2023/11/01 by Camilla Predella, Daniela Iezza, Michael L. Miller +5
Medicine · #Chronic Obstructive Pulmonary Disease (COPD) Research #Neonatal Respiratory Health Research #Respiratory Support and Mechanisms
paper · doi:10.1165/rcmb.2023-0182le
openalex publication_date 2023/11/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Histological evidence of tissue injury is considered the most relevant defining feature of experimental acute lung injury (ALI).In humans, ALI/acute respiratory distress syndrome (ARDS) criteria follow the 2012 Berlin definition (1): 1) a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 ) <300 mm Hg while receiving invasive or noninvasive ventilation with a tight-fitting mask and positive end-expiratory pressure or continuous positive airway pressure of at least 5 cm H 2 O; 2) three severity levels of initial arterial hypoxemia (categories of PaO 2 /FiO 2 ratio of <100 mm Hg [severe], 101-200 mm Hg [moderate], and 201-300 mm Hg [mild]), which correlate with mortality (45%, 35%, and 27%, respectively); 3) timing (respiratory failure should have developed within 1 week of a known clinical insult); 4) inability of cardiac failure to fully explain respiratory failure; and 5) radiological evidence of diffuse bilateral pulmonary infiltrates.However, these criteria cannot be directly translated to laboratory animals, especially to small animals.Furthermore, although arterial blood gas analysis, chest radiography, and other ancillary tests can be performed on some animal models, not all laboratories are equipped for these techniques, or their application on an experimental group with many animals is impractical.Thus, the 2011 American Thoracic Society (ATS) workshop report on features and measurements of experimental acute lung injury in animals (2) and the 2022 update (3) emphasized that histological features remain the most relevant feature of ALI, and these should be assessed in a rigorous manner.In 2011, ATS committee proposed a lung injury scoring (LIS) system to histologically quantify five parameters (alveolar space neutrophils, interstitial neutrophils, hyaline membranes, proteinaceous debris, and septal thickening) in at least 20 random high-power fields (total magnification 4003) with at least 1 high-power field distance between regions of interest (ROIs) and at least 50% of each field occupied by lung alveoli (2).The committee also suggested conditions for preparing lung tissues under physiologic pressure parameters of perfusion and inflation (2, 4).Since the 2011 report (2), LIS has been applied in several studies involving different species, including mouse (5-7), rat (8, 9), pig (10, 11), monkey (12), and human (13).In the 2022 update (3), participants were surveyed after the meeting regarding how histological injury should be quantified, and 57% respondents reaffirmed the 2011 parameters of blinded assessment in several nonoverlapping fields.Although we agree with