Sex susceptibility to ventilator-induced lung injury

Abstract

* Correspondence: [email protected] Instituto de Investigación Sanitaria del Principado de Asturias, Avda de Roma s/n, 33011 Oviedo, Spain Centro de investigación biomédica en Red-Enfermedades Respiratorias. Instituto de Salud Carlos III, Madrid, Spain Full list of author information is available at the end of the article To the editor, Avoidance of ventilator-induced lung injury (VILI), defined as the damage caused by the application of large pressures or volumes to the lung parenchyma, is one of the main objectives of contemporary ventilatory management. This specific form of injury is triggered by a variety of molecular mechanisms involving mechanosensation and mechanotransduction of physical forces, inflammatory responses, activation of intracellular signals, extracellular matrix remodeling, and dysregulation of different forms of cell death. Among these, inflammation plays a key role in the induction of early damage, but also in later repair. In spite of this knowledge, no treatment aimed to reduce VILI based on these mechanisms has been translated into the clinical practice. The outcome of critically ill ventilated patients depends on the cause of the disease, the specific characteristics of the patient (including comorbidities), and the response to therapies and their consequences. The impact of VILI in outcome falls in this latter category. However, it is not known how previous baseline conditions and applied therapies interact. Sex is one of the main determinants of health and disease. It has been reported that males show worse intensive care unit (ICU) outcomes [1]. In the specific field of lung injury and mechanical ventilation, females may receive lung protective ventilation less frequently, due to miscalculation of target tidal volumes [2]. Some studies have reported higher incidence of acute respiratory distress syndrome (ARDS) [3] and mortality rates [4] and worse long-term outcomes [5] in mechanically ventilated women, but others have failed to confirm these results [6, 7]. The mechanisms behind these differences have been addressed in several experimental studies (reviewed in [8]). Male and female animals have different responses in models of respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, and fibrosis. The effects of sex hormones on inflammation and cell metabolism mediate the majority of these differences. The role of VILI in the difference in ICU outcome between sexes has not been addressed. Most of the experimental research has been conducted in male animals, discarding their female counterparts, and no study has compared male and female animals after mechanical ventilation. To address this question, we ventilated male and female C57BL/6 mice to induce a moderate lung injury (peak pressure 15 cmH2O, PEEP 0 cmH2O, respiratory rate 100 breaths/minute, inspiratory to expiratory ratio Intensive Care Medicine Experimental