FeNO Method and Clinical Interpretation of FeNO FAQ 1-21; NIOX VERO® FAQ 22-24

FeNO Method and Clinical Interpretation of FeNO


1.     Can Allergic Rhinitis elevate FeNO?

Allergic Rhinitis can cause mild elevations of exhaled nitric oxide, and in some cases, where the allergic reaction is significant, even more pronounced elevations of exhaled nitric oxide. Of course, asthma and allergic rhinitis are often found together in patients, so even previous negative methacholine and mannitol challenge tests in the absence of symptoms does not rule out asthma, and a high FeNO with symptoms should cause one to reconsider this as a possibility.


2.     How does Allergic Rhinitis impact FeNO?

Allergic inflammation in the nasal cavity causes the release of NO just as it does in the airways. Circulating levels of IL-4 and IL-13 may cause increased release of NO from bronchial epithelial cells. Additionally, allergens that are causing reactions in the nose are also being inhaled and may be causing mild reactions in the airway, without leading to asthma.


3.     Is nasal NO useful for allergic rhinitis?

Nasal NO (nNO) is much higher than exhaled NO, and as such measuring nNO for allergic rhinitis is of limited value. However, low nNO can be useful for helping to detect other conditions such as Primary Ciliary Dyskinesia.  Note that all use of nasal application with NIOX devices are for research use only and not part of the Intended use, see question 4.


4.     Can I utilize nasal NO testing at my clinic?

This is not approved and can only be performed under the auspices of research (an approved protocol and ethics committee approval.)


5.     Is the FeNO test suitable for children?

US: FeNO can be measured in younger children* with high success rates after coaching them through the procedure. Since approximately 80% of children have atopic asthma, FeNO can play an important role in the diagnosis and management of their disease. In several recent studies (Peirsman 2014, Petsky 2014, Mahr 2013), asthma therapy directed by FeNO has been shown to reduce asthma exacerbations in children when compared to symptom based or usual care.

* Intended use limits the use down to approximately the age of 7 years


6.     What do I do if the patient’s FeNO value is on the border – 24ppb?

FeNO is just like any other medical test and you need to use your clinical judgment, so it would depend on the clinical situation of the patient and the symptoms (or lack of symptoms) they were having.


7.     Why is GINA not recommending FeNO?

While we can’t speak for GINA, we can say that every year more and more studies are being published that show the benefit of using FeNO to manage the treatment of allergic asthma.


8.     Should I replace spirometry with FeNO?

FeNO is not a replacement for spirometry. FeNO measures allergic (Th2) airway inflammation while spirometry measures airflow limitation. They provide important information about different aspects of the disease. For example, FeNO can provide information on the level of underlying allergic airway inflammation, but it cannot tell you the degree of airflow obstruction, which is important to know when asthma is severe.  However, for treatment optimization there are recent publications which indicate that adjusting ICS dose according to FeNO value gives reductions in exacerbations up to 50%. So for maximal risk reduction FeNO measurement is advised in addition to spirometry.


9.  What is the explanation for patients with low FeNO but with asthma? Should these patients be treated with ICS or not?

Not all asthma is allergic (atopic or Th2 High or eosinophilic) asthma. In fact, only 50-60% of adults have allergic asthma. The best treatment for the remainder of these patients is not well known. ICS therapy is generally prescribed for these patients as it is believed to confer some benefit and risk reduction. However, when patients have minor symptoms and low risk of exacerbations, and a low FeNO, ICS are unlikely to improve lung function (Smith 2005)


10.  What about patients who have a high FeNO but do not have asthma?

There are other causes of elevated exhaled nitric oxide. After carefully excluding asthma with challenge testing, then considerations for significant allergic rhinitis and eczema should be considered. Also food allergies and other bowel diseases have been reported to increase exhaled NO. A diet rich in nitrate containing foods can also raise exhaled NO.


11.  How long does it takes for FeNO to respond to treatment with corticosteroids?

In a paper (Anderson 2012), the t1/2 for FeNO after starting treatment with ICS was 2.5-3 days. FeNO had reached a new plateau by 2 weeks. Thus, rechecking FeNO 2 weeks after starting ICS would be the earliest we would recommend.


12.  How long before an exacerbation, will FeNO increase?

Unknown as long term studies looking at variation in FeNO and its time course in relation to an exacerbation have not been performed.


13.  What is the explanation for high FeNO results in patients diagnosed with asthma who are asymptomatic with long term normal spirometry results?

