• Ground-glass attenuation with superimposed interlobular septal thickening and intralobular lines
• Resembles irregular paving stones

Comment

• Initially considered pathognomonic for pulmonary alveolar proteinosis
• Now recognized as a non-specific finding
• Associated with a variety of lung diseases

Citation

• Abraham JL, et al. Radiology. 1980

• Ground-glass attenuation represents hazy increased density on CT scans
• Mosaic attenuation refers to a heterogeneous appearance of lung attenuation
• The combination suggests alveolar filling or interstitial thickening

Comment

• Often seen in conjunction with other patterns like crazy paving
• Can indicate conditions such as interstitial lung disease, infection, or edema

Citation

• Harding PC, et al. Chest. 1998

• Preservation of lung parenchyma in the subpleural regions
• Contrast with abnormalities seen more centrally or diffusely

Comment

• Can be a helpful distinguishing feature in certain interstitial lung diseases
• May suggest specific etiologies based on distribution patterns

Citation

• Naidich DP, et al. J Thorac Imaging. 2005

• Abnormal accumulation of fluid in the pleural space
• May be unilateral or bilateral

Comment

• Indicates an underlying inflammatory, infectious, or neoplastic process
• The character of the effusion (e.g., transudative vs. exudative) can provide diagnostic clues

Citation

• Light RW. Chest. 2007

• Air-containing bronchi visualized within an area of lung opacity
• Indicates that the surrounding lung parenchyma is consolidated or filled with fluid/cells

Comment

• A common finding in pneumonia and atelectasis
• Helps differentiate alveolar filling from interstitial processes

Citation

• Fraser RS, et al. Diagnosis of Diseases of the Chest. 1999

A. Direct activation of pro-fibrotic signaling pathways via TGF-β.

B. Inhibition of lysosomal phospholipases, causing phospholipidosis.

C. Generation of reactive oxygen species leading to widespread mitochondrial damage.

D. Competitive inhibition of surfactant protein B, causing alveolar collapse.

A. High degree of plasma protein binding (>95%).

B. Metabolism primarily by CYP2C8 and CYP3A4.

C. Extensive tissue accumulation, particularly in adipose tissue, and a very long elimination half-life.

D. Enterohepatic recirculation of its primary metabolite, desethylamiodarone.

A. Serum amiodarone and desethylamiodarone levels above the therapeutic range.

B. The presence of ‘foamy’ macrophages on bronchoalveolar lavage (BAL).

C. A significant decrease in diffusing capacity for carbon monoxide (DLCO) of >20% from baseline.

D. Isolation of Pneumocystis jirovecii from a BAL sample.

A. Immediate cessation of amiodarone and initiation of systemic corticosteroids.

B. Reduction of the amiodarone dose and addition of an antioxidant like N-acetylcysteine.

C. Continuation of amiodarone with empiric broad-spectrum antibiotic coverage.

D. Initiation of an antifibrotic agent such as pirfenidone while continuing amiodarone.

A. Bilateral, basal-predominant ground-glass opacities.

B. Centrilobular nodules with a tree-in-bud appearance.

C. High-attenuation (hyperdense) parenchymal consolidation and/or pleural thickening.

D. Diffuse interlobular septal thickening without ground-glass opacity.

A. Usual Interstitial Pneumonia (UIP).

B. Pulmonary Alveolar Proteinosis (PAP).

C. Miliary tuberculosis.

D. Sarcoidosis.

A. Diffuse, symmetric ground-glass opacities with traction bronchiectasis.

B. Lower-lobe predominant reticulation with honeycombing.

C. Patchy, migratory, and often peripheral or peribronchial airspace consolidation.

D. Innumerable small, well-defined nodules in a random distribution.

• Incorrect.
• While fibrosis can be a downstream consequence of the chronic inflammation and injury from APT, the primary initiating mechanism is not direct activation of TGF-β but rather the drug-induced phospholipidosis.

• Correct.
• Amiodarone and its primary metabolite are cationic amphiphilic compounds that accumulate in acidic lysosomes.
• Here, they potently inhibit lysosomal phospholipases, which are crucial for degrading phospholipids.
• This leads to the accumulation of phospholipids within intracellular lamellar bodies (phospholipidosis).
• The characteristic ‘foamy macrophages’ seen on histology are a result of this process.
• (Pollak PT, J Am Coll Cardiol, 1999)

• Incorrect.
• While oxidative stress is a proposed secondary mechanism of injury in APT, the most fundamental and characteristic process is the disruption of lipid metabolism due to phospholipase inhibition.

• Incorrect.
• Amiodarone does not act as a competitive inhibitor of surfactant proteins.
• The imaging patterns seen are related to a combination of alveolar and interstitial processes, not a primary deficiency in surfactant protein B.

