pulmicort and Systemic-Inflammatory-Response-Syndrome

To define the mechanisms by which inhaled glucocorticosteroid regulates allergen-induced airway inflammation, a double-blind, placebo-controlled, cross-over study with inhaled budesonide was conducted in 14 subjects with allergic asthma. After baseline bronchoscopy and bronchoalveolar lavage (BAL), subjects were randomized to budesonide (400 microgram, twice daily) or placebo treatment for 4 wk. At the end of each treatment phase, whole-lung allergen inhalation challenge was performed, followed by BAL 48 h later. Budesonide treatment improved the FEV(1), attenuated both the immediate- and late-phase response to allergen, and prevented the increase in bronchial hyperresponsiveness after allergen challenge. Budesonide treatment also decreased allergen-induced airway eosinophilia. To determine the effects of budesonide on airway cell function, BAL cells were stimulated ex vivo with the T cell mitogen PHA, and cytokine generation was measured by ELISA. Budesonide decreased ex vivo generation of IL-5 and IFN-gamma by BAL cells. Ex vivo IL-5 production was significantly correlated with the number of airway eosinophils (r(s) = 0.61), and levels of eosinophil-derived neurotoxin (EDN) (r(s) = 0.57) and IL-5 (r(s) = 0.52) in BAL fluid. Moreover, PHA-induced IL-5 generation correlated with FEV(1) fall during the late-phase response to allergen (r(s) = 0.60). Budesonide decreased circulating eosinophils and serum levels of IL-5, but did not reduce IL-5 generation by peripheral blood mononuclear cells. The reduction in circulating eosinophils correlated with the decrease in levels of EDN (r(s) = 0.61) in BAL fluid and late response to inhaled allergen (r(s) = 0.51). These findings suggest that long-term treatment with inhaled budesonide reduces airway cell generation of cytokines, specifically IL-5, which then decreases circulating eosinophils and their availability for recruitment to the airway after allergen exposure.

Topics: Administration, Inhalation; Adult; Allergens; Anti-Inflammatory Agents; Asthma; Budesonide; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Inflammation Mediators; Male; Respiratory Hypersensitivity; Systemic Inflammatory Response Syndrome

Chorioamnionitis is associated with increased rates of bronchopulmonary dysplasia (BPD) in ventilated preterm infants. Budesonide when added to surfactant decreased lung and systemic inflammation from mechanical ventilation in preterm lambs and decreased the rates and severity of BPD in preterm infants. We hypothesized that the addition of budesonide to surfactant will decrease the injury from mechanical ventilation in preterm lambs exposed to intra-amniotic (IA) lipopolysaccharide (LPS).. Lambs at 126 ± 1 day GA received LPS 10 mg IA 48 h prior to injurious mechanical ventilation. After 15 min, lambs received either surfactant mixed with: (1) saline or (2) Budesonide 0.25 mg/kg, then ventilated with normal tidal volumes for 4 h. Injury markers in the lung, liver, and brain were compared.. Compared with surfactant alone, the addition of budesonide improved blood pressures, dynamic compliance, and ventilation, while decreasing mRNA for pro-inflammatory cytokines in the lung, liver, and multiple areas of the brain. LPS caused neuronal activation and structural changes in the brain that were not altered by budesonide. Budesonide was not retained within the lung beyond 4 h.. In preterm lambs exposed to IA LPS, the addition of budesonide to surfactant improved physiology and markers of lung and systemic inflammation.. The addition of budesonide to surfactant decreases the lung and systemic responses to injurious mechanical ventilation preterm lambs exposed to fetal LPS. Budesonide was present in the plasma by 15 min and the majority of the budesonide is no longer in the lung at 4 h of ventilation. IA LPS and mechanical ventilation caused structural changes in the brain that were not altered by short-term exposure to budesonide. The budesonide dose of 0.25 mg/kg being used clinically seems likely to decrease lung inflammation in preterm infants with chorioamnionitis.

Topics: Animals; Biological Products; Brain; Bronchopulmonary Dysplasia; Budesonide; Chorioamnionitis; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Female; Fetal Diseases; Gestational Age; Glucocorticoids; Inflammation Mediators; Lipopolysaccharides; Lung; Phospholipids; Pneumonia; Pregnancy; Pulmonary Surfactants; Respiration, Artificial; Sheep, Domestic; Systemic Inflammatory Response Syndrome