Bronchiectasis is a pathologic description of lung damage characterized by inflamed and dilated thick-walled bronchi. These findings may result from a number of possible causes and these may influence treatment and prognosis. The aim of this study was to determine causative factors in 150 adults with bronchiectasis (56 male, 94 female) identified using high-resolution computerized tomography. Relevant factors were identified in the clinical history; cystic fibrosis gene mutation analysis was performed; humoral immune defects were determined by measuring immunoglobulins, IgG subclasses and functional response to Pneumovax II vaccine; assessment was made of neutrophil function (respiratory burst, adhesion molecule expression, and chemotaxis); ciliary function was observed and those likely to have allergic bronchopulmonary aspergillosis (ABPA) were identified. Causes identified were: immune defects (12 cases), cystic fibrosis (4), Young's syndrome (5), ciliary dysfunction (3), aspiration (6), panbronchiolitis (1), congenital defect (1), ABPA (11), rheumatoid arthritis (4), and early childhood pneumonia, pertussis, or measles (44). Intensive investigation of this population of patients with bronchiectasis led to identification of one or more causative factor in 47% of cases. In 22 patients (15%), the cause identified had implications for prognosis and treatment.
The humoral immune responses to the D2 peptide of fibronectin-binding protein B (FnBP) of Staphylococcus aureus, expressed on the plant virus cowpea mosaic virus (CPMV), were evaluated after mucosal delivery to mice. Intranasal immunization of these chimeric virus particles (CVPs), either alone or in the presence of ISCOM matrix, primed CPMV-specific T cells and generated high titers of CPMV-and FnBP-specific immunoglobulin G (IgG) in sera. Furthermore, CPMV-and FnBP-specific IgA and IgG could also be detected in the bronchial, intestinal, and vaginal lavage fluids, highlighting the ability of CVPs to generate antibody at distant mucosal sites. IgG2a and IgG2b were the dominant IgG subclasses in sera to both CPMV and FnBP, demonstrating a bias in the response toward the T helper 1 type. The sera completely inhibited the binding of human fibronectin to the S. aureus FnBP. Oral immunization of the CVPs also generated CPMV-and FnBP-specific serum IgG; however, these titers were significantly lower and more variable than those generated by the intranasal route, and FnBP-specific intestinal IgA was undetectable. Neither the ISCOM matrix nor cholera toxin enhanced these responses. These studies demonstrate for the first time that recombinant plant viruses have potential as mucosal vaccines without the requirement for adjuvant and that the nasal route is most effective for the delivery of these nonreplicating particles.
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