Thomas Frischer

Lung transplantation in adults is an accepted therapeutic option, whereas there is ongoing debate on its positive impact on survival in children. We report our experience of the first 20 yrs of paediatric lung transplantation at a single centre in Austria.Patient survival, organ survival and freedom from bronchiolitis obliterans were estimated by Kaplan–Meier curves. Pre- and post-transplant parameters were assessed and their influence on patient and organ survival evaluated by univariate tests and stepwise multivariate analyses.A total of 55 transplantations were performed in 43 patients. 1- and 5-yr patient survival rates were 72.1% and 60.6%, respectively, and 52.6% of patients were found to be free from bronchiolitis obliterans syndrome at 5 yrs post-transplant. Analysing different eras of transplantation suggests an improvement over the years with a 5-yr survival rate of 70.6% in the second decade. A positive effect of pre-transplant diabetes mellitus and immunosuppression was found with the newer drug tacrolimus, and a negative effect of pre-transplant in-hospital admission was reported. A high rate of successful re-transplantation prolonged total patient survival.

Primary ciliary dyskinesia (PCD) is a hereditary disorder of mucociliary clearance causing chronic upper and lower airways disease. We determined the number of patients with diagnosed PCD across Europe, described age at diagnosis and determined risk factors for late diagnosis.Centres treating children with PCD in Europe answered questionnaires and provided anonymous patient lists.In total, 223 centres from 26 countries reported 1,009 patients aged situs inversus. Median age at diagnosis was 5.3 yrs, lower in children withsitus inversus(3.5versus5.8 yrs; pversus4.8 yrs; p = 0.002). Adjusted age at diagnosis was 5.0 yrs in Western Europe, 4.8 yrs in the British Isles, 5.5 yrs in Northern Europe, 6.8 yrs in Eastern Europe and 6.5 yrs in Southern Europe (p<0.001). This strongly correlated with general government expenditures on health (p<0.001).This European survey suggests that PCD in children is under-diagnosed and diagnosed late, particularly in countries with low health expenditures. Prospective studies should assess the impact this delay might have on patient prognosis and on health economic costs across Europe.

Primary ciliary dyskinesia (PCD) is a rare hereditary recessive disease with symptoms of recurrent pneumonia, chronic bronchitis, bronchiectasis, and chronic sinusitis. Chronic rhinitis is often the presenting symptom in newborns and infants. Approximately half of the patients show visceral mirror image arrangements (situs inversus). In this study, we aimed 1) to determine the number of paediatric PCD patients in Austria, 2) to show the diagnostic and therapeutic modalities used in the clinical centres and 3) to describe symptoms of children with PCD.For the first two aims, we analysed data from a questionnaire survey of the European Respiratory Society (ERS) task force on Primary Ciliary Dyskinesia in children. All paediatric respiratory units in Austria received a questionnaire. Symptoms of PCD patients from Vienna Children's University Hospital (aim 3) were extracted from case histories.In 13 Austrian clinics 48 patients with PCD (36 aged from 0-19 years) were identified. The prevalence of reported cases (aged 0-19 yrs) in Austria was 1:48000. Median age at diagnosis was 4.8 years (IQR 0.3-8.2), lower in children with situs inversus compared to those without (3.1 vs. 8.1 yrs, p = 0.067). In 2005-2006, the saccharine test was still the most commonly used screening test for PCD in Austria (45%). Confirmation of the diagnosis was usually by electron microscopy (73%). All clinics treated exacerbations immediately with antibiotics, 73% prescribed airway clearance therapy routinely to all patients. Other therapies and diagnostic tests were applied very inconsistently across Austrian hospitals. All PCD patients from Vienna (n = 13) had increased upper and lower respiratory secretions, most had recurring airway infections (n = 12), bronchiectasis (n = 7) and bronchitis (n = 7).Diagnosis and therapy of PCD in Austria are inhomogeneous. Prospective studies are needed to learn more about the course of the disease and to evaluate benefits and harms of different treatment strategies.

