-reported symptom scores, and safety monitoring. MEASUREMENTS AND MAIN RESULTS All doses of MP-376 resulted in reduced sputum PA density at Day 28, with MP-376 240 mg twice a day showing a 0.96 log difference compared with placebo (P = 0.001). There was a dose-dependent increase in FEV(1) for MP-376, with a difference of 8.7% in FEV(1) between the 240 mg twice a day group and placebo (P = 0.003). Significant reductions (61-79%) in the need for other anti-PA antimicrobials were observed with all MP-376 treatment groups compared with placebo. MP-376 was generally well tolerated relative to placebo. CONCLUSIONS Nebulized MP-376was well tolerated and demonstrated significant clinical efficacy in heavily treated patients with CF with PA lung infection. Clinical trial registered with www.clinicaltrials.gov (NCT00677365).

Low-dose cyclosporin A microemulsion in children with severe atopic dermatitis : Clinical and immunological effects

Cyclosporin A (CsA) is an effective and well‐tolerated treatment for severe childhood atopic dermatitis (AD). By starting at a low dose, the therapeutic safety should be further increased. The aim of this study was to evaluate low‐dose CsA in childhood AD with respect to clinical outcome and modulation of T‐cell dysregulation. In an open prospective study, 10 children (age: 22–106 months) with severe AD (mean objective SCORAD score > 40 on two baseline measurements at a minimum interval of 2 weeks) were treated with CsA solution for 8 weeks. All patients received a starting dose of 2.5 mg/kg/day, which was increased stepwise in non‐responders to a maximum of dose of 5 mg/kg/day. Disease activity was monitored using the SCORAD index. The frequency of cytokine‐producing peripheral blood T lymphocytes was analyzed by intracellular cytokine staining, and T‐cell numbers were measured by fluorescence‐activated cell sorter (FACS) analysis. Twenty healthy age‐matched children were included as controls for the immunological data. Nine of the 10 patients had a SCORAD reduction of at least 35%. In seven patients this was achieved with low‐dose CsA at 2.5 mg/kg/day (n = 4) and 3.5 mg kg/day (n = 3). Seven of the nine responders experienced no relapse within the 4‐week follow‐up period. At baseline the percentage of interleukin‐4 (IL‐4), IL‐13, and human leucocyte antigen (HLA)‐DR‐positive CD3+ cells was higher in the patient group than in the controls. After CsA treatment there was a significant reduction in interferon‐γ (IFN‐γ), IL‐2, IL‐4, IL‐13, and HLA‐DR‐positive CD3+ cells. Hence, in severe pediatric AD, CsA microemulsion, when started at a low dose (2.5 mg/kg/day), improves clinical measures of disease, reduces T‐lymphocyte cytokine production, and regulates T‐cell activation.

Inhalation Treatment with Glutathione in Patients with Cystic Fibrosis. A Randomized Clinical Trial

RATIONALE Glutathione is the major antioxidant in the extracellular lining fluid of the lungs and depleted in patients with cystic fibrosis (CF). OBJECTIVES We aimed to assess glutathione delivered by inhalation as a potential treatment for CF lung disease. METHODS This randomized, double-blind, placebo-controlled trial evaluated inhaled glutathione in subjects with CF 8 years of age and older and FEV1 of 40-90% of predicted. Subjects were randomized to receive 646 mg glutathione in 4 ml (n = 73) or placebo (n = 80) via an investigational eFlow nebulizer every 12 hours for 6 months. MEASUREMENTS AND MAIN RESULTS FEV1 (absolute values), both as pre-post differences (P = 0.180) and as area under the curves (P = 0.205), were the primary efficacy endpoints, and were not different between the glutathione group and the placebo group over the 6-month treatment period. Exploratory analysis showed an increase of FEV1 from baseline over placebo of 100 ml or 2.2% predicted; this was significant at 3 months, but not later. Subjects receiving glutathione had neither fewer pulmonary exacerbations, nor better scores for quality of life. Whereas increased glutathione and metabolites in sputum demonstrated significant delivery to the lungs, there was no indication of diminished oxidative stress to proteins or lipids, and no evidence for anti-inflammatory or antiproteolytic actions of glutathione supplemented to the airways. The adverse event incidence was similar between glutathione and placebo. CONCLUSIONS Inhaled glutathione in the dose administered did not demonstrate clinically relevant improvements in lung function, pulmonary exacerbation frequency, or patient-reported outcomes. Glutathione delivery to the airways was not associated with changes in markers of oxidation, proteolysis, or inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT00506688) and https://eudract.ema.europa.eu/index.html (EudraCT 2005-003870-88).

