An overview of international literature from cystic fibrosis registries. Part 3. Disease incidence, genotype/phenotype correlation, microbiology, pregnancy, clinical complications, lung transplantation, and miscellanea.

This is the third article related to a review of the literature based on data from national cystic fibrosis (CF) patient registries up to June 2008 and covering a total of 115 published studies. It focuses on several topics: CF incidence, genotype/phenotype correlation, microbiology, pregnancy/paternity, clinical complications, lung transplantation, and others. Seventy seven papers meeting the inclusion criteria were found to be related to the topics listed above. Another seven studies, already evaluated in previous papers of this series, were recalled for specific topics. Incidence is described by several studies, results being quite different from one country to another and quite inhomogeneous among regions within the same country. Studies on genetics address the genotype/phenotype correlation and look for a predictive value of CFTR mutations in terms of clinical outcome, with controversial results. Papers on microbiology describe the clinical relevance of different pathogens and their role in the progress of CF lung disease. A few articles give information on the features of CF women undergoing a pregnancy and try to identify the ones associated with a better outcome. Studies on clinical complications discuss prevalence and the role of haemoptysis, pneumothorax, CF related diabetes, ABPA and cancer. Papers on lung transplantation focus on models able to improve the selection criteria for transplantation candidates and the factors linked to post transplantation survival. Finally, several studies deal with a number of interesting topics related to CF epidemiology: clinical trial methodology, quality of care comparison among countries and centers, relationship between diagnosis and age/gender, and evaluation of pharmacological therapy. On the whole, CF Registries have already contributed to important advances in the knowledge of the natural history of CF, establishing the foundations for future improvement in CF research and care.

An overview of international literature from cystic fibrosis registries 2. Neonatal screening and nutrition/growth.

BACKGROUND: This is the second article related to a review of the literature based on data from national cystic fibrosis (CF) registries up to June 2008 and covering a total of 115 studies. It focuses on two topics: neonatal screening (NS) and nutritional status, with particular reference to growth. METHODS: Ten papers meeting the inclusion criteria were found on the topic of NS and its impact on the course of the disease, and were analyzed according to a dedicated grid. The issue of nutrition was addressed by 14 studies, analyzed according to similar criteria. RESULTS: Most of the studies report benefits of early diagnosis by NS, albeit to variable degrees. The benefits were assessed in terms of better nutritional status and growth, but also in terms of lower overall morbidity rate as compared to subjects diagnosed by symptoms. The main biases of these studies, which partly undermine the validity of their results, are also analyzed. A part of our analysis on nutrition/growth is dedicated to the identification of the most suitable parameters to define malnutrition: in children older than two years the body mass index percentile (BMIp) appears to be the most sensitive and significantly associated with respiratory function. Better nutritional status and satisfactory growth appear to be associated with better lung function and lower risk of death. The relationship between nutritional status and socio-economic status is also of interest. CONCLUSIONS: CF registry studies support the outcome of cohort observational studies i.e. that pre-symptomatic early diagnosis is beneficial, especially in terms of nutritional status and growth. Studies on nutrition indicate that good nutritional status is associated with better respiratory function and prognosis. Regarding methods, the need emerged to manage potential biases of this kind of non randomized studies, resorting to suitable statistical techniques, such as matching and stratification and, above all, to multivariate methods able to provide estimates adjusted for the main covariates tested.

Reference values of Forced Expiratory Volumes and pulmonary flows in 3-6 year children: a cross-sectional study.

BACKGROUND: The aims of this study were to verify the feasibility of respiratory function tests and to assess their validity in the diagnosis of respiratory disorders in young children. METHODS: We performed spirometry and collected information on health and parents' lifestyle on a sample of 960 children aged 3-6. RESULTS: The cooperation rate was 95.3%. Among the valid tests, 3 or more acceptable curves were present in 93% of cases. The variability was 5% within subjects in 90.8% of cases in all the parameters. We propose regression equations for FVC (Forced Vital Capacity), FEV1, FEV0.5, FEV0.75 (Forced Expiratory Volume in one second, in half a second and in 3/4 of a second), and for Maximum Expiratory Flows at different lung volume levels (MEF75, 50, 25). All parameters are consistent with the main reference values reported in literature. The discriminating ability of respiratory parameters versus symptoms always shows a high specificity (>95%) and a low sensitivity (<20%) with the highest OR (10.55; CI 95% 4.42-25.19) for MEF75. The ability of FEV0.75 to predict FEV1 was higher than that of FEV0.50: FEV0.75 predicts FEV1 with a determination coefficient of 0.95. CONCLUSION: Our study confirms the feasibility of spirometry in young children; however some of the current standards are not well suited to this age group. Moreover, in this restricted age group the various reference values have similar behaviour.

Neonatal screening for cystic fibrosis does not affect time to first infection with Pseudomonas aeruginosa.

OBJECTIVE: Newborn screening for cystic fibrosis was introduced in the Piedmont region of Italy in the year 2000. Our aim with this study was to estimate the effect of newborn screening on the risk of Pseudomonas aeruginosa infection at the regional cystic fibrosis pediatric reference center. METHODS: The time to first infection with P aeruginosa within the historical cohort of cystic fibrosis children diagnosed between January 1, 1997, and June 30, 2004, was investigated, comparing survival functions and the adjusted hazard ratio of children diagnosed before and after newborn screening introduction. The role of pancreatic insufficiency was also concurrently investigated. RESULTS: Overall, 71 children diagnosed with cystic fibrosis were identified, 27 cases were clinically diagnosed before newborn screening introduction, and 5 of them presented with meconium ileus, whereas 44 were identified by newborn screening. Among them 35 needed pancreatic enzyme supplementation, whereas 34 children were infected with P aeruginosa. Both the nonparametric and semiparametric survival estimates failed to show any significant increase in the risk of P aeruginosa infection among screened children compared with historical controls. However, the median time from cystic fibrosis diagnosis to P aeruginosa infection among screened children was significantly shorter (183 vs 448 days). Children with impaired pancreatic function were at high risk of P aeruginosa infection. CONCLUSIONS: The results of the study suggest that health authorities should regard newborn screening for cystic fibrosis as an opportunity to improve care and outcomes among affected children and shift the focus from whether it is appropriate to screen to how to optimize biomedical and psychosocial outcomes of screening.