THE USMLE TIMES - #102
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Welcome to issue #102 of The USMLE Times! Welcome to all new members—and welcome back to those returning!
I’m Paul Ciurysek, MD, founder of The USMLE Guys, and this is The USMLE Times. This daily newsletter aims to provide super high-yield USMLE concepts commonly tested on exam day. All content is FREE! If you’d like to work with me and my team, please see the options at the bottom of today’s newsletter. If you’d like to support my efforts, please share the newsletter with a friend.
Here’s what’s on tap for issue #102 of the USMLE Times:
Question of the Week (Respiratory Pathology)
This week’s video training (5 Tips For a 250+ On CK)
Question deep-dive & breakdown
Let’s dive in!
A 45-year-old male presents to the emergency department with progressive dyspnea and wheezing. The patient has a history of poorly controlled asthma and recurrent episodes of acute bacterial rhinosinusitis. He reports recently using aspirin for a calf muscle strain sustained while playing tennis. Physical examination reveals diffuse wheezing, decreased breath sounds, and bilateral nasal polyps. What is the most likely underlying cause of this patient’s symptoms?
A) Bacterial-induced alteration of salicylate metabolism
B) Salicylate allergy
C) Genetic overactive COX enzyme activity
D) Leukotriene and prostaglandin Imbalance
E) Virus-induced alteration of salicylate metabolism
The answer & question breakdown is at the bottom of the post 👇🏼
🔗 LINKS TO RECENT POSTS
USMLE Times Issue #101 - READ HERE
USMLE Practice Question #94 - TRY IT HERE
USMLE Practice Question #93 - TRY IT HERE
This week’s recommended video 👇🏼
ANSWER + QUESTION BREAKDOWN
The mental model used to answer this question comes from our detailed test-taking skills masterclass (check it out if you want to elevate your USMLE test-taking skills) Here’s how to think through this question:
Step 1. Read the vignette and get the actual question: “What is the most likely underlying cause of this patient’s symptoms?”
Step 2. Determine if this is a 1st order, 2nd order, or 3rd order question. This is 2nd order: 1st. Make a diagnosis; 2nd. Identify the underlying cause of the diagnosis.
Step 3. Based on the thought process in ‘Step 2’ above, ask yourself: “What’s the likely reason for this patient’s condition?”
Step 4. Look at the answer choices and select the one most closely resembling your determination from ’Step 3’ above.
** Aim to take this mental model into all of your USMLE practice questions **
GENERAL ANALYSIS
This vignette describes a 45-year-old male with a history of poorly controlled asthma, recurrent bacterial rhinosinusitis, and recent aspirin use. His symptoms include progressive dyspnea and wheezing, and physical examination reveals bilateral nasal polyps. These findings strongly suggest Aspirin-Exacerbated Respiratory Disease (AERD), also known as Samter’s Triad, which is characterized by asthma, nasal polyps, and sensitivity to aspirin or other NSAIDs. The task is determining the most likely underlying cause of this patient’s symptoms.
ANSWER CHOICES:
CHOICE A: Bacterial-induced alteration of salicylate metabolism
Explanation: This option suggests that a bacterial infection has altered the metabolism of salicylates (aspirin). While this patient does have a history of recurrent bacterial rhinosinusitis, there is no evidence to suggest that bacterial infections alter the metabolism of aspirin or salicylates in a way that would cause respiratory symptoms.
CHOICE B: Salicylate allergy
Explanation: This option suggests that the patient has an allergic reaction to aspirin. While AERD involves sensitivity to aspirin, it is not considered a true IgE-mediated allergy. AERD is not an allergic reaction in the traditional sense (i.e., IgE-mediated hypersensitivity), but rather a result of altered eicosanoid metabolism involving overproduction of leukotrienes and reduced prostaglandins.
CHOICE C: Genetic overactive COX enzyme activity
Explanation: This option suggests that overactivity of cyclooxygenase (COX) enzymes is responsible for the patient’s symptoms. In AERD, the problem is not overactive COX enzyme activity, rather reduced COX activity, particularly COX-2. Aspirin inhibits COX enzymes, which leads to decreased production of prostaglandins (particularly PGE2) and increased production of leukotrienes.
CHOICE D: Leukotriene and prostaglandin imbalance
Explanation: In patients with AERD, inhibition of COX enzymes by aspirin reduces prostaglandin E2 (PGE2) production, which normally has anti-inflammatory effects. This leads to an overproduction of leukotrienes (pro-inflammatory mediators), causing bronchoconstriction and exacerbating asthma symptoms.
CHOICE E: Virus-induced alteration of salicylate metabolism
Explanation: This option suggests that a viral infection has altered how salicylates are metabolized in the body. There is no evidence to suggest that viral infections alter salicylate metabolism in a way that would cause respiratory symptoms similar to those seen in AERD.
THE VERDICT…
The most likely underlying cause of this patient’s symptoms is an imbalance between leukotrienes and prostaglandins, characteristic of Aspirin-Exacerbated Respiratory Disease (AERD).
In individuals with AERD, aspirin inhibits cyclooxygenase (COX), particularly COX-1, leading to reduced production of prostaglandins like PGE2. PGE2 normally has anti-inflammatory effects and helps regulate bronchoconstriction. When its production is inhibited by aspirin, there is an overproduction of leukotrienes (such as LTC4, LTD4, LTE4), which are potent pro-inflammatory mediators that cause bronchoconstriction, increased mucus production, and airway inflammation.
The triad of asthma, nasal polyps, and sensitivity to aspirin or NSAIDs strongly points toward AERD as the diagnosis. The key pathophysiological mechanism involves an altered arachidonic acid pathway where leukotriene production increases due to reduced inhibition by prostaglandins. This imbalance causes severe respiratory reactions when patients with AERD take aspirin or other NSAIDs.
Correct answer: D) Leukotriene and prostaglandin imbalance
That’s it for issue #102 of The USMLE Times!
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