8.2 Evaluation of toxicity 
The primary indicators of acute and chronic toxicity will be as follows: 
8.2.1 A thorough daily clinical assessment during admission by one of the primary 
investigators, which will allow detection of and response to any acute compromise 
of pulmonary status, respiratory distress, or bronchospasm. 
8.2.2 The measurement of pulmonary function, consisting of spirometry and flow- 
volume loops, which would allow detection and quantitation of any worsening of 
airway obstruction and expiratory outflow limitations. 
8.2.3 Measurements of complete blood counts, differential leukocyte counts, prothrombin 
time, partial thromboplastin time, serum electrolytes, transaminases, BUN and 
creatinine, which would allow detection of any acute reactions resulting in 
hemolysis, coagulopathy, renal compromise, or hepatotoxicity. 
8.2.4 Bronchoalveolar lavage (BAL) for bacterial culture, special recombinant virus 
culture in the principal investigator's laboratory, a direct assessment of the 
inflammatory mediators IL-6 and IL-8 by ELISA, and cell counts with differential. 
These will allow detection of changes in sputum flora, recombinant or wild-type 
viral shedding, and markers of the degree of airway inflammation. 
8.2.5 Chest X-ray and CT scanning to define morphological evidence of airway 
obstruction (hyperinflated segments or areas of atelectasis) or parenchymal injury. 
8.2.6 Anti- AAV, anti-adenovirus, and anti-CFTR antibody studies from serum and BAL 
fluid to assess the presence and degree of immunologic reaction to the vector 
particles, any residual adenoviral proteins, or presence of novel epitopes derived 
from the expressed normal CFTR protein. 
8.2.7 Periodic anthropometric/nutritional assessments, as a global indicator of the 
patient's health. 
8.2.8 Shwachman clinical score as a long-term global assessment of disease severity. 
8.2.9 An acute clinical score which has been shown to correlate with changes in 
pulmonary function in cystic fibrosis, as a more near-term indicator of global 
disease severity. 
8.2.10 Although each of the above indicators is primarily designed as a measure of 
toxicity, these may also serve as measures of clinical activity, if there were 
physiologic correction of the chloride channel defect and improvement in lung 
function. 
8.3 Environmental Monitoring 
Based on a variety of animal data, it appears extremely unlikely that recombinant virus 
would be shed to an extent capable of infecting health care providers. Furthermore, patients 
will be kept on respiratory virus isolation during the entire inpatient stay. Even so, the 
possibility of environmental exposure will be studied. Special viral cultures of nasal 
washings, capable of detecting wild-type or recombinant AAV virions, will be performed 
to screen all regularly involved health care providers at least four times per year. These 
cultures will be performed in the principal investigator's laboratory. 
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