BACKGROUND: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD. METHODS AND FINDINGS: A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi procedure. The aim was to reach a consensus regarding clinical trial design, best treatment comparator, clinical outcomes, measurement of those clinical outcomes and inclusion and exclusion criteria. Consensus results of this initiative included: the selection of the adaptative clinical trial as the ideal study design and agalsidase beta as ideal comparator treatment due to its longstanding use in FD. Renal and cardiac outcomes, such as glomerular filtration rate, proteinuria and left ventricular mass index, were prioritised, whereas neurological outcomes including cerebrovascular and white matter lesions were dismissed as a primary or secondary outcome measure. Besides, there was a consensus regarding the importance of patient-related outcomes such as general quality of life, pain, and gastrointestinal symptoms. Also, unity about lysoGb3 and Gb3 tissue deposits as useful surrogate markers of the disease was obtained. The group recognised that cardiac T1 mapping still has potential but requires further development before its widespread introduction in clinical trials. Finally, patients with end-stage renal disease or renal transplant should be excluded unless a particular group for them is created inside the clinical trial. CONCLUSION: This consensus will help to shape the future of clinical trials in FD. We note that the FDA has, coincidentally, recently published draft guidelines on clinical trials in FD and welcome this contribution.

• Klíčová slova
• Clinical outcomes, Clinical trial, Delphi consensus, Fabry disease, Inherited metabolic disorders, Lysosomal storage disorders,
• MeSH
• alfa-galaktosidasa genetika   MeSH
• delfská metoda MeSH
• dospělí MeSH
• enzymová substituční terapie * MeSH
• Fabryho nemoc farmakoterapie   genetika   metabolismus   patologie   MeSH
• globosidy terapeutické užití   MeSH
• glykolipidy terapeutické užití   MeSH
• izoenzymy genetika   MeSH
• klinické zkoušky jako téma * MeSH
• konsensus MeSH
• kvalita života MeSH
• ledviny účinky léků   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• sfingolipidy terapeutické užití   MeSH
• trihexosylceramidy terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• agalsidase beta MeSH Prohlížeč
• alfa-galaktosidasa MeSH
• globosidy MeSH
• globotriaosyl lysosphingolipid MeSH Prohlížeč
• globotrihexosylceramide MeSH Prohlížeč
• glykolipidy MeSH
• izoenzymy MeSH
• sfingolipidy MeSH
• trihexosylceramidy MeSH

OBJECTIVES: Air pollution has been linked to respiratory outcomes but controversy persists about its long-term effects. We used a novel technique to estimate the outdoor concentrations of sulphur dioxide (SO2) at small-area level to study the long-term effects on respiratory symptoms and disease in children. METHODS: As part of the international SAVIAH study, parents of 8,013 children aged 7-10 studied in Prague (Czech Republic) and Poznan (Poland) completed a questionnaire covering respiratory health, demographic and socio-economic factors and health behaviours (response rate 91%). This report is based on 6,959 children with complete data. Outdoor SO2 was measured by passive samplers at 80 sites in Poznan and 50 sites in Prague during 2-week campaigns. Concentrations of SO2 at each point (location) in the study areas were estimated from these data by modelling in a geographical information system. The mean of the estimated SO2 concentrations at children's homes and schools was used as an indicator of exposure to outdoor SO2. RESULTS: The prevalence of respiratory outcomes was similar in both cities. In the pooled data, 12% of children had experienced wheezing/whistling in the past 12 months; 28% had a lifetime prevalence of wheezing/whistling; 14% had a dry cough at night; and 3% had had asthma diagnosed by a doctor. The estimated mean exposure to outdoor SO2 was 80 (range 44-140) microg/m3 in Poznan and 84 (66-97) microg/m3 in Prague. After socio-economic characteristics and other covariates were controlled for, SO2 was associated with wheezing/whistling in the past 12 months (adjusted OR per 50 microg/m3 1.32, 95% CI 1.10-1.57), lifetime prevalence of wheezing/whistling (OR 1.13, 95% CI 0.99-1.30), and lifetime prevalence of asthma diagnosed by a doctor (OR 1.39, 95% CI 1.01-1.92). The association with dry cough at night did not reach statistical significance. CONCLUSIONS: In these two Central European cities with relatively high levels of air pollution, small-area based indicators of long-term outdoor winter concentrations of SO2 were associated with wheezing/whistling and with asthma diagnosed by a doctor.

• MeSH
• analýza malých oblastí MeSH
• bronchiální astma epidemiologie   MeSH
• dítě MeSH
• kašel epidemiologie   MeSH
• látky znečišťující vzduch škodlivé účinky   analýza   MeSH
• lidé MeSH
• oxid siřičitý škodlivé účinky   analýza   MeSH
• prevalence MeSH
• respirační zvuky * MeSH
• socioekonomické faktory MeSH
• zdravé chování MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Polsko epidemiologie   MeSH
• Názvy látek
• látky znečišťující vzduch MeSH
• oxid siřičitý MeSH

We report analysis of data on outdoor air pollution and respiratory symptoms in children collected in the Czech part of the international Small Area Variations in Air pollution and Health (SAVIAH) Project, a methodological study designed to test the use of geographical information systems (GIS) in studies of environmental exposures and health at small area level. We collected the following data in two districts of Prague: (1) individual data on 3,680 children (response rate 88%) by questionnaires; (2) census-based socio-demographic data for small geographical units; (3) concentrations of nitrogen dioxide (NO2) and sulfur dioxide (SO2) measured by passive samplers in three 2-week surveys at 80 and 50 locations, respectively. We integrated all data into a geographical information system. Modeling of NO2 and SO2 allowed estimation of exposure to outdoor NO2 and SO2 at school and at home for each child. We examined the associations between air pollution and prevalence of wheezing or whistling in the chest in the last 12 months by logistic regression at individual level, weighted least squares regression at small area (ecological) level and multilevel modeling. The results varied by the level of analysis and method of exposure estimation. In multilevel analyses using individual data, odds ratios per 10 microg/m3 increase in concentrations were 1.16 (95% CI = 0.95-1.42) for NO2, and 1.08 (95% CI = 0.97-1.21) for SO2. While mapping of spatial distribution of NO2 and SO2 in the study area appeared valid, the interpolation from outdoor to personal exposures requires consideration.

• MeSH
• dítě MeSH
• látky znečišťující vzduch škodlivé účinky   analýza   MeSH
• lidé MeSH
• lineární modely MeSH
• oxid dusičitý škodlivé účinky   analýza   MeSH
• oxid siřičitý škodlivé účinky   analýza   MeSH
• poruchy dýchání chemicky indukované   epidemiologie   MeSH
• prevalence MeSH
• průzkumy a dotazníky MeSH
• respirační zvuky * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• látky znečišťující vzduch MeSH
• oxid dusičitý MeSH
• oxid siřičitý MeSH