Diagnostic performance of the measurement of nitric oxide in exhaled air in the diagnosis of COPD phenotypes
Introduction
COPD is a widely occurring disease with significant associated morbidity and mortality. About 10% of the adult population in Spain were affected in 2010 [1], while COPD is the third leading cause of death worldwide [2]. At present it is considered a heterogeneous disease for which patients cannot be only categorized on the basis of functional parameters [3]. In this context, the concept of COPD phenotype has been generalized in recent years. This takes into consideration additional information and facilitates more personalized treatments in accordance with the clinical presentation of patients'symptoms [4].
In the assessment of COPD, recognition of the disease's heterogeneity has led to the development of guidelines and strategies which include factors not exclusively related to lung function, such as the clinical impact of the disease [5]. Further, the Spanish guidelines for COPD (GesEPOC) [6] proposes treatment for four phenotypes: non-exacerbators with emphysema or chronic bronchitis; frequent exacerbators with chronic bronchitis; frequent exacerbators with emphysema; and asthma-COPD overlap syndrome (ACOS) [7].
Although bronchial asthma and COPD have different pathogenic mechanisms, namely inflammatory, genetic and immunological airway patterns [8], [9], [10], [11], there is a subgroup of patients with COPD who share mechanisms of both conditions, for which this differentiation is complex. They are now known as ACOS patients [12], [13], [14], [15]. To identify patients with ACOS, some approaches have been published in the literature, but none of these have been validated or replicated in different scenarios and this fact has led to controversies in how these patients should be diagnosed [16], although the majority of these approaches are based on the detection of eosinophilic bronchial inflammation. For example, the Spanish Guidelines for COPD (GesEPOC) suggests a number of factors that may indicate eosinophilic airway inflammation and an increased likelihood of response to inhaled corticosteroid treatments [12]and, to date, is the only one that has been validated in real practice [17]. However, some of these factors included in the proposal, such as sputum eosinophilia, are difficult to measure in a conventional assessment, whereas others that are easier to measure, such as the determination of fraction of nitric oxide in exhaled air (FENO50) are not included. Several papers have shown that FENO50 is associated with the presence of eosinophils in sputum, bronchial hyperresponsiveness, and a better response to inhaled corticosteroid treatments [18], [19]suggesting perhaps that FENO50 is a marker for ACOS.
The objective of this study is to evaluate the diagnostic performance of FENO50 measurement in exhaled air for phenotype diagnosis in a cohort of COPD patients who received outpatient assistance.
Section snippets
Material and methods
A cross-sectional observational study was conducted on patients who received assistance consecutively in an outpatient pulmonary care facility. The individuals involved met the following eligibility criteria: they were 40 years of age or older and were suitable for a lung function test; showed no respiratory disease other than asthma and COPD; had not experienced episodes of respiratory infection in the 6 weeks prior to the visit; and had not used any oral corticosteroids in the previous 4
Results
Of 219 candidates who participated in the study, 192 were eligible. They were divided into healthy non-smokers (8%), healthy smokers (15. %), patients with bronchial asthma (22%), and patients with COPD (53%) (Fig. 1). The characteristics of the study population are summarized in Table 1. There was a little proportion of patients without respiratory disease (healthy smokers and non smokers), but ICS use was detected also in those groups. Patients with bronchial asthma showed higher FENO50
Discussion
The results of this study show that the measurement of FENO50 may be more useful than a bronchodilator test in the diagnosis of COPD phenotype in patients who receive assistance at a respiratory clinic, with an optimal cut-off value of 19 ppb. Although this levels are in the normal range for the general population [23], data on FENO distribution in COPD patients are scarce and could not be extrapolated from general population.
These results are similar to those published by other groups, which
Authors contribution
BAN had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. BAN, PJR, ARS and ORR contributed substantially to the study design, data analysis and interpretation, and the writing of the manuscript.
Funding
This article was made possible by a research grant received by the Neumosur (1/2012) Foundation.
Conflict of interests
Dr. Alcázar reports personal fees from Novartis AG, personal fees from Boehringer–Ingelheim, personal fees from GSK, personal fees from Almirall, grants and personal fees from Menarini, personal fees from Astra- Zeneca, outside the submitted work.
Dr. Romero-Palacios has nothingtodisclose.
Dr. Ruiz Sancho has nothingtodisclose.
Dr. Ruiz Rodriguez has nothingtodisclose.
Acknowledgments
We would like to thank Ms Bárbara Cordova for helping us with the translation issues of the study.
References (32)
- et al.
Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010
Lancet
(2012) - et al.
Spanish guideline for COPD (GesEPOC). Update 2014
Arch. Bronconeumol.
(2014 Jan) - et al.
New insights into the immunology of chronic obstructive pulmonary disease
Lancet
(2011) - et al.
Asthma and chronic obstructive pulmonary disease: similarities and differences
Clin. Chest Med.
(2014) - et al.
Fixed air flow obstruction due to asthma or chronic obstructive pulmonarydisease: 5-year follow-up
J. Allergy Clin. Immunol.
(2010) - et al.
Consensus document on the overlap phenotype COPD-asthma in COPD
Arch. Bronconeumol.
(2012) - et al.
Defining the asthma-COPD overlap syndrome in a COPD cohort
Chest
(2016) - et al.
Spanish society of pulmonology and thoracic surgery (SEPAR). spirometry. Spanish society of pulmonology and thoracic surgery (SEPAR)
Arch. Bronconeumol.
(2013) - et al.
Fraction of exhaled nitric oxide at 50 mL/s: reference values for adult lifelong never-smokers
Chest
(2007) - et al.
The influence of inhaled corticosteroids on exhaled nitric oxide in stable chronic obstructive pulmonary disease
Respir. Med.
(2005)
Exhaled nitric oxide measurement is useful for the exclusion of nonasthmatic eosinophilic bronchitis in patients with chronic cough
Chest
Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials
Lancet Respir. Med.
Prevalence of COPD in Spain: impact of undiagnosed COPD on quality of life and daily life activities
Thorax
Evaluation of COPD longitudinally to identify predictive surrogate endpoints (ECLIPSE) investigators. Characterisation of COPD heterogeneity in the ECLIPSE cohort
Respir. Res.
Chronic obstructive pulmonary disease phenotypes: the future of COPD
Am. J. Respir. CritCare Med.
Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary
Am. J. Respir. Crit. Care Med.
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