A multimodal approach to detect and monitor early lung disease in cystic fibrosis

ABSTRACT

Introduction: In the early stages, lung involvement in cystic fibrosis (CF) can be silent, with disease progression occurring in the absence of clinical symptoms. Irreversible airway damage is present in the early stages of disease; however, reliable biomarkers of early damage due to inflammation and infection that are universally applicable in day-to-day patient management have yet to be identified.

Areas covered: At present, the main methods of detecting and monitoring early lung disease in CF are the lung clearance index (LCI), computed tomography (CT), and magnetic resonance imaging (MRI). LCI can be used to detect patients who may require more intense monitoring, identify exacerbations, and monitor responses to new interventions. High-resolution CT detects structural alterations in the lungs of CF patients with the best resolution of current imaging techniques. MRI is a radiation-free imaging alternative that provides both morphological and functional information. The role of MRI for short-term follow-up and pulmonary exacerbations is currently being investigated.

Expert opinion: The roles of LCI and MRI are expected to expand considerably over the next few years. Meanwhile, closer collaboration between pulmonology and radiology specialties is an important goal toward improving care and optimizing outcomes in young patients with CF.

KEYWORDS:

• Cystic fibrosis
• lung clearance index
• magnetic resonance imaging

Abbreviations

BAL	=	bronchoalveolar lavage
CF	=	cystic fibrosis
CFTR	=	cystic fibrosis transmembrane conductance regulator
CT	=	computed tomography
EBC	=	exhaled breath concentrate
FEV1	=	forced expiratory volume in 1 second
FVC	=	forced vital capacity
LCI	=	lung clearance index
MBW	=	multiple-breath washout
MRI	=	magnetic resonance imaging
RVRTC	=	raised-volume rapid thoracoabdominal compression
SF6	=	sulfur hexafluoride
UTE	=	ultrashort echo time
VIPS	=	ventilation inflammation perfusion and structure

Article highlights

• In the early stages, lung involvement in CF can be silent, with inflammation and airway damage occurring in the absence of infection or symptoms.

• Disease progression can be delayed or ameliorated by reducing inflammation and treating infections.

• Sensitive, safe, easy-to-perform, and preferably low-cost methods are needed in order to better detect and monitor early lung disease in young children with CF.

• The most appropriate methods for detecting and monitoring early lung disease in CF are currently LCI, CT, and MRI.

• LCI is a reproducible technique that is used to detect early airway dysfunction, especially in children, and to monitor responses to new interventions.

• CT detects structural alterations in CF with the best resolution of current imaging techniques.

• MRI is a sensitive ionizing radiation-free technique that provides both morphological and functional imaging.

• LCI, CT, and MRI provide complementary information.

• Increased access to these technologies over the next several years may improve short- and long-term outcomes for children with CF.

Declaration of interest

P Mondéjar-López has received speaker fees and personal honoraria as a consultant for Vertex. O Asensio de la Cruz has received speaker fees from Chiesi and Vertex, and has acted as a consultant to Vertex. O Asensio de la Cruz has also received funding for Vertex-sponsored studies and has been Chief/Principal investigator on studies sponsored by Gilead and Vertex. A Horsley has received funding from the Cystic Fibrosis Foundation, the Cystic Fibrosis Trust, and the National Institute of Health Research (NIHRCS012-13). A Horsley has participated in educational activities funded by Vertex and has performed advisory board work for Boehringer Ingelheim, Chiesi, and Vertex. A Horsley also has a collaboration agreement with Innocor ApS, has acted as a consultant for Celtaxsys, and has been Chief/Principal investigator on studies sponsored by Boehringer Ingelheim, Flatley Discovery Lab, Galapagos, Novartis, Proteostasis, and Vertex. F Ratjen has acted as a consultant to Vertex, has received funding for Vertex-sponsored studies, and has received reimbursement and travel support for presentations at meetings sponsored by Vertex. S Bertolo has received personal honoraria as a consultant from Vertex. H de Vicente is an employee of Vertex Pharmaceuticals Spain S.L. and may own stock or stock options in that company. The author(s) have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Previous presentations

The topics in this manuscript were previously presented by the authors at an educational meeting that was organized and funded by Vertex Pharmaceuticals (Europe) Ltd.

Additional information

Funding

Writing assistance was provided by Robert Furlong and Kerry Dechant of Content Ed Net (Madrid, Spain), which was funded by Vertex Pharmaceuticals (Europe) Ltd. Editorial assistance was provided by Laura Gibbons, PhD, of Complete HealthVizion, which was funded by Vertex Pharmaceuticals (Europe) Ltd.