Sleep deficiency and untreated sleep disorders threaten the health of 20-30 percent of US adults through an increased risk of stroke, hypertension, diabetes, inflammatory disease, and all-cause mortality. Developing the scientific evidence-base of validated interventions will enhance the management of cardiometabolic and pulmonary risks to health, present new opportunities for secondary prevention, and reduce associated burden on health care systems.

Improving sleep health through informed public recognition of decision-relevant science, and relatively low cost therapies for management of sleep disorders are available for immediate assessment of impact in appropriate clinical trials to demonstrate efficacy and effectiveness.
Discovery research advances implicate an array of cellular sleep and circadian mechanisms in pathophysiological pathways leading to cardiometabolic and pulmonary disease.

Irregular and disturbed sleep impairs cellular biological rhythm in all tissues and organs leading to oxidative stress, unfolded protein responses, and impaired cell function. The pathophysiological findings juxtaposed with epidemiological evidence of disease risk indicate that sleep deficiency contributes to an erosion of health across the lifespan over and above the effects of aging.

Discovery of mechanisms of lung injury in the HCT setting are likely to be relevant for the non HCT setting.
The BMT CTN prospectively collects data on lung toxicity on all HCT recipients on trial, samples exist in the repository that could be used for biomarker discovery.

Main challenge is to get the two teams of investigators working together

Hydroxyurea is a widely available disease-modifying therapy for sickle cell disease (SCD), but its effectiveness is currently limited by inadequate utilization, and less than optimal response. Research is needed to improve adherence to this evidence-based therapy and emphasis needs to be placed on determining whether therapy with hydroxyurea can prevent or even reverse organ dysfunction. In addition, research identifying new adjunct therapies to blood transfusion and hydroxyurea, as well as disease-specific therapies for co-morbidities such as kidney disease, hypertension, obstructive lung disease, and pulmonary hypertension will be valuable in the management and treatment of SCD.

Patients who are fortunate to receive a matched heart or one or two lungs transplants are at high risk of dying from rejection early and even years after the operation. Thus, they are given cocktails of highly toxic anti-rejection drugs for the rest of their lives. Unfortunately, despite compliance with their drug regimens, many patients still suffer repeated episodes of rejection that may be fatal. In addition, they develop serious side-effects such as diabetes, infections, malignancies, renal failure, etc. ECP has been shown efficacy in preventing and treating cardiac transplant rejection, but the data are limited. ECP appears to benefit such patients by causing an increase in the number of circulating T regulatory (“T regs”) cells. T regs are known to mediate immune tolerance, the ultimate goal of a long-term successful transplant. The role of ECP in lung transplantation is mostly unknown. Very preliminary data have been gathered from retrospective studies. We suspect that patients with early bronchiolitis obliterans syndrome (“BOS”) will benefit from ECP prior to developing irreversible pulmonary damage. In both types of transplants, however, it is unknown when should ECP be started, how often it should be employed (treatment schedule), and for how long. Finally, the most compelling argument to use ECP in heart and lung transplantation is its excellent side-effect profile. Furthermore, ECP may allow a decrease in the number of drugs needed to prevent rejection.

Many patients with heart and lung transplants develop severe and often fatal rejection despite the current drug options to prevent rejection. ECP could be added to their treatment regimens and decrease side-effects, improving long-term survival.

ECP is generally well tolerated and complications are extremely infrequent.

There is a great potential for multi-disciplinary collaboration between Apheresis Medicine, Cardiology, and Pulmonary specialists.

It is conceivable that manufacturers of ECP instruments will be interested in contributing to the design and support of these studies.

Such studies could shed light in the mechanism of action of ECP in heart and lung transplantation.

There is a need to develop standardized treatment regimens based on well designed clinical trials to further optimize the use of ECP. Development and standardization of measurable outcomes is critical for the success of clinical studies in apheresis in general, and ECP in particular.

Challenges:

1. Limited number of institutions providing ECP treatment.
2. Cost of ECP procedures.
3. Small number of animal models available for apheresis research. Thus, limited studies of ECP mechanism(s) of action. However, understanding pathological mechanisms and their relationship to response to apheresis is critical for optimization and advancement of patient care in heart and lung transplantation.
4. Lack of infra-structure for apheresis research.

To deal end-stage CHF will need team efforts from heart, lung, blood and immunology.

The tissue alterations in COPD and their physiologic consequences of those changes are reasonable well described. It is now clear that, like all organs, the lung can repair damaged tissue and that repair processed can be modulated. Strategies for assessing restoration of lost tissue structure and function should be developed, together with the development of clinical measures that can gauge progress of treatment.

Animal studies demonstrate that emphysema can be repaired, at least in some species. Several forms of airways disease in humans are also reversible. Studies of interventions to augment tissue repair are needed with the goal of applying them to clinical interventions.

