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Background: Infection by nontuberculous mycobacteria (NTM) in patients with cystic fibrosis (CF) is often associated with significant morbidity. Limited, conflicting results are published regarding risk factors for pulmonary NTM disease. We analysed factors potentially associated with NTM in a large population of European patients with CF., Methods: We investigated associations between presence of NTM and various factors for patients registered in the European Cystic Fibrosis Society Patient Registry., Results: 374 (2.75%) of 13,593 patients studied had at least one positive NTM culture within the study year. Age- and FEV1-adjusted odds of NTM infection was more than 2.5 times higher (95%CI: 1.79; 3.60) in patients infected by Stenotrophomonas maltophilia than in patients not infected (p<0.0001), 2.36 times higher (95%CI: 1.80;3.08) in patients with ABPA than without (p<0.0001), 1.79 times higher (95%CI: 1.34; 2.38) in patients who use bronchodilators than in patients who don't (p<0.0001), 1.49 times higher (95%CI: 1.18; 1.89) in patients who use inhaled antibiotics than in patients who don't (p=0.001), and 1.30 times higher (95%CI: 1.02; 1.66) in patients who use rhDNase than in patients who don't (p=0.032)., Conclusions: NTM-positive cultures in individuals with CF are associated with distinct clinical variables. Improved data collection identifying risk factors for NTM infection will allow more focused screening strategies, and influence therapeutic choices and infection control measures in high-risk patients., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major life-threatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly reccommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme., (Copyright ©ERS 2016.)

Median survival has increased in people with cystic fibrosis (CF) during the past six decades, which has led to an increased number of adults with CF. The future impact of changes in CF demographics has not been evaluated. The aim of this study was to estimate the number of children and adults with CF in 34 European countries by 2025. Data were obtained from the European Cystic Fibrosis Society Patient Registry. Population forecasts were performed for countries that have extensive CF population coverage and at least 4 years of longitudinal data by modelling future entering and exiting flows in registry cohorts. For the other countries, population projections were performed based on assumptions from knowledge of current CF epidemiology. Western European countries' forecasts indicate that an increase in the overall number of CF patients by 2025, by approximately 50%, corresponds to an increase by 20% and by 75% in children and adults, respectively. In Eastern European countries the projections suggest a predominant increase in the CF child population, although the CF adult population would also increase.It was concluded that a large increase in the adult CF population is expected in the next decade. A significant increase in adult CF services throughout Europe is urgently required., (Copyright ©ERS 2015.)

Background: Disease registries have the invaluable potential to provide an insight into the natural history of the disease under investigation, to provide useful information (e.g. through health indicators) for planning health care services and to identify suitable groups of patients for clinical trials enrolment. However, the establishment and maintenance of disease registries is a burdensome initiative from economical and organisational points of view and experience sharing on registries management is important to avoid waste of resources. The aim of this paper is to discuss the problems embedded in the institution and management of an international disease registry to warn against common mistakes that can derail the best of intentions: we share the experience of the European Cystic Fibrosis Society Patient Registry, which collects data on almost 30,000 patients from 23 countries., Methods: We discuss the major problems that researchers often encounter in the creation and management of disease registries: definition of the aims the registry has to reach, definition of the criteria for patients referral to the registry, definition of the information to record, set up of a data quality process, handling of missing data, maintenance of data confidentiality, regulation of data use and dissemination of research results., Results: We give examples on how many crucial aspects were solved by the European Cystic Fibrosis Society Patient Registry regarding objectives, inclusion criteria and variables definition, data management, data quality controls, missing data handling, confidentiality maintenance, data use and results dissemination., Conclusions: We suggest an extensive literature research and discussions in working groups with different stake holders, including patient representatives, on the objectives, inclusion criteria and the information to record. We propose to pilot the recording of few variables and test the applicability of their definition first. The use of a shared electronic platform for data collection that automatically computes derived variables, and automatically performs basic data quality controls is a good data management practice, that also helps in reducing missing data. We found crucial for success the collaboration with existing national and international registries, cystic fibrosis organisations and patients' associations.

Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful treatments and patient outcomes to be recognized and improvement programmes to be implemented in specialist CF centres. Over the past decades, the greater volumes of data becoming available through Centre databases and patient registries led to the possibility of making comparisons between different therapies, approaches to care and indeed data recording. The quality of care for individuals with CF has become a focus at several levels: patient, centre, regional, national and international. This paper reviews the quality management and improvement issues at each of these levels with particular reference to indicators of health, the role of CF Centres, regional networks, national health policy, and international data registration and comparisons., (Copyright © 2014 European Cystic Fibrosis Society. All rights reserved.)

Pulmonary insufficiency is the main cause of death in cystic fibrosis (CF). We analysed forced expiratory volume in 1 s (FEV1) data of 14,732 patients registered in the European Cystic Fibrosis Society Patient Registry (ECFSPR) database in 2007. We used linear and logistic regressions to investigate associations between FEV1 % predicted and clinical outcomes. Body mass index (BMI), chronic infection by Pseudomonas aeruginosa, pancreatic status and CF-related diabetes (CFRD) showed a statistically significant (all p<0.0001) and clinically relevant effect on FEV1 % pred after adjusting for age. Patients with a lower BMI experience a six-fold increased odds ratio (95% CI 5.0-7.3) of having severe lung disease (FEV1 <40% pred) compared to patients with normal BMI. Being chronically infected with P. aeruginosa increases the odds ratio of severe lung disease by 2.4 (95% CI 2.0-2.7), and patients with pancreatic insufficiency experience a 2.0-fold increased odds ratio (95% CI 1.6-2.5) of severe lung disease compared to pancreatic sufficient patients. Patients with CFRD have a 1.8-fold increased odds ratio (95% CI 1.6-2.2) compared to patients not affected. These potential risk factors for pulmonary disease in patients with CF are to some degree preventable or treatable. We emphasise the importance of their early identification through frequent routine tests, the implementation of infection control measures, and a timely initiation of relevant therapies.

Background: The clinical course of Cystic Fibrosis (CF) is usually measured using the percent predicted FEV(1) and BMI Z-score referenced against a healthy population, since achieving normality is the ultimate goal of CF care. Referencing against age and sex matched CF peers may provide valuable information for patients and for comparison between CF centers or populations. Here, we used a large database of European CF patients to compute CF specific reference equations for FEV(1) and BMI, derived CF-specific percentile charts and compared these European data to their nearest international equivalents., Methods: 34859 FEV(1) and 40947 BMI observations were used to compute European CF specific percentiles. Quantile regression was applied to raw measurements as a function of sex, age and height. Results were compared with the North American equivalent for FEV(1) and with the WHO 2007 normative values for BMI., Results: FEV(1) and BMI percentiles illustrated the large variability between CF patients receiving the best current care. The European CF specific percentiles for FEV(1) were significantly different from those in the USA from an earlier era, with higher lung function in Europe. The CF specific percentiles for BMI declined relative to the WHO standard in older children. Lung function and BMI were similar in the two largest contributing European Countries (France and Germany)., Conclusion: The CF specific percentile approach applied to FEV(1) and BMI allows referencing patients with respect to their peers. These data allow peer to peer and population comparisons in CF patients.

