American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2019
Multicenter StudyMechanical Ventilation Management during ECMO for ARDS: An International Multicenter Prospective Cohort.
Rationale: Current practices regarding mechanical ventilation in patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome are unknown. Objectives: To report current practices regarding mechanical ventilation in patients treated with ECMO for severe acute respiratory distress syndrome (ARDS) and their association with 6-month outcomes. Methods: This was an international, multicenter, prospective cohort study of patients undergoing ECMO for ARDS during a 1-year period in 23 international ICUs. ⋯ A higher Vt and lower driving pressure (likely markers of static compliance improvement) across the ECMO course were also associated with better outcomes. Conclusions: Ultraprotective lung ventilation on ECMO was largely adopted across medium- to high-case volume ECMO centers. In contrast with previous observations, mechanical ventilation settings during ECMO did not impact patients' prognosis in this context.
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Am. J. Respir. Crit. Care Med. · Oct 2019
Understanding and Enhancing Sepsis Survivorship: Priorities for Research and Practice.
An estimated 14.1 million patients survive sepsis each year. Many survivors experience poor long-term outcomes, including new or worsened neuropsychological impairment; physical disability; and vulnerability to further health deterioration, including recurrent infection, cardiovascular events, and acute renal failure. However, clinical trials and guidelines have focused on shorter-term survival, so there are few data on promoting longer-term recovery. ⋯ The top short-term priorities identified by nominal group technique culminating in formal voting were to better leverage existing databases for research, develop and disseminate educational resources on postsepsis morbidity, and partner with sepsis survivors to define and achieve research priorities. The top longer-term priorities were to study mechanisms of long-term morbidity through large cohort studies with deep phenotyping, build a harmonized global sepsis registry to facilitate enrollment in cohorts and trials, and complete detailed longitudinal follow-up to characterize the diversity of recovery experiences. This perspective reviews colloquium discussions, the identified priorities, and current initiatives to address them.
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Am. J. Respir. Crit. Care Med. · Oct 2019
Effect of Including Important Clinical Variables on Accuracy of the Lung Allocation Score for Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.
Rationale: Clinical variables associated with shortened survival in patients with advanced-stage cystic fibrosis (CF) are not included in the lung allocation score (LAS). Objectives: To identify variables associated with wait-list and post-transplant mortality for CF lung transplant candidates using a novel database and to analyze the impact of including new CF-specific variables in the LAS system. Methods: A deterministic matching algorithm identified patients from the Scientific Registry of Transplant Recipients and the Cystic Fibrosis Foundation Patient Registry. ⋯ Priority for transplant increased for COPD candidates. Access did not change for other diagnosis groups. Conclusions: Adding CF-specific variables improved discrimination among wait-listed CF candidates and benefited COPD candidates.
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Am. J. Respir. Crit. Care Med. · Oct 2019
Lung Computational Models and the Role of the Small Airways in Asthma.
Rationale: Asthma is characterized by disease within the small airways. Several studies have suggested that forced oscillation technique-derived resistance at 5 Hz (R5) - resistance at 20 Hz (R20) is a measure of small airway disease; however, there has been limited validation of this measurement to date. Objectives: To validate the use of forced oscillation R5 - R20 as a measure of small airway narrowing in asthma, and to investigate the role that small airway narrowing plays in asthma. ⋯ Measurements and Main Results: Simulations demonstrated that narrowing of the small airways had a greater impact on R5 - R20 than narrowing of the larger airways and was associated (above a threshold of approximately 40% narrowing) with marked deterioration in both asthma control and asthma quality of life, above the minimal clinical important difference. The observed treatment effect on R5 - R20 in the pooled trials equated to a predicted small airway narrowing reversal of approximately 40%. Conclusions: We have demonstrated, using computational modeling, that forced oscillation R5 - R20 is a direct measure of anatomical narrowing in the small airways and that small airway narrowing has a marked impact on both asthma control and quality of life and may be modified by biologics.
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Am. J. Respir. Crit. Care Med. · Oct 2019
Role of B7H3/IL-33 Signaling in Pulmonary Fibrosis-induced Profibrogenic Alterations in Bone Marrow.
Rationale: The impact of lung insult on the bone marrow (BM) and subsequent disease is unknown. Objectives: To study alterations in the BM in response to lung injury/fibrosis and examine their impact on subsequent lung insult. Methods: BM cells from control or bleomycin-treated donor mice were transplanted into naive mice, which were subsequently evaluated for bleomycin-induced pulmonary fibrosis. ⋯ Notably, soluble B7H3 was elevated in plasma of patients with idiopathic pulmonary fibrosis and in BAL fluid in those with acute exacerbation. Finally, ST2 deficiency diminished the bleomycin-induced B7H3 and IL-13 upregulation, suggesting a role for type 2 innate lymphoid cells. Conclusions: Pulmonary fibrosis caused significant alterations in BM with expansion and activation of monocytic cells, which enhanced fibrosis when transplanted to naive recipients with potential mediation by a novel role for B7H3 in the pathophysiology of pulmonary fibrosis in both mice and humans.