The Aerocrine exhaled nitric oxide monitoring system NIOX is cleared by the US Food and Drug Administration for monitoring therapy in asthma - 24/08/11

Doi : 10.1016/j.jaci.2004.08.042

Philip E. Silkoff, MD ^a,^⁎ : (guest editor), Mats Carlson, MSc ^b, Trevor Bourke, BSc ^c, Rohit Katial, MD ^a, Elisabeth Ögren, MPharm ^b,^{^{†
We regret to announce that Elisabeth Ögren from Aerocrine passed away tragically during the preparation of this article.}}, Stanley J. Szefler, MD ^a
^a From National Jewish Medical and Research Center, Denver
^b Aerocrine AB, Stockholm
^c Aerocrine Inc, New York

Reprint requests: Philip E. Silkoff, MD, 224 Spruce Tree Rd, Radner, PA 19087.

Denver, Colo, Stockholm, Sweden, and New York, NY

Abstract

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.

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Key words : Exhaled, nitric oxide, asthma, inflammation, monitoring

Abbreviations used : ATS, C_alv, C_w, D_NO, FDA, Fe_NO, ICS, NO, ppb, TSS

Plan

The history of exhaled nitric oxide

Exhaled NO measurement issues

Factors influencing Fe_NO levels

Reference values of Fe_NO

Evidence that Fe_NO is a marker of airway inflammation

Targeting asthma control

Modeling NO secretion in the airway

Measurement scenarios

The NIOX no monitoring system

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

The clinical trial required for FDA clearance

Inclusion and exclusion criteria

Measurement of Fe_NO levels

Point-of-care analysis

The FDA labeling of NIOX

Clinical application

Exhaled NO as an index of response to anti-inflammatory therapy

Future clinical uses for exhaled NO testing in patients with asthma

Future technical developments

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.