Respiratory syncytial virus (RSV) infection is a leading cause of severe lower respiratory tract illness in young infants, the elderly and immunocompromised individuals. We demonstrate here that the co-inhibitory molecule programmed cell death 1 (PD-1) is selectively upregulated on T cells within the respiratory tract during both murine and human RSV infection. Importantly, the interaction of PD-1 with its ligand PD-L1 is vital to restrict the pro-inflammatory activities of lung effector T cells in situ, thereby inhibiting the development of excessive pulmonary inflammation and injury during RSV infection. We further identify that PD-L1 expression on lung inflammatory dendritic cells is critical to suppress inflammatory T-cell activities, and an interferon–STAT1–IRF1 axis is responsible for increased PD-L1 expression on lung inflammatory dendritic cells. Our findings suggest a potentially critical role of PD-L1 and PD-1 interactions in the lung for controlling host inflammatory responses and disease progression in clinical RSV infection.
In general, the TPRA model identifies patients at low or high risk for allogeneic transfusion and provides guidelines for preoperative counseling regarding the risk of receiving a transfusion. Knowledge of a patient's risk can help direct cost-effective utilization of type and crossmatch, preoperative autologous blood donation, and preoperative priming with erythropoietin.
BACKGROUND: Status asthmaticus is one of the most frequent admission diagnoses in the pediatric ICU (PICU). Collaboration between respiratory therapists (RTs) and physicians may help efficiently deliver care to a patient in status asthmaticus. The Pediatric Asthma Severity Score (PASS) is a measure of severity of a patient's asthma exacerbation at a point in time. The aim of this quality improvement initiative was to establish an RT-driven continuous albuterol weaning protocol using the PASS score. We hypothesized that this would decrease the duration of continuous albuterol without increasing adverse events. METHODS: This was a single-center implementation study in the PICU of a quaternary care children's hospital. Patients with a diagnosis of status asthmaticus who met criteria on continuous albuterol between September 2015 and September 2017 were included. An interdisciplinary team established the protocol, order sets, documentation, and education for involved staff. Qualifying subjects were assessed by an RT per protocol and assigned a PASS score, and the albuterol dose was adjusted on the basis of the PASS score. RESULTS: We compared 104 subjects studied before the implementation of this protocol (September 2015 to August 2016) to 117 subjects after the implementation of this protocol (September 2016 to October 2017). Median (interquartile range) duration of continuous albuterol in the PICU post-implementation was unchanged compared to pre-implementation: 12.1 (7.2-21.0) h versus 11.1 (6-19) h (P ؍ .22). Median PICU length of stay was also unchanged post-implementation compared to pre-implementation: 19.5 (14.3-29.7) h versus 23.2 (15.2-31.3) h (P ؍ .16). Using control charts, these processes were stable. There was no difference in adverse events. CONCLUSIONS: An interprofessionally-developed, RT-driven continuous albuterol weaning protocol can be implemented without negatively impacting duration of continuous albuterol or PICU length of stay and without increasing adverse events.
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