The CFTR Modulator Treatment for Cystic Fibrosis Increases Life Expectancy Even Further

The CFTR Modulator Treatment for Cystic Fibrosis Increases Life Expectancy Even Further

A conversation with Prof. Ernst Eber, the Head of Paediatric Pulmonology in Graz and an invited speaker at the Scientific Conference, about recent advances and AI use in the field

Ernst Eber, MD, ATSF, FERS is a paediatric pulmonologist, Professor of Paediatrics, Chair of the Department of Paediatrics and Adolescent Medicine, and Head of the Division of Paediatric Pulmonology and Allergology and Cystic Fibrosis Centre at the Medical University of Graz.

He was Secretary and Chair of the Bronchology Group of the Paediatric Assembly of the European Respiratory Society (ERS), Secretary and Head of the Paediatric Assembly of the ERS, and Curriculum Design Director of the ERS. He has been member of a variety of (ERS and American Thoracic Society/ATS) task forces (on flexible bronchoscopy in children, bronchoalveolar lavage, interstitial lung diseases, wheezing disorders, medicines in children, Paediatric and Adult HERMES, primary ciliary dyskinesia, monitoring of asthma, interventional bronchoscopy in children), committees, consensus groups, and scientific advisory boards. He has performed many educational activities in several Postgraduate and School Courses of the ERS and ATS. Further, he is Associate Editor of Paediatric Respiratory Reviews and Associate Editor of Respiration. He is editor of several books including Pediatric Pulmonary Function Testing and Pediatric Bronchoscopy (both Karger) and of the ERS Handbook Paediatric Respiratory Medicine. His main topics of research projects and publications include: various aspects of cystic fibrosis, assessment of bronchial responsiveness, (infant) lung function testing, flexible bronchoscopy, congenital malformations of the upper and lower respiratory tract, interstitial lung diseases, primary ciliary dyskinesia, and various aspects of bronchial asthma.

Cystic fibrosis transmembrane conductance regulator (CFTR) therapy is a recent method of treating cystic fibrosis. What does it consist in and what is its efficiency?

As yet, more than 2,100 mutations have been described in the CFTR gene; they are typically classified in six mutation classes. The most common mutation is F508del, a type II mutation. The wild type CFTR protein consists of 1,480 amino acids; there are only 1,479 amino acids with F508del. CFTR modulators (CFTRm) are small molecules which may correct dysfunctional CFTR proteins: they are grouped into CFTR correctors and potentiators. CFTR correctors stabilise the membrane spanning domain 1 (e.g. tezacaftor) or the interactions between the membrane spanning domain 2 and the nucleotide binding domain 1 (e.g. elexacaftor), resulting in more CFTR protein present in the cell membrane. CFTR potentiators (e.g. ivacaftor) improve the function of the CFTR protein. The so-called triple therapy, consisting of the correctors tezacaftor and elexacaftor in combination with the potentiator ivacaftor, is licensed for all people with cystic fibrosis above six years of age with at least one F508del mutation. In central European countries including the Czech Republic, about 85 percent of people with cystic fibrosis carry at least one F508del mutation. While individual responses with respect to lung function or sweat chloride concentration may vary, the median improvement due to this highly effective therapy in a number of aspects is both significant and clinically relevant.

Does it significantly improve quality of life and life expectancy in people with cystic fibrosis?

Yes, CFTRm treatment significantly improves lung function and body mass index, reduces pulmonary exacerbations, and also significantly improves quality of life and life expectancy in people with cystic fibrosis. This has been shown in particular for ivacaftor, which was the first CFTRm to be licensed – already in 2012. With progress in conventional therapy, life expectancy in people with cystic fibrosis has continuously increased over the last decades, i.e. before the availability of CFTRm treatment. With the advent of the latter, it will increase even further, especially for people with cystic fibrosis who will be treated already in preschool years.

How far are we from using CFTR therapy across all needy patients – I refer to the question of costs versus health insurance budgets. Or are there any other obstacles?

Costs are definitely an issue, on a global perspective but also in Europe. It is estimated that across the world only approximately 12 percent of the estimated number of people with cystic fibrosis (approximately 160,000 of which two thirds have an established diagnosis) have access to this treatment. Data from the European cystic fibrosis patient registry clearly show that – even when only conventional cystic fibrosis treatment was available – median life expectancy was associated with the health care expenditure in percent of the GDP of countries, with a difference of more than ten years of life expectancy between the first and the third tertile.

An ultimate technological innovation that hit medicine and especially imaging methods is the use of artificial intelligence. How is this tool proving itself in lung imaging? How is machine learning being integrated into the interpretation of these images? Or also somewhere else in pulmonology?

Today, artificial intelligence already has started to play a role in paediatric chest imaging. There is a range of applications, including deep learning algorithms for detecting clinically important diseases in chest radiographs; scoring automation of CT scans of people with cystic fibrosis; automatic bronchus and artery analysis on chest CT again in cystic fibrosis, but also primary ciliary dyskinesia, or bronchopulmonary dysplasia patients; and new AI-powered applications such as from MRI to synthetic CT, i.e. synthetic imaging with ventilation, perfusion, angiography and structure in a single examination.

You are dedicated to education in pneumology at the European level – are there any new recommendations for managing paediatric respiratory conditions that parents or caregivers should be aware of?

The European Respiratory Society has a leading role in producing and publishing guidelines, statements and technical standards. It is mandatory that a patient or caregiver representative contribute to these recommendations. All ERS recommendations are freely accessible on its website. At this point, I want to make you aware of the European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged five to sixteen years and the ERS guidelines on the diagnosis and treatment of chronic cough in adults and children in particular.

What can visitors expect from your lecture at the Second Faculty´s Scientific Conference?

I will try to give a short overview of recent advances in Paediatric Pulmonology, including CFTR modulator treatment in people with cystic fibrosis, diagnosis and management of primary ciliary dyskinesia, therapeutic strategies in paediatric severe asthma, lung imaging, lung function testing with the MBW technique, and interventional bronchoscopy, obviously without going into detail due to time restriction.

Vytvořeno: 23. 10. 2023 / Upraveno: 12. 6. 2024 / Mgr. Petr Andreas, Ph.D.