MIAMI BEACH — Measuring airway responsiveness to inhaled adenosine helps discriminate between a diagnosis of asthma and chronic obstructive pulmonary disease.
It's also a valuable clinical tool for monitoring airway inflammation and response to anti-inflammatory treatment in asthma, Dr. Riccardo Polosa reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. “AMP challenge is noninvasive, non-time consuming, low cost, has good reproducibility and patient acceptability, and safety is optimal,” he said.
Adenosine 5′-monophosphate (AMP) is a proinflammatory mediator that induces bronchoconstriction in patients with inflammatory lung diseases. Response to AMP is determined by measuring the concentration of inhaled AMP causing the forced expiratory volume in 1 second (FEV1) to decrease by 20%. The exact cutoff point between normal and abnormal PC20 AMP, as it is known, remains somewhat unclear. But a cutoff of 160 mg/mL has been used successfully to discriminate between asthmatics and healthy controls. AAAAI is considering standardizing and writing protocols for AMP and other indirect challenges, said session moderator Dr. Richard A. Nicklas, of George Washington University, Washington.
Dr. Polosa and his colleagues at the University of Catania (Italy) have shown that airway responsiveness to inhaled AMP is closely related to the number of eosinophils in the airways of atopic patients, whereas no association was observed with methacholine, an agent commonly used to assess bronchial hyperresponsiveness (Eur. Respir. J. 2000;15:30–5). Dr. Polosa and other researchers from the university also showed that PC20 AMP could detect inflammatory changes as early as the first week of treatment with inhaled budesonide 0.8 mg per day in mild to moderate asthmatics, while methacholine responsiveness and changes in the percentage of sputum eosinophils could be observed only by the fourth week (J. Allergy Clin. Immunol. 2002;110:855–61).
Investigators at King's College, London, were able to demonstrate in three consecutive studies that a single dose of intranasal fluticasone propionate 100–1,000 mcg inhibited an asthmatic response to AMP in just 2 hours in patients with mild, stable asthma. A single inhalation of fluticasone 1,000 mcg had no effect on airway responsiveness to histamine (J. Allergy Clin. Immunol. 2002;110:603–6).
But when Dr. Polosa's team performed a similarly designed randomized, double-blind study using a single inhalation of fluticasone 1,000 mcg in 14 patients with chronic obstructive pulmonary disease (COPD) and 13 with mild asthma, there was a change in response in only one of the COPD patients, he said. The experiment was repeated with similar results in 10 patients with a clear history of asthma and 10 patients with COPD and comparable fixed airway obstruction. “This tells me very nicely that AMP challenge can be used as a strong discriminator for COPD and asthma,” he said of the unpublished findings.
AMP also has been used to assess the nonsteroidal anti-inflammatory potential of several therapeutic agents including allergen immunotherapy (Clin. Exp. Allergy. 2003;33:873–81), the leukotriene receptor antagonist montelukast (Am. J. Respir. Crit. Care Med. 2003;167:1232–8), and the humanized monoclonal anti-IgE antibody omalizumab (Int. Arch. Allergy Immunol. 2006;139:122–31).
AMP may be a more useful and sensitive tool than methacholine and histamine because of its mechanism of action, Dr. Polosa said. Histamine and methacholine have a direct spasmogenic effect on airway smooth muscle cells. AMP acts indirectly via the secondary release of mediators. Inhaled AMP is rapidly converted to adenosine and mainly induces mast cell degranulation and release of mediators such as histamine, prostanoids, and eicosanoids that cause smooth muscle constriction and mucosal edema, resulting in bronchoconstriction.