Browsing by Author "Feng, Rui"

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    A cortactin CTTN coding SNP contributes to lung vascular permeability and inflammatory disease severity in African descent subject
    (Elsevier, 2022) Belvitch, Patrick; Casanova, Nancy; Sun, Xiaoguang; Camp, Sara M.; Sammani, Saad; Brown, Mary E.; Mascarhenas, Joseph; Lynn, Heather; Adyshev, Djanybek; Siegler, Jessica; Desai, Ankit; Seyed-Saadat, Laleh; Rizzo, Alicia; Bime, Christian; Shekhawat, Gajendra S.; Dravid, Vinayak P.; Reilly, John P.; Jones, Tiffanie K.; Feng, Rui; Letsiou, Eleftheria; Meyer, Nuala J.; Ellis, Nathan; Garcia, Joe G. N.; Dudek, Steven M.; Medicine, School of Medicine
    The cortactin gene (CTTN), encoding an actin-binding protein critically involved in cytoskeletal dynamics and endothelial cell (EC) barrier integrity, contains single nucleotide polymorphisms (SNPs) associated with severe asthma in Black patients. As loss of lung EC integrity is a major driver of mortality in the Acute Respiratory Distress Syndrome (ARDS), sepsis, and the acute chest syndrome (ACS), we speculated CTTN SNPs that alter EC barrier function will associate with clinical outcomes from these types of conditions in Black patients. In case-control studies, evaluation of a nonsynonymous CTTN coding SNP Ser484Asn (rs56162978, G/A) in a severe sepsis cohort (725 Black subjects) revealed significant association with increased risk of sepsis mortality. In a separate cohort of sickle cell disease (SCD) subjects with and without ACS (177 SCD Black subjects), significantly increased risk of ACS and increased ACS severity (need for mechanical ventilation) was observed in carriers of the A allele. Human lung EC expressing the cortactin S484N transgene exhibited: (i) delayed EC barrier recovery following thrombin-induced permeability; (ii) reduced levels of critical Tyr486 cortactin phosphorylation; (iii) inhibited binding to the cytoskeletal regulator, nmMLCK; and (iv) attenuated EC barrier-promoting lamellipodia dynamics and biophysical responses. ARDS-challenged Cttn+/- heterozygous mice exhibited increased lung vascular permeability (compared to wild-type mice) which was significantly attenuated by IV delivery of liposomes encargoed with CTTN WT transgene but not by CTTN S484N transgene. In summary, these studies suggest that the CTTN S484N coding SNP contributes to severity of inflammatory injury in Black patients, potentially via delayed vascular barrier restoration.
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    Tidal Breathing Measurements at Discharge and Clinical Outcomes in Extremely Low Gestational Age Neonates
    (ATA, 2018-03) Ren, Clement L.; Feng, Rui; Davis, Stephanie D.; Eichenwald, Eric; Jobe, Alan; Moore, Paul E.; Panitch, Howard B.; Sharp, Jack K.; Kisling, Jeff; Clem, Charles; Kemp, James S.; Pediatrics, School of Medicine
    Rationale: The relationship between respiratory function at hospital discharge and the severity of later respiratory disease in extremely low gestational age neonates is not well defined. Objectives: To test the hypothesis that tidal breathing measurements near the time of hospital discharge differ between extremely premature infants with BPD or respiratory disease in the first year of life compared to those without these conditions. Methods: Study subjects were part of the Prematurity and Respiratory Outcomes Program (PROP) study, a longitudinal cohort study of infants born <29 gestational weeks followed from birth to 1 year of age. Respiratory inductance plethysmography was used for tidal breathing measurements before and after inhaled albuterol 1 week prior to anticipated hospital discharge. Infants were breathing spontaneously and were receiving ≤1 liter per minute (lpm) nasal cannula flow at 21-100% FiO2. A survey of respiratory morbidity was administered to caregivers at 3, 6, 9, and 12 months corrected age to assess for respiratory disease. We compared tidal breathing measurements in infants with and without bronchopulmonary dysplasia (BPD, oxygen requirement at 36 wk) and with and without respiratory disease in the first year of life. Measurements were also performed in a comparison cohort of term infants. Results: 765 infants survived to 36 weeks post-menstrual age, with research-quality tidal breathing data in 452 out of 564 tested (80.1%). Among these 452 infants, the rate of post-discharge respiratory disease was 65.7%. Compared to a group of 18 term infants, PROP infants had abnormal tidal breathing patterns. However, there were no significant differences in tidal breathing measurements in PROP infants who had BPD or who had respiratory disease in the first year of life compared to those without these diagnoses. Bronchodilator response was not significantly associated with respiratory disease in the first year of life. Conclusions: Extremely premature infants receiving <1 lpm nasal cannula support at 21-100% FiO2 have tidal breathing measurements that differ from term infants, but these measurements do not differentiate those preterm infants who have BPD or will have respiratory disease in the first year of life from those who do not.