Latin American Newborn and Early Screening of Cystic Fibrosis Patients (LANES)
1st Expert Consensus Meeting in collaboration with the ECFS Diagnostic Network Working Group and Novartis
Objectives: Establishing an early diagnosis of CF in Latin America is suspected to be challenging due to several reasons, including heterogeneity of the population, availability and costs of diagnostic tests and lack of public awareness for CF in some countries.
Methods: An initiative by the ECFS Diagnostic Network Working Group aimed to better understand the current status of early CF diagnosis in Latin America. Expert representatives from 13 Latin American countries (Mexico, Guatemala, Costa Rica, Panama, Dominican Republic,Venezuela, Colombia, Ecuador, Uruguay, Brazil, Peru, Argentina, Chile) were invited to prepare a structured summary on the history and current situation of CF diagnosis in their country, and to share their experiences at the first Latin American Newborn and Early Screening of Cystic Fibrosis Patients (LANES) consensus meeting which was held in August 2015 in Sao Paolo, Brazil together with representatives from the ECFS DNWG and ECFS Patient Registry.
Results: Important differences and challenges in diagnosing CF were discussed, including epidemiology, CF newborn screening, sweat test, CFTR genotyping and use of CF registries.
Conclusion: The LANES project is the first joint initiative to summarise current practices and future perspectives for early CF diagnosis in Latin America. Increasing public awareness for early CF diagnosis was agreed to be of critical importance. Results from all attendees highlighted the significance and success of the LANES meeting, allowing for shared experiences to be discussed and future relationships and collaborations to achieve the best outcomes for CF patients in Latin America.
Results of this project were presented at ECFC Basel (Workshop 11) and at the ECFS DNWG Meeting in London. Publication of results is underway.
CFTR biomarker: standardisation and diagnostic reference values (I. Sermet, I. Bronsveld, M. Wilschanski, H. De Jonge, N. Derichs)The "standard" test for diagnosing CF is the sweat test. However, an increasing group of patients cannot be diagnosed with the sweat test as results are in an intermediate range of CFTR dysfunction. Therefore, also newer tests have been developed to ascertain and further quantify the basic defect in CF, the lack of CFTR-mediated chloride ion transport. The nasal potential difference (NPD) test examines the chloride transport in the nose and the intestinal current measurement (ICM) examines CFTR function ex vivo in rectal biopsies. Both these tests have been further optimised, and new European SOPs have been developed by the ECFS DNWG for use as a diagnostic aid and for therapeutic outcome strategies in Europe. These SOPs for ICM and NPD will allow centre-independent comparison of results and reference values. In the last WG period, we extensively worked together on a multicenter basis to validate the new SOPs. Results of this project were presented at ECFC Basel (Workshop 18) and at the ECFS DNWG Meeting in Ljubljana 2017. Publication of results is being planned within 2017/18.
Real life practice of sweat testing in Europe and development of an ECFS sweat test guideline for diagnosis of CF (N.Cirilli, N.Derichs)
Project Core Group: Natalia Cirilli, Kevin Southern, Jürg Barben, Lutz Nährlich, Anne Munck, Michael Wilschanski, Kris De Boeck, Nico Derichs
The aim of the project is to better understand and improve sweat test practices in European countries, and to develop harmonised European recommendations on sweat testing in real life settings.
1) to assess current sweat test practice across Europe
2) to identify examples of good practice and challenges
3) to develop and agree minimal sweat test standards
4) to form a European consensus on recommendations for good real life practice
5) to develop training resources to support sweat testing services across Europe
This project started by performing a survey about the current sweat test practice in Europe.
First results of this project were presented at ECFC Basel (Workshop 11) and at the ECFS DNWG Meeting in Ljubljana 2017. The results of the survey have now been published in the Journal of Cystic Fibrosis 2017.
Next steps will focus on the development of training resources and recommendations to improve sweat test performance in Europe.
Complete CFTR gene mutation analysis in European patients with Cystic Fibrosis
(Project Leader: Harry Cuppens (geneticist) and Kris De Boeck (clinician))
To provide a service for highly parallel sequencing of the complete CFTR gene (including intronic and promoter regions) in patients with confirmed CF (maximum 5 patients per individual site) in whom a disease-causing mutation was not found on both CFTR genes
CFTR3: Personalised characterization of rare Cystic Fibrosis genotypes
(Project Leader: N. Derichs)
The CFTR3 consortium is equipped with the leading European experts in the field of CF diagnosis and clinical care. This prospective project aims to newly establish a European database on the functional and clinical consequences of rare CFTR mutations/variants that are not possible to be characterised within CFTR2. In synergistic addition to CFTR2, the CFTR3 project will use personalised characterisation of in vivo and ex vivo CFTR function in native human epithelia by 3-organ targeted CFTR biomarkers.
The rationale of CFTR3 is that a complete description of the basic disease defect and characterisation of rare CFTR gene variants/mutations can lead to a highly personalised medicine using diagnostic classification and clinical care as a typical example of patients stratification. Results of functional CFTR analysis in patients respiratory and intestinal epithelia will create a basis for new therapeutic approaches on an individualised level, e.g. CFTR modulators focusing on rare single CFTR mutations with otherwise unknown ability to increase residual CFTR activity.
If you are interested to contribute to CFTR3 by submission of individual cases of subjects with rare CFTR genotypes please contact: firstname.lastname@example.org.
ECFS DNWG CF Diagnosis Registry project
(Project Leader: K. De Boeck)
The ECFS DNWG started a project to evaluate current documentation of CF diagnosis in the CF registries and to connect the work of the ECFS DNWG and the ECFS Patient Registry. It was hypothesized that diagnosis data are incomplete e.g. due to changing techniques and terminology, lack of harmonized criteria for relevance of CFTR mutations and insufficient quality control systems.
The ECFS DNWG CF Diagnosis Registry project is closely collaborating with the ECFS Patient Registry and National CF registries, and includes the following workpackages:
- Workpackage 1: Determine the scope of the problem: who is reported in national CF registries? (K. De Boeck)
- Workpackage 2: Measures to improve documentation of CF diagnosis in CF registries (N. Derichs)
- Workpackage 3: Are national registries with and without neonatal screening comparable? Is the cohort of patients younger than 8 years different in national registries with and without newborn screening? (A. Munck, K. De Boeck)
- Workpackage 4: How to define CF diagnosis by CFTR biomarker NPD and ICM (M. Wilschanski, N. Derichs)
ECFS DNWG CF Diagnostic Expert Webforum
(Project Leader: V.Mühlbacher, N.Derichs)
This new project is providing a diagnostic expert service to ECFS members from all countries. Difficult cases can be submitted online in a structured phenotype description form and will be discussed among a group of experts from all fields of CF diagnosis. The submitting physicians will receive feedback, and patients with questionable CF might profit from this diagnostic consultation service on an individual basis. More details will be announced soon.