Lung clearance index to characterize clinical phenotypes of children and adolescents with cystic fibrosis

Abstract

Background Lung clearance index (LCI) is accepted as an early marker of lung disease in cystic fibrosis (CF), however the utility of LCI to identify subgroups of CF disease in the paediatric age group has never been explored. The aim of the study was to characterize phenotypes of children with CF using LCI as a marker of ventilation inhomogeneity and to investigate whether these phenotypes distinguished patients based on time to pulmonary exacerbation (PE). Methods Data were collected on patients with CF aged < 18 years old, attending the CF Center of Milan during outpatient follow-up visits between October 2014 and September 2019. Cluster analysis using agglomerative nesting hierarchical method was performed to generate distinct phenotypes. Time-to-recurrent event analysis investigated association of phenotypes with PE. Results We collected 313 multiple breath washout tests on 125 children aged 5.5–16.8 years. Cluster analysis identified two divergent phenotypes in children and adolescents of same age, presenting with almost normal FEV1 but with substantial difference in markers of ventilation inhomogeneity (mean LCI difference of 3.4, 95% Confidence Interval [CI] 2.6–4.2). A less severe phenotype was associated with a lower risk of PE relapse (Hazard Ratio 0.45, 95% CI 0.34–0.62). Conclusions LCI is useful in clinical practice to characterize distinct phenotypes of children and adolescents with mild/normal FEV1. A less severe phenotype translates into a lower risk of PE relapse.

Time Free From Hospitalization in Children and Adolescents With Cystic Fibrosis: Findings From FEV1, Lung Clearance Index and Peak Work Rate

“…Our results confirm the clinical utility of MBWN 2 as a fundamental means to monitor lung disease in children with CF, tracking pulmonary abnormalities when spirometry is within the normal range ( 6 , 27 – 29 ). Combining results from MBWN 2 and exercise testing, we have further shown that LCI (both at 1/40th and 1/20th of the starting concentration) and ppWpeak are correlated, even in children with CF, and that these two measures can help profiling adolescents with normal FEV 1 .…”

Highly effective cystic fibrosis transmembrane conductance (regulator) modulator therapy: shifting the curve for most while leaving some further behind

“…ETI, as well as ivacaftor alone for ivacaftor responsive mutations, are now referred to as highly effective CFTR modulator therapy (HEMT) [7], leaving previous modulators, lumacaftor-ivacaftor and tezacaftor-ivacaftor to be used only in age categories yet to receive ETI approval. We have seen a decrease in pulmonary exacerbation from 31 ]. Although the initiation of ETI therapy and the COVID-19 pandemic coincided, it is difficult to determine the true effects of ETI versus social distancing and the alteration in respiratory virus seasonality that followed the early pandemic.…”

“…Chest radiographs have poor sensitivity with detecting early lung disease and even spirometry may not identify early disease. Therefore, new strategies to study and monitor lung function in infants and young children are being evaluated, such as magnetic resonance imaging (MRI) and lung clearance index (LCI) [29][30][31]. We hope these new modalities can help assess HEMT's efficacy in early lung disease and guide therapies in children.…”

Perceived burden of respiratory physiotherapy in people with cystic fibrosis taking elexacaftor–tezacaftor–ivacaftor combination: a 1-year observational study

“…The lung clearance index (LCI), convective gas mixing in the conducting airways (Scond*VT) and the diffusion–convection interaction within the acinus (Sacin*VT), was measured using an open-circuit multiple breath washout (MBW) hard- and software package with nitrogen as tracer gas (N 2 MBW) (Exhalyzer ® D and Spiroware 3.3.1 Ecomedics AG, Switzerland), as described elsewhere. 19 The LCI in the children was considered normal when below 7.1. 20 …”