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The history of FeNO: The scientific milestones behind asthma management today

FeNO (fractional exhaled nitric oxide) testing has proved to be a useful addition to asthma management. In this article, we look back at the scientific milestones that paved the way for today’s FeNO devices like NIOX®.

Asthma, a lung disease that affects over 340 million people worldwide1, can be difficult to diagnose correctly. Figures show that as many as 50% of children's and 33% of adults' asthma diagnoses may be wrong.1,2 Thanks to scientific progress in the last 30 years, traditional asthma tests can now be supported by FeNO testing.

Nitric oxide and the Nobel Prize in medicine

The importance of nitric oxide (NO) was only established in the late 1980s. Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad’s research led to the discovery that this small molecule has signaling properties. Their achievements would eventually earn them a well-deserved Nobel Prize in medicine, and also paved the way for a breakthrough in asthma research.4

In the early 1990s, researchers at the Karolinska Institute in Stockholm discovered the presence of NO in human lungs. Two years later, it was established that asthma patients exhale higher levels of NO. Soon it was also shown that as steroid therapy reduces inflammation, it also results in lower levels of NO.5

Another important discovery came in 1997, when it was found that FeNO levels vary depending on the exhaled air flow rate. The European Respiratory Society and the American Thoracic Society (ATS) made a great effort to standardize the methods for comparison. In particular, the joint guideline published in 2005 set the standard flow rate at which all FeNO measurements should be performed.6

First NIOX Device - NIOX FLEX - © Circassia

Aerocrine, the first NIOX® device, and Circassia

In 1997, researchers at the Karolinska Institute in Stockholm founded Aerocrine AB. Focusing entirely on inflammatory airway diseases, Aerocrine started developing a device that would measure FeNO levels quickly and accurately. The result was NIOX® FLEX, which was approved as a medical device in Europe in 2000. Together with conventional methods such as peak flow and spirometry, FeNO testing devices like NIOX® make a considerable difference in diagnosing, treating, and managing asthma.7

Research on the relationship between FeNO levels and asthma continued, and the early 2000s saw considerable progress. It was found that exhaled NO levels correlate with certain standard outcomes in asthma, for example how the airways react to inhaled histamine and methacholine.8,9 Experiments were carried out to explain the flow dependency of exhaled NO. It was further shown that exhaled NO can be used to predict asthma exacerbations.9

The most recent NIOX device - NIOX VERO® - © Circassia

In 2001, Aerocrine Inc was established in the USA. Two years later, the NIOX® system was cleared by the FDA (US Food and Drug Administration) for use in monitoring asthma.11

Aerocrine continued to innovate and develop the NIOX® system. NIOX FLEX® was replaced by NIOX MINO® in 2005, and NIOX VERO® in 2013.

Circassia (founded 2006) acquired Aerocrine and NIOX® in 2015.

FeNO endorsements

In the last few years, the benefits of FeNO testing in asthma management have continued to be recognized. Both the American Thoracic Society (ATS) and the Global Initiative for Asthma (GINA) have confirmed that they recommend FeNO for asthma management.12,13

13For the first time, FeNO is now recommended by the National Heart, Lung, and Blood Institute (NHLBI) in the 2020 Focused Updates to the Asthma Guidelines.14

FeNO is also recognized by many other asthma advocates associations in the United States, including the American Academy of Allergy Asthma & Immunology (AAAAI),15 the American College of Allergy, Asthma & Immunology (ACAAI),15 the Agency for Healthcare Research and Quality (AHRQ),16 the Allergy and Asthma Foundation of America (AAFA),17 and the Allergy & Asthma Network (AAN).18

More about NIOX® and FeNO testing

Today, over 40 million tests have been performed using a NIOX device.19 For more information on how FeNO testing can aid asthma management, please visit niox.com or contact us directly with any questions you may have:

Related Articles:

The history of FeNO: The scientific milestones behind asthma management today

How certain foods affect FeNO testing results

An introduction to international guidelines for FeNO testing.

References

1. Global Asthma Network. The Global Asthma Report. 2018.
2. Looijmang-van den Akker I et al. Overdiagnosis of asthma in children in primary care: a retrospective analysis. Br J Gen Pract. 2016;66 (644): e152-e157
3. Aaron SD et al. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317(3):269-279
4. Nobel Prize Website. https://www.nobelprize.org/prizes/medicine/1998/summary/. Last accessed 24th June 2020.
5. Yates DH et al. Effect of a nitric oxide synthase inhibitor and a glucocorticosteroid on exhaled nitric oxide. Am J Respir Crit Care Med. 1995;152:892-6.
6. American Thoracic Society, European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005;171(8):912-930.
7. National Institute for Health and Clinical Excellence (NICE). Asthma: diagnosis, monitoring and chronic asthma management. NICE guideline [NG80]. 2017.
8. Franklin PJ et al. Exhaled nitric oxide and asthma: complex interactions between atopy, airway responsiveness, and symptoms in a community population of children. Thorax. 2003;58(12):1048-1052.
9. Reid DW et al. Exhaled nitric oxide continues to reflect airway hyperresponsiveness and disease activity in inhaled corticosteroid-treated adult asthmatic patients. Respirology. 2003;8(4):479-486.
10. Jones SL et al. The predictive value of exhaled nitric oxide measurements in assessing changes in asthma control. Am J Respir Crit Care Med. 2001;164:738-43.
11. Silkoff PE et al. The Aerocrine exhaled nitric oxide monitoring system NIOX is cleared by the US Food and Drug Administration for monitoring therapy in asthma. The Journal of Allergy and Clinical Immunology. 2004;114(5):1241-56
12. Dweik RA et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602-15.
13. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention, 2018 Update. 2018.
14. Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC) et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-1270.
15. American Academy of Allergy, Asthma, and Immunology and American College of Allergy, Asthma, and Immunology. AAAAI/ACAAI joint statement of support of the ATS clinical practice guideline: interpretation of exhaled nitric oxide for clinical applications. Feb 2012.
16. Wang Z et al. Agency for Healthcare Research and Quality (AHRQ). The clinical utility of fractional exhaled nitric oxide (FeNO) in asthma management. Comparative Effectiveness Reviews, 197. 2017.
17. Data on file. Circassia Inc. January 2019.
18. Data on file. Circassia Inc. January 2019.
19. Internal data on file. Circassia Ltd. C-NIOX-0002.