Background: The existence of gender-related differences since childhood in survival of cystic fibrosis (CF) patients has been recently challenged., Methods: We evaluated the effect of gender on survival of 2293 CF patients born after 01/01/1988, followed up by 29 CF centres until 31/12/2004 and recorded in the Italian Registry for CF (IRCF)., Results: We observed similar annual mortality rates in females (3.59‰) and males (4.00‰), similar survival curves (log-rank test p=0.64) and similar hazards of death (hazard ratio adjusted for presence of symptoms at diagnosis, meconium ileus, F508del mutation and age at diagnosis: 1.29, 95%CI: 0.60; 2.76). However, excess mortality due to CF was higher for females (5.9) than males (5.1)., Conclusions: In our population CF females do not experience higher mortality than males but, due to the disease, they lose the expected survival advantage occurring in the general population at this age. We do not exclude, however, that differences in mortality will establish after adolescence., (Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Influenza, like other respiratory viral infections, can cause acute deterioration of lung function in patients with cystic fibrosis (CF). Previous studies on a small number of patients reported that most people with CF infected with A (H1N1) influenza experienced a mild course of disease., Aim: To characterise the impact of A (H1N1) infection on CF in a large number of patients from different centres and countries., Methods: CF centres accessing the web-site of the European Cystic Fibrosis Society (ECFS) were asked to report clinical data on patients with an ascertained diagnosis of influenza caused by the A (H1N1) virus. The study was web-based and data were collected through an electronic data sheet on the ECFS website., Results: Twenty-five centres from 10 countries caring for 4698 patients with CF reported data on 110 patients (2.3%), median age 13 years (range 1-39 years). The prevalence of infection in each centre ranged from 0% to 9.4%. Only 8.8% of the patients had been vaccinated. The main symptoms were fever and respiratory exacerbation requiring IV antibiotics in 53% of the patients; 48% of the patients were hospitalised for an average of 12.9 days (range 2-56) and 31% required oxygen treatment during the time of the infection. Most of the patients recovered and FEV(1) 1 month after the infection was similar to that before the infection. However, 6 patients were admitted to ICU, 5 with mechanical ventilation. Three patients with severe respiratory disease died., Conclusions: A (H1N1) influenza infection caused transient but significant morbidity in most of the patients with CF. However, in a small number of patients with severe lung disease, A (H1N1) influenza was associated with respiratory deterioration, mechanical ventilation and even death., (Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Evaluation of cystic fibrosis transmembrane conductance regulator (CFTR) functional activity to assess new therapies and define diagnosis of cystic fibrosis (CF) is cumbersome. It is known that leukocytes express detectable levels of CFTR but the molecule has not been characterized in these cells. In this study we aim at setting up and validating a blood test to evaluate CFTR expression and function in leukocytes., Description: Western blot, PCR, immunofluorescence and cell membrane depolarization analysis by single-cell fluorescence imaging, using the potential-sensitive DiSBAC(2)(3) probe were utilized. Expression of PKA phosphorylated, cell membrane-localized CFTR was detected in non-CF monocytes, being undetectable or present in truncated form in monocytes derived from CF patients presenting with nonsense mutations. CFTR agonist administration induced membrane depolarization in monocytes isolated from non-CF donors (31 subjects) and, to a lesser extent, obligate CFTR heterozygous carriers (HTZ: 15 subjects), but it failed in monocytes from CF patients (44 subjects). We propose an index, which values in CF patients are significantly (p<0.001) lower than in the other two groups. Nasal Potential Difference, measured in selected subjects had concordant results with monocytes assay (Kappa statistic 0.93, 95%CI: 0.80-1.00)., Results and Significance: CFTR is detectable and is functional in human monocytes. We also showed that CFTR-associated activity can be evaluated in 5 ml of peripheral blood and devise an index potentially applicable for diagnostic purposes and both basic and translational research: from drug development to evaluation of functional outcomes in clinical trials.

Background: Country-specific patients' registries are rarely used to make international comparisons because of protocol discrepancies in data collation. We present data from a European cystic fibrosis registry that is dedicated to collection of demographic data, and assess whether the resources available in countries with and without European Union (EU) membership affects care and survival of patients., Methods: Data for demographic indicators-age, age at diagnosis, sex, and genotype-for patients with cystic fibrosis from 35 European countries were combined, and used to establish the differences in demographic indicators between EU and non-EU countries. EU membership status in 2003 was used to divide countries. We modelled demographic indicators of EU countries on non-EU countries to estimate the size of the cystic fibrosis population if non-EU countries had had the same resources available for patients as did EU countries., Findings: Data were gathered for 29 025 patients, who had a median age of 16.3 years (IQR 8.9-24.8), with a difference of 4.9 years (95% CI 4.4-5.1; p<0.0001) between EU (median 17.0 years, IQR 9.5-25.6) and non-EU countries (12.1 years, 6.0-19.2). The proportion of patients older than 40 years was higher in EU countries (1205 [5%]) than in non-EU countries (76 [2%]), with an odds ratio of 2.4 (95% CI 1.9-3.0, p<0.0001). We estimated that the cystic fibrosis population in non-EU countries would increase by 84% if patients had a demographic profile comparable to that of patients in EU countries., Interpretation: Future studies need to establish the reasons for the lower proportion of patients with cystic fibrosis in non-EU countries than in EU countries, such as underdiagnosis and premature childhood mortality., Funding: European Community's Sixth Framework Programme for Research, and Czech Ministry of Health., (Copyright 2010 Elsevier Ltd. All rights reserved.)

