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Nasal and Bronchial Provocation Tests

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Chulalongkorn Allergy and Clinical Immunology Research Group
Chulalongkorn Allergy and Clinical Immunology Research Group

This document summarizes nasal and bronchial provocation tests. It describes the indications, contraindications, and methods for nasal provocation tests including nasal allergen provocation. It also discusses direct and indirect bronchial provocation tests using stimuli like methacholine or exercise, their clinical utility for diagnosis, occupational asthma, and monitoring treatment. Allergen bronchial provocation tests can help study asthma pathogenesis and evaluate new medications.

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Nasal & Bronchial Provocation Test P. Putivoranat, MD. 22/05/09
Bronchial Provocation Test ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Bronchoprovocation stimuli Adapted from Eur Respir J 2003; 21: 1050-68 & Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Non-Immunologic Indirect ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Immunologic Direct Selective Non-selective
Non-Selective Bronchial Provocation Test
Metacholine vs Histamine challenges ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Am J Respir Crit Care Med 2000; 161: 309-29. Clin Exp Allergy 2004; 34: 9-16.
Contraindications for Metacholine challenge test ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Am J Respir Crit Care Med 2000; 161: 309-29.
F actors Decrease Bronchial Responsiveness Am J Respir Crit Care Med 2000; 161: 309-29.
F actors Increase Bronchial Responsiveness ,[object Object],[object Object],Am J Respir Crit Care Med 2000; 161: 309-29. Days to months Chemical irritants Uncertain* Cigarette smoke 1 wk Air pollutants 3–6 wk Respiratory infection Months Occupational sensitizers 1–3 wk Exposure to environmental Ag s Duration of Effect Factor
Hypothetical methacholine dose–response curves Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308.
2 Metacholine challenge methods Am J Respir Crit Care Med 2000; 161: 309-29. Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308. False Negative
Metacholine challenge test Am J Respir Crit Care Med 2000; 161: 309-29.
C ut points of Methacholine BPT ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Am J Respir Crit Care Med 2000; 161: 309-29.
P ediatric BPT ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308.
Indirect Airway Hyperresponsiveness ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Clin Exp Allergy 2004; 34: 9-16. Middleton’s Allergy : principles and practice. 7th ed. 2008; 1295-308.
Mechanism of Indirect Bronchial Challenge Eur Respir J 2003; 21: 1050-68
Methacholine vs. Non-selective Indirect BPT Adapted from Eur Respir J 2003; 21: 1050-68 & Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308. ,[object Object],40 min. 5 min. 30 & 90 sec. PC 20 Adenosine Monophosphate up to 400 mg. Non -Osmotic ,[object Object],[object Object],[object Object],50 min. 5 min. 30 & 90 sec. PC 20 Methacholine 0.03-16 mg/ml Direct ,[object Object],1 min. 30 & 90 sec. 10-15 min. 10-15 min. min. Measure 2 min. 0.5-8 min. 3 min. 10-15 min. 5 min. Interval ,[object Object],[object Object],PC 20 4.5% NSS Ultrasonic nebulizer Osmotic ,[object Object],[object Object],[object Object],20-25 min. PD 15 Dry powder Mannitol 0-635 mg. Osmotic ,[object Object],[object Object],30 min.  FEV 1 10-15% Exercise 80-90% Max.HR for 6 min. Osmotic ,[object Object],[object Object],[object Object], 10% FEV 1 Dry air with 5% CO 2 for 6 min. Osmotic ,[object Object],[object Object],12 min. PD 20 18 º C 0% Humidity Osmotic ,[object Object],Target Mechanism Duration Note Methods
Clinical Utility of Non-Selective BPT ,[object Object],[object Object],[object Object],[object Object]
Non-Selective BPT for Diagnosis ,[object Object],[object Object],[object Object],[object Object],Am J Respir Crit Care Med 2000; 161: 309-29. Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308.
Non-Selective BPT for Diagnosis ,[object Object],[object Object],[object Object],[object Object],Am J Respir Crit Care Med 2000; 161: 309-29. Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308.
FN & FP results for Non-selective BPT Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308. Indirect (Exercise, EVH, etc.) Direct (Metacholine) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],False Positive False Negative
Selective Bronchial Provocation Test
Allergen BPT ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Allergen-induced EAR 32% early A sthmatic response ,[object Object],[object Object],Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308.
Allergen-induced LAR Late ≥ 40% E arly 33% Dual Asthmatic response ,[object Object],[object Object],Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308.
Allergen-induced increase in AHR AHR: 2-3 hrs. after Challenge, may persist several days DAR Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308.
Allergen-induced Eosinophils ,[object Object],[object Object],[object Object],[object Object],Allergy 2006: 61: 111–8 . Placebo Grass pollens Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308.
Medications inhibit Allergen-induced responses Diamant Z. et al. + 0 + ± ,[object Object],Pepys J et al, Hedardt et al, Cockcroft et al. ? ++ ++ ++ ,[object Object],Diamant et al., Leigh et al., Davis et al. ++ ++ ++ ++ ,[object Object],Rafferty et al, Twentyman et al, Bentley et al. ? ? ± + ,[object Object],Boulet LP et al., Fahy JV et al. +++ +++ +++ +++ ,[object Object],Gauvreau G.M. et al. ++ + + 0 ,[object Object],Leckie M.J. et al. +++ 0 0 0 ,[object Object],Cockcroft DW et al. ? ++ +++ N/A Single dose after EAR Van Der Star et al., Swystun VA. et al. +++ +++ +++ ++ Regular Twentyman OP et al., Wong BJ. et al. 0 0 mask +++ ,[object Object],Yu DYC et al., Cockcroft DW et al. 0 0 + + ,[object Object],Hendeles L et al., Cockcroft DW et al. ? 0 + + ,[object Object],Cockcroft DW et al. ++ ++ +++ 0 ,[object Object],Bryan S.A. et al. +++ ± 0 0 ,[object Object],+ 0 LAR ++ +++ EAR 0 0 AHR ? 0 EOS Bianco S. et al. ,[object Object],Hedardt B et al., Cockcroft DW et al. ,[object Object],References Drug
Summary of BPT ,[object Object],[object Object],[object Object],[object Object]
 
