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Background and Objective: Acute respiratory distress syndrome (ARDS) has a high mortality rate of 35-46% depending on its severity. Animal models are crucial to better understand the pathophysiology of diseases, including ARDS. This study presents a feasible animal model of acute lung injury (ALI) using nebulized lipopolysaccharide (LPS) in a non-invasive approach, focusing on its short and long-term effects., Methods: Mice received nebulized LPS or vehicle only (control group). Blood, BALF and lung tissue were collected 24 hours (LPS 24h) or 5 weeks (LPS 5w) after the nebulized LPS-induced lung injury. Inflammatory cytokines were assessed in the blood serum, BALF and lung tissue. Stereological analyses and remodeling changes were assessed by histology and immunohistochemistry at the specified time points., Results: The LPS 24h group showed increased pro-inflammatory cytokine levels, intense cell influx, increased total septal volume, septal thickening and decreased surface density of the alveolar septa. The LPS 5w group showed persistent lung inflammation, septal thickening, increased total lung volume, accentuated collagen deposition, especially of collagen type I, and decreased MMP-2 protein expression., Conclusion: We present a feasible, reproducible and non-invasive nebulized-LPS animal model that allows the assessment of both the acute and late phases of acute lung injury. The presence of lung remodeling with collagen deposition after 5 weeks makes it useful to study the pathophysiology, complications, and possible therapeutic intervention studies that aim to understand and reduce pulmonary fibrosis in the late phases of ALI.

Background: Smoking is associated with a mixed inflammatory infiltrate in the airways. We evaluated whether airway inflammation in smokers is related to lung function parameters and inflammatory markers in exhaled breath., Methods: Thirty-seven smokers undergoing lung resection for primary lung cancer were assessed pre-operatively by lung function testing including single-breath-nitrogen washout test (sb-N2-test), measurement of fractional exhaled nitric oxide (FeNO) and pH/8-isoprostane in exhaled breath condensate (EBC). Lung tissue sections containing cancer-free large (LA) and small airways (SA) were stained for inflammatory cells. Mucosal (MCT) respectively connective tissue mast cells (MCTC) and interleukin-17A (IL-17A) expression by mast cells was analysed using a double-staining protocol., Results: The median number of neutrophils, macrophages and mast cells infiltrating the lamina propria and adventitia of SA was higher than in LA. Both MCTC and MCT were higher in the lamina propria of SA compared to LA (MCTC: 49 vs. 27.4 cells/mm2; MCT: 162.5 vs. 35.4 cells/mm2; P<0.005 for both instances). IL-17A expression was predominantly detected in MCTC of LA. Significant correlations were found for the slope of phase III % pred. of the sb-N2-test (rs= -0.39), for the FEV1% pred. (rs= 0.37) and for FEV1/FVC ratio (rs=0.38) with MCT in SA (P<0.05 for all instances). 8-isoprostane concentration correlated with the mast cells in the SA (rs=0.44), there was no correlation for pH or FeNO with cellular distribution in SA., Conclusions: Neutrophils, macrophages and mast cells are more prominent in the SA indicating that these cells are involved in the development of small airway dysfunction in smokers. Among these cell types, the best correlation was found for mast cells with lung function parameters and inflammatory markers in exhaled breath. Furthermore, the observed predominant expression of IL-17A in mast cells warrants further investigation to elucidate their role in smoking-induced lung injury, despite the lack of correlation with lung function and exhaled breath parameters.