A 21-year-old man presents with eye redness, itching, and watering; nasal congestion, and rhinorrhea. He reports that these symptoms have been occurring every year in the late spring since he was 18 years old. The patient’s medical history is significant for endoscopic resection of a right maxillary sinus polyp at the age of 16. His father and younger sister have bronchial asthma. He takes oxymetazoline as needed to decrease nasal congestion. The patient’s blood pressure is 120/80 mm Hg, heart rate is 71/min, respiratory rate is 18/min, and temperature is 36.7°C (98.0°F). On physical examination, there is conjunctival injection and clear nasal discharge bilaterally. His lymph nodes are not enlarged and his sinuses do not cause pain upon palpation. Heart and lung sounds are normal. Which of the following is most likely to be a part of his condition’s pathogenesis?

Excessive release of histamine by the mast cells

Secretion of granzymes and perforin by cytotoxic T lymphocytes

Production of specific IgM antibodies by B lymphocytes

Release of reactive oxygen species by neutrophils

IL-2 secretion by Th1 lymphocytes

A 60-year-old woman presents to the emergency department due to progressive shortness of breath and a dry cough for the past week. She notes that her symptoms are exacerbated by physical activity and relieved by rest. The woman was diagnosed with chronic kidney disease 2 years ago and was recently started on regular dialysis treatment. Her pulse rate is 105/min, blood pressure is 110/70 mm Hg, respiratory rate is 30/min, and temperature is 37.8°C (100.0°F). On examination of the respiratory system, there is dullness on percussion, decreased vocal tactile fremitus, and decreased breath sounds over the right lung base. The rest of the physical exam is within normal limits. Which of the following is the most likely cause of this patient’s symptoms?

Primary spontaneous pneumothorax (PSP)

A 28-year-old man makes an appointment with his general practitioner for a regular check-up. He has recently been diagnosed with asthma and was given a short-acting β2-agonist to use during acute exacerbations. He said he usually uses the medication 1–2 times per week. Which of the following is the most appropriate treatment in this case?

Inhaled corticosteroids should be added as controller therapy.

He should start using a short-acting β2-agonist every day, not just when he has symptoms.

Long-acting β2-agonists should be added to his treatment regimen.

Systemic corticosteroids should be added to his treatment regimen.

He should continue with current treatment.

A 28-year-old man presents to his primary care provider because of shortness of breath, cough, and wheezing. He reports that in high school, he occasionally had shortness of breath and would wheeze after running. His symptoms have progressively worsened over the past 6 months and are now occurring daily. He also finds himself being woken up from sleep by his wheeze approximately 3 times a week. His medical history is unremarkable. He denies tobacco use or excessive alcohol consumption. His temperature is 37.1°C (98.8°F), blood pressure is 121/82 mm Hg, and heart rate is 82/min. Physical examination is remarkable for expiratory wheezing bilaterally. Spirometry shows an FEV1 of 73% of predicted, which improves by 19% with albuterol. In addition to a short-acting beta-agonist as needed, which of the following is the most appropriate therapy for this patient?

A low-dose inhaled corticosteroid and a long-acting beta-agonist

A high-dose inhaled corticosteroid and a long-acting beta-agonist

A long-acting beta-agonist alone

A low-dose inhaled corticosteroid alone

A medium-dose inhaled corticosteroid and a long-acting beta-agonist

A 24-year-old woman presents with episodic shortness of breath, chest tightness, and wheezing. She has noticed an increased frequency of such episodes in the spring season. She also has a history of urticaria. She has smoked a half pack of cigarettes per day over the last 5 years. Her mother also has similar symptoms. The physical exam is within normal limits. Which of the following findings is characteristic of her condition?

Decrease in forced expiratory volume in 1 second (FEV1) after methacholine

Decreased forced vital capacity (FVC) on pulmonary tests

Chest X-ray showing hyperinflation

A previously healthy 64-year-old woman comes to the physician because of a dry cough and progressively worsening shortness of breath for the past 2 months. She has not had fever, chills, or night sweats. She has smoked one pack of cigarettes daily for the past 45 years. She appears thin. Examination of the lung shows a prolonged expiratory phase and end-expiratory wheezing. Spirometry shows decreased FEV1:FVC ratio (< 70% predicted), decreased FEV1, and a total lung capacity of 125% of predicted. The diffusion capacity of the lung (DLCO) is decreased. Which of the following is the most likely diagnosis?

