IU Indianapolis ScholarWorks :: Browsing by Author "Ren, Clement L."

Browsing by Author "Ren, Clement L."

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Antibiotic Regimen Changes during Cystic Fibrosis Pediatric Pulmonary Exacerbation Treatment
(American Thoracic Society, 2023) Cogen, Jonathan D.; Sanders, Don B.; Slaven, James E.; Faino, Anna V.; Somayaji, Ranjani; Gibson, Ron L.; Hoffman, Lucas R.; Ren, Clement L.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
Rationale/Objectives: Antibiotic selection for in-hospital treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) is typically guided by previous respiratory culture results or past PEx antibiotic treatment. In the absence of clinical improvement during PEx treatment, antibiotics are frequently changed in search of a regimen that better alleviates symptoms and restores lung function. The clinical benefits of changing antibiotics during PEx treatment are largely uncharacterized. Methods: This was a retrospective cohort study using the Cystic Fibrosis Foundation Patient Registry Pediatric Health Information System. PEx were included if they occurred in children with CF from 6 to 21 years old who had been treated with intravenous antibiotics between January 1, 2006, and December 31, 2018. PEx with lengths of stay <5 or >21 days or for which treatment was delivered in an intensive care unit were excluded. An antibiotic change was defined as the addition or subtraction of any intravenous antibiotic between Hospital Day 6 and the day before hospital discharge. Inverse probability of treatment weighting was used to adjust for disease severity and indication bias, which might influence a decision to change antibiotics. Results: In all, 4,099 children with CF contributed 18,745 PEx for analysis, of which 8,169 PEx (43.6%) included a change in intravenous antibiotics on or after Hospital Day 6. The mean change in pre- to post-treatment percent predicted forced expiratory volume in 1 second (ppFEV1) was 11.3 (standard error, 0.21) among events in which an intravenous antibiotic change occurred versus 12.2 (0.18) among PEx without an intravenous antibiotic change (P = 0.001). Similarly, the odds of return to ⩾90% of baseline ppFEV1 were less for PEx with antibiotic changes than for those without changes (odds ratio [OR], 0.89 [95% confidence interval (CI), 0.80–0.98]). The odds of returning to ⩾100% of baseline ppFEV1 did not differ between PEx with versus without antibiotic changes (OR, 0.94 [95% CI, 0.86–1.03]). In addition, PEx treated with intravenous antibiotic changes were associated with higher odds of future PEx (OR, 1.17 [95% CI, 1.12–1.22]). Conclusions: In this retrospective study, changing intravenous antibiotics during PEx treatment in children with CF was common and not associated with improved clinical outcomes.
Building on the essential foundation of physiology
(Wiley, 2020-10) Ren, Clement L.; Gaston, Benjamin; Pediatrics, School of Medicine
Changes in Care during the COVID-19 Pandemic for People with Cystic Fibrosis
(American Thoracic Society, 2022) Sanders, Don B.; Wu, Runyu; O’Neil, Tom; Elbert, Alexander; Petren, Kris; Jain, Raksha; Ren, Clement L.; Pediatrics, School of Medicine
Rationale: Cystic fibrosis (CF) centers transitioned to telemedicine during the spring 2020 peak of the coronavirus disease (COVID-19) pandemic. Objectives: We hypothesized that people with CF (pwCF) with more severe disease would be more likely to be seen in-person. Methods: We used paired t tests to compare within-subject changes in body mass index (BMI) and percentage predicted forced expiratory volume in one second (FEV1) and calculated relative risk (RR) to compare pulmonary exacerbations (PEx) between pwCF enrolled in the CF Foundation Patient Registry with at least one in-person clinic visit after March 15 in both 2019 and 2020. Results: Overall, the proportion of clinical encounters that were in-person clinic visits decreased from 91% in 2019 to a low of 9% in April 2020. Among pwCF seen after March 15 in both 2019 and 2020, the mean (95% confidence interval [CI]) FEV1 percentage predicted was 1.3% (0.1-2.4) predicted higher in 2020 for children 6 to <12 years of age, and 7.5% (7.1-7.9) predicted higher in 2020 among pwCF ⩾12 years of age eligible for the highly effective CF transmembrane conductance regulator modulator, elexacaftor-tezacaftor-ivacaftor (ETI). There was no difference in FEV1 percentage predicted for pwCF ⩾12 years of age who were not eligible for ETI. Similarly, the mean (95% CI) BMI was 2.4 (2.0-2.8) percentile higher in 2020 for children 6 to <12 years of age and 5.2 (4.8-5.7) percentile higher in 2020 among children 12 to <18 years of age eligible for ETI. Mean (95% CI) BMI was 1.2 (1.2-1.3) (kg/m2) higher for pwCF ⩾18 years of age eligible for ETI, and 0.2 (0.1-0.3) (kg/m2) higher for pwCF ⩾18 years of age not eligible for ETI. The proportion of in-person clinic visits where any PEx was present was lower in 2020 compared with 2019, 25% compared with 38%, RR 0.82 (0.79-0.86). Conclusions: The care of pwCF was substantially changed during the spring 2020 peak of the COVID-19 pandemic. Among pwCF seen in-person in both 2019 and 2020 after the spring peak of the COVID-19 pandemic, lung function and BMI were higher in 2020 for children 6 to <12 years of age and pwCF eligible for ETI.
