• Investigating the utility of the lung clearance index to guide clinical care for children with cystic fibrosis

    NCRC supported investigators at the Royal College of Surgeons in Ireland and The Hospital for Sick Children, Toronto, Canada have shown that the Lung Clearance Index is more sensitive than the standard spirometry test at detecting functional changes in the lung during acute respiratory events. The study provides additional evidence to support the clinical use of the Lung Clearance Index to track lung disease and guide treatment in children with Cystic Fibrosis.

    Cystic fibrosis (CF) is a genetic disorder characterized by lung disease which begins early in life and progresses over time. This disease affects approximately 1,300 children and adults in Ireland. Pulmonary exacerbations or episodes of acute worsening of respiratory symptoms directly contribute to disease progression and lung function tests are important gauging the severity of pulmonary exacerbations, guiding treatment, and tracking the progression of early lung disease

    Spirometry is the primary lung function test used to guide treatment decisions in school-age children. The test measures how much air a child inhales/exhales, as well as how quickly they exhale (Forced Expiratory Volume). Acute decreases in the FEV­1 (Forced Expiratory Volume in 1 second) usually triggers treatment with antibiotics. However, severe pulmonary exacerbations are rare in children and milder respiratory events are often not associated with significant spirometry changes, which complicates treatment decision making processes. There is also evidence that mild respiratory events also contribute to disease progression in children with CF.  As such, there is an urgent need for alternative more sensitive tests to track lung function and guide treatment in children with CF.

    The Lung Clearance Index (LCI) is a promising test that measures how efficiently a gas is cleared from the lungs. In patients with CF, mucus retention occurs in the lung and this results in uneven gas mixing. This increases the time to clear a tracer gas from the lung and thus increases the lung clearance index. Importantly, the LCI has been shown to reflect problems in the smaller airways of the lung which are considered the site of early lung injury in CF.

    In their recent study, lead investigator Dr. Lucy Perrem, Prof. Felix Ratjen, and colleagues sought to investigate the benefit of using the LCI to monitor changes in lung function in school-age children with CF.  In a multisite prospective observational study, the team followed a large cohort of children with CF (n = 98) over a 2-year period, measuring the LCI and FEV1 at routine clinical visits and during pulmonary exacerbations.  They found that in school-age children with CF, the LCI is more sensitive than the FVE1 at detecting functional changes in the lung during acute respiratory events. They also show that lung function, measured by both the LCI and FEV1, dies not return to baseline levels following pulmonary exacerbations, further demonstrating that even milder respiratory event contribute to disease progression. However, the results of LCI and FVE1 test were discordant suggesting that the use of both measurements in combination is superior to using either measure alone. Together, the results provide new evidence to support the clinical use of the LCI for monitoring lung function in children with CF.

    On publication of the study results, Dr. Lucy Perrem said:

    “LCI has great potential as a monitoring tool in children with CF who have early lung disease. Our results strengthen the case for using LCI as a clinical test”.


    This research is published in the “American Journal of Respiratory and Critical Care Medicine”, an international peer reviewed journal published by the American Thoracic Society.

    The complete publication can be found through the following link:

    L Perrem*, S Stanojevic, M Shaw, R Jensen, N McDonald, SM Isaac, M Davis, C Clem, J Guido, S Jara, L France, M Solomon, H Grasemann, V Waters, N Sweezey, DB. Sanders, S D. Davis, and F Ratjen. Lung Clearance Index to Track Acute Respiratory Events in School-Age Children with Cystic Fibrosis. Am J Respir Crit Care Med. 2021 Apr 15;203(8):977-986.
    doi: 10.1164/rccm.202006-2433OC.

    *Lucy Perrem is a Cystic Fibrosis Canada Fellow and has received funding support from the National Children’s Research Centre, Crumlin through our Research Education Support Grant scheme. She is currently completing at PhD at the Royal College of Surgeons in Ireland under the supervision of Prof. Paul McNally and Prof. Felix Ratjen.

    Funding for the study was obtained from the Cystic Fibrosis Foundation (award number RATJEN16A0), Cystic Fibrosis Canada (grant ID 3187), and the Cystic Fibrosis Foundation Therapeutics Development Network National Resource Centre (Center for Pediatric Lung Function).