Mechanical ventilation and histological fibrosis in patients with acute respiratory distress syndrome undergoing open lung biopsy

Background: Mechanical ventilation is the most important support treatment for acute respiratory distress syndrome (ARDS); however, it brings with it the risk of ventilator-induced lung injury, which can lead to pulmonary fibrosis and prolonged mechanical ventilation. Our objective in this study was to examine the correlation between ventilator settings and histological fibrosis in ARDS patients. We also examined the impact of histological fibrosis on clinical outcomes and mortality. Methods: We performed a retrospective analysis of patients with ARDS who received open lung biopsy in a tertiary care referral center in Taiwan between March 2006 and December 2019. Mechanical ventilator settings were recorded at the time of ARDS diagnosis and on the day of biopsy. Results: A total of 68 ARDS patients who had received open lung biopsy with diffuse alveolar damage (DAD; the hallmark pathology of ARDS) were analyzed and stratified into non-fibrosis (n = 56) and fibrosis groups (n = 12). Mechanical power and airway pressures at the time of ARDS diagnosis and airway pressures on the day of biopsy were significantly higher in the fibrosis group than in the non-fibrosis group, and lung compliance on the day of biopsy was significantly lower. The duration of ventilator usage and time spent in the intensive care unit and hospital stay were all significantly higher in the fibrosis group. Hospital mortality was higher in the fibrosis than in the non-fibrosis group (67% vs. 57%, p = 0.748). In the fibrosis group, patients with AE-IPF (n = 5) received higher ventilator load and faced higher hospital mortality than DAD with fibrotic phase (n = 7) (80% vs. 57%, p = 0.242). A multivariable logistic regression model demonstrated that mechanical power at ARDS diagnosis and ARDS duration before biopsy were independently associated with histological fibrosis at open lung biopsy (odds ratio 1.493 [95% CI 1.014–2.200], p = 0.042; odds ratio 1.160 [95% CI 1.052–1.278], p = 0.003, respectively). Conclusions: Our findings indicate that prompt action aimed at staving off injurious mechanical stretching of lung parenchyma and subsequent progression to fibrosis may have a positive effect on clinical outcomes. Keywords: Mechanical ventilation, Acute respiratory distress syndrome, Open lung biopsy, Histology, Diffuse alveolar damage, Pulmonary fibrosis, Idiopathic pulmonary fibrosis, Outcomes