Lung Diffusion & Bronchoprovocation Studies

Objectives — Perform a lung diffusion capacity test and perform bronchoprovocation testing when airway hyper-reactivity or exercise-induced bronchospasm is suspected.

---

Lung Diffusion Study

Definition

DLCO is a test that measures the gas exchange capacity of the lungs.

Carbon monoxide (CO) is used as a surrogate for oxygen because the test uses CO movement across the alveolar-capillary membrane to estimate diffusion capacity.

DLCO techniques include:

• Single breath
• Steady state
• Rebreathing

The single-breath technique is the most commonly used method in this lesson.

---

DLCO Indications, Contraindications & Hazards

Indications

DLCO testing is used to evaluate or follow parenchymal lung disease, including:

• Asbestosis
• Silicosis
• Allergic alveolitis

It is also used to evaluate, differentiate, or follow obstructive lung disease, including:

• Emphysema
• Cystic fibrosis
• Asthma
• Chronic bronchitis

DLCO testing can evaluate pulmonary involvement in systemic disease, including:

• Sarcoidosis
• Rheumatoid arthritis
• Lupus

DLCO can also monitor patients at risk for drug toxicity that can affect the alveolar-capillary membrane:

• Amiodarone
• Bleomycin

Contraindications

Hazards

Hazards include hazards common to all pulmonary function testing and interruption of supplemental O2 resulting in desaturation.

---

DLCO Equipment

Special analyzers are required to perform DLCO.

Test Gas

DLCO test gas contains:

Water vapor must be removed from gas samples before CO analysis, such as with a desiccator column.

---

DLCO Pre-Procedure

Before DLCO testing:

• The patient should not smoke the day of the test to reduce CO levels in the blood.
• The patient should be off supplemental O2 for 10 minutes before testing.
• Wait 20 minutes after shunt studies or nitrogen washout.

---

Modified Krogh Technique: Single-Breath DLCO

The modified Krogh technique is the single-breath DLCO technique, also called DLCO-SB.

It is:

• Most commonly used
• Simple
• Non-invasive
• Useful for screening and clinical application

Disadvantages

Single-breath DLCO is:

• Sensitive to distribution of ventilation
• Sensitive to V/Q mismatching
• Nonphysiological because of the breath hold
• Not practical for exercise

Procedure

DLCO measurements are performed in the sitting position.

The patient:

1. Expires to RV.
2. Inspires quickly to TLC.
3. Holds the breath for 8-12 seconds.
4. Exhales normally.

Washout and Alveolar Sample

The first 0.75-1 L of exhaled gas is vented into the room as washout volume. This removes anatomic dead space from the sample.

The next 0.5-1 L of gas is analyzed for:

• CO, which measures DL
• He or CH4, which measures VA

Washout volume may need to be reduced if the patient's VC is less than 2.0 L.

If washout volume is reduced, more dead space gas may enter the analyzed sample. If washout gas is analyzed as part of the alveolar sample, DL will be underestimated.

Correct for hemoglobin and carboxyhemoglobin if values are available from ABG.

Wait at least 4 minutes between tests to allow test gas to wash out of the lungs.

---

DLCO ATS Criteria

Acceptability

An acceptable single-breath DLCO effort must meet all of the following:

Tests outside these limits should be discarded.

Reproducibility

At least two tests are performed and final results can be averaged.

Efforts must meet all acceptability criteria.

DL values must be within:

• 3 mL of each other, or
• 10% of the highest value

---

DLCO Values and Interpretation

Average DLCO-SB is:

25 mL CO/min/mmHg (STPD)

Diffusion capacity for oxygen can be estimated from DLCO:

DLO2 = DLCO x 1.23

DLCO is normally the value reported clinically.

Conditions Associated With Decreased DLCO

DLCO may be decreased in:

• Sarcoidosis
• Asbestosis
• Berylliosis
• O2 toxicity
• Pulmonary edema
• Emphysema
• Space occupying lesions
• Lung resections
• V/Q mismatch

Severity

DL, VA, and DL/VA

DL is diffusion rate.

VA is alveolar volume.

The test gas components connect to these values:

• 10% He or CH4 measures VA.
• 0.3% CO measures DL.

