ATS core curriculum 2023. Pediatric pulmonary medicine: Respiratory disorders in infants.

The American Thoracic Society Core Curriculum updates clinicians annually in pediatric pulmonary disease. This is a summary of the Pediatric Pulmonary Medicine Core Curriculum presented at the 2023 American Thoracic Society International Conference. The respiratory disorders of infancy discussed in this year's review include: the care of the patient with bronchopulmonary dysplasia in the neonatal intensive care unit, clinical phenotypes and comorbidities; diffuse lung disease; pulmonary hypertension; central and obstructive sleep apnea.

Predicting Adverse Neonatal Outcomes for Preterm Neonates with Multi-Task Learning.

Diagnosis of adverse neonatal outcomes is crucial for preterm survival since it enables doctors to provide timely treatment. Machine learning (ML) algorithms have been demonstrated to be effective in predicting adverse neonatal outcomes. However, most previous ML-based methods have only focused on predicting a single outcome, ignoring the potential correlations between different outcomes, and potentially leading to suboptimal results and overfitting issues.

Differential placental CpG methylation is associated with chronic lung disease of prematurity.

Background: Chronic lung disease (CLD) is the most common pulmonary morbidity in extremely preterm infants. It is unclear to what extent prenatal exposures influence the risk of CLD. Epigenetic variation in placenta DNA methylation may be associated with differential risk of CLD, and these associations may be dependent upon sex.

Genomic biomarkers in chronic beryllium disease and sarcoidosis.

Background Previous gene expression studies have identified genes IFNγ, TNFα, RNase 3, CXCL9, and CD55 as potential biomarkers for sarcoidosis and/or chronic beryllium disease (CBD). We hypothesized that differential expression of these genes could function as diagnostic biomarkers for sarcoidosis and CBD, and prognostic biomarkers for sarcoidosis. Study Design/Methods We performed RT-qPCR on whole blood samples from CBD (n = 132), beryllium sensitized (BeS) (n = 109), and sarcoidosis (n = 99) cases and non-diseased controls (n = 97) to determine differential expression of target genes.

Intentional Discontinuation of Psychostimulants Used to Treat ADHD in Youth: A Review and Analysis.

This paper reviews the literature on intentional discontinuation of psychostimulants in ADHD to summarize what is known about clinical course of controlled discontinuation and guide practitioners who are considering stopping these medications for youth with ADHD. A systematic search was executed in Cochrane CENTRAL, EMBASE, Psychinfo, and MEDLINE databases to identify all articles that addressed the topic of deprescribing of psychotropic medications in children and adolescents. Keywords and search strings were developed using "PICO" framework, involving Population of interest (<18 y.

Effect of Intrauterine Smoke Exposure on microRNA-15a Expression in Human Lung Development and Subsequent Asthma Risk.

In utero smoke (IUS) exposure is associated with asthma susceptibility. We sought to test the hypothesis that changes in miRNA expression by IUS exposure during human lung development is associated with asthma susceptibility. Gene expression was profiled from 53 IUS unexposed and 51 IUS exposed human fetal lung tissues.

Integrating multiomics longitudinal data to reconstruct networks underlying lung development.

A comprehensive understanding of the dynamic regulatory networks that govern postnatal alveolar lung development is still lacking. To construct such a model, we profiled mRNA, microRNA, DNA methylation, and proteomics of developing murine alveoli isolated by laser capture microdissection at 14 predetermined time points. We developed a detailed comprehensive and interactive model that provides information about the major expression trajectories, the regulators of specific key events, and the impact of epigenetic changes.

Selecting the most appropriate time points to profile in high-throughput studies.

Biological systems are increasingly being studied by high throughput profiling of molecular data over time. Determining the set of time points to sample in studies that profile several different types of molecular data is still challenging. Here we present the Time Point Selection () method that solves this combinatorial problem in a principled and practical way.

Spontaneous Single-Copy Loss of TP53 in Human Embryonic Stem Cells Markedly Increases Cell Proliferation and Survival.

