Reading III
Respiratory diseases cover a broad spectrum, from upper respiratory tract infections to serious conditions
like chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis (PF), acute respiratory distress
syndrome (ARDS), acute lung injury (ALI), lung ischemia–reperfusion injury (LIRI), pulmonary hypertension
(PH), and lung cancer. These conditions, characterized by structural changes in airway and lung tissues and
reduced respiratory function, pose significant health and economic burdens worldwide. Notably, COVID-19
caused 18 million deaths between 2020 and 2021, further emphasizing the global challenge of respiratory
diseases.
COPD is the third leading cause of death globally, while ARDS and ALI account for no less than 4% of
U.S. hospitalizations annually. Lung cancer, leading in cancer-related deaths, saw 2.24 million new cases and 1.8 million fatalities in 2020, as reported by the International Agency for Research on Cancer. Risk factors
include smoking, air pollution, infections, and obesity. Despite the availability of treatments like antibiotics and
lung transplants, their side effects have prompted the search for innovative therapeutic approaches.
First introduced by Dixon et al. in 2012, ferroptosis is a form of programmed cell death (PCD), a term
distinct from other modes of cell death such as necrosis, apoptosis, autophagy, necroptosis, and pyroptosis,
which is essential for maintaining homeostatic balance. Morphologically, ferroptosis features mitochondrial
shrinkage, denser membranes, and reduced mitochondrial cristae, with an intact cell membrane and normalsized nucleus without chromatin condensation. Biochemically, ferroptosis is triggered by the depletion of
intracellular glutathione (GSH) and a decrease in the activity of glutathione peroxidase 4 (GPX4). This
imbalance leads to lipid peroxidation, further exacerbated by Fe2+ through the Fenton reaction, generating a
high concentration of reactive oxygen species (ROS). 【題組】49. Which of the following is NOT listed as a risk factor for respiratory diseases in the passage?
(A) Smoking
(B) High blood pressure
(C) Air pollution
(D) Obesity
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