Bronchial Challenge Testing

Bronchial Challenge Testing

Yoavanit Srivaro M.D.

Outlines

• Airway Hyperresponsiveness

• Direct Challenge Tests

: Methacholine Challenge Tests

• Indirect Challenge Tests

: Exercise challenge tests

: Eucapnic voluntary hyperpnea

: Hypertonic saline

: Dry powder mannitol

: Adenosine challange

• Allergen induced asthmatic response

Airway Hyperresponsiveness

• Characteristic feature of asthma

• Variable airflow obstruction

Cockcroft DW. Bronchial Challenge Testing . In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, et al., editors. Middleton's allergy principle and practice. Vol. 1. 8th ed. Philadelphia: Elsevier Saunders; 2014. p. 1042-55.

Why are asthmatic airway hyperresponsiveness?

• Airway epithelial damage

• Airway smooth muscle hypertrophy

Irvin CG. Development, Structure, and Physiology in Normal Lung and in Asthma . In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, et al., editors. Middleton's allergy principle and practice. Vol. 1. 8th ed. Philadelphia:

Elsevier Saunders; 2014. p. 700-14.


• Increase in magnitude of bronchoconstriction

• Increase in ease of induced bronchoconstriction


Figure 64-1 Hypothetical methacholine dose-response curves

in magnitude of bronchoconstriction












the ease of induced bronchoconstriction













Direct agents trigger bronchoconstriction

• Acting directly on airway smooth muscle receptors

- Cholinergic agonists acting on muscarinic receptor

- Histamine acting on H1 receptors

Pauwels R, Joos G, Van der Straeten M. Bronchial hyperresponsiveness is not bronchial hyperresponsivenessis not bronchial asthma. Clin Allergy 1988;18:317-21.

Figure 97-1 Muscarinic receptor subtypes found in the lung and on inflammatory cells.

Peters SP, Dykewicz MS. Anticholinergic Therapies. In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, LemanskeRF, et al., editors. Middleton's allergy principle and practice. Vol. 2. 8th ed. Philadelphia: Elsevier Saunders; 2014. p. 1552-

66.

Indirect agents stimuli bronchoconstriction(1)

• Act through one or more intermediate pathways

• Release of mediators from inflammatory cells

: Mast cells

• More clinically relevant for asthma


Indirect agents stimuli bronchoconstriction(2)

• Osmotic

: Exercise, cold air, hyperventilation, mannitol

• Nonosmotic

: Adenosine monophosphate






GINA Guideline 2015

Outlines



: Methacholine challenge tests




: Hypertonic saline




Indication

• Asthma dx in cases where spirometry &reversibility

tests are not enough.

• Occupational asthma

• Asthma severity

• Treatment response evaluation

• ResearchCrapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, et al. Guidelines for methacholine and exercise

challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 2000;161:309-29.

Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, et al. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors,

July 1999. Am J Respir Crit Care Med 2000;161:309-29.









Methacholine challenge tests

• Two-minute tidal breathing dosing protocol

• Five-breath dosimeter protocol



Two-minute tidal breathing dosing protocol

Step 1

http://www.provocholine.com


Step 2



Step 3


Step 4

• Dry compressed air to power the nebulizer• Set the pressure regulator to 50 lb/in2• Nebulizer output 0.13 ml/min



Step 5




Step 6

• Breathe quietly (tidal breathing) for 2 min


Step 7


Step 7

• Measure the FEV1 about 30 and 90 s after the nebulization is completed.• Perform no more than three or four maneuvers after each dose.• Take no more than 3 min to perform• Time interval between the commencement of two subsequent concentrations

should be kept to 5 min.http://www.provocholine.com


Step 7

• Report the highest FEV1 from the acceptable maneuvers.


Five-breath dosimeter protocol.



Step 1


Step 2




Step 3



Step 4

• Open the dosimeter solenoid to make sure the nebulizer is nebulizing.


Step 5

• Instruct the patient to inhale slowly and deeply from the nebulizer. • Trigger the dosimeter soon after the inhalation begins


Step 5

• Encourage the patient to continue inhaling slowly (about 5 s to complete the inhalation) • Encourage the patient to hold the breath (at total lung capacity, TLC) for another 5 s..



Step 5

• Repeat step for a total of five inspiratory capacity inhalations.• Take no more than a total of 2 min to perform these five inhalations.


Step 6

• Measure the FEV1 about 30 and 90 s after the nebulization is completed.• Perform no more than three or four maneuvers after each dose.• Take no more than 3 min to perform• Time interval between the commencement of two subsequent concentrations

should be kept to 5 min.