DL/VA is used to help differentiate disease processes that decrease DLCO.

In healthy patients:

DL/VA = 4-5 mL CO/min/L lung volume

Obstructive Pattern

In obstruction:

• DLCO is decreased.
• VA is normal.
• DL/VA is low.

DL = less than LLN
VA = normal
DL/VA = less than LLN

This is caused by uneven V/Q or uneven distribution of inspired gas.

Restrictive Pattern

In restriction:

• DLCO is decreased.
• VA is decreased.
• DL/VA is normal.

DL = less than LLN
VA = less than LLN
DL/VA = normal

The decrease is a direct result of loss of lung tissue.

---

Bronchoprovocation Studies

Definition

Bronchoprovocation is a test where bronchospasm is induced.

It is used to determine whether airway hyper-reactivity, a component of asthma, is present.

Two bronchoprovocation studies in this lesson are:

• Methacholine challenge test
• Exercise-induced asthma / exercise-induced bronchospasm testing (EIA/EIB)

---

Methacholine Challenge

Definition

Methacholine is a drug that increases parasympathetic tone in bronchial smooth muscle and causes bronchoconstriction.

In people who do not have asthma, the dose used will not cause a significant response. This makes the test highly specific for airway hyper-reactivity.

Indications

Methacholine challenge is used for patients who have history or symptoms suggestive of asthma but show:

• No evidence of airflow obstruction on PFTs, or
• Uncertain bronchodilator study results

Symptoms of asthma include:

• Wheezing
• Dyspnea
• Chest tightness
• Persistent cough

Contraindications

Relative contraindications:

• Inability to perform acceptable spirometry
• Pregnancy or nursing mothers

Absolute contraindications:

• Severe airflow obstruction, FEV1 less than 60% predicted
• Heart attack or stroke within the last 3 months
• Uncontrolled hypertension, systolic greater than 200 or diastolic greater than 100
• Known aortic aneurysm

Hazards

Hazards include:

• Shortness of breath
• Cough
• Chest tightness
• Wheezing
• Headache

Methacholine challenge testing presents risk to the patient, so a physician should be immediately available.

---

Methacholine Equipment and Preparation

Equipment includes:

• Methacholine or histamine
• Hand-held nebulizer
• Fast-acting bronchodilator

Methacholine or histamine is usually mixed in batches by pharmacy. It should be kept refrigerated until 30 minutes before the test and brought to room temperature before use.

The hand-held nebulizer delivers the drug. The exhalation port should be filtered.

The nebulizer may be:

• Powered from a wall outlet
• Powered by a dosimeter, an electrically valved system that enables manual triggering of the nebulizer

A fast-acting bronchodilator is available to reverse bronchospasm.

Medication and Exposure Restrictions

The patient should withhold the following before methacholine challenge:

Patients on corticosteroids should be challenged while taking a stable dosage.

The patient should have no coffee, tea, cola drinks, chocolate, or smoking on the day of the study.

---

Methacholine Procedure and Interpretation

The patient should be asymptomatic at the time of testing.

Perform baseline spirometry. FEV1 must be at least 60-70% predicted to begin.

An optional nebulized diluent step with NaCl may be used. This lets the patient become familiar with breathing through a nebulizer and performing spirometry properly. Patients with highly reactive airways may respond to the diluent alone.

Breathing method:

• Slow and deep breaths to TLC with a 5-second breath hold at TLC, or
• Tidal breathing for 2 minutes

Perform three acceptable FVC maneuvers 30 seconds after the last inhalation from the nebulizer.

If nebulized diluent is used, the post-diluent FEV1 is used to calculate percent change.

If post-diluent FEV1 is reduced by 10% or greater from baseline, the test is considered positive.

If post-diluent FEV1 is not reduced by 10%, the challenge begins.

Methacholine Dosing

Begin with the lowest concentration and continue to higher concentrations if necessary.

Dose range:

0.0625-16 mg/mL

Two dosing protocols:

The patient takes five breaths of the solution, with slow deep breaths to TLC and a 5-second breath hold, or breathes at tidal volume for 2 minutes.

Perform three acceptable FVC maneuvers 30 seconds after the last inhalation from the nebulizer. FVC maneuvers should be completed within 3 minutes.

