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Lung fibrosis results from the synergic interplay between regenerative deficits of the alveolar epithelium and dysregulated mechanisms of repair in response to alveolar and vascular damage, which is followed by progressive fibroblast and myofibroblast proliferation and excessive deposition of the extracellular matrix. The increased parenchymal stiffness of fibrotic lungs significantly affects respiratory mechanics, making the lung more fragile and prone to non-physiological stress during spontaneous breathing and mechanical ventilation. Given their parenchymal inhomogeneity, fibrotic lungs may display an anisotropic response to mechanical stresses with different regional deformations (micro-strain). This behavior is not described by the standard stress–strain curve but follows the mechano-elastic models of “squishy balls”, where the elastic limit can be reached due to the excessive deformation of parenchymal areas with normal elasticity that are surrounded by inelastic fibrous tissue or collapsed induration areas, which tend to protrude outside the fibrous ring. Increasing evidence has shown that non-physiological mechanical forces applied to fibrotic lungs with associated abnormal mechanotransduction could favor the progression of pulmonary fibrosis. With this review, we aim to summarize the state of the art on the relation between mechanical forces acting on the lung and biological response in pulmonary fibrosis, with a focus on the progression of damage in the fibrotic lung during spontaneous breathing and assisted ventilatory support.

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 PaO 2 /FiO 2 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] cmH 2 O versus 11.4 [10.3–14.6] cmH 2 O, 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.

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 PaO 2 /FiO 2 ratio). Three PEEP levels (zero =  ZEEP , 4–8 cmH 2 O =  PEEP LOW , and titrated to achieve positive end-expiratory transpulmonary pressure P L,EE  =  PEEP TITRATED ) were used for measurements. Results Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median P L,EE at ZEEP was − 4.3 [− 7.6– − 2.3] cmH 2 O and lung elastance ( E L ) 44 [40–51] cmH 2 O/L. At PEEP LOW , P L,EE remained negative and E L did not change ( p  = 0.995) versus ZEEP. At PEEP TITRATED , P L,EE increased to 0.8 [0.3–1.5] cmH 2 O and E L to 49 [43–59] ( p  = 0.004 and p  < 0.001 compared to ZEEP and PEEP LOW , respectively). Δ P L decreased at PEEP LOW ( p  = 0.018) and increased at PEEP TITRATED ( p  = 0.003). In matched ARDS control PEEP titration to obtain a positive P L,EE did not result in significant changes in E L and Δ P L . Conclusions In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive P L,EE significantly worsened lung mechanics.

Mechanical Ventilation (MV) is a critical medical intervention used to support patients with impaired lung function caused by severe conditions such as pneumonia or COVID‐19. Model‐based Methods, particularly computational models, are employed to simulate and analyze lung mechanics under MV. Among these, the Single Compartment Lung Model (SCLM) remains the most commonly adopted framework for replicating lung behavior during MV, facilitating optimal treatment strategies. This review critically analyzes existing literatures on SCLM applications, focusing on key parameters such as lung elastance (E), airway resistance (Rrs), and Dynamic Functional Residual Capacity (dFRC). Methodologies, evaluation metrics, and clinical applications were examined to identify common trends, inconsistences, and research gaps. The findings indicate that E has been the primary focus due to its relevance in assessing lung mechanism, especially under MV. This parameter often evaluated alongside variables like Positive End‐Expiratory Pressure (PEEP), Peak Inspiratory Pressure (PIP), Peak Inspiratory Volume (PIV), and Tidal Volume (Vt). Additionally, FRC and Rrs are also considered in some models. The review emphasizes the need for standardized evaluation protocols, simplified input models, and disease‐specific adaptations to enhance clinical applicability. Our findings provide valuable guidance for future research aiming to refine SCLM‐based approaches and improve personalized mechanical ventilation strategies.

