Pulmonary granulocyte accumulation is reduced by nebulized corticosteroid in septic pigs

Abstract

Nebulized beclomethasone dipropionate was administered to 14 anesthetized and artificially ventilated pigs at 6-hourly intervals after infusion of live S. aureus (BDP group). Changes in pulmonary activity from autologous granulocytes labeled with In-111 was detected externally for 12 (n = 8) to 44 h (n = 6). The changes were compared with those in ten pigs (12 h n = 7, 44 h n = 3) subjected to the same insults but given no corticosteroid (placebo group). Serial measurements of blood radioactivity, and cardiac output were performed in animals observed for 12 h. Corticosteroid-treated pigs showed a gradual decline in decay-corrected pulmonary In-111 activity. The placebo group displayed a more varied reaction, but most animals had an increased activity compared to the corticosteroid group. The difference between the groups was significant at 8 h (BDP-group 92% (88-98), placebo-group 107% (97-121), median (lower-upper quartiles), baseline = 100%. P < 0.01, U-test). Blood radioactivity and cardiac output did not differ significantly between the two groups. Nebulized corticosteroid thus diminished pulmonary granulocyte accumulation, which may be of value in the treatment of septic respiratory distress.

The Acute Respiratory Distress Syndrome: From Mechanism to Translation

“…Currently untested alternatives for the treatment and prevention of ARDS in human randomized controlled trials (RCT) are inhaled corticosteroids, angiotensin converting enzyme (ACE) inhibitors, and peroxisome proliferator receptor (PPAR) agonists. Animal data suggests that nebulized corticosteroids improve dynamic lung compliance and oxygenation, and decrease lung inflammation in sepsis-induced ARDS models (78). Angiotensin II induces NF-κB gene expression (79), hence, blocking the renin-angiotensin axis may be beneficial to ARDS patients based on animal data (80) and an observational human study (81).…”

Emerging Pharmacological Therapies for Prevention and Early Treatment of Acute Lung Injury

“…60 Walther et al reported that treatment with inhaled beclomethasone prevented pulmonary neutrophil sequestration in septic pigs pretreated with an intravenous infusion of Staphylococcus aureus. 61 Using a similar experimental protocol, a subsequent study by Walther and colleagues found the following differences in the ICS group versus placebo groups: decreased pulmonary vascular resistance, attenuated reduction of mean arterial pressure, attenuated reduction in lung and chest wall compliance, and improvement in arterial oxygen tension. 62 Wang et al studied a chlorine gas model of direct pulmonary injury in pigs.…”

Clinical Strategies to Prevent Acute Respiratory Distress Syndrome

“…Inhaled β agonists are thought to increase the rate of alveolar fluid clearance 54 and inhaled corticosteroids can help reduce inflammation. 55 Perkins et al evaluated the use of inhaled β agonist in a phase II randomized control trial. In 362 patients undergoing esophagectomy, inhaled salmeterol was associated with decreased incidence of postoperative adverse events (mostly pneumonia) and reduced several biomarkers of alveolar inflammation.…”