Primary prevention of chronic lung disease: a role for basic science.

Abstract

Biomedical research has led to improvements in the diagnosis and treatment of chronic lung diseases, but the burden of these diseases to the U.S. population remains high. Advances in understanding the mechanisms of lung disease have led to the development of clinical management strategies and therapies to control symptoms and reduce progression of disease. However, there has been less emphasis on advancing our understanding of the mechanisms that underlie protective responses to injury or the aberrant host responses that precede disease. Improving our understanding of the preclinical state could lead to identification of modifiable targets for the primary prevention of incident disease. It is not always clear where basic science fits when describing an agenda for primary prevention research. Important concepts for the primary prevention of chronic lung disease include understanding what exposures and host responses contribute to disease pathogenesis, and why many individuals with the same exposures are resilient and never develop disease; for example, are there protective host factors that explain why only about 20% of life-long smokers develop clinically recognizable symptoms of chronic obstructive lung disease? Disease susceptibility and/or initiation likely begin before clinically apparent symptoms and signs. Disease definitions in clinical research and medical care are based on symptoms and signs of disease often complemented and confirmed by diagnostic tests (e.g., imaging, spirometry). It is not clear if individuals without symptoms and with “abnormal” test results have a preclinical disease process evolving, or if these tests represent a reversible state of host response/repair. The stages of the host from normal to abnormal to resolution or inevitable disease onset is the spectrum that needs further study to develop new strategies for the primary prevention of chronic lung disease. Primary prevention also includes the concept of health promotion and in this regard little is known about early life influences (prenatal/perinatal/postnatal and even transgenerational) that set the stage for life-long respiratory system health. Lung development begins during embryogenesis, rapidly accelerates in the fetus, and continues for years after birth. Lung health is more than optimal structural development and includes critical host defense functions such as immunological and cellular responses in the face of challenging exposures (e.g., pollutants, tobacco, viruses). What factors optimize the complex and critical responses to maintain lung health? The April supplement to the Annals of the American Thoracic Society, which was published online on April 15, contains a series of articles on Primary Prevention of Chronic Lung Diseases. This supplement resulted from multiple National Heart, Lung, and Blood Institute (NHLBI)-sponsored working groups and workshops. The charge to the workshop participants was to identify the current landscape of primary prevention research, gaps in knowledge that would inform primary prevention in clinical care, new opportunities for research in this area, and high priorities for research that would inform primary prevention intervention strategies to improve the health of the nation. Reflected in these reports and in the Executive Summary of the workshop are the deliberations from a year-long process of developing research recommendations to NHLBI for lung health and the prevention of specific diseases (asthma, bronchopulmonary dysplasia, chronic obstructive lung disease, cystic fibrosis, interstitial lung disease, and pulmonary hypertension). Furthermore, the contributions of early life events to life-long lung health or disease were discussed, and challenging questions for basic scientific exploration were raised, such as: are bigger lungs/bigger airways “protective “against some forms of lung disease and/or confer resistance to age-related decline in lung function? Does enhancement of maximal lung function have any impact on survival? What are the factors that contribute to “resilience” of the lung in the face of toxic exposures? Are there critical windows of host susceptibility to common exposures? What are mechanisms of resilience that re-equilibrate the perturbed lung back to homeostasis? We are calling on the entire scientific community to consider the scientific priorities described in these reports and help advance efforts for primary prevention of lung disease research. Basic science discovery is an important foundation that will contribute to advancing the goals of better defining respiratory system health and preventing lung disease. We believe there is an opportunity for basic lung scientists to play a significant role in advancing an agenda around the primary prevention theme. We are optimistic that the basic science community will rise to the challenge and make our fundamental discoveries and investments pay off.