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.
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.
|Martinez, Fernando D (2014) The human microbiome. Early life determinant of health outcomes. Ann Am Thorac Soc 11 Suppl 1:S7-12|
|Jackson, Daniel J; Hartert, Tina V; Martinez, Fernando D et al. (2014) Asthma: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases. Ann Am Thorac Soc 11 Suppl 3:S139-45|
|Voraphani, Nipasiri; Stern, Debra A; Wright, Anne L et al. (2014) Risk of current asthma among adult smokers with respiratory syncytial virus illnesses in early life. Am J Respir Crit Care Med 190:392-8|
|Guerra, Stefano; Stern, Debra A; Zhou, Muhan et al. (2013) Combined effects of parental and active smoking on early lung function deficits: a prospective study from birth to age 26 years. Thorax 68:1021-8|
|Marri, Pradeep Reddy; Stern, Debra A; Wright, Anne L et al. (2013) Asthma-associated differences in microbial composition of induced sputum. J Allergy Clin Immunol 131:346-52.e1-3|
|Kurzius-Spencer, Margaret; Guerra, Stefano; Sherrill, Duane L et al. (2012) Familial aggregation of allergen-specific sensitization and asthma. Pediatr Allergy Immunol 23:21-7|
|Simpson, Angela; Custovic, Adnan; Tepper, Robert et al. (2012) Genetic variation in vascular endothelial growth factor-a and lung function. Am J Respir Crit Care Med 185:1197-204|
|Sherrill, Duane L; Guerra, Stefano; Wright, Anne L et al. (2011) Relation of early childhood growth and wheezing phenotypes to adult lung function. Pediatr Pulmonol 46:956-63|
|Garcia-Marcos, Luis; Martinez, Fernando D (2010) Multitrigger versus episodic wheeze in toddlers: new phenotypes or severity markers? J Allergy Clin Immunol 126:489-90|
|Martinez, Fernando D (2009) The origins of asthma and chronic obstructive pulmonary disease in early life. Proc Am Thorac Soc 6:272-7|
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