Monitoring Exhaled Nitric Oxide Does Not Help Manage Asthma
A new study shows that monitoring levels of exhaled nitric oxide in adolescents with asthma and adjusting treatment accordingly does not improve the course of their disease.
The study was conducted by the Inner City Asthma Consortium (ICAC), which is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The Sept. 20 issue of The Lancet reports the ICAC findings.
Approximately 550 adolescents in 10 cities across the United States participated in the study. It was designed to examine whether in addition to treating asthma based on national guidelines developed at NIH, measurements of exhaled nitric oxide would allow even better control of the disease. This was the largest study to date testing exhaled nitric oxide as a biomarker for asthma management.
Asthma is a chronic disorder of the airways that affects approximately 9 percent of children under age 17 in the United States. The causes of asthma are still unknown, but allergens, air pollution and infections can provoke its symptoms, which include wheezing, chest tightness, shortness of breath and coughing. Asthma symptoms occur when the tissues of the lungs become inflamed and the muscles in the airways contract, making breathing difficult. One measurable marker of asthma-related inflammation is high levels of nitric oxide (NO) in the breath; it is known that the higher the exhaled NO, the greater the inflammation of the lungs. Equipment is now available to easily measure exhaled NO. Widely used asthma treatments, such as inhaled corticosteroids, reduce both lung inflammation and exhaled NO. Exhaled NO would potentially be a good biomarker—a measurable feature of a disease that indicates its severity—of asthma inflammation.
“A biomarker of airway inflammation could be a useful clinical tool for gauging medical needs and clinical responses in asthma patients,” says Anthony S. Fauci, M.D., director of NIAID. “Although this study reinforces the importance of the NIH asthma guidelines for disease control, it did not find that measuring exhaled nitric oxide provided any additional clinical benefit.”
The new research was led by Stanley Szefler, M.D., of National Jewish Health in Denver, in conjunction with William Busse, M.D., of the University of Wisconsin in Madison. Participants were randomly assigned to one of two equal-sized groups: one group received treatment based on the NIH National Asthma Education and Prevention Program (NAEPP) guidelines alone, and the other received treatment based on the guidelines plus measurement of exhaled NO. The year-long study compared participants’ symptoms and asthma exacerbations.
According to Dr. Szefler, “The hypothesis was that adding exhaled NO monitoring to the NIH asthma guidelines-based approach would improve asthma control over the guidelines-based approach alone.” Researchers had hoped that exhaled NO would indicate if there was a need for increased treatment dosage in the participants who had few asthma symptoms but who had ongoing high levels of lung inflammation. Although measuring exhaled NO is not routine practice in asthma management, this study was aimed at determining whether it should be included in treating patients in the future.
In the end, the study found that the group whose treatment was guided by exhaled NO did not end up with fewer or less severe asthma symptoms or fewer asthma exacerbations compared with the group that received treatment based on the NAEPP guidelines alone.
Most patients in each group had marked improvement in their asthma initially and throughout the study, highlighting the importance of optimizing asthma treatment according to the NIH guidelines. According to Dr. Busse, the upside of the study is that “good adherence to the current guidelines [for treating asthma patients] can mean good disease management without the need for a biomarker.” This is particularly important because the study was conducted in an inner-city population, which historically has suffered from more difficult-to-treat asthma and disproportionately higher mortality from asthma due to the lack of optimal management, according to Peter Gergen, M.D., the NIAID medical officer overseeing the study.
Since 1991, NIAID has funded research on asthma in inner-city areas with the goal of improving the treatment of children living in environments where the prevalence and severity of asthma is particularly high. Further information about this trial (NCT 00114413) can be found at www.clinicaltrials.gov.
NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
The National Institutes of Health (NIH)—The Nation's Medical Research Agency—includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
SJ Szefler et al. Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial. The Lancet. DOI 10.1016/S0140-6736(08)61448-8 (2008).
National Asthma Education and Prevention Program, Guidelines for the Diagnosis and Management of Asthma. National Heart, Lung, and Blood Institute, National Institutes of Health. (2007).
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