COPD is currently diagnosed by spirometry, but many other individuals (primarily smokers) have respiratory symptoms and/or imaging abnormalities that suggest lung damage. Identifying subjects with pre-obstruction manifestations of COPD could lead to more effective treatment and prevention.

COPD subjects often develop ongoing inflammation that persists long after smoking cessation. It is unknown when this cycle of inflammation begins or what causes it.

Low lung function during childhood tracks to early adulthood and contributes to early onset disease. Lung health promotion is needed, but we know little about what can enhance and protect human health during rapid phases of lung development in utero and growth postnatally to adulthood.

Researchers could turn their attention on healthy and “maximally” health populations (human and model organisms) to understand genetic and environmental exposures that influence lung function at upper ends of the spectrum (>2 SD from the mean).
Recent findings suggest that there is an urban-rural continuum of lung function in specific ethnic groups; and interventions with maternal dietary supplements can enhance lung function in offspring. These set the stage for further study on developing knowledge of early life events that can inform lung health promotion.

Increasing the pool of and enhancing the skills of diverse senior mentors is critical to the development of young investigators in appropriate scientific disciplines. This would promote the development of strategies to improve the quality and number of available mentors and promote an approach to mentoring that includes science, career development and research management.

The development of the next generation of talented new investigators who are committed to conducting research related to the mission of NHLBI can be accomplished through mechanisms that provide protected time and resources to senior investigators.

Neonatal and early life events can be essential elements for risk of development of chronic lung disease developing after age 40. Prevention of late life chronic lung disease may require that action takes place during the neonatal and childhood periods.

Early life and late life events can be readily studied; however, integrating cause and effect relationships between the two is challenging due to the multiple decades of time separating these events.

While we are fully supportive of the recent emphasis on patient‐centered outcomes and implementation science, we are also reminded of the critical importance of investigating underlying mechanisms of pulmonary, critical care and sleep disorders. Recent discoveries have created exciting progress in the areas of cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and biological therapies in asthma. Only through further efforts to elucidate underlying mechanisms are new therapeutic approaches likely to emerge. Promoting further academic‐industry interactions are likely to yield benefits, which will ultimately lead to improvements in the health of our nation.

This program would support investigator initiated translational work by supporting pre-clinical proof of principle data before involvement of a company. This would allow for better development of IP, and better developed projects would be more attractive to industry. The work would have to involve some support for project development, so access to regulatory and pharmacological resources and/or consultants to develop the idea could be supported. These could be reviewed by existing SBIR/STTR study sections and funded by the set aside funds.

A pipeline for investigato-initiated translational science
http://nhlbistrategicvisioning.ideascale.com/a/dtd/74967-32287

This might be considered a "phase 0" SBIR/STTR and as such would not need to be a large grant (say $150K). These could be used to supplement institutional grants for entrepreneur activity (which are not usually sufficient) for synergy. We have the perfect study sections that already review SBIR/STTRs and funding some of these might impact the SBIR/STTR funding levels, which are fairly generous, but not by much. Would be filling one missing link in the process of funding translation form NIH funded research.

Asthma is, to some extent, an umbrella term that encompasses a broadly heterogenous (in severity, symptoms, and pathophysiology) group of obstructive lung diseases. This is even more true if we examine the "wheezy infant," a population defined almost exclusively by the presence of wheeze, cough, or noisy breathing with very little understanding of disease mechanism or pathophysiology, and few evidence-based treatment options. Improving our understanding of the pathophysiology of wheeze and recurrent cough in early childhood, and how these evolve into various phenotypes of "asthma," through comprehensive longitudinal study of infants and young children may lead to better endotyping of disease and improved therapeutic options, as well as the possibility of disease prevention.

We lack adequate biomarkers (of inflammation, structural and functional lung disease, microbiome, nutrition, etc) to investigate lung disease in infancy and early childhood. Identifying biomarkers with adequate sensitivity, and with a safety profile that allows for repeated measures in large groups of children, will be key to identifying the early childhood origins of all lung diseases.

Enable the next generation to develop a research career to promote the field for the future

Very easy to redefine "Early Stage Investigator" to be fair to all clinicians applying for RO1. One could also give some type of advantage for short period of time to "New Investigators" now beyond 10 yrs of last training who did not have that advantage when they applied