BME PhD Dissertation Defense - John Casey Olson

Starts:
9:30 am on Monday, November 4, 2013
Location:
44 Cummington Mall, Room 203
Title: Pathophysiology and Treatment of Thoracic Insufficiency Syndrome in Animal Model

Committee:
Dr. Brian Snyder (Advisor, Harvard Medical School, Orthopaedic Surgery)
Prof. Bela Suki (BU, BME)
Prof. Dimitrije Stamenovic (BU, BME) *Chair
Prof. Thomas Szabo (BU, BME)

Abstract:
In young children, deformity of the spine and chest wall is associated with declining respiratory function and increased morbidity at adulthood in comparison to adults with adolescent onset deformities of comparable severity. In children it is presumed that the inhibition of thoracic growth during the late stages of pulmonary alveolarization leads to an irreversible loss of pulmonary growth and compromised respiratory function. Thus there is clinical incentive to treat children with early onset scoliosis and thoracic deformity as early as possible to preserve growth. Such growth preserving surgery has gained clinical acceptance over the past 15 years with encouraging results, however due to the delicate nature of these patients there is limited prospective evidence to objectively evaluate the benefits of these surgeries on respiratory health. In particular there is controversy with regard to the proper timing of surgical interventions - does performing surgery at an earlier age provide improved respiratory function at adulthood?
The aims of this study were: 1) develop a rabbit model of early onset thoracic deformity by surgically creating a unilateral right rib fusion in very young rabbits to induce inhibited thoracic growth and progressive scoliosis, and 2) to evaluate the effectiveness of a surgical treatment known as expansion thoracoplasty to preserve pulmonary growth and function in rabbits with induced pulmonary hypoplasia from aim 1, in particular effectiveness with regard to the post-natal timing of intervention is considered by evaluating separate early and late treatment cohorts. All rabbits were evaluated longitudinally up to skeletal maturity using breath-hold CT imaging and pulmonary function tests to quantitatively establish expected pulmonary growth and function based on severity of induced thoracic deformity in disease control rabbits and likewise the relative gains in treatment rabbits. Our findings highlight the nature of pulmonary hypoplasia under functionally restrictive conditions, associating thoracic deformity with reduced growth and alveolar hypertrophy, the severity of which is highly predictable from thoracic geometry. From this predictive knowledge on expected growth we show that pulmonary gains in the expansion thoracoplasty procedure are offset by the growth and functional detriments associated with surgical trauma. Our evidence suggests that any surgical benefits to lung growth when provided late are nearly completely offset by detrimental effects where early surgery can provide improvements in severe cases when expected outcomes are very poor. This study is complimentary to retrospective clinical studies on early onset scoliosis and expansion thoracoplasty from which a benefit-risk analysis for patient care is derived.