Understanding the biological rationale behind the benefit of a particular dietary component that promotes CV health will substantiate public health recommendations about diet.

Our understanding of the nitrate/nitrite cycle and of cardiovascular activity of nitric oxide has advanced rapidly in the past 10-15 years. The time is ripe for linking these advances in the science of nitrates to the consequences of dietary nitrate.
The role of dietary fruits and vegetables in the protection against cardiovascular disease is supported by many studies, especially leafy green vegetables. However, identification of the component of fruits and vegetables affording this protection has been elusive. Recent discoveries about the ability of the body to cycle dietary nitrates to produce bioactive nitric oxide via the enterosalivary cycle and lingual microbiome lends strength to the argument that leafy green vegetables may be protective due to their high nitrate content. This possibility should be examined in both large cohort studies and in clinical series. Would be helpful for the USDA to add nitrates to their standard database of food nutrients. NHLBI needs to partner with NCI to coordinate with ongoing research about the potential nitrosylation of dietary nitrites to carcinogenic n-nitrosamines in the setting of low antioxidant intake.

Exploring and understanding the molecular determinants of pulmonary failure will impact not only the predictable complications of acute respiratory illnesses such as influenza, but also inform our understanidng and treatment of myriad other common respiratory illnesses resulting in pulmonary failure, such as pneumonia, chronic obstructive pulmonary disease, asthma, obesity hypoventilation, etc.

Patients receiving critical care services in the United States are among the most close monitored, including continuous monitoring of cardiorespiratory physiology. This highly monitored population is a nature source for studying longitudinal changes in molecular patterns and respiratory physiology.

Mortality rates for acute lung injury in pediatrics vary from about 10-30%. Immunosuppressed patients and those with cancer have higher rates. Morbidity following long ICU stays have social impacts on family and education, and can put patients at risk of future lung complications.

Though ECMO shows promise of improving outcomes, large clinical studies are lacking. ECMO is also fraught with signifiant risks and high costs. A molecular understanding of the pathobiology of lung injury could lead to specific therapies to improve survival and decrease morbidity.

(1) The heterogeneity of both adults and children with lung injury hinders the applicability of clinical and translational studies. (2) Reliable animal models of pediatric lung injury are lacking.

Developing a national network to address important aspects of sepsis (causes and consequences of cardiac dysfunction, molecular determinants of respiratory failure) and serve as a trials group for testing novel interventions for new discoveries.

Complications of critical illness are frequent and the most common are cardiovascular in nature but not well understood. Understanding the pathogenesis of these consequences will lead to improve treatments, acute survival of critical illness and injury, and improved long-term outcomes.

Patients receiving critical care services in the United States are among the most close monitored, including continuous monitoring of cardiorespiratory physiology. Integrating high dimensional data from ICU data streams and applying big data analytics, in combination with primetime genomic and metabolomic technologies, makes this question imminently feasible.

Can be modeled on the ARDS/PETAL Network, but more broadly implemented for epidemiology and pragmatic studies.