Percent Decrease

Percent decrease = ((x - y) / x) x 100

x = baseline
y = current

If FEV1 does not decrease by 20%, administer the next higher dose.

A sustained decrease in all three efforts of 20% in FEV1 is a positive test, and the methacholine test is terminated.

Bronchospasm should be reversed by administering a bronchodilator. Spirometry is performed to document how effectively the bronchodilator reverses bronchospasm.

---

Exercise-Induced Asthma / Bronchospasm

Definition

Exercise-induced asthma (EIA) or exercise-induced bronchospasm (EIB) is bronchospasm that occurs during or immediately after vigorous exercise.

It is caused by:

1. Water loss from conditioning large volumes of air during exercise.
2. Heat exchange and airway cooling during exercise, followed by rewarming after exercise stops.

During exercise, ventilation can exceed 200 L/min and breathing occurs through the mouth. The nose, pharynx, and first seven generations of bronchi normally condition air. During heavy exercise, the upper airways must contribute water vapor from the respiratory epithelial surface liquid to warm and saturate the air.

After exercise stops, the bronchial vasculature dilates and engorges to rewarm the epithelium. Rebound hyperemia can narrow the airway, and engorged vessels can leak, causing mediator release and bronchospasm. This may explain why EIA/EIB can occur after exercise has stopped.

Indications

EIA/EIB testing is used for:

• Patients with shortness of breath on exertion but normal resting PFTs
• Symptomatic patients with negative or uncertain methacholine challenge results
• Patients with known EIA/EIB whose therapy is being evaluated
• Evaluating exercise limitation in asthmatics

Contraindications and Hazards

Contraindications are the same as methacholine challenge.

Relative contraindications:

• Inability to perform acceptable spirometry
• Pregnancy or nursing mothers

Absolute contraindications:

• Severe airflow obstruction, FEV1 less than 60% predicted
• Heart attack or stroke within the last 3 months
• Uncontrolled hypertension, systolic greater than 200 or diastolic greater than 100
• Known aortic aneurysm

Hazards are the same as methacholine challenge:

• Shortness of breath
• Cough
• Chest tightness
• Wheezing
• Headache

EIA/EIB challenge testing presents risk to the patient, so a physician should be immediately available.

Equipment

Equipment includes:

• EKG monitor
• Treadmill or bicycle ergometer
• Pulse oximeter
• Spirometer
• Defibrillator and code cart

---

EIA/EIB Preparation, Procedure and Interpretation

The patient should withhold the same medication list used for methacholine challenge.

The patient should:

• Avoid heavy exercise at least 4 hours before the test.
• Report for testing in comfortable clothing and running shoes.
• Be asymptomatic at the time of testing.

Baseline

Perform pre-test baseline FVC.

FEV1 must be at least 70% predicted to begin.

Connect the patient to:

• EKG monitor
• Pulse oximeter

Calculate predicted maximum heart rate:

220 - age = MHR

The patient wears nose clips to ensure mouth breathing.

Exercise

Exercise should be vigorous enough to elicit work rates between 80-90% of the patient's predicted maximum heart rate for 6-8 minutes.

Exercise continues until:

• The patient reaches target heart rate for the set time, or
• The patient becomes symptomatic

Post-Exercise Spirometry

FVC is performed within 1-2 minutes after exercise.

Then FVC is repeated at 5-minute intervals for a total of 20-30 minutes.

Interpretation

Use the same percent decrease equation:

Percent decrease = ((x - y) / x) x 100

x = baseline
y = current

A sustained decrease in all three efforts of 10-15% in FEV1 is a positive test, and the EIA/EIB test is terminated.

Bronchospasm should be reversed with a bronchodilator. Spirometry is then performed to document how effectively the bronchodilator reverses bronchospasm.

---

Quick Review

DLCO

• DLCO measures gas exchange capacity.
• CO is used as a surrogate for O2.
• 10% He or CH4 measures VA.
• 0.3% CO measures DL.
• Single-breath DLCO uses inspiration to TLC, an 8-12 second breath hold, and analysis of the alveolar sample.
• DL/VA helps differentiate obstructive and restrictive patterns when DLCO is decreased.

Bronchoprovocation

Both tests should have bronchodilator reversal followed by spirometry to document response.