title: Evaluation of exposure and health care worker response to nebulized administration of tgAAVCF to patients with cystic fibrosis.
abstract: A study was conducted to assess health care worker exposure to tgAAVCF during the aerosolized administration of this experimental gene transfer agent in clinical trials for the treatment of cystic fibrosis (CF). tgAAVCF is a recombinant adeno-associated virus (AAV) genetically engineered to contain the human CF transmembrane conductance regulator cDNA. Study subjects included eight health care workers involved in the administration of tgAAVCF in a phase II study and 12 control health care workers who were involved with the treatment of CF patients, but not administration of the study drug. The exposure assessment entailed the determination of personal and area airborne tgAAVCF concentrations. In addition, serologic status of the health care workers was evaluated throughout the study for the presence of antibodies to AAV. A symptom survey was also completed by both the active and control health care workers. Air samples were analyzed by an infectivity assay (active vector) and a DNA polymerase chain reaction amplification procedure (vector DNA). Air monitoring was conducted during 13 tgAAVCF and seven placebo administrations. Active vector and vector particles were detected in four of 51 and 48 of 51 air samples collected during the administration of tgAAVCF, respectively. Based on the airborne vector particle concentration, the workers' exposure was estimated to be 0.0006% of the administered dose. At this level of exposure, the prevalence of symptoms was very low, the spectrum was similar in both study groups and did not result in any reported negative health effects.
authors.affiliation: University of Washington, Department of Environmental and Occupational Health Sciences, Field Research & Consultation Group, 4225 Roosevelt Way NE, Suite 100, Seattle, WA 98105-6099, USA. croteau@u.washington.edu
authors.forename: Gerry A
authors.initials: GA
authors.lastname: Croteau
authors.forename: Dana B
authors.initials: DB
authors.lastname: Martin
authors.forename: Janice
authors.initials: J
authors.lastname: Camp
authors.forename: Michael
authors.initials: M
authors.lastname: Yost
authors.forename: Carol
authors.initials: C
authors.lastname: Conrad
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Zeitlin
authors.forename: Alison E
authors.initials: AE
authors.lastname: Heald
mesh_terms: D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D000229:Dependovirus / Q000235:genetics / Q000302:isolation & purification; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D019570:Inhalation Exposure / Q000032:analysis*; D009330:Nebulizers and Vaporizers; D016273:Occupational Exposure / Q000032:analysis*; D010348:Patient Care Team
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator