A 62-year-old man comes to the office for evaluation of progressive exertional dyspnea. His medical history is significant for pneumonia and hypertension. He has a 45-pack-year smoking history. On physical examination, breath sounds are decreased bilaterally and wheezes are heard. A CT scan of the chest is shown below.
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Increased activity of which of the following cells is most likely responsible for the development of this patient's lung condition?
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This patient's heavy smoking history, exertional dyspnea, and dilated airspaces on CT scan are consistent with centriacinar emphysema.
The pathogenesis of smoking-induced emphysema involves oxidative injury to the respiratory bronchioles and activation of resident alveolar macrophages by components of cigarette smoke. This is followed by inflammatory recruitment of neutrophils into the affected airspaces. Activated macrophages and neutrophils release proteases, including elastase and others (eg, cathepsins, matrix metalloproteinases), that degrade the extracellular matrix; they also generate oxygen free radicals that impair the function of protease inhibitors (eg, alpha-1 antitrypsin).
The resultant protease-antiprotease imbalance leads to acinar wall destruction and irreversible airspace dilation distal to the terminal bronchioles. Excess protease activity is also involved in panacinar emphysema, such as occurs with alpha-1 antitrypsin deficiency.
(Choice A) Club cells are nonciliated, secretory constituents of the terminal respiratory epithelium. They secrete club cell secretory protein and surfactant components and also help detoxify inhaled substances (eg, tobacco smoke) by a cytochrome P450 mechanism.
(Choice B) Eosinophils play an important role in the late-phase component of Type I immediate hypersensitivity reactions. In the lung, they are recruited to help sustain the localized inflammatory response that follows exposure to allergens.
(Choice C) Interstitial pulmonary mast cells play a central role in the pathogenesis of allergic asthma by releasing histamine and leukotrienes that induce bronchospasm.
(Choice E) Type I pneumocytes constitute >95% of the inner epithelial lining of the alveoli. In emphysema, these cells are destroyed by the acinar wall damage inflicted by neutrophils and other inflammatory cells.
(Choice F) Type II pneumocytes are the source of pulmonary surfactant and the main cell type responsible for repair of alveolar epithelium after destruction of Type I pneumocytes.
Educational objective:
The pathogenesis of centriacinar emphysema associated with chronic, heavy smoking predominantly involves the release of proteases, especially elastase, from infiltrating neutrophils and alveolar macrophages.