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Airway Hyperresponsiveness in Asthma: Its Measurement and Clinical Significance |

Conclusion: Airway Hyperresponsiveness in Asthma: Its Measurement and Clinical Significance FREE TO VIEW

Paul M. O’Byrne, MBBCh, FCCP
Author and Funding Information

From the Firestone Institute for Respiratory Health, St. Joseph’s Healthcare, Department of Medicine, McMaster University, Hamilton, ON, Canada.

Correspondence to: Paul M O’Byrne, MBBCh, FCCP, Firestone Institute for Respiratory Health, St. Joseph’s Healthcare, Department of Medicine, McMaster University, 1200 Main St W, Hamilton, ON, Canada; e-mail: obyrnep@mcmaster.ca


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(2_suppl):44S-45S. doi:10.1378/chest.10-0726
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Airway hyperresponsiveness is a characteristic feature of asthma, and its measurement using direct inhalation challenges, particularly with inhaled methacholine,1 or indirect challenges with inhaled mannitol2 or exercise3 is important in establishing a correct diagnosis. This is particularly true in excluding asthma as a diagnosis in patients with symptoms that suggest asthma, but are caused by another condition. This is because airway hyperresponsiveness measurements are very sensitive in determining a diagnosis of asthma (therefore, they have a high negative predictive value) but are not very specific because patients with other diseases, such as allergic rhinitis4 or COPD,5 can have airway hyperresponsiveness without asthma.

This supplement to CHEST highlighted the many insights that have been made into the role of measuring both airway hyperresponsiveness and airway inflammation. These methods have proven very helpful clinically, as well as in mechanistic studies of asthma. The importance of airway inflammation in increasing airway responsiveness after exposure to environmental or occupational stimuli, such as allergens,6 or small-molecular-weight chemicals, such as toluene diisocyanate,7 is now established; however, the role of airway inflammation and its associated structural changes (airway remodeling) in initiating airway hyperresponsiveness remains unclear.

Finally, the value of measuring both airway hyperresponsiveness and airway inflammation in making treatment decisions, particularly about the doses of inhaled corticosteroids (ICS) used in patients, has been evaluated. Adjusting the doses of ICS to optimize the measurements of methacholine airway responsiveness leads to improved asthma control,8 whereas adjusting ICS doses to minimize sputum eosinophils reduces asthma exacerbations.9,10 These studies have not been conducted yet for the indirect airway challenges, such as mannitol or exercise.

The symposium described in this supplement has identified the many advances that have been made since the original symposium in 1979 in understanding the value of measuring airway hyperresponsiveness and airway inflammation for establishing a diagnosis of asthma and optimizing treatment, as well as the association between these two markers of asthma. However, the concluding statement made by Dr Roland Ingram at that meeting that “neither I, nor I suspect anyone else here, truly understands the genesis or modulating mechanisms”11 of airway hyperresponsiveness remains almost as true today. Although this could be regarded as a failure of the past research efforts into understanding the mechanisms of airway hyperresponsiveness, it is almost certain that, with the extent of the research endeavors into clarifying these issues, this problem will be solved and likely soon.

Financial/nonfinancial disclosures: The author has reported to CHEST the following conflicts of interest: Dr O’Byrne has been on advisory boards for Abbott Laboratories, AstraZeneca, Asmacure, GlaxoSmithKline, Merck, Topigen, and Wyeth and has received lecture fees from these and other pharmaceutical companies, including Chiesi Pharmaceuticals, Inc. In addition, he has received grants-in-aid for research studies from AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Medimmune, Merck, Pfizer, and Wyeth.

ICS

inhaled corticosteroids

Adelroth E, Hargreave FE, Ramsdale EH. Do physicians need objective measurements to diagnose asthma? Am Rev Respir Dis. 1986;1344:704-707. [PubMed]
 
Brannan JD, Anderson SD, Perry CP, Freed-Martens R, Lassig AR, Charlton B. Aridol Study Group Aridol Study Group The safety and efficacy of inhaled dry powder mannitol as a bronchial provocation test for airway hyperresponsiveness: a phase 3 comparison study with hypertonic (4.5%) saline. Respir Res. 2005;6:144. [CrossRef] [PubMed]
 
