Genomic and epidemiologic investigation of Mycobacterium abscessus isolates in a cystic fibrosis center to determine potential routes of transmission.

Background: Cystic Fibrosis (CF) Centers worldwide have reported healthcare-associated outbreaks of nontuberculous mycobacteria (NTM). We report a retrospective investigation of shared Mycobacterium abscessus strains among people with cystic fibrosis (pwCF) receiving care at Dell Children's/Ascension combined Pediatric and Adult CF Program (DCMC).

Methods: Whole genome sequencing (WGS) was used to identify genetically similar isolates among 167 NTM isolates from 57 pwCF.

Uncertainty-aware quantitative CT evaluation of emphysema and mortality risk from variable radiation dose images.

Objective: To develop an automated method for the joint and consistent evaluation of emphysema and mortality risk that provides quantification of data and model uncertainty.

Materials And Methods: Participants from the prospective COPDGene study who underwent both full radiation dose (FD) and reduced radiation dose (RD) chest CT scans at 5-year follow-up were included and divided into training (80%), validation (10%), and testing (10%) datasets. We trained a multi-task Bayesian neural network (BNN) to estimate the FD volume-adjusted lung density (ALD) regardless of acquisition protocol, in addition to the 5-year mortality risk.

Clinical factors associated with racial differences in the prevalence of occult hypoxemia: a retrospective case-control study.

Background: Recent studies showed that Black patients more often have falsely normal oxygen saturation on pulse oximetry compared to White patients. However, whether the racial differences in occult hypoxemia are mediated by other clinical differences is unknown.

Methods: We conducted a retrospective case-control study utilizing two large ICU databases (eICU and MIMIC-IV).

Deep Learning Classification of Usual Interstitial Pneumonia Predicts Outcomes.

Computed tomography (CT) enables noninvasive diagnosis of usual interstitial pneumonia (UIP), but enhanced image analyses are needed to overcome the limitations of visual assessment. Apply multiple instance learning (MIL) to develop an explainable deep learning algorithm for prediction of UIP from CT and validate its performance in independent cohorts. We trained an MIL algorithm using a pooled dataset ( = 2,143) and tested it in three independent populations: data from a prior publication ( = 127), a single-institution clinical cohort ( = 239), and a national registry of patients with pulmonary fibrosis ( = 979).

FEV/FVC Severity Stages for Chronic Obstructive Pulmonary Disease.

The diagnosis of chronic obstructive pulmonary disease (COPD) is based on a low FEV/FVC ratio, but the severity of COPD is classified using FEV% predicted (ppFEV). To test a new severity classification scheme for COPD using FEV/FVC ratio, a more robust measure of airflow obstruction than ppFEV. In COPDGene (Genetic Epidemiology of COPD) ( = 10,132), the severity of airflow obstruction was categorized by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-4 (ppFEV of ⩾80%, ⩾50-80%, ⩾30-50%, and <30%).

Molecular Epidemiologic Investigation of Subspecies Lung Infections at an Adult Cystic Fibrosis Program.

Outbreaks of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) have been reported at CF centers with conflicting conclusions. The occurrence of NTM at the UVMC (University of Vermont Medical Center) adult CF program was investigated. Use the HALT NTM (Healthcare-associated Links in Transmission of NTM) toolkit to investigate the healthcare-associated transmission and/or acquisition of NTM among pwCF having genetically similar NTM isolates.

Molecular networks in atopic mothers impact the risk of infant atopy.

Background: The prevalence of atopic diseases has increased with atopic dermatitis (AD) as the earliest manifestation. We assessed if molecular risk factors in atopic mothers influence their infants' susceptibility to an atopic disease.

Methods: Pregnant women and their infants with (n = 174, high-risk) or without (n = 126, low-risk) parental atopy were enrolled in a prospective birth cohort.

Biology vs. ecology: a longitudinal examination of sleep, development, and a change in school start times.

Background: Secondary school start times are associated with student sleep and daytime functioning; however, no study examining this association has included linked longitudinal data for both primary and secondary students. To understand the interplay between biology (ie, normal developmental changes in sleep) and ecology (ie, school start times), this study examined sleep and daytime functioning in elementary/primary and secondary school students over a three-year period that included changes to school start times.

Methods: Students (grades 3-10, n = 6168) and parents (for student grades Kindergarten-2, n = 2772) completed annual surveys before (pre-change) and for two-years after (post-change, follow-up) implementation of new school start times (elementary/primary: 60 min earlier, secondary: 50-80 min later).

Changing school start times: impact on sleep in primary and secondary school students.

Study Objectives: To examine the impact of changing school start times on sleep for primary (elementary school: ES) and secondary (middle and high school: MS/HS) students.

Methods: Students (grades 3-12) and parents (grades K-12) were surveyed annually, before and for 2 years after school start time changes (ES: 60 min earlier, MS: 40-60 min later; HS: 70 min later). Student sleep and daytime sleepiness were measured with school-administered student surveys and parent-proxy online surveys.

Efficacy and safety of reslizumab in the treatment of eosinophilic granulomatosis with polyangiitis.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), a rare vasculitis with substantial morbidity, is characterized by asthma, eosinophilia, sinusitis, pulmonary infiltrates, neuropathy, positivity for antineutrophil cytoplasmic antibody, and multiorgan vasculitis. Although treatment options previously included corticosteroids and immunosuppressants, anti-interleukin 5 therapies have gained interest in EGPA treatment. Mepolizumab was approved for and recently benralizumab was found to have safety and efficacy in EGPA.

Fleischner Society Visual Emphysema CT Patterns Help Predict Progression of Emphysema in Current and Former Smokers: Results from the COPDGene Study.

Background The correlation between visual emphysema patterns and subsequent progression of disease may provide a way to enrich a study population for treatment trials of emphysema. Purpose To evaluate the potential relationship between emphysema visual subtypes and progression of emphysema and gas trapping. Materials and Methods Current and former smokers with and without chronic obstructive pulmonary disease (COPD) enrolled in the prospective Genetic Epidemiology of COPD (COPDGene) study (ClinicalTrials.

Benralizumab as a Steroid-Sparing Treatment Option in Eosinophilic Granulomatosis with Polyangiitis.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis associated with significant morbidity and mortality that has historically been treated with systemic corticosteroids and immunosuppressants. The IL-5 antagonist mepolizumab was Food and Drug Administration approved in 2017 after demonstrating safety and efficacy in EGPA. We hypothesized that benralizumab, an IL-5 receptor antagonist approved for eosinophilic asthma, would demonstrate safety and efficacy in EGPA.

Expression and activation of the steroidogenic enzyme CYP11A1 is associated with IL-13 production in T cells from peanut allergic children.

Activation of the steroidogenic enzyme CYP11A1 was shown to be necessary for the development of peanut-induced intestinal anaphylaxis and IL-13 production in allergic mice. We determined if levels of CYP11A1 in peripheral blood T cells from peanut-allergic (PA) children compared to non-allergic controls were increased and if levels correlated to IL-13 production and oral challenge outcomes to peanut. CYP11A1 mRNA and protein levels were significantly increased in activated CD4+ T cells from PA patients.

Deep Learning Enables Automatic Classification of Emphysema Pattern at CT.

BackgroundPattern of emphysema at chest CT, scored visually by using the Fleischner Society system, is associated with physiologic impairment and mortality risk.PurposeTo determine whether participant-level emphysema pattern could predict impairment and mortality when classified by using a deep learning method.Materials and MethodsThis retrospective analysis of Genetic Epidemiology of COPD (COPDGene) study participants enrolled between 2007 and 2011 included those with baseline CT, visual emphysema scores, and survival data through 2018.

Impact of sleep opportunity on asthma outcomes in adolescents.

Rationale: Insufficient sleep is associated with a number of negative health outcomes; as most adolescents obtain <7 h of sleep per night, it is important to understand how sleep impacts asthma among adolescents.

Objectives: To examine the impact of sleep opportunity on asthma in adolescents.

Methods: In this study, 54 adolescents with asthma (12-17 years, 69% female, 65% Caucasian) participated in a randomized, cross-over sleep manipulation trial, including a sleep stabilization week, five nights of a "Short" sleep opportunity (time in bed: 6.

Corticosteroid use and increased CXCR2 levels on leukocytes are associated with lumacaftor/ivacaftor discontinuation in cystic fibrosis patients homozygous for the F508del CFTR mutation.

Cystic fibrosis (CF) is the most common life-shortening genetic disease and is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Several current therapies aim at improving availability and/or function of the mutant CFTR proteins. The combination therapeutic lumacaftor/ivacaftor (Orkambi, luma/iva) partially corrects folding and potentiates CFTR function impaired by the F508del mutation.

Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline: Five-Year Follow-up in Adult Smokers From the COPDGene Study.

Background: Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions.