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Katherine O’Neill, PhD; J. Stuart Elborn, MD; Michael M. Tunney, PhD; Judy M. Bradley, PhD
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FINANCIAL/NONFINANCIAL DISCLOSURES: See earlier cited article for author conflicts of interest.

aCentre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern Ireland

bSchool of Pharmacy, Queen’s University Belfast, Belfast, Northern Ireland

cClinical Research Facility, Queen’s University Belfast, Belfast, Northern Ireland

CORRESPONDENCE TO: Katherine O’Neill, PhD, Centre for Experimental Medicine, 3rd Floor, Medical Biology Centre, Lisburn Rd, Queen's University Belfast, BT9 7BL Northern Ireland


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(6):1413-1414. doi:10.1016/j.chest.2016.09.037
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We thank Dr Oude Engberink and colleagues for their helpful and insightful commentary regarding our article recently published in CHEST on aspects of intra-visit and inter-visit repeatability of the lung clearance index (LCI) in health and in cystic fibrosis (CF) disease. The primary aim of our study was to compare adults and children with CF, and thus this area was the focus of our report. However, we agree that further analysis and comparison of healthy control (HC) and disease data can add to existing findings and further inform thresholds for clinically meaningful changes.

We showed that data regarding adults and children with CF had similar coefficients of variation (%CV) compared with their HC counterparts. On further analysis, we can report a coefficient of repeatability (CoR) of 0.6 in HC adults and 0.9 in HC children (Figs 1A, 1B) compared with values of 1.2 and 1.3 for adults and children with CF, respectively. These findings emphasize that there is greater intra-visit variability in subjects with CF compared with HC subjects, which is in agreement with other reports.

Figure Jump LinkFigure 1 Bland-Altman plot for the first and third washout repeats for (A) healthy control adults (n = 28) and (B) healthy control children (n = 28). LCI = lung clearance index.Grahic Jump Location

Concerning inter-visit repeatability, the data from 56 subjects with CF (adult and children) exhibited stability across the two measurements, with no significant difference between LCI measurements (paired t test, P = .80). The mean %CV for visit 1 (4.3%) and visit 2 (4.7%) were also not significantly different (paired t test, P = .21). These results were comparable to the intra-visit %CV reported in the larger cohort of adults and children with CF. Figure 2 presents the limits of agreement between visits, which equates to a CoR of 1.4.

Figure Jump LinkFigure 2 Bland-Altman plot for LCI visit 1 and LCI visit 2 in patients with cystic fibrosis (n = 56). LCI = lung clearance index.Grahic Jump Location

These data underline our findings that LCI has good short- and long-term repeatability in CF but highlights that variability is greater in disease compared with health. These results emphasize that sample size estimates should be informed by CF data (and not by HC data) to avoid study underpowering. In our study, variability was comparable in children and adults with CF in contrast to some evidence that shows increased variation with disease severity and/or age.,

Using %CV, CoR, and Bland-Altman statistics to assess inter-visit repeatbility, our combined child and adult CF data across 2 stable visits show levels of variation similar to those reported in the intra-visit data. We hope that this additional analysis can provide further insight into the natural variability of LCI across the age range in CF and help inform the question of what is a clinically meaningful change in LCI.

O'Neill K. .Tunney M.M. .Johnston E. .et al Lung clearance index in adults and children with cystic fibrosis. Chest. 2016;150:1323-1332 [PubMed]journal
 
Kent L. .Reix P. .Innes J.A. .et al Lung clearance index: evidence for use in clinical trials in cystic fibrosis. J Cyst Fibros. 2014;13:123-138 [PubMed]journal. [CrossRef] [PubMed]
 
Jensen R. .Stanojevic S. .Gibney K. .et al Multiple breath nitrogen washout: a feasible alternative to mass spectrometry. PLoS One. 2013;8:e56868- [PubMed]journal. [CrossRef] [PubMed]
 
Lum S. .Stocks J. .Stanojevic S. .et al Age and height dependence of lung clearance index and functional residual capacity. Eur Respir J. 2013;41:1371-1377 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 Bland-Altman plot for the first and third washout repeats for (A) healthy control adults (n = 28) and (B) healthy control children (n = 28). LCI = lung clearance index.Grahic Jump Location
Figure Jump LinkFigure 2 Bland-Altman plot for LCI visit 1 and LCI visit 2 in patients with cystic fibrosis (n = 56). LCI = lung clearance index.Grahic Jump Location

Tables

References

O'Neill K. .Tunney M.M. .Johnston E. .et al Lung clearance index in adults and children with cystic fibrosis. Chest. 2016;150:1323-1332 [PubMed]journal
 
Kent L. .Reix P. .Innes J.A. .et al Lung clearance index: evidence for use in clinical trials in cystic fibrosis. J Cyst Fibros. 2014;13:123-138 [PubMed]journal. [CrossRef] [PubMed]
 
Jensen R. .Stanojevic S. .Gibney K. .et al Multiple breath nitrogen washout: a feasible alternative to mass spectrometry. PLoS One. 2013;8:e56868- [PubMed]journal. [CrossRef] [PubMed]
 
Lum S. .Stocks J. .Stanojevic S. .et al Age and height dependence of lung clearance index and functional residual capacity. Eur Respir J. 2013;41:1371-1377 [PubMed]journal. [CrossRef] [PubMed]
 
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