Fractional exhaled nitric oxide (FeNO) has been proposed as a non‑invasive marker of airway inflammation in asthma. In this article Lara Marín, Professional Services Pharmacist at the IPU discusses the role of FeNO testing in the diagnosis and management of asthma.
Asthma is a lung condition that causes respiratory symptoms such as wheezing, shortness of breath, tightness in the chest and cough that vary over time. It is estimated that 300 million of individuals are affected worldwide. It is a global health problem affecting all age groups and is prevalent in many developing countries. 1 in 13 people in Ireland currently have asthma and it is estimated that 890,000 people in Ireland experience asthma at some stage of their life.
Nitric oxide is produced in the lungs and is present in exhaled breath. The amount of nitric oxide in an exhaled breath is known as fractional exhaled nitric oxide (FeNO). It is modestly associated with levels of sputum and blood eosinophils and it is a biomarker for airway inflammation. The FeNO test is a point of care test that measures the level of nitric oxide gas in an exhaled sample of a patient’s breath. The sample is collected by having the patient breathe slowly and steadily into a mouthpiece that is attached to a machine that performs the measurement. It is used worldwide as part of the diagnosis and management of asthma. A positive test increases the probability of a person having Type 2/allergic/eosinophilic asthma, but a negative test does not exclude asthma; rather it suggests other differential diagnoses, such as non-type 2 asthma, other respiratory pathology, or other non-respiratory pathology.
FeNO is lower in smokers and during bronchoconstriction and it can be increased or decreased during viral respiratory infections. Elevated FeNO in adults with allergic asthma taking an inhaled corticosteroid (ICS) is recognised as a potentially modifiable risk factor for asthma.
Where FeNO is used in the diagnostic work-up for asthma it only forms one part of the diagnosis. It should never be the sole basis for diagnosis.
The Global Initiative for Asthma (GINA) note in their 2022 Global Strategy for Asthma Management and Prevention that, “FeNO has not been established as useful for ruling in or ruling out a diagnosis of asthma because while FeNO is higher in asthma that is characterised by Type 2 airway inflammation, it is also elevated in non-asthma conditions (for example eosinophilic bronchitis, atopy, allergic rhinitis, eczema) and it is not elevated in some asthma phenotypes (for example neutrophilic asthma)”.
The European Respiratory Society recommend FeNo in the diagnosis of asthma if there is uncertainty after spirometry and bronchodilator reversibility testing. They also strongly recommend the measurement of FeNO as part of the diagnostic work-up of children aged 5–16 years with suspected asthma.
The National Institute for Health and Care Excellence (NICE) in the UK support the use of FeNO testing alongside clinical assessment, spirometry and peak flow as part of the diagnostic algorithm for adults with respiratory symptoms suggestive of asthma. The British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS-SIGN) also support the use of FeNO as part of the initial assessment process where asthma is considered possible.
FeNO testing has a role in the management of asthma. GINA note that, “In patients with a diagnosis or suspected diagnosis of asthma FeNO can support the decision to start an ICS but it cannot be used to decide against treatment with an ICS”. NICE recommends FeNO as “an option to support asthma management in people who are symptomatic despite using inhaled corticosteroids”. The American Thoracic Society (ATS) in their Clinical Practice Guideline on Fractional Exhaled Nitric Oxide (FeNO) to Help Guide Asthma Treatment suggest the use of FeNO in addition to usual care, over usual care alone, in patients with asthma in whom treatment is being considered.
FeNO testing is also used when considering/evaluating the use of biologic therapy for severe asthma with type 2 inflammation who are inadequately controlled with high dose ICS plus another medicinal product for maintenance. In addition, the NHS South West Cardiovascular, Respiratory and Diabetes Clinical Network suggest the following scenarios where FeNO testing may be of benefit:
Knowing a patient’s FeNO level, and any changes over time, can help a patient, doctor and pharmacy team recognise how well your asthma is being controlled and help to avoid asthma episodes.”
To date FeNO testing has predominantly been available in secondary care, but with the development of newer validated point of care devices, testing is now becoming more available in the primary care setting including in the community pharmacy setting. In Ireland a few innovative pharmacies have been leading the way by introducing a FeNO testing service. Nigel Moloney, community pharmacist and Regional Representative for the South on the IPU Community Pharmacy Committee uses the Circassia Niox Vero® FeNO testing device, as evaluated by NICE when developing their recommendation on the use of FeNO testing in asthma diagnosis, to help improve outcomes for patients with asthma in his practice. Mr Moloney decided to include FeNO testing in his new asthma management service, which also involves a questionnaire about asthma control, peak flow measurement and an inhaler technique check.
According to Mr Moloney, “a person with a high FeNO level is four times more at risk of potentially severe exacerbations than someone with well-managed asthma. Knowing a patient’s FeNO level, and any changes over time, can help a patient, doctor and pharmacy team recognise how well your asthma is being controlled and help to avoid asthma episodes. Furthermore, tracking a patient’s FeNO level over time can be a useful tool in considering de-prescribing, changes to the asthma medication regimen and referral to a respiratory specialist for additional testing/challenges.”
Patients can self-refer to the service, and GPs locally are also referring patients for testing. Where FeNO levels in treated patients suggest that there may be sub-optimal adherence to treatment, the interaction with the pharmacist provides the opportunity to review inhaler technique and discuss both the benefits of adherence to treatment, and strategies to support this.
“We really value the opportunity to support patient outcomes and help people to manage their condition more effectively.” Local GPs have been quick to recognise the benefit of the service with Mr Moloney noting that the most interesting element to rolling out this service has been the number of referrals from GPs for this test: “80% of our FeNO tests are GP referrals. We perform the service and feedback both the results, and our interpretation of those results, to the GP for consideration. This allows the GP to make more informed decisions about asthma management plans and is particularly useful in patients who have a new differential diagnosis of asthma where the GP is considering which treatment options to initiate.”
The service is also valued by specialists in secondary care, and Mr Moloney said; “we have also had some very positive feedback from respiratory physicians who are very receptive to the patient attending their outpatient clinics ‘tooled-up’ with their FeNO and peak flow results. We are now in the early stages of expanding this service to include spirometry, so the arsenal of information available to prescribers to help them make decisions is becoming increasingly powerful.”
Finally, Mr Moloney advises anyone thinking of implementing such a service to carefully consider the device they use to ensure it is validated and can be safely used in the community pharmacy setting. Considerations include initial and ongoing costs, associated software, ongoing maintenance, in use considerations such as populations that the device is validated for use in, functionality and data storage. Training in device use will be required as will an assessment as to service inclusion and exclusion criteria. Results interpretation and referral criteria are also important considerations.
”Mr Moloney advises anyone thinking of implementing such a service to carefully consider the device they use to ensure it is validated and can be safely used in the community pharmacy setting.”
A range of resources to support patients with asthma management are available on the IPU website ipu.ie > Pharmacy Services > Supporting Patients > Management of Asthma.
References available on request
Lara Marín
Professional Services Pharmacist, IPU
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