STRUCTURAL AND FUNCTIONAL CORRELATES OF EXERCISE VENTILATORY INEFFICIENCY IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS WITH MILD-TO-MODERATE SPIROMETRIC ABNORMALITIES

Background: Individuals with chronic obstructive pulmonary disease (COPD) have higher than normal ventilatory equivalents for carbon dioxide (VE/VCO2) during exercise. There is growing evidence that emphysema on thoracic computed tomography (CT) scans is associated with poor exercise capacity in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that emphysema is an underlying cause of microvascular dysfunction and ventilatory inefficiency, which in turn contributes to reduced exercise capacity. We expected ventilatory inefficiency to be associated with a) the extent of emphysema; b) lower diffusing capacity for carbon monoxide; c) a reduced pulmonary blood flow response to exercise; and d) reduced exercise capacity. Methods: In a cross-sectional study, 19 subjects with mild-to-moderate COPD (mean ± SD FEV1= 82 ± 13% predicted, 12 GOLD grade 1) and 26 age-, sex-, and activity-matched controls underwent a ramp-incremental symptom-limited exercise test on a cycle ergometer. Ventilatory inefficiency was assessed by the minimum VE/VCO2 value (nadir). A subset of subjects also completed repeated constant work rate exercise bouts with non-invasive measurements of pulmonary blood flow. Emphysema was quantified as the percentage of attenuation areas below -950 Housefield Units on CT scans. An electronic scoresheet was used to keep track of emphysema sub-types. Results: COPD subjects typically had centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/lower lobe ratio= 0.82 ± 0.04). They had lower peak oxygen uptake (VO2), higher VE/VCO2 nadir and greater dyspnea scores than controls (p<0.05). Lower peak O2 and worse dyspnea were found in COPD subjects with VE/VCO2 nadirs ≥ 30. COPD subjects had blunted increases in pulmonary blood flow from rest to iso-VO2 exercise (p<0.05). Higher VE/VCO2 nadir in COPD subjects correlated with emphysema severity (r= 0.63), which in turn correlated with reduced lung diffusing capacity (r= -0.72) and blunted changes in pulmonary blood flow from rest to exercise (r= -0.69) (p<0.01). Conclusions: Ventilation “wasted” in emphysematous areas is associated with reduced exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (gas transfer) to a key clinical outcome (reduced exercise capacity) in COPD patients with modest spirometric abnormalities.

Analysis of Cosmogenic Impurities in Tellurium and Development of Tellurium Loading for the SNO+ Experiment

For the SNO+ neutrinoless double beta decay search, various backgrounds, ranging from impurities present naturally to those produced cosmogenically, must be understood and reduced. Cosmogenic backgrounds are particularly difficult to reduce as they are continually regenerated while exposed to high energy cosmic rays. To reduce these cosmogenics as much as possible the tellurium used for the neutrinoless double beta decay search will be purified underground. An analysis of the purification factors achievable for insoluble cosmogenic impurities found a reduction factor of $>$20.4 at 50\% C.L.. During the purification process the tellurium will come into contact with ultra pure water and nitric acid. These liquids both carry some cosmogenic impurities with them that could be potentially transferred to the tellurium. A conservative limit is set at $<$18 events in the SNO+ region of interest (ROI) per year as a result of contaminants from these liquids. In addition to cosmogenics brought underground, muons can produce radioactive isotopes while the tellurium is stored underground. A study on the rate at which muons produce these backgrounds finds an additional 1 event per year. In order to load the tellurium into the detector, it will be combined with 1,2-butanediol to form an organometallic complex. The complex was found to have minimal effect on the SNO+ acrylic vessel for 154 years.