Lung strain and biological response in mechanically ventilated patients

Lung tissue may exhibit a biochemical response to excessive deformation. Since strain has been proposed as a marker of such deformation, we studied the relationships between strain and matrix remodeling and inflammation markers in mechanically ventilated patients with and without acute lung injury (ALI). Twenty-two ventilated patients were studied (16 with ALI, 6 controls). Clinical data, gas exchange and respiratory mechanics were recorded, and end-expiratory lung volume (EELV) was measured by oxygen washin/washout. Extracellular matrix remodeling markers (procollagen, matrix metalloproteinases -2 and -9, TIMP-1) and inflammation markers (IL-6, IL-8, IL-10, IFN gamma, IL-17A, and VEGF) were measured in bronchoalveolar lavage fluid (BALF). Strain was computed as the ratio between tidal volume and EELV. Patients with ALI were divided into two subgroups according to the median strain value (0.27). Patients in the ALI group exhibited higher airway pressures, lower EELV and higher strain than the control group. There were no significant differences in gas exchange, respiratory mechanics, or the matrix remodeling markers between ALI patients with normal and high strain. The subgroup of patients with high strain showed a fourfold increase of IL-6 and IL-8 concentrations in BALF, compared with patients with ALI and normal strain or patients without ALI. In the whole sample, IL-6 and IL-8 concentrations in BALF were correlated with strain (Spearman's rho = 0.67 and 0.77, respectively). Increased strain is associated with a proinflammatory lung response in patients with ALI.