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The Diffusing Capacity of the Lung for Carbon Monoxide (DLCO, also called TLCO — transfer factor for CO) measures the efficiency of gas transfer across the alveolar-capillary membrane. A small, safe concentration of carbon monoxide is inhaled; CO is used because it binds to haemoglobin with very high affinity, so its transfer is limited only by the diffusion capacity of the lungs rather than by pulmonary blood flow. The DLCO is calculated as the amount of CO taken up by the blood divided by the alveolar CO concentration (driving pressure) per unit time. It is expressed in mL/min/mmHg (or mmol/min/kPa in SI units). The measured DLCO is compared to the predicted value for the patient's age, sex, height, and ethnicity using established reference equations (most commonly GLI-2017 or Crapo). Results above 80% of predicted are considered normal; 61–80% represents a mild reduction; 41–60% a moderate reduction; and ≤40% a severe reduction. DLCO is sensitive to diseases that damage the alveolar-capillary interface (emphysema, interstitial lung disease, pulmonary hypertension, pulmonary embolism) or reduce the effective alveolar surface area. It is also reduced by anaemia (because CO binds haemoglobin — less Hb means less CO uptake) and elevated in polycythaemia. The DLCO must always be interpreted alongside spirometry (FEV1/FVC ratio, TLC) and the clinical context to determine whether the pattern is obstructive (emphysema — low DLCO + obstructive spirometry), restrictive (ILD — low DLCO + restrictive spirometry), or vascular (pulmonary hypertension — isolated low DLCO with normal spirometry).
DLCO = CO uptake (mL/min) / Alveolar CO concentration (mmHg); % predicted = measured DLCO / predicted DLCO × 100
- 1Patient performs a full exhalation then inhales a gas mixture containing 0.3% CO, 10% helium (or methane for single-breath), 21% oxygen, and balance nitrogen.
- 2After a 10-second breath-hold, the patient exhales; the initial portion is discarded (representing dead space), and the alveolar sample is collected.
- 3CO uptake is calculated from the difference between inspired and expired CO concentrations, corrected for the breath-hold time.
- 4Alveolar volume (VA) is derived from the helium or methane dilution.
- 5DLCO = (CO inspired − CO expired) / (mean alveolar CO × breath-hold time).
- 6Result is expressed as % of predicted based on age, sex, height, ethnicity using GLI-2017 or Crapo reference equations.
- 7Correct DLCO for haemoglobin: adjusted DLCO = measured DLCO × (10.22 + Hb) / (1.7 × Hb) for males; (9.38 + Hb) / (1.7 × Hb) for females.
Low DLCO in COPD distinguishes emphysematous phenotype from chronic bronchitis (which has relatively preserved DLCO)
Emphysema destroys alveolar walls, reducing the surface area available for gas exchange and lowering DLCO, combined with airflow obstruction on spirometry.
Request HRCT chest and rheumatological screen
Restrictive spirometry (low TLC) with low DLCO suggests thickening of the alveolar membrane, typical of interstitial lung diseases.
Isolated DLCO reduction is a hallmark of pulmonary arterial hypertension and thromboembolic disease
When DLCO is low but spirometry is normal, the problem is at the vascular level — reduced pulmonary capillary blood volume limits CO uptake without affecting airflow.
Always correct DLCO for haemoglobin before interpreting as truly abnormal
Anaemia reduces CO uptake because there is less haemoglobin to bind CO, artificially lowering the measured DLCO. Haemoglobin correction reveals the true diffusion capacity.
Diagnosing and monitoring interstitial lung diseases (IPF, hypersensitivity pneumonitis, NSIP) alongside HRCT and spirometry.. This application is commonly used by professionals who need precise quantitative analysis to support decision-making, budgeting, and strategic planning in their respective fields
Differentiating emphysematous COPD (low DLCO) from chronic bronchitis phenotype (relatively preserved DLCO).. Industry practitioners rely on this calculation to benchmark performance, compare alternatives, and ensure compliance with established standards and regulatory requirements
Screening for pulmonary arterial hypertension in systemic sclerosis and other connective tissue diseases.. Academic researchers and students use this computation to validate theoretical models, complete coursework assignments, and develop deeper understanding of the underlying mathematical principles
Pre-operative lung function assessment before thoracic surgery (lobectomy, pneumonectomy) to estimate post-resection residual function.. Financial analysts and planners incorporate this calculation into their workflow to produce accurate forecasts, evaluate risk scenarios, and present data-driven recommendations to stakeholders
Post-COVID sequelae assessment: objective measurement of gas transfer impairment in patients with persistent dyspnoea.. This application is commonly used by professionals who need precise quantitative analysis to support decision-making, budgeting, and strategic planning in their respective fields
DLCO After Lung Resection
After pneumonectomy or lobectomy, DLCO falls proportionally to the volume of lung removed. Predicted post-operative DLCO is calculated as: pre-op DLCO × (1 − fraction of functional lung removed). Post-operative DLCO above 40% predicted is generally required for safe surgical resection in lung cancer. Serial monitoring post-resection establishes the new baseline.
DLCO in Connective Tissue Disease
Systemic sclerosis (scleroderma) causes both ILD (which reduces DLCO with restriction) and pulmonary arterial hypertension (which reduces DLCO with normal spirometry). An isolated DLCO fall in systemic sclerosis should always prompt echocardiography for PAH screening. Annual DLCO monitoring is recommended in systemic sclerosis patients.