Neurodermitis S2-Leitlinie

© Dt. Dermatologische Gesellschaft u. a. • Journal compilation

Structured parent education in the management of childhood atopic dermatitis: The Berlin model

Childhood atopic dermatitis (AD) is a common disease with the prevalence rates increasing. Its chronic course with frequent relapses puts a special burden on both children and their parents. To maximise positive long-term outcome in the management of AD it is important to support parents in dealing with the chronic condition of their child in addition to treating symptoms. In the present article, we describe in detail the goals, structure, and content of the Berlin education program for parents of children with AD. The program aims to contribute towards a comprehensive, family-oriented management of childhood AD. Its objective is to improve parents self-management skills with regard to their childs disease and to positively impact the course of the disease as well as the familys quality of life. Medical, nutritional and psychological issues are covered in six group sessions which are conducted by a multiprofessional team of paediatricians, psychologists and dieticians. Preliminary data show that the program has a desirable effect on aspects of quality of life and coping.

Efficacy of a self-management program for childhood asthma–: A prospective controlled study

Asthma training programs for parents and children have been developed to increase both the self-management skills of asthmatic children and compliance with medical regimes. In order to evaluate two training programs for asthmatic children aged 7-14, 81 patients were randomly assigned to three groups. Group 1 consisted of 27 patients and their parents who participated in a five-day standardized family-oriented clinical asthma training program. They had monthly follow-up meetings with the training team for a period of six months. Group 2 (n = 29) had the same clinical training without follow-up interventions; a control group (n = 25) received regular medical treatment according to the international guidelines at the asthma clinics without a training program and served as control group. Questionnaires regarding self-management aspects, coping and anxiety were filled out by patients, parents, family doctors and the training team prior to as well as twelve months after the training. The results indicate that Training group 1 benefitted most with respect to active asthma self-management, Training group 2 to some degree while the control group showed no significant effects. The differences after one year between the three groups regarding physical parameters such as lung-function and days missed in school did not reach the level of significance. Our results indicate that the long-term efficacy of self management courses for asthmatic children is enhanced by regular follow-up training sessions.

Once-weekly azithromycin in cystic fibrosis with chronic Pseudomonas aeruginosa infection

BACKGROUND Data on the effects of long-term treatment with azithromycin (AZM) on inflammatory markers in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa are scarce. So far there is no pharmacokinetic and clinical data on once-weekly dosage of AZM in CF patients. METHODS In a randomised double-blind, placebo-controlled trial, patients received AZM or placebo 1 per week for 8 weeks (AZM dosage--20-29 kg: 500 mg, 30-39 kg: 750 mg, 40-49 kg: 1000 mg and > or = 50 kg: 1250 mg) after a course of intravenous antipseudomonal antibiotics. Pulmonary function tests, the serum markers LPS-binding protein (LBP), interleukin-8 (IL-8), CRP, P. aeruginosa alginate in sputum samples and quality of life scores were evaluated. RESULTS Thirty-eight patients (21 AZM/17 placebo) (mean age: 23.7 years; mean FEV(1): 62% of predicted) were recruited. After treatment (mean dose of 21.2 mg/kg body weight once a week) pulmonary function declined in both groups compared to baseline (i.e. after cessation of i.v. antibiotics). The AZM group was significantly better for mean changes in serum CRP (AZM: +0.9 mg/l, placebo: +21.6 mg/l, p=0.019), lipopolysaccharide binding protein in serum, LBP (AZM: +0.9 microg/ml, placebo: +7.0 microg/ml, p=0.015), serum interleukin-8 (AZM: -3.1 pg/ml, placebo: +2.9 pg/ml, p=0.001) and alginate in sputum (AZM: +85 microg/ml, placebo: +353 microg/ml, p=0.048). Quality of life was significantly better after AZM and there was no increase in treatment-related adverse events. CONCLUSION Once-weekly azithromycin ameliorated inflammatory reactions and improved quality of life. A decline of pulmonary function after cessation of i.v. antibiotics could not be prevented.