A research study is conducted to evaluate the effects of various serum proteins in health and disease states. Healthy volunteers and patients with various medical conditions are recruited. In an experiment, purified insoluble elastin is exposed to stimulated neutrophils, which results in the degradation of the elastin molecules into smaller peptides. This process can be inhibited by adding serum from healthy volunteers but not from a specific patient population. Which of the following is the strongest recommendation for patients in this specific population?

Question

A research study is conducted to evaluate the effects of various serum proteins in health and disease states.  Healthy volunteers and patients with various medical conditions are recruited.  In an experiment, purified insoluble elastin is exposed to stimulated neutrophils, which results in the degradation of the elastin molecules into smaller peptides.  This process can be inhibited by adding serum from healthy volunteers but not from a specific patient population.  Which of the following is the strongest recommendation for patients in this specific population?

Quizplus · Accepted Answer

Neutrophil elastase is released by both neutrophils and macrophages and is the primary protease responsible for extracellular elastin degradation. The major serum inhibitor of elastase is alpha-1 antitrypsin (AAT). In this study, the patients whose serum is unable to inhibit elastin degradation likely have AAT deficiency, a condition characterized by early-onset panacinar emphysema due to the unopposed action of neutrophil elastase on alveolar walls. Tobacco exposure dramatically accelerates the development of emphysema in patients with AAT deficiency by inducing inflammation (increasing neutrophil and macrophage activation) and permanently inactivating the already low quantities of AAT through oxidation of a crucial methionine residue. Therefore, patients with AAT deficiency should be counseled to avoid smoking and exposure to second-hand smoke. (Choice A) Patients with hypertrophic cardiomyopathy are at risk for sudden cardiac arrest with exertion and are typically counseled to avoid participation in most competitive sports. (Choice B) Patients with chronic granulomatous disease (impaired phagocytic intracellular killing due to a defect in nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) should avoid certain immunosuppressive agents (eg, tumor necrosis factor-alpha blockers) due to risk of overwhelming infection. (Choice D) Periodic aortic diameter monitoring is indicated in patients with Marfan syndrome (impaired fibrillin synthesis), who are at risk for both aortic dissection and chronic aortic regurgitation due to aortic root dilation. (Choice E) Patients with osteogenesis imperfecta (decreased production of type 1 collagen) are at high risk of developing osteoporosis and should undergo regular bone density monitoring. (Choice F) Patients with Ehlers-Danlos syndrome (impaired collagen synthesis) are at risk for scleral fragility, ocular globe rupture, and retinal detachment and should undergo routine ophthalmologic exams. Educational objective: The major serum inhibitor of extracellular elastase is alpha-1 antitrypsin (AAT); patients with AAT deficiency typically develop early-onset panacinar emphysema due to unchecked elastase activity. Exposure to tobacco smoke dramatically accelerates the development of emphysema in patients with AAT deficiency and should be avoided. __________ References: Diagnosis and management of patients with a1-antitrypsin (A1AT) deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/22200689) Alpha-1 antitrypsin deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/20303723)

A Research Study Is Conducted to Evaluate the Effects of Various