Lung Function and Structure in Healthy Infants and Infants With Recurrent Wheezing

Among asymptomatic healthy infants decreased airway function is found in infants exposed to environmental tobacco smoke (ETS) or with history of family asthma (Fm Asthma), or male gender. These infants are at significantly greater risk of wheezing during infancy. These findings indicate that genetic and environmental factors affect the mechanical determinants of airway function and that among healthy infants variations of these mechanical determinants contribute to the increased risk of developing airway obstruction severe enough to result in clinical symptoms of wheezing. The mechanisms of reduced airway function in these at risk infants are not known. In adults reduced airway function is a result of airway narrowing, increased airway compliance, or decreased pulmonary elastic recoil. The same is thought to be true in infants. The cause of airway narrowing may be functional (reversible by bronchodilators) or structural (fixed, not reversible by bronchodilators) or have components of both. Fixed determinants of airway narrowing include small absolute airway size, thickened airway wall, decreased elastic recoil, and small airway size relative to lung volume. Reversible determinants include airway hyper-responsiveness and inflammation. Understanding the alterations of airway function that increase the risk of airway disease will be decisive in the development of strategies for the prevention and treatment of wheezing in infants and children, and hence, a reduction of morbidity and mortality.

It is not known whether infants with recurrent wheezing have persistent airway narrowing when not acutely symptomatic, and whether airway function in these infants is related to ETS exposure, Fm Asthma, and male gender. When recurrently wheezy infants are asymptomatic, airway function may be low or normal, and low airway function may be fixed or reversible with a bronchodilator. It is important to determine whether these infants have functional and structural abnormalities when they are not acutely symptomatic, and to determine how lung structure relates to lung function. Only then can we design effective therapeutic interventions for recurrently symptomatic infants, as well as, design early intervention strategies.

The Specific aims of this project are:

Specific Aim # 1: To determine whether asymptomatic groups of infants at high risk for wheezing (Environmental tobacco smoke (ETS) exposure, Fm Asthma, male Gender) have fixed or reversible airway narrowing.

Specific Aim # 2: To determine the relative contributions of fixed and reversible airway narrowing in infants with recurrent symptomatic wheezing, and to determine whether fixed and reversible airway narrowing is related to ETS exposure, Fm Asthma, and male Gender.

We propose to answer these important questions of lung function and structure in infants using state of the art methodologies