A 61-year-old male presents to your office with fever and dyspnea on exertion. He has been suffering from chronic, non-productive cough for 1 year. You note late inspiratory crackles on auscultation. Pulmonary function tests reveal an FEV1/FVC ratio of 90% and an FVC that is 50% of the predicted value. Which of the following would you most likely see on a biopsy of this patient's lung?

Linear immunofluorescence along alveolar basement membranes

A 60-year-old woman presents to the clinic with a 3-month history of shortness of breath that worsens on exertion. She also complains of chronic cough that has lasted for 10 years. Her symptoms are worsened even with light activities like climbing up a flight of stairs. She denies any weight loss, lightheadedness, or fever. Her medical history is significant for hypertension, for which she takes amlodipine daily. She has a 70-pack-year history of cigarette smoking and drinks 3–4 alcoholic beverages per week. Her blood pressure today is 128/84 mm Hg. A chest X-ray shows flattening of the diaphragm bilaterally. Physical examination is notable for coarse wheezing bilaterally. Which of the following is likely to be seen with pulmonary function testing?

Decreased FEV1: FVC and increased total lung capacity

Decreased FEV1: FVC and decreased total lung capacity

Normal FEV1: FVC and decreased total lung capacity

Increased FEV1: FVC and decreased total lung capacity

Increased FEV1: FVC and normal total lung capacity

A 60-year-old man presents with breathlessness for the past 3 months. His symptoms have been getting progressively worse during this time. He denies any history of cough, fever, or chest pain. He works at a local shipyard and is responsible for installing the plumbing aboard the vessels. His past medical history is significant for hypertension for which he takes metoprolol every day. He denies smoking and any illicit drug use. His pulse is 74/min, respiratory rate is 14/min, blood pressure is 130/76 mm Hg, and temperature is 36.8°C (98.2°F). Physical examination is significant for fine bibasilar crackles at the end of inspiration without digital clubbing. Which of the following additional findings would most likely be present in this patient?

Decreased diffusing capacity of CO

Increased pulmonary capillary wedge pressure

Decreased pulmonary arterial pressure

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 49-year-old woman comes to the physician because of a 4-month history of a dry cough and shortness of breath on exertion. She also reports recurrent episodes of pain, stiffness, and swelling in her wrist and her left knee over the past 6 months. She had two miscarriages at age 24 and 28. Physical examination shows pallor, ulcerations on the palate, and annular hyperpigmented plaques on the arms and neck. Fine inspiratory crackles are heard over bilateral lower lung fields on auscultation. Which of the following additional findings is most likely in this patient?

Decreased right atrial pressure

A 62-year-old man presents to the emergency department for evaluation of a 2-year history of increasing shortness of breath. He also has an occasional nonproductive cough. The symptoms get worse with exertion. The medical history is significant for hypertension and he takes chlorthalidone. He is a smoker with a 40-pack-year smoking history. On physical examination, the patient is afebrile; the vital signs include: blood pressure 125/78 mm Hg, pulse 90/min, and respiratory rate 18/min. The body mass index (BMI) is 31 kg/m2. The oxygen saturation is 94% at rest on room air. A pulmonary examination reveals decreased breath sounds bilaterally, but is otherwise normal with no wheezes or crackles. The remainder of the examination is unremarkable. A chest radiograph shows hyperinflation of both lungs with mildly increased lung markings, but no focal findings. Based on this clinical presentation, which of the following is most likely?

FEV1/FVC of 80% with an FEV1 of 82%

A 31 year-old African-American female presents with painful shin nodules, uveitis, and calcified hilar lymph nodes. A transbronchial biopsy of the lung would most likely show which of the following histologies?

Inflammation, fibrosis and cyst formation that is most prominent in subpleural regions

Silica particles (birefringent) surrounded by collagen

Patchy interstitial lymphoid infiltrate into walls of alveolar units

Restrictive lung diseases for USMLE Step 1: High-Yield Pathology Lessons

Restrictive Lung Dx - The Suffocating Squeeze

Characterized by ↓ lung compliance & volume; patients can't get air IN. Key feature is a normal or ↑ FEV1/FVC ratio (≥ 0.8), with ↓ FVC & TLC.

Intrinsic (Pulmonary Parenchyma):
- Idiopathic Pulmonary Fibrosis (IPF): "honeycombing" on CT.
- Sarcoidosis, Pneumoconioses (asbestosis, silicosis).
Extrinsic (Extra-parenchymal):
- Chest wall (kyphoscoliosis), obesity.
- Pleural disease (effusions).
- Neuromuscular weakness (e.g., Guillain-Barré).

CT and histology of idiopathic pulmonary fibrosis

⭐ Both FEV1 and FVC are reduced, but FVC is reduced more, leading to a preserved or increased FEV1/FVC ratio.

Idiopathic Fibrosis - Scarred for Life

Chronic, progressive, fibrosing interstitial pneumonia of unknown cause, typically affecting older adults (>60 years).
Clinical: Insidious onset dyspnea, dry cough, digital clubbing, and characteristic bibasilar "Velcro-like" crackles.
Pathology: Histological pattern is Usual Interstitial Pneumonia (UIP).
- Patchy, peripheral, subpleural fibrosis.
- Temporal heterogeneity: areas of established fibrosis (collagen) adjacent to early fibroblastic foci.
- Late stage: Honeycomb lung (cystic fibrotic airspaces).

UIP Histopathology: Fibroblastic Foci & Honeycomb Lung

⭐ Exam Favorite: The hallmark of UIP is spatial and temporal heterogeneity, meaning scarred and normal lung tissue coexist, reflecting ongoing, asynchronous injury.

Prognosis: Poor (median survival 3-5 years).
Tx: Pirfenidone, Nintedanib (slow decline); Lung transplant definitive.

Pneumoconioses - Dust Bunnies' Revenge

Chronic fibrosing lung diseases from inhalation of mineral dusts, leading to inflammation and interstitial fibrosis. Primarily affects workers in specific industries.

Asbestosis:
- Source: Insulation, shipbuilding, roofing.
- Pathology: Affects lower lobes. Ferruginous bodies (asbestos fibers coated with iron/protein), calcified pleural plaques.
Silicosis & Coal Workers' (CWP):
- Source: Mining, sandblasting (Silica); Coal mining (CWP).
- Pathology: Affects upper lobes. Macrophages ingest particles, leading to fibrosis.
- 📌 Mnemonic: Asbestos from the roof (insulation) hits the base (lower lobes); Silica/Coal from the earth hit the roof (upper lobes).
Berylliosis:
- Source: Aerospace, electronics manufacturing.
- Pathology: Non-caseating granulomas, mimicking sarcoidosis.

⭐ Silicosis is associated with "eggshell calcification" of hilar lymph nodes and impairs macrophage function, increasing susceptibility to Tuberculosis.

Granuloma Gangs - Sarcoid & Friends

Sarcoidosis: Multisystem disorder defined by non-caseating granulomas, common in African American females.
- Path: Unknown antigen drives a CD4+ T-cell response.
- Features: Dyspnea, cough, uveitis, erythema nodosum. Bilateral hilar lymphadenopathy on CXR.
- Labs: ↑ Serum ACE, ↑ CD4+/CD8+ ratio (>2:1) in BAL fluid, hypercalcemia.
- Histo: Tightly-formed granulomas; may show Schaumann or asteroid bodies.
⭐ Hypercalcemia is due to PTH-independent production of active Vitamin D by epithelioid macrophages in granulomas.
Hypersensitivity Pneumonitis (HP): Immune reaction to inhaled organic antigens (e.g., Farmer's Lung).
- Histo: Poorly-formed non-caseating granulomas.
Berylliosis: Occupational lung disease (aerospace, electronics) that mimics sarcoidosis; history is crucial.

High‑Yield Points - ⚡ Biggest Takeaways

Characterized by ↓ lung volumes (especially TLC) and a normal or ↑ FEV1/FVC ratio.

Presents with progressive dyspnea due to stiff, non-compliant lungs from interstitial fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is the most common, showing honeycombing on imaging.

Sarcoidosis is marked by non-caseating granulomas and bilateral hilar lymphadenopathy.

Asbestosis classically affects the lower lobes and is linked to mesothelioma.

Hypersensitivity pneumonitis is a reaction to inhaled organic dusts.

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