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Lung Blood Flow Must Be Considered When Prescribing a Long-Acting β2-Agonist/Inhaled Corticosteroid CombinationLung Blood Flow Considerations

Mario Cazzola, MD, FCCP; Maria Gabriella Matera, MD, PhD
Author and Funding Information

From the Department of Internal Medicine (Dr Cazzola), University of Rome Tor Vergata, and Department of Pulmonary Rehabilitation (Dr Cazzola), San Raffaele Pisana; and Department of Experimental Medicine (Dr Matera), Second University.

Correspondence to: Mario Cazzola, MD, FCCP, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Via Montpellier 1, 00133 Roma, Italy; e-mail: mario.cazzola@uniroma2.it


Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Cazzola has received honoraria for speaking and consulting and/or financial support for attending meetings from Abbott, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Dey, GlaxoSmithKline, Lallemand, Menarini Farmaceutici, Mundipharma, Novartis, Nycomed, Pfizer, Sanovel, Sigma Tau, and Valeas. Dr Matera has received honoraria for speaking and consulting and/or financial support for attending meetings from AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Novartis, Nycomed, and Pfizer.

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


© 2012 American College of Chest Physicians


Chest. 2012;141(5):1134-1136. doi:10.1378/chest.11-2497
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Years ago, we documented that formoterol taken in recommended dosages resulted in a significant decline in Pao2,1 ascribable to a pulmonary vasodilator effect mediated via β2-adrenoceptors on vascular smooth muscle. This phenomenon is considered dangerous because it diverts blood flow to poorly ventilated lung regions, thus causing further ventilation/perfusion ratio (V˙ /Q˙ ) worsening and hypoxemia, compounded by increases in perfusion and oxygen consumption.2 However, we also observed that the addition of budesonide reduced this effect of formoterol.1 We justified the interference of budesonide on the impact of formoterol on blood-gas tensions with the documented potential of corticosteroids to exert an acute reduction of lung blood flow.3 Corticosteroids could interfere with noradrenaline uptake by smooth muscle cells of human bronchial arteries (extraneural uptake: uptake2) and, consequently, increase noradrenaline concentration at α-adrenoceptor sites of the pulmonary vascular smooth muscle,4 whose stimulation induces vasoconstriction.5 This effect might divert blood flow away from poorly ventilated alveoli to the regions that are better ventilated, thereby optimizing V˙ /Q˙  matching and maintaining an adequate systemic Pao2. Afterward, we also provided evidence of the protective action of fluticasone on the decrease in Pao2 induced by salmeterol.6

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