The aim of this study was to investigate repeatability of cysteinyl-leukotrienes (cys-LT) measurements in nasal lavage fluid (NLF) and to determine if cys-LT levels in NLF are related to asthma severity in children. As a second outcome, we investigated if cys-LT in NLF reflect lower airway inflammation as assessed by exhaled NO measurement. To assess the repeatability of cys-LT measurements, two NLF samples were obtained from eight healthy controls 24 h apart. Sixty-nine asthmatic children (mean age; range: 12.8; 7.3-17.7 yr), which were grouped according to asthma severity were studied cross-sectionally on one occasion. Cys-LT in NLF were analyzed using a specific enzyme immunoassay, exhaled NO, and pulmonary function parameters were measured. The coefficient of repeatability for the repeated cys-LT measurements was 1.45 pg/ml. Cys-LT levels in NLF differed significantly between asthma severity groups (p < 0.001): mild intermittent: [median (IQR)] 6.88 pg/ml (2.00-27.87); mild persistent: 21.09 pg/ml (4.50-84.67); and moderate persistent asthmatics: 36.41 pg/ml (11.03-118.40). Concentration of cys-LT in NLF and exhaled NO was positively correlated (r = 0.85; p < 0.001). In conclusion, concentration of cys-LT in NLF correlates with asthma severity in children and is related to lower airway inflammation.

Fractional exhaled nitric oxide (FeNO) is elevated in asthma and reflects eosinophilic airway inflammation. The aim of this prospective, randomized, single‐blind study was to examine whether the inclusion of repeated FeNO measurements into asthma monitoring leads to an improvement in asthma outcome. Forty‐seven children with mild to moderate asthma were allocated to a FeNO group (n = 22) and to a control group (n = 25). In the FeNO group therapy was based on symptoms, β‐agonist use, lung function, and FeNO whereas in the control group therapy was based on symptoms, β‐agonist use and lung function only. Patients performed five visits in 6 weeks intervals. Frequency of respiratory symptoms, β‐agonist use, FEV₁% predicted and the frequency of exacerbations were similar between groups. Patients in the FeNO group received higher doses of inhaled corticosteroids (ICS) (control group: median (interquartile range): 241 µg (26–607 µg); FeNo group: 316 µg (200–500 µg) and had significantly higher MEF₅₀% predicted (control group: median (interquartile range): 68.5% (55.8–83.1%); FeNO group: 83.2% (62.9%–98.3%). At a cut‐off point of 22.9 ppb FeNO the best predictive value for exacerbations with a sensitivity of 80% and specificity of 60% was found. Significant relationships were observed between FeNO and dose of ICS (β = −8.77; P < 0.002), β‐agonist use 2 weeks prior to a visit (β = 0.11; P < 0.05), asthma symptoms (β = 0.02; P < 0.0001), and bronchial hyperresponsiveness (β = 0.04; P = 0.02). In conclusion, FeNO was related to important markers of asthma control. A therapy regimen aimed at lowering FeNO in children with asthma improved parameters of small airway function, but was not able to improve clinical markers of asthma control. Pediatr Pulmonol.

Summary: Background Sensitization to house dust mite (HDM) is an important risk factor for the development of asthma and allergic disease in childhood. Higher levels of HDM allergen are linked to increased sensitization to HDM.Objective To study the effect of mite‐impermeable mattress encasings and an educational package on the development of allergies in a newborn cohort.Methods Six hundred and ninety‐six newborns at high risk of developing allergies were enrolled in three European countries (Germany, Austria, UK) in a prospective, randomized, controlled birth‐cohort study. Children were randomly assigned to an intervention and control group. Intervention measures included the use of mite‐impermeable mattress encasings for the child's bed and a simple educational package on allergen avoidance. The control group received basic information about allergies. Children were followed up at age 6, 12, 18 and 24 months.Results 80.9% of the children were followed up to the age of 24 months. No difference in the prevalence of sensitization to HDM (control vs. intervention group: 8.4% vs. 6.1%, P=0.33) or the development of symptoms (recurrent wheezing 10.3% vs. 10.7%, nocturnal cough 12.5% vs. 12.5%) or allergic diseases (asthma 3.5% vs. 5.1%, eczema 20.0% vs. 19.6%, rhinitis 28.9% vs. 25.8%) could be found between the control and intervention group.Conclusion In this study, HDM avoidance did not show a protective effect on the development of sensitization to HDM or symptomatic allergy in children at age 24 months.