The document discusses the diffusion capacity (DLCO) test, which measures gas diffusion across the alveolo-capillary membrane, particularly the uptake of oxygen by red blood cells. It outlines determinants of normal and abnormal DLCO values, indications for evaluation, and interpretation of results, emphasizing its relevance in diagnosing parenchymal lung diseases and monitoring treatment efficacy. Additionally, it highlights potential pitfalls in DLCO testing and interpretation, stressing the importance of clinical context.

1. Diffusion Capacity
Indications and interpretation
Surinder K. Jindal
(Emeritus Professor, Pulm Med, PGIMER, Chandigarh)
Medical Director, Jindal Clinics, Chandigarh
www.jindalchest.com

2. Mechanisms of gas-exchange
from air to tissues

3. Alveolo-capillary membrane

4. Diffusion Capacity
• It is a test to measure diffusion of
gases across the alveolo-capillary
membrane.
• Misnomer: It is not merely diffusion
of gases – it is uptake of oxygen by
RBCs in the capillary blood.
• It is not a lung capacity
• Preferred terminology: Transfer
Factor i.e. transfer of oxygen from
alveolar air to RBCs
Clinically it is assessed by using a gas
with low solubility in pulm membrane
and high capacitance in blood (binds
to Hb) such as CO. (O2 or NO are not
routinely used)

5. DLCO estimation – Single breath

6. Normal DLCO - Determinants
1. Area of the alveolo-capillary
membrane –
alveolar surface and capillary
blood
2. Thickness of the membrane
3. Driving pressure i.e. Difference
of oxygen tension between the
alveolar gas and venous blood
• Resting level: 20-30 mL/min/ mmHg
• Normal variations:
Age
Sex
Height, weight
Alveolar volume
Ethnicity
Smoking (decreases)
Exercise (increases)
Circadian rhythm
Menstrual cycle

7. Causes of abnormal values
Decrease
• COPD – Emphysema
• Lung resection
• Bronchial obstruction
• Anemia
• Multiple Pulm emboli
• Thickened aveolo-capillary
membrane:
ILDs - IPF
Increase
• Exercise
• Asthma
• Obesity
• Polycythemia
• L to R intra-cardiac shunts
• Alveolar hemorrhage

8. Severity classification of DLCO
• Normal: >75% of predicted, up to 140%
• Mild decrease: 60% to 74%
• Moderate decrease: 40% to 59%
• Severe decrease: <40%

9. Indications
Evaluation
1. Parenchymal diseases:
IPF
H.P, CTD lung disease
Pneumoconioses
Sarcoidosis
2. Emphysema
3. Pulm vascular diseases
4. Systemic diseases
5. Interstitial infections
6. Alveolar Hmge
7. Drug pulm- toxicity
Follow-up assessment
• Severity assessment
• Disease progression
• Treatment efficacy
Parenchymal lung diseases – IPF
COPD – Emphysema
Pulm drug toxicity

10. Other uses of DLCO
• DLCO is a specific but insensitive predictor of abnormal gas exchange
during exercise. Low DLCO less than or equal to 50% predicted can
predict hypoxemia with exercise. A normal DLCO does not rule out
oxygen desaturation with exercise.
• A decrease in DLCO in persons with HIV independently predicts the
development of opportunistic pneumonia
• In the setting of a normal chest radiograph, early ILD or pulmonary
vascular disease or both can be present.
• A DLCO below 30% predicted is required by Social Security for total
disability (USA)

11. Interpretation
DLCO is the product of two primary components:
i. Surface area of the lung available for gas exchange (VA)
ii. Rate of alveolar capillary blood CO uptake (KCO)
It is always important to determine whether the reduction in DLCO is due to
reduction in VA or KCO or both.
DLCO can be falsely reduced in patients with severe COPD or severe
restrictive lung disease when the inspired CO does not completely reach the
functioning alveolo-capillary units.