Anderson SD. Provocative challenges to help diagnose and monitor asthma: exercise, methacholine, adenosine, and mannitol. Curr Opin Pulm Med. 2008;141:39-45. [CrossRef] [PubMed]
 
Ramsdale EH, Morris MM, Roberts RS, Hargreave FE. Asymptomatic bronchial hyperresponsiveness in rhinitis. J Allergy Clin Immunol. 1985;755:573-577. [CrossRef] [PubMed]
 
Ramsdale EH, Roberts RS, Morris MM, Hargreave FE. Differences in responsiveness to hyperventilation and methacholine in asthma and chronic bronchitis. Thorax. 1985;406:422-426. [CrossRef] [PubMed]
 
Gauvreau GM, Watson RM, O’Byrne PM. Kinetics of allergen-induced airway eosinophilic cytokine production and airway inflammation. Am J Respir Crit Care Med. 1999;1602:640-647. [PubMed]
 
Mapp CE, Polato R, Maestrelli P, Hendrick DJ, Fabbri LM. Time course of the increase in airway responsiveness associated with late asthmatic reactions to toluene diisocyanate in sensitized subjects. J Allergy Clin Immunol. 1985;755:568-572. [CrossRef] [PubMed]
 
Sont JK, Willems LN, Bel EH, van Krieken JH, Vandenbroucke JP, Sterk PJ. The AMPUL Study Group The AMPUL Study Group Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. Am J Respir Crit Care Med. 1999;1594 Pt 1:1043-1051. [PubMed]
 
Green RH, Brightling CE, McKenna S, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002;3609347:1715-1721. [CrossRef] [PubMed]
 
Jayaram L, Pizzichini MM, Cook RJ, et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J. 2006;273:483-494. [CrossRef] [PubMed]
 
Hargreave FE. Airway Reactivity: Measurement and Clinical Relevance. 1980; Ontario, Canada Mississauga
 

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References

Adelroth E, Hargreave FE, Ramsdale EH. Do physicians need objective measurements to diagnose asthma? Am Rev Respir Dis. 1986;1344:704-707. [PubMed]
 
Brannan JD, Anderson SD, Perry CP, Freed-Martens R, Lassig AR, Charlton B. Aridol Study Group Aridol Study Group The safety and efficacy of inhaled dry powder mannitol as a bronchial provocation test for airway hyperresponsiveness: a phase 3 comparison study with hypertonic (4.5%) saline. Respir Res. 2005;6:144. [CrossRef] [PubMed]
 
Anderson SD. Provocative challenges to help diagnose and monitor asthma: exercise, methacholine, adenosine, and mannitol. Curr Opin Pulm Med. 2008;141:39-45. [CrossRef] [PubMed]
 
Ramsdale EH, Morris MM, Roberts RS, Hargreave FE. Asymptomatic bronchial hyperresponsiveness in rhinitis. J Allergy Clin Immunol. 1985;755:573-577. [CrossRef] [PubMed]
 
Ramsdale EH, Roberts RS, Morris MM, Hargreave FE. Differences in responsiveness to hyperventilation and methacholine in asthma and chronic bronchitis. Thorax. 1985;406:422-426. [CrossRef] [PubMed]
 
Gauvreau GM, Watson RM, O’Byrne PM. Kinetics of allergen-induced airway eosinophilic cytokine production and airway inflammation. Am J Respir Crit Care Med. 1999;1602:640-647. [PubMed]
 
Mapp CE, Polato R, Maestrelli P, Hendrick DJ, Fabbri LM. Time course of the increase in airway responsiveness associated with late asthmatic reactions to toluene diisocyanate in sensitized subjects. J Allergy Clin Immunol. 1985;755:568-572. [CrossRef] [PubMed]
 
Sont JK, Willems LN, Bel EH, van Krieken JH, Vandenbroucke JP, Sterk PJ. The AMPUL Study Group The AMPUL Study Group Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. Am J Respir Crit Care Med. 1999;1594 Pt 1:1043-1051. [PubMed]
 
Green RH, Brightling CE, McKenna S, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002;3609347:1715-1721. [CrossRef] [PubMed]
 
Jayaram L, Pizzichini MM, Cook RJ, et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J. 2006;273:483-494. [CrossRef] [PubMed]
 
Hargreave FE. Airway Reactivity: Measurement and Clinical Relevance. 1980; Ontario, Canada Mississauga
 
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