Nasal Provocation Test ,[object Object],[object Object],[object Object],[object Object],[object Object]
Clinical Indications for NPT ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Ann Allergy Asthma Immunol 2001; 86:355-365. Middleton’s Allergy : principles and practice. 6 th ed. 2003; 644-55.
Scientific Indications for NPT ,[object Object],[object Object],[object Object],Ann Allergy Asthma Immunol 2001; 86:355-365. Middleton’s Allergy : principles and practice. 6 th ed. 2003; 644-55.
Contraindications for NPT ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Ann Allergy Asthma Immunol 2001; 86:355-365. Middleton’s Allergy : principles and practice. 6 th ed. 2003; 644-55.
Washout periods for different drugs before NPT Ann Allergy Asthma Immunol 2001; 86:355-365. Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94. 3 days Chromones, nasal None Inhaled bronchodilators 7 days Leukotriene (cysLT1) receptor antagonists 1 day α -adrenergic agonists, oral or nasal 3 days Antihistamines, nasal 3–10 days Antihistamines, oral None Inhaled corticosteroids 7 days Corticosteroids, oral 7 days Corticosteroids, nasal Withdrawal Medications
Local delivery systems ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Ann Allergy Asthma Immunol 2001; 86:355-365. Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94.
Filter paper disc Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94.
Exposure Chambers ,[object Object],[object Object],Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94.
Outcomes of NPT ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Symptom outcome ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Middleton’s Allergy : principles and practice. 6th ed. 2003; 644-55. Middleton’s Allergy : principles and practice. 7th ed. 2008; 1281-94.
Nasal Peak Flow ,[object Object],[object Object],[object Object]
Rhinomanometry ,[object Object],[object Object],[object Object]
Acoustic Rhinometry ,[object Object],[object Object]
Nasal Cells & Tissue ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Nasal Cytology & Tissue Adapted from Ann Allergy Asthma Immunol 2001; 86:355-365. & Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94. - - + Inadq. Specimen, poor reproducibility E as y , Non-invasive ,[object Object],+ + + - + - Lymp + + + - + - Mono + Pain, Trauma, Bleeding All mucosal layers ,[object Object],+ No deep mucosal layers E as y , R epea tibility , well tolerated both E pi . & S ecretions ,[object Object],+ Pain, Trauma, Bleeding No deep mucosal layers E as y , time-course studies ,[object Object],+ D iluted to variable extent E as y , R epea tibility , both E pi . & S ecretions ,[object Object],+ Operator’ technique mucus may interfere identification of cells both E pi . & S ecretions ,[object Object],+ poor reproducibility E as y , Non-invasive ,[object Object],Disadvantages Eo Advantages Methods
Response of Unilateral NPT ,[object Object],[object Object],[object Object],Ann Allergy Asthma Immunol 2001; 86:355-365. Norciceptive n.  Neuropeptides : - SP  Glandular secretion - CGRP  Vasodilation - ‘Axon Responses’ NASONASAL REFLEX
Nasal Allergen Provocation Test ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Ann Allergy Asthma Immunol 2001; 86:355-365. Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94.
Ann Allergy Asthma Immunol 2001; 86:355-365.
Allergen challenge-induced leukocyte influx in nasal lavage fluids Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94.
Causes of FP & FN NPT results ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Ann Allergy Asthma Immunol 2001; 86:355-365. Middleton’s Allergy : principles and practice. 6th ed. 2003; 644-55..
NPT with Physical, Chemical & Biochemical stimuli ,[object Object],[object Object],[object Object]
NPT with Physical stimuli ,[object Object],[object Object],[object Object],[object Object],Ann Allergy Asthma Immunol 2001; 86:355-365. Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94.
NPT with Neural & Irritant stimuli ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Ann Allergy Asthma Immunol 2001; 86:355-365. Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94.
NPT with Biochemical stimuli ,[object Object],[object Object],[object Object],[object Object],[object Object]
Unilateral NPT with H istamine & M ethacholine Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94. ,[object Object],[object Object]
NPT with Neuropeptides ,[object Object],[object Object],[object Object],[object Object],Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94.
NPT with Adenosine 5’-monophosphate (AMP) ,[object Object],[object Object],[object Object],[object Object],[object Object],Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94.
Summary of NPT ,[object Object],[object Object],[object Object],[object Object]
QUIZ
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Thank you

