Pulmonary function test and bronchial challenge test

P U L M O N A R Y F U N C T I O N T E S T
A N D
B R O N C H I A L C H A L L E N G E T E S T
K U L L A P O R N PA S B E N YA J I R A PA C H , M D

PULMONARY
FUNCTION
TEST
Acknowledgement:
Chutima Phuaksaman, MD

INDICATIONS FOR
PULMONARY FUNCTION TEST
• Detect mechanical dysfunction of the respiratory system
• Quantify the degree of dysfunction detected
• Define the nature of dysfunction
– Obstructive
– Restrictive
– Mixed
• Follow the course of diseases
• Evaluate the effect of therapeutic interventions
Kendig’s Disorders of the Respiratory Tract in Children 8th Edition

INDICATIONS FOR SPIROMETRY
• Diagnostic:
– To evaluate symptoms, signs or abnormal laboratory tests
– To measure the effect of disease on pulmonary function
– To screen individuals at risk of having pulmonary disease
– To assess pre-operative risk
– To assess prognosis
– To assess health status before beginning strenuous physical activity
program
Eur Respir J 2005: 26: 319-338.

• Monitoring:
– To assess therapeutic intervention
– To describe the course of disease that affect lung function
– To monitor people exposed to injurious agents
– To monitor for adverse reactions to drugs with known pulmonary toxicity
• Disability/impairment evaluations
– To assess patients as part of a rehabilitation program
– To assess risks as part of an insurance evaluation
– To assess individuals for legal reasons
Eur Respir J 2005: 26: 319-338.

• Public health
– Epidemiological surveys
– Derivation of reference equations
– Clinical research
Eur Respir J 2005: 26: 319-338.

CONTRAINDICATIONS
• Hemoptysis
• Recent pneumothorax
• Recent stroke, abdominal/thoracic/eye surgery
• Cardiovascular instability
• Vascular aneurysm
Relative contraindications: dizziness, nausea, vomiting, chest-abdominal-facial
pain
Manual of Pulmonary Function Testing 9th Edition, 2009

COMPLICATIONS
• Pneumothorax
• Paroxysmal cough
• Bronchospasm
• Chest pain
• Transient hypoxia in oxygen dependent patient
• Increased ICP
• Dizziness
Manual of Pulmonary Function Testing 9th Edition, 2009

SPIROMETRY
• Volume displacement spirometer
– Water seal spirometer
– Dry rolling seal spirometer
– Bellows-Type Spirometers
• Flow-sensing spirometer
– Pneumotachometer or pressure differential type
– Thermistor , hot-wire anemometer
– Turbine flow sensor
– Ultrasonic flow sensor
Jones and Bartlett. Chapter1: Forced Spirometry and Related Tests

SPIROMETRY IN CHILDREN
• Age at least 5-6 years up
– Ability to perform maneuver follow command
– Able to take deep breaths, cough and blowout forcefully
• Experienced technicians
• Environment:
- Bright, pleasant atmosphere
- Quiet and free of distraction
- Room not use for other unpleasant procedure
- May be permit parents in room (but not disturb the test)

SUBDIVISIONS OF LUNG VOLUME

PROCEDURES FOR RECORDING
FORCED VITAL CAPACITY
• Check the spirometer calibration
• Explain the test Prepare the subject
• Ask about smoking, recent illness, medication use, etc.
– Measure weight and height without shoes
• Wash hands
• Instruct and demonstrate the test to the subject, to include
– Correct posture with head slightly elevated
– Inhale rapidly and completely
– Position of the mouthpiece (open circuit)
– Exhale with maximal force
ATS/ERS Task Force Standardization of Spirometry, Eur Resp J 2005.

