Mechanistic Understanding of Lung Inflammation: Recent Advances and Emerging Techniques

Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury characterized by an acute inflammatory response in the lung parenchyma. Hence, it is considered as the most appropriate clinical syndrome to study pathogenic mechanisms of lung inflammation. ARDS is associated with increased morbidity and mortality in the intensive care unit (ICU), while no effective pharmacological treatment exists. It is very important therefore to fully characterize the underlying pathobiology and the related mechanisms, in order to develop novel therapeutic approaches. In vivo and in vitro models are important pre-clinical tools in biological and medical research in the mechanistic and pathological understanding of the majority of diseases. In this review, we will present data from selected experimental models of lung injury/acute lung inflammation, which have been based on clinical disorders that can lead to the development of ARDS and related inflammatory lung processes in humans, including ventilation-induced lung injury (VILI), sepsis, ischemia/reperfusion, smoke, acid aspiration, radiation, transfusion-related acute lung injury (TRALI), influenza, Streptococcus (S.) pneumoniae and coronaviruses infection. Data from the corresponding clinical conditions will also be presented. The mechanisms related to lung inflammation that will be covered are oxidative stress, neutrophil extracellular traps, mitogen-activated protein kinase (MAPK) pathways, surfactant, and water and ion channels. Finally, we will present a brief overview of emerging techniques in the field of omics research that have been applied to ARDS research, encompassing genomics, transcriptomics, proteomics, and metabolomics, which may recognize factors to help stratify ICU patients at risk, predict their prognosis, and possibly, serve as more specific therapeutic targets.

Keywords: acute respiratory distress syndrome; biomarkers; lung inflammation; mechanisms; omics.

Figure 1

Key mechanisms of lung injury that contribute to the progression of acute lung inflammation/acute respiratory distress syndrome (ARDS).

Figure 2

Emerging techniques in lung injury. The application of emerging high throughput techniques that analyze DNA (genomics) and its modifications (epigenomics), RNA (transcriptomics), proteins (proteomics), metabolites (metabolomics), microbiomes (metagenomics), and systems (multiomics) could provide important information for the stratification of critically ill patients, in terms of risk evaluation, prognosis prediction, and guidance for novel therapeutic approaches.