What baseline laboratory studies should be ordered for a patient with suspected pneumonitis?

Blood Tests for Pneumonitis

Laboratory tests such as serologic testing and microbial cultures may help establish infectious or other etiologies for pulmonary infiltrates but are not useful in specifically diagnosing drug-related pneumonitis. 1

Baseline Laboratory Studies for Suspected Pneumonitis

Essential Blood Work

• Complete blood count (CBC) with differential should be obtained to assess for leukocytosis (>14,000 cells/mm³), left shift (band neutrophils ≥6% or >1,500/mm³), lymphopenia, or eosinophilia, which help differentiate bacterial infection from drug-related or immune-mediated pneumonitis. 1

• Serum electrolytes, renal function, and liver function tests are required to identify multiple organ dysfunction and define severity of illness, particularly in hospitalized patients. 1

• Arterial blood gas or oxygen saturation monitoring must be performed to determine the need for supplemental oxygen and assess for metabolic or respiratory acidosis; oxygen saturation <90% is a critical threshold indicating severe disease. 1

Additional Laboratory Studies Based on Clinical Context

• Blood cultures (≥2 sets from separate sites) should be collected before antibiotic administration in all patients with suspected ventilator-associated or hospital-acquired pneumonia, as positive results may indicate pneumonia or extrapulmonary infection. 1

• Inflammatory markers including C-reactive protein (CRP) and procalcitonin help differentiate bacterial pneumonia (CRP >50 mg/L, elevated procalcitonin) from viral or drug-induced causes (typically normal or mildly elevated procalcitonin). 2

• Lactate dehydrogenase (LDH), D-dimer, and fibrinogen may be elevated in COVID-19 pneumonia and other viral pneumonitis, providing additional diagnostic context. 2

Critical Distinction: Laboratory Tests Do NOT Diagnose Pneumonitis

The diagnosis of pneumonitis fundamentally requires radiographic evidence (chest CT is preferred over chest X-ray) combined with clinical features—laboratory tests serve only to exclude alternative diagnoses and assess severity. 1

What Laboratory Tests Cannot Do

• No blood test is specific for drug-related pneumonitis (DRP), hypersensitivity pneumonitis, or immune checkpoint inhibitor-related pneumonitis—these remain clinical-radiographic diagnoses. 1

• Pulmonary function testing (showing restrictive pattern with reduced diffusion capacity) confirms pulmonary impairment but does not establish the diagnosis of pneumonitis. 1

When Invasive Testing Is Required

• Bronchoalveolar lavage (BAL) with lymphocyte cellular analysis is indicated when the differential diagnosis includes hypersensitivity pneumonitis (lymphocytosis >30% supports HP), drug-related pneumonitis (lymphocytosis >20% is typical), or to exclude infection. 1, 3

• BAL lymphocyte differential >25% suggests granulomatous disease (sarcoidosis, hypersensitivity pneumonitis, chronic beryllium disease), drug reaction, or organizing pneumonia. 1

• BAL eosinophil count >25% is virtually diagnostic of acute or chronic eosinophilic pneumonia. 1

• Transbronchial lung biopsy or surgical lung biopsy should be considered when diagnosis remains uncertain after non-invasive evaluation, when competing diagnoses require histologic confirmation, or when treatment decisions hinge on definitive diagnosis—but the benefit-risk analysis must be individualized. 1

Algorithmic Approach to Laboratory Evaluation

Step 1: Initial Blood Work (All Patients)

• CBC with differential 1
• Comprehensive metabolic panel (electrolytes, renal, liver function) 1
• Oxygen saturation or arterial blood gas 1

Step 2: Severity and Etiology Assessment

• Inflammatory markers (CRP, procalcitonin) if bacterial vs. non-bacterial differentiation needed 2
• Blood cultures if hospitalized or sepsis suspected 1
• Viral testing (COVID-19, influenza) if clinically indicated 2

Step 3: Chest Imaging (Mandatory)

• Thin-section chest CT (≤2.5 mm sections) is the imaging modality of choice for confirming pneumonitis and characterizing patterns 1

Step 4: Invasive Testing (Selected Cases)

• BAL with cellular analysis when diagnosis uncertain or infection must be excluded 1, 3
• Lung biopsy when non-invasive evaluation is inconclusive and diagnosis will alter management 1

Common Pitfalls to Avoid

• Do not rely on laboratory tests alone to diagnose pneumonitis—radiographic confirmation is mandatory. 1, 2

• Do not skip chest CT in favor of chest X-ray when pneumonitis is suspected, as CT is far more sensitive for early disease and pattern characterization. 1

• Do not obtain BAL or lung biopsy reflexively—reserve invasive testing for cases where diagnosis remains uncertain after clinical-radiographic assessment or when infection must be definitively excluded. 1

• Do not interpret lymphocytosis in BAL as specific for any single diagnosis—it occurs in hypersensitivity pneumonitis, drug-induced pneumonitis, organizing pneumonia, and other conditions. 1, 3