Asthma Studies You Shouldn’t Miss

Vol. 14 •Issue 7 • Page 18
Airways Disorders

Asthma Studies You Shouldn’t Miss

A Look Back at Important Research Developments From 2004-2005

At least one positive can come from the country’s current asthma epidemic. The spiraling rates of breathlessness have translated into a wealth of research.

Medical journals have furiously pumped out impressive asthma studies, said Kevin D. Hamilton, BS, RRT, coordinator of the Asthma Education and Management Program, Community Medical Centers, Fresno, Calif. He declared it a banner year for asthma science and optimistically looks toward the future. “It’s just awesome,” he said.

Let’s take a closer look at what a few experts see as the most intriguing developments during 2004-2005.


“Cause is probably the most dif-ficult question,” said William J. Calhoun, MD, FACP, FCCP, FAAAAI.

He, like many of his colleagues, is intrigued by the hygiene hypothesis. This notion could answer why some people develop asthma and others don’t. It states that early exposure in life to microproducts — bacteria, viruses, fungi — helps to settle the immune system down into a protective role.

“That continues to be a focus of significant lab and clinical investigation,” said Dr. Calhoun, director of the division of allergy, pulmonary, immunology, critical care medicine and sleep, University of Texas Medical Branch, Galveston. “It’s very controversial, and it’s very hot.”

Most asthmatic children develop their symptoms in the first few years of life, said Steven M. Julius, MD, a pulmonologist with Georgia Pediatric Pulmonology Associates, Atlanta. “Clearly, the development of asthma is strongly impacted by the events that occur then.”

However, what particular exposures play a role remains questionable.

“We just don’t know enough,” Dr. Julius admitted.

Dr. Calhoun points to several studies that offer mixed results.

One team reviewed recent epidemiologic studies of the hygiene hypothesis and asthma.1 Previous findings show an inverse association between increased exposure to other children during childhood and either allergen sensitization or hay fever, but conflicting evidence exists regarding this relationship.

Also, even though some believe that vaccinations and antibiotic use may influence the development of asthma, recent studies don’t support this connection.

In addition, the link between asthma and exposure to certain gastrointestinal pathogens (e.g., hepatitis A virus), as well as infestation with particular parasites (e.g., helminths), has presented contradictory results.

“For every exposure studied with regard to the hygiene hypothesis, there are inconsistent findings in relation to asthma,” the reviewers stated. “The hygiene hypothesis is not likely to be the sole explanation for the ongoing asthma epidemic in industrialized nations.”

Dr. Calhoun described another study that suggested the hygiene hypothesis might work beyond childhood.2

“Assuming that the immune system is not fixed after the first years of life, we hypothesize that endotoxin exposure might not only inhibit the development of sensitization and disease at any time throughout life but might also reverse this process,” the investigators stated. “This novel extension of the hygiene hypothesis is primarily based on the indirect evidence of several epidemiologic observations showing a reduction in atopy in adults highly exposed to endotoxin that is unlikely to be explained by protective effects alone.”

However, currently little direct evidence shows that endotoxin might reverse atopy and allergic diseases, they added.


The hygiene hypothesis doesn’t have the asthma market cornered on controversy. Research in the New England Journal of Medicine has questioned the standard treatment methods for patients with mild persistent asthma.3

These investigators evaluated the efficacy of intermittent short-course corticosteroids guided by a symptom-based action plan alone versus the action plan plus daily treatment with either inhaled budesonide or oral zafirlukast.

After testing 225 adults over a one-year period, they found that the three treatments produced similar increases in morning peak expiratory flow and similar rates of asthma exacerbations, even though the intermittent treatment group took budesonide, on average, for only 0.5 week of the year.

However, daily budesonide therapy produced greater improvements in pre-bronchodilator FEV1, bronchial reactivity, the percentage of eosinophils in sputum, exhaled nitric oxide levels, scores for asthma control, and the number of symptom-free days, but not in post-bronchodilator FEV1 or in the quality of life.

Daily zafirlukast therapy didn’t differ significantly from intermittent treatment in any outcome measured.

“It may be possible to treat mild persistent asthma with short, intermittent courses of inhaled or oral corticosteroids taken when symptoms worsen,” the researchers suggested. “Further studies are required to determine whether this novel approach to treatment should be recommended.”

The study could have huge ramifications, if the findings are confirmed. The number of medication side effects would be reduced, and people would have to dish out less money for drugs.

“Members of the asthma community are back on their heels about it because we’ve been teaching for the past 15 years that more treatment is better and undertreatment is the problem,” Dr. Calhoun said.

Not everyone is ready to put away the prescription pad, though.

“The study wasn’t conclusive, and I don’t think anyone is basing his or her practice on it,” Hamilton said.

Dr. Julius isn’t comfortable taking these patients off their regular doses of asthma therapy. “I feel like we would be doing them a disservice,” he said.


What is the proper medication regimen probably will remain uncertain for the foreseeable future. Fewer questions exist about asthma drug delivery devices. On March 31, the Food and Drug Administration announced that albuterol metered dose inhalers using chlorofluorocarbon (CFC) propellants must no longer be produced, marketed or sold in the United States after Dec. 31, 2008.

CFCs are well-known ozone-depleting substances, so the government made the final push for more environmentally friendly products. CFCs in consumer aerosols, like hairspray, have been banned for years.

The FDA said sufficient supplies of environmentally friendly albuterol inhalers (hydrofluoroalkane or HFA formulations) will exist by the end of 2008, allowing doctors to phase out the CFC variety.

The agency added that three companies who already manufacture HFA inhalers have implemented programs such as giveaways and coupons to help ensure access for patients for whom price could be a significant barrier.

Although it’s tough to tell what the cost of meds will be more than three years from now, CFC inhalers currently run about one-fifth to one-third the cost of branded HFA alternatives.4

As for the quality of the drugs, a pair of 2005 studies pitting CFC and HFA against each other showed both formulations had similar incidences of adverse events, and no safety concerns were generated.5

“These data demonstrate salmeterol HFA MDI to be as effective as salmeterol CFC MDI in adults and children,” the researchers stated.

And salmeterol HFA MDIs aren’t associated with a significantly different pharmacodynamic, safety and tolerability profile compared with the salmeterol CFC MDIs.6

Hamilton doesn’t need anymore convincing. In addition to being better for the environment, HFA-propellant drugs have superior deposition in the lungs. He only gripes that the government gave manufacturers too much time to comply.

Mike Bederka is associate editor of ADVANCE. He can be reached at [email protected].

For a list of references, please call Mike Bederka at (610) 278-1400, ext. 1128, or visit