Lung fibrosis (LF) is a chronic and progressive lung disease characterized by pulmonary parenchyma progressive lesion, inflammatory infiltration, and interstitial fibrosis. It is developed by excessive collagen deposition and other cellular matrix components, resulting in severe changes in the alveolar architecture. Considering the absence of effective treatment, the aim of this study was to investigate the effect of photobiomodulation therapy (PBMT) on the development of PF. For this purpose, we used C57BL6 mice subjected to induction of LF by bleomycin administration (1.5 U/kg) by orotracheal route and, after 14 days of the induction, mice were treated with PBMT applied to the thorax 1×/day for 8 days (wavelength 660 ± 20 nm, power 100 mW, radiant exposure 5 J/cm 2 , irradiance 33.3 mW/cm 2 , spot size 2.8cm 2 , total energy 15 J, time of irradiation: 150 s) and inflammatory and fibrotic parameters were evaluated with or without PBMT. Our results showed that PBMT significantly reduced the number of inflammatory cells in the alveolar space, collagen production, interstitial thickening, and static and dynamic pulmonary elastance. In addition, we observed reduced levels of IL-6 e CXCL1/KC released by pneumocytes in culture as well as reduced level of CXCL1/KC released by fibroblasts in culture. We can conclude that the PBMT improves both inflammatory and fibrotic parameters showing a promising therapy which is economical and has no side effects.

Background Even through narrowing of the upper-airway plays an important role in the generation of obstructive sleep apnea (OSA), the peripheral airways is implicated in pre-obese and obese OSA patients, as a result of decreased lung volume and increased lung elastic recoil pressure, which, in turn, may aggravate upper-airway collapsibility. Methods A total of 263 male ( n  = 193) and female ( n  = 70) subjects who were obese to various degrees without a history of lung diseases and an expiratory flow limitation, but troubled with snoring or suspicion of OSA were included in this cross-sectional study. According to nocturnal-polysomnography the subjects were distributed into OSA and non-OSA groups, and were further sub-grouped by gender because of differences between males and females, in term of, lung volume size, airway resistance, and the prevalence of OSA among genders. Lung volume and respiratory mechanical properties at different-frequencies were evaluated by plethysmograph and an impulse oscillation system, respectively. Results Functional residual capacity (FRC) and expiratory reserve volume were significantly decreased in the OSA group compared to the non-OSA group among males and females. As weight and BMI in males in the OSA group were greater than in the non-OSA group (90 ± 14.8 kg vs. 82 ± 10.4 kg, p <  0.001; 30.5 ± 4.2 kg/m 2 vs. 28.0 ± 3.0 kg/m 2 , p <  0.001), multiple regression analysis was required to adjust for BMI or weight and demonstrated that these lung volumes decreases were independent from BMI and associated with the severity of OSA. This result was further confirmed by the female cohort. Significant increases in total respiratory resistance and decreases in respiratory conductance (Grs) were observed with increasing severity of OSA, as defined by the apnea-hypopnea index (AHI) in both genders. The specific Grs (sGrs) stayed relatively constant between the two groups in woman, and there was only a weak association between AHI and sGrs among man. Multiple-stepwise-regression showed that reactance at 5 Hz was highly correlated with AHI in males and females or hypopnea index in females, independently-highly correlated with peripheral-airway resistance and significantly associated with decreasing FRC. Conclusions Total respiratory resistance and peripheral airway resistance significantly increase, and its inverse Grs decrease, in obese patients with OSA in comparison with those without OSA, and are independently associated with OSA severity. These results might be attributed to the abnormally increased lung elasticity recoil pressure on exhalation, due to increase in lung elasticity and decreased lung volume in obese OSA.

Respiratory system modelling can assist clinicians in making clinical decisions during mechanical ventilation (MV) management in intensive care. However, there are some cases where the MV patients produce asynchronous breathing (asynchrony events) due to the spontaneous breathing (SB) effort even though they are fully sedated. Currently, most of the developed models are only suitable for fully sedated patients, which means they cannot be implemented for patients who produce asynchrony in their breathing. This leads to an incorrect measurement of the actual underlying mechanics in these patients. As a result, there is a need to develop a model that can detect asynchrony in real-time and at the bedside throughout the ventilated days. This paper demonstrates the asynchronous event detection of MV patients in the ICU of a hospital by applying a developed extended time-varying elastance model. Data from 10 mechanically ventilated respiratory failure patients admitted at the International Islamic University Malaysia (IIUM) Hospital were collected. The results showed that the model-based technique precisely detected asynchrony events (AEs) throughout the ventilation days. The patients showed an increase in AEs during the ventilation period within the same ventilation mode. SIMV mode produced much higher asynchrony compared to SPONT mode (p < 0.05). The link between AEs and the lung elastance (AUC Edrs) was also investigated. It was found that when the AEs increased, the AUC Edrs decreased and vice versa based on the results obtained in this research. The information of AEs and AUC Edrs provides the true underlying lung mechanics of the MV patients. Hence, this model-based method is capable of detecting the AEs in fully sedated MV patients and providing information that can potentially guide clinicians in selecting the optimal ventilation mode of MV, allowing for precise monitoring of respiratory mechanics in MV patients.

