Guest Author - Cheryl Tidball, DO

The mainstays of inhaled asthma treatment include three types of medications including rapid-acting inhalers including albuterol, long-acting beta-agonist (LABA) inhalers such as salmeterol and formoterol, and inhaled corticosteroid (ICS) inhalers. Rapid-acting, or “rescue” inhalers can immediately open the airways during an asthma attack, but their effect is relatively short-lived. LABA bronchodilators, also sold under the brand names Serevent (which is also part of the ingredients of the Advair inhaler) and Foradil, take longer to start working, but may be effective in keeping the airways relaxed for up to twelve hours. Although these medications may help prevent acute asthma attacks in some individuals, concern has arisen that there may actually be an increase in asthma deaths among individuals who use LABA inhalers.

Two studies in particular seem to support these concerns, including the Serevent Nationwide Surveillance study by Castle and colleagues (BMJ 1993; 306:1034-1037) and the Salmeterol Multicenter Asthma Research Trial by Nelson and colleagues (SMART) study (Chest 2006; 129:15-26). In the Surveillance study, over 25,000 asthmatics continued their previous asthma treatment and used either albuterol inhalers four times a day or salmeterol twice a day for sixteen weeks. It found that although there was a decrease in asthma exacerbations in the salmeterol group, there was a very small increase in asthma-related deaths. One concern with this study is that subjects were randomized and no measures of ICS inhaler usage were kept during the study.

The SMART study was developed to examine the safety of LABA inhaler usage among 60,000 asthmatics. It found that there was a potential increase in fatal or near-fatal asthma exacerbations among LABA users, particularly African-Americans. Again, the SMART study randomized participants without regards to their steroid inhaler usage, and many used salmeterol alone instead of with an ICS, so it is uncertain whether or not the findings reflect a possible subgroup of individuals that are particularly prone to a rare reaction to these drugs, or whether it simply reflects the problems with using salmeterol alone instead of with a steroid (ICS) inhaler.

The FDA has requested that an advisory committee as well as the manufacturers of Advair, Brovana, Foradil, Perforomist, Serevent, and Symbicort provide more information regarding the safety of LABA inhalers in children and adults. The FDA plans to readdress these issues in an advisory committee that will be meeting in the fall or winter of 2008 (www.fda.gov/CDER/Drug/infopage/LABA/default.htm). In the meantime, it is recommended that for most individuals, LABA inhalers should not be used alone, but in combination with steroid inhalers in those asthmatics who are not well-controlled by steroid inhalers alone.