Genomic aberrations have been identified in many human pluripotent stem cell (hPSC) cultures. Commonly observed duplications in portions of chromosomes 12p and 17q have been associated with increases in genetic instability and resistance to apoptosis, respectively. However, the phenotypic consequences related to sporadic mutations have not been evaluated to date.

Gene expression network analyses in response to air pollution exposures in the trucking industry.

Background: Exposure to air pollution, including traffic-related pollutants, has been associated with a variety of adverse health outcomes, including increased cardiopulmonary morbidity and mortality, and increased lung cancer risk.

Methods: To better understand the cellular responses induced by air pollution exposures, we performed genome-wide gene expression microarray analysis using whole blood RNA sampled at three time-points across the work weeks of 63 non-smoking employees at 10 trucking terminals in the northeastern US. We defined genes and gene networks that were differentially activated in response to PM (particulate matter ≤ 2.

The Role of Vitamin D in the Transcriptional Program of Human Pregnancy.

Background: Patterns of gene expression of human pregnancy are poorly understood. In a trial of vitamin D supplementation in pregnant women, peripheral blood transcriptomes were measured longitudinally on 30 women and used to characterize gene co-expression networks.

Objective: Studies suggest that increased maternal Vitamin D levels may reduce the risk of asthma in early life, yet the underlying mechanisms have not been examined.

Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome.

The fetal origins of disease hypothesis suggests that variations in the course of prenatal lung development may affect life-long pulmonary function growth, decline, and pathobiology. Many studies support the existence of differences in the developing lung trajectory in males and females, and sex-specific differences in the prevalence of chronic lung diseases, such as asthma and bronchopulmonary dysplasia. The objectives of this study were to investigate the early developing fetal lung for transcriptomic correlates of postconception age (maturity) and sex, and their associations with chronic lung diseases.

Identifying a gene expression signature of frequent COPD exacerbations in peripheral blood using network methods.

Background: Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors. Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility. Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.

Fetal lung and placental methylation is associated with in utero nicotine exposure.

In utero smoke exposure has been shown to have detrimental effects on lung function and to be associated with persistent wheezing and asthma in children. One potential mechanism of IUS effects could be alterations in DNA methylation, which may have life-long implications. The goal of this study was to examine the association between DNA methylation and nicotine exposure in fetal lung and placental tissue in early development; nicotine exposure in this analysis represents a likely surrogate for in-utero smoke.

Glucocorticoid genes and the developmental origins of asthma susceptibility and treatment response.

Antenatal corticosteroids enhance lung maturation. However, the importance of glucocorticoid genes on early lung development, asthma susceptibility, and treatment response remains unknown. We investigated whether glucocorticoid genes are important during lung development and their role in asthma susceptibility and treatment response.

Delivery-related knowledge of mothers of NICU infants compared with well-baby-nursery infants.

Objective: The objective of this study was to compare the knowledge of mothers of newborns in a neonatal intensive care unit (NICU) and well-baby nursery (WBN) regarding their understanding of term gestation, delivery mode safety, and elective late preterm delivery.

Methods: Mothers of newborns admitted to either an NICU (n=88) or a WBN (n=145) were surveyed (March 2008-September 2010).

Results: Of all mothers, regardless of infant location, 7% were unable to define term gestation, 33% were unaware that scheduling delivery at 35-36 weeks is not advisable, and 30% lacked the knowledge that cesareans are not safer than vaginal deliveries.

The genomic origins of asthma.

Lung function tracks from the earliest age that it can be reliably measured. Genome wide association studies suggest that most variants identified for common complex traits are regulatory in function and active during fetal development. Fetal programming of gene expression during development is critical to the formation of a normal lung.

Locally generated methylseleninic acid induces specific inactivation of protein kinase C isoenzymes: relevance to selenium-induced apoptosis in prostate cancer cells.

In this study, we show that methylselenol, a selenometabolite implicated in cancer prevention, did not directly inactivate protein kinase C (PKC). Nonetheless, its oxidation product, methylseleninic acid (MSA), inactivated PKC at low micromolar concentrations through a redox modification of vicinal cysteine sulfhydryls in the catalytic domain of PKC. This modification of PKC that occurred in both isolated form and in intact cells was reversed by a reductase system involving thioredoxin reductase, a selenoprotein.