Journal Information
Vol. 14. Issue 2.
Pages 195-218 (March - April 2008)
Share
Share
Download PDF
More article options
Vol. 14. Issue 2.
Pages 195-218 (March - April 2008)
Full text access
The clinical use of exhaled nitric oxide in wheezing children
Medição do óxido nítrico no ar exalado: Utilização na avaliação de crianças com história de sibilância
Visits
897
Pedro Martins1, Iolanda Caires2, José Rosado Pinto3, Pedro Lopes da Mata4, Simões Torres5, Joana Valente6, Carlos Borrego7, Nuno Neuparth8
1 Assistente Convidado, Departamento Universitário de Fisiopatologia, Faculdade de Ciências Médicas, Universidade Nova de Lisboa (Centro de Estudos de Patologia Respiratória); Assistente Eventual, Serviço de Imunoalergologia, Hospital de Dona Estefânia / Guest Consultant, Department of Physiopathology, Faculty of Medical Sciences, Universidade Nova de Lisboa (Centre for Respiratory Pathology Studies); Future Consultant, Allergy and Clinical Immunology Unit, Hospital de Dona Estefânia
2 Técnica de Cardiopneumologia, Departamento Universitário de Fisiopatologia, Faculdade de Ciências Médicas, Universidade Nova de Lisboa (Centro de Estudos de Patologia Respiratória) / Cardiopulmonology Technician, Department of Physiopathology, Faculty of Medical Sciences, Universidade Nova de Lisboa (Centre for Respiratory Pathology Studies)
3 Director de Serviço, Serviço de Imunoalergologia, Hospital de Dona Estefânia / Allergy and Clinical Immunology Unit, Hospital de Dona Estefânia
4 Especialista em Imunoalergologia, Instituto Clínico de Alergologia / Allergy and Clinical Immunology Specialist, Allergy and Clinical Immunology Institute
5 Director de Serviço, Serviço de Pneumologia, Hospital de São Teotónio / Director, Pulmonology Unit, Hospital de São Teotónio
6 Engenheira do Ambiente, Departamento de Ambiente e Ordenamento, Universidade de Aveiro / Environmental Engineer, Department of Environmental and Land Planning, Universidade de Aveiro
7 Professor Catedrático, Departamento de Ambiente e Ordenamento, Universidade de Aveiro / Cathedratic Professor, Department of Environmental and Land Planning, Universidade de Aveiro
8 Professor Auxiliar, Departamento Universitário de Fisiopatologia, Faculdade de Ciências Médicas, Universidade Nova de Lisboa (Centro de Estudos de Patologia Respiratória); Especialista em Imunoalergologia, Serviço de Imunoalergologia, Hospital de Dona Estefânia / Assistant Professor, Department of Physiopathology, Faculty of Medical Sciences, Universidade Nova de Lisboa (Centre for Respiratory Pathology Studies); Allergy and Clinical Immunology Specialist, Allergy and Clinical Immunology Unit, Hospital de Dona Estefânia
This item has received
Article information
Abstract

The body of published work on the role of exhaled nitric oxide (FENO) in the study of bronchial inflammation allows it to be classed as a simple, non-invasive measurement that is very useful in evaluating asthmatic patients.

During a prospective study into the effects of air pollution on the health of the population of Viseu (Saud’AR Project), children with a clinical history of wheezing were identified through using the International Study of Asthma and Allergy in Childhood (ISAAC) questionnaire. Children later filled in a new standardised questionnaire and underwent skin-prick-tests, spirometry and FENO measurement. Their mean age was 7.8±1.1 years. Comparing those who wheezed in the 6 months before evaluation (n=27) with those who didn’t, statistical differences for ΔFEV1 (8% median versus 4.5%, p=0.0399) and for FENO (23 ppb median versus 12 ppb, p=0.0195, respectively) were observed. Concerning children who needed a bronchodilator in the six previous months (n=19) and those who didn’t, there was also a statistically significant difference in FENO: 27 ppb median versus 11 ppb median, respectively; p<0.0001. When comparing children who needed an unscheduled medical appointment in the six months previous to the evaluation (n=9) and those who didn’t, there was also significant differences for FENO: 28 ppb median versus 13 ppb median, p=0.0029. In conclusion, the existence of symptoms seems to be better related to FENO than spirometry.

