A randomized controlled trial to evaluate the lung clearance index as an outcome measure for early phase studies in patients with cystic fibrosis

Amin, Reshma; Stanojevic, Sanja; Webster, H. L.; Ratjen, Félix

doi:10.1016/j.rmed.2016.01.020

Cited by 34 publications

(28 citation statements)

References 12 publications

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“…Adult and child CF subjects had similar intra-visit variability in LCI compared with their HC counterparts, with no significant difference in the mean differences between the first and third tests. The CoR (1.2 in CF adults and 1.3 in CF children) was similar to levels considered to represent significant change in recent trials (0.96-1.30) 5, 11, 34 . The CoR statistic is useful to indicate the degree of variability above which a treatment effect would be expected to be observed 36 ; however caution is required with respect to the direct interpretation of CoR as the level of treatment effect.…”

Section: Discussionsupporting

confidence: 65%

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Lung Clearance Index in Adults and Children With Cystic Fibrosis

O’Neill¹,

Tunney

Johnston³

et al. 2016

Chest

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Section: Discussionsupporting

confidence: 65%

“…Journal of Cystic Fibrosis. 2003;2(1):[29][30][31][32][33][34]. CF and HC subject characteristics LCI CV% calculated from 49/67 adult CF subject data i.e.…”

mentioning

confidence: 99%

Lung Clearance Index in Adults and Children With Cystic Fibrosis

O’Neill¹,

Tunney

Johnston³

et al. 2016

Chest

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“…The LCI measures ventilation inhomogeneity, is able to distinguish between health and disease, and is more sensitive at detecting early lung changes than the FEV 1 [18,32,[35][36][37][38][39][40]. In addition, greater ventilation inhomogeneity, higher LCI values, are correlated with structural damage measured by high resolution CT in both pediatric and adult patients with CF [18,[41][42][43][44]. Since elevated LCI and structural damage are often observed in patients whose FEV 1 is in the normal range there is the potential to identify early lung disease and intervene before permanent lung damage occurs.…”

Section: The Lung Clearance Indexmentioning

confidence: 99%

Physiologic endpoints for clinical studies for cystic fibrosis

Stanojevic¹,

Ratjen²

2016

Journal of Cystic Fibrosis

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The cystic fibrosis (CF) drug development pipeline promises many exciting new treatments for patients with CF, all which will require clinical studies to prove their benefits on CF lung disease. Historically many pivotal CF studies have used the Forced Expiratory Volume in 1s (FEV1) as the primary outcome measure, and after demonstrating significant improvements in the treatment group relative to placebo have led to regulatory approval of therapies for routine clinical care. Widespread implementation of these therapies has subsequently led to significant improvements in outcomes for patients with CF. While preserving lung function has obvious benefits to CF patients, as more patients maintain FEV1 in the normal range, it has become increasingly difficult to conduct clinical trials using FEV1 as the primary outcome measure. With multiple concurrent trials competing to enroll from the same pool of patients, there is a need for novel approaches to study end points as well as new physiological outcomes for CF therapeutic trials. In this review we will discuss some of the limitations of FEV1 in the current era of CF care, describe alternative physiological endpoints and outline areas for further research.

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“…Investigators report differing findings for the inter-test reproducibility of the LCI due to variability in protocol designs, study population and MBW methodology [5][6][7][8][9][10][11][12][13][14]. Most notably, time intervals between repeated tests range from hours to years, and none report reproducibility for time intervals typically used to clinically track patients with cystic fibrosis (e.g.…”

Section: Introductionmentioning

confidence: 99%

Inter-test reproducibility of the lung clearance index measured by multiple breath washout

et al. 2017

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The lung clearance index (LCI) has strong intra-test repeatability; however, the inter-test reproducibility of the LCI is poorly defined.The aim of the present study was to define a physiologically meaningful change in LCI in preschool children, which discriminates changes associated with disease progression from biological variability.Repeated LCI measurements from a longitudinal cohort study of children with cystic fibrosis and age-matched controls were collected to define the inter-visit reproducibility of the LCI. Absolute change, the coefficient of variation, Bland-Altman limits of agreement, the coefficient of repeatability, intra-class correlation coefficient, and percentage changes were calculated.LCI measurements (n=505) from 71 healthy and 77 cystic fibrosis participants (aged 2.6-6 years) were analysed. LCI variability was proportional to its magnitude, such that reproducibility defined by absolute changes is biased. A physiologically relevant change for quarterly LCI measurements in health was defined as exceeding ±15%. In clinically stable cystic fibrosis participants, the threshold was higher (±25%); however, for measurements made 24 h apart, the threshold was similar to that observed in health (±17%).A percentage change in LCI greater than ±15% in preschool children can be considered physiologically relevant and greater than the biological variability of the test.

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A randomized controlled trial to evaluate the lung clearance index as an outcome measure for early phase studies in patients with cystic fibrosis

Abstract: These data suggest that LCI may potentially be used as an outcome measure in early phase trials with therapeutic agents that have a larger treatment effects than a single inhalation of HS.

Cited by 34 publications

References 12 publications

Lung Clearance Index in Adults and Children With Cystic Fibrosis

Lung Clearance Index in Adults and Children With Cystic Fibrosis

Physiologic endpoints for clinical studies for cystic fibrosis

Inter-test reproducibility of the lung clearance index measured by multiple breath washout

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