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Nasal and Bronchial Provocation Tests

  • 1. Nasal & Bronchial Provocation Test P. Putivoranat, MD. 22/05/09
  • 2.
  • 3.
  • 5.
  • 6.
  • 7. F actors Decrease Bronchial Responsiveness Am J Respir Crit Care Med 2000; 161: 309-29.
  • 8.
  • 9. Hypothetical methacholine dose–response curves Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308.
  • 10. 2 Metacholine challenge methods Am J Respir Crit Care Med 2000; 161: 309-29. Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308. False Negative
  • 11. Metacholine challenge test Am J Respir Crit Care Med 2000; 161: 309-29.
  • 12.
  • 13.
  • 14.
  • 15. Mechanism of Indirect Bronchial Challenge Eur Respir J 2003; 21: 1050-68
  • 16.
  • 17.
  • 18.
  • 19.
  • 20.
  • 22.
  • 23.
  • 24.
  • 25. Allergen-induced increase in AHR AHR: 2-3 hrs. after Challenge, may persist several days DAR Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1295-308.
  • 26.
  • 27.
  • 28.
  • 29.  
  • 30.
  • 31.
  • 32.
  • 33.
  • 34. Washout periods for different drugs before NPT Ann Allergy Asthma Immunol 2001; 86:355-365. Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94. 3 days Chromones, nasal None Inhaled bronchodilators 7 days Leukotriene (cysLT1) receptor antagonists 1 day α -adrenergic agonists, oral or nasal 3 days Antihistamines, nasal 3–10 days Antihistamines, oral None Inhaled corticosteroids 7 days Corticosteroids, oral 7 days Corticosteroids, nasal Withdrawal Medications
  • 35.
  • 36. Filter paper disc Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94.
  • 37.
  • 38.
  • 39.
  • 40.
  • 41.
  • 42.
  • 43.
  • 44.
  • 45.
  • 46.
  • 47. Ann Allergy Asthma Immunol 2001; 86:355-365.
  • 48. Allergen challenge-induced leukocyte influx in nasal lavage fluids Middleton’s Allergy : principles and practice. 7 th ed. 2008; 1281-94.
  • 49.
  • 50.
  • 51.
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  • 54.
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  • 56.
  • 57.
  • 58. QUIZ
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  • 68.