Chronic obstructive pulmonary disease

A 28-year-old man comes to his general practitioner for a regular checkup. He has had trouble breathing lately with coughing, shortness of breath, and wheezing. Problems first started when he went running (outside), but he is also observing the problems when taking a light walk or resting. As a child, he suffered from atopic dermatitis, just like his father and sister. He also has a history of hay fever. What is the most likely cause of his symptoms?

Chronic obstructive pulmonary disease

Asthma pathophysiology and diagnosis for USMLE Step 2 CK: High-Yield Internal Medicine Lessons

Pathophysiology - Bronchial Bedlam

Core Mechanism: Chronic airway inflammation driven by a Type I (IgE-mediated) hypersensitivity reaction, leading to bronchial hyperresponsiveness and reversible obstruction.
Key Cellular Players: Th2 lymphocytes, eosinophils, mast cells, and IgE antibodies.
Phases:
- Early: Trigger exposure → mast cell degranulation → release of histamine & leukotrienes → acute bronchoconstriction.
- Late: Cytokine-mediated influx of inflammatory cells (esp. eosinophils) → sustained inflammation and edema.

Asthmatic vs. Non-Asthmatic Bronchus Histology

⭐ Aspirin-Exacerbated Respiratory Disease (AERD) / Samter's Triad: A distinct asthma phenotype characterized by asthma, chronic rhinosinusitis with nasal polyps, and severe reactions to aspirin/NSAIDs.

Clinical Presentation - The Wheezing Wail

Episodic symptoms: dyspnea, chest tightness, and cough (often worse at night).
Classic sign: High-pitched, polyphonic expiratory wheeze.
Common Triggers:
- Allergens (dust mites, pollen), exercise, cold air.
- Viral infections, GERD, stress.
- Medications: Aspirin (AERD), non-selective β-blockers.
Associated Conditions: 📌 Atopic Triad (Asthma + Allergic Rhinitis + Atopic Dermatitis).

Asthma: Airway Changes and Lung Anatomy

Severe Exacerbation Signs:
- Accessory muscle use, tripoding posture.
- Pulsus paradoxus: Inspiratory SBP drop > 10 mmHg.

⭐ A "silent chest" in an acutely dyspneic patient is an ominous sign indicating severe airflow limitation and impending respiratory failure.

Diagnosis - The Spirometry Story

Spirometry: The cornerstone of asthma diagnosis, measuring airflow and lung volumes.
Key Finding: Reversible obstructive pattern.
- Initial Test: ↓ Forced Expiratory Volume in 1 second (FEV1) and ↓ FEV1/FVC ratio ($< \textbf{0.7}$ in adults).
- Flow-volume loop shows a "scooped-out" or concave pattern during exhalation.

Spirometry flow-volume loops in asthma

Confirmation Algorithm:

⭐ Fractional Exhaled Nitric Oxide (FeNO): A non-invasive test measuring eosinophilic airway inflammation. An elevated FeNO level ($> \textbf{50}$ ppb in adults) can support a diagnosis of asthma, particularly in cases with normal spirometry.

Severity Classification - The Asthma Ladder

Classification is based on impairment (symptoms, SABA use, lung function) and risk of exacerbations. Assessed before treatment is initiated.

Asthma Severity Classification by Clinical Features

Intermittent
- Symptoms: ≤2 days/week
- Nighttime awakenings: ≤2x/month
- SABA use: ≤2 days/week
- FEV1: >80% predicted
Mild Persistent
- Symptoms: >2 days/week (not daily)
- Nighttime awakenings: 3-4x/month
- FEV1: >80% predicted
Moderate Persistent
- Symptoms: Daily
- Nighttime awakenings: >1x/week (not nightly)
- FEV1: 60-80% predicted
Severe Persistent
- Symptoms: Throughout the day
- Nighttime awakenings: Often 7x/week
- FEV1: <60% predicted

⭐ The goal of the "ladder" approach is to step up therapy to gain control, then step down to the minimum level needed to maintain control.

High‑Yield Points - ⚡ Biggest Takeaways

Asthma is a chronic inflammatory disorder characterized by bronchial hyperresponsiveness and reversible airflow obstruction.

It's a Type I hypersensitivity reaction involving IgE, mast cells, and eosinophils.

Diagnosis is confirmed by spirometry showing an obstructive pattern (FEV1/FVC < 0.7).

Reversibility is key: >12% and 200 mL ↑ in FEV1 post-bronchodilator.

A methacholine challenge can diagnose asthma if initial spirometry is normal.

Classic sputum findings include Curschmann spirals and Charcot-Leyden crystals.

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