Browsing by Author "Ratjen, Felix"

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    Infant lung function tests as endpoints in the ISIS multicenter clinical trial in cystic fibrosis
    (Elsevier, 2016-05) Davis, Stephanie D.; Ratjen, Felix; Brumback, Lyndia C.; Johnson, Robin C.; Filbrun, Amy G.; Kerby, Gwendolyn S.; Panitch, Howard B.; Donaldson, Scott H.; Rosenfeld, Margaret; Department of Pediatrics, IU School of Medicine
    BACKGROUND: The Infant Study of Inhaled Saline (ISIS) in CF was the first multicenter clinical trial to utilize infant pulmonary function tests (iPFTs) as an endpoint. METHODS: Secondary analysis of ISIS data was conducted in order to assess feasibility of iPFT measures and their associations with respiratory symptoms. Standard deviations were calculated to aid in power calculations for future clinical trials. RESULTS: Seventy-three participants enrolled, 70 returned for the final visit; 62 (89%) and 45 (64%) had acceptable paired functional residual capacity (FRC) and raised volume measurements, respectively. Mean baseline FEV0.5, FEF75 and FRC z-scores were 0.3 (SD: 1.2), -0.2 (SD: 2.0), and 1.8 (SD: 2.0). CONCLUSIONS: iPFTs are not appropriate primary endpoints for multicenter clinical trials due to challenges of obtaining acceptable data and near-normal average raised volume measurements. Raised volume measures have potential to serve as secondary endpoints in future clinical CF trials.
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    Inter-test reproducibility of the lung clearance index measured by multiple breath washout
    (ERS, 2017-10-01) Engberink, Esther Oude; Ratjen, Felix; Davis, Stephanie D.; Retsch-Bogart, George; Amin, Reshma; Stanojevic, Sanja; Pediatrics, School of Medicine
    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. Biological variability of lung clearance index is dependent on magnitude; % change is better for tracking patients http://ow.ly/tgbX30dBbCX
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    Lung Clearance Index to Track Acute Respiratory Events in School-Age Children with Cystic Fibrosis
    (ATS, 2021-04) Perrem, Lucy; Stanojevic, Sanja; Shaw, Michelle; Jensen, Renee; McDonald, Nancy; Isaac, Sarah M.; Davis, Miriam; Clem, Charles; Guido, Julia; Jara, Sylvia; France, Lisa; Soloman, Melinda; Grasemann, Hartmut; Waters, Valerie; Sweezey, Neil; Sanders, Don B.; Davis, Stephanie D.; Ratjen, Felix; Pediatrics, School of Medicine
    Rationale: The lung clearance index (LCI) is responsive to acute respiratory events in preschool children with cystic fibrosis (CF), but its utility to identify and manage these events in school-age children with CF is not well defined. Objectives: To describe changes in LCI with acute respiratory events in school-age children with CF. Methods: In a multisite prospective observational study, the LCI and FEV1 were measured quarterly and during acute respiratory events. Linear regression was used to compare relative changes in LCI and FEV1% predicted at acute respiratory events. Logistic regression was used to compare the odds of a significant worsening in LCI and FEV1% predicted at acute respiratory events. Generalized estimating equation models were used to account for repeated events in the same subject. Measurements and Main Results: A total of 98 children with CF were followed for 2 years. There were 265 acute respiratory events. Relative to a stable baseline measure, LCI (+8.9%; 95% confidence interval, 6.5 to 11.3) and FEV1% predicted (−6.6%; 95% confidence interval, −8.3 to −5.0) worsened with acute respiratory events. A greater proportion of events had a worsening in LCI compared with a decline in FEV1% predicted (41.7% vs. 30.0%; P = 0.012); 53.9% of events were associated with worsening in LCI or FEV1. Neither LCI nor FEV1 recovered to baseline values at the next follow-up visit. Conclusions: In school-age children with CF, the LCI is a sensitive measure to assess lung function worsening with acute respiratory events and incomplete recovery at follow-up. In combination, the LCI and FEV1 capture a higher proportion of events with functional impairment.
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    Multiple-Breath Washout as a Lung Function Test in Cystic Fibrosis: A Cystic Fibrosis Foundation Workshop Report
    (2015-06) Subbarao, Padmaja; Milla, Carlos; Aurora, Paul; Davies, Jane C.; Davis, Stephanie D.; Hall, Graham L.; Heltshe, Sonya; Latzin, Philipp; Lindblad, Anders; Pittman, Jessica E.; Robinson, Paul D.; Rosenfeld, Margaret; Singer, Florian; Starner, Tim D.; Ratjen, Felix; Morgan, Wayne; Department of Pediatrics, IU School of Medicine
    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 FEV1 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.