It has become clear that the seeds of many adult diseases are sown in childhood. The objective of the current project is to identify infant and childhood predictors of chronic adult asthma, smoking related symptoms, deficits in lung function, and altered airway structure, all of which are associated with risk for development of chronic obstructive pulmonary disease (COPD).
Specific aims are to: 1. Identify the early molecular, phenotypic and environmental predictors of respiratory symptoms and asthma into the fourth decade of life. 2. Identify the early molecular, phenotypic and environmental predictors of lung function deficits into the fourth decade of life, and 3. Utilize noninvasive imaging techniques to detect the structural alterations that characterize distinct patterns of airway dysfunction. This project will utilize the Tucson Children's Respiratory Study (CRS), the first large birth cohort of non-selected children followed into adult life, to investigate directlythe childhood origins of adult airway disease. The respiratory health of CRS subjects has been extensively characterized from birth to age 26, and we have available thousands of stored serum samples, repeated pulmonary function measurements at 5 yr intervals, and questionnaires from 13 surveys between birth and 26 yrs. Over 800 subjects from this large population sample (~2/3s of those enrolled) still participate. In the next project period, we propose to evaluate the respiratory status of these subjects at age 32, when the plateau phase of lung function has ended and aging-associated lung function decline starts. In addition to lung function measurements and extensive questionnaires, two new technologies will be utilized to elucidate further the early roots and physiologic consequences of the development of adult chronic airway disease. Pilot studies reported herein indicate that serum biomarkers identifiable from birth predict increased peak flow variability, and lung function deficits associated with asthma symptoms. Thus we will measure 89 proteins in early sera to identify biomarkers of the complex, interrelated inflammatory and immune processes that lead to later chronic asthma and COPD-related airflow limitation. Helical CT scans will confirm preliminary findings of the complex relation of airway wall thickness to lung function and symptoms, and relate the structural outcomes to early life biomarkers. Elucidating the different respiratory phenotypes and biomarker patterns that lead to persistence of airway symptoms and lung function deficits in adulthood will advance efforts to identify novel strategies for prevention and early intervention i asthma and COPD.

Public Health Relevance

This study provides the first opportunity to investigate directly the childhood origins of adult airway disease. The early 30s is a critical age at which to assess respiratory health, as aging-associated lung function decline begins and the first clinical manifestations of COPD appear. Understanding the childhood origins of adult airway disease will identify novel mechanisms underlying the development of asthma and chronic airflow limitation, and suggest strategies for intervention.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-PSE-K (04))
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Taggart, Virginia
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University of Arizona
Schools of Medicine
United States
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Martinez, Fernando D (2017) Bending the Twig Does the Tree Incline: Lung Function after Lower Respiratory Tract Illness in Infancy. Am J Respir Crit Care Med 195:154-155
Oren, Eyal; Gerald, Lynn; Stern, Debra A et al. (2017) Self-Reported Stressful Life Events During Adolescence and Subsequent Asthma: A Longitudinal Study. J Allergy Clin Immunol Pract 5:427-434.e2
Beamer, Paloma I; Lothrop, Nathan; Lu, Zhenqiang et al. (2016) Spatial clusters of child lower respiratory illnesses associated with community-level risk factors. Pediatr Pulmonol 51:633-42
Martinez, Fernando D (2016) Early-Life Origins of Chronic Obstructive Pulmonary Disease. N Engl J Med 375:871-8
von Mutius, Erika; Martinez, Fernando D (2016) Inconclusive Results of Randomized Trials of Prenatal Vitamin D for Asthma Prevention in Offspring: Curbing the Enthusiasm. JAMA 315:347-8
Berry, Cristine E; Billheimer, Dean; Jenkins, Isaac C et al. (2016) A Distinct Low Lung Function Trajectory from Childhood to the Fourth Decade of Life. Am J Respir Crit Care Med 194:607-12
Guerra, Stefano; Halonen, Marilyn; Vasquez, Monica M et al. (2015) Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study. Lancet Respir Med 3:613-20
Voraphani, Nipasiri; Martinez, Fernando D (2015) Postnatal growth and the heterogeneity of preschool wheeze. J Pediatr 166:226-8
McGeachie, Michael J; Wu, Ann C; Tse, Sze Man et al. (2015) CTNNA3 and SEMA3D: Promising loci for asthma exacerbation identified through multiple genome-wide association studies. J Allergy Clin Immunol 136:1503-1510
Chan, Johnny Y C; Stern, Debra A; Guerra, Stefano et al. (2015) Pneumonia in childhood and impaired lung function in adults: a longitudinal study. Pediatrics 135:607-16

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