The Impact of Aging in Acute Respiratory Distress Syndrome: A Clinical and Mechanistic Overview

Abstract

Acute respiratory distress syndrome (ARDS) is associated with increased morbidity and mortality in the elderly population (≥65 years of age). Additionally, age is widely reported as a risk factor for the development of ARDS. However, the underlying pathophysiological mechanisms behind the increased risk of developing, and increased severity of, ARDS in the elderly population are not fully understood. This is compounded by the significant heterogeneity observed in patients with ARDS. With an aging population worldwide, a better understanding of these mechanisms could facilitate the development of therapies to improve outcomes in this population. In this review, the current clinical evidence of age as a risk factor and prognostic indicator in ARDS and the potential underlying mechanisms that may contribute to these factors are outlined. In addition, research on age-dependent treatment options and biomarkers, as well as future prospects for targeting these underlying mechanisms, are discussed.

Evidence That SARS-CoV-2 Induces Lung Cell Senescence: Potential Impact on COVID-19 Lung Disease

“…Thus, counteracting the cell senescence process or eliminating senescent lung cells might lessen lung damage severity. This may be of therapeutic importance as strategies are now proposed to control senescence in various lung diseases, as well as in acute respiratory distress syndrome due to other causes ( 13 , 14 ). A recent study in mice showed that lung inflammation caused by a mouse β-coronavirus was markedly reduced by senolytic treatment, which also decreased mortality in old mice ( 7 ).…”

Donor factors and risk of primary graft dysfunction and mortality post lung transplantation: A proposed conceptual framework

“…Thus, an independent association between the development PGD and donor age remains unclear. More studies will be required, but it is difficult to ignore the possibility that donor age is relevant, especially considering that increasing age is associated with enhanced susceptibility to ARDS 29,30 …”

Acute Respiratory Distress Syndrome: Focus on Viral Origin and Role of Pulmonary Lymphatics

“…Chemotaxis, phagocytosis, microbial killing, and NET formation are impaired in neutrophils of older individuals. Further, endothelial permeability regulated by Ang2 is higher in older lungs and NADPH oxidase 4 (ROS production) upregulated [ 7 ]. Animal data showed higher CD80 and CD86 expression upon lipopolysaccharide (LPS) challenge in older mice and increased MIF-1α levels, whereas antigen presentation and bacterial and viral clearance were decreased.…”

“…The incidence of ARDS is lower in 15–19-year-old individuals (16/100,000 person-years) compared to 75–84-year-old persons (306/100,000 person-years) [ 6 ]. Among the hospitalized patients, there was, however, no clear difference regarding admission to ICU, ventilation length, and length of hospitalization between patients younger or older than 65 y [ 7 ]. Neonatal ARDS is due to immaturity of the lung, and standard treatment consists of the administration of an exogenous surfactant.…”