• Perform maneuver (closed circuit method)
• Have subject assume the correct posture
• Attach nose clip, place mouthpiece in mouth and close lips around the
mouthpiece
• Inhale completely and rapidly with a pause of ,1 s at TLC
• Exhale maximally until no more air can be expelled while maintaining an upright
posture
• Repeat instructions as necessary, coaching vigorously
• Repeat for minimum of 3 maneuvers; no more than 8
• Check test repeatability and perform more maneuvers as necessary
ATS/ERS Task Force Standardization of Spirometry, Eur Resp J 2005.
PROCEDURES FOR RECORDING
FORCED VITAL CAPACITY

INTERPRETING PFT
1. Acceptability of test
2. Flow volume curve/loop
3. Parameter
– FVC
– FEV1
– FEV1/FVC ratio
– FEF25-75%
4. Reversibility

ACCEPTABILITY CRITERIA FOR FVC
MANEUVER

FREE FROM ARTIFACT
– No cough, early terminate
– Maximal effort
– No leak, obstructed mouthpiece
ATS/ERS Task Force Standardization of Lung Function Test, Eur Resp J 2005.

UNSATISFIED FLOW-VOLUME
CURVE
Hesitating start
Early termination Stopped exhaling
momentarily
Coughing during 1st s
Not exert maximal effort at start of expiration

START OF TEST CRITERIA
• Extrapolated volume < 5% of FVC or 0.15 L (which is greater)

END OF TEST CRITERIA
1) Cannot or should not continue further exhalation: marked discomfort, near
syncope
2) No change in volume-time curve (< 0.025 L) for at least 1 sec and exhaled
duration
≥ 3 sec in children < 10 yr
≥ 6 sec in children > 10 yr

INTERPRETING PFT
1. Acceptability of test
2. Flow-Volume curve/loop
3. Parameter
– FVC
– FEV1
– FEV1/FVC ratio
– FEF25-75%
4. Reversibility

QUALITY OF FLOW-VOLUME LOOP
(a) a rapid rising to peak
flow
(b) fairly smooth curve,
continuous decrease in
flow
(c) terminates at a flow
within 0 to 0.1 L/s of
zero flow or ideally at
zero flow
TLC
RV

FLOW-VOLUME CURVE
Steep slope and decrease volume Scoop out with decrease slope
Restrictive lung defect Obstructive lung defect

FORCED VITAL CAPACITY (FVC)
“Maximal volume of air exhaled from maximally forced
expiration as effort from a maximal inspiration”
• Normal host: FVC ~ VC (difference < 200 ml)
• Depend on effort and adequate exhalation
Disease with low FVC
- Restrictive lung disease from chest wall, lung parenchyma,
respiratory muscle
- Severe airflow obstruction with air trapping
- Inadequate exhalation

FORCED EXPIRATORY VOLUME IN
1 SEC (FEV1)
“Maximal volume of air exhaled in first second of forced expiration”
• Less variation (normal 10-15%)
• Good correlation with PEFR
• Good for diagnosis, follow up and evaluate reversibility
Disease with low FEV1
• obstructive lung disease (large airway)
• restrictive lung disease from chest wall, lung parenchyma,
respiratory muscle
• increase age, poor effort

FORCED EXPIRATORY VOLUME IN
1 SEC (FEV1)

Eur Respir J 2005; 26: 948–968.

FEV1/FVC RATIO (FEV1%)
“Maximal volume of air exhaled in the first second of forced expiration
compared to FVC”
• More sensitive than FEV1 for detecting mild airway obstruction
• More variation than FEV1  less benefit for F/U or assess reversibility
test
• Advantage for DDx obstructive and restrictive lung disease

NORMAL VALUES OF LUNG
FUNCTION
• <80% predicted is still quite commonly applied to FVC, FEV1,TLC, etc.
• Fixed values (80% of predicted FVC, 0.7 for FEV1/FVC) estimated based on
middle age adults, erroneous clinical decision in children, sex bias
• Using reference data in interpretation of results
– z-score (-1.645) = 5th percentile Lower limit of normal
– The true LLN = age- and/or height-dependent, varying percent values in
different individuals
ARCCM Vol.196 Dec 1, 2017.

GRADING THE QUALITY OF
PULMONARY FUNCTION TESTS
ARCCM Vol.196 Dec 1, 2017.

