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Abnormal Lung Clearance Index in Cystic Fibrosis Children with Normal FEV1 and Single-Breath Nitrogen Washout Test

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Abstract

Single- and multiple-breath washout tests (SBW and MBW) measure ventilation inhomogeneity, but the relationship between them is unclear. Forty-three subjects with cystic fibrosis (CF) and healthy controls (HC) 8–21 years of age were recruited (CF = 30 and HC = 13) and performed nitrogen MBW, vital capacity SBW, spirometry, and plethysmography. Mean phase III slope from SBW (SIII) and lung clearance index (LCI) were significantly different between CF and HC (p = 0.017 and p < 0.0001, respectively). Based on Pearson correlation, SIII and LCI showed strong correlation (ρ = 0.81, p < 0.0001). Both SIII and LCI significantly correlated with spirometry (all p < 0.05). Among CF subjects with normal FEV1 (≥ 80%; n = 17), 76% (n = 13) had normal SIII but abnormal LCI. We conclude that LCI can be abnormal despite normal SIII and FEV1 in CF children. Although LCI and SIII showed strong correlation, our results suggest that LCI is a better test to detect ventilation inhomogeneity in CF children with normal FEV1.

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References

  1. Gustafsson PM, De Jong PA, Tiddens HAWM, Lindblad A (2008) Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis. Thorax 63:129–134. https://doi.org/10.1136/thx.2007.077784

    Article  CAS  PubMed  Google Scholar 

  2. Subbarao P, Milla C, Aurora P et al (2015) Multiple-breath washout as a lung function test in cystic fibrosis: a cystic fibrosis foundation workshop report. Ann Am Thorac Soc 12:932–939. https://doi.org/10.1513/AnnalsATS.201501-021FR

    Article  PubMed  PubMed Central  Google Scholar 

  3. Robinson PD, Goldman MD, Gustafsson PM (2009) Inert gas washout: theoretical background and clinical utility in respiratory disease. Respiration 78:339–355. https://doi.org/10.1159/000225373

    Article  PubMed  Google Scholar 

  4. Robinson PD, Latzin P, Verbanck S et al (2013) Consensus statement for inert gas washout measurement using multiple- and singlebreath tests. Eur Respir J 41:507–522. https://doi.org/10.1183/09031936.00069712

    Article  CAS  PubMed  Google Scholar 

  5. Gozal D, Bailey SL, Keens TG (1993) Evolution of pulmonary function during an acute exacerbation in hospitalized patients with cystic fibrosis. Pediatr Pulmonol 16:347–353

    Article  CAS  PubMed  Google Scholar 

  6. Van Muylem A, Baran D (2000) Overall and peripheral inhomogeneity of ventilation in patients with stable cystic fibrosis. Pediatr Pulmonol 30:3–9

    Article  PubMed  Google Scholar 

  7. Wanger J, Clausen JL, Coates A et al (2005) Standardisation of the measurement of lung volumes. Eur Respir J 26:511–522. https://doi.org/10.1183/09031936.05.00035005

    Article  CAS  PubMed  Google Scholar 

  8. Miller MR, Hankinson J, Brusasco V et al (2005) Standardisation of spirometry. Eur Respir J 26:319–338. https://doi.org/10.1183/09031936.05.00034805

    Article  CAS  PubMed  Google Scholar 

  9. Aurora P, Bush A, Gustafsson P et al (2005) Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis. Am J Respir Crit Care Med 171:249–256. https://doi.org/10.1164/rccm.200407-895OC

    Article  PubMed  Google Scholar 

  10. Pellegrino R, Viegi G, Brusasco V et al (2005) Interpretative strategies for lung function tests. Eur Respir J 26:948–968. https://doi.org/10.1183/09031936.05.00035205

    Article  CAS  PubMed  Google Scholar 

  11. Rosenthal M, Cramer D, Bain SH et al (1993) Lung function in white children aged 4 to 19 years: II—single breath analysis and plethysmography. Thorax 48:803–808. https://doi.org/10.1136/thx.48.8.803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Quanjer PH, Stanojevic S, Cole TJ et al (2012) Multi-ethnic reference values for spirometry for the 3–95-year age range: the global lung function 2012 equations. Eur Respir J 40:1324–1343. https://doi.org/10.1183/09031936.00080312

