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Therapeutic Advances in Respiratory Disease
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Review: Safety of long-acting ß2 -agonists in the treatment of asthma

Mario Cazzola

Unit of Respiratory Diseases, Department of Internal Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy, mcazzola{at}qubisoft.it Tel.

Maria Gabriella Matera

Matera Unit of Pharmacology, Department of Experimental Medicine, Second University of Naples, Naples, Italy

Several studies suggested an association between the regular use of ß2-agonists and asthma deaths. Whether this association represents adverse effects of ß -agonist use or is entirely due to disease severity is a matter of ongoing debate. Previous literature indicates that confounding by poor asthma control may explain the apparent deleterious effects of inhaled ß2-agonists. Tolerance to nonbronchodilator effects of ß2-agonists may account for the increase in reactivity to indirect bronchoconstrictor challenges and explain why some studies have demonstrated enhanced bronchoconstriction in patients with asthma after regular ß 2-agonist therapy. Nonetheless, the salmeterol multi-centre asthma research trial (SMART) found more asthma deaths (13 vs 3) and life-threatening asthma events (37 vs 22) in the salmeterol-treated asthmatic patients, although it was documented that among African-Americans, 5 times as many deaths and near-deaths from asthma occurred in those given salmeterol than in those given placebo, and among patients with asthma not using an inhaled corticosteroid (ICS) as a preventive (controller) medication, again more deaths and near-deaths from asthma occurred in those given salmeterol than in those given placebo. Only 38% of the African-Americans who participated in the study used an ICS. As a result of the findings from the SMART, FDA issued a public health advisory to highlight that long-acting ß2-agonists (LABAs) should not be the first medicine used to treat asthma. LABAs should be added to the asthma treatment plan only if other medicines, including the use of low-or-medium dose ICSs, do not control asthma. However, despite all of the concerns raised by the SMART, inhaled ß2-agonists remain the most effective bronchodilators available for the immediate relief of asthma symptoms and, as such, remain an important component of asthma management. Obviously, there are concerns about LABA treatment as monotherapy for asthma. Patients with asthma should be initiated and maintained on sufficiently high doses of ICSs and only patients whose asthma cannot be controlled should receive additional LABAs on a regular basis.

Key Words: Asthma • inhaled ß2-agonists • death from asthma • long-acting ß2-agonists • salmeterol.

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Therapeutic Advances in Respiratory Disease, Vol. 1, No. 1, 35-46 (2007)
DOI: 10.1177/1753465807081747
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