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

Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) 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 EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index 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. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8-33.2] cmH2O versus 11.4 [10.3-14.6] cmH2O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress 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 EUIP lungs. During MV, patients with EUIP 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 EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS.

Physiological effects of lung-protective ventilation in patients with lung fibrosis and usual interstitial pneumonia pattern versus primary ARDS: a matched-control study.

BACKGROUND: Although patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung-protective ventilation in patients with AE-ILD-UIP compared with primary ARDS. METHODS: Partitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO2/FiO2 ratio). Three PEEP levels (zero = ZEEP, 4-8 cmH2O = PEEPLOW, and titrated to achieve positive end-expiratory transpulmonary pressure PL,EE = PEEPTITRATED) were used for measurements. RESULTS: Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median PL,EE at ZEEP was - 4.3 [- 7.6- - 2.3] cmH2O and lung elastance (EL) 44 [40-51] cmH2O/L. At PEEPLOW, PL,EE remained negative and EL did not change (p = 0.995) versus ZEEP. At PEEPTITRATED, PL,EE increased to 0.8 [0.3-1.5] cmH2O and EL to 49 [43-59] (p = 0.004 and p < 0.001 compared to ZEEP and PEEPLOW, respectively). ΔPL decreased at PEEPLOW (p = 0.018) and increased at PEEPTITRATED (p = 0.003). In matched ARDS control PEEP titration to obtain a positive PL,EE did not result in significant changes in EL and ΔPL. CONCLUSIONS: In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive PL,EE significantly worsened lung mechanics.

Numerical Assessment of Damage Parameters for a Hard Interface Model.

Adhesive interfaces are suitable modelling tools to describe very thin elastic layers and the related occurring phenomena (such as damage, viscosity, friction, etc.), without using a volumetric description, which is often computationally prohibitive in a large-scale numerical simulation. A major drawback of these kinds of models is the identification of free parameters, because of the smallness of a direct observation scale. This paper proposes a numerical assessment of two model parameters, a damage energy threshold and a damage viscosity, of a hard interface model previously formulated by authors. The proposed assessment protocol uses macroscopic experimental data, available in the literature, on structural adhesives under standard characterization tests. The numerical results obtained give insights into the physical interpretation of these parameters.