Dorota Sands

Newborn screening for cystic fibrosis: Polish 4 years’ experience with CFTR sequencing strategy

Newborn screening for cystic fibrosis (NBS CF) in Poland was started in September 2006. Summary from 4 years’ experience is presented in this study. The immunoreactive trypsin/DNA sequencing strategy was implemented. The group of 1u2009212u2009487 newborns were screened for cystic fibrosis during the programme. We identified a total of 221 CF cases during this period, including, 4 CF cases were reported to be omitted by NBS CF. Disease incidence in Poland based on the programme results was estimated as 1/4394 and carrier frequency as 1/33. The frequency of the F508del was similar (62%) to population data previously reported. This strategy allowed us to identify 29 affected infants with rare genotypes. The frequency of some mutations (eg, 2184insA, K710X) was assessed in Poland for the first time. Thus, sequencing assay seems to be accurate method for screening programme using blood spots in the Polish population.

Bilateral sweat tests with two different methods as a part of cystic fibrosis newborn screening (CF NBS) protocol and additional quality control.

Infants with positive CF newborn screening (NBS) results are called to a CF Centre for verification. Those, in whom the sweat test is elevated, undergo further medical procedures. The aim of our study was to evaluate the applicability of Nanoduct - a new system measuring sweat conductivity and giving immediate results in a CF NBS protocol. Measurements with Nanoduct were compared with the classic pilocarpine method. During 3 years 487 infants from CF NBS had both sweat tests performed on the same day, at the same CF centre. CF infants had a mean conductivity of 99.8 ± 1 8.8 mmol/L and a mean chloride concentration of 74.0 ± 18.4 mmol/L. Non-CF infants values were 29.8 ± 7.7 mmol/L and 19.2 ± 6.6 mmol/L respectively. A good correlation between both tests was found (95% confidence level (CI); r=0.87). The optimal cut off, based on follow up experience of screened children, for conductivity tests was 50 mmol/L and for chloride concentration was 34 mmol/L (no lost CF, 11 false positive) with 100% sensitivity and 97.5 % specificity. In conclusion Nanoduct is a very useful and reliable tool in CF NBS protocol, allowing more time efficient organization of the diagnostic and training procedures. Simultaneous bilateral sweat testing with two different methods (concentration and conductivity) provides an extra quality control system.

Comparison of two tobramycin nebuliser solutions: Pharmacokinetic, efficacy and safety profiles of T100 and TNS

BACKGROUNDnTobramycin inhalation is an accepted treatment of chronic pseudomonal infection in cystic fibrosis (CF) patients. Twice daily inhalation is efficacious, but time-consuming.nnnMETHODSnIn this randomized, open-label, multicentre, two-period, crossover study, 58 patients with CF and chronic Pseudomonas aeruginosa (PA) infection received two tobramycin nebuliser solutions: T100/eFlow or TNS/PARI LC PLUS. The primary objective was to demonstrate the equivalence of both treatments with respect to pharmacokinetics (area under the concentration-time curve and maximum concentration in plasma). Secondary endpoints were tobramycin sputum pharmacokinetics, reduction in PA colony forming units, improvement of lung function, incidence of adverse drug reactions and reduction of inhalation times.nnnRESULTSnTobramycin plasma AUC and Cmax were lower after administration of T100 than after TNS. The study failed to demonstrate systemic bioequivalence of the two treatments. After T100 administration, tobramycin sputum AUC and Cmax achieved higher values than after TNS. Changes in efficacy parameters from baseline were similar. Safety profiles were not different or unexpected. Inhalation time per inhalation was shorter during treatment with T100.nnnCONCLUSIONnThe lower systemic drug burden and the higher local drug deposition together with a comparable efficacy/safety profile and a shorter inhalation time render T100/eFlow an attractive treatment option for CF patients. (www.controlled-trials.com/ISRCTN85410458).

