Asthma diagnosis and treatment
The role of endogenous and exogenous AMP in asthma and chronic obstructive pulmonary disease

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Bronchial hyperresponsiveness is present in virtually all patients with asthma and in more than two thirds of patients with chronic obstructive pulmonary disease. Thus far, methacholine and histamine are usually used to measure bronchial hyperresponsiveness. Both are direct stimuli, because they act directly on airway smooth muscle. Another possible stimulus to measure bronchial hyperresponsiveness is AMP. AMP is an indirect stimulus, because it acts via the release of histamine and other mediators from immunologically primed mast cells. There is increasing interest in the role of AMP as a bronchoconstrictor stimulus because it has been suggested that the concentration of AMP causing the FEV1 to decrease by 20% (PC20 AMP) may be used as a noninvasive marker of airway inflammation. The aim of this article was to review the literature assessing AMP's value in asthma and chronic obstructive pulmonary disease.

Section snippets

Role of endogenous adenosine in asthmatic airway inflammation

Adenosine is a signaling nucleotide that acts on extracellular cell-surface receptors.11., 12. Four different 7-transmembrane-spanning adenosine receptors have been described, namely, adenosine A1, A2A, A2B, and A3 receptors.13 Human lung mast cells have been shown to express A2A and A2B receptors, but not A1 or A3 receptors.14., 15. In a recent study, only activation of the A2B receptor resulted in mast cell activation.16., 17. Thus, there is evidence suggesting that AMP-induced

Asthma

Although it is generally accepted that airway inflammation contributes to both the presence and the severity of BHR, the association between airway inflammation and direct BHR is weak.43., 44., 45., 46., 47. Other factors also contribute to the presence and severity of BHR. Indeed, recent morphologic and functional studies have demonstrated that BHR may be compounded by airway remodeling.48 It is interesting to note that it has been demonstrated in patients with asthma that both AMP and

Drawbacks of amp challenge

There are several possible drawbacks to the use of AMP challenge. First, the cutoff point between normal and abnormal for the PC20 AMP is arbitrary, because no population-based data are available. It has been proposed to use a cutoff point of 160 mg/mL because this was discriminatory between patients with asthma and healthy controls in a study of Oosterhoff et al79 with a limited number of patients. However, in other studies it was found that a large percentage of patients with asthma is

Mast cells, β2-adrenoceptor agonists, and bronchoprotection against PC20 AMP

In recent years, there has been a tendency to attach less importance to the role of the mast cell as an effector cell in asthma. However, new findings have led to a resurgence of interest in the mast cell and support a re-evaluation of its role. In particular, the discovery that mast cells are a source of cytokines has suggested new ways in which mast cell activation could also participate in more persistent and even chronic inflammatory responses.86., 87., 88. These observations have obvious

Conclusions

Measurement of BHR not only seems to be of pathophysiological interest, but may also be of clinical importance. It is interesting to note that the PC20 AMP (1) is more closely associated with airway inflammation in asthma than the PC20 methacholine and (2) better reflects corticosteroid-induced reduction airway inflammation. Moreover, the PC20 AMP seems to offer substantial advantages over other noninvasive markers of inflammation because of its exquisite sensitivity in probing changes to

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    The authors declare no conflict of interest.

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