American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Jul 2020
Association of Pre-Morbid Blood Pressure with Vasopressor Infusion Duration in Patients with Shock.
Rationale: Guidelines for vasopressor titration suggest a universal target-mean arterial pressure (MAP) >65 mm Hg. The implications for patients with premorbid low/high blood pressure are unknown. Objectives: To investigate the relationship between premorbid blood pressure and vasopressor duration for patients with shock. ⋯ After adjustment, premorbid low admissions had longer vasopressor use (median, 1.35 d vs. 1.04 d for normal; hazard ratio for discontinuation vs. normal, 0.78 [0.73-0.85]; P < 0.001) and premorbid high admissions had shorter use (median, 0.84 d; hazard ratio, 1.22 [1.12-1.33]; P < 0.001). Premorbid low admissions had longer adjusted length of stay and higher adjusted mortality than premorbid normal admissions. Conclusions: Premorbid blood pressure was inversely associated with vasopressor duration.
-
Am. J. Respir. Crit. Care Med. · Jul 2020
A Network of Sputum MicroRNAs is Associated with Neutrophilic Airway Inflammation in Asthma.
Rationale: MicroRNAs are potent regulators of biologic systems that are critical to tissue homeostasis. Individual microRNAs have been identified in airway samples. However, a systems analysis of the microRNA-mRNA networks present in the sputum that contribute to airway inflammation in asthma has not been published. ⋯ Multiple microRNAs in the nely module correlated with two mRNA modules enriched for TLR (Toll-like receptor) and T-helper cell type 17 (Th17) signaling and endoplasmic reticulum stress. hsa-miR-223-3p was a key regulator of the TLR and Th17 pathways in the sputum of subjects with asthma. Conclusions: This study of sputum microRNA and mRNA expression from patients with asthma demonstrates the existence of microRNA networks and genes that are associated with features of asthma severity. Among these, hsa-miR-223-3p, a neutrophil-derived microRNA, regulates TLR/Th17 signaling and endoplasmic reticulum stress.
-
Am. J. Respir. Crit. Care Med. · Jul 2020
Nanoparticle Delivery of Proangiogenic Transcription Factors into the Neonatal Circulation Inhibits Alveolar Simplification Caused by Hyperoxia.
Rationale: Advances in neonatal critical care have greatly improved the survival of preterm infants, but the long-term complications of prematurity, including bronchopulmonary dysplasia (BPD), cause mortality and morbidity later in life. Although VEGF (vascular endothelial growth factor) improves lung structure and function in rodent BPD models, severe side effects of VEGF therapy prevent its use in patients with BPD. Objectives: To test whether nanoparticle delivery of proangiogenic transcription factor FOXM1 (forkhead box M1) or FOXF1 (forkhead box F1), both downstream targets of VEGF, can improve lung structure and function after neonatal hyperoxic injury. ⋯ FOXM1 and FOXF1 improved elastin fiber organization, decreased alveolar simplification, and preserved lung function in mice reaching adulthood. Conclusions: Nanoparticle delivery of FOXM1 or FOXF1 stimulates lung angiogenesis and alveolarization during recovery from neonatal hyperoxic injury. Delivery of proangiogenic transcription factors has promise as a therapy for BPD in preterm infants.