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Published online before print February 20, 2008
Eur Respir J 2008, doi:10.1183/09031936.00116207
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ORIGINAL ARTICLE

Adenosine 5'-monophosphate in asthma: gas exchange and sputum cellular responses

H.A. Manrique 1, F.P. Gómez 1, P.A. Muñoz 1, A.M. Peña 1, J.A. Barberà 1, J. Roca 1, R. Rodríguez-Roisin 1*

1 Servei de Pneumologia (Institut del Tòrax), Hospital Clínic, Institut d'Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Ciber Enfermedades Respiratorias, Universitat de Barcelona, Barcelona, Spain

* To whom correspondence should be addressed. E-mail: rororo{at}clinic.ub.es.


  Abstract

Adenosine 5'-monophosphate (AMP) bronchoprovocation could reproduce the lung function abnormalities spontaneously occurring during acute asthma and detect peripheral airway inflammation better than direct bronchoconstrictive agents. Pulmonary gas exchange disturbances may reflect changes in small airways related to airway inflammation rather than bronchoconstriction alone.

We investigated whether AMP induces more ventilation-perfusion (VA/Q) imbalance than methacholine (MCh) at equivalent degree of bronchoconstriction with and without salbutamol pre-medication. We studied 36 asthmatics in three randomised, double-blinded, cross-over studies: before and after AMP/MCh (Study-1); and before and 30 min after salbutamol/placebo, followed by AMP (Study-2)/MCh (Study-3) challenge. Sputum was collected before and 4 h post-challenge.

Compared to MCh, AMP provoked similar pulmonary gas exchange abnormalities at an equivalent degree of intense bronchoconstriction (FEV1 fall, range 28–44%). While salbutamol blocked AMP/MCh-induced bronchoconstriction, PaO2 and AaPO2 disturbances were partially blocked (AMP, by 46% and 58%; MCh, by 42% and 57%, respectively). Compared to MCh, AMP increased neutrophils (from 28±17% to 38±16%, p<0.05) but not after salbutamol pre-treatment.

Both AMP and MCh induce similar peripheral airway dysfunction. The fully inhibited AMP-induced neutrophilia with residual hypoxaemia observed after salbutamol is likely related to beta-agonists acting on both bronchial and pulmonary circulations.

Keywords:  Direct and indirect bronchial challenges, induced sputum, multiple inert gas elimination technique, pulmonary gas exchange, short-acting bronchodilators




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P. A. Munoz, F. P. Gomez, H. A. Manrique, J. Roca, J. A. Barbera, I. H. Young, S. D. Anderson, and R. Rodriguez-Roisin
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[Abstract] [Full Text] [PDF]


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