In this review, we discuss the role of pulmonary surfactant in the host defense against respiratory pathogens, including novel coronavirus SARS-CoV-2. In the lower respiratory system, the virus uses angiotensin-converting enzyme 2 (ACE2) receptor in conjunction with serine protease TMPRSS2, expressed by alveolar type II (ATII) cells as one of the SARS-CoV-2 target cells, to enter. ATII cells are the main source of surfactant. After their infection and the resulting damage, the consequences may be severe and may include injury to the alveolar-capillary barrier, lung edema, inflammation, ineffective gas exchange, impaired lung mechanics and reduced oxygenation, which resembles acute respiratory distress syndrome (ARDS) of other etiology. The aim of this review is to highlight the key role of ATII cells and reduced surfactant in the pathogenesis of the respiratory form of COVID-19 and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS patients.
The development of acute respiratory distress syndrome (ARDS) is known to be independently attributable to aspiration-induced lung injury. Mechanical ventilation as a high pressure/volume support to maintain sufficient oxygenation of a patient could initiate ventilator-induced lung injury (VILI) and thus contribute to lung damage. Although these phenomena are rare in the clinic, they could serve as the severe experimental model of alveolar-capillary membrane deterioration. Lung collapse, diffuse inflammation, alveolar epithelial and endothelial damage, leakage of fluid into the alveoli, and subsequent inactivation of pulmonary surfactant, leading to respiratory failure. Therefore, exogenous surfactant could be considered as a therapy to restore lung function in experimental ARDS. This study aimed to investigate the effect of modified porcine surfactant in animal model of severe ARDS (P/F ratio ≤13.3 kPa) induced by intratracheal instillation of hydrochloric acid (HCl, 3 ml/kg, pH 1.25) followed by VILI (VT 20 ml/kg). Adult rabbits were divided into three groups: untreated ARDS, model treated with a bolus of poractant alfa (Curosurf®, 2.5 ml/kg, 80 mg phospholipids/ml), and healthy ventilated animals (saline), which were oxygen-ventilated for an additional 4 h. The lung function parameters, histological appearance, degree of lung edema and levels of inflammatory and oxidative markers in plasma were evaluated. Whereas surfactant therapy with poractant alfa improved lung function, attenuated inflammation and lung edema, and partially regenerated significant changes in lung architecture compared to untreated controls. This study indicates a potential of exogenous surfactant preparation in the treatment of experimental ARDS.
The recently reported differences between pulmonary and extrapulmonary acute respiratory distress syndromes (ARDSp, ARDSexp) are the main reasons of scientific discussion on potential differences in the effects of current ventilatory strategies. The aim of this study is to assess whether the presence of ARDSp or ARDSexp can differently affect the beneficial effects of high-frequency oscillatory ventilation (HFOV) upon physiological and clinical parameters. Thirty adults fulfilling the ARDS criteria were indicated for HFOV in case of failure of conventional
ventilation strategy. According to the ARDS type, each patient was included either in the group of patients with ARDSpor ARDSexp. Six hours after normocapnic HFOV introduction, there was no significant increase in PaO
2/FIO2 in ARDSpgroup (from 129±47 to 133±50 Torr), but a significant improvement was found in ARDSexp (from 114±54 to 200±65 Torr, p<0.01). Despite the insignificant difference in the latest mean airway pressure (MAP) on conventional mechanical ventilation (CMV) between both groups, initial optimal continuous distension pressure (CDP) for the best
PaO2/FIO2 during HFOV was 2.0±0.6 kPa in ARDSp and 2.8±0.6 kPa in ARDS
exp (p<0.01). HFOV recruits and thus it is more effective in ARDSexp. ARDS
exp patients require higher CDP levels than ARDSp patients. The testing period for positive effect of HFOV is recommended not to be longer than 24 hours.