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Browsing by Author "Clem, Charles"
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Item 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 MedicineBackground 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.Item In Vivo Analysis of Tissue S-Nitrosothiols in Pediatric Sepsis(MDPI, 2024-02-21) Cater, Daniel T.; Clem, Charles; Marozkina, Nadzeya; Gaston, Benjamin; Pediatrics, School of MedicineS-nitrosothiols are endogenous, bioactive molecules. S-nitrosothiols are implicated in many diseases, including sepsis. It is currently cumbersome to measure S-nitrosothiols clinically. We have previously developed an instrument to measure tissue S-nitrosothiols non-invasively using ultraviolet light. We have performed a prospective case control study of controls and children with sepsis admitted to the PICU. We hypothesized that tissue S-nitrosothiols would be higher in septic patients than controls. Controls were patients with no cardiopulmonary instability. Cases were patients with septic shock. We measured S-nitrosothiols, both at diagnosis and after resolution of shock. A total of 44 patients were enrolled: 21 controls and 23 with sepsis. At baseline, the controls were younger [median age 5 years (IQR 0, 9) versus 11 years (IQR: 6, 16), p-value = 0.012], had fewer comorbidities [7 (33.3%) vs. 20 (87.0%), p-value < 0.001], and had lower PELOD scores [0 (IQR: 0, 0) vs. 12 (IQR: 11, 21), p-value < 0.001]. S-nitrosothiol levels were higher in sepsis cohort (1.1 ppb vs. 0.8 ppb, p = 0.004). Five patients with sepsis had longitudinal measures and had a downtrend after resolution of shock (1.3 ppb vs. 0.9 ppb, p = 0.04). We dichotomized patients based on S-nitrosothiol levels and found an association with worse clinical outcomes, but further work will be needed to validate these findings.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 Multiple-Breath Washout Outcomes Are Sensitive to Inflammation and Infection in Children with Cystic Fibrosis(ATS, 2017-09) Ramsey, Kathryn A.; Foong, Rachel E.; Grdosic, Jasmine; Harper, Alana; Skoric, Billy; Clem, Charles; Davis, Miriam; Turkovic, Lidija; Stick, Stephen M.; Davis, Stephanie D.; Ranganathan, Sarath C.; Hall, Graham L.; Pediatrics, School of MedicineRationale: The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. The lung clearance index is increased in the presence of lower respiratory tract inflammation and infection in infants with cystic fibrosis; however, the associations during the preschool years are unknown. Objectives: We assessed the ability of the lung clearance index to detect the presence and extent of lower respiratory tract inflammation and infection in preschool children with cystic fibrosis. Methods: Ventilation distribution outcomes were assessed at 82 visits with 58 children with cystic fibrosis and at 38 visits with 31 healthy children aged 3–6 years. Children with cystic fibrosis also underwent bronchoalveolar lavage fluid collection for detection of lower respiratory tract inflammation and infection. Associations between multiple-breath washout indices and the presence and extent of airway inflammation and infection were assessed using linear mixed effects models. Results: Lung clearance index was elevated in children with cystic fibrosis (mean [SD], 8.00 [1.45]) compared with healthy control subjects (6.67 [0.56]). In cystic fibrosis, the lung clearance index was elevated in individuals with lower respiratory tract infections (difference compared with uninfected [95% confidence interval], 0.62 [0.06, 1.18]) and correlated with the extent of airway inflammation. Conclusions: These data suggest that the lung clearance index may be a useful surveillance tool for monitoring the presence and extent of lower airway inflammation and infection in preschool children with cystic fibrosis.Item Photolytic Measurement of Tissue S-Nitrosothiols in Rats and Humans In Vivo(MDPI, 2022-02) Neidigh, Noah; Alexander, Alyssa; van Emmerik, Parker; Higgs, Allison; Plack, Logan; Clem, Charles; Cater, Daniel; Marozkina, Nadzeya; Gaston, Benjamin; Pediatrics, School of MedicineS-nitrosothiols are labile thiol-NO adducts formed in vivo primarily by metalloproteins such as NO synthase, ceruloplasmin, and hemoglobin. Abnormal S-nitrosothiol synthesis and catabolism contribute to many diseases, ranging from asthma to septic shock. Current methods for quantifying S-nitrosothiols in vivo are suboptimal. Samples need to be removed from the body for analysis, and the S-nitrosothiols can be broken down during ex vivo processing. Here, we have developed a noninvasive device to measure mammalian tissue S-nitrosothiols in situ non-invasively using ultraviolet (UV) light, which causes NO release in proportion to the S-nitrosothiol concentration. We validated the assay in vitro; then, we applied it to measure S-nitrosothiols in vivo in rats and in humans. The method was sensitive to 0.5 µM, specific (did not detect other nitrogen oxides), and was reproducible in rats and in humans. This noninvasive approach to S-nitrosothiol measurements may be applicable for use in human diseases.Item Tidal Breathing Measurements at Discharge and Clinical Outcomes in Extremely Low Gestational Age Neonates(ATA, 2018-03) Ren, Clement L.; Feng, Rui; Davis, Stephanie D.; Eichenwald, Eric; Jobe, Alan; Moore, Paul E.; Panitch, Howard B.; Sharp, Jack K.; Kisling, Jeff; Clem, Charles; Kemp, James S.; Pediatrics, School of MedicineRationale: The relationship between respiratory function at hospital discharge and the severity of later respiratory disease in extremely low gestational age neonates is not well defined. Objectives: To test the hypothesis that tidal breathing measurements near the time of hospital discharge differ between extremely premature infants with BPD or respiratory disease in the first year of life compared to those without these conditions. Methods: Study subjects were part of the Prematurity and Respiratory Outcomes Program (PROP) study, a longitudinal cohort study of infants born <29 gestational weeks followed from birth to 1 year of age. Respiratory inductance plethysmography was used for tidal breathing measurements before and after inhaled albuterol 1 week prior to anticipated hospital discharge. Infants were breathing spontaneously and were receiving ≤1 liter per minute (lpm) nasal cannula flow at 21-100% FiO2. A survey of respiratory morbidity was administered to caregivers at 3, 6, 9, and 12 months corrected age to assess for respiratory disease. We compared tidal breathing measurements in infants with and without bronchopulmonary dysplasia (BPD, oxygen requirement at 36 wk) and with and without respiratory disease in the first year of life. Measurements were also performed in a comparison cohort of term infants. Results: 765 infants survived to 36 weeks post-menstrual age, with research-quality tidal breathing data in 452 out of 564 tested (80.1%). Among these 452 infants, the rate of post-discharge respiratory disease was 65.7%. Compared to a group of 18 term infants, PROP infants had abnormal tidal breathing patterns. However, there were no significant differences in tidal breathing measurements in PROP infants who had BPD or who had respiratory disease in the first year of life compared to those without these diagnoses. Bronchodilator response was not significantly associated with respiratory disease in the first year of life. Conclusions: Extremely premature infants receiving <1 lpm nasal cannula support at 21-100% FiO2 have tidal breathing measurements that differ from term infants, but these measurements do not differentiate those preterm infants who have BPD or will have respiratory disease in the first year of life from those who do not.