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.
Airway Hyperresponsiveness
• Increase in magnitude of bronchoconstriction
• Increase in ease of induced bronchoconstriction
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.
Figure 64-1 Hypothetical methacholine dose-response curves
in magnitude of bronchoconstriction
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.
Figure 64-1 Hypothetical methacholine dose-response curves
in magnitude of bronchoconstriction
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.
Figure 64-1 Hypothetical methacholine dose-response curves
in magnitude of bronchoconstriction
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.
Figure 64-1 Hypothetical methacholine dose-response curves
in magnitude of bronchoconstriction
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.
Figure 64-1 Hypothetical methacholine dose-response curves
the ease of induced bronchoconstriction
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.
Figure 64-1 Hypothetical methacholine dose-response curves
the ease of induced bronchoconstriction
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.
Figure 64-1 Hypothetical methacholine dose-response curves
the ease of induced bronchoconstriction
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.
Figure 64-1 Hypothetical methacholine dose-response curves
the ease of induced bronchoconstriction
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.
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.
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.
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
Pauwels R, Joos G, Van der Straeten M. Bronchial hyperresponsiveness is not bronchial hyperresponsivenessis not bronchial asthma. Clin Allergy 1988;18:317-21.
Indirect agents stimuli bronchoconstriction(2)
• Osmotic
: Exercise, cold air, hyperventilation, mannitol
• Nonosmotic
: Adenosine monophosphate
Pauwels R, Joos G, Van der Straeten M. Bronchial hyperresponsiveness is not bronchial hyperresponsivenessis not bronchial asthma. Clin Allergy 1988;18:317-21.
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.
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.
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.
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.
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
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.
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.
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.
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.
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
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.
Step 4
• Dry compressed air to power the nebulizer• Set the pressure regulator to 50 lb/in2• Nebulizer output 0.13 ml/min
Two-minute tidal breathing dosing protocol
http://www.provocholine.com
Two-minute tidal breathing dosing protocol
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
Two-minute tidal breathing dosing protocol
Step 7
• Report the highest FEV1 from the acceptable maneuvers.
http://www.provocholine.com
Five-breath dosimeter protocol.
Step 4
• Open the dosimeter solenoid to make sure the nebulizer is nebulizing.
Five-breath dosimeter protocol.
Step 5
• Instruct the patient to inhale slowly and deeply from the nebulizer. • Trigger the dosimeter soon after the inhalation begins
Five-breath dosimeter protocol.
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..
http://www.provocholine.com
Five-breath dosimeter protocol.
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.
http://www.provocholine.com
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.
Five-breath dosimeter protocol.
http://www.provocholine.com
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.
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.
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.
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.
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.
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.
Interpretation
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.
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.
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.
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.
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.
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.
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.
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.
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.
Figure 64-2 Comparison of two methacholine challenge methods in 55 patients with asthma.
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.
Figure 64-2 Comparison of two methacholine challenge methods in 55 patients with asthma.
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.
Figure 64-2 Comparison of two methacholine challenge methods in 55 patients with asthma.
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.
Figure 64-2 Comparison of two methacholine challenge methods in 55 patients with asthma.
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.
Figure 64-2 Comparison of two methacholine challenge methods in 55 patients with asthma.
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.
Figure 64-2 Comparison of two methacholine challenge methods in 55 patients with asthma.
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.
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
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.
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
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.
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
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.
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
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.
Airway Hyperresponsiveness
• : 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
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.
Airway Hyperresponsiveness
• Interprete negative methacholine challenge
:clinical current
• Negative histamine or methacholine challenge in
the winter does not exclude seasonal pollen
induced asthma.
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.
Outlines
• Airway Hyperresponsiveness
• Direct Challenge Tests
: Methacholine Challenge Tests
• Indirect Challenge Tests
: Exercise challenge tests
: Eucapnic voluntary hyperpnea
: Hypertonic saline
: Adenosine challenge
: Dry powder mannitol
• Allergen induced asthmatic response
Indirect Challenge Tests(1)
• Act through one or more intermediate pathways
• Release of mediators from inflammatory cells
: Mast cells
• More clinically relevant for asthma
Pauwels R, Joos G, Van der Straeten M. Bronchial hyperresponsiveness is not bronchial hyperresponsivenessis not bronchial asthma. Clin Allergy 1988;18:317-21.
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.
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.
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.
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.
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.
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.
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.
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.
Indirect Challenge Tests(2)
• Osmotic
: Exercise, cold air, hyperventilation, mannitol
• Nonosmotic
: Adenosine monophosphate
Pauwels R, Joos G, Van der Straeten M. Bronchial hyperresponsiveness is not bronchial hyperresponsivenessis not bronchial asthma. Clin Allergy 1988;18:317-21.
Indirect Challenge Tests(3)
• Differentiate asthma from COPD
• Correlate better with airway eosinophilia
• Improve more with anti-inflammatory therapy
Pauwels R, Joos G, Van der Straeten M. Bronchial hyperresponsiveness is not bronchial hyperresponsivenessis not bronchial asthma. Clin Allergy 1988;18:317-21.
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.
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.
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.
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.
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
• Airway Hyperresponsiveness
• Direct Challenge Tests
: Methacholine Challenge Tests
• Indirect Challenge Tests
: Exercise challenge tests
: Eucapnic voluntary hyperpnea
: Hypertonic saline
: Adenosine challenge
: Dry powder mannitol
• Allergen induced asthmatic response
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
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.
Contraindication
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.
Contraindication
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.
• Unstable cardiac ischemia
• Malignant arrhythmias
• Orthopedic limitation
Mode of exercise
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.
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)
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.
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
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.
Pre-Exercise Measurement of FEV(1)
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
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.
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
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
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
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
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
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
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)
• 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
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.
Bruce Protocol Stage??????
: Speed greater than 3 mph (about 4.5 km/h) : Gradient greater than 15% or
oxygen consumption of 35 ml/min/kg
: Speed greater than 3 mph (about 4.5 km/h) : Gradient greater than 15% or
oxygen consumption of 35 ml/min/kg
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.
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.
Outlines
• Airway Hyperresponsiveness
• Direct Challenge Tests
: Methacholine challenge tests
• Indirect Challenge Tests
: Exercise challenge tests
: Eucapnic voluntary hyperpnea
: Hypertonic saline
: Adenosine challange
: Dry powder mannitol
• Allergen induced asthmatic response
Eucapnic voluntary hyperpnea(4)
• Patient breath at 30 x FEV1= 85% MVV • For 6 minutes
Step 2
http://www.youtube.com
Eucapnic voluntary hyperpnea(4)
•
Step 3
• FEV1 is measured after EVH for up to 10 or 15 minutes. • A 10% reduction in FEV1 is considered positive.
http://www.youtube.com
Eucapnic voluntary hyperpnea(5)
• 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.
Outlines
• Airway Hyperresponsiveness
• Direct Challenge Tests
: Methacholine challenge tests
• Indirect Challenge Tests
: Exercise challenge tests
: Eucapnic voluntary hyperpnea
: Hypertonic saline
: Dry powder mannitol
: Adenosine challenge
• Allergen induced asthmatic response
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
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.
Outlines
• Airway Hyperresponsiveness
• Direct Challenge Tests
: Methacholine Challenge Tests
• Indirect Challenge Tests
: Exercise challenge tests
: Eucapnic voluntary hyperpnea
: Hypertonic saline
: Dry powder mannitol
: Adenosine challenge
• Allergen induced asthmatic response
Dry powder mannitol(2)
• Progressive Protocol: 0, 5, 10, 20, 40, 80, 160, 160, 160 mg
• Measurements : FEV1 Pre & 60 sec post dose with
highest value for FEV1 recorded
• Positive Response: Fall FEV1 ≥15% between consecutive
doses
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.
Dry powder mannitol(3)
• Expression of result:
Sensitivity PD15
Reactivity Response Dose Ratio
Final % fall FEV1 / Cumulative dose
• Recovery: Bronchodilator or spontaneous
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.
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
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
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.
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.
Tilley SL, Boucher RC. A1 antagonism in asthma: better than coffee? J Clin Invest 2005;115:13-6.
Figure 2Model of receptors and cell types mediating the pro and anti-inflammatory effects of adenosine in the lung.
Tilley SL, Boucher RC. A1 antagonism in asthma: better than coffee? J Clin Invest 2005;115:13-6.
Figure 2Model of receptors and cell types mediating the pro and anti-inflammatory effects of adenosine in the lung.
Tilley SL, Boucher RC. A1 antagonism in asthma: better than coffee? J Clin Invest 2005;115:13-6.
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
highest value for FEV1 recorded
• Positive Response: Fall FEV1 ≥20% between consecutive doses
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.
Outlines
• Airway Hyperresponsiveness
• Direct Challenge Tests
: Methacholine challenge tests
• Indirect Challenge Tests
: Exercise challenge tests
: Eucapnic voluntary hyperpnea
: Hypertonic saline
: Dry powder mannitol
: Adenosine challenge
• Allergen induced asthmatic response
Allergen induced early asthmatic response
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.
Allergen induced early asthmatic response
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.
Allergen induced late asthmatic response
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.
Allergen induced late asthmatic response
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.
Allergen induced late asthmatic response
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.
Allergen induced late asthmatic response
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.
Allergen induced late asthmatic response
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.
Allergen induced late asthmatic response
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.
Allergen induced late asthmatic response
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.
Allergen induced late asthmatic response
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.
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