Step 7

Step 7

Step 8






Bronchoprovocative Test





Interpretation



















Figure 64-2 Comparison of two methacholine challenge methods in 55 patients with asthma.












Caveat regarding interpretation

• AHR is variable

: From time to time

: Increasing with inflammatory stimuli

• Baseline airway caliber

• Medications

• Severity of AHR does not equate with asthma severity



• AHR is variable

: From time to time



• Medications




• AHR is variable

: From time to time



• Medications




• AHR is variable

: From time to time



• Medications




• : recent onset of disease

• : longer duration of disease

• Reverse in pt with recent onset of occupational

asthma who had no exposure 48 hours

• Reverse in children



• Interprete negative methacholine challenge

:clinical current

• Negative histamine or methacholine challenge in

the winter does not exclude seasonal pollen

induced asthma.


Outlines







: Hypertonic saline

: Adenosine challenge



Indirect Challenge Tests(1)

• Act through one or more intermediate pathways

• Release of mediators from inflammatory cells

: Mast cells

• More clinically relevant for asthma


Figure 50-12 Schematic diagram to demonstrate mechanisms of exercise-induced bronchoconstriction in asthma.

Holgate ST, Sly PD. Asthma pathogenesis. In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, et al., editors. Middleton's allergy principle and practice. Vol. 1. 8th ed. Philadelphia: Elsevier Saunders; 2014. p. 812-41.
















• Osmotic

: Exercise, cold air, hyperventilation, mannitol

• Nonosmotic

: Adenosine monophosphate



• Differentiate asthma from COPD

• Correlate better with airway eosinophilia

• Improve more with anti-inflammatory therapy






Cockcroft DW. Anticholinergic Therapies. In: Adkinson NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF, et al., editors. Middleton's allergy principle and practice. Vol. 1. 8th ed. Philadelphia: Elsevier Saunders; 2014. p. 1042-55.

Outlines







: Hypertonic saline




Indication

• Asthmatic patients with a hx of breathlessness during or

after exertion

• EIB would impair ability of a person with a hx suggesting

asthma to perform demanding or lifesaving work

• Evaluate effectiveness & optimal dosages

of medications prescribed to prevent EIB



Contraindication



Contraindication



• Unstable cardiac ischemia

• Malignant arrhythmias

• Orthopedic limitation

Mode of exercise



Motor-driven treadmill with adjustable speed and grade

Electromagnetically braked cycle ergometer

Inhalate(1)

• Inspires dry air less than 25 ◦c with a noseclip

• Conducting the study in an air-conditioned room

:Temperature of 20–25 ◦c

:Low relative humidity (50% or

less)



Inhalate(2)

• Inspire dry air through mouthpiece & two-way

breathing valve

• Dry inhalate is obtained by filling talc-free

meteorological balloons with gas from a medical-

grade compressed air source



Pre-Exercise Measurement of FEV(1)


6-8 minute treadmill test at 80-90%maximum HR


6-8 minute treadmill test at 80-90%maximum HR

Post-Exercise Measurement of FEV(1)• Record with in 30 min• Decrease more than 10% • Indicates exercise induce asthma

Parsons JP, Hallstrand TS, Mastronarde JG, Kaminsky DA, Rundell KW, Hull JH, et al. An official American Thoracic Society clinical practice guideline: exercise-induced

bronchoconstriction. Am J Respir Crit Care Med 2013;187:1016-27.

Protocol(1)

• Starting at a low speed & grade 2-4 min

• Speed and grade are chosen to produce 4–6 min of

exercise at near-maximum targets

• Total duration of exercise of 6–8 min

Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, et al. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med

2000;161:309-29.Parsons JP, Hallstrand TS, Mastronarde JG, Kaminsky DA, Rundell KW, Hull JH, et al. An official American Thoracic Society clinical practice

guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med 2013;187:1016-27.

Protocol(2)

• Targets exercise HR of 80% to 90% of the

predicted maximum, or 220 minus age.

• Achieve target ventilation or heart rate

: Speed greater than 3 mph (about 4.5 km/h)

: Gradient greater than 15% or

oxygen consumption of 35 ml/min/kg



Age 20 yearsMaximum heart rate=220 minus age

=220-20=200

Targets exercise HR of 80% to 90% of Maximum heart rate= 200x0.8 to 200x 0.9= 160 to 180 beat per min


=220-20=200



=220-20=200



=220-20=200



=220-20=200


Protocol(2)









Protocol(2)









Bruce Protocol Stage??????

