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Left untreated, asthma of all severities can become out of control. Patients with uncontrolled asthma usually have high FeNO, a trait associated with up to 3.2x greater risk of exacerbations when compared to low FeNO levels, faster decline in lung function and long-term airway remodelling.1-3
Patients have uncontrolled asthma if at least one of the following applies:
- Poor symptom control: frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma
- Frequent exacerbations (≥2/year) requiring oral corticosteroids (OCS) or serious exacerbations (≥1/year) requiring hospitalisation
Only 20% of patients considered to have poor symptom control despite high-dose treatment have severe asthma. The other 80% suffer from difficult-to-treat asthma, which may be improved by reviewing adherence or inhaler technique.4
A FeNO suppression test, usually performed over five to seven days with inhaled corticosteroids (ICS) doses being observed, can help determine whether a patient on ICS has been adherent with therapy. In non-compliant patients, FeNO levels will reduce by up to 50% through the test period.5 Patients with persistent high FeNO are likely to have severe asthma.
Uncontrolled asthma despite medium- or high-dose ICS with a second controller (usually LABA) or with maintenance OCS, or that requires high-dose treatment to maintain good symptom control and reduce the risk of hospitalisation.
This type of asthma can usually be controlled by reducing risk factors such as incorrect inhaler technique, poor adherence, smoking or comorbidities. Other diseases presenting similar symptoms (such as COPD, GERD) may also be incorrectly diagnosed as asthma.
Uncontrolled asthma despite adherence with maximal optimised high-dose ICS-LABA treatment and management of contributory factors, or that worsens when high-dose treatment is decreased.
Asthma is not classed as severe if it markedly improves when contributory factors such as inhaler technique and adherence are addressed.
The currently available biologics mostly include Type 2-targeted therapies.
Before being prescribed this type of biologic, patients should be evaluated to ensure their asthma is caused by underlying Type 2 inflammation.4
FeNO testing is strongly recommended to diagnose Type 2 airway inflammation.6 The severe asthma guidelines produced by GINA, ERS and ATS suggest that a FeNO value >20 ppb supports a diagnosis of Type 2 inflammation.
Once a case of Type 2 inflammation and severe asthma has been established, FeNO testing can help with the selection of a personalised, targeted therapy by identifying appropriate candidates for biologic treatments.
Different biologics target different pathways, most of which have a role for FeNO. For example, a FeNO measurement >20 ppb predicts a good response to anti-IgE therapy (omalizumab), while a FeNO value >25 ppb indicates the patient is likely to respond well to anti-IL4R (dupilumab).7 Evidence shows FeNO levels can be reduced by up to 40% with dupilumab.8
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1. Busse, W.W et al. Baseline FeNO as a prognostic biomarker for subsequent severe asthma exacerbations in patients with uncontrolled, moderate-to-severe asthma receiving placebo in the LIBERTY ASTHMA QUEST study: a post-hoc analysis. The Lancet Respir Med. 2021:9(10): pp.1165-1173. 2. Bai TR et al. Severe exacerbations predict excess lung function decline in asthma. Eur Respir J. 2007;30(3):452-6. 3. Matsunaga K et al. Persistently high exhaled nitric oxide and loss of lung function in controlled asthma. Allergol Int. 2016;65(3):266-71. 4. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2021 update. 5. Heaney LG et al. Medical Research Council UK Refractory Asthma Stratification Programme (RASP-UK). Remotely monitored therapy and nitric oxide suppression identifies nonadherence in severe asthma. Am J Respir Crit Care Med. 2019;199(4):454-464. 6. 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. 7. Holguin F et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020;55(1):1900588. 8. Corren J et al. Dupilumab efficacy in patients with uncontrolled, moderate-to-severe allergic asthma. J Allergy Clin Immunol Pract. 2020;8(2):516-526.