A 65-year-old man comes to the office due to a 6-month history of exertional dyspnea. Over the past few weeks he has also developed a nonproductive cough. Medical history is notable for hypertension and hypercholesterolemia. The patient does not use tobacco, alcohol, or illicit drugs. Temperature is 36.9 C (98.4 F), blood pressure is 130/80 mm Hg, pulse is 80/min, and respirations are 18/min. Examination shows late inspiratory crackles in both lung bases and mild digital clubbing. The patient undergoes lung biopsy; histologic examination shows areas of interstitial inflammation, foci of proliferating fibroblasts, dense collagen fibrosis, and honeycomb changes. The interstitial inflammation is patchy and consists of a lymphoplasmacytic infiltrate in the alveolar septa associated with hyperplasia of type 2 pneumocytes. Pharmacotherapy aimed at which of the following is most helpful in treating this patient's lung condition?

Question

A 65-year-old man comes to the office due to a 6-month history of exertional dyspnea.  Over the past few weeks he has also developed a nonproductive cough.  Medical history is notable for hypertension and hypercholesterolemia.  The patient does not use tobacco, alcohol, or illicit drugs.  Temperature is 36.9 C (98.4 F), blood pressure is 130/80 mm Hg, pulse is 80/min, and respirations are 18/min.  Examination shows late inspiratory crackles in both lung bases and mild digital clubbing.  The patient undergoes lung biopsy; histologic examination shows areas of interstitial inflammation, foci of proliferating fibroblasts, dense collagen fibrosis, and honeycomb changes.  The interstitial inflammation is patchy and consists of a lymphoplasmacytic infiltrate in the alveolar septa associated with hyperplasia of type 2 pneumocytes.  Pharmacotherapy aimed at which of the following is most helpful in treating this patient's lung condition?

Quizplus · Accepted Answer

This patient with progressive dyspnea, dry cough, digital clubbing, and crackles on examination has signs of an interstitial lung disease. The histologic findings of patchy lymphoplasmacytic infiltrates, focal fibroblastic proliferation, areas of dense fibrosis and honeycombing, and hyperplasia of type 2 pneumocytes are highly suggestive of idiopathic pulmonary fibrosis (IPF). IPF is a chronic, progressive fibrotic lung disease thought to be due to recurrent episodes of lung injury and disordered healing. Persistent inflammation likely triggers excessive activity of growth factors normally involved in wound healing, including transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), fibroblastic growth factor (FGF), and vascular endothelial growth factor (VEGF). This leads to increased fibroblast activity, myofibroblast formation, and collagen production, which contribute to pulmonary fibrosis. Pirfenidone is an antifibrotic agent that inhibits TGF-β; another treatment option is nintedanib, a tyrosine kinase inhibitor that inhibits PDGF, FGF, and VEGF. Although neither drug is curative, these therapies have been shown to slow progressive fibrosis in patients with IPF. (Choice A) Alpha-1 antitrypsin infusion is used to treat patients with alpha-1 antitrypsin deficiency, which causes panacinar emphysema and typically presents in young patients with dyspnea and cough. Histologic findings in emphysema include large alveoli with thin septa. (Choice B) Endothelin-1 inhibitors (eg, ambrisentan, bosentan) are used to treat idiopathic pulmonary hypertension. Histologic findings of pulmonary hypertension include pulmonary vascular media and intima hypertrophy and intimal fibrosis. (Choice C) Monoclonal antibodies directed at interleukin-5 (eg, reslizumab) inhibit eosinophil recruitment and proliferation, and are used in patients with severe eosinophilic asthma. Histologic findings in asthma include goblet cell hyperplasia, bronchial smooth muscle hypertrophy, edema, eosinophilia, and Charcot-Leyden crystals. (Choice D) Phosphodiesterase-4 inhibitors (ie, roflumilast) block the degradation of cyclic AMP, leading to reduced airway inflammation and smooth muscle relaxation in patients with chronic obstructive pulmonary disease. Histologic findings include both airspace enlargement with thin septa (emphysema) and goblet cell hyperplasia with excess mucus production (chronic bronchitis). Educational objective: Histologic findings of idiopathic pulmonary fibrosis include patchy lymphoplasmacytic infiltrates, focal fibroblastic proliferation with dense fibrosis, honeycombing, and hyperplasia of type 2 pneumocytes. Therapies are directed at slowing the progression of fibrosis by inhibiting transforming growth factor-beta and other fibrogenic growth factors (eg, PDGF, fibroblastic growth factor, and VEGF).

A 65-Year-Old Man Comes to the Office Due to a 6-Month