12. Interpretation is step-wise progress
Look at DLCO – reduced by either a decrease in VA
or KCO; we need to look for both
components
1. Remember: DLCO = VA X KCO and
KCO = DLCO / VA
2. Look at VA – within 5% of TLC; If not, suspect loss of lung volume (collapse,
resection, NM diseases, embolic disease); DLCO reduced proportionately.
3. Look at KCO (DLCO / VA) – reduced in anemia, ILD and pulm vascular
diseases

13. Clinical problem - 1
• 45 year old male
• No known lung disease
• On amiodarone for 6 mths for cardiac problem
• Now c/o non-productive cough, dyspnea, and weight loss
• Scattered crackles on physical examination
• Suspected to develop ‘drug-induced ILD’
• Lung function tests: Normal spirometry

14. • Abnormal chest radiograph showing
chronic interstitial lung changes.
• DLCO: 62% of predicted
• Diagnosis
Amiodarone induced ILD
Amiodarone stopped
Improved after a week

15. Drug-induced lung disease
• New or worsening symptoms or
signs;
• New abnormalities on chest
radiographs;
• Decline in TLC of 15% or more, or
a decline in DlCO of more than
20%.
Chronic interstitial pneumonitis is the
most common form of drug-induced
lung disease,
The condition may improve when the
drug is stopped, with or without
adding systemic corticosteroids
Amiodarone
Amphotericin,
Methotrexate,
Cyclophosphamide,
Nitrofurantoin,
Cocaine,
Bleomycin,
Tetracycline,
Many newer biologics

16. Clinical problem 2
• A 38 year old house-wife with history of asthma since childhood; multiple anti-
asthma therapies but poorly controlled
• Normal CXR, spirometry and lung function. ECHO revealed elevated PA pressure
• DLCO: unexpectedly reduced DLCO (35% predicted)
Diagnosis: difficult-to-control young adult asthmatic woman with PAH ? COPD x
?Drugs ?Secondary to CTD
• Detailed history revealed that she was on dieting pills, methamphetamines.
• The diagnosis was made after decreased DLCO prompted a search for the reasons.

17. Clinical problem 3
• A 54 year old shopkeeper; mild smoker of over 25 years was following the Chest
Clinic with intermittent symptoms of breathlessness, wheezing, cough and phlegm.
• Chest showed increased AP diameter.
• CXR - mild hyperinflation
• Spirometry – Moderate airways obstruction with partial bronchodilatory
responsiveness.
Diagnosis: ? COPD ? Ch Bronchial Asthma
How to confirm the diagnosis?

18. DLCO in IPF
1. Evaluation of abnormal gas exchange in early IPF esp when
spirometry is normal
Normal spirometry and disproportionately low DLCO may indicate
CPFE
2. More reliable indicator of disease-outcome than other resting lung
function indices:
i. DLCO of <40% indicates advanced disease
ii. Fall of >15% from baseline value in 6-12 months
implies poor outcome and higher mortality
iii. Should be performed every 6-12 months

19. Pitfalls of DLCO
Technical
• Lack of uniformity and standardization
between different laboratories
• Lack of nomograms in India – ‘difficulty
of predicted norms’
• Routine reporting of DlCO “corrected to
normal with VA” is misleading and can
cause under-diagnosis when in fact DlCO
still is abnormal.
• Difficulties of performance – patients
with severe obstructive or restrictive dis.
Clinical Interpretation
• May be normal in:
Early ILD; PVD,
Early COPD
May be markedly reduced even in the
presence of a normal chest skiagram
• May be abnormally high (140% or
more) in: Asthma, polycythemia,
obesity, L to R shunts, hemoptysis

20. Conclusions
1. DLCO is an important PFT in the evaluation and follow-up
assessments of lung diseases; A decreasing DLCO is superior to
following changes in slow vital capacity (SVC) or TLC in ILDs.
2. Reduced DlCO in the context of normal spirometry, lung volumes, and
chest radiographs suggests underlying lung disease such as ILD,
emphysema, or PAH.
3. DLCO should always be interpreted in the context of clinical data of
the individual patient; decrease or increase in DLCO is not diagnostic
of a particular lung disease

21. THANK YOU