: Speed greater than 3 mph (about 4.5 km/h) : Gradient greater than 15% or


: Speed greater than 3 mph (about 4.5 km/h) : Gradient greater than 15% or


Protocol(1)

• Target work rate (watts) =(53.76 x measured FEV1)- 11.07

• Work rate is set to

: 60% of the target in the first minute

: 75% in the second minute

: 90% in the third minute

: 100% in the fourth minute Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, et al. Guidelines for methacholine and exercise

challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 2000;161:309-29.

Protocol(2)

• Target exercise intensity to be sustained for 4–6 min

• Work rate may need to be reduced in the final minutes

of exercise

• The test ends when the patient

has exercised at the target

work rate for 6 min.



Outlines







: Hypertonic saline




Eucapnic voluntary hyperpnea(1)





•

Step 1

• FEV1 is measured before EVH .

http://www.youtube.com


Step 1



• Patient breath at 30 x FEV1= 85% MVV • For 6 minutes

Step 2



•

Step 3

• FEV1 is measured after EVH for up to 10 or 15 minutes. • A 10% reduction in FEV1 is considered positive.




• Produce similar results to exercise challenge test

• Less expensive

• Less sophisticated equipment

• High sensitivity than exercise challange

Anderson SD, Sue-Chu M, Perry CP, Gratziou C, Kippelen P, McKenzie DC, et al. Bronchial challenges in athletes applying to inhale a beta2-agonist at the 2004 Summer Olympics. J Allergy Clin Immunol 2006;117:767-73.

http://www.Olympic.org

Outlines







: Hypertonic saline




Hypertonic saline(1)

• Inhaling 4.5% saline from a high-output ultrasonic

nebulizer

• Doubling-dose challenge 1 to 2 mL/min

• Time ranging from 0.5 to 8 minutes (total 15.5 min)

• Measure the FEV1 about 60 s after the nebulization

is completed.

Parsons JP, Hallstrand TS, Mastronarde JG, Kaminsky DA, Rundell KW, Hull JH, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med 2013;187:1016-27.

Hypertonic saline(2)

• Time Protocol: 30 sec, 1min, 2 min, 4 min, 8 min

• Measurements : FEV1 Pre & 60 sec. post dose with

highest value for FEV1 recorded

• Positive Response: Fall FEV1 ≥15% between consecutive

doses


http://www.aquaworld.com.mx

Outlines







: Hypertonic saline




Dry powder mannitol(1)

http://www.aridol.info


• Progressive Protocol: 0, 5, 10, 20, 40, 80, 160, 160, 160 mg

• Measurements : FEV1 Pre & 60 sec post dose with


• Positive Response: Fall FEV1 ≥15% between consecutive

doses



• Expression of result:

Sensitivity PD15

Reactivity Response Dose Ratio

Final % fall FEV1 / Cumulative dose

• Recovery: Bronchodilator or spontaneous


Outlines







: Hypertonic saline




Adenosine challenge(1)

• Adenosine or adenosine monophosphate

• Results in nonosmotic release of mast cell

mediators

• Methods for AMP challenge are identical to that for

histamine and methacholine


Figure 1Extracellular adenosine is produced predominantly by the metabolism of ATP released from cells.

Tilley SL, Boucher RC. A1 antagonism in asthma: better than coffee? J Clin Invest 2005;115:13-6.

Figure 1Extracellular adenosine is produced predominantly by the metabolism of ATP released from cells.


Figure 2Model of receptors and cell types mediating the pro and anti-inflammatory effects of adenosine in the lung.


Figure 2Model of receptors and cell types mediating the pro and anti-inflammatory effects of adenosine in the lung.


Adenosine challenge(2)

• Progressive Protocol: 3.125, 6.25, 12.5, 25, 50, 100, 200, 400mg/ml

• Measurements : FEV1 Pre & 30,90 sec. post dose with


• Positive Response: Fall FEV1 ≥20% between consecutive doses


Fig. 1Diagnosing Asthma & Bronchoconstriction in Athletes





Outlines







: Hypertonic saline




Allergen induced early asthmatic response


Allergen induced early asthmatic response


Allergen induced late asthmatic response
















Take Home Message

• Nonselective direct challenges (e.g. methacholine)

: Highly sensitive

: Function best to exclude asthma

Take Home Message

• Important caveats for interpretation of direct

(methacholine) challenges

: Normal FEV1

: Clinical currency

: Avoidance of deep inhalations

Take Home Message

• Nonselective indirect challenges

: More specific for asthma

: Less sensitive for asthma

: Function best to confirm the diagnosis of asthma

Bronchial Challenge Testing

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