What are the causes of a low DLCO on pulmonary function tests (PFTs)?

Causes of Low DLCO on Pulmonary Function Tests

A low diffusing capacity for carbon monoxide (DLCO) on pulmonary function tests can be caused by various conditions affecting the alveolar-capillary membrane, pulmonary vasculature, or hemoglobin availability, with the most common causes being interstitial lung diseases, emphysema, pulmonary vascular disorders, and anemia. 1

Classification of DLCO Reduction

The European Respiratory Society classifies DLCO reduction severity as:

• Mild: >60% predicted but below lower limit of normal (LLN)
• Moderate: 40-60% predicted
• Severe: <40% predicted 1

Major Causes of Low DLCO Based on Associated PFT Patterns

Normal Spirometry and Lung Volumes with Low DLCO

• Anemia (reduced hemoglobin available for CO binding)
• Pulmonary vascular disorders:
  • Pulmonary hypertension
  • Pulmonary embolism
  • Primary pulmonary vascular diseases
• Early interstitial lung disease (ILD)
• Early emphysema 1

Restrictive Pattern with Low DLCO

• Interstitial lung diseases:
  • Idiopathic pulmonary fibrosis
  • Sarcoidosis
  • Connective tissue disease-associated ILD
• Pulmonary fibrosis 1

Obstructive Pattern with Low DLCO

• Emphysema
• Lymphangioleiomyomatosis 1

Diagnostic Value of DLCO/VA (KCO) Patterns

The relationship between DLCO and alveolar volume (VA) provides additional diagnostic information:

1. Low DLCO, High KCO:

   • Indicates inability to achieve full lung distension despite normal alveolar-capillary membrane
   • Seen in respiratory muscle weakness, pleural disease, rib cage abnormalities, or obesity 2

2. Low DLCO, Low or Normal KCO:

   • Suggests loss of alveolar surface area with air trapping
   • Characteristic of emphysema 2

3. Low DLCO, Variable KCO:

   • Indicates diffuse loss of alveolar units with thickened alveolar-capillary membrane
   • Typical of interstitial lung disease 2

4. Low DLCO, Low KCO:

   • Suggests reduced pulmonary capillary blood volume
   • Seen in pulmonary hypertension, pulmonary embolism, or primary pulmonary vascular diseases 2

Special Clinical Scenarios

Combined Pulmonary Fibrosis and Emphysema

• May have relatively preserved spirometry and lung volumes despite significant pathology
• DLCO may be the only sensitive marker of this combined disease pattern 3

Systemic Sclerosis

• Isolated DLCO reduction (normal FVC and FEV1/FVC) occurs in approximately 19% of patients
• DLCO <55% predicted with FVC%/DLCO% ratio >1.4 strongly associated with development of pulmonary hypertension 4

Sickle Cell Anemia

• 90% of adult patients have abnormal pulmonary function
• Restrictive physiology (74%) and isolated low DLCO (13%) are common patterns
• Decreased DLCO associated with thrombocytosis and hepatic/renal dysfunction 5

Clinical Significance

• A DLCO below 40% predicted is associated with increased morbidity and mortality 6
• A decline in DLCO of more than 4 units is clinically significant 6
• In patients with dyspnea of unknown cause, low DLCO with normal spirometry increases likelihood of pulmonary vascular disease 6

Important Considerations for DLCO Interpretation

• Adjust DLCO for hemoglobin and carboxyhemoglobin concentrations
• Consider technical factors that may affect measurement
• Interpret in conjunction with other PFT parameters and clinical context 1
• Serial measurements provide more reliable information than isolated tests 1

Common Pitfalls to Avoid

• Failing to adjust for hemoglobin levels (especially important in anemia or polycythemia)
• Overlooking carboxyhemoglobin levels in smokers
• Misinterpreting normal KCO in restrictive disorders
• Ignoring VA measurement when interpreting DLCO 2

Remember that a high DLCO (>140% predicted) is most commonly associated with obesity, asthma, or large lung volumes, and may mask underlying conditions that typically reduce DLCO 7.