Clinical utility of exhaled nitric oxide fraction in the management of asthma and COPD

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Abstract

Exhaled nitric oxide fraction ( F _ENO) values can be easily measured using portable analysers and are a surrogate marker of airway eosinophilia. F _ENO may be useful in diagnosing and monitoring conditions characterised by airway eosinophilia, i.e. asthma and possibly COPD. Many factors other than asthma and COPD affect F _ENO, especially atopy, which is associated with elevated F _ENO. One guideline recommends that F _ENO should be used as part of the diagnostic pathway for asthma diagnosis in adults and children aged >5 years. The role of F _ENO in monitoring asthma is even less clear, and most guidelines do not recommend its use outside of specialist asthma clinics. Currently, F _ENO is not recommended for diagnosis or monitoring of COPD. Although F _ENO is starting to find a place in the management of asthma in children and adults, considerably more research is required before the potential of F _ENO as an objective measurement in asthma and COPD can be realised.

Key points

For individuals aged ≥12 years, F _ENO is not recommended by all guidelines as a test to diagnose asthma (recommended only by the UK National Institute for Health and Care Excellence guideline for asthma symptoms, which are likely to respond to corticosteroid treatment).
F _ENO may be used in conjunction with other investigations to diagnose asthma in 5–16-year-olds where there is diagnostic uncertainty, but further evidence is required.
F _ENO is not recommended as a routine test to monitor all patients with asthma or to titrate asthma treatment.
F _ENO is not recommended for routine clinical testing in adults with COPD.
F _ENO may be useful to identify patients with COPD who could benefit from the use of inhaled corticosteroids (asthma–COPD overlap).

Educational aims

To understand what factors other than asthma and COPD affect F _ENO
To understand the current controversies in the application of F _ENO to diagnosis and management of asthma in children
To understand the current controversies in the application of F _ENO to diagnosis and management of asthma and COPD in adults

Abstract

Exhaled nitric oxide fraction ( F _ENO ) may be a useful test for diagnosing asthma in adults and in children but is currently not recommended for monitoring all patients with asthma or COPD   http://bit.ly/2lmjXpm

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Most cited references 33

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Lebrikizumab treatment in adults with asthma.

Jonathan Corren, Robert Lemanske, Nicola Hanania … (2011)

Many patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids. One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype. We hypothesized that anti-interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity. We conducted a randomized, double-blind, placebo-controlled study of lebrikizumab, a monoclonal antibody to interleukin-13, in 219 adults who had asthma that was inadequately controlled despite inhaled glucocorticoid therapy. The primary efficacy outcome was the relative change in prebronchodilator forced expiratory volume in 1 second (FEV(1)) from baseline to week 12. Among the secondary outcomes was the rate of asthma exacerbations through 24 weeks. Patient subgroups were prespecified according to baseline type 2 helper T-cell (Th2) status (assessed on the basis of total IgE level and blood eosinophil count) and serum periostin level. At baseline, patients had a mean FEV(1) that was 65% of the predicted value and were taking a mean dose of inhaled glucocorticoids of 580 μg per day; 80% were also taking a long-acting beta-agonist. At week 12, the mean increase in FEV(1) was 5.5 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.02). Among patients in the high-periostin subgroup, the increase from baseline FEV(1) was 8.2 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.03). Among patients in the low-periostin subgroup, the increase from baseline FEV(1) was 1.6 percentage points higher in the lebrikizumab group than in the placebo group (P = 0.61). Musculoskeletal side effects were more common with lebrikizumab than with placebo (13.2% vs. 5.4%, P = 0.045). Lebrikizumab treatment was associated with improved lung function. Patients with high pretreatment levels of serum periostin had greater improvement in lung function with lebrikizumab than did patients with low periostin levels. (Funded by Genentech; ClinicalTrials.gov number, NCT00930163 .).

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Carl Nathan, Qiao-wen Xie (1994)

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Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial.

Alexander Wong, Nicola Hanania, Mark Eisner … (2011)

Inhaled corticosteroids (ICS) and long-acting β(2)-agonists (LABAs) are recommended in patients with asthma that is not well-controlled; however, many patients continue to have inadequately controlled asthma despite this therapy. To evaluate the efficacy and safety of omalizumab in patients with inadequately controlled severe asthma who are receiving high-dose ICS and LABAs, with or without additional controller therapy. Prospective, multicenter, randomized, parallel-group, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00314575). 193 investigational sites in the United States and 4 sites in Canada. 850 patients aged 12 to 75 years who had inadequately controlled asthma despite treatment with high-dose ICS plus LABAs, with or without other controllers. Omalizumab (n = 427) or placebo (n = 423) was added to existing medication regimens for 48 weeks. The primary end point was the rate of protocol-defined exacerbations over the study period. Secondary efficacy end points included the change from baseline to week 48 in mean daily number of puffs of albuterol, mean total asthma symptom score, and mean overall score on the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]). Safety end points included the frequency and severity of treatment-emergent adverse events. During 48 weeks, the rate of protocol-defined asthma exacerbations was significantly reduced for omalizumab compared with placebo (0.66 vs. 0.88 per patient; P = 0.006), representing a 25% relative reduction (incidence rate ratio, 0.75 [95% CI, 0.61 to 0.92]). Omalizumab improved mean AQLQ(S) scores (0.29 point [CI, 0.15 to 0.43]), reduced mean daily albuterol puffs (-0.27 puff/d [CI, -0.49 to -0.04 puff/d]), and decreased mean asthma symptom score (-0.26 [CI, -0.42 to -0.10]) compared with placebo during the 48-week study period. The incidence of adverse events (80.4% vs. 79.5%) and serious adverse events (9.3% vs. 10.5%) were similar in the omalizumab and placebo groups, respectively. The results are limited by early patient discontinuation (20.8%). The study was not powered to detect rare safety events or the treatment effect in the oral corticosteroid subgroup. In this study, omalizumab provided additional clinical benefit for patients with severe allergic asthma that is inadequately controlled with high-dose ICS and LABA therapy. Genentech and Novartis Pharmaceuticals.

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Author and article information

Journal

Journal ID (nlm-ta): Breathe (Sheff)

Journal ID (iso-abbrev): Breathe (Sheff)

Journal ID (publisher-id): BREATHE

Journal ID (hwp): breathe

Title: Breathe

Publisher: European Respiratory Society

ISSN (Print): 1810-6838

ISSN (Electronic): 2073-4735

Publication date (Print): December 2019

Volume: 15

Issue: 4

Pages: 306-316

Affiliations

[1 ]Child Health, University of Aberdeen, Aberdeen, UK

[2 ]Dept of Respiratory and Sleep Medicine, Queensland Children's Hospital, Queensland University of Technology, Brisbane and Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia

[3 ]Dept of Thoracic Medicine, The Prince Charles Hospital and Faculty of Medicine, The University of Queensland, Brisbane, Australia

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E-mail: s.w.turner@ 123456abdn.ac.uk

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Steve W. Turner https://orcid.org/0000-0001-8393-5060

Article

Publisher ID: EDU-0268-2019

DOI: 10.1183/20734735.0268-2019

PMC ID: 6885348

PubMed ID: 31803265

SO-VID: 46453b5b-bc83-4e93-b0b7-7988a12b45ab

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Breathe articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

Clinical utility of exhaled nitric oxide fraction in the management of asthma and COPD

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Most cited references 33

Lebrikizumab treatment in adults with asthma.

Nitric oxide synthases: roles, tolls, and controls.

Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial.

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