Comment on Munck et al., Feb, 2021
(Elsevier, 2021) Sontag, Marci K.; Farrell, Phillip M.; Kellar-Guenther, Yvonne; Martiniano, Stacey L.; Miller, Joshua I.; Ren, Clement L.; McColley, Susanna A.; Pediatrics, School of Medicine
Decreased vascular reactivity associated with increased IL-8 in 6-month-old infants of mothers with pre-eclampsia
(Springer Nature, 2024) Kua, Kok Lim; Rhoads, Eli; Slaven, James E.; Edwards, Shanique; Haas, David M.; Ren, Clement L.; Tiller, Christina; Bjerregaard, Jeffrey; Haneline, Laura S.; Tepper, Robert S.; Pediatrics, School of Medicine
Background: Offspring born to mothers with pre-eclampsia (Pre-E) suffer higher risks of adult cardiovascular diseases, suggesting that exposure to an antiangiogenic environment in-utero has a lasting impact on the development of endothelial function. The goal of this study is to test the hypothesis that in-utero exposure to Pre-E results in alterations of angiogenic factors/cytokines that negatively impact vascular development during infancy. Methods: Infants born from mothers with and without Pre-E were recruited and followed up at 6 months. Plasma cytokines, blood pressure, microvessel density, and vascular reactivity were assessed. Results: 6-month-old infants born to mothers with Pre-E had unchanged blood pressure (p = 0.86) and microvessel density (p = 0.57). Vascular reactivity was decreased in infants born to mothers with Pre-E compared to infants born to healthy mothers (p = 0.0345). Interleukin 8 (IL-8) (p = 0.03) and Angiopoeitin-2 (Ang-2) (p = 0.04) were increased in infants born to mothers with Pre-E. We observed that higher IL-8 was associated with lower vascular reactivity (rho = -0.14, p < 0.0001). Conclusion: At 6 months of age, infants born to mothers with Pre-E had impaired vascular reactivity and higher IL-8 and Ang-2, but similar blood pressure and microvessel density compared to infants born to non-Pre-E mothers. Impact statement: Changes in cord blood antiangiogenic factors are documented in infants of mothers with pre-eclampsia and may contribute to offspring risks of adult cardiovascular disease. How these factors evolve during early infancy and their correlation with offspring vascular development have not been studied. This study found that 6-month-old infants born to mothers with pre-eclampsia had decreased vascular reactivity, which was correlated with higher IL-8. These findings underscore the lasting impact of maternal pre-eclampsia on offspring vascular development and highlight the need for long-term follow-up in children born to mothers with pre-eclampsia.
Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation
(Elsevier, 2017-02) Farrell, Philip M.; White, Terry B.; Ren, Clement L.; Hempstead, Sarah E.; Accurso, Frank; Derichs, Nico; Howenstine, Michelle; McColley, Susanna A.; Rock, Michael; Rosenfeld, Margaret; Sermet-Gaudelus, Isabelle; Southern, Kevin W.; Marshall, Bruce C.; Sosnay, Patrick R.; Department of Pediatrics, School of Medicine
Objective Cystic fibrosis (CF), caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, continues to present diagnostic challenges. Newborn screening and an evolving understanding of CF genetics have prompted a reconsideration of the diagnosis criteria. Study design To improve diagnosis and achieve standardized definitions worldwide, the CF Foundation convened a committee of 32 experts in CF diagnosis from 9 countries to develop clear and actionable consensus guidelines on the diagnosis of CF and to clarify diagnostic criteria and terminology for other disorders associated with CFTR mutations. An a priori threshold of ≥80% affirmative votes was required for acceptance of each recommendation statement. Results After reviewing relevant literature, the committee convened to review evidence and cases. Following the conference, consensus statements were developed by an executive subcommittee. The entire consensus committee voted and approved 27 of 28 statements, 7 of which needed revisions and a second round of voting. Conclusions It is recommended that diagnoses associated with CFTR mutations in all individuals, from newborn to adult, be established by evaluation of CFTR function with a sweat chloride test. The latest mutation classifications annotated in the Clinical and Functional Translation of CFTR project (http://www.cftr2.org/index.php) should be used to aid in diagnosis. Newborns with a high immunoreactive trypsinogen level and inconclusive CFTR functional and genetic testing may be designated CFTR-related metabolic syndrome or CF screen positive, inconclusive diagnosis; these terms are now merged and equivalent, and CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis may be used. International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for use in diagnoses associated with CFTR mutations are included.
