The utility of nasal nitric oxide in the diagnostic evaluation of primary ciliary dyskinesia.

BACKGROUND: There is no gold-standard test for primary ciliary dyskinesia (PCD), rather American Thoracic Society guidelines recommend starting with nasal nitric oxide (nNO) in children ≥5 years old and confirming the diagnosis with genetic testing or ciliary biopsy with transmission electron microscopy (TEM). These guidelines have not been studied in a clinical setting. We present a case series describing the PCD diagnostic process at our pediatric PCD center. METHODS: Diagnostic data from 131 patients undergoing PCD consultation were reviewed. RESULTS: In all participants ≥ 5 years old and who completed nNO using resistor methodology, the first diagnostic test performed was nNO in 77% (73/95), genetic testing in 14% (13/95), and TEM in <1% (9/95). nNO was the only diagnostic test performed in 75% (55/73) of participants who completed nNO first. Seventy-five percent (55/73) had a single above the cutoff nNO value and PCD was determined to be unlikely in 91% (50/55) without performing additional confirmatory testing. Eleven percent (8/73) had multiple below the cutoff nNO values, with 38% (3/8) being diagnosed with PCD by confirmatory testing and 50% (4/8) with negative confirmatory testing, but being managed as PCD. The genetic testing positivity rate was 50% in participants who completed nNO first and 8% when genetic testing was completed first. CONCLUSION: nNO is useful in three situations: an initial above the cutoff nNO value makes PCD unlikely and prevents additional confirmatory testing, repetitively below the cutoff nNO values without positive confirmatory testing suggests a probable PCD diagnosis and the yield of genetic testing is higher when nNO is performed first.

The US national registry for childhood interstitial and diffuse lung disease: Report of study design and initial enrollment cohort.

INTRODUCTION: Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare disorders. The Children's Interstitial and Diffuse Lung Disease Research Network (chILDRN) established a prospective registry to advance knowledge regarding etiology, phenotype, natural history, and management of these disorders. METHODS: This longitudinal, observational, multicenter registry utilizes single-IRB reliance agreements, with participation from 25 chILDRN centers across the U.S. Clinical data are collected and managed using the Research Electronic Data Capture (REDCap) electronic data platform. RESULTS: We report the study design and selected elements of the initial Registry enrollment cohort, which includes 683 subjects with a broad range of chILD diagnoses. The most common diagnosis reported was neuroendocrine cell hyperplasia of infancy, with 155 (23%) subjects. Components of underlying disease biology were identified by enrolling sites, with cohorts of interstitial fibrosis, immune dysregulation, and airway disease being most commonly reported. Prominent morbidities affecting enrolled children included home supplemental oxygen use (63%) and failure to thrive (46%). CONCLUSION: This Registry is the largest longitudinal chILD cohort in the United States to date, providing a powerful framework for collaborating centers committed to improving the understanding and treatment of these rare disorders.

Urinary tract infections in cystic fibrosis patients.

Improved understanding of non-respiratory infections in cystic fibrosis (CF) patients will be vital to sustaining the increased life span of these patients. To date, there has not been a published report of urinary tract infections (UTIs) in CF patients. We performed a retrospective chart review at a major academic medical center during 2010-2020 to determine the features of UTIs in 826 CF patients. We identified 108 UTI episodes during this period. Diabetes, distal intestinal obstruction syndrome (DIOS), and nephrolithiasis were correlated with increased risk of UTIs. UTIs in CF patients were less likely to be caused by Gram-negative rods compared to non-CF patients and more likely to be caused by Enterococcus faecalis. The unique features of UTIs in CF patients highlight the importance of investigating non-respiratory infections to ensure appropriate treatment.

Implementation and Improvement of Pediatric Asthma Guideline Improves Hospital-Based Care.

