Discussion P W5 Reply to peer 2-1

Emphysema, a hallmark of chronic obstructive pulmonary disease, is primarily caused by prolonged exposure to cigarette smoke, which leads to irreversible alveolar damage. Smoking initiates an inflammatory response characterized by increased neutrophils and macrophages, which release proteolytic enzymes such as elastase and matrix metalloproteinases (Barnes et al., 2020). These enzymes degrade elastin, an essential component of alveolar walls, resulting in the destruction of alveolar septa and the formation of enlarged air spaces. This structural damage reduces alveolar surface area, impairing gas exchange and leading to ventilation-perfusion mismatch. Additionally, smoking-induced oxidative stress further exacerbates lung injury by depleting protective antioxidants like glutathione, amplifying inflammation, and inducing apoptosis in epithelial and endothelial cells (Aghapour et al., 2021). Over time, emphysema results in progressive airflow limitation, hyperinflation, and reduced lung compliance, contributing to dyspnea and decreased exercise tolerance.

     β-Agonists are central to managing diseases with increased airway resistance, such as asthma and COPD. These drugs, primarily short-acting such as, albuterol and long-acting such as, salmeterol and formoterol, stimulate β2-adrenergic receptors on airway smooth muscle cells, leading to cyclic adenosine monophosphate activation and smooth muscle relaxation (Rabe & Celli, 2022). By reducing bronchoconstriction, β-agonists improve airflow and alleviate symptoms of wheezing and dyspnea. In addition to bronchodilation, these agents may modulate airway inflammation by inhibiting the release of pro-inflammatory mediators from mast cells and cytokines from immune cells. Their therapeutic role is particularly crucial in COPD, where chronic inflammation and mucus hypersecretion contribute to airway obstruction. Long-acting β-agonists, often combined with inhaled corticosteroids, enhance symptom control, reduce exacerbations, and improve quality of life for patients with obstructive lung diseases.

References

Aghapour, M., Raee, P., Moghaddam, S. J., Hiemstra, P. S., & Smit, J. J. (2021). Airway epithelial barrier dysfunction in chronic obstructive pulmonary disease: Role of cigarette smoke exposure. American Journal of Respiratory Cell and Molecular Biology, 64(2), 163-174. https://doi.org/10.1165/rcmb.2020-0244TR

Barnes, P. J., Baker, J., & Donnelly, L. E. (2020). Cellular senescence as a mechanism and target in chronic lung diseases. Nature Reviews Immunology, 20(12), 707-721. https://doi.org/10.1038/s41577-020-0370-1

Rabe, K. F., & Celli, B. R. (2022). Pharmacological treatment of chronic obstructive pulmonary disease: The ABCD revised. European Respiratory Journal, 59(2), 2100939. https://doi.org/10.1183/13993003.00939-2021