Cellular senescence is a state of permanent cell cycle arrest triggered by various intrinsic and extrinsic stressors. Cellular senescence results in impaired tissue repair and remodeling, loss of physiological integrity, organ dysfunction, and changes in the secretome. The systemic accumulation of senescence cells has been observed in many age-related diseases. Likewise, cellular senescence has been implicated as a risk factor and driving mechanism in chronic obstructive pulmonary disease (COPD) pathogenesis. Airway epithelium exhibits hallmark features of senescence in COPD including activation of the p53/p21WAF1/CIP1 and p16INK4A/RB pathways, leading to cell cycle arrest. Airway epithelial senescent cells secrete an array of inflammatory mediators, the so-called senescence-associated secretory phenotype (SASP), leading to a persistent low-grade chronic inflammation in COPD. SASP further promotes senescence in an autocrine and paracrine manner, potentially contributing to the onset and progression of COPD. In addition, cellular senescence in COPD airway epithelium is associated with telomere dysfunction, DNA damage, and oxidative stress. This review discusses the potential mechanisms of airway epithelial cell senescence in COPD, the impact of cellular senescence on the development and severity of the disease, and highlights potential targets for modulating cellular senescence in airway epithelium as a potential therapeutic approach in COPD.

SARS-CoV-2 binds to ACE2 receptors, expressed within the lungs. Risk factors for hospitalization include hypertension, diabetes, ischaemic heart disease and obesity–conditions linked by the presence of endothelial pathology. Viral infection in this setting causes increased conversion of circulating Factor XII to its active form (FXIIa). This is the first step in the contact-kinin pathway, leading to synchronous activation of the intrinsic coagulation cascade and the plasma Kallikrein-Kinin system, resulting in clotting and inflammatory lung disease. Temporal trends are evident from blood results of hospitalized patients. In the first week of symptoms the activated partial thromboplastin time (APTT) is prolonged. This can occur when clotting factors are consumed as part of the contact (intrinsic) pathway. Platelet counts initially fall, reflecting their consumption in coagulation. Lymphopenia occurs after approximately 1 week, reflecting the emergence of a lymphocytic pneumonitis [COVID-19 acute respiratory distress syndrome (ARDS)]. Intrinsic coagulation also induces the contact-kinin pathway of inflammation. A major product of this pathway, bradykinin causes oedema with ground glass opacities (GGO) on imaging in early COVID-19. Bradykinin also causes release of the pleiotrophic cytokine IL-6, which causes lymphocyte recruitment. Thromobosis and lymphocytic pneumonitis are hallmark features of COVID-19 ARDS. In this review we examine the literature with particular reference to the contact-kinin pathway. Measurements of platelets, lymphocytes and APTT should be undertaken in severe infections to stratify for risk of developing ARDS.