Early-Life Height Attainment in Cystic Fibrosis Is Associated with Pulmonary Function at Age 6 Years
(ATS, 2021-08) Sanders, Don B.; Slaven, James E.; Maguiness, Karen; Chmiel, James F.; Ren, Clement L.; Biostatistics, School of Public Health
Rationale: In contrast to the well-described association between early-life weight for age, body mass index (BMI), and later lung disease in people with cystic fibrosis (CF), the relationship between height-for-age (HFA) percentiles and respiratory morbidity is not as well-studied. We hypothesized that changes in HFA in children with CF in the first 6 years of life would be associated with pulmonary function at the age of 6–7 years. Objectives: To determine if an association exists between changes in HFA in early life and pulmonary function in school-aged children with CF. Methods: We performed a retrospective longitudinal cohort study of children with CF followed in the CF Foundation Patient Registry who were born between 2003 and 2010, had CF diagnosed before the age of 2 years, and were followed through at least the age of 7 years. Changes in annualized HFA were classified into mutually exclusive categories. Multivariable analysis of covariance models were used to test for an association between the percent-predicted forced expiratory volume in 1 second (FEV1) at the age of 6–7 years and height-trajectory categories. Results: There were 5,388 eligible children in the CF Foundation Patient Registry. The median (interquartile range) HFA at the age of 6–7 years was in the 39.5th (17.2th–64.9th) percentile. The mean (95% confidence interval) FEV1% predicted at the age of 6–7 years was 95.6% (95.1–96.1%). In a multivariable regression model, the mean (95% confidence interval) FEV1% predicted was higher for children with HFA that was always above the 50th percentile (97.8% [96.3–99.4%]) than for children whose height had been below the 50th percentile for at least 1 year and increased by ≥10 percentile points (95.1% [93.7–96.6%]), was stable (94.3% [92.8–95.7%]), or decreased by ≥10 percentile points (95.7% [94.2–97.3%]). The association between HFA categories and FEV1% predicted was not affected by adding the mean annualized BMI percentile at the age of 6–7 years to the regression model. Among those with HFA that decreased by ≥10 percentile points, there was a correlation between the nadir annualized HFA percentile and the FEV1% predicted at the age of 6–7 years. Conclusions: Children with CF with HFA that is always above the 50th percentile have the highest pulmonary function at the age of 6–7 years. Maintaining a BMI above the 50th percentile remains an important achievable goal for children with CF but is not the sole marker that should be examined in evaluating nutrition.
Evaluating FEV1 decline in diagnosis and management of pulmonary exacerbations in children with cystic fibrosis
(Wiley, 2022) Bouzek, Drake C.; Ren, Clement L.; Thompson, Misty; Slaven, James E.; Sanders, Don B.; Pediatrics, School of Medicine
Rationale: Forced expiratory volume in 1 s (FEV1) decline (ΔFEV1) is associated with pulmonary exacerbation (PEx) diagnosis in cystic fibrosis (CF). Spirometry may not be available during telehealth visits and could impair clinician ability to diagnose PEx. This study aims to (1) identify the associations between degrees of ΔFEV1 (decrease of <5% predicted vs. 5%-9% predicted vs. ≥10% predicted from baseline), clinical symptoms, and clinician-diagnosed PEx and (2) evaluate the correlation between respiratory symptoms, ΔFEV1, and antibiotic treatment. Methods: Retrospective, descriptive study of PEx diagnosis and management in 628 outpatient clinical encounters with spirometry in 178 patients with CF ages 6-17 years at Riley Hospital for Children during 2019. Odds ratios (OR) of symptoms associated with clinician-defined PEx diagnosis and antibiotic management stratified by ΔFEV1 decline were determined. Results: Clinician-diagnosed PEx occurred at 199 (31.7%) visits; increased cough (77.4%) and sputum/wet cough (57.8%) were the most frequently reported symptoms. Compared to no ΔFEV1, the odds of a clinician-diagnosed PEx were increased when ΔFEV15%-9% and ΔFEV1≥10% was present with increased cough (OR 1.56, 95% confidence interval [CI] 1.25-1.94 and OR 1.82, 95% CI 1.52-2.19, respectively), increased sputum (OR 1.59, 95% CI 1.20-2.12 and OR 1.78, 95% CI 1.37-2.32, respectively), and increased cough and sputum together (OR 1.51, 95% CI 1.08-2.13 and OR 1.68, 95% CI 1.22-2.31, respectively). Conclusions: ΔFEV1 is associated with increased likelihood that cough and sputum are diagnosed as a PEx. Spirometry is essential for PEx diagnosis and treatment and is a necessary component of all clinical encounters.