Management of ALI/ARDS involves supportive ventilation at low tidal volumes ( V t ) to minimize the rate at which ventilator induced lung injury (VILI) develops while the lungs heal. However, we currently have few details to guide the minimization of VILI in the ALI/ARDS patient. The goal of the present study was to determine how VILI progresses with time as a function of the manner in which the lung is ventilated in mice. We found that the progression of VILI caused by over-ventilating the lung at a positive end-expiratory pressure of zero is accompanied by progressive increases in lung stiffness as well as the rate at which the lung derecruits over time. We were able to accurately recapitulate these findings in a computational model that attributes changes in the dynamics of recruitment and derecruitment to two populations of lung units. One population closes over a time scale of minutes following a recruitment maneuver and the second closes in a matter of seconds or less, with the relative sizes of the two populations changing as VILI develops. This computational model serves as a basis from which to link the progression of VILI to changes in lung mechanical function.

Background Prone position is used to recruit collapsed dependent lung regions during severe acute respiratory distress syndrome, improving lung elastance and lung gas content. We hypothesised that, in the absence of recruitment, prone position would not result in any improvement in lung mechanical properties or gas content compared to supine position. Methods Ten healthy pigs under general anaesthesia and paralysis underwent a pressure–volume curve of the respiratory system, chest wall and lung in supine and prone positions; the respective elastances were measured. A lung computed tomography (CT) scan was performed in the two positions to compute gas content (i.e. functional residual capacity (FRC)) and the distribution of aeration. Recruitment was defined as a percentage change in non-aerated lung tissue compared to the total lung weight. Results Non-aerated (recruitable) lung tissue was a small percentage of the total lung tissue weight in both positions (4 ± 3 vs 1 ± 1 %, supine vs prone, p  = 0.004). Lung elastance decreased (20.5 ± 1.8 vs 15.5 ± 1.6 cmH 2 O/l, supine vs prone, p  < 0.001) and functional residual capacity increased (380 ± 82 vs 459 ± 60 ml, supine vs prone, p  = 0.025) in prone position; specific lung elastance did not change (7.0 ± 0.5 vs 6.5 ± 0.5 cmH 2 O, supine vs prone, p  = 0.24). Lung recruitment was low (3 ± 2 %) and was not correlated to increases in functional residual capacity ( R 2 0.2, p  = 0.19). A higher amount of well-aerated and a lower amount of poorly aerated lung tissue were found in prone position. Conclusions In healthy pigs, prone position ameliorates lung mechanical properties and increases functional residual capacity independently from lung recruitment, through a redistribution of lung aeration.

Background We have shown in acute lung injury patients that lung elastance can be determined by a positive end-expiratory pressure (PEEP) step procedure and proposed that this is explained by the spring-out force of the rib cage off-loading the chest wall from the lung at end-expiration. The aim of this study was to investigate the effect of the expanding chest wall on pleural pressure during PEEP inflation by building a model with an elastic recoiling lung and an expanding chest wall complex. Methods Test lungs with a compliance of 19, 38, or 57 ml/cmH 2 O were placed in a box connected to a plastic container, 3/4 filled with water, connected to a water sack of 10 l, representing the abdomen. The space above the water surface and in the lung box constituted the pleural space. The contra-directional forces of the recoiling lung and the expanding chest wall were obtained by evacuating the pleural space to a negative pressure of 5 cmH 2 O. Chest wall elastance was increased by strapping the plastic container. Pressure was measured in the airway and pleura. Changes in end-expiratory lung volume (ΔEELV), during PEEP steps of 4, 8, and 12 cmH 2 O, were determined in the isolated lung, where airway equals transpulmonary pressure and in the complete model as the cumulative inspiratory-expiratory tidal volume difference. Transpulmonary pressure was calculated as airway minus pleural pressure. Results Lung pressure/volume curves of an isolated lung coincided with lung P/V curves in the complete model irrespective of chest wall stiffness. ΔEELV was equal to the size of the PEEP step divided by lung elastance (EL), ΔEELV = ΔPEEP/EL. The end-expiratory “pleural” pressure did not increase after PEEP inflation, and consequently, transpulmonary pressure increased as much as PEEP was increased. Conclusions The rib cage spring-out force causes off-loading of the chest wall from the lung and maintains a negative end-expiratory “pleural” pressure after PEEP inflation. The behavior of the respiratory system model confirms that lung elastance can be determined by a simple PEEP step without using esophageal pressure measurements.