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Background: Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) suffer from a high burden of pulmonary diseases, even after accounting for their smoking status. Cytotoxic CD8 T-cells are likely implicated in this phenomenon and may act as a double-edged sword. While being essential in viral infection control, their hyperactivation can also contribute to lung mucosal tissue damage. The effects of HIV and smoking on pulmonary mucosal CD8 T-cell dynamics has been a neglected area of research, which we address herein. Methods: Bronchoalveolar lavage (BAL) fluid were obtained from ART-treated PLWH (median duration of supressed viral load: 9 years; smokers: n = 14; non-smokers: n = 21) and HIV-uninfected controls (smokers: n = 11; non-smokers: n = 20) without any respiratory symptoms or active infection. Lymphocytes were isolated and CD8 T-cell subsets and homing markers were characterized by multiparametric flow cytometry. Results: Both smoking and HIV infection were independently associated with a significant increase in frequencies of total pulmonary mucosal CD8 T-cell. BAL CD8 T-cells were primarily CD69 + expressing CD103 and/or CD49a, at least one of the two granzymes (GzmA/GzmB), and little Perforin. Higher expression levels of CD103, CD69, and GzmB were observed in smokers versus non-smokers. The ex vivo phenotype of GzmA + and GzmB + cells revealed increased expression of CD103 and CXCR6 in smokers, while PLWH displayed elevated levels of CX3CR1 compared to controls. Conclusion: Smoking and HIV could promote cytotoxic CD8 T-cell retention in small airways through different mechanisms. Smoking likely increases recruitment and retention of GzmB + CD8 Trm via CXCR6 and CD103. Heightened CX3CR1 expression could be associated with CD8 non-Trm recruitment from the periphery in PLWH. [ABSTRACT FROM AUTHOR]

Background: Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants caused by therapeutic oxygen supplemental and characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD have been increasing with limited therapeutic options for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight, and estimated blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD. Methods: Cord blood DNA from preterm neonates that went on to develop BPD (n = 14) or not (non-BPD, n = 93) was applied to Illumina 450 K methylation arrays. Blood cell-type compositions were estimated using DNA methylation profiles. Multivariable robust regression analysis elucidated CpGs associated with BPD risk. cDNA microarray analysis of cord blood RNA identified differentially expressed genes in neonates who later developed BPD. Results: The development of BPD and the need for oxygen supplementation were strongly associated with GA (BPD, p < 1.0E−04; O2 supplementation, p < 1.0E−09) and birth weight (BPD, p < 1.0E−02; O2 supplementation, p < 1.0E−07). The estimated nucleated red blood cell (NRBC) percent was negatively associated with birth weight and GA, positively associated with hypomethylation of the tobacco smoke exposure biomarker cg05575921, and high-NRBC blood samples displayed a hypomethylation profile. Epigenome-wide association study (EWAS) identified 38 (Bonferroni) and 275 (false discovery rate 1%) differentially methylated CpGs associated with BPD. BPD-associated CpGs in cord blood were enriched for lung maturation and hematopoiesis pathways. Stochastic epigenetic mutation burden at birth was significantly elevated among those who developed BPD (adjusted p = 0.02). Transcriptome changes in cord blood cells reflected cell cycle, development, and pulmonary disorder events in BPD. Conclusions: While results must be interpreted with caution because of the small size of this study, NRBC content strongly impacted DNA methylation profiles in preterm cord blood and EWAS analysis revealed potential insights into biological pathways involved in BPD pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Childcare settings are important environments for influencing child eating and physical activity (PA). Family childcare homes (FCCH) care for many children of low-income and diverse racial/ethnic backgrounds who are at greater risk for poor diet quality, low PA, and obesity, but few interventions have targeted this setting. The aim of this study was to assess the efficacy of a multicomponent intervention conducted in FCCH on the diet quality and PA of 2–5 year old children in their care. Trial design: Cluster randomized trial. Methods: The cluster-randomized trial, Healthy Start/Comienzos Sanos (2015–2019) evaluated an 8-month nutrition and PA intervention that included four components: (1) monthly telephone calls from a support coach using brief motivational interviewing, (2) tailored reports, newsletters and videos, (3) group support meetings, and (4) active play toys. After completing baseline measurement, FCCH were randomized into intervention or comparison groups in matched pairs. Both groups received the same intervention components but on different topics (intervention: nutrition/PA vs. comparison: reading readiness/literacy). Evaluation staff were blinded to group assignment. Child primary outcome measures collected at baseline and 8-months included: 1) Healthy Eating Index (HEI-2015) scores calculated from diet observation, and 2) accelerometer measurement of PA. Process measures were collected from field data and provider surveys. Generalized Estimating Equation Models assessed changes in HEI-2015 scores and PA over time by experimental condition. Results: Ethnically diverse FCCH providers (n = 119) and 2-to-5-year-old children in their care (n = 377) were included in the final analysis. Process evaluation showed high participation in all intervention components except for group meetings. Compared to children in comparison group FCCH, children in intervention FCCH increased total HEI-2015 scores by 7.2 points (p <.001) including improvement in component scores for vegetables (0.84 points, p =.025) and added sugar (0.94 points, p =.025). For PA, compared to children in the comparison group, children in intervention FCCH decreased sedentary time by 5.7% (p =.021). Conclusions: The multicomponent Healthy Start intervention was effective in improving diet quality and sedentary behavior of children in FCCH, which demonstrates the promise of obesity prevention interventions in this setting. Future research could include enhancing the Healthy Start intervention to strengthen the PA component, considering virtual peer support, and determining how to best translate and disseminate the intervention into FCCH nationally. Trial registration: National Institutes of Health, NCT02452645. Registered 5 May 2015. [ABSTRACT FROM AUTHOR]