New products
The Aerocrine exhaled nitric oxide monitoring system NIOX is cleared by the US Food and Drug Administration for monitoring therapy in asthma

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The Aerocrine exhaled nitric oxide (NO) monitoring system NIOX was cleared by the US Food and Drug Administration for clinical application in patients with asthma in May 2003. The fractional concentration of exhaled NO has been extensively researched as a marker of airway inflammation in asthma and other diseases and is now poised to enter clinical application. The American Thoracic and European Respiratory Societies' current guidelines recommend measurement at constant expiratory flow, which is difficult for some adults and children. The NIOX NO monitoring system was designed to facilitate standardized measurement according to guidelines. A clinical study was performed together with in vitro testing to obtain clearance. Exhaled NO levels were measured in unstable steroid-naive adult and pediatric asthmatic subjects and again after a 2-week treatment with inhaled corticosteroids. Exhaled NO levels decreased highly significantly, with 95% confidence limits for the decrease of −40% to −60% accompanied by clinical improvement. This trial, together with extensive in vitro testing, led to the clearance of NIOX by the US Food and Drug Administration. This article in the journal's “New products” feature section will describe background material regarding exhaled NO, special features of the NIOX NO monitoring system, and how this tool can be incorporated into clinical asthma management.

Section snippets

The history of exhaled nitric oxide

It was only in the late 1980s that the small molecule nitric oxide (NO) was found to be an endogenous mediator of profound importance in both health and disease synthesized by complex heme-containing NO synthases.1 It is hard to imagine biologic science without this mediator today, which is reflected in NO being crowned “Molecule of the Year” by Science in 1992.2 The profound achievements of Furchgott, Ignarro, and Murad in unraveling the NO story brought them the Nobel Prize for Medicine in

The NIOX no monitoring system

Aerocrine AB was founded by researchers at the Karolinska Institute in Stockholm, Sweden, in 1997, and a US subsidiary, Aerocrine Inc, Chicago, Illinois, was established in 2001. The company is entirely dedicated to the field of exhaled NO instrumentation and its clinical applications.

The Aerocrine NO Monitoring System, NIOX, was designed to facilitate constant-flow online measurement of FeNO according to European Respiratory Society and ATS guidelines (Fig 2). The NO sensor is based on

The process to obtain US Food and Drug Administration clearance for NIOX

The NIOX NO monitoring system was approved for clinical use in the European Union in April 2000. In the United States market authorization for medical devices is the responsibility of the US Food and Drug Administration (FDA) Center of Devices and Radiological Health. The NIOX NO monitoring system was deemed an in vitro diagnostic and nonsignificant risk device by the FDA, which required validation of the intended clinical application and safety assurances. The first 510(k) application was

The clinical trial required for FDA clearance

An open-label and prospective study was performed at 6 centers in the United States. Children (5-17 years old) and adults (>18 years old) with asthma, as defined by the National Asthma Expert Panel Report II,88 were recruited. The protocol was approved by institutional review boards, and informed consent was obtained from all subjects, legal guardians, or both. Subjects were recruited from outpatient clinics by physicians who also served as study investigators.

The FDA labeling of NIOX

The FDA cleared NIOX for clinical use in patients with asthma in May 2003. The labeling of this device is currently restricted to the monitoring of the response to anti-inflammatory medications, as an adjunct to established clinical and laboratory assessments, in adults up to 65 years old and children older than 4 years. The point-of-care study guided the labeling to restrict the operation of NIOX to trained physicians, respiratory therapists, nurses, and laboratory technicians. Physicians are

Clinical application

After FDA clearance of NIOX, a new phase of clinical application has arrived. There are several potential applications for FeNO in the clinic, although for now, the FDA has only cleared the system for monitoring the effect of anti-inflammatory medication in patients with asthma.

Sensor technologies

Chemiluminescence is the current technology used in most commercial NO analyzers both for medical and nonmedical use, but other technologies exist.103., 104., 105. Chemiluminescence is likely to be replaced soon by simpler, more robust, and more economic approaches to NO measurement. In the future, difficult asthmatic patients might measure exhaled NO levels at home and adjust therapy on a day-to-day basis.

Flow control

As discussed above, exhalation flow must be standardized in the single-breath maneuver,

Overall summary

Exhaled NO has stood the test of time and has now moved from research to clinical application with the FDA's clearance of the NIOX NO monitoring system. Exhaled NO serves as a prototype for the application of biomarkers to the management of the inflammatory component of asthma. This novel marker should be used in conjunction with standard asthma outcomes, and future guidelines on asthma management might include the testing of inflammation as an additional aid to improving asthma control and

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    • Cited by (0)

    Series editors: Donald Y. M. Leung, MD, PhD, Harold S. Nelson, MD, Stanley J. Szefler, MD, Philip S. Norman, MD, and Andrea Apter, MD, MSc

    Supported by an unrestricted education grant from Aerocrine, Solna, Sweden

    This article is a peer-reviewed, invited article prepared on behalf of Aerocrine by Philip E. Silkoff, MD (guest editor), Mats Carlson, MSc, Trevor Bourke, BSc, Rohit Katial, MD, Elisabeth Ögren, MPharm, and Stanley J. Szefler, MD.

    Disclosure of potential conflict of interest: P. E. Silkoff has previous consultant arrangements with Aerocrine AB, has patent licensing arrangements from Ionics Instruments and is currently an employee of AstraZeneca Pharm. M. Carlson and T. Bourke are employees of Aerocrine, Inc. R. Katial—none disclosed. S. J. Szefler—none disclosed.

    †

    We regret to announce that Elisabeth Ögren from Aerocrine passed away tragically during the preparation of this article.

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    Copyright © 2004 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.