Progression of Lung Disease in Preschool Patients with Cystic Fibrosis

Stanojevic, Sanja; Davis, Stephanie D.; Retsch‐Bogart, George; Webster, H. L.; Davis, Michael F.; Johnson, Robert P.; Jensen, Renée; Pizarro, María Ester; Kane, Mica; Clem, Charles; Schornick, Leah; Subbarao, Padmaja; Ratjen, Félix

doi:10.1164/rccm.201610-2158oc

Cited by 135 publications

(151 citation statements)

References 27 publications

Supporting

Mentioning

131

Contrasting

Unclassified

Order By: Relevance

“…This z-score range is similar to a previous study in children reporting reproducibility for measurements made 12 months apart [20]. 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].…”

Section: Discussionsupporting

confidence: 84%

“…LCI=16), the LCI would need to change by more than 2.5 units to be considered physiologically relevant, highlighting the limitations of using absolute LCI as a threshold for a relevant change. We also observed greater variability for the LCI5 between visits than for LCI (at 1/40 the starting N 2 concentration), which is opposite to the within-visit variability [3] but corresponds to the effects observed for interventional studies [19].…”

Section: Discussioncontrasting

confidence: 42%

“…clinical symptoms; however, differentiating biological variability from changes in disease state in this population is challenging and requires further investigation. Our previous work highlighted the population-level changes in LCI in preschool children over time and identified changes in LCI are associated with lower respiratory symptoms [3]. The in-depth analyses of the individual-level biological variability of the LCI presented here provide further evidence and tools to interpret clinical changes in LCI in young children with cystic fibrosis.…”

Section: Discussionmentioning

confidence: 66%

“…The same analyses were conducted for FEV1 and FEF25-75% z-scores and % predicted. The sample size was a convenience sample size based on available data from the primary research study [3]. All statistical analyses were performed using Stata version 14 (StataCorp, College Station, TX, USA).…”

Section: Spirometrymentioning

confidence: 99%

“…The LCI identifies early obstructive lung disease [1] and is feasible to perform in young children [2,3]. In addition, the LCI has good intra-test repeatability [4][5][6]; however, there are limited longitudinal data describing inter-test reproducibility.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Section: Discussionsupporting

confidence: 84%

Section: Discussioncontrasting

confidence: 42%

Section: Discussionmentioning

confidence: 66%

Section: Spirometrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

show abstract

Real-world Associations of US Cystic Fibrosis Newborn Screening Programs With Nutritional and Pulmonary Outcomes

et al. 2022

View full text Add to dashboard Cite

ImportanceNewborn screening (NBS) for cystic fibrosis (CF) has been universal in the US since 2010, but its association with clinical outcomes is unclear.ObjectiveTo describe the real-world effectiveness of NBS programs for CF in the US on outcomes up to age 10 years.Design, Setting, and ParticipantsThis was a retrospective cohort study using CF Foundation Patient Registry data from January 1, 2000, to December 31, 2018. The staggered implementation of NBS programs by state was used to compare longitudinal outcomes among children in the same birth cohort born before vs after the implementation of NBS for CF in their state of birth. Participants included children with an established diagnosis of CF born between January 1, 2000, to December 31, 2018, in any of the 44 states that implemented NBS for CF between 2003 and 2010. Data were analyzed from October 5, 2020, to April 22, 2022.ExposuresBirth before vs after the implementation of NBS for CF in the state of birth.Main Outcomes and MeasuresLongitudinal trajectory of height and weight percentiles from diagnosis, lung function (forced expiratory volume in 1 second, [FEV1] percent predicted) from age 6 years, and age at initial and chronic infection with Pseudomonas aeruginosa using linear mixed-effects and time-to-event models adjusting for birth cohort and potential confounders.ResultsA total of 9571 participants (4713 female participants [49.2%]) were eligible for inclusion, with 4510 (47.1%) in the pre-NBS cohort. NBS was associated with higher weight and height percentiles in the first year of life (weight, 6.0; 95% CI, 3.1-8.4; height, 6.6; 95% CI, 3.8-9.3), but these differences decreased with age. There was no association between NBS and FEV1 at age 6 years, but the percent-predicted FEV1 did increase more rapidly with age in the post-NBS cohort. NBS was associated with older age at chronic P aeruginosa infection (hazard ratio, 0.69; 95% CI, 0.54-0.89) but not initial P aeruginosa infection (hazard ratio, 0.88; 95% CI, 0.77-1.01).Conclusions and RelevanceNBS for CF in the US was associated with improved nutritional status up to age 10 years, a more rapid increase in lung function, and delayed chronic P aeruginosa infection. In the future, as highly effective modulator therapies become available for infants with CF, NBS will allow for presymptomatic initiation of these disease-modifying therapies before irreversible organ damage.

