(122) Changes in the lung clearance index in individuals who are newborn screening positive for CF with an inconclusive diagnosis (CFSPID)

Background: Routine follow-up of individuals who are newborn screening positive for CF with an inconclusive diagnosis (CFSPID) is considered standard of care to observe for indications of clinical features of disease [1]. Standard measures of lung function may not be sensitive enough to pick up early signs of disease. The lung clearance index (LCI), as measured by multiple breath washout (MBW), has been found to be a sensitive measure of early lung disease and progression in cystic fibrosis and could be a useful tool for tracking the CFSPID population over time. Our previous analysis of this cohort was limited to primarily preschool-aged children [2], and with the availability of school-aged data in this group, this study aims to describe changes in LCI over time within CFSPID individuals.

Methods: Children identified as CFSPID were prospectively followed annually with routine sweat chloride testing and clinical assessments as outlined previously [1]. A subset of patients performed MBW during their annual visits, using the Exhalyzer D® (Eco Medics AG, Switzerland) with nitrogen as a tracer gas, and results were generated out of Spiroware v3.3.1 (Eco Medics AG). Visits were classified to be stable or symptomatic, if the individual had respiratory symptoms at the time of testing based on physician assessment. Spirometry, and sweat chloride results were collected for each visit.

Results: A total of 58 MBW measurements were collected in 20 children (55% female). CFSPID children had a median (IQR) 3 (2, 5) MBW measurements. The mean (SD) age at first MBW measurement was 5.4 (1.1) years of age. Overall, the mean (SD) LCI of all visits was 6.34 (0.67). The LCI was 0.48 units lower in school age (≥6 years) than preschool ( < 6 years) (95% CI -0.83, -0.12; p=0.009). Additionally, the LCI was 1.05 units higher for symptomatic visits compared to stable visits (95% CI 0.60, 1.51; p< 0.001) with most (6/7) of the symptomatic visits occurred under the age of 7 reflecting the higher incidence of viral infections in younger children. During school age, all individuals with previously elevated LCI for whom repeated measures in school age were available demonstrated decline (improvement) of LCI on follow-up and LCI remained within the range defined for healthy children (Figure 1) [3].

Conclusions: Our current analysis suggests that children with CFSPID have normal lung function when measured by LCI during early school age. Follow-up measurements in children with previously elevated LCI may be useful to ensure that the initial measurement is not interpreted as evidence of significant lung disease.

Acknowledgements:

References: [1] Gonska T et al. Outcomes of Cystic Fibrosis Screening-Positive Infants With Inconclusive Diagnosis at School Age. Pediatrics. 2021; 148(6):e2021051740.

[2] Au JW et al. Can the LCI identify early lung disease in children with CFSPID? Pediatric Pulmonology. 2017; 52 (S47): 294.

[3] Anagnostopoulou P et al. Normative data for multiple breath washout outcomes in school-aged Caucasian children. Eur Respir J. 2020. 55(4):1901302.