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Characterizing mucociliary clearance in young children with cystic fibrosis

Abstract

Background

This research characterized mucociliary clearance (MCC) in young children with cystic fibrosis (CF).

Methods

Fourteen children (5–7 years old) with CF underwent: two baseline MCC measurements (Visits 1 and 2); one MCC measurement approximately 1 year later (Visit 3); and measurements of lung clearance index (LCI), a measure of ventilation inhomogeneity.

Results

Median (range) percent MCC through 60 min (MCC60) was similar on Visits 1 and 2 with 11.0 (0.9–33.7) and 12.8 (2.7–26.8), respectively (p = 0.95), and reproducible (Spearman Rho = 0.69; p = 0.007). Mucociliary clearance did not change significantly over 1 year with median percent MCC60 on Visit 3 [12.8 (3.7–17.6)] similar to Visit 2 (p = 0.58). Lower percent MCC60 on Visit 3 was significantly associated with higher LCI scores on Visit 3 (N = 14; Spearman Rho = −0.56; p = 0.04).

Conclusions

Tests of MCC were reproducible and reliable over a 2-week period and stable over a 1-year period in 5–7-year-old children with CF. Lower MCC values were associated with increased ventilation inhomogeneity. These results suggest that measurements of MCC could be used in short-term clinical trials of interventions designed to modulate MCC and as a new, non-invasive test to evaluate early lung pathology in children with CF.

Impact

  • This is the first study to characterize mucociliary clearance (MCC) in children with cystic fibrosis (CF) who were 5–7 years old.

  • Measurements of mucociliary clearance were reproducible and reliable over a 2-week period and stable over a 1-year period.

  • Variability in MCC between children was associated with differences in ventilation homogeneity, such that children with lower MCC values had increased ventilation inhomogeneity.

  • These results suggest that measurements of MCC could be used in short-term clinical trials of interventions designed to modulate MCC and as a new, non-invasive test to evaluate early lung pathology in children with CF.

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Fig. 1: Percent MCC60 and MCC90 on study Visits 1 and 2.
Fig. 2: Reproducibility of percent MCC60.
Fig. 3: Reproducibility of O:I ratio.
Fig. 4: Relationship between percent MCC60 and LCI2.5%.
Fig. 5: Relationship between percent MCC90 and LCI2.5%.

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Acknowledgements

The authors wish to thank Douglas Walker for performing MBW and induced sputum tests and lung function procedures and Jane Benson, MD and Emily Dunn, MD for scoring HCRT scans. Douglas Walker, Jane Benson, and Emily Dunn were supported by the NIH (R01 HL129925). We also wish to thank Andrew Lipton, MD, Chief, Pediatric Pulmonology, the Walter Reed National Military Medical Center and his clinical coordinators, Funmilola Crawford and Jane Jacknewitz-Woolard, and Dr. Edith Zemanick, MD, Associate Professor, Pediatrics, University of Colorado Denver and her clinical coordinators, Dana Coyle and Meg Anthony, for their referrals to this study. B.L.L., K.A.C., J.M.C., P.J.M., P.L.Z., C.M.E. and G.S. were supported by the NIH (R01 HL129925). B.L.L. and K.A.C. were also supported by the Johns Hopkins Institute for Clinical and Translational Research, which was funded in part by the NIH (UL1 TR001079). C.M.E. and V.L.R. were supported by the NIH (R01 HL130938, R01 HL080396) and by the Cystic Fibrosis Foundation (CFF EVANS18I0).

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B.L.L., K.A.C., C.M.E., J.M.C., P.L.Z., G.R.C. and P.J.M. made substantial contributions to the study’s conception and design and analysis and interpretation of the data. M.A.A., V.L.R. and G.S. made substantial contributions to analysis and interpretation of the data. B.L.L. drafted the article. All authors contributed to revising the article critically for important intellectual content and all authors provided final approval of the version to be published.

Corresponding author

Correspondence to Beth L. Laube.

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The authors declare no competing interests.

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Written, informed consent was obtained from parents, or guardians, of children who participated in the study. The study was approved by the Johns Hopkins Institutional Review Board.

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Laube, B.L., Carson, K.A., Evans, C.M. et al. Characterizing mucociliary clearance in young children with cystic fibrosis. Pediatr Res (2021). https://doi.org/10.1038/s41390-021-01453-2

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