Comparative sensitivity of Early Cystic Fibrosis Lung Disease detection tools in school aged children

Abstract

ABSTRACTBackgroundEffective detection of early lung disease in cystic fibrosis (CF) is critical to understanding early pathogenesis and evaluating early intervention strategies. We aimed to compare ability of several proposed sensitive functional tools to detect early CF lung disease as defined by CT structural disease in school aged children.Methods50 CF subjects (mean±SD 11.2±3.5y, range 5-18y) with early lung disease (FEV1≥70% predicted: 95.7±11.8%) performed spirometry, Multiple breath washout (MBW, including trapped gas assessment), oscillometry, cardiopulmonary exercise testing (CPET) and simultaneous spirometer-directed low-dose CT imaging. CT data were analysed using well-evaluated fully quantitative software for bronchiectasis and air trapping (AT).ResultsCT bronchiectasis and AT occurred in 24% and 58% of patients, respectively. Of the functional tools, MBW detected the highest rates of abnormality: Scond82%, MBWTG RV78%, LCI 74%, MBWTG IC68% and Sacin51%. CPET VO2peak detected slightly higher rates of abnormality (9%) than spirometry (FEV1/FVC 8%, FEF25-758%, FEV12%). For oscillometry AX (14%) performed better than Rrs (2%) whereas Xrs and R5-19 failed to detect any abnormality. LCI and Scondcorrelated with bronchiectasis (r=0.55-0.64, p<0.001) and AT (r=0.73-0.74, p<0.001). MBW-assessed trapped gas was detectable in 92% of subjects and concordant with CT-assessed AT in 74%.ConclusionsSignificant structural and functional deficits occur in early CF lung disease, as detected by CT and MBW. For MBW, additional utility, beyond that offered by LCI, was suggested for Scondand MBW-assessed gas trapping. Our study reinforces the complementary nature of these tools and the limited utility of conventional oscillometry and CPET in this setting.AUTHOR CONTRIBUTIONSConception and design: KB, OW, MOW, BB, TER, PG, DF, HS, PRAcquisition, analysis and interpretation of data: KB, OW, CB, AB, RF, PG, AM, HS, BK, MOW, LY, CG, BB, TER, PRWriting the manuscript or revising it critically for important intellectual content: KB, OW, CB, AB, RF, AM, BK, GJ, NC, PG, DF, HS, CG, MOW, BB, TER, PRHIGHLIGHTSIn early lung disease, multiple breath washout and CT are complementary toolsMBW and CT detect more abnormality than oscillometry, CPET and spirometrySensitivity of MBW to detect abnormality can be increased by Scondand MBW-assessed trapped gasGRANT SUPPORTAustralian Cystic Fibrosis Research Trust: 2018 Innovation Grant. This study was supported by grants from the German Federal Ministry of Education and Research (82DZL004A1) (to OW, MOW).