Key-words:
Wheezing
asthma
nitric oxide
FENO
Resumo

Encontram-se publicados múltiplos trabalhos sobre o papel das determinações do óxido nítrico no ar exalado (FENO) no âmbito do estudo da inflamação brônquica que nos permitem afirmar que se trata duma medição simples, não invasiva e de grande utilidade na avaliação do doente asmático.

No decurso de um estudo prospectivo sobre o impacto da poluição do ar sobre a saúde da população na cidade de Viseu (Projecto Saud’AR), foram identificadas crianças com história clínica de sibilância, mediante a aplicação de questionários do International Study of Asthma and Allergy in Childhood (ISAAC). As crianças foram submetidas posteriormente a um questionário padronizado, testes cutâneos prick para aeroalergénios, espirometria com prova de broncodilatação e medição de FENO. A idade média era de 7,8±1,1 anos. Comparando os doentes com queixas de sibilância e/ou dispneia nos 6 meses anteriores à avaliação (n=27) com os que não apresentaram estes sintomas, observaram -se diferenças estatisticamente significativas para o ΔFEV1 (mediana: 4,5% vs 8%, p=0,0399) e para o FENO (mediana: 12 ppb vs 23 ppb, p=0,0195, respectivamente). Se olharmos para as crianças que recorreram a broncodilatador nos seis meses anteriores à avaliação (n=19) e as compararmos com as que não necessitaram, encontramos diferenças para o FENO: mediana de 27 ppb versus mediana de 11 ppb, respectivamente; p<0,0001. Ao compararmos as crianças que recorreram a uma consulta de urgência nos seis meses anteriores à avaliação (n=9) e as compararmos com as que não recorreram, encontramos também diferenças estatisticamente significativas para o FENO: mediana de 28 ppb versus mediana de 13 ppb, p=0.0029.

Constatou-se assim que a existência de sintomas se associou melhor com o FENO de que com a espirometria.

