Race-Neutral Equations and Pulmonary Function Test Interpretation in Two Pediatric Cohorts.

OBJECTIVE: To investigate the changes in predicted lung function measurements when using race-neutral equations in children, based upon the new Global Lung Initiative (GLI) reference equations, utilizing a race-neutral approach in interpreting spirometry results compared with the 2012 race-specific GLI equations. STUDY DESIGN: We analyzed data from 2 multicenter prospective cohorts comprised of healthy children and children with history of severe (requiring hospitalization) bronchiolitis. Spirometry testing was done at the 6-year physical exam, and 677 tests were analyzed using new GLI Global and 2012 GLI equations. We used multivariable logistic regression, adjusted for age, height, and sex, to examine the association of race with the development of new impairment or increased severity (forced expiratory volume in the first second (FEV1) z-score ≤ -1.645) as per 2022 American Thoracic Society (ATS) guidelines. RESULTS: Compared with the race-specific GLI, the race-neutral equation yielded increases in the median forced expiratory volume in the first second and forced vital capacity (FVC) percent predicted in White children but decreases in these two measures in Black children. The prevalence of obstruction increased in White children by 21%, and the prevalence of possible restriction increased in Black children by 222%. Compared with White race, Black race was associated with increased prevalence of new impairments (aOR 7.59; 95%CI, 3.00-19.67; P < .001) and increased severity (aOR 35.40; 95%CI, 4.70-266.40; P = .001). Results were similar across both cohorts. CONCLUSIONS: As there are no biological justifications for the inclusion of race in spirometry interpretation, use of race-neutral spirometry reference equations led to an increase in both the prevalence and severity of respiratory impairments among Black children.

Late Pre-term Infants with Severe Bronchiolitis and Risk of Asthma by Age 5 Years.

In a prospective, multicenter cohort of infants hospitalized with bronchiolitis, we found infants born late pre-term (ie, gestational age of 34-36.9 weeks) had 35% higher odds of having asthma by age 5 years compared with infants born at full-term.

Availability of Pediatric Emergency Care Coordinators in United States Emergency Departments.

OBJECTIVE: To determine the availability of pediatric emergency care coordinators (PECCs) in US emergency departments (EDs) in 2015, and to determine the change in availability of PECCs in US EDs from 2015 to 2017. STUDY DESIGN: As part of the National Emergency Department Inventory-USA, we administered a survey to all 5326 US EDs open in 2015; all 5431 in 2016; and all 5489 in 2017. Through these surveys, we assessed the availability of PECCs. Descriptive statistics characterized EDs with and without PECCs; multivariable logistic regressions identified characteristics independently associated with PECC availability. RESULTS: Among the 4443 (83%) EDs with 2015 data, 763 (17.2%) reported the availability of at least 1 PECC. The states with the largest proportion of EDs with PECCs were Delaware (78%, 7/9 EDs) and Maryland (48%, 20/42 EDs), and no PECCs were reported in Mississippi, North Dakota, or Wyoming. Availability of a PECC was associated (P < .001) with larger annual total ED visit volume and a dedicated pediatric ED area. Compared with the 17.2% of EDs reporting a PECC in 2015, 833 (18.6%) reported 1 in 2016, and 917 (19.8%) reported 1 in 2017 (P < .001). CONCLUSIONS: Availability of at least 1 PECC increased slightly (2.6%) between 2015 and 2017, but ∼80% of EDs continue without one.

Vitamin D Status at the Time of Hospitalization for Bronchiolitis and Its Association with Disease Severity.

OBJECTIVE: To investigate the association between circulating 25-hydroxyvitamin D [25(OH)D] status at admission and disease severity among infants hospitalized for bronchiolitis and to determine whether the association differs by the form of 25(OH)D-total, bioavailable or free 25(OH)D. STUDY DESIGN: We conducted a 17-center prospective cohort study of 1016 US infants <12 months old hospitalized with bronchiolitis. Vitamin D status was defined by total 25(OH)D levels, and by calculated levels of bioavailable and free 25(OH)D. Bronchiolitis severity was defined by requirement for intensive care and hospital length-of-stay (LOS). Logistic and Poisson regression were used for unadjusted and multivariable analyses. RESULTS: The median age of hospitalized infants was 3.2 months (IQR 1.6-6.0). The median total 25(OH)D was 26.5 ng/mL (IQR 18.0-33.1); 298 (29%) infants had total 25(OH)D <20 ng/mL. In multivariable models, infants with total 25(OH)D <20 ng/mL had higher risk of requiring intensive care (aOR 1.72, 95% CI 1.12-2.64) and longer LOS (adjusted rate ratio 1.39, 95% CI 1.17-1.65) compared with infants with total 25(OH)D ≥30 ng/mL. Infants with the lowest tertile of bioavailable 25(OH)D, compared with those with the highest tertile, had longer LOS (adjusted rate ratio 1.32, 95% CI 1.07-1.62); admission to the intensive care unit was not statistically significant in the adjusted model (aOR 1.39, 95% CI 0.96-2.64). Free 25(OH)D level was not associated with severity of bronchiolitis in either unadjusted or adjusted models. CONCLUSION: In a large, multicenter cohort of US infants hospitalized for bronchiolitis, infants with total 25(OH)D <20 ng/mL had increased risk of intensive care and longer hospital LOS.

Children Hospitalized with Rhinovirus Bronchiolitis Have Asthma-Like Characteristics.

Children with bronchiolitis often are considered a homogeneous group. However, in a multicenter, prospective study of 2207 young children hospitalized for bronchiolitis, we found that children with respiratory syncytial virus detected differ from those with rhinovirus detected; the latter patients resemble older children with asthma, including more frequent treatment with corticosteroids.

Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse.

The CLN6 gene that causes variant late-infantile neuronal ceroid lipofuscinosis (vLINCL), a recessively inherited neurodegenerative disease that features blindness, seizures, and cognitive decline, maps to 15q21-23. We have used multiallele markers spanning this approximately 4-Mb candidate interval to reveal a core haplotype, shared in Costa Rican families with vLINCL but not in a Venezuelan kindred, that highlighted a region likely to contain the CLN6 defect. Systematic comparison of genes from the minimal region uncovered a novel candidate, FLJ20561, that exhibited DNA sequence changes specific to the different disease chromosomes: a G-->T transversion in exon 3, introducing a stop codon on the Costa Rican haplotype, and a codon deletion in exon 5, eliminating a conserved tyrosine residue on the Venezuelan chromosome. Furthermore, sequencing of the murine homologue in the nclf mouse, which manifests recessive NCL-like disease, disclosed a third lesion-an extra base pair in exon 4, producing a frameshift truncation on the nclf chromosome. Thus, the novel approximately 36-kD CLN6-gene product augments an intriguing set of unrelated membrane-spanning proteins, whose deficiency causes NCL in mouse and man.