We have conducted a pilot trial of a home telemonitoring system involving 60 adult patients with cystic fibrosis (CF) enrolled at four Italian CF centres. Thirty randomly selected patients received a home device to perform spirometry and to measure oxygen saturation. The data were transferred to a data centre which forwarded them to the patient's CF clinic. The telemonitoring system was evaluated using questionnaires completed by patients and their doctors. The doctors reported that telemonitoring was useful in monitoring their patients' health status and in decreasing the CF centre workload. The data transfer procedure posed no particular problems for the patients. The major difficulties reported by the patients were night-time saturimetry measurements, and in the first week of the study, data transmission to the data centre. The pilot trial was positive and therefore merits a larger study.

Cystic Fibrosis is the most common life-shortening autosomal recessive disease of Caucasian population. The clinical expression of the disease is heterogeneous and the treatment of CF patients requires high qualification of medical and paramedical staff. In 1992 and 1993, in Italy, two national laws (104/92 and 548/93) were enacted in favour of people affected by CF. Data gathered in the Italian Registry for CF (started on 1.1.1988) allow us to monitor changes occurred in the age structure of patients and diagnosis methods. This also thanks to the laws mentioned above. Data here presented refer to 4,209 patients, 1,964 of whom were alive on 1.1.1988, and 2,245 were diagnosed afterwards. A remarkable increase in early diagnosis (within the 3rd month of life) was noticed (from 41% to 65%), together with an increasing percentage of subjects who underwent a neonatal screening program (+34%). An increase in late diagnoses is also apparent: the frequency for patients diagnosed after 18 years of life ranged from 8% to 12%. The proportion of adult patients is more than doubled between 1988 (17%) and 2000 (41%) and the number of patients over 30 is now about 400. 512 patients died during the study period. Median age at death increased from 14 (1988) to 22 (2000) years. This trend can be observed also for patients diagnosed within the first year of life. All these changes have contributed in modifying age structure of CF population. In late 80's, the latter was mostly composed by children, while now 50% of patients are adolescents or adults. Therefore, it is now necessary to involve specialists of adult diseases in CF care.

Background: The clinical course of Cystic Fibrosis (CF) is usually measured using the percent predicted FEV1 and BMI Z-score referenced against a healthy population, since achieving normality is the ultimate goal of CF care. Referencing against age and sex matched CF peers may provide valuable information for patients and for comparison between CF centers or populations. Here, we used a large database of European CF patients to compute CF specific reference equations for FEV1 and BMI, derived CF-specific percentile charts and compared these European data to their nearest international equivalents. Methods: 34859 FEV1 and 40947 BMI observations were used to compute European CF specific percentiles. Quantile regression was applied to raw measurements as a function of sex, age and height. Results were compared with the North American equivalent for FEV1 and with the WHO 2007 normative values for BMI. Results: FEV1 and BMI percentiles illustrated the large variability between CF patients receiving the best current care. The European CF specific percentiles for FEV1 were significantly different from those in the USA from an earlier era, with higher lung function in Europe. The CF specific percentiles for BMI declined relative to the WHO standard in older children. Lung function and BMI were similar in the two largest contributing European Countries (France and Germany). Conclusion: The CF specific percentile approach applied to FEV1 and BMI allows referencing patients with respect to their peers. These data allow peer to peer and population comparisons in CF patients. [ABSTRACT FROM AUTHOR]