DLCO in COVID-19 Sequelae
Persistent dyspnoea in post-COVID syndrome may be associated with reduced DLCO from parenchymal fibrosis, microvascular damage, or pulmonary microthrombi. Studies have shown 20–40% of hospitalised COVID-19 patients have reduced DLCO at 3–6 months follow-up. DLCO is a useful tool for objective assessment of post-COVID respiratory sequelae.
Technical Factors Affecting DLCO
DLCO measurement is effort-dependent and technique-sensitive. Common technical issues: incomplete inhalation (underestimates DLCO), breath-hold less than 8 or more than 12 seconds (alters CO kinetics), carboxyhaemoglobin from smoking (falsely lowers DLCO), and poor exhalation manoeuvres. Three acceptable and reproducible manoeuvres with ≤3 mL/min/mmHg variability are required for a valid test.
| % Predicted | Severity | Common Causes |
|---|---|---|
| >80% | Normal | Healthy individual; polycythaemia (if elevated) |
| 61–80% | Mild reduction | Early ILD, mild emphysema, pulmonary HTN |
| 41–60% | Moderate reduction | Moderate emphysema, ILD (IPF, HP), pulmonary HTN, PE |
| ≤40% | Severe reduction | Severe emphysema, advanced ILD, severe pulmonary HTN, anaemia (uncorrected) |
Why is CO used to measure diffusing capacity?
CO has an extremely high affinity for haemoglobin (200–250× that of oxygen), so essentially all CO that crosses the alveolar membrane is immediately bound to haemoglobin in the pulmonary capillaries. This means the CO tension in pulmonary capillary blood remains near zero throughout the measurement — making CO transfer entirely dependent on diffusion capacity rather than blood flow, which is exactly what we want to measure.
What is the difference between DLCO and TLCO?
DLCO (Diffusing Capacity for Carbon Monoxide) and TLCO (Transfer factor for CO) refer to the same measurement — the difference is geographic convention. DLCO terminology is used predominantly in North America; TLCO is the preferred terminology in Europe and the UK. Some labs also report KCO (DLCO/VA), which corrects DLCO for alveolar volume — useful when lung volumes are reduced.
What conditions cause a high DLCO?
DLCO is elevated (>120% predicted) in: polycythaemia vera (more haemoglobin available to bind CO), pulmonary haemorrhage (free haemoglobin in alveoli binds CO — an important clue to alveolar bleeding), left-to-right cardiac shunts (more pulmonary blood flow), asthma (mild elevation due to increased lung volume), and obesity (more blood in pulmonary circulation). A high DLCO in the context of haemoptysis strongly suggests alveolar haemorrhage.
How does DLCO help differentiate COPD phenotypes?
In COPD, a significantly reduced DLCO (<60% predicted) indicates predominant emphysematous destruction of alveolar walls, predicting worse exercise tolerance and poorer prognosis. Patients with chronic bronchitis (mucus hypersecretion phenotype) have relatively preserved DLCO despite significant airflow obstruction. The DLCO-spirometry pattern helps guide management — emphysema patients may particularly benefit from lung volume reduction surgery if appropriately selected.
What should I do before a DLCO test?
Patients should avoid smoking for at least 4 hours (ideally 24 hours) before testing, as carboxyhaemoglobin from smoking occupies haemoglobin binding sites and falsely lowers DLCO. Avoid vigorous exercise for 4 hours before. Patients should not eat a large meal within 2 hours. Supplemental oxygen should be stopped before testing as oxygen affects alveolar CO concentration measurements.
What causes DLCO to fall in pulmonary embolism?
Pulmonary embolism occludes pulmonary vasculature, reducing the effective capillary blood volume available for CO uptake. The dead space created by PE — ventilated alveoli with no perfusion — does not contribute to CO uptake, lowering the measured DLCO. DLCO reduction in PE is proportional to the extent of vascular occlusion and can persist if chronic thromboembolic disease develops.
What is KCO and when is it useful?
KCO (also called DLCO/VA or transfer coefficient) is DLCO corrected for alveolar volume. It is particularly useful when lung volume is reduced (e.g., after pneumonectomy or in ILD) — in these settings, a low DLCO may simply reflect small lung volume rather than intrinsic membrane disease. If DLCO is low but KCO is preserved, the impairment is due to reduced lung volume rather than membrane damage.
How often should DLCO be monitored in ILD?
In interstitial lung diseases (IPF, NSIP, hypersensitivity pneumonitis), serial DLCO measurements every 3–6 months are used to track disease progression and treatment response. A decline in DLCO of >10–15% over 6–12 months is clinically significant and associated with increased mortality risk, often prompting escalation of antifibrotic therapy (nintedanib, pirfenidone) or referral for lung transplantation.
Pro Tips
The pattern of DLCO relative to spirometry is diagnostically powerful: DLCO low + obstruction = emphysema; DLCO low + restriction = ILD; DLCO low + normal spirometry = vascular disease (PAH or PE). Use this triad to guide the next investigation.
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Carbon monoxide was first proposed as a test gas for measuring pulmonary diffusing capacity in 1909 by the physiologists Marie Krogh and August Krogh (the latter later won the Nobel Prize for his work on capillary physiology). Marie Krogh conducted the initial studies by having patients inhale CO and measuring its disappearance from alveolar air — a technique that, with modern refinements, remains essentially unchanged today.
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