FORCED EXPIRATORY FLOW RATE
AT 25-75% OF FVC (FEF 25-75%)
“Mean forced expiratory flow between 25% and 75% of the FVC”
• Maximum mid-expiratory flow
• The hypothesis that reduced mid-expiratory flow =specific for
small airways disease has been shown to be incorrect
• The limitation of instantaneous and mid expiratory flows: make
the recommendation to disregards this value
• Discordance between FEF25-75% and FEV1 to detect air flow
obstruction
Eur Respir J 2014; 43: 1051-1058.

FEF 25-75%
FVC
Calculated by determining the slope of the line drawn connecting
points on the spirogram at 25% to 75% of expiratory vital capacity
△V
△T

SEVERITY OF DYSFUNCTION
Parameters Obstructive
(FEV1)
Restrictive
(TLC)
Normal ≥ 80% ≥ 80%
Mild 60-79% 70-79%
Moderate 40-59% 50-69%
Severe < 40% < 50%
Kendig’s Disorders of the Respiratory Tract in Children 7th Edition 2006

AIRWAY REACTIVITY TEST
• Bronchodilator challenge “reversibility test”
- most choice of an aerosolized bronchodilator (albuterol, metaproterenol,
isoetharine, isoproterenol, or ipratropium bromide)
• Bronchoconstrictor challenge: methacholine challenge test, histamine,
leukotriene, prostaglandin
• Exercise challenge

REVERSIBILITY TESTING
• Post-bronchodilator response
• Method:
1. Three acceptable tests of FEV1, FVC and PEF recorded
2. Inhaled bronchodilator administration
• 100 mcg of Albuterol / Salbutamol X 4 doses (30 sec interval) (4
puff of salbutamol)
• Anticholinergic agent (ipratropium bromide) 40 mcg X 4 doses
3. Three additional acceptable tests are recorded
• 10-15 min later for short-acting B2 agonists
• 30 min later for short-acting anticholinergic agents

PREPARING BEFORE REVERSIBILITY
TEST
Medications Time to withhold (hr)
Regular β2 agonist 4-8
Ipratropium bromide 4-8
Cromolyn sodium 8-12
Sustained action β2 agonist 12
Methylxanthines 12
Slow-release methylxanthines 24
Inhaled steroids no need

% Change = Postdrug – Predrug
Predrug
x 100
Parameters Minimum significant changes from
baseline (%)
FVC +10
FEV1 +12
FEF25-75% + 25
PEFR + 12
Pediatr Clin North Am 1992; 39:1243-59.
Post drug test : PFT at 15 minutes after inhaled bronchodilator inhalation
BRONCHODILATOR RESPONSE TEST

PEAK EXPIRATORY FLOW
Peak
expiratory
flow
measure for the air expired from
the large upper airways (trachea-bronchi)

CLINICAL APPLICATIONS OF PEAK
FLOW METER
• Serial measurements of PEFR are essential
• Monitoring, not diagnostic
• Single value is of very limited use
• Highly effort dependent
• Height variation

INDICATION FOR USE PEAK FLOW
METER
Asthma (age > 5yr, moderate to severe)
Consider long-term daily peak flow monitoring:
—moderate or severe persistent asthma (Evidence B)
—history of severe exacerbations (Evidence B)
—patients who poorly perceive airflow obstruction and
worsening asthma (Evidence D)

TECHNIQUE
• The peak flow meter should read zero
• Standing up straight or sitting upright
• Take in as deep a breath as possible
• Place the peak flow meter in the mouth, with the tongue
under the mouthpiece
• Close the lips tightly around the mouthpiece
• Blow out as hard and fast as possible
• Write down the number obtained
• Repeat the process two more times.
Write down the highest number obtained.
Do not average the numbers

PEFR (L/Min) = [ 5 x Height (cm) ] - 400
Polgar G., Promadhat V., Pulmonary function
testing in children: techniques and standards.
Philadelphia: WB Saunders, 1971

