Asthma: Long-Acting Bronchodilators

What's the place of long-acting bronchodilators in treating asthma? Here's an interesting discussion about whether the risks outweigh the benefits.

Serevent was one one of the five dangerous drugs mentioned by an FDA division director last year when he testified to Congress, and it subsequently got a "black box warning" on the label.

There are now three long-acting bronchodilator (LAB) inhalers available by prescription in the United States: Serevent (salmeterol), Foradil (formoterol), and Spiriva (tiotropium). Since inhaled corticosteroids (ICSs) are also frequently prescribed for patients with asthma and COPD, the combination of a LAB and ICS makes treatment more convenient for patients who need both types of medications (and faster for the doctor to write a prescription for one drug instead of two), so more than 6 billion dollars of Advair (a combination of salmeterol and fluticasone) was sold world-wide last year, and Symbicort (a combination of formoterol and budesonide) is pending approval in the United States, but meanwhile very popular in other countries. Due to the massive market for these drugs, other "me-too" ICS+LAB combination inhalers have been developed and are undergoing clinical trials.

A couple of decades ago, it became clear that trying to treat asthma with short-acting bronchodilators alone was dangerous, as dozens of patients with asthma died "clutching their inhaler." It took a few years to confirm that the reason was that their underlying airway inflammation was not treated by the bronchodilators and they developed a tolerance to them. A malignant cardiac arrhythmia caused by the low oxygen levels in their blood (caused by the severe airway edema), low intracellular potassium levels (caused by the beta-agonists), and cardiac stimulant effects of the bronchodilator was a likely "coup de grace" causing an out-of-hospital demise (usually officially attributed to various other causes). It's a shame that it took a decade of use (in one country or another) before it finally became apparent that the new long-acting bronchodilators (LABs) also increased the risk of similar deaths (probably with similar mechanisms). Most doctors now know that they should not prescribe a LAB unless the patient is also taking an ICS every day.

When asthma is poorly controlled in patients faithfully taking an ICS twice-a-day, the addition of a LAB does result in better control for many of them, thus there is a good place for ICS+LAB combo inhalers in the treatment of asthma. But I'd call this step-up in treatment evolutionary, not "revolutionary."

The largest remaining problem with LABs in patients with asthma is that they are often unnecessary after the asthma exacerbation for which they were prescribed has subsided. Thus the patient suffers from unnecessary expense and sometimes LAB side-effects, which include muscle cramps or pain, nervous stimulation, and cardiac arrhythmias. Patients see doctors during exacerbations, but follow-up appointments are much less likely to be scheduled or completed. There is also lots of pressure to "just keep using the inhaler that obviously worked."

A footnote: The companies which make and market Spiriva are obviously unhappy when their ultra-long-acting bronchodilator is placed in the same group as the black-boxed Serevent. They will say that it's an entirely different drug with an entirely different mechanism of action. Indeed, Spiriva is an anti-cholinergic instead of a beta-agonist (like Serevent and Foradil); but all three are bronchodilators designed to relax bronchial smooth muscle. No bronchodilator reduces airway inflammation (although considerable effort is spent to find just a smidgen of some type of anti-inflammatory effect). This "misunderstanding" probably causes less harm because very few folks with asthma respond well to anticholinergic bronchodilators, so Spiriva and Atrovent are prescribed primarily to relieve shortness-of breath in smokers with severe COPD. However, an increased risk of severe cardiac side-effects as a result of anticholinergic inhaler treatment has been found in such patients. (I was a coauthor of one such study.)

Related Topics: Stress and Asthma, Use a Peak Flow Meter to Manage Asthma

Tags: bronchodilator,serevent,advair,,asthma,webmd