Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D- CFTR mutation and preserved spirometry: a randomised controlled trial

Davies, Jane C.; Sheridan, Helen; Bell, Nicholas; Cunningham, Steve; Davis, Stephanie D.; Elborn, J. Stuart; Milla, Carlos; Starner, Timothy D.; Weiner, Daniel J.; Lee, Po Shun; Ratjen, Félix

doi:10.1016/s2213-2600(13)70182-6

Cited by 215 publications

(177 citation statements)

References 24 publications

Supporting

Mentioning

163

Contrasting

Unclassified

Order By: Relevance

“…Of note, 75% of patients in this age group showed an improvement in FEV1 % pred by o5% and therapeutic effects on lung function were independent from baseline FEV1, age or sex [63]. Similar effects with an overall improvement of FEV1 % pred of 12.5% were observed in younger CF patients (6-11 years of age) with a G551D mutation, and it was shown that ivacaftor improves the lung clearance index in children with CF with normal spirometry [64,66]. While it remains to be seen to what extent these therapeutic benefits on pulmonary function are cumulative to already existing symptomatic therapies [67][68][69][70], this breakthrough provides an important proof-of-concept that mutation-specific therapy is possible and may, therefore, mark the beginning of a new era of personalised medicine for CF, a topic that has been discussed in several recent reviews [71][72][73].…”

Section: Emerging Novel Therapies To Rescue Mutant Cftr: Breakthroughmentioning

confidence: 55%

CFTR: cystic fibrosis and beyond

2014

View full text Add to dashboard Cite

Cystic fibrosis (CF) remains the most common fatal hereditary lung disease. The discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene 25 years ago set the stage for: 1) unravelling the molecular and cellular basis of CF lung disease; 2) the generation of animal models to study in vivo pathogenesis; and 3) the development of mutation-specific therapies that are now becoming available for a subgroup of patients with CF. This article highlights major advances in our understanding of how CFTR dysfunction causes chronic mucus obstruction, neutrophilic inflammation and bacterial infection in CF airways. Furthermore, we focus on recent breakthroughs and remaining challenges of novel therapies targeting the basic CF defect, and discuss the next steps to be taken to make disease-modifying therapies available to a larger group of patients with CF, including those carrying the most common mutation DF508-CFTR. Finally, we will summarise emerging evidence indicating that acquired CFTR dysfunction may be implicated in the pathogenesis of chronic obstructive pulmonary disease, suggesting that lessons learned from CF may be applicable to common airway diseases associated with mucus plugging. @ERSpublications CFTR dysfunction causes CF and may be implicated in more common chronic obstructive lung diseases, such as COPD

show abstract

Section: Emerging Novel Therapies To Rescue Mutant Cftr: Breakthroughmentioning

confidence: 55%

CFTR: cystic fibrosis and beyond

2014

View full text Add to dashboard Cite

show abstract

“…One multicenter interventional study enrolled patients, older than 8 years, with at least one copy of the G551D mutation and normal FEV 1 (above 90% predicted at baseline) and assessed the ability of LCI to detect a treatment effect of ivacaftor (52). The magnitude of the treatment effect detected in this group of patients was twice as high when compared with the hypertonic saline and dornase alfa studies and provided evidence that LCI could be a responsive alternative outcome for pulmonary abnormalities in patients with mild lung disease.…”

Section: Clinical Trialsmentioning

confidence: 99%

Multiple-Breath Washout as a Lung Function Test in Cystic Fibrosis. A Cystic Fibrosis Foundation Workshop Report

et al. 2015

Self Cite

View full text Add to dashboard Cite

The lung clearance index (LCI) is a lung function parameter derived from the multiple-breath washout (MBW) test. Although first developed 60 years ago, the technique was not widely used for many years. Recent technological advances in equipment design have produced gains in popularity for this test among cystic fibrosis (CF) researchers and clinicians, particularly for testing preschool-aged children. LCI has been shown to be feasible and sensitive to early CF lung disease in patients of all ages from infancy to adulthood. A workshop was convened in January 2014 by the North American Cystic Fibrosis Foundation to determine the readiness of the LCI for use in multicenter clinical trials as well as clinical care. The workshop concluded that the MBW text is a valuable potential outcome measure for CF clinical trials in preschool-aged patients and in older patients with FEV 1 in the normal range. However, gaps in knowledge about the choice of device, gas, and standardization across systems are key issues precluding its use as a clinical trial end point in infants. Based on the current evidence, there are insufficient data to support the use of LCI or MBW parameters in the routine clinical management of patients with CF.

show abstract

“…Furthermore, multiple studies demonstrate that the "signal" such as treatment differences, or changes related to worsening symptoms, from both of these lung function tests is much greater than the "noise" or biological variability and can be useful for tracking cystic fibrosis lung disease over time [1,3,[21][22][23][24]. The similar within-subject variability observed for LCI and FEV1 is in contrast to the lower between-subject variability observed for LCI compared to FEV1 in interventional studies [7,8,25]. This paradox is not unexpected, since changes at a group level are often lower than changes observed within an individual [26,27].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D- CFTR mutation and preserved spirometry: a randomised controlled trial

Cited by 215 publications

References 24 publications

CFTR: cystic fibrosis and beyond

CFTR: cystic fibrosis and beyond

Multiple-Breath Washout as a Lung Function Test in Cystic Fibrosis. A Cystic Fibrosis Foundation Workshop Report

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

Contact Info

Product

Resources

About