Are beta2-agonists effective treatment for acute bronchitis or acute cough in patients without underlying pulmonary disease? A systematic review.

OBJECTIVE: Our goal was to determine whether beta2-agonists improve the symptoms of acute bronchitis or acute cough in patients who do not have underlying pulmonary disease. STUDY DESIGN: We performed a systematic review including meta-analysis. DATA SOURCES: We included randomized controlled trials comparing beta2-agonists with placebo or alternative therapies identified from the Cochrane Library, MEDLINE, EMBASE, conference proceedings, Science Citation Index, the System for Information on Grey Literature in Europe, and letters to manufacturers of beta2-agonists. OUTCOMES MEASURED: We measured duration, persistence, severity or frequency of cough, productive cough, and night cough; duration of activity limitations; and adverse effects. RESULTS: Two trials in children with cough and no obvious airway obstruction did not find any benefits from beta2-agonists. Five trials in adults with cough and with or without airway obstruction had mixed results, but summary statistics did not reveal any significant benefits from beta2-agonists. Studies that enrolled more wheezing patients were more likely to show benefits from beta2-agonists, and in one study only patients with evidence of airflow limitation were more likely to benefit. Patients given beta2-agonists were more likely to report tremor, shakiness, or nervousness than those in the control groups. CONCLUSIONS: There is no evidence to support using beta2-agonists in children with acute cough and no evidence of airflow obstruction. There is little evidence that the routine use of beta2-agonists for adults with acute cough is helpful. These agents may reduce symptoms, including cough, in patients with evidence of airflow obstruction, but this potential benefit is not well-supported by the available data and must be weighed against the adverse effects associated with beta2-agonists.

Safety and immunogenicity of NYVAC-JEV and ALVAC-JEV attenuated recombinant Japanese encephalitis virus--poxvirus vaccines in vaccinia-nonimmune and vaccinia-immune humans.

A controlled, randomized, double-blind clinical trial evaluated whether two attenuated recombinant poxviruses with identical Japanese encephalitis virus (JEV) gene insertions, NYVAC-JEV and ALVAC-JEV, were safe and immunogenic in volunteers. Groups of 10 volunteers distinguished by vaccinia immune status received two doses of each vaccine. The vaccines appeared to be equally safe and well tolerated in volunteers, but more reactogenic than licensed formalin-inactivated JE and placebo vaccines given as controls. NYVAC-JEV and ALVAC-JEV vaccine recipients had frequent occurrence of local warmth, erythema, tenderness, and/or arm pain after vaccination. There was no apparent effect of vaccinia immune status on frequency or magnitude of local and systemic reactions. NYVAC-JEV elicited antibody responses to JEV antigens in recipients but ALVAC-JEV vaccine poorly induced antibody responses. However, NYVAC-JEV vaccine induced neutralizing antibody responses only in vaccinia-nonimmune recipients while vaccinia-immune volunteers failed to develop protective antibodies (5/5 vs. 0/5 seroconversion, p<0.01). These data suggest that preexisting immunity to poxvirus vector may suppress antibody responses to recombinant gene products.

Are antibiotics effective treatment for acute bronchitis? A meta-analysis.

BACKGROUND: Most clinicians prescribe antibiotics for acute bronchitis in spite of recommendations against this practice. Because the results of individual clinical trials have been mixed, we conducted a meta-analysis to determine whether antibiotics are effective treatment for acute bronchitis. METHODS: We conducted a comprehensive search to identify all trials in which patients who had a diagnosis of acute bronchitis were randomly assigned to treatment with an antibiotic or placebo. Patient-oriented outcomes of importance that were reported in at least 3 studies were quantitatively summarized. RESULTS: Nine studies met the inclusion criteria, but not all trials provided data for each outcome. Patients given antibiotics were less likely to have a cough (relative risk [RR] = 0.69; 95% confidence interval [CI], 0.49 -0.98) and be considered unimproved (RR = 0.51; 95% CI, 0.30-0.88) at a follow-up visit; but they were not less likely to have a productive cough (RR = 0.79; 95% CI, 0.60-1.03), activity limitations (RR = 0.59; 95% CI, 0.24-1.44), or feel ill (RR = 0.70; 95% CI, 0.31-1.58). Antibiotic-treated patients had a slightly shorter duration of productive cough (weighted mean difference [WMD] = -0.56 days; 95% CI, -1.09 to -0.04), but not of overall cough (WMD = -0.94; 95% CI, -2.08 to 0.21) or activity limitations (WMD = -0.49; 95% CI, -1.07 to 0.10). Patients treated with antibiotics did not report significantly more adverse effects (RR = 1.47; 95% CI, 0.82-2.65). CONCLUSIONS: Antibiotics may be modestly effective for a minority of patients with acute bronchitis. It is not clear which patient subgroups might benefit, and the failure of some studies to report negative findings may have resulted in overestimates of the benefits of antibiotics. Antibiotics are not necessary for every patient with acute bronchitis.

Induction of Japanese encephalitis virus-specific cytotoxic T lymphocytes in humans by poxvirus-based JE vaccine candidates.

Poxvirus-based recombinant Japanese encephalitis (JE) vaccine candidates, NYVAC-JEV and ALVAC-JEV, were examined for their ability to induce JE virus-specific cytotoxic T lymphocytes (CTLs) in a phase I clinical trial. These vaccine candidates encoded the JE virus premembrane (prM), envelope (E) and non-structural 1 (NS1) proteins. The volunteers received subcutaneous inoculations with each of these candidates on days 0 and 28, and blood was drawn 2 days before vaccination and on day 58. Anti-E and anti-NS1 antibodies were elicited in most vaccinees inoculated with NYVAC-JEV and in some vaccinees inoculated with ALVAC-JEV. Peripheral blood mononuclear cells (PBMCs) obtained from approximately one half of vaccines showed positive proliferation in response to stimulation with live JE virus. Cytotoxic assays demonstrated the presence of JE virus-specific CTLs in in vitro-stimulated PBMCs obtained from two NYVAC-JEV and two ALVAC-JEV vaccinees. Cell depletion tests using PBMCs from one NYVAC-JEV recipient indicated that the phenotype of CTLs was CD8+CD4-.

Murine immunoglobulin G subclass responses following immunization with live dengue virus or a recombinant dengue envelope protein.

Murine immunoglobulin G (IgG) subclass responses to immunization are restricted to certain subclasses depending on the nature of the immunogen. Immunization with live viruses generally leads to a predominant IgG2a response, which may be the most effective at resisting future challenge due to the unique effector functions of IgG2a. Knowledge of subclass responses following immunization with dengue vaccine candidates may be helpful in determining which candidates are most efficacious. We measured the dengue-specific IgG subclass responses of BALB/c mice following immunization with live dengue-2 virus or with a partially purified recombinant dengue-2 envelope (E) protein. Subclass responses following immunization with live virus were IgG2a > IgG1 > IgG2b > IgG3, as opposed to IgG1 > IgG2a > IgG2b > IgG3 after immunization with recombinant protein. Responses of all subclasses except IgG1 were greater following immunization with live dengue than with the recombinant E protein. Neutralizing antibody titers were also higher after immunization with live virus than with E protein and were positively correlated with dengue-specific IgG2a responses in mice immunized with recombinant E protein. Following separation of the four IgG subclasses by chromatography, the IgG2a fraction exhibited the greatest neutralizing activity. The results seen after immunization with live dengue virus or recombinant E protein in this study are in concordance with studies involving other viruses and viral proteins and may have implications for the development of an effective vaccine for dengue.