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The Use of Exhaled Nitric Oxide The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia and Induced Sputum Eosinophilia
in the Diagnosis of Asthmain the Diagnosis of Asthma
– a systematic review– a systematic review – –
Introdução à Medicina 2006/2007
Class 3, First YearJoão Almeida Lopes Fonseca Altamiro Manuel Rodrigues da Costa Pereira
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 22
SummarySummary Introduction
• Current Tests• Inflammatory Biomarkers• Aim
Methods • Study Design• Data source• Study Selection• Quality Criteria• Statistical Analysis
Flow Chart
Results
Gantt chart
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 33
IntroductionIntroduction Asthma is an inflammatory disorder
Asthma diagnosis:
• Mostly based on the clinical observation complemented with lung function tests
• Bronchodilatation and hiperreactivity tests (methacholine)
• There is growing interest in exhaled nitric oxide (Fe(NO)) and induced sputum eosinophilia
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 44
Introduction Introduction Current Tests
GINA. 2006 Nov
Dundas I. Thorax. 2005 Jan
Busse WW. Am J Respir Crit Care Med. 2005 Oct
Lung function
Bronchodilatation Methacholine Bronchial
Biopsy
Safe
Non-Invasive Quick and
Easy
Sensitive
Specific
Tests
Parameters
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 55
Introduction Introduction Inflammatory Biomarkers
Lemiere C et al. Can J Physiol Pharmacol. 2006 Jan Joos GF et al. Curr Opin Pharmacol. 2003 Jun
Dinakar C et al. Curr Allergy Asthma Rep. 2004 Nov
Kim CK et al. Ann Allergy Asthma Immunol. 2004 Aug
Fe(NO)Induced Sputum
Eosinophilia
Safe
Non-Invasive
Quick and Easy
Sensitive ? ?
Specific ? ?
Tests
Parameters
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 66
Introduction Introduction Aim
To evaluate the sensitivity and the
specificity of Fe(NO) and
induced sputum eosinophilia
in asthma diagnosis
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 77
Methods Methods Study Design
A meta-analysis of the published
studies on the sensitivity and
specificity of measurements of
Fe(NO) and induced sputum
eosinophilia
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 88
Methods Methods Data sourceResearch was made using Medline, Scopus and references of
used articles.• Query of Medline was:
(("Asthma"[MeSH] OR Asthma OR Asthm*) AND (("Nitric Oxide"[MeSH] OR feno OR ENO OR exhaled
air) OR ((Eosinophil[MeSH] OR Eosinophil* OR Eosinophilia[MeSH])AND
(Sputum[MeSH] OