Building a bioresource for esophageal research: lessons from the early experience of an academic medical center.

The establishment of biorepositories, linked to clinical and epidemiologic data, are central to the goals of personalized medicine and individualized cancer therapy. Repositories of DNA, RNA, and serum samples are valuable resources for cancer research, enabling the investigation of the underlying causes of cancer development, progression, and prognosis, as well as providing a resource for the investigation of biomarkers for early detection and prediction of response. With a greater reliance on sample-derived data for molecular-based research and clinical care, improved standards and informatics for sample procurement, storage, and analysis are necessary to maximize the value of tissue collection for research participants, investigators, and academic medical centers. We present herein the experience of an academic medical center in establishing a repository for esophageal research, with discussion of elements to be considered when establishing such a resource, from the quality assurance of samples to the organized collection and storage of associated clinical data. The development of this biorepository required significant planning to identify and consent participants by dedicated clinical and research personnel. Ensuring the quality of any biobank is of utmost importance, and one must understand the sample variability that exists during the acquisition of biospecimens. The time and type of fixative have been optimized in our unit by standard operating protocols. Methods for biomolecule extraction were tested by examining both the quality and the quantity of recovered sample. These procedures were overseen by a designated biobank manager, responsible for the acquisition of the sample from surgery, which limits variability in sample collection. Our unit also has a dedicated database manager for the maintenance of quality clinical data linked to the bioresource. The development and expansion of such repositories, at local and national levels, is required to enable leading academic medical centers and their investigators to provide optimal and molecularly guided care to their patients.

Prior Bordetella pertussis infection modulates allergen priming and the severity of airway pathology in a murine model of allergic asthma.

BACKGROUND: It has been proposed that T helper (Th)2-driven immune deviation in early life can be countered by Th1 inducing childhood infections and that such counter-regulation can protect against allergic asthma. OBJECTIVE: To test whether Th1-inducing infection with Bordetella pertussis protects against allergic asthma using well-characterized murine models. METHODS: Groups of mice were sensitized to ovalbumin (OVA) in the presence or absence of B. pertussis, a well-characterized Th1 inducing respiratory infection. Immunological, pathological and physiological parameters were measured to assess the impact of infection on immune deviation and airway function. RESULTS: We demonstrate that OVA sensitization does not affect the development of B. pertussis-specific immune responses dominated by IgG2a and IFN-gamma and does not impair Th1-mediated clearance of airway infection. In contrast, B. pertussis infection at the time of sensitization modulated the response to OVA and significantly reduced total serum and OVA-specific IgE. The pattern of cytokine responses, in particular OVA-specific IL-5 responses in the spleen was also modulated. However, B. pertussis did not cause global suppression as IL-10 and IL-13 levels were enhanced in OVA-stimulated spleen cell cultures and in lavage fluid from infected co-sensitized mice. Histopathological examination revealed that B. pertussis infection prior to OVA sensitization resulted in increased inflammation of bronchiolar walls with accompanying hyperplasia and mucous metaplasia of lining epithelia. These pathological changes were accompanied by increased bronchial hyper-reactivity to methacholine exposure. CONCLUSION: Contrary to the above premise, a Th1 response induced by a common childhood infection does not protect against bronchial hyper-reactivity, but rather exacerbates the allergic asthmatic response, despite modulation of immune mediators.