• Incorrect.
• While high protein binding affects the free drug concentration and distribution, it is the extensive tissue storage and long half-life that are the dominant factors for its persistent effects.

• Incorrect.
• The specific CYP enzymes involved in metabolism are important for drug-drug interactions but do not inherently explain the persistence of toxicity after cessation.

• Correct.
• Amiodarone is highly lipophilic and is distributed extensively into tissues like adipose tissue, lung, and liver, where it accumulates.
• This sequestration, combined with its exceptionally long terminal elimination half-life (15 to 142 days), means the drug persists in the body for months after discontinuation.
• This prolonged tissue exposure accounts for both the delayed presentation of toxicity and the potential for symptoms to persist after the drug is stopped.
• (Kodama S, Am J Cardiol, 1997)

• Incorrect.
• Enterohepatic recirculation contributes to the overall drug exposure but is not the primary reason for its extremely long half-life compared to the vast tissue storage.

• Incorrect.
• Serum drug levels do not correlate well with toxicity and are not used for diagnosis.
• Toxicity can occur at any dose or serum level.

• Incorrect.
• The finding of foamy macrophages indicates amiodarone exposure, but it is not specific for toxicity, as these cells can be found in asymptomatic patients receiving the drug.
• Their absence, however, makes APT unlikely.

• Correct.
• The diagnosis of APT is one of exclusion.
• A decline in the DLCO of more than 15-20% from the patient’s pre-treatment baseline is a highly suggestive finding of pulmonary toxicity and a key monitoring parameter.
• It often represents the earliest functional abnormality.
• (Schwaiblmair M, Chest, 2010)

• Incorrect.
• The isolation of an organism like Pneumocystis jirovecii would establish an infectious etiology for the symptoms, arguing against a diagnosis of drug toxicity.

• Correct.
• The primary and most critical step is the immediate discontinuation of amiodarone.
• For patients with significant symptoms or hypoxemia, systemic corticosteroids (e.g., prednisone 40-60 mg/day) are administered to control the inflammatory response.
• The corticosteroid dose is then tapered slowly over several months to prevent relapse.
• (Schwaiblmair M, Clin Gov, 2012)

• Incorrect.
• Simply reducing the dose is insufficient for established, significant toxicity.
• Antioxidants are not a standard part of acute management.

• Incorrect.
• While infection must be excluded, this approach fails to address the underlying drug-induced inflammation and inappropriately continues the offending agent.

• Incorrect.
• Antifibrotic agents are used for chronic progressive fibrosing lung diseases and have no role in the management of acute/subacute inflammatory drug toxicity.

• Incorrect.
• Ground-glass opacities are a very common but non-specific finding in APT and many other lung diseases.

• Incorrect.
• Tree-in-bud opacities are characteristic of small airway disease (bronchiolitis), not typically APT.

• Correct.
• Amiodarone is an iodinated compound with a high atomic number.
• It accumulates within the lung parenchyma and pleura.
• As a result, involved areas of consolidation, nodules, or pleural thickening often appear hyperattenuating (denser than surrounding muscle) on non-contrast CT.
• This finding is highly specific for amiodarone toxicity.
• (Kuhlman JE, Radiology, 1987)

• Incorrect.
• Isolated septal thickening is more typical of pulmonary edema or lymphangitic carcinomatosis.
• In APT, septal thickening is usually seen with ground-glass opacity (crazy-paving).

• Incorrect.
• The characteristic pattern of UIP is basal and subpleural predominant reticulation and honeycombing. Crazy-paving is not a feature of UIP.

• Correct.
• The ‘crazy-paving’ pattern was first described and is considered a classic hallmark of Pulmonary Alveolar Proteinosis (PAP).
• It represents a combination of ground-glass opacity (due to alveoli filled with lipoproteinaceous material) and superimposed interlobular septal thickening.
• (Johkoh T, Radiology, 1999)

• Incorrect.
• Miliary tuberculosis presents as innumerable tiny, randomly distributed micronodules.

• Incorrect.
• Sarcoidosis typically presents with perilymphatic nodules and lymphadenopathy. Crazy-paving is not a characteristic feature.

• Incorrect.
• This pattern is more characteristic of a Nonspecific Interstitial Pneumonia (NSIP) pattern.

• Incorrect.
• This is the hallmark of a Usual Interstitial Pneumonia (UIP) pattern.

• Correct.
• Regardless of the cause, the classic imaging presentation of Organizing Pneumonia (OP) is bilateral, patchy areas of airspace consolidation.
• These opacities often have a peripheral or peribronchial distribution and can be migratory on follow-up imaging.
• (Cordier JF, Eur Respir J, 2006)

• Incorrect.
• Randomly distributed nodules suggest a hematogenous process, such as miliary infection or metastatic disease.