In a patient with CT showing multiple bilateral peribronchovascular centrilobular nodules and fibro‑atelectatic changes, without consolidation, cavitation, bronchiectasis, air‑trapping, or significant mediastinal lymphadenopathy, what is the most likely diagnosis and what diagnostic and therapeutic steps should be taken?

Diagnosis and Management of Bilateral Centrilobular Nodules with Fibro-atelectatic Changes

The most likely diagnosis is organizing pneumonia (OP), and you should proceed with bronchoscopy and bronchoalveolar lavage to exclude infectious etiologies before initiating corticosteroid therapy. 1

Primary Diagnostic Consideration

Organizing pneumonia is the leading diagnosis given the constellation of peribronchovascular centrilobular nodules with fibro-atelectatic densities in the absence of cavitation, bronchiectasis, or significant lymphadenopathy. 1 The peribronchovascular distribution of consolidation with nodular density is highly suggestive of OP according to the American Thoracic Society. 1

The fibro-atelectatic changes in the right middle lobe lateral segment, inferior lingular segment, and left lower lobe suggest a subacute to chronic process, which is consistent with organizing pneumonia that may be progressing toward a fibrosing variant. 1

Critical Differential Diagnoses to Exclude

Hypersensitivity Pneumonitis (HP)

You must systematically exclude HP before finalizing the diagnosis, as this is the most important alternative that completely changes management. 2, 3 HP characteristically presents with:

• Poorly defined centrilobular nodules (which this patient has) 2
• Ground-glass opacities 2
• Mosaic attenuation with air trapping on expiratory images 2
• The "three-density pattern" (ground-glass, decreased attenuation lobules, and normal lung) 2

The absence of air trapping and mosaic attenuation in this case argues against HP, though you must still obtain a detailed exposure history focusing on bird/down feather exposure, mold, and occupational exposures. 2, 3

Drug-Induced Pneumonitis

Review all medications systematically, as drug-related pneumonitis can manifest with organizing pneumonia patterns and centrilobular nodules. 2, 4 Key medications to consider include:

• Salicylates (sulfasalazine, 5-ASA) 4
• Methotrexate 4
• Anti-TNF monoclonal antibodies 4
• Amiodarone, nitrofurantoin 3

The diagnosis relies on temporal relationships between drug initiation and symptom onset. 4

Infectious Etiologies

Tuberculosis must be excluded, particularly given the centrilobular nodules and fibro-atelectatic changes. 5 Early bronchogenic spread of postprimary tuberculosis presents with:

• Centrilobular 2-4 mm nodules 5
• Poorly defined 5-8 mm nodules 5
• Lobular consolidation 5

However, the absence of cavitation and the bilateral symmetric distribution make tuberculosis less likely. 5

Nontuberculous mycobacterial infection (NTMB) should also be considered, as it presents with centrilobular nodules and bronchiectasis, though the absence of bronchiectasis in this case makes NTMB less probable. 2

Connective Tissue Disease

Screen for underlying connective tissue disease, as inflammatory bowel disease (particularly ulcerative colitis) and polymyositis are associated with organizing pneumonia. 4 Check ANA, rheumatoid factor, anti-CCP antibodies, and anti-synthetase antibodies. 3, 4

Diagnostic Algorithm

Step 1: Bronchoscopy with Bronchoalveolar Lavage (BAL)

Perform bronchoscopy with BAL as the initial invasive diagnostic procedure to rule out infectious etiologies and obtain samples for cytology and culture. 1 This is essential before initiating corticosteroid therapy, which could mask or worsen an underlying infection. 1

Send BAL fluid for:

• Bacterial, fungal, and mycobacterial cultures 1
• Cell count and differential (elevated lymphocytes suggest HP) 2
• Cytology to exclude malignancy 1

Step 2: Multidisciplinary Discussion (MDD)

Convene a multidisciplinary discussion involving pulmonologist, radiologist, and pathologist before finalizing the diagnosis, as this changes the diagnosis in a significant proportion of cases. 2, 1, 3 The MDD should review:

• Clinical presentation and exposure history 2
• HRCT patterns and distribution 2
• BAL results 1
• Need for surgical lung biopsy 2

Step 3: Consider Surgical Lung Biopsy

Surgical lung biopsy is indicated if the diagnosis remains uncertain after bronchoscopy, particularly to differentiate between organizing pneumonia and other interstitial lung diseases. 2, 1 However, biopsy should not be performed if:

• The patient has significant comorbidities 3
• The patient declines the procedure 3
• Clinical and radiologic features are sufficiently characteristic for OP 1

The American Thoracic Society recommends open lung biopsy over transthoracic needle biopsy for diffuse lung disease to obtain larger and more representative samples. 2

Treatment Approach

Corticosteroid Therapy

Once infectious etiologies are excluded, initiate oral corticosteroids as the mainstay of treatment for organizing pneumonia. 1 Most patients recover completely with corticosteroid therapy, though relapses are common. 1

Monitoring for Progression

Close monitoring is essential, as some cases of organizing pneumonia may progress to a fibrosing variant despite treatment. 1 The presence of fibro-atelectatic changes in this patient suggests possible early fibrotic evolution. 1

Regular follow-up imaging is recommended to assess treatment response and monitor for potential progression to fibrotic disease. 1 Some patients develop organizing pneumonia with prominent fibrosis, particularly those with underlying connective tissue disease. 4

Critical Pitfalls to Avoid

Do not initiate corticosteroids before excluding infection, as this could worsen an underlying mycobacterial or fungal infection. 1 The centrilobular nodules and fibro-atelectatic changes could represent tuberculosis or NTMB. 5, 2

Do not miss hypersensitivity pneumonitis, as continued antigen exposure leads to preventable progression. 3 The presence of centrilobular nodules should prompt detailed exposure history even when air trapping is absent. 2

Do not rely on imaging alone—the CT patterns are nonspecific and overlap significantly between organizing pneumonia, HP, drug-induced pneumonitis, and infection. 2, 4 Tissue diagnosis or BAL is often necessary. 1

Monitor for development of residual or progressive interstitial fibrosis, as it can occur in a subgroup of patients despite treatment. 1 The fibro-atelectatic changes already present suggest this patient may be at higher risk. 1