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2015 ; 19
(82
): 1-330
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Measurement of exhaled nitric oxide concentration in asthma: a systematic review
and economic evaluation of NIOX MINO, NIOX VERO and NObreath
#MMPMID26484874
Harnan SE
; Tappenden P
; Essat M
; Gomersall T
; Minton J
; Wong R
; Pavord I
; Everard M
; Lawson R
Health Technol Assess
2015[Oct]; 19
(82
): 1-330
PMID26484874
show ga
BACKGROUND: High 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. OBJECTIVE: To 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 SOURCES: Systematic 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 the metaRegister of Controlled Trials were also searched
in March 2013. All searches were updated in September 2013. REVIEW METHODS: A
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. RESULTS:
The 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 (generally r?>?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. CONCLUSIONS: Limitations 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 REGISTRATION: This study is
registered as PROSPERO CRD42013004149. FUNDING: The National Institute for Health
Research Health Technology Assessment programme.
|*Breath Tests/instrumentation
[MESH]
|Adrenal Cortex Hormones/economics/*therapeutic use
[MESH]