Stress-strain curve and elastic behavior of the fibrotic lung with usual interstitial pneumonia pattern during protective mechanical ventilation

Abstract

Background Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (AE-ILD-UIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress-strain behavior and the specific elastance of patients with AE-ILD-UIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung.Methods Partitioned lung and chest wall mechanics were assessed for patients with AE-ILD-UIP and primary ARDS (1:1 matched based on BMI and PaO2/FiO2 ratio) during a PEEP trial performed within 24 h from intubation. Patient’s stress-strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix (ECM).Results Five patients with AE-ILD-UIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Specific elastance was significantly higher in AE-ILD-UIP as compared to ARDS (28.9 [24.8–33.2] cmH2O/l versus 11.4 [11.1–14.5] cmH2O/l, respectively). Compared to ARDS and healthy lung, the stress/strain curve of AE-ILD-UIP showed a steeper increase, crossing the VILI threshold risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to AE-ILD-UIP lungs.Conclusions During MV, patients with AE-ILD-UIP showed different respiratory mechanics, stress-strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with AE-ILD-UIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS.