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Randomized Controlled Trial
. 2013 Aug 15;188(4):456-60.
doi: 10.1164/rccm.201302-0219OC.

Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis. A pilot study using inhaled hypertonic saline

Padmaja Subbarao  1 , Sanja Stanojevic, Meghan Brown, Renee Jensen, Margaret Rosenfeld, Stephanie Davis, Lyndia Brumback, Per Gustafsson, Felix Ratjen
Affiliations
Randomized Controlled Trial

Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis. A pilot study using inhaled hypertonic saline

Padmaja Subbarao et al. Am J Respir Crit Care Med. .

Abstract

Rationale: Lung clearance index (LCI), measured by multiple breath washout (MBW), is a noninvasive measure of ventilation inhomogeneity that holds promise as an objective physiologic endpoint for clinical trials in infants and preschool children with cystic fibrosis (CF).

Objectives: To study the feasibility of using LCI to assess treatment effect outcomes in CF trials of infants and preschoolers.

Methods: The Infant Study of Inhaled Saline trial was a multicenter, randomized, controlled trial of hypertonic (7%) versus isotonic (0.9%) saline inhaled twice daily for 48 weeks in children with CF under 6 years of age. LCI measurements were performed in a single-center pilot substudy at baseline and 48 weeks using a respiratory mass spectrometer and sulfur hexafluoride as the tracer gas. LCI measurements were standardized using published normative data (zLCI) to account for height-related changes in LCI during early childhood. A generalized estimating equation model with an interaction between treatment group and test occasion was used to estimate a treatment effect.

Measurements and main results: A total of 27 participants were randomized; 25 participants, aged (median [range]) 2.6 (0.34-4.95) years, had acceptable baseline and follow-up LCI measures. On average, LCI decreased in the hypertonic saline group (n = 12) by 1.19 z-scores units (95% confidence interval [CI] = -2.46 to 0.06), and remained stable in the isotonic saline group (n = 13) at 0.81 (95% CI = -0.40 to 2.02). A significant treatment effect was observed for zLCI (2.01; 95% CI = 0.26 to 3.76; P = 0.025).

Conclusions: MBW testing is feasible in an interventional study in infants and preschool children with CF. These pilot findings support the development of MBW and LCI as an objective outcome measure in interventional trials in young children with CF, and provide estimates for sample size calculations for future studies.

Trial registration: ClinicalTrials.gov NCT00709280.

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Figures

<i>Figure 1.</i>
Figure 1.
Lung clearance index (LCI) at baseline. Closed symbols indicate the isotonic saline (IS) group and open symbols indicate the hypertonic saline (HS) group. The upper limit of normal (ULN) was defined using a reference population (18).
<i>Figure 2.</i>
Figure 2.
Individual changes in lung clearance index (LCI) expressed as z scores (15) between baseline and follow-up, followed by the average change in LCI in the (A) hypertonic saline group and (B) isotonic saline group. Open circles represent infant subjects and closed triangles represent preschool subjects. CI = confidence interval.
See this image and copyright information in PMC

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References

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