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Browsing by Author "Jensen, Renee"
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Item Determinants of lung disease progression measured by lung clearance index in children with cystic fibrosis(ERS, 2021-07) Stanojevic, Sanja; Davis, Stephanie D.; Perrem, Lucy; Shaw, Michelle; Retsch-Bogart, George; Davis, Miriam; Jensen, Renee; Clem, Charles C.; Isaac, Sarah M.; Guido, Julia; Jara, Sylvia; France, Lisa; McDonald, Nancy; Solomon, Melinda; Sweezey, Neil; Grasemann, Hartmut; Waters, Valerie; Sanders, D. B.; Ratjen, Felix A.; Pediatrics, School of MedicineThe lung clearance index (LCI) measured by the multiple breath washout (MBW) test is sensitive to early lung disease in children with cystic fibrosis. While LCI worsens during the preschool years in cystic fibrosis, there is limited evidence to clarify whether this continues during the early school age years, and whether the trajectory of disease progression as measured by LCI is modifiable. A cohort of children (healthy and cystic fibrosis) previously studied for 12 months as preschoolers were followed during school age (5–10 years). LCI was measured every 3 months for a period of 24 months using the Exhalyzer D MBW nitrogen washout device. Linear mixed effects regression was used to model changes in LCI over time. A total of 582 MBW measurements in 48 healthy subjects and 845 measurements in 64 cystic fibrosis subjects were available. The majority of children with cystic fibrosis had elevated LCI at the first preschool and first school age visits (57.8% (37 out of 64)), whereas all but six had normal forced expiratory volume in 1 s (FEV1) values at the first school age visit. During school age years, the course of disease was stable (−0.02 units·year−1 (95% CI −0.14–0.10). LCI measured during preschool years, as well as the rate of LCI change during this time period, were important determinants of LCI and FEV1, at school age. Preschool LCI was a major determinant of school age LCI; these findings further support that the preschool years are critical for early intervention strategies.Item 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 MedicineRationale: 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.Item Progression of Lung Disease in Preschool Patients with Cystic Fibrosis(American Thoracic Society, 2017-05-01) Stanojevic, Sanja; Davis, Stephanie D.; Retsch-Bogart, George t; Webster, Hailey; Davis, Miriam; Johnson, Robin C.; Jensen, Renee; Pizarro, Maria Ester; Kane, Mica; Clem, Charles C.; Schornick, Leah; Subbarao, Padmaja; Ratjen, Felix A.; Pediatrics, School of MedicineRATIONALE: Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. OBJECTIVES: To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progression in preschool children with CF. METHODS: Children with CF between the ages of 2.5 and 6 years with a confirmed diagnosis of CF and age-matched healthy control subjects were enrolled at three North American CF centers. Multiple breath washout tests were performed at baseline, 1, 3, 6, and 12 months to mimic time points chosen in clinical care and interventional trials; spirometry was also conducted. A generalized linear mixed-effects model was used to distinguish LCI changes associated with normal growth and development (i.e., healthy children) from the progression of CF lung disease. MEASUREMENTS AND MAIN RESULTS: Data were collected on 156 participants with 800 LCI measurements. Although both LCI and spirometry discriminated health from disease, only the LCI identified significant deterioration of lung function in CF over time. The LCI worsened during cough episodes and pulmonary exacerbations, whereas similar symptoms in healthy children were not associated with increased LCI values. CONCLUSIONS: LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF.