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, Sanja Stanojevic, Meghan Brown, Renee Jensen, Margaret Rosenfeld, Stephanie Davis, Lyndia Brumback, Per Gustafsson, Felix Ratjen

Research output: Contribution to journalArticle

111 Citations (Scopus)

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 singlecenter 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 accountfor height-related changesin 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]=22.46 to 0.06), and remained stable in the isotonic saline group (n = 13) at 0.81 (95% CI = 20.40 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 ofMBWand LCI as an objective outcome measure in interventional trials in young children with CF, and provide estimates for sample size calculations for future studies.

Original languageEnglish
Pages (from-to)456-460
Number of pages5
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume188
Issue number4
DOIs
StatePublished - Aug 15 2013

Fingerprint

Cystic Fibrosis
Outcome Assessment (Health Care)
Clinical Trials
Lung
Preschool Children
Confidence Intervals
Sulfur Hexafluoride
Noninvasive Ventilation
Feasibility Studies
Sample Size
Therapeutics
Randomized Controlled Trials
Gases

Keywords

  • Cystic fibrosis
  • Hypertonic saline
  • Infant
  • Lung clearance index
  • Preschool child

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis : A pilot study using inhaled hypertonic saline. / Subbarao, Padmaja; Stanojevic, Sanja; Brown, Meghan; Jensen, Renee; Rosenfeld, Margaret; Davis, Stephanie; Brumback, Lyndia; Gustafsson, Per; Ratjen, Felix.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 188, No. 4, 15.08.2013, p. 456-460.

Research output: Contribution to journalArticle

Subbarao, Padmaja ; Stanojevic, Sanja ; Brown, Meghan ; Jensen, Renee ; Rosenfeld, Margaret ; Davis, Stephanie ; Brumback, Lyndia ; Gustafsson, Per ; Ratjen, Felix. / Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis : A pilot study using inhaled hypertonic saline. In: American Journal of Respiratory and Critical Care Medicine. 2013 ; Vol. 188, No. 4. pp. 456-460.
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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 singlecenter 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 accountfor height-related changesin 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]=22.46 to 0.06), and remained stable in the isotonic saline group (n = 13) at 0.81 (95{\%} CI = 20.40 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 ofMBWand LCI as an objective outcome measure in interventional trials in young children with CF, and provide estimates for sample size calculations for future studies.",
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T2 - A pilot study using inhaled hypertonic saline

AU - Subbarao, Padmaja

AU - Stanojevic, Sanja

AU - Brown, Meghan

AU - Jensen, Renee

AU - Rosenfeld, Margaret

AU - Davis, Stephanie

AU - Brumback, Lyndia

AU - Gustafsson, Per

AU - Ratjen, Felix

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N2 - 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 singlecenter 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 accountfor height-related changesin 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]=22.46 to 0.06), and remained stable in the isotonic saline group (n = 13) at 0.81 (95% CI = 20.40 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 ofMBWand LCI as an objective outcome measure in interventional trials in young children with CF, and provide estimates for sample size calculations for future studies.

AB - 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 singlecenter 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 accountfor height-related changesin 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]=22.46 to 0.06), and remained stable in the isotonic saline group (n = 13) at 0.81 (95% CI = 20.40 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 ofMBWand LCI as an objective outcome measure in interventional trials in young children with CF, and provide estimates for sample size calculations for future studies.

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