Asthma Clinical Research Network Devotes a Decade to Providing Practical Information

Vol. 13 •Issue 6 • Page 16
Allergy & Asthma

Asthma Clinical Research Network Devotes a Decade to Providing Practical Information

Perhaps no other disease presents the respiratory therapist with a unique opportunity for successful intervention, prevention and the ability to have a positive influence on the patient’s quality of life as asthma does.

Considering the occurrence of this disease — 465,000 hospitalizations and 1.8 million visits to emergency departments in 2000 —the delivery of aerosolized bronchodilators is undoubtedly the most prevalent procedure for inpatient therapy by RTs.1 To a large extent, it’s what RTs do. And the science of what RTs do continues to evolve, thanks to the Asthma Clinical Research Network (ACRN).

Established in 1993 by the Division of Lung Diseases, National Heart, Lung, and Blood Institute, the ACRN was born from the observation that basic asthma research needed more rigorous clinical trials to test how to use treatment regimens that would be included in clinical guidelines.

“There were gaps in the evidence that had to be tested to enhance the care for patients with asthma,” said James P. Kiley, PhD, director of the Division of Lung Diseases, NHLBI, who has been involved with the ACRN for the past 10 years.

The ACRN develops short-term protocols, 12 to 18 months, to support practitioners’ care of patients with asthma. This information then goes to high profile journals to update evidence-based guidelines.

“There is a plethora of basic science that has to be tested in a rigorous fashion,” Dr. Kiley said. “Our primary interest is to provide practical information to those taking care of asthma patients on a day-to-day basis.”


During its initial funding period of 1993 to 2003, the ACRN consisted of six clinical centers that read like a “Who’s Who list” of prestigious research and academic centers: Columbia University, New York; Brigham and Women’s Hospital, Boston; and National Jewish Medical and Research Center, Denver, to name a few. A data coordinating center is located at the Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pa.

“The ACRN tests questions concerning medications already approved, but we look at optimal ways to use the medications, such as the right dose or the right combinations with other medications to form asthma treatment guidelines,” said Gail Weinmann, MD, program director of the NHLBI’s Airway Biology and Disease Program. “These are pieces of a puzzle that complete the picture; they’re interdependent, and one question leads to another.”

The first question addressed by the ACRN concerned the use of albuterol, a bronchodilator well known to every RT. This question took the form of the “BAGS” study: “The Addition of Regular-use to Intermittent Rescue Beta-agonist for Patients with Mild Asthma.”

Results showed that there were no clinical advantages in the regular use of albuterol compared to intermittent use.2 The authors concluded that patients with mild asthma should use albuterol on an “as-needed” basis only.

Other clinical trials followed, and studies examined the use of long-acting bronchodilators. For example, the “Salmeterol Off Corticosteroids” study showed that patients on both salmeterol and triamcinolone couldn’t be switched to only salmeterol alone without the risk of “clinically significant loss of asthma control.”3

Still more research from the ACRN identified that there could potentially be significant reductions (50 percent) in triamcinolone therapy for patients who also receive salmeterol therapy.4 The authors cautioned, though, that total elimination of the inhaled corticosteroid component of this tandem approach could result in deterioration in asthma control.

The clinical trials clearly have shown there’s huge variability in patients’ response to the use of inhaled corticosteroids: one-third respond, one-third don’t respond, and one-third have a questionable response.

“The big take-home message is that asthma is not a single disease but a pattern of disease,” said ACRN investigator Robert Lemanske, MD, professor of pediatrics and medicine, and head of the division of pediatric allergy, immunology and rheumatology at University of Wisconsin Hospital, Madison.

“There are variations in an exercise component, daily symptoms, adult vs. childhood onset, male vs. female prevalence, and overall severity of the disease. We also know that different patient outcomes traditionally used clinically and in asthma research may not track in parallel. For example, PFT results such as the FEV1 may not change after a bronchodilator, but the patient might feel better and have less .nocturnal awakenings.”


In the future, pharmacogenetics may allow clinicians to individualize treatment for each patient. The ACRN will study how drugs are metabolized, how the medications interact with receptor sites, and how inflammation occurs in the airway.

“We need to know the genetic background of the patient,” Dr. Kiley said. “This is a very powerful way to intervene, to provide maximum therapy.”

In five to 10 years, clinicians may be doing a test of the patient’s genotype, no more complex than doing a white blood cell count, that will predict whether a patient will respond to therapy.

This doesn’t hold true just for inhaled corticosteroids; albuterol response also might be regulated with a genetically based pathway. An earlier retrospective study identified that polymorphisms or differences in structure of the beta-2 adrenergic receptor may account for why some patients do or do not respond to albuterol.5

“Based on these retrospective analyses, the Beta Adrenergic Response by Genotype trial was designed and conducted, which is a prospective evaluation of chronic albuterol use in patients who are randomized by genotype at codon 16 for the beta receptor,” Dr. Lemanske said. “To our knowledge, this was the first trial in asthma that was randomized by genotype.”

The ACRN is poised to produce many potential innovations in asthma care from a steady stream of research data. The NHLBI has funded the ACRN for another five years with eight clinical centers and one data coordinating center. There’s also the option to apply for an additional five years of funding should the need be present.

“We will stay with cutting-edge kinds of approaches,” Dr. Kiley said. “We will always be looking for novel compounds and lead agents to test clinically. Immunotherapy will also play a big role in the future. That is, we will look for potential ways to target the immune pathway in asthma to abate the inflammatory process.”

In many clinical centers, there’s a significant RT presence involved with this research. “We have a great team of physicians, nurses and RTs contributing to good studies, good data,” Dr. Lemanske said. “RTs have contributed a lot to the ACRN, and the profession should be very proud of that.”


1. National Center for Health Statistics. Available from: URL:

2. Drazen JM, Israel E, Boushey HA, Chinchilli VM, Fahy JV, Fish JE, et al. Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. N Engl J Med. 1996;335:841-7.

3. Lazarus S, Boushey H, Fahy J, Chinchilli V, Lemanske R, Sorkness C, et al. Long-acting .§2-agonist monotherapy vs. continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial. JAMA. 2001;285(20):2583-93.

4. Lemanske J, Sorkness C, Mauger E, Lazarus S, Boushey H, Fahy J, et al. Inhaled corticosteroid reduction and elimination in patients with persistent asthma receiving salmeterol: a randomized controlled trial. JAMA. 2001;285(20):2594-603.

5. Israel E, Drazen JM, Liggett SB, Boushey HA, Cherniack RM, Chinchilli VM. The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med. 2000;162:75-80.

Bakow is the manager of respiratory care and pulmonary diagnostics at the Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pa.