What is the diffusing capacity of the lung for carbon monoxide (DLCO) test, and how is it performed, interpreted, and applied in clinical practice?

DLCO Test: Comprehensive Clinical Overview

What is the DLCO Test?

The diffusing capacity of the lung for carbon monoxide (DLCO) is a pulmonary function test that measures the transfer of gas from the alveolar space into pulmonary capillary blood, providing a quantitative assessment of gas exchange efficiency in the lungs. 1, 2

Test Performance and Technique

The test requires minimal patient effort compared to spirometry 3:

• Patient breathes quietly at rest, then inhales a test gas mixture containing a small amount of carbon monoxide and a tracer gas (typically helium or methane) 4, 2
• Breath is held for approximately 10 seconds at total lung capacity 3
• Patient then exhales, and the exhaled gas is analyzed to determine CO uptake 2
• The test measures both the DLCO value and the alveolar volume (VA) from which the transfer coefficient (KCO) can be calculated 4, 2

Quality Considerations

• Sample volume must be displayed on the report 4
• Values should be corrected to standard barometric pressure, particularly important at altitude 4
• Modern analyzers use rapid-acting technology with "virtual" sample volumes adjusted for patient size 4

Interpretation Framework

Severity Grading

The European Respiratory Society provides clear severity thresholds for DLCO reduction 4:

• Mild: ≥60% predicted and below lower limit of normal (LLN)
• Moderate: 40-60% predicted
• Severe: <40% predicted

Critical Adjustments Required

Always adjust DLCO for hemoglobin levels first, as anemia falsely lowers DLCO without reflecting true gas exchange abnormalities. 4, 5 This adjustment is especially important when monitoring for drug toxicity or in patients undergoing chemotherapy where hemoglobin fluctuates significantly 4.

Carboxyhemoglobin adjustments are also important in smokers and those with carbon monoxide exposure 4.

Clinical Diagnostic Patterns

Normal Spirometry with Low DLCO

This pattern suggests 4:

• Anemia (check hemoglobin first)
• Pulmonary vascular disorders (pulmonary hypertension, chronic pulmonary embolism)
• Early interstitial lung disease
• Early emphysema

Restrictive Pattern (Low Lung Volumes) with Low DLCO

This combination strongly indicates parenchymal lung disease, specifically interstitial lung diseases, sarcoidosis, or pulmonary fibrosis. 4, 5

Restrictive Pattern with Normal DLCO

Normal DLCO in the presence of restriction suggests extraparenchymal causes 4, 5:

• Chest wall disorders
• Neuromuscular disorders
• Obesity

Obstructive Pattern with Low DLCO

In adult smokers with post-bronchodilator airway obstruction, a low DLCO greatly increases the probability of the emphysema phenotype of COPD. 4, 3 A normal DLCO in this context makes chronic asthma more likely 3.

Lymphangioleiomyomatosis also presents with obstruction and low DLCO 4.

Elevated DLCO

High DLCO is associated with 4:

• Asthma
• Obesity
• Intrapulmonary hemorrhage

Understanding DLCO/VA (KCO) and Common Pitfalls

The European Respiratory Society emphasizes that the relationship between DLCO and lung volume is not linear, making DLCO/VA an imperfect normalization method. 4, 5 The term "DL/VA" should be avoided as it is commonly misunderstood 4.

Interpretation of DLCO/VA Patterns

• Low DLCO with high DLCO/VA (KCO): Suggests extraparenchymal abnormality such as pneumonectomy or chest wall restriction 4
• Low DLCO with low DLCO/VA (KCO): Suggests parenchymal abnormalities like interstitial lung disease or emphysema 4, 5

The European Respiratory Society recommends examining DLCO/VA and VA separately rather than using their ratio to normalize DLCO for lung volume. 4

Prognostic Significance

Reduced DLCO predicts cardiopulmonary complications and mortality even when FEV1 is normal, making it a critical risk stratification tool beyond diagnosis. 5

Specific prognostic thresholds 3:

• DLCO below 40% predicted is associated with increased morbidity and mortality
• A decline in DLCO of more than 4 percentage points indicates disease progression

Clinical Decision-Making Algorithm

Step 1: Verify Hemoglobin Adjustment

Check if DLCO has been corrected for anemia or polycythemia 4, 5

Step 2: Interpret in Context of Spirometry and Lung Volumes

• Obtain complete lung volumes with body plethysmography to confirm true restriction 5
• A normal TLC (VA from single-breath helium dilution) rules out restriction without need for body plethysmography 3

Step 3: Pattern Recognition

Apply the diagnostic patterns outlined above based on the combination of spirometry, lung volumes, and DLCO results 4, 5

Step 4: Consider Advanced Imaging

Obtain high-resolution CT imaging to evaluate for interstitial lung disease, pulmonary vascular disease, or early emphysema when DLCO is reduced. 5

Emerging Technology

DLNO (diffusing capacity for nitric oxide) has several technical advantages over DLCO 6:

• Unaffected by carboxyhemoglobin
• Minimally affected by hemoglobin concentration (no correction needed)
• Unaffected by inspired oxygen concentration or ambient pressure
• More stable measure over time

However, DLCO remains the established standard in clinical practice 6, 1.