Combination therapy best for severe asthma, studies find

Controlling the underlying inflammation is key and often involves multiple agents.

By Susan J. Landers — Posted Aug. 11, 2008

Print  |   Email  |   Respond  |   Reprints  |   Like Facebook  |   Share Twitter  |   Tweet Linkedin

Two recent analyses on the use of a long-acting beta agonist for treating asthma have renewed a long-running controversy. But at the same time, the studies served to drive home the point that the medication should be used in conjunction with inhaled corticosteroids.

A Cochrane review, published July 15 by the Cochrane Library, found that people with asthma who regularly use the beta agonist, salmeterol, are at greater risk of nonfatal, serious adverse events than those using placebos.

But a review appearing a few weeks earlier in the July 1 Annals of Internal Medicine found that salmeterol, combined with inhaled corticosteroids, decreased the risk for severe exacerbations of the disease and did not seem to raise the risk of hospitalizations, death or intubations resulting from asthma.

So what do these studies mean for the 20 million people in the U.S. who, according to the Centers for Disease Control and Prevention, have asthma? Clearly, sorting through the data to devise a proper treatment is a top concern. After all, this disease resulted in more than 13 million office visits in 2004, according to the CDC. Both studies emphasize the need to use salmeterol with an inhaled steroid, although the Cochrane review sounded a more cautionary note. "We found that the biggest increase in the risk was seen in people with asthma who were not taking inhaled corticosteroids; however, there is no guarantee that inhaled corticosteroids abolish the risk altogether," said the lead author of the Cochrane review, Dr. Christopher Cates, a physician in Community Health Sciences at St. George's Medical School in London.

Dr. Cates believes there is an ongoing need for wariness regarding the use of salmeterol. "From my experience in family practice ... many patients default on their inhaled corticosteroid inhaler. My concern is that salmeterol is such an effective bronchodilator that some will feel much better and default on their ICS treatment," he wrote in an e-mail.

This worry was echoed by allergist Harold Nelson, MD, a co-author of the Annals study and a professor of medicine at National Jewish Health in Denver, although he faulted the Cochrane review for "plowing old ground" and possibly stirring up unnecessary concern about beta agonists. "There is nothing new here, but it will get a lot of scary newspaper headlines."

It has long been known what will happen if a person with asthma relies solely on salmeterol, Dr. Nelson said. "You control symptoms, but inflammation is uncontrolled. It's a perfect setup for someone to have a severe attack, because they don't appreciate the inflammation that is going on."

The Annals study was funded by GlaxoSmithKline, the manufacturer of a leading asthma medication that combines salmeterol and a steroid in a single inhaler. In a response to the Cochrane finding, the pharmaceutical company noted that large studies have found that treatment with salmeterol plus an inhaled steroid was effective. "Today, nearly all patients with a diagnosis of asthma who receive salmeterol also receive an inhaled corticosteroid," explained the firm.

The statement also noted that, while the Cochrane analysis did not provide new information on the management of asthma, it reinforced the need for patients and physicians to follow evidence-based treatment guidelines.

Asthma guidelines released last year by the National Heart, Lung and Blood Institute state that patients should not be on salmeterol without also using an oral inhaled corticosteroid, said Richard G. Gower, MD, president-elect of the American College of Allergy, Asthma & Immunology. "So there is no place for a long-acting beta agonist without an inhaled corticosteroid."

In addition, the guidelines state that people with mild asthma probably don't need to be on a long-acting beta agonist, Dr. Gower said. Inhaled steroids are probably enough. About 20% of patients were on the medications unnecessarily, he estimated.

Asthma's origins

As treatment issues are thrashed out, researchers continue to delve into the possible causes of asthma, which has been on the increase for the past half-century.

New findings suggest that this rise may be linked to the decline in Helicobacter pylori in humans because of the increased use of antibiotics.

"Among teens and children ages 3 to 19 years, carriers of H. pylori were 25% less likely to have asthma," said Yu Chen, PhD, assistant professor of epidemiology at New York University School of Medicine. Chen is a co-author of a new study linking the two that appeared in the July 15 online edition of The Journal of Infectious Diseases.

The researchers hypothesize that their result could stem from the fact that a stomach that harbors H. pylori has a different immunological status from one lacking the bacteria. When H. pylori is present, the stomach is lined with immune cells called regulatory T cells that control the body's response to invaders. Without these cells, a child can be more sensitive to allergens.

Another group of researchers investigated the eating habits of pregnant women for clues to the origins of asthma. They found that women who ate nuts or nut products frequently during pregnancy increased their child's risk of developing asthma by more than 50% over women who rarely or never consumed nut products during pregnancy.

Nearly 4,000 pregnant women participated in the Prevention and Incidence of Asthma and Mite Allergy study conducted by the Dutch government. The results were in the second July issue of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

The women completed questionnaires on their eating habits during the last month of their pregnancy. Their children's diets also were assessed at age 2, and their asthma and allergy symptoms were assessed yearly until they were 8 years old.

Back to top



Read story

Confronting bias against obese patients

Medical educators are starting to raise awareness about how weight-related stigma can impair patient-physician communication and the treatment of obesity. Read story

Read story


American Medical News is ceasing publication after 55 years of serving physicians by keeping them informed of their rapidly changing profession. Read story

Read story

Policing medical practice employees after work

Doctors can try to regulate staff actions outside the office, but they must watch what they try to stamp out and how they do it. Read story

Read story

Diabetes prevention: Set on a course for lifestyle change

The YMCA's evidence-based program is helping prediabetic patients eat right, get active and lose weight. Read story

Read story

Medicaid's muddled preventive care picture

The health system reform law promises no-cost coverage of a lengthy list of screenings and other prevention services, but some beneficiaries still might miss out. Read story

Read story

How to get tax breaks for your medical practice

Federal, state and local governments offer doctors incentives because practices are recognized as economic engines. But physicians must know how and where to find them. Read story

Read story

Advance pay ACOs: A down payment on Medicare's future

Accountable care organizations that pay doctors up-front bring practice improvements, but it's unclear yet if program actuaries will see a return on investment. Read story

Read story

Physician liability: Your team, your legal risk

When health care team members drop the ball, it's often doctors who end up in court. How can physicians improve such care and avoid risks? Read story

  • Stay informed
  • Twitter
  • Facebook
  • RSS
  • LinkedIn