PEFR INTERPRETATION
Zone PEFR
(% Personal best)
Actions
GREEN 80-100 Continue routine Rx
↓ meds
YELLOW
(Acute exacerbation)
50-80 ↑ Rx
↑ maintenance Rx
RED
(Severe exacerbation)
<50 Immediate
bronchodilator, call Dr. if
no improvement

DIURNAL VARIATION OF PEFR
Daily variability (%) = PEFRevening- PEFRmorning x 100
½ (PEFRmorning + PEFRevening )
more than 20% indicates a poor controlled asthma

Obstructive Mild Moderate Severe
VC 79-70 69-50 <50
FEV1 79-60 59-40 <40
FEF25-75% 60-50 49-35 <35
Restrictive Mild Moderate Severe
VC 80-65 65-50 <50
TLC 80-70 70-50 <50

INTERPRETATION
Condition VA KCO or DLCO/VA DLCO
Incomplete lung
expansion
Discrete loss of alveolar
units
Diffuse loss of alveolar
units
Emphysema
Pulmonary vascular
disease
Normal
High pulmonary blood
volume
Normal
Alveolar hemorrhage

SEVERITY CLASSIFICATION
• Normal DLCO 80 – 120% of predicted
• Grades of severity in DLCO reduction
• Diffusion defect
Grading DLCO
(%Predicted)
Normal > 80
Mild 60 – 80
Moderate 40 – 60
Severe < 40

• ↑ Chemical reaction between Hb and CO
– Polycythemia
– Left-to-right shunt
– Increase cardiac output
– Pulmonary / alveolar hemorrhage
– ↓ FiO2
– Exercise immediately before DLCO test
– Supine position
– Obesity
– Increase altitude
HIGH DLCO ADJUSTED

LOW DLCO ADJUSTED
• ↓ Membrane transfer
– ↓ Respiratory effort
– Respiratory m. weakness
– Thoracic deformity
preventing full inflation
– Interstitial disease
– Lung resection
– Emphysema
– Smoking
• ↓ Chemical reaction
between Hb and CO
• Anemia
• Pulmonary emboli
• ↑HbCO
• ↑Inspired O2 (FiO2)
• Combined
• Pulmonary edema
• Pulmonary vasculitis
• Pulmonary hypertension

AIRWAY HYPERRESPONSIVENESS
• Airway hyperresponsiveness (AHR) to exogenous stimuli - characteristic
feature of asthma
• When assessed with nonselective direct-acting stimuli such as histamine or
methacholine - defined as increase in both magnitude and the ease of induced
bronchoconstriction
Middleton’s 8th Edition

AIRWAY HYPERRESPONSIVENESS
• Increase in the magnitude of
bronchoconstriction = progressive elevation of
the plateau response on the concentration-
response (or dose-response) curve
• Increase in the ease of developing
bronchoconstriction = leftward shift of the
concentration response curve.
• Left shift = reduced provocation concentration
or dose producing a 20% fall in forced
expiratory volume in 1 second (FEV1), called
PC20 or PD20
• Hyperresponsiveness measured by the PC20 or
PD20 reflecting the leftward shift of the curve

INDICATIONS
• To exclude or confirm a suspected diagnosis of asthma (when inconclusive
spirometry, especially in those with normal or near-normal lung function
values)
• Screening applicants for situations where AHR would present a high safety
risk, such as commercial diving, submarine service and some occupational
exposures
• Diagnosis of occupational asthma (specific inhalation challenges)
Eur Respir J 2017.

CONTRAINDICATIONS
Eur Respir J 2017.

BRONCHOPROVOCATION STIMULI

MEDICATION WITHDRAW
BEFORE TEST
Practice Parameter 2016

DIRECT CHALLENGE TESTS
• Histamine and Methacholine most widely performed
2 METHODS
• 2-minute tidal breathing method
• 5 total lung capacity (TLC)–breath dosimeter method
• Results expressed as the PC20 (or PD20)

BRONCHIAL PROVOCATION TEST
• Bronchoconstrictor challenge: methacholine
• Methacholine from 0.0625 - 16 mg/mL are given by nebulization
in stepwise progression
• Pulmonary function at baseline and after each increasing dose of
methacholine until FEV1 decreases by 20% or the maximum dose
(16 mg/mL) is reached
Result: dose of methacholine that produce decline 20% of FEV1 >> lower
dose indicative of greater degrees of airway response

METHACHOLINE CHALLENGE TESTS
Eur Respir J 2017.

