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.

Keywords: acute lung injury; acute respiratory distress syndrome; aging; biomarkers; immunosenescence.

Figure 1

Age-associated changes in the ARDS lung. The aged alveolus in acute respiratory distress syndrome (ARDS) demonstrates a number of age-related changes in the alveolar epithelium, vasculature and immune cells that may contribute to disease pathogenesis in elderly patients. Vascular permeability may be affected by changes in angiopoietin-2 (Ang-2) expression and receptor for advanced glycation end products (RAGE) signaling is associated with inflammation and progression of the exudative and fibroproliferative phases of ARDS. Accumulation of senescent cells and the senescence-associated secretory phenotype (SASP) results in the release of soluble pro-inflammatory mediators such as IL-6 and IL-8. Although increased levels of inflammatory factors are observed, neutrophils and macrophages may have attenuated functional activities. AT1, alveolar type I; ATII, alveolar type II; NET, neutrophil extracellular trap; tPA, tissue plasminogen activator.