PROJECT SUMMARY
Approximately 10-12% of all live births occur before completion of 37 weeks of gestation and because of the
advances of neonatal medicine, fortunately, a significant proportion of these individuals survive to adulthood.
Preterm birth results in underdeveloped lungs causing a number of cardiopulmonary limitations that persist into
adulthood including low pulmonary function and aerobic exercise capacity. However, the medical management
of these cardiopulmonary impairments are evidence-free because the underlying mechanisms/causes are
unknown. This is problematic because the population of adult survivors of preterm birth (PRET) will continue to
grow with advances in neonatal medicine, as will the associated health care costs. Likewise, cardiopulmonary
function declines with age, which may result in PRET developing disabling cardiopulmonary function at an
earlier age than their counterparts born at full term (CONT). The proposed work is important because it will
identify potential targets for therapeutic interventions to improve and/or maintain cardiopulmonary function in
PRET. Preliminary and published data from the PI’s lab, suggests that low resting cardiopulmonary function in
PRET may not be due to abnormal respiratory muscle strength/function or pulmonary system compliance, but,
rather, smaller airways than CONT. Additionally, previous work from the PI suggests that aerobic exercise
capacity in PRET is limited by mechanical constraints to ventilation. Specifically, preliminary data suggests
PRET have an excessive work of breathing. Based upon this previous and preliminary work our central
hypotheses are that 1) low pulmonary function in PRET is not due to abnormal respiratory muscle
strength/function and/or pulmonary system compliance, but rather 2) due to airways that are anatomically small
and not constricted, and 3) low aerobic exercise capacity in PRET is due to an excessive work of breathing,
caused by an excessive airway resistive work, that can be reduced with low-density gas. To test our central
hypotheses the following Specific Aims are proposed: (1): Identify that respiratory pressure generation
and pulmonary compliance are not major contributors to low resting pulmonary function in adult
survivors of preterm birth. Based on previous work and our preliminary data, our working hypothesis is that
mPRE, vPRE, and BPD have normal respiratory muscle strength and total pulmonary compliance; (2): Identify
that airflow resistance is the major contributor to low resting pulmonary function in adult survivors of
preterm birth. Based on previous work and our preliminary data, our working hypothesis is that mPRE, vPRE,
and BPD have small airways and a normal incidence of airway hyperresponsiveness; and (3): Determine
whether or not an excessive work of breathing limits aerobic exercise capacity in PRET individuals.
Based on previous work and our preliminary data, our working hypothesis is that mPRE, vPRE, and BPD have
an excessive Wb that is a primary cause of their lower-than-normal aerobic exercise capacity.