5.3.3 Baseline Inflammation in Respiratory Epithelium of Individuals with CF 
The type and number of inflammatory cells in nasal epithelium and bronchial 
epithelium and respiratory epithelial lining fluid will be used as safety and 
efficacy parameters, with increases in numbers of inflammatory cells 
suggesting adverse events and decreasing numbers suggesting efficacy (see 
below for caveats regarding these parameters) . The extent of inflammation in 
each site in a group of individuals with CF as compared to non-smoking normals 
is detailed in Section 4.4. 
In the nasal epithelium of individuals with CF there is more inflammation 
compared to normals, but it is relatively mild. In contrast, in the bronchial 
epithelium in CF there is an intense, neutrophil dominated inflammatory 
process with a more than 30- fold increase in the numbers of neutrophils 
present among the epithelial cells recovered by bronchial brush compared to 
normals (Table 4.4-A). The extent of the inflammation on the epithelial 
surface of the CF lung is further documented by quantification of the numbers 
of inflammatory cells recovered by bronchoalveolar lavage: in CF more than 4- 
fold more inflammatory cells are recovered and there is a 300- fold increase in 
the number of neutrophils present (Table 4.4-A). 
These observations highlight the extensive epithelial-based inflammation in CF 
which are consistent with morphologic observations of the CF lung in specimens 
obtained at autopsy or at lung transplantation (Bedrossian et al , 1976). The 
methods used to quantify these parameters (nasal brush, bronchial brush and 
bronchoalveolar lavage), however, are not sufficiently well established to 
permit their use as definitive criteria for establishing the presence or 
absence of adverse effects or efficacy. Therefore, these parameters will be 
collected throughout the protocol, but will not be used as criteria for safety 
and efficacy unless the observations are dramatic and repeated. 
5.3.4 DNA Containing Ela Sequences in Nasal Epithelial Cells, Bronchial 
Epithelial Cells, Lung Inflammatory Cells, Blood Lymphocytes and Blood 
Neutrophils of Individuals with CF 
Based on the knowledge that AdCFTR could theoretically recombine with 
exogenous adenovirus sequences, or that El sequences could provide sufficient 
information, in trans . to complement the El sequences deleted from AdCFTR, to 
minimize the risks of recombination or complementation, all individuals 
entered into the baseline period of the protocol will be assessed for the 
presence of adenovirus Ela sequences in the airway epithelium. Only those 
negative for the presence of Ela sequences will be accepted to move to the 
vehicle control period (see inclusion criteria, section 5.4). These criteria 
were developed based on assessment of respiratory epithelium of individuals 
with CF for the presence of Ela sequences (see Section 4.9, Table 4.9-C). 
The data demonstrate that Ela DNA sequences are found in the epithelium of the 
respiratory tract of 10% of individuals with CF. Of those individuals that are 
Ela + , there were an average of 87 + 26 copies of Ela/10 3 epithelial cells. 
This is no different from normal individuals (see Table 4.9-C for details). 
5.4 Patient Eligibility and Selection 
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