Clinical usefulness of fractional exhaled nitric oxide for diagnosing prolonged cough

Sato, Suguru; Saito, Junpei; Sato, Yasuko; Ishii, Taeko; Wang, Xintao; Tanino, Yoshinori; Ishida, Takashi; Munakata, Mitsuru

doi:10.1016/j.rmed.2008.04.018

Cited by 61 publications

(38 citation statements)

References 26 publications

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“…Our findings confirm the previous observation that FeNO could be used in the diagnosis of CVA Fujimura et al 2008;Sato et al 2008). However, there was no relationship between FeNO and nNO levels; also, FeNO levels in UACS, regardless of the presence of sinusitis, did not differ from those in the other etiologies.…”

Section: Discussionsupporting

confidence: 92%

“…Patients with asthma have shown higher levels of FeNO (Alving et al 1993) and can be diagnosed more readily and accurately with FeNO measure-ments (Smith et al 2004). In the diagnosis of prolonged cough, FeNO has been shown to be useful in the diagnosis of CVA Fujimura et al 2008;Sato et al 2008) and non-asthmatic eosinophilic bronchitis (Oh et al 2008), as well as in the prediction of responses to inhaled corticosteroids (Hahn et al 2007). While measurement of nitric oxide (NO) has been attempted in the evaluation of lower airway causes of prolonged cough, it has not been assessed for its usefulness in the diagnosis of UACS.…”

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confidence: 99%

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Measurement of Nasal Nitric Oxide Is Useful for the Diagnosis of Sinusitis-Induced Prolonged Cough

Kim

Jeong

Kwak

et al. 2011

Tohoku J. Exp. Med.

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Upper airway cough syndrome (UACS), the most common cause of prolonged cough, is diagnosed based on clinical findings without specific diagnostic test. The concentration of nitric oxide in nasal cavity air (nNO) is influenced by allergic rhinitis and/or sinusitis, both of which are common causes of UACS. We measured nNO levels in patients with UACS and those with other causes. We also examined the usefulness of measuring nNO for differentiating patients with sinusitis from those without sinusitis. The study included 93 adult patients with prolonged cough lasting more than three weeks. Etiologies of cough were identified and nNO was measured at the initial investigation. UACS was diagnosed in 58 patients (62.4%), and sinusitis was identified in 11 (19.0%) of the 58 patients with UACS. Levels of nNO in UACS did not differ from non-UACS etiologies (316.2 ± 129.2 vs. 334.9 ± 88.2 ppb; p = 0.452), suggesting that the measurement of nNO could not discriminate UACS from other etiologies of prolonged cough. However, patients with sinusitis showed significantly decreased nNO levels (190.1 ± 114.8 ppb) compared with patients with UACS without sinusitis (345.7 ± 114.6 ppb; p < 0.001) and non-UACS patients (334.9 ± 88.2 ppb; p < 0.001). In a receiver operating characteristic curve analysis for the diagnosis of sinusitis in prolonged cough, the best sensitivity (73.2%) and specificity (81.8%) were obtained with a nNO cutoff value of 279.0 ppb. These findings imply that the measurement of nNO could be useful for diagnosis of prolonged cough associated with sinusitis.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Measurement of Nasal Nitric Oxide Is Useful for the Diagnosis of Sinusitis-Induced Prolonged Cough

Kim

Jeong

Kwak

et al. 2011

Tohoku J. Exp. Med.

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“…Inflammatory phenotype groups in asthma distinquished by blood Eos, either with 36 or without Neu 17 , have been investigated and recently employed in a clinical trial 13 . In the study with Lebrikizumab, subjects were initially characterized for T H 2 phenotypes based on combined blood Eos and IgE.…”

Section: Discussionmentioning

confidence: 99%

Biomarker surrogates do not accurately predict sputum eosinophil and neutrophil percentages in asthmatic subjects

Hastie

Moore

et al. 2013

Journal of Allergy and Clinical Immunology

233

158

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Background Sputum eosinophils (Eos) are a strong predictor of airway inflammation, exacerbations, and aid asthma management, whereas sputum neutrophils (Neu) indicate a different severe asthma phenotype, potentially less responsive to TH2-targeted therapy. Variables such as blood Eos, total IgE, fractional exhaled nitric oxide (FeNO) or FEV1% predicted, may predict airway Eos, while age, FEV1%predicted, or blood Neu may predict sputum Neu. Availability and ease of measurement are useful characteristics, but accuracy in predicting airway Eos and Neu, individually or combined, is not established. Objectives To determine whether blood Eos, FeNO, and IgE accurately predict sputum eosinophils, and age, FEV1% predicted, and blood Neu accurately predict sputum neutrophils (Neu). Methods Subjects in the Wake Forest Severe Asthma Research Program (N=328) were characterized by blood and sputum cells, healthcare utilization, lung function, FeNO, and IgE. Multiple analytical techniques were utilized. Results Despite significant association with sputum Eos, blood Eos, FeNO and total IgE did not accurately predict sputum Eos, and combinations of these variables failed to improve prediction. Age, FEV1%predicted and blood Neu were similarly unsatisfactory for prediction of sputum Neu. Factor analysis and stepwise selection found FeNO, IgE and FEV1% predicted, but not blood Eos, correctly predicted 69% of sputum Eos

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“…Of these, six 69,71,72,[82][83][84]86,87 were considered to be of most relevance to the decision problem, although the studies had not necessarily been conducted in the UK. l Nine studies [73][74][75][76][77]81,85,88,89,91 recruited patients who could be considered 'difficult to diagnose' and are located at other points along the diagnostic pathway. These patients had already undergone some of the tests in the UK pathway and had tested negative for asthma thus far.…”

Section: Studies Meeting the Inclusion Criteriamentioning

confidence: 99%

Measurement of exhaled nitric oxide concentration in asthma: a systematic review and economic evaluation of NIOX MINO, NIOX VERO and NObreath

Harnan

Tappenden

Essat

et al. 2015

Health Technol Assess

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BackgroundHigh fractions of exhaled nitric oxide (FeNO) in the breath of patients with symptoms of asthma are correlated with high levels of eosinophils and indicate that a patient is likely to respond to inhaled corticosteroids. This may have a role in the diagnosis and management of asthma.ObjectiveTo assess the diagnostic accuracy, clinical effectiveness and cost-effectiveness of the hand-held electrochemical devices NIOX MINO®(Aerocrine, Solna, Sweden), NIOX VERO®(Aerocrine) and NObreath®(Bedfont Scientific, Maidstone, UK) for the diagnosis and management of asthma.Data sourcesSystematic searches were carried out between March 2013 and April 2013 from database inception. Databases searched included MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Science Citation Index Expanded and Conference Proceedings Citation Index – Science. Trial registers such as ClinicalTrials.gov and themetaRegister of Controlled Trials were also searched in March 2013. All searches were updated in September 2013.Review methodsA rapid review was conducted to assess the equivalence of hand-held and chemiluminescent FeNO monitors. Systematic reviews of diagnostic accuracy and management efficacy were conducted. A systematic review of economic analyses was also conducted and two de novo health economic models were developed. All three reviews were undertaken according to robust high-quality methodology.ResultsThe rapid review (27 studies) found varying levels of agreement between monitors (Bland–Altman 95% limits of agreement up to ±10 parts per billion), with better agreement at lower FeNO values. Correlation was good (generallyr > 0.9). The diagnostic accuracy review identified 22 studies in adults (all ages) and four in children. No studies used NObreath or NIOX VERO and seven used NIOX MINO. Estimates of diagnostic accuracy varied widely. FeNO used in combination with another test altered diagnostic accuracy only slightly. High levels of heterogeneity precluded meta-analysis. Limited observations included that FeNO may be more reliable and useful as a rule-in than as a rule-out test; lower cut-off values in children and in smokers may be appropriate; and FeNO may be less reliable in the elderly. The management review identified five randomised controlled trials in adults, one in pregnant asthmatics and seven in children. Despite clinical heterogeneity, exacerbation rates were lower in all studies but not generally statistically significantly so. Effects on inhaled corticosteroid (ICS) use were inconsistent, possibly because of differences in management protocols, differential effectiveness in adults and children and differences in population severity. One UK diagnostic model and one management model were identified. Aerocrine also submitted diagnostic and management models. All had significant limitations including short time horizons and the selective use of efficacy evidence. The de novo diagnostic model suggested that the expected difference in quality-adjusted life-year (QALY) gains between diagnostic options is likely to be very small. Airway hyper-responsiveness by methacholine challenge test is expected to produce the greatest QALY gain but with an expected incremental cost-effectiveness ratio (ICER) compared with FeNO (NObreath) in combination with bronchodilator reversibility of £1.125M per QALY gained. All remaining options are expected to be dominated. The de novo management model indicates that the ICER of guidelines plus FeNO monitoring using NObreath compared with guidelines alone in children is expected to be approximately £45,200 per QALY gained. Within the adult subgroup, FeNO monitoring using NObreath compared with guidelines alone is expected to have an ICER of approximately £2100 per QALY gained. The results are particularly sensitive to assumptions regarding changes in ICS use over time, the number of nurse visits for FeNO monitoring and duration of effect.ConclusionsLimitations of the evidence base impose considerable uncertainty on all analyses. Equivalence of devices was assumed but not assured. Evidence for diagnosis is difficult to interpret in the context of inserting FeNO monitoring into a diagnostic pathway. Evidence for management is also inconclusive, but largely consistent with FeNO monitoring resulting in fewer exacerbations, with a small or zero reduction in ICS use in adults and a possible increased ICS use in children or patients with more severe asthma. It is unclear which specific management protocol is likely to be most effective. The economic analysis indicates that FeNO monitoring could have value in diagnostic and management settings. The diagnostic model indicates that FeNO monitoring plus bronchodilator reversibility dominates many other diagnostic tests. FeNO-guided management has the potential to be cost-effective, although this is largely dependent on the duration of effect. The conclusions drawn from both models require strong technical value judgements with respect to several aspects of the decision problem in which little or no empirical evidence exists. There are many potential directions for further work, including investigations into which management protocol is best and long-term follow-up in both diagnosis and management studies.Study registrationThis study is registered as PROSPERO CRD42013004149.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Clinical usefulness of fractional exhaled nitric oxide for diagnosing prolonged cough

Abstract: FeNO could be used as a diagnostic marker of prolonged cough, especially for the differential diagnosis BA and CVA from EB and others.

Cited by 61 publications

References 26 publications

Measurement of Nasal Nitric Oxide Is Useful for the Diagnosis of Sinusitis-Induced Prolonged Cough

Measurement of Nasal Nitric Oxide Is Useful for the Diagnosis of Sinusitis-Induced Prolonged Cough

Biomarker surrogates do not accurately predict sputum eosinophil and neutrophil percentages in asthmatic subjects

Measurement of exhaled nitric oxide concentration in asthma: a systematic review and economic evaluation of NIOX MINO, NIOX VERO and NObreath

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