show abstract

Intra‐ and Inter‐visit Repeatability of ¹²⁹Xenon Multiple‐Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease

Alam

Zanette

Munidasa

et al. 2023

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Background Multiple‐breath washout (MBW) 129Xe MRI (MBW Xe‐MRI) is a promising technique for following pediatric cystic fibrosis (CF) lung disease progression. However, its repeatability in stable CF needs to be established to use it as an outcome measure for novel therapies. Purpose To assess intravisit and intervisit repeatability of MBW Xe‐MRI in healthy and CF children. Study Type Prospective, longitudinal cohort study. Subjects A total of 18 pediatric subjects (7 healthy, 11 CF). Field Strength/Sequence A 3 T/2D coronal hyperpolarized (HP) 129Xe images using GRE sequence. Assessment All subjects completed MBW Xe‐MRI, pulmonary function tests (PFTs) (spirometry, nitrogen [N2] MBW for lung clearance index [LCI]) and ventilation defect percent (VDP) at baseline (visit 1) and 1‐month after. Fractional ventilation (FV), coefficient of variation (CoVFV) maps were calculated from MBW Xe‐MRI data acquired between intervening air washout breaths performed after an initial xenon breath‐hold. Skewness of FV and CoVFV map distributions was also assessed. Statistical Tests Repeatability: intraclass correlation coefficients (ICC), within‐subject coefficient of variation (CV%), repeatability coefficient (CR). Agreement: Bland–Altman. For correlations between MBW Xe‐MRI, VDP and PFTs: Spearman's correlation. Significance threshold: P < 0.05. Results For FV, intravisit median [IQR] ICC was high in both healthy (0.94 [0.48, 0.99]) and CF (0.83 [0.04, 0.97]) subjects. CoVFV also had good intravisit ICC in healthy (0.92 [0.42, 0.99]) and CF (0.79 [0.02, 0.96]) subjects. Similarly, for FV, intervisit ICC was high in health (0.94 [0.68, 0.99]) and CF (0.89 [0.61, 0.97]). CoVFV also had good intervisit ICC in health (0.92 [0.42, 0.99]) and CF (0.78 [0.26, 0.94]). FV had better intervisit repeatability than VDP. CoVFV correlated significantly with LCI (R = 0.56). Skewness of FV distributions significantly distinguished between cohorts at baseline. Data Conclusion MBW Xe‐MRI had high intravisit and intervisit repeatability in healthy and stable CF subjects. CoVFV correlated with LCI, suggesting the importance of ventilation heterogeneity to early CF. Evidence Level 1. Technical Efficacy Stage 2.

show abstract

Progression of Lung Disease in Preschool Patients with Cystic Fibrosis

Abstract: LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF.

Cited by 135 publications

References 27 publications

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

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

Real-world Associations of US Cystic Fibrosis Newborn Screening Programs With Nutritional and Pulmonary Outcomes

Intra‐ and Inter‐visit Repeatability of ¹²⁹Xenon Multiple‐Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease

Contact Info

Product

Resources

About

Progression of Lung Disease in Preschool Patients with Cystic Fibrosis

Abstract: LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF.

Cited by 135 publications

References 27 publications

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

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

Real-world Associations of US Cystic Fibrosis Newborn Screening Programs With Nutritional and Pulmonary Outcomes

Intra‐ and Inter‐visit Repeatability of 129Xenon Multiple‐Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease

Contact Info

Product

Resources

About

Intra‐ and Inter‐visit Repeatability of ¹²⁹Xenon Multiple‐Breath Washout MRI in Children With Stable Cystic Fibrosis Lung Disease