Forced expiratory flows and diffusion capacity in infants born from mothers with pre‐eclampsia
(Wiley, 2022) Ren, Clement L.; Slaven, James E.; Haas, David M.; Haneline, Laura S.; Tiller, Christina; Hogg, Graham; Bjerregaard, Jeffrey; Tepper, Robert S.; Biostatistics, School of Public Health
Rationale: Animal models suggest pre-eclampsia (Pre-E) affects alveolar development, but data from humans are lacking. Objective: Assess the impact of Pre-E on airway function, diffusion capacity, and respiratory morbidity in preterm and term infants born from mothers with Pre-E. Methods: Infants born from mothers with and without Pre-E were recruited for this study; term and preterm infants were included in both cohorts. Respiratory morbidity in the first 12 months of life was assessed through monthly phone surveys. Raised volume rapid thoracoabdominal compression and measurement of diffusion capacity of the lung to carbon monoxide (DLCO) were performed at 6 months corrected age. Measurements and main results: There were 146 infants in the Pre-E cohort and 143 in the control cohort. The Pre-E cohort was further divided into nonsevere (N = 41) and severe (N = 105) groups. There was no significant difference in DLCO and DLCO/alveolar volume among the three groups. Forced vital capacity was similar among the three groups, but the nonsevere Pre-E group had significantly higher forced expiratory flows than the other two groups. After adjusting for multiple covariates including prematurity, the severe Pre-E group had a lower risk for wheezing in the first year of life compared to the other two groups. Conclusions: Pre-E is not associated with reduced DLCO, lower forced expiratory flows, or increased wheezing in the first year of life. These results differ from animal models and highlight the complex relationships between Pre-E and lung function and respiratory morbidity in human infants.
Hyperinflation is Associated with Increased Respiratory Rate and is a More Sensitive Measure of Cystic Fibrosis Lung Disease During Infancy Compared to Forced Expiratory Measures
(Wiley, 2021-09) Muston, Heather N.; Slaven, James E.; Tiller, Christina; Clem, Charles; Ferkol, Thomas W.; Ranganathan, Sarath; Davis, Stephanie D.; Ren, Clement L.; Pediatrics, School of Medicine
Background The goal of this study was to identify clinical features associated with abnormal infant pulmonary function tests (iPFTs), specifically functional residual capacity (FRC), in infants with cystic fibrosis (CF) diagnosed via newborn screen (NBS). We hypothesized that poor nutritional status in the first 6-12 months would be associated with increased FRC at 12-24 months. Methods This study utilized a combination of retrospectively and prospectively collected data from ongoing research studies and iPFTs performed for clinical indications. Demographic and clinical features were obtained from the electronic medical record. Forced expiratory flows and volumes were obtained using the raised volume rapid thoracoabdominal technique (RVRTC) and FRC was measured via plethysmography. Results A total of 45 CF NBS infants had iPFTs performed between 12-24 months. Mean forced vital capacity, forced expiratory volume in 0.5 second, and forced expiratory flows were all within normal limits. In contrast, the mean FRC z-score was 2.18 (95%CI=1.48, 2.88) and the mean respiratory rate (RR) z-score was 1.42 (95%CI=0.95, 1.89). There was no significant association between poor nutritional status and abnormal lung function. However, there was a significant association between higher RR and increased FRC, and a RR cutoff of 36 breaths/min resulted in 92% sensitivity to detect hyperinflation with 32% specificity. Conclusions These results suggest that FRC is a more sensitive measure of early CF lung disease than RVRTC measurements and that RR may be a simple, non-invasive clinical marker to identify CF NBS infants with hyperinflation. This article is protected by copyright. All rights reserved.

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