Age of menarche in girls with cystic fibrosis

UNLABELLEDnMalnutrition, delayed growth and puberty are commonly observed in children suffering from cystic fibrosis. The aim of this study was to assess the age of menarche in girls with CF using status quo analysis. The relationship between types of CFTR mutations and onset of the first menstruation was also evaluated. Material was based on somatic data gathered from medical history records of 47 girls with cystic fibrosis, aged 11-18 years. All girls were patients of the Mother and Child Institute in Warsaw (Poland).nnnRESULTSnThe age of menarche in the girls in the study group was 14.65+/-1.21 years. In comparison with the healthy child population, girls with cystic fibrosis experienced menarche with 2 years delay. Menstruating girls were found to be statistically older and taller than their non-menstruating consorts. Regarding body mass and BMI, a marked tendency towards higher parameter values was noted in the menstruating group, although the differences did not reach statistical significance. A significant relationship between onset of menarche and type of CFTR mutation was found. Girls with cystic fibrosis enter puberty later than their peers, in spite of intensive medical care. The issue of growth and puberty in children with CF requires further detailed investigation under clinical and auxological aspects.

Gastroesophageal Reflux Disease in Children with Cystic Fibrosis

Previously published studies have indicated that gastroesophageal reflux (GER) disease is common in pediatric patients with cystic fibrosis. The aim of the present study was to get insight into the incidence of GER and to characterize the nature of reflux episodes in children with cystic fibrosis. This was a multicenter, prospective study of children with cystic fibrosis older than 18 months. Forty four consecutive patients (22 boys, mean age 10.4u2009±u20093.6, range 3.0-17.8 years) were enrolled into the study. All patients underwent 24 h pH-impedance monitoring. GER were classified according to the widely recognized criteria as an acid, weakly acid, weakly alkaline, or proximal. The pH-impedance trace was considered abnormal when acid exposure was >6 %. GER was diagnosed in 24/44 (54.5 %) children. A total of 1585 (median 35, range 7-128) reflux episodes were detected; 1199 (75.6 %) were acidic, 382 (24.1 %) weakly acidic, and 4 (0.3 %) weakly alkaline. Six hundred and ninety-one (43.6 %) reflux episodes reached the proximal esophagus. In 14/44 patients typical GER symptoms were present. We conclude that the incidence of GER in children with cystic fibrosis is very high. In the majority of patients typical GER symptoms are absent. Therefore, diagnostic procedures should be considered, regardless of lacking symptoms. Although acid reflux episodes predominate in children with cystic fibrosis, classical pH-metry may not constitute a sufficient diagnostic method in this population because of a relatively high number of proximal reflux episodes. Such episodes also indicate an increased risk for aspiration. The pH-impedance diagnostic measurement is advocated when suspecting GER in children with cystic fibrosis.

Physical development in children and adolescents with bronchial asthma

Bronchial asthma is the most common chronic disease in children of developmental age. Data from the auxological literature indicate that children with disturbances in growth may also suffer from atopic disorders. The aim of the present study was to evaluate somatic growth in children with bronchial asthma using anthropological methods. The study was carried out using anthropometric measurements and information on the severity and course of the disease on 261 children with bronchial asthma. Mean body height was lower than in healthy peers and about 5% of subjects were short. Mean BMI and skinfold thicknesses were significantly higher and lean body mass was lower in the study group. Seventeen percent of the children were overweight or obese, and 8% were underweight. Body build was more robust in the girls examined. Longitudinal studies will help determine to what degree the disease itself directly affects physical development, and to what degree treatment does.

Evaluation of factors related to bone disease in Polish children and adolescents with cystic fibrosis

PURPOSEnThe aim of the study was to evaluate factors related to bone formation and resorption in Polish children and adolescents with cystic fibrosis and to examine the effect of nutritional status, biochemical parameters and clinical status on bone mineral density.nnnMATERIALS AND METHODSnThe study group consisted of 100 children and adolescents with cystic fibrosis with a mean age 13.4 years old. Anthropometric measurements, included body height, body mass and body mass index (BMI); bone mineral densitometry and biochemical testing were performed. Bone mineral density was measured using a dual-energy X-ray absorption densitometer. Biochemical tests included serum calcium, phosphorus, parathyroid hormone and vitamin D concentrations, as well as 24-h urine calcium and phosphorus excretion. Pulmonary function was evaluated using FEV1%, and clinical status was estimated using the Shwachman-Kulczycki score.nnnRESULTSnStandardized body height, body mass and BMI were significantly lower than in the reference population. Mean serum vitamin D concentration was decreased. Pulmonary disease was generally mild, with a mean FEV1% of 81%. Multivariate linear regression revealed that the only factors that had a significant effect on bone marrow density were BMI and FEV1%. There were no significant correlations between bone mineral density and the results of any of the biochemical tests performed.nnnCONCLUSIONSnNutritional status and bone mineral density were significantly decreased in children and adolescents with cystic fibrosis. In spite of abnormalities in biochemical testing, the factors that were found to have the strongest effect on bone mineral density were standardized BMI and clinical status.

Insights into the cystic fibrosis care in Eastern Europe: Results of survey

BACKGROUNDnThe European cystic fibrosis (CF) Society Standards of Care were set to facilitate the delivery of high-quality care throughout Europe. However, their implementation may be difficult for less economically advantaged countries. This survey was performed to explore the gap in the knowledge of the level of CF care in Eastern Europe.nnnMETHODSnQuestionnaires were sent online to one CF professional and one CF patient representative for every Eastern European country.nnnRESULTSnAlthough most respondents indicated the presence of CF centres, disparities in their framework among individual countries and between them and the European CF Standards of Care became apparent. A minority of countries achieved CF centre recognition by the government (6 of 16), provided CF care for adults (6 countries) and had a multidisciplinary team with all team members represented (2 countries). Patients were significantly more critical in the evaluation of various aspects of CF care than physicians, especially in the Balkan region.nnnCONCLUSIONSnThe survey results indicate that the organization and level of CF care across Eastern Europe is largely variable and lacks some of its fundamental attributes in several countries.

Comparison of health-related quality of life among children with cystic fibrosis and their parents in two Eastern European countries

BACKGROUNDnIn the optimal care of cystic fibrosis (CF) patients, not only medical parameters are respected but also health-related quality of life (HRQOL). The aim of our study was to compare HRQOL of CF patients from two Eastern European countries.nnnMETHODSn141 patients with CF (6-18 years) and 102 parents completed the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Data about disease severity, type of childrens education and questions about parents employment status were collected.nnnRESULTSnIn the patient group, a significant difference was found only in Treatment burden, whereas in the parent group, there were significant differences in Treatment burden, Emotional functioning, Eating and Digestive symptoms between the two countries. School attendance was revealed as an important factor influencing HRQOL.nnnCONCLUSIONSnObserved differences in evaluation of HRQOL may be caused by different therapeutic and diagnostic challenges between countries. To identify possible presence of psychosocial problems, monitoring of HRQOL is recommended.

A cross-sectional study of growth, nutritional status and body proportions in children and adolescents at a medical center specializing in the treatment of cystic fibrosis in Poland

Introduction Malnutrition, delayed growth and delayed puberty are commonly seen in children with cystic fibrosis. The aim of this study was to evaluate growth, nutritional status and body proportions in children and adolescents suffering from cystic fibrosis. Material and methods The evaluation was based on 19 somatic measurements and indices calculated from these measurements. Somatic development was evaluated in relation to several factors connected to the clinical picture or the course of the disease. Anthropometric data were extracted from the medical histories of 41 boys and 48 girls diagnosed and treated at the Institute of Mother and Child in Warsaw (Poland). Mean values for somatic parameters and body build indices for the children suffering from CF were compared to those for the reference group. Results The results revealed that growth in these children was significantly delayed in comparison to that seen in the healthy population (Z-score = –0.56, p < 0.001). Nutritional status was also adversely affected (Z-score = –0.85, p < 0.001). The children suffered more from a deficit in muscularity than in adiposity (Z-score = –0.75 and Z-score = –0.34, p < 0.01, respectively). This was especially true for boys. The children had infantile body proportions and defects in trunk and chest structure. Conclusions The factors that most affected somatic development were infection by Pseudomonas aeruginosa and the time at which the disease was diagnosed. Chronic infection by P. aeruginosa and type of CFTR mutation were the factors that most affected pulmonary function parameters.