    Article  PubMed  PubMed Central  Google Scholar 

  13. Kjellberg S, Viklund E, Robinson PD et al (2018) Utility of single versus multiple breath washout in adult asthma. Clin Physiol Funct Imaging. https://doi.org/10.1111/cpf.12503

    Article  PubMed  Google Scholar 

  14. Stevens D (2018) Static hyperinflation is associated with ventilatory limitation and exercise tolerance in adult cystic fibrosis. Clin Respir J 12:1949–1957. https://doi.org/10.1111/crj.12763

    Article  CAS  PubMed  Google Scholar 

  15. Yammine S, Ramsey KA, Skoric B et al (2019) Single-breath washout and association with structural lung disease in children with cystic fibrosis. Pediatr Pulmonol 54:587–594. https://doi.org/10.1002/ppul.24271

    Article  PubMed  Google Scholar 

  16. Verbanck S, Paiva M (2015) Dual gas techniques for peripheral airway function: diffusing the issues. Eur Respir J 45:1491–1494

    Article  PubMed  Google Scholar 

  17. Anagnostopoulou P, Latzin P, Jensen R et al (2020) Normative data for multiple breath washout outcomes in school-aged Caucasian children. Eur Respir J. https://doi.org/10.1183/13993003.01302-2019

    Article  PubMed  Google Scholar 

  18. Singer F, Stern G, Thamrin C et al (2013) A new double-tracer gas single-breath washout to assess early cystic fibrosis lung disease. Eur Respir J 41:339–345. https://doi.org/10.1183/09031936.00044312

    Article  CAS  PubMed  Google Scholar 

  19. Latzin P, Thompson B (2014) Double tracer gas single-breath washout: promising for clinics or just a toy for research? Eur Respir J 44:1113–1115

    Article  PubMed  Google Scholar 

  20. Michaelson ED, Wanner A, Watson H et al (1979) Distribution of ventilation in normal children. Chest 76:658–662. https://doi.org/10.1378/chest.76.6.658

    Article  CAS  PubMed  Google Scholar 

  21. Ramsey KA, Rosenow T, Turkovic L et al (2016) Lung Clearance index and structural lung disease on computed tomography in early cystic fibrosis. Am J Respir Crit Care Med 193:60–67. https://doi.org/10.1164/rccm.201507-1409OC

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank Dr. Sally L. Davidson Ward and the Cystic Fibrosis team at CHLA for supporting this study. The authors thank Whitney Gore, Cynthia Leyva, Monique Margetis, Maria Carmen Reyes, and Alejandra Franquez for their help with patient recruitment. The authors thank the lab personnel Jeff Vega, Valerie Mendoza, David Martinez, and Edwin Gutierrez for their help with performing tests. They also thank the children and families who participated in this study.

Funding

This project was supported by the Webb Family and National Institute of Health (NIH)/ National Center for Research Resources Southern California Clinical and Translational Science Institute (NCRR SC-CTSI)—Grant Number UL1 TR000130. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

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  1. Ajay S. Kasi

    Present address: Emory University, Atlanta, GA, USA

Authors and Affiliations

  1. Division of Pediatric Pulmonology, Department of Pediatrics, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Ajay S. Kasi, Choo Phei Wee, Thomas G. Keens & Danieli B. Salinas

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  1. Ajay S. Kasi
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  2. Choo Phei Wee
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Correspondence to Ajay S. Kasi.

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Kasi, A.S., Wee, C.P., Keens, T.G. et al. Abnormal Lung Clearance Index in Cystic Fibrosis Children with Normal FEV1 and Single-Breath Nitrogen Washout Test. Lung 199, 37–41 (2021). https://doi.org/10.1007/s00408-020-00412-8

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  • DOI: https://doi.org/10.1007/s00408-020-00412-8

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