Inflammation will proceed lung function changes and symptoms which is why it is beneficial to measure it. In studies that showed a reduction in exacerbations, measuring FeNO every 2-4 months and titrating ICS until FeNO was in the low/normal range resulted in nearly 50% reduction in exacerbations when compared to protocols that used symptom based treatments (ACQ) or usual care.


14.  What is the explanation for low FeNO results in patients diagnosed with asthma that are symptomatic, with +skin tests indicating atopy and abnormal spirometry results?

There are many causes of symptoms in a patient with asthma. In this case, FeNO is telling us that the patient has low levels of allergic (Th2) airway inflammation. However, they may have GERD, aspiration, ABPA, OSA, or other causes of their symptoms that need to be explored.


15.  How often should a FeNO test be conducted?

In studies that showed a reduction in exacerbations, measuring FeNO every 2-4 months and titrating ICS until FeNO was in the low/normal range resulted in nearly 50% reduction in exacerbations when compared to protocols that used symptom based treatments (ACQ) or usual care.


16.  Is FeNO measurement useful in COPD?

Approximately 15-25% of COPD patients will have concomitant asthma according to most studies that have been done on this topic. In a recent paper (Donohue 2014) FeNO was elevated in a similar number of patients with COPD. Hence, FeNO may be useful in identifying COPD patients with asthma, though more work needs to be done in this area.



17.  The study of Peirsman 2014 did not show more symptom free days, but less exacerbations in the asthma patient group managed with a FeNO strategy. How is this possible?

Symptoms of asthma are mostly due to cough and wheeze, secondary to mucous production and bronchoconstriction. Questionnaires are used to elicit these symptoms, and patients may have a short term allergen exposure that cause some early and late phase effects, but does not rise to the level of even needing a rescue inhaler, and certainly not an exacerbation. On the other hand, exacerbations are generally caused by viruses and bacteria, and the persistent nature of these infections, leads to an exacerbation. Patients with higher levels of inflammation are more susceptible to these respiratory infections, and have more severe symptoms when infected. Thus, keeping inflammation under better control with FeNO directed therapy reduces the risk of exacerbation.


18.  Should FeNO be measured out of the "allergen" season?

To see the benefit of reduced exacerbation rates, studies have had to regularly measure FeNO in their patients, ranging from every 2-4 months.


19.  What about asthma patients with no symptoms and a FeNO in the medium range?

To see the benefit of reduced exacerbation rates, studies generally titrated ICS to FeNO <20-25 ppb, regardless of symptoms. Remember that inflammation and symptoms may not be concurrent, and inflammation will proceed symptoms by weeks in many cases.


20.  Will FeNO reflect the level of mast cells as well? What about the use of anti-histamine and anti-leukotrienes?

FeNO will not reflect the level of mast cells. While mast cells can and do produce IL-13 that can stimulate epithelial cells to transcribe iNOS and produce more NO, other immune mediator cells also function in this capacity. Anti-histamines will not affect this function of mast cells and thus will not alter NO production. Anti-Leukotriene receptor antagonists have not been shown to have definitive effects on exhaled nitric oxide in patients with atopic asthma though there are some theoretical reasons they might.



21.     Are the values obtained with NIOX VERO the same as those obtained with NIOX MINO ®®?

Aerocrine has performed a clinical study to demonstrate substantial equivalence in the clinic between NIOX VERO and NIOX MINO ®. Data available upon request (Product labelling summary).


22.     Can I measure nasal FeNO (nNO) with the NIOX VERO?

No, there is no nasal application for NIOX VERO. There is a research nasal application for NIOX MINO ®.


23.     Is the NIOX VERO more expensive in price? 

The cost is comparable with the cost for NIOX MINO ® . The NIOX VERO device lasts for 5 years or 15 000 measurements. Corresponding values for NIOX MINO ® are 3 years and 3000 measurements.



Important Information Regarding NIOX® Devices

Aerocrine manufactures hand-held devices for measuring the fractional NO concentration in expired breath (FeNO).  The devices can only be used by trained healthcare professionals.  NIOX is suitable for children and adults 18 years.  Consult User Manual for age restrictions in children.  FeNO measurements provide the physician with means of evaluating asthma patients’ response to anti-inflammatory therapy, as an adjunct to the established clinical and laboratory assessments in asthma.  Not all patients with asthma will have an elevated FeNO level.  FeNO levels should be interpreted in the clinical context.