The Utility of Fractional Exhaled Nitric Oxide Suppression in the Identification of Nonadherence in Difficult Asthma

Centre for Infection and Immunity, Queen's University Belfast, Belfast, United Kingdom.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 09/2012; 186(11). DOI: 10.1164/rccm.201204-0587OC
Source: PubMed


RATIONALE: Non-adherence to inhaled corticosteroid therapy (ICS) is a major contributor to poor control in difficult asthma, yet it is challenging to ascertain. OBJECTIVES: Identify a test for non-adherence using fractional exhaled nitric oxide (FeNO) suppression following directly observed inhaled corticosteroid (DOICS) treatment. METHODS: Difficult asthma patients with an elevated FeNO (>45 ppb) were recruited as adherent (ICS prescription filling >80%) or non-adherent (filling <50%). They received 7 days of DOICS (budesonide 1600 μg) and a test for non-adherence based on changes in FeNO was developed. Using this test, clinic patients were prospectively classified as adherent/non-adherent and this was then validated against prescription filling records, prednisolone assay and concordance interview. MEASUREMENTS AND MAIN RESULTS: After 7 days of DOICS non-adherent (n=9) compared with adherent subjects (n=13) had a greater reduction in FeNO to 47 ± 21% vs 79 ± 26% of baseline measurement (p=0.003), which was also evident after 5 days (p=0.02) and a FeNO test for non-adherence (AUC=0.86, 95%CI: 0.68-1.00) was defined. Prospective validation in 40 subjects found the test identified 13 as non-adherent; 8 confirmed non-adherence during interview (3 of whom had excellent prescription filling but did not take medication), 5 denied non-adherence - 2 had poor inhaler technique (unintentional non-adherence), 1 also denied non-adherence to prednisolone despite non-adherent blood level. Twenty-seven participants were adherent on testing, which was confirmed in 21. Five admitted poor ICS adherence but of these, 4 were adherent with oral steroids and 1 with Omalizumab. CONCLUSIONS: FeNO suppression following DOICS provides an objective test to distinguish adherent from non-adherent patients with difficult asthma.

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    • "The authors suggested that improving parental knowledge of drug characteristics and feedback of FeNO readings could positively influence adherence and thus improve asthma control [86]. Finally, McNicholl et al. showed that when patients with difficult-to-treat asthma treated with budesonide were monitored based on changes in FeNO levels, adherent subjects had a greater reduction in FeNO [87]. "
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    ABSTRACT: Although not yet widely implemented, fraction of exhaled nitric oxide (FeNO) has emerged in recent years as a potentially useful biomarker for the assessment of airway inflammation both in undiagnosed patients with non-specific respiratory symptoms and in those with established airway disease. Research to date essentially suggests that FeNO measurement facilitates the identification of patients exhibiting T-helper cell type 2 (Th2)-mediated airway inflammation, and effectively those in whom anti-inflammatory therapy, particularly inhaled corticosteroids (ICS), is beneficial. In some studies, FeNO-guided management of patients with established airway disease is associated with lower exacerbation rates, improvements in adherence to anti-inflammatory therapy, and the ability to predict risk of future exacerbations or decline in lung function. Despite these data, concerns regarding the applicability and utility of FeNO in clinical practice still remain. This article reviews the current evidence, both supportive and critical of FeNO measurement, in the diagnosis and management of asthma and other inflammatory airway diseases. It additionally provides suggestions regarding the practical application of FeNO measurement: how it could be integrated into routine clinical practice, how its utility could be assessed and its true value to both clinicians and patients could be established. Although some unanswered questions remain, current evidence suggests that FeNO is potentially a valuable tool for improving the personalised management of inflammatory airway diseases.
    Respiratory medicine 06/2014; 108(6). DOI:10.1016/j.rmed.2014.02.005 · 3.09 Impact Factor
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    • "We have recently demonstrated that the degree of suppression in fractional exhaled nitric oxide (FeNO) occurring with directly observed inhaled steroid therapy can be used to identify nonadherence to ICS in a difficult asthma population.37 This test could be used prior to the introduction to complex biological therapies targeting eosinophilic disease (eg, mepolizumab), to ensure the clinical problem is not due to nonadherence with inhaled steroids. "
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    ABSTRACT: Nonadherence to prescribed treatment is an important cause of difficult asthma. Rates of nonadherence amongst asthmatic patients have been shown to range between 30% and 70%. This is associated with poor health care outcomes and increased health care costs. There is no such thing as a "typical" nonadherent patient. The reasons driving nonadherence are multifactorial. Furthermore, adherence is a variable behavior and not a trait characteristic. Adherence rates can vary between the same individual across treatments for different conditions. There is no consistent link between socioeconomic status and nonadherence, and although some studies have shown that nonadherence is more common amongst females, this is not a universal finding. The commonly held perception that better adherence is driven by greater disease severity has been demonstrated to not be the case, in both pediatric and adult patients. Identification of nonadherence is the first step. If adherence is not checked, it is likely that poor adherence will be labeled as refractory disease. Failure to identify poor adherence may lead to inappropriate escalation of therapy, including the potential introduction of complex biological therapies. Surrogate measures, such as prescription counting, are not infallible. Nonadherence can be difficult to identify in clinical practice, and a systematic approach using a variety of tools is required. Nonadherence can be successfully addressed. Therefore, assessment of adherence is of paramount importance in difficult asthma management, in order to reduce exacerbations and steroid-related side effects as well as hospital and intensive care admissions, health care cost, and inappropriate treatment escalation. In this paper, we present an overview of the literature surrounding nonadherence in difficult asthma. We explore the facts and myths surrounding the factors driving nonadherence as well as how it can be identified and addressed.
    Patient Preference and Adherence 04/2013; 7:329-36. DOI:10.2147/PPA.S38208 · 1.68 Impact Factor
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    American Journal of Respiratory and Critical Care Medicine 03/2012; 185(5):476-8. DOI:10.1164/rccm.201112-2249ED · 13.00 Impact Factor
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