Palavras-chave:
Sibilância
asma
óxido nítrico
FENO
Full text is only aviable in PDF
Bibliography/Bibliografia
[1.]
N. Marsh, A. Marsh.
A short history of nitroglycerine and nitric oxide in pharmacology and physiology.
Clin Exp Pharmacol Physiol, 27 (2000), pp. 313-319
[2.]
K. Alving, C. Fornhem, J.M. Lundberg.
Pulmonary effects of endogenous and exogenous nitric oxide in the pig: relation to cigarette smoke inhalation.
Br J Pharmacol, 110 (1993), pp. 739-746
[3.]
L.E. Gustafsson, A.M. Leone, M.G. Persson, N.P. Wiklund, S. Moncada.
Biochemi Biophys Res Commun, 181 (1991), pp. 852-857
[4.]
K. Alving, E. Weitzberg, J.M. Lundberg.
Increased amount of nitric oxide in exhaled air of asthmatics.
Eur Respir J, 6 (1993), pp. 1368-1370
[5.]
S.A. Kharitonov, D. Yates, R.A. Robbins, R. Logan -Sinclair, E.A. Shinebourne, P.J. Barnes.
Increased nitric oxide in exhaled air of asthmatic patients.
Lancet, 343 (1994), pp. 133-135
[6.]
P. Araujo Goncalves, P. Lopes da Mata, N. Neuparth, A. Bensabat Rendas.
Papel do oxido nitrico como marcador de inflamacao em doencas respiratorias.
Rev Port Pneumol, 6 (2000), pp. 309-318
[7.]
N. Neuparth, T. Gamboa, A. Bugalho de Almeida, A. Caires, J. Rosado Pinto, A.B. Rendas.
Relation between exhaled nitric oxide and bronchial reactivity during induced maximal airway narrowing in asthma.
Eur Repir J, 12 (1998), pp. 364s
[8.]
S. Kharitonov, K. Alving, P.J. Barnes.
ERS TASK FORCE REPORT – Exhaled and nasal nitric oxide measurements: recommendations.
Eur Respir J, 10 (1997), pp. 1683-1693
[9.]
M. Barreto, M.P. Villa, S. Martella, F. Ronchetti, M.T. Darder, C. Falasca, J. Pagani, F. Massa, R. Ronchetti.
Exhaled nitric oxide in asthmatic and non -asthmatic children: influence of type of allergen sensitization and exposure to tobacco smoke.
Pediatr Allergy Immunol, 12 (2001), pp. 247-256
[10.]
F. Cardinale, F.M. de Benedictis, V. Muggeo, P. Giordano, M.S. Loffredo, G. Iacoviello, L. Armenio.
Exhaled nitric oxide, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis.
Pediatr Allergy Immunol, 16 (2005), pp. 236-242
[11.]
J.G. van Amsterdam, N.A. Janssen, G. de Meer, P.H. Fischer, S. Nierkens, H. van Loveren, A. Opperhuizen, P.A. Steerenberg, B. Brunekreef.
The relationship between exhaled nitric oxide and allergic sensitization in a random sample of school children.
Clin Exp Allergy, 33 (2003), pp. 187-191
[12.]
A.J. Spanier, R. Hornung, M. Lierl, B.P. Lanphear.
Environmental exposures and exhaled nitric oxide in children with asthma.
J Pediatr, 149 (2006), pp. 220-226
[13.]
F. Buchvald, E. Barladi, S. Carraro, et al.
Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years.
J Allergy Clin Immunol, 115 (2005), pp. 1130-1136
[14.]
F. Santamaria, S. Montella, S. De Stefano, F. Sperli, F. Barbarano, G. Valerio.
Relationship between exhaled nitric oxide and body mass index in children and adolescents.
J Allergy Clin Immunol, 115 (2005), pp. 1163-1164
[15.]
K.M. de Winter-de Groot, C.K. van der Ent, I. Prins, J.M. Tersmette, C.S.P.M. Uiterwaal.
Exhaled nitric oxide: the missing link between asthma and obesity?.
J Allergy Clin Immunol, 115 (2005), pp. 419-420
[16.]
K.W. Tsang, S.K. Ip, R. Leung, et al.
Exhaled nitric oxide: the effects of age, gender and body size.
Lung, 179 (2001), pp. 83-91
[17.]
A.C. Olin, A. Rosengren, D. Thelle, L. Lissner, B. Bake, K. Toren.
Sample Height, Age, and Atopy Are Associated With Fraction of Exhaled Nitric Oxide in a Large Adult General Population.
Chest, 130 (2006), pp. 1319-1325
[18.]
A.C. Olin, B. Bake, K. TorAcn.
Fraction of exhaled nitric oxide at 50 mL/s: reference values for adult lifelong never-smokers.
Chest, 131 (2007), pp. 1852-1856
[19.]
ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005.
Am J Respir Crit Care Med, 171 (2005), pp. 912-930
[20.]
R. Taylor, M. Pijnenburg, A.D. Smith, J.C.D. Jongste.
Exhaled nitric oxide measurements: clinical application and interpretation.
Thorax, 61 (2006), pp. 817-827
[21.]
S.A. Kharitonov, F. Gonio, C. Kelly, S. Meah, P.J. Barnes.
Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children.
Eur Respir J, 21 (2003), pp. 433-438
[22.]
A.D. Smith, J.O. Cowan, S. Filsell, et al.
Diagnosing asthma: comparisons between exhaled nitric oxide measurements and conventional tests.
Am J Respir Crit Care Med, 169 (2004), pp. 473-478
[23.]
L.P. Malmberg, A.S. Pelkonen, T. Haahtela, M. Turpeinen.
Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma.
Thorax, 58 (2003), pp. 494-499
[24.]
A. Prasad, B. Langford, J.R. Stradling, L.P. Ho.
Exhaled nitric oxide as a screening tool for asthma in school children.
Respir Med, 100 (2006), pp. 167-173
[25.]
T.J. Warke, P.S. Fitch, V. Brown, et al.
Exhaled nitric oxide correlates with airway eosinophils in childhood asthma.
Thorax, 57 (2002), pp. 383-387
[26.]
C. Lopes, J. Fonseca, J. Moreira da Silva, M.G. Castel-Branco.
Oxido nitrico exalado: utilizacao clinica na asma.
Rev Port Imunoalergol, 13 (2005), pp. 7-17
[27.]
F. Costa, A. Arrobas.
Oxido nitrico exalado no diagnostico de asma.
Rev Port Imunoalergologia, 15 (2007), pp. 163-177
[28.]
R. Pellegrino, Viegi, V. Brusasco, R.O. Crapo, F. Burgos, R. Casaburi, A. Coates, C.P.M. van der Grinten, P. Gustafsson, J. Hankinson, R. Jensen, D.C. Johnson, N. MacIntyre, R. McKay, M.R. Miller, D. Navajas, O.F. Pedersen, J. Wanger.
Interpretative strategies for lung function tests.
Eur Respir J, 26 (2005), pp. 948-968
[29.]
I. Dundas, S. Mckenzie.
Spirometry in the diagnosis of asthma in children.
Curr Opin Pulm Med, 12 (2006), pp. 28-33
[30.]
J.M. Spergel, M.I. Fogg, A. Bokszczanin-Knosala.
Correlation of exhaled nitric oxide, spirometry and asthma symptoms.
J Asthma, 42 (2005), pp. 879-883
[31.]
A.J. Colon-Semidey, P. Marshik, M. Crowley, R. Katz, H.W. Kelly.
Correlation between reversibility of airway obstruction and exhaled nitric oxide levels in children with stable bronchial asthma.
Pediatric Pulmonol, 30 (2000), pp. 385-392
[32.]
Z. Zietkowski, A. Bodzenta-Lukaszyk, M.M. Tomasiak, R. Skiepko, M. Szmitkowski.
Comparison of exhaled nitric oxide measurement with conventional tests in steroid-naive asthma patients.
J Investig Allergol Clin Immunol, 16 (2006), pp. 239-246
[33.]
P. Rosias, E. Dompelling, M. Dentener, H.J. Pennings, H. Hendriks, M. Van lersel, Q. Jobsis.
Childhood asthma: exhaled markers of airway inflammation, asthma control score and lung function tests.
Pediatric Pulmonology, 38 (2004), pp. 107-114
[34.]
Global Strategy for Asthma Managemet and Prevention (Revisao 2006): Global Initiative for Asthma (GINA). URL: http://www.ginasthma.org; 2006.
[35.]
K. Alving, C. Jansson, L. Nordvall.
Performance of a new hand -held device for exhaled nitric oxide measurement in adults and children.
Respiratory Research, 7 (2006), pp. 67
[36.]
C. McGill, G. Malik, S.W. Turner.
Validation of a hand-held exhaled nitric oxide analyzer for use in children.
Pediatr Pulmonol, 41 (2006), pp. 1053-1057
[37.]
D. Menzies, A. Nair, B. Lipworth.
Portable Exhaled Nitric Oxide Measurement: Comparison With the “Gold Standard” Technique.
Chest, 131 (2007), pp. 410-414
[38.]
P. Martins, I. Caires, S. Torres, C. Borrego, N. Neuparth.
Reproducibility of eNO measurements in children using a hand -held analyser.
Eur Respir J, 28 (2006), pp. 791s
[39.]
P. Martins, I. Caires, S. Torres, N. Neuparth.
Oxido nitrico no ar exalado: comparacao de medicoes com dois analisadores.
Rev Port Pneumol, 12 (2006), pp. 91
[40.]
P. Martins, I. Caires, J. Rosado Pinto, N. Neuparth.
Oxido nitrico no ar exalado: comparacao das medidas com dois analisadores.
Rev Port Imunoalergologia, 14 (2006), pp. 55
[41.]
J.J. Quackenboss, M.D. Lebowitz, M. Krzyzanowski.
The normal range of diurnal changes in peak expiratory flow rates. Relation ship to symptoms and respiratory disease.
Am Rev Respir Dis, 143 (1991), pp. 323-330
[42.]
P. Jain, M.S. Kavuru, C.L. Emerman, M. Ahmad.
Utility of peak expiratory flow monitoring.
Chest, 114 (1998), pp. 861-876
[43.]
