The beta-agonist lung injury trial (BALTI) - a randomized placebo-controlled clinical trial

Rationale: Experimental data suggest that manipulation of alveolar fluid clearance with β-agonists can accelerate the resolution of alveolar edema and improve survival. Objective: To determine if a sustained infusion of intravenous salbutamol (albuterol) would accelerate the resolution of alveolar edema in adult patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Methods: This was a single-center, double-blind, randomized controlled trial. Patients with ALI/ARDS were randomized to treatment with intravenous salbutamol (15 μg kg-1 h-1) or placebo for 7 d. The primary endpoint was extravascular lung water measured by thermodilution (PiCCO) at Day 7. Measurements and Main Results: Sixty-six patients were screened; of these, 40 met the inclusion criteria and were enrolled during 2001-2003. Patients in the salbutamol group had significantly lower lung water at Day 7 than the placebo group (9.2 ± 6 vs. 13.2 ± 3 ml kg-1; 95% confidence interval difference, 0.2-8.3 ml kg-1; p = 0.038). Plateau airway pressure was lower at Day 7 in the salbutamol group (23.9 ± 3.8 cm H2O) versus placebo (29.5 ± 7.2 cm H2O; p = 0.049). There was a trend toward lower Murray lung injury score at Day 7 in the salbutamol group (1.7 ± 0.9) versus placebo (2.0 ± 0.6; p = 0.2). Patients in the salbutamol group had a higher incidence of supraventricular arrhythmias (26 vs. 10%; p = 0.2). Conclusion: Although further research is required to confirm the efficacy and safety of intravenous salbutamol in ALI/ARDS, this trial provides the first proof of principle that, in humans with ALI/ARDS, sustained treatment with intravenous β-agonists reduces extravascular lung water

Epithelial-mesenchymal transition in lung development and disease: Does it exist and is it important?

Epithelial-mesenchymal transition (EMT) is a process when epithelial cells gradually transform into mesenchymal-like cells losing their epithelial functionality and characteristics. EMT is thought to be involved in the pathogenesis of numerous lung diseases ranging from developmental disorders, fibrotic tissue remodelling to lung cancer. The most important question-namely what is the importance and contribution of EMT in the pathogenesis of several chronic lung conditions (asthma, COPD, bronchiolitis obliterans syndrome and lung fibrosis)-is currently intensely debated. This review gives a brief insight into the mechanism and assessment methods of EMT in various pulmonary diseases and summarises the recent literature highlighting the controversial experimental data and conclusions

Statins and sepsis

Severe sepsis and septic shock is common and frequently fatal. Over the last few years, the primary treatments demonstrated to improve outcome from several major clinical trials have finally emerged. However, translating these recent therapeutic advances to routine clinical practice has proven controversial, and new approaches of additional strategies are continued to be developed. Given their pleiotropic effects related to many pathophysiological determinants of sepsis, statin therapy could be the next step in the search for adjuvant therapy. A future challenge may be to test both the efficacy and the safety by large randomized controlled clinical trials ascertaining the effects of statins administered at the onset of sepsis and in patients with severe sepsis or septic shock admitted into intensive care units