• AHR increase: inflammatory stimuli (and allergens), occupational sensitizers, viral infections
• AHR improve: environmental control, anti-inflammatory medications, spontaneously
• Deep inhalations to TLC followed by a breathhold causes bronchoprotection in asthmatic patients
with mild AHR (e.g., PC20 > 2 mg/mL)  false-negative
• Pediatrics population – age > 6 years, cut points same as adults
• 3 Important points for interpretation of direct (methacholine) challenges
– Normal FEV1
– Requirement of clinical currency and exposures (past few days) of suspicious symptoms
– Avoidance of deep inhalation during methacholine inhalation

INDIRECT CHALLENGE TESTS
• Direct challenges more sensitive
• Indirect challenges more specific for asthma, probably correlate
better with asthma severity, activity

INDIRECT CHALLENGE TESTS

EXERCISE-INDUCED
BRONCHOCONSTRICTION
• Single, relatively high-dose challenge of near-maximal exercise for about 6 minutes
• Treadmill (> cycle ergometer)
• Dry and cool air (< 50% relative humidity, < 25 C)
• Target HR = 80 - 90% of predicted maximum (220 - age)
Positive: > 10% drop of FEV1

EUCAPNIC VOLUNTARY HYPERPNEA
• Inhale dry air with 5% CO2 for 6 minutes, targeting a minute ventilation of 30 × FEV1,
equivalent to 85% of the calculated maximum voluntary ventilation (MVV)
• Measure FEV1 before and after EVH for up to 10 or 15 minutes
Positive: > 10% drop of FEV1
• Mechanism of bronchoconstriction: osmotic challenge from excessive drying of airway mucosa
same to EIB
• EVH - current test of choice recommended by the International Olympic Committee for the
assessment of athletes with EIB

HYPERTONIC SALINE
• Indirect challenges more specific for asthma, probably correlate better with asthma severity,
activity complementary to hi
• Inhaling 4.5% saline from a high-output ultrasonic nebulizer (1-2 mL/min) for doubling
amounts of time ranging from 0.5-8 minutes
• Measure FEV1 at time points similar to those of the histamine and methacholine challenges
• Mechanism of bronchoconstriction: osmotic effect

ADENOSINE CHALLENGE
• Adenosine or adenosine monophosphate  nonosmotic release of mast cell mediators
• Methods identical to that for histamine and methacholine except for concentrations used
(doubling concentrations up to 400 mg/mL)

DRY POWDER MANNITOL
• Osmotic challenge
• The doses are 0 (placebo control), 5, 10, 20, 40, 80, 160, 160, and 160 mg, giving a cumulative
dose-response curve ranging from 0 to 635 mg
• Endpoint = targeted 15% fall in FEV1 measured 1 minute after each dose
• Interval between doses should be 2 minutes or only slightly longer
• Mannitol PD15 > 635 mg = Normal

NONSELECTIVE BRONCHIAL
CHALLENGES

SUMMARY
• Direct (e.g., methacholine) challenges with no deep inhalations - tests of choice
 Negative: rule out clinically current asthma with reasonable certainty
 Positive: support a diagnosis of asthma
• Negative direct challenges in possible EIB should be followed by more specific test
• Indirect challenges (e.g., EVH, mannitol) - tests of choice
– Assess EIB especially for regulatory agencies (e.g., athletic, military, SCUBA diving)
– Assess asthma control, monitoring asthma treatment
– Differentiating asthma from other airway disease (COPD)
– Inferring exposure to a sensitizer in evaluation of occupational asthma
• Positive indirect challenge and a methacholine PC20 < 1 mg/mL (normal spirometry) probably high
specificity and PPV for asthma

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