Acute respiratory distress syndrome (ARDS) is a life‐threatening inflammatory lung condition associated with significant morbidity and mortality. Unfortunately, the current treatment for this disease is mainly supportive. Mesenchymal stem cells (MSCs) due to their immunomodulatory properties are increasingly being studied for the treatment of ARDS and have shown promise in multiple animal studies. The therapeutic effects of MSCs are exerted in part in a paracrine manner by releasing extracellular vesicles (EVs), rather than local engraftment. MSC‐derived EVs are emerging as potential alternatives to MSC therapy in ARDS. In this review, we will introduce EVs and briefly discuss current data on EVs and MSCs in ARDS. We will discuss current literature on the role of MSC‐derived EVs in pathogenesis and treatment of ARDS and their potential as a treatment strategy in the future.

COPD exacerbation care bundle improves standard of care, length of stay, and readmission rates Raj Parikh,1 Trushil G Shah,2 Rajive Tandon2 1Department of Internal Medicine, 2Department of Pulmonary and Critical Care Medicine, Rush University Medical Center, Chicago, IL, USA Introduction: COPD is the third leading cause of death in the world. Utilizing care bundles during acute COPD exacerbations results in fewer complications and lower costs. Our aim was to construct a COPD exacerbation care bundle and evaluate the effects on patient care. Methods: We conducted a prospective analysis of 44 patients admitted with a COPD exacerbation to a single tertiary care facility. Primary outcomes included length of stay, readmission rates, and hospital costs. Secondary outcomes included patient education, pulmonologist follow-up, and timeliness of medication administration. Two cohorts were analyzed: those treated with an electronic COPD care bundle (cases; N=22) versus those treated without the care bundle (controls; N=22). Results: Mean length of stay (51.2 vs 101.1 hours in controls; P-value =0.001), 30-day readmission rates (9.1% vs 54.4% in controls; P-value =0.001), and 60-day readmission rates (22.7% vs 77% in controls; P-value =0.0003) decreased in the care bundle group. Ninety-day hospital costs had a significant difference in the care bundle group (US$7,652 vs US$19,954 in controls; P-value =0.044). Secondary outcomes included a 100% rate of COPD inhaler teaching (vs 27.3% in controls; P-value <0.001), 59.1% rate of pulmonologist follow-up after discharge (vs 18.2% in controls; P-value =0.005), and a mean reduction in time to steroid administration (7.0 hours; P-value =0.015) seen in the care bundle cases. Conclusion: Our significant findings coupled with the recent success of standardized algorithms in managing COPD exacerbations stress the importance of enforcing clinical guidelines that can enhance patient care. We demonstrated improved care for COPD exacerbation patients during hospitalizations, thereby decreasing morbidity and the financial burden hospitals face in regard to this increasingly prevalent disease. Keywords: acute exacerbation of chronic obstructive lung disease, COPD, care bundle

Background: Pulmonary endothelial cells’ (ECs) injury and apoptotic death are necessary and sufficient for the pathogenesis of the acute respiratory distress syndrome (ARDS), regardless of epithelial damage. Interaction of dysfunctional ECs with circulatory extracellular vesicles (EVs) holds therapeutic promise in ARDS. However, the presence in the blood of long‐term ARDS survivors of EVs with a distinct phenotype compared to the EVs of non‐surviving patients is not reported. With a multidisciplinary translational approach, we studied EVs from the blood of 33 patients with moderate‐to‐severe ARDS.Results: The EVs were isolated from the blood of ARDS and control subjects. Immunoblotting and magnetic beads immunoisolation complemented by standardized flow cytometry and nanoparticles tracking analyses identified in the ARDS patients a subset of EVs with mesenchymal stem cell (MSC) origin (CD73⁺CD105⁺Cd34⁻CD45⁻). These EVs have 4.7‐fold greater counts compared to controls and comprise the transforming growth factor‐beta receptor I (TβRI)/Alk5 and the Runx1 transcription factor. Time course analyses showed that the expression pattern of two Runx1 isoforms is critical for ARDS outcome: the p52 isoform shows a continuous expression, while the p66 is short‐lived. A high ratio Runx1p66/p52 provided a survival advantage, regardless of age, sex, disease severity or length of stay in the intensive care unit. Moreover, the Runx1p66 isoform is transiently expressed by cultured human bone marrow‐derived MSCs, it is released in the EVs recoverable from the conditioned media and stimulates the proliferation of lipopolysaccharide (LPS)‐treated ECs. The findings are consistent with a causal effect of Runx1p66 expression on EC proliferation. Furthermore, morphological and functional assays showed that the EVs bearing the Runx1p66 enhanced junctional integrity of LPS‐injured ECs and decreased lung histological severity in the LPS‐treated mice.Conclusions: The expression pattern of Runx1 isoforms might be a reliable circulatory biomarker of ARDS activity and a novel determinant of the molecular mechanism for lung vascular/tissue repair and recovery after severe injury.

Right ventricular (RV) dysfunction in acute respiratory distress syndrome (ARDS) contributes to increased mortality. Our aim is to identify reproducible transthoracic echocardiography (TTE) parameters of RV dysfunction that can be used to predict outcomes in ARDS. We performed a retrospective single‐center cohort pilot study measuring tricuspid annular plane systolic excursion (TAPSE), Tei index, RV‐fractional area change (RV‐FAC), pulmonary artery systolic pressure (PASP), and septal shift, reevaluated by an independent blinded cardiologist (JK). Thirty‐eight patients were included. Patients were divided on the basis of 30‐day survival. Thirty‐day mortality was 47%. Survivors were younger than nonsurvivors. Survivors had a higher pH, PaO₂: FiO₂ ratio, and TAPSE. Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores were lower in survivors. TAPSE has the strongest association with increased 30‐day mortality from date of TTE. Accordingly, TAPSE has a strong positive correlation with PaO₂: FiO₂ ratios, and Tei index has a strong negative correlation with PaO₂: FiO₂ ratios. Septal shift was associated with lower PaO₂: FiO₂ ratios. Decrease in TAPSE, increase in Tei index, and septal shift were seen in the severe ARDS group. In multivariate logistic regression models, TAPSE maintained a significant association with mortality independent of age, pH, PaO₂: FiO₂ ratios, positive end expiratory pressure, PCO₂, serum bicarbonate, plateau pressures, driving pressures, APACHE II, SAPS II, and SOFA scores. In conclusion, TAPSE and other TTE parameters should be used as novel predictive indicators for RV dysfunction in ARDS. These parameters can be used as surrogate noninvasive RV hemodynamic measurements to be manipulated to improve mortality in patients with ARDS and contributory RV dysfunction.