BACKGROUND: Standardized pediatric asthma care has been shown to improve measures in specific hospital areas, but to our knowledge, the implementation of an asthma clinical practice guideline (CPG) has not been demonstrated to be associated with improved hospital-wide outcomes. We sought to implement and refine a pediatric asthma CPG to improve outcomes and throughput for the emergency department (ED), inpatient care, and the ICU. METHODS: An urban, quaternary-care children's hospital developed and implemented an evidence-based, pediatric asthma CPG to standardize care from ED arrival through discharge for all primary diagnosis asthma encounters for patients ≥2 years old without a complex chronic condition. Primary outcomes included ED and inpatient length of stay (LOS), percent ED encounters requiring admission, percent admissions requiring ICU care, and total charges. Balancing measures included the number of asthma discharges between all-cause 30-day readmissions after asthma discharges and asthma relapse within 72 hours. Statistical process control charts were used to monitor and analyze outcomes. RESULTS: Analyses included 3650 and 3467 encounters 2 years pre- and postimplementation, respectively. Postimplementation, reductions were seen in ED LOS for treat-and-release patients (3.9 hours vs 3.3 hours), hospital LOS (1.5 days vs 1.3 days), ED encounters requiring admission (23.5% vs 18.8%), admissions requiring ICU (23.0% vs 13.2%), and total charges ($4457 vs $3651). Guideline implementation was not associated with changes in balancing measures. CONCLUSIONS: The hospital-wide standardization of a pediatric asthma CPG across hospital units can safely reduce overall hospital resource intensity by reducing LOS, admissions, ICU services, and charges.

Pulmonary hypertension in the premature infant population: Analysis of echocardiographic findings and biomarkers.

OBJECTIVE: Extremely low gestational age neonates (ELGANs) are at risk for pulmonary hypertension (PH). We hypothesized that PH, defined by echocardiogram at 36 weeks gestational age (GA), would associate with respiratory morbidity, increased oxidant stress, and reduced nitric oxide production. STUDY DESIGN: ELGANs in the Vanderbilt fraction of the Prematurity and Respiratory Outcomes Program (PROP) who had echocardiograms at 36 ± 1 weeks GA were studied. Echocardiogram features of PH were compared with clinical characteristics as well as markers of oxidant stress and components of the nitric oxide pathway. Biomarkers were obtained at enrollment (median day 3), 7, 14, and 28 days of life. RESULTS: Sixty of 172 infants had an echocardiogram at 36 weeks; 11 had evidence of PH. Infants did not differ by PH status in regards to demographics, respiratory morbidity, or oxidant stress. However, odds of more severe PH were significantly higher in infants with higher nitric oxide metabolites (NOx) at enrollment and with a lower citrulline level at day 7. CONCLUSIONS: Respiratory morbidity may not always associate with PH at 36 weeks among ELGANs. However, components of nitric oxide metabolism are potential biologic markers of PH in need of further study.

Respiratory Difficulties in Children With Underlying Asthma During Immunotherapy for High-risk Neuroblastoma.

Treatment of high-risk neuroblastoma now includes antibody based antitumor immunotherapy as part of standard care. Although this therapy has resulted in dramatic improvements in survival, it is associated with significant side effects. Children with underlying respiratory issues, and in particular asthma, may be more susceptible to immunotherapy associated respiratory compromise and pulmonary complications. Early routine involvement of pulmonology care is warranted for these patients in an effort to allow maximal delivery of immunotherapy and minimize acute and long-term complications.

Use of the aspartate aminotransferase to platelet ratio index to follow liver fibrosis progression in infants with short gut.

BACKGROUND: Infants with parenteral nutrition dependence may develop liver dysfunction and progress to liver failure requiring transplantation. The aspartate aminotransferase-to-platelet ratio index (APRI) has good correlation with liver fibrosis progression in adults. This study applies APRI scoring to parenteral nutrition-dependant, short-gut infants to determine hepatic fibrosis progression. METHODS: Laboratory values and biopsies were collected from initial intestinal resection (time 0) up to transplantation (end). Fibrosis scoring ranged from F0 (normal) to F4 (cirrhosis). Children were divided into 3 groups: (1) isolated intestine; and combined liver/intestine with gestational age (2) 34 weeks or greater and (3) 30 weeks or less. Liver function values over time, including calculated APRI, were analyzed as predictors of fibrosis. RESULTS: Fifteen children who had 33 biopsies were included. Median APRI by fibrosis grade was F < or = 2: 1.88, F3: 3.23, and F4: 14.16 (P < .01). Median APRI at transplant by study group was (1) isolated intestine: 2.47, (2) liver/intestine 35 weeks or longer EGA: 14.16, and (3) liver/intestine 30 weeks or less EGA: 14.74 (P = .04). CONCLUSION: Progression of APRI up to 60 days initially demonstrates similar values among study groups, but over time the score distinguishes those children with impending liver cirrhosis and differentiates fibrosis grade and study group.