Effect of dexamethasone on respiratory syncytial virus-induced lung inflammation in children: results of a randomized, placebo controlled clinical trial.

Inflammatory mediators play a major role in the pathogenesis of respiratory syncytial virus (RSV) infection. The objective of this study was to evaluate the effect of i.v. dexamethasone on cytokine concentrations in tracheal aspirates (TA) of children with severe RSV disease and to correlate them with disease severity. Twenty-five cytokines were measured in TA obtained from children <2 yr old intubated for severe RSV disease, and enrolled in a double-blind study of i.v. dexamethasone (0.5 mg/kg; n = 22) vs. placebo (n = 19). Cytokine concentrations, measured at baseline and days 1 and 5 post-randomization using a multiplex assay, were compared within both treatment groups and correlated with: (i) tracheal white blood cell counts, (ii) tracheal RSV loads by culture and (iii) parameters of disease severity, including number of days of requirement for mechanical ventilation, intensive care unit (ICU), and hospitalization. At baseline interleukin (IL)-13 and IL-15 concentrations were significantly higher in the dexamethasone treatment group. On day 1 post-treatment, only MCP-1, eotaxin and IL-6 concentrations were significantly different but higher in the placebo group. On day 5: IL-13, IL-7, IL-8 and MIP-1alpha concentrations were higher in dexamethasone-treated patients. In both groups MIP-1beta inversely correlated with the days of ventilator support; MIP-1alpha, MIP-1beta and eotaxin inversely correlated with ICU days; and IL-6 inversely correlated with hospitalization regardless of the treatment assigned. Systemic administration of dexamethasone did not have a consistent effect on TA concentrations of pro-inflammatory cytokines. This may help explain, at least in part, the lack of clinical benefit of steroid treatment in children with severe RSV bronchiolitis.

A randomized, double-blind, placebo-controlled trial of dexamethasone in severe respiratory syncytial virus (RSV) infection: effects on RSV quantity and clinical outcome.

Forty-one previously healthy children <2 years of age who required mechanical ventilation for respiratory syncytial virus (RSV) infection were randomized to receive dexamethasone (0.5 mg/kg; n=22) or saline placebo (n=19) intravenously every 12 h for 4 days. RSV quantity was measured by quantitative plaque assay in fresh tracheal and nasal aspirates obtained at intervals of 24+/-3 h on days 0, 1, 2, 5, and 7 following entry. Analysis by linear mixed-effects modeling demonstrated a significantly greater decline in mean tracheal RSV quantity in the placebo group than in the dexamethasone group from day 0 to day 1 (0.82 vs. 0.21 log pfu/mL; P=.01) and from day 0 to day 2 (1.45 vs. 0.53 log pfu/mL; P=.03). No differences were found between groups in nasal RSV quantity, white blood cell counts in tracheal or nasal aspirates, serum neutralizing antibody titers during convalescence, or duration of mechanical ventilation, intensive care unit stay, or hospital stay.