American journal of respiratory and critical care medicine
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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
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
The S52F FOXF1 Mutation Inhibits STAT3 Signaling and Causes Alveolar Capillary Dysplasia.
Rationale: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal congenital disorder causing respiratory failure and pulmonary hypertension shortly after birth. There are no effective treatments for ACDMPV other than lung transplant, and new therapeutic approaches are urgently needed. Although ACDMPV is linked to mutations in the FOXF1 gene, molecular mechanisms through which FOXF1 mutations cause ACDMPV are unknown. ⋯ Furthermore, we have developed a novel formulation of highly efficient nanoparticles and demonstrated that nanoparticle delivery of STAT3 cDNA into the neonatal circulation restored endothelial proliferation and stimulated lung angiogenesis in Foxf1WT/S52F mice. Conclusions: FOXF1 acts through STAT3 to stimulate neonatal lung angiogenesis. Nanoparticle delivery of STAT3 is a promising strategy to treat ACDMPV associated with decreased STAT3 signaling.
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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
Long-Term Exposure to Ozone and Cause-Specific Mortality Risk in the United States.
Rationale: Many studies have linked short-term exposure to ozone (O3) with morbidity and mortality, but epidemiologic evidence of associations between long-term O3 exposure and mortality is more limited. Objectives: To investigate associations of long-term (annual or warm season average of daily 8-h maximum concentrations) O3 exposure with all-cause and cause-specific mortality in the NIH-AARP Diet and Health Study, a large prospective cohort of U. S. adults with 17 years of follow-up from 1995 to 2011. ⋯ The results were robust to alternative models and adjustment for copollutants (fine particulate matter and nitrogen dioxide), although some evidence of confounding by temperature was observed. Significantly elevated respiratory disease mortality risk associated with long-term O3 exposure was found among those living in locations with high temperature (Pinteraction < 0.05). Conclusions: This study found that long-term exposure to O3 is associated with increased risk for multiple causes of mortality, suggesting that establishment of annual and/or seasonal federal O3 standards is needed to more adequately protect public health from ambient O3 exposures.