Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome*

Abstract

Objective Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome (ARDS) are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to ARDS by reducing lung inflammation and enhancing alveolar fluid clearance. Design Double-blind, randomized clinical trial (ClinicalTrials.gov: NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the fraction of inspired oxygen (S/F) through day 5. We also analyzed categorical change in S/F by > 20%. Other outcomes included need for mechanical ventilation and development of ARDS. Setting Five academic centers in the United States. Patients Adult patients admitted through the emergency department at risk for ARDS. Interventions Aerosolized budesonide/formoterol vs. placebo twice daily for up to 5 days. Measurements and Main Results Sixty-one patients were enrolled from September 3, 2013 to June 9, 2015. Median time from presentation to first study drug was < 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p=0.02) and independent of shock (p=0.04). Categorical change in S/F improved (p=0.01) but not after adjustment for shock (p=0.15). More patients in the placebo group developed ARDS (7 versus 0) and required mechanical ventilation (53% versus 21%). Conclusions Early treatment with inhaled budesonide/formoterol in patients at-risk for ARDS is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of ARDS.

Risk modifiers of acute respiratory distress syndrome in patients with non-pulmonary sepsis: a retrospective analysis of the FORECAST study

“…Including a combination of smoking-related biomarkers might have identified more current smokers than the smoking history obtained from patients, surrogates, and medical records [41]. Second, unrecorded medication histories, including the use of inhaled corticosteroids and inhaled beta agonist may have been a confounding factor [42]. It is conceivable that smoking and indirect ARDS are not associated, as is the case with smoking and direct ARDS [23,25].…”

How Should Aerosols Be Delivered During Invasive Mechanical Ventilation?

“…In hypoxemic subjects at risk of developing ARDS, early intervention with inhaled formoterol and budesonide combination was shown to lead to more rapid improvement in oxygenation. 174 In this study, a higher proportion of subjects in the placebo group were in shock at baseline, and the reported differences in need for mechanical ventilation and frequency of ARDS that favored the treatment group were no longer observed after correction for baseline shock. 174 Thus, there is no conclusive benefit of using ICS, and further investigations are needed to determine the appropriate dosing regimen and the risks and benefits of using ICS or ICS and long-acting ␤-agonist in mechanically ventilated patients.…”

Clinical Strategies to Prevent Acute Respiratory Distress Syndrome

“…56 Most recently, Festic et al investigated a combination of an inhaled corticosteroid and inhaled longacting β agonist (budesonide and formoterol) in patients at an increased risk of ARDS (LIPS >4) in a phase IIa double-blind multicenter randomized controlled trial. 57 An improvement in oxygenation when compared with placebo was observed, and although this was a feasibility study, there was a lower incidence of ARDS in the treatment group versus placebo group (0 vs. 7, p ¼ 0.01 patients). Although not powered to study the effect on prevention of ARDS, this result will inform future studies.…”