Understanding the molecular and cellular bases of differences in prevalence and outcomes of lung diseases will offer insight into disease mechanisms and help to address disease disparities. Some potential bases for disparities, such as differences in hormone levels between men and women, could potentially be therapeutically modulated to mitigate the effects of disease.

The increased understanding of lung cell biology, along with a renewed focus on sex and gender differences, make this the perfect time to start addressing these questions.
Multiple diseases affecting the lung, such as LAM (lymphangioleiomyomatosis), sarcoidosis, asthma, and COPD, have distinct prevalence or associated mortality in a sex-dependent manner. The reasons for these differences are still unknown.

Addressing the impact of maternal exposures on fetal lung disease would make a major impact on human health by giving regulatory agencies the data they need to make educated decisions with respect to issues such as nicotine regulation, air pollution, water pollution, and other sources of maternal exposures.

With the established animal and stem cell models of development, this research is immediately feasible.

Imaging plays a crucial role in the initial evaluation of patients with suspected or surveillance of those with confirmed diffuse chronic lung disease. Attention towards developing alternative non-ionizing imaging technologies and evaluating the efficacy of radiation dose saving techniques will impact a large patient population.

Imaging, particularly computed tomography (CT) plays a major role in the evaluation of diffuse pulmonary disease. High resolution CT (HRCT) characterizes parenchymal patterns of lung disease, identifies areas amenable to biopsy, and aids in decisions pertaining to workup and therapy of lung disease. With multidetector CT technology, volumetric HRCT enables evaluation of the entire lung volume for diffuse lung disease. The utility of CT needs to be balanced with the exposure of patients to ionizing radiation, particularly younger-aged individuals who are more sensitive to ionizing radiation. In CT, dose-saving techniques enable imaging of the parenchyma at ultra-low dose levels. Additionally, an understanding of low radiation-dose CT techniques that preserve the diagnostic ability for diffuse lung disease, while maintaining the precision of quantitative measures, is needed. Magnetic resonance imaging (MR) is underutilized as an imaging tool given respiratory motion and limitations in spatial resolution. A need exists to develop and apply MR imaging techniques with spatial resolution approaching that of high resolution CT. Promising advances in the MR technology has occurred, and continued development and application will provide alternative and non-ionizing options for imaging patients with diffuse lung disease affecting both the parenchyma and airways.

may be able to target multiple diseases with new or repurposed therapies. Might narrow down the broad array of potential "high value" targets to study.

Despite high mortality rates and frustrating disease management marked by exacerbations and uncertainty including chronic oxygen supplementation, pulmonary fibrosis patients lack evidence-based treatments to reverse and repair the fibrotic process. These patients comprise a comparatively smaller proportion of lung disease patients such as chronic obstructive pulmonary disease and asthma and owing to their smaller number, have not been studied in large-scale randomized controlled trials. Treatments that need to be critically studied include regenerating lung tissue through stem cell treatment, artificial/ mechanical lung (augmentation) technology, and new drugs to directly reverse scar tissue, not simply to arrest the fibrotic process as with the two new available drugs for IPF patients.

Challenges are smaller numbers of available patients available for clinical trials compared with other lung conditions such as COPD and asthma and lack of research funding. Also the etiology of the disease is multifactorial and the categories of fibrosis difficult to accurately diagnose and understand.

Methods for stratifying patients with diffuse lung disease are crucial for predicting their clinical course and directing appropriate therapies accordingly. Currently imaging markers for prognostic stratification are limited, due to observer variability in characterizing the type and degree of computed tomography (CT) abnormalities. A reproducible method for categorizing varying diffuse lung diseases on CT imaging is needed, particularly in combination with other biomarkers in a multidisciplinary approach. With lung cancer screening, the characterization and stratification of patients with varying COPD phenotypes and interstitial lung disease are essential to aid in management of the large number of patients who currently satisfy criteria for CT lung cancer screening.

Currently the classification of diffuse lung disease on CT is based upon visual evaluation and qualitative or semi-quantitative evaluation of CT data. Diffuse lung disease manifests with varying CT findings and distribution within the lung. Computer-assisted tools for quantifying airways and parenchymal disease have been developed. More-sophisticated quantitative computer image-analysis methods, such as those that address three-dimensional spatial orientation, are possible given advances in computer capabilities yet remain in need of further development. Advances in magnetic resonance imaging (MR) technology, positron emission tomography (PET), and PET/MR will increase the ability to characterize diffuse lung disease quantitatively. The ability of such technology to differentiate subtypes within more frequently occurring and clinically-significant diffuse lung disease is feasible. Such tools would impact a large population, particularly given the potential need to phenotype emphysema and smoking-related interstitial pneumonias in those undergoing CT screening.