Kerstjens HA, Brand PL, de Jong PM, Koeter GH, Postma DS. Influence of treatment on peak expiratory flow and its relation to airway hyperresponsiveness.
[44.]
N. Kunzli, E.Z. Stutz, A.P. Perruchoud, et al.
Peak flow variability in the SAPALDIA study and its validity in screening for asthma-61 related conditions. The SPALDIA Team.
Am J Respir Crit Care Med, 160 (1999), pp. 427-434
[45.]
S. Troyanov, H. Ghezzo, A. Cartier, J.L. Malo.
Comparison of circadian variations using FEV1 and peak expiratory flow rates among normal and asthmatic subjects.
Thorax, 49 (1994), pp. 775-780
[46.]
R. Gandhi, M. Blaiss.
What are the best estimates of pediatric asthma control?.
Curr Opin Allergy Clin Immunol, 6 (2006), pp. 106-112
[47.]
J. Sippel, W. Holden, S. Tilles, et al.
Exhaled nitric oxide levels correlate with measures of disease control in asthma.
J Allergy Clin Immunol, 106 (2000), pp. 645-650
[48.]
M. Silvestri, F. Sabatini, R. Sale, A.C. Defilippi, L. Fregonese, E. Battistini, M.G. Biraghi, G.A. Rossi.
Correlations between exhaled nitric oxide levels, blood eosinophilia, and airway obstruction reversibility in childhood asthma are detectable only in atopic individuals.
Pediatric Pulmonol, 35 (2003), pp. 358-363
[49.]
S. Godfrey, C. Springer, E. Bar -Yishay, A. Avital.
Cut-off points defining normal and asthmatic bronchial reactivity to exercise and inhalation challenges in children and young adults.
Eur Respir J, 14 (1999), pp. 659-668
[50.]
J. Britton, A.E. Tattersfield.
Does measurement of bronchial hyperreactivity help in the clinical diagnosis of asthma?.
Eur J Respir Dis, 68 (1986), pp. 233-238
[51.]
B. Burrows, M. Sears, E. Flanneery, G. Herbison, M. Holdaway, P. Silva.
Relation of the course of bronchial responsiveness from age 9 to age 15 to allergy.
Am J Respir Crit Care Med, 152 (1995), pp. 1302-1308
[52.]
D. Gautrin, J.G. Lapierre, J.L. Malo, C. Infante-Rivard.
Airway hyperresponsiveness and symptoms of asthma in a six-year follow-up study of childhood asthma.
Chest, 116 (1999), pp. 1659-1664
[53.]
L.M. Fabbri, M. Romagnoli, L. Corbetta, G. Casoni, K. Busljetic, G. Turato, G. Ligabue, A. Ciaccia, M. Saetta, A. Papi.
Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease.
Am J Respir Crit Care Med, 167 (2003), pp. 418-424
[54.]
A. Jatakanon, S. Lim, S.A. Kharitonov, K.F. Chung, P.J. Barnes.
Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma.
Thorax, 53 (1998), pp. 91-95
[55.]
A.C. Olin, G. Ljungkvist, B. Bake, S. Hagberg, L. Henriksson, K. Toren.
Exhaled nitric oxide among pulpmill workers reporting gassing incidents involving ozone and chlorine dioxide.
Eur Respir J, 14 (1999), pp. 828-831
[56.]
M. Silvestri, D. Spallarossa, E. Battistini, V. Brusasco, G.A. Rossi.
Dissociation between exhaled nitric oxide and hyperresponsiveness in children with mild intermittent asthma.
Thorax, 55 (2000), pp. 484-488
[57.]
A.D. Smith, J.O. Cowan, K.P. Brasset, S. Filsell, C. McLachlan, G. MontiSheehan, et al.
Exhaled nitric oxide: a predictor of steroid response.
Am J Respir Crit Care Med, 172 (2005), pp. 453-459

Este estudo foi realizado no âmbito do projecto Saud’AR (A Saúde e o Ar que Respiramos), uma parceria entre o Departamento de Ambiente e Ordenamento da Universidade de Aveiro e a Faculdade de Ciências Médicas da Universidade Nova de Lisboa, e foi financiado pela Fundação Calouste Gulbenkian. Os doentes foram avaliados no Serviço de Pneumologia do Hospital de São Teotónio (Director: Dr. Simões Torres) / This study was part of the Saud’AR (Health is the Air that we Breathe) Project and was undertaken jointly with the Department of Environmental and Land Planning of the Universidade de Aveiro and the Faculty of Medical Sciences, Universidade Nova de Lisboa. It was funded by the Calouste Gulbenkian Foundation. Patients were evaluated by the Pulmonology Unit of the Hospital de São Teotónio (Director: Dr. Simões Torres).

Copyright © 2008. Sociedade Portuguesa de Pneumologia
Download PDF
Pulmonology
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?