The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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Randomized Controlled Trial
Stability or improvement in forced vital capacity with nintedanib in patients with idiopathic pulmonary fibrosis.
In the Phase III INPULSIS® trials, nintedanib reduced the annual rate of decline in forced vital capacity (FVC) versus placebo in patients with idiopathic pulmonary fibrosis (IPF). We conducted post hoc analyses of the distribution of changes in FVC in the INPULSIS® trials and FVC changes in the open-label extension trial INPULSIS®-ON in subgroups of patients based on whether patients had shown an improvement or no decline in FVC in INPULSIS®. Analyses were descriptive. ⋯ Changes in FVC from baseline to week 48 of INPULSIS®-ON were similar in patients whose FVC improved or declined in the preceding INPULSIS® trial. In the INPULSIS® trials, treatment with nintedanib resulted in a greater proportion of patients with IPF showing an improvement/no decline in FVC compared to taking placebo. Mechanisms underlying improvement in FVC in patients with IPF are unknown.
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Observational Study
Impaired efferocytosis and neutrophil extracellular trap clearance by macrophages in ARDS.
Exaggerated release of neutrophil extracellular traps (NETs) along with decreased NET clearance and inability to remove apoptotic cells (efferocytosis) may contribute to sustained inflammation in acute respiratory distress syndrome (ARDS). Recent studies in experimental models of ARDS have revealed the crosstalk between AMP-activated protein kinase (AMPK) and high-mobility group box 1 (HMGB1), which may contribute to effectiveness of efferocytosis, thereby reducing inflammation and ARDS severity. We investigated neutrophil and NET clearance by macrophages from control and ARDS patients and examined how bronchoalveolar lavage (BAL) fluid from control and ARDS patients could affect NET formation and efferocytosis. ⋯ Macrophage engulfment of NETs and apoptotic neutrophils was diminished in ARDS patients. Notably, activation of AMPK in macrophages or neutralisation of HMGB1 in BAL fluid improved efferocytosis and NET clearance. In conclusion, restoration of AMPK activity with metformin or specific neutralisation of HMGB1 in BAL fluid represent promising therapeutic strategies to decrease sustained lung inflammation during ARDS.