Usefulness of Exhaled Nitric Oxide for Diagnosing Asthma

Pedrosa, María; Cancelliere, Nataly; Paredes, Pilar; López-Carrasco, Valentín; Quirce, Santiago

doi:10.3109/02770903.2010.491147

Cited by 52 publications

(51 citation statements)

References 15 publications

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“…Since the risk of bias was unclear or high in about half of the studies, the SOE was rated down to moderate. Using Deeks' funnel plot asymmetry tests and visual inspection of funnel plots, we found potential publication bias for cutoffs<20, and no indication of publication bias for cutoffs [20][21][22][23][24][25][26][27][28][29][30] (Appendix Figures D.10-11). We were not able to evaluate potential publication bias for other cutoffs.…”

Section: )mentioning

confidence: 99%

“…We did not rate down for statistical heterogeneity (which is always high in diagnostic meta-analyses) or consider diagnostic accuracy measures as surrogate outcomes. 28,29 When studies were heterogeneous in population, intervention and methods; and not appropriate for meta-analysis, we have narratively provided a summary statement about the findings and conveyed our certainty in such findings as a SOE rating. [30][31][32] In this case and in the absecnce of a single pooled estimate of the effect size, we narratively rated the SOE considering the meaning and connotation of SOE domains (methodological limitations of the studies, precision, directness, consistency and the likelihood of publication bias).…”

Section: Grading the Strength Of Evidence For Major Comparisons And Omentioning

confidence: 99%

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The Clinical Utility of Fractional Exhaled Nitric Oxide (FeNO) in Asthma Management

Wang¹,

Pianosi²,

Keogh³

et al. 2017

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Section: )mentioning

confidence: 99%

Section: Grading the Strength Of Evidence For Major Comparisons And Omentioning

confidence: 99%

The Clinical Utility of Fractional Exhaled Nitric Oxide (FeNO) in Asthma Management

Wang¹,

Pianosi²,

Keogh³

et al. 2017

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“…Adults, adults plus adolescents, all age groups and unspecified age groups ), adults plus adolescents (three studies, four citations [82][83][84][85] ), all age groups (three studies, three citations [86][87][88] or an unspecified age range (three studies, three citations 89,90,92 ). Table 21 summarises the characteristics of the studies and provides a brief description explaining their relevance to the decision problem (note: Schneider et al 71,72 appears twice in this table as this study reported two differently defined populations).…”

Section: Diagnostic Reviewmentioning

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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“…It is not surprising that published results on FeNO50 during baseline and during methacholine challenge produced conflicting data. Most studies have reported only modest relationships between PD20 and FeNO50 [11,[24][25][26]. Further complication could arise if the exhaled maneuver is influenced by changes in gas distribution due to broncho constriction [27] or if expiratory flow rates exceed 150 ml/sec [28].…”

Section: Discussionmentioning

confidence: 99%

“…It has become clearer that NO levels in the exhaled gas involves a complicated series of events and depends on the severity of inflammation, location of inflammation and type of inflammatory cells involved [10]. It remains unclear if exhaled NO bears any relationship to pulmonary function, airway inflammation or airway reactivity in all asthmatics [11]. Taylor et al [12] suggested that in mild asthmatics, endogenous NO neither protects against nor contributes to the processes underlying airways responses to inhaled allergens.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2015

JLPRR

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Increased nitric oxide in exhaled gas in patients with asthma is thought to reflect the severity of airway inflammation and perhaps airway reactivity. Several studies attempted to identify a relationship between exhaled NO levels and airway reactivity or severity of airway inflammation for the purpose of finding out if exhaled NO could be used in place of pulmonary function testing and airway provocation test. Unfortunately, the relationship is not always evident. In recent years, it has become clearer that exhaled NO becomes elevated primarily in atopic asthma patients. All previous studies have used the single vital capacity slow exhalation maneuver to measure ENO (FeNO50). This method is subject to errors because it requires patient cooperation, is flow rate dependent and adds more stress on the patient. Recently, we showed that end tidal NO concentration (NOet) is clinically relevant, is much easier to measure and is not subject to flow variation or patient cooperation. We used NOet (ppb) measurement before and during methacholine challenge in patients with symptoms of mild, persistent asthma. In addition we calculated NO production (NOpr) (nmole/ min) to correct for possible changes in ventilation. Eleven patients exhibited hyper-responsiveness to methacholine (responders) and 17 exhibited negative response (non-responders). The responders had a slightly higher NO level than the non-responders whether expressed in ppb or in nmol/min but did not reach statistical significance: NOet values were 15.1±2.4 ppb (±SE) and 11.7±2.3 ppb respectively and NOpr values were 5.83±0.86 nmol/min and 5.12±1.13 nmol/min respectively.There was no correlation between baseline NOet levels and the change in FEV1 in the responders. Furthermore, there was no consistent change in NOet or NOpr levels during broncho-constriction with methacholine. We conclude that although exhaled NO levels may serve as a helpful adjunct in treatment of asthma, its level alone does not reflect severity of the disease in mild asthmatics nor the airway responsiveness to methacholine. Exhaled NO was estimated using the average NO value at end expiration during normal tidal breathing. This method was quicker, repeatable and much easier on the patients and none of the patients objected to doing the measurement. There was no need to put patients through the complicated single full vital capacity slow exhaled maneuver to obtain this information.

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Usefulness of Exhaled Nitric Oxide for Diagnosing Asthma

Cited by 52 publications

References 15 publications

The Clinical Utility of Fractional Exhaled Nitric Oxide (FeNO) in Asthma Management

The Clinical Utility of Fractional Exhaled Nitric Oxide (FeNO) in Asthma Management

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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