129Xe MRI as a measure of clinical disease severity for pediatric asthma.

BACKGROUND: Measurement of regional lung ventilation with hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI) in pediatric asthma is poised to advance our understanding of disease mechanisms and pathophysiology in a disorder with diverse clinical phenotypes. 129Xe MRI has not been investigated in a pediatric asthma cohort. OBJECTIVE: We hypothesized that 129Xe MRI is feasible and can demonstrate ventilation defects that relate to and predict clinical severity in a pediatric asthma cohort. METHODS: Thirty-seven children (13 with severe asthma, 8 with mild/moderate asthma, 16 age-matched healthy controls) aged 6 to 17 years old were imaged with 129Xe MRI. Ventilation defect percentage (VDP) and image reader score were calculated and compared with clinical measures at baseline and at follow-up. RESULTS: Children with asthma had higher VDP (P = .002) and number of defects per image slice (defects/slice) (P = .0001) than children without asthma. Children with clinically severe asthma had significantly higher VDP and number of defects/slice than healthy controls. Children with asthma who had a higher number of defects/slice had a higher rate of health care utilization (r = 0.48; P = .03) and oral corticosteroid use (r = 0.43; P = .05) at baseline. Receiver-operating characteristic analysis demonstrated that the VDP and number of defects/slice were predictive of increased health care utilization, asthma, and severe asthma. VDP correlated with FEV1 (r = -0.35; P = .04) and FEV1/forced vital capacity ratio (r = -0.41; P = .01). CONCLUSIONS: 129Xe MRI correlates with asthma severity, health care utilization, and oral corticosteroid use. Because delineation of clinical severity is often difficult in children, 129Xe MRI may be an important biomarker for severity, with potential to identify children at higher risk for exacerbations and improve outcomes.

Telehealth delivery of adherence and medication management system improves outcomes in inner-city children with asthma.

Healthcare disparities exist in pediatric asthma in the United States. Children from minority, low-income families in inner-city areas encounter barriers to healthcare, leading to greater rates of poorly controlled asthma and healthcare utilization. Finding an effective way to deliver high-quality healthcare to this underserved population to improve outcomes, reduce morbidity and mortality, and reduce healthcare utilization is of the utmost importance. The purpose of this study was to assess the feasibility and efficacy of a novel school-based care delivery model that incorporates video-based telehealth (VBT) medical and self-management visits with electronic inhaler monitoring to improve asthma outcomes. Over a 6-month period, children from inner-city, low-income schools with uncontrolled asthma completed seven scheduled medical visits with an asthma specialist and five self-management visits with an adherence psychologist at school using VBT. Composite Asthma Severity Index (CASI) scores and electronic inhaler monitor data were recorded and analyzed. A total of 21 patients were enrolled in the study. Study subjects with higher baseline severity (CASI ≥ 4 at visit 1) demonstrated a greater reduction in their score than those with lower baseline severity (CASI < 4 at visit 1). The CASI domains showed improvement in daytime symptoms, nighttime symptoms, and exacerbations. Adherence results demonstrated a significant improvement in adherence from baseline to postintervention. Study retention was 100%. This study demonstrates that a multicomponent medical and behavioral interventional program delivered by VBT to a school-based setting is feasible and can significantly improve asthma outcomes and care in a challenging population.

Transport of galectin-3 between the nucleus and cytoplasm. II. Identification of the signal for nuclear export.

Galectin-3, a factor involved in the splicing of pre-mRNA, shuttles between the nucleus and the cytoplasm. Previous studies have shown that incubation of fibroblasts with leptomycin B resulted in the accumulation of galectin-3 in the nucleus, suggesting that the export of galectin-3 from the nucleus may be mediated by the CRM1 receptor. A candidate nuclear export signal fitting the consensus sequence recognized by CRM1 can be found between residues 240 and 255 of the murine galectin-3 sequence. This sequence was engineered into the pRev(1.4) reporter system, in which candidate sequences can be tested for nuclear export activity in terms of counteracting the nuclear localization signal present in the Rev(1.4) protein. Rev(1.4)-galectin-3(240-255) exhibited nuclear export activity that was sensitive to inhibition by leptomycin B. Site-directed mutagenesis of Leu247 and Ile249 in the galectin-3 nuclear export signal decreased nuclear export activity, consistent with the notion that these two positions correspond to the critical residues identified in the nuclear export signal of the cAMP-dependent protein kinase inhibitor. The nuclear export signal activity was also analyzed in the context of a full-length galectin-3 fusion protein; galectin-3(1-263; L247A) showed more nuclear localization than wild-type, implicating Leu247 as critical to the function of the nuclear export signal. These results indicate that residues 240-255 of the galectin-3 polypeptide contain a leucine-rich nuclear export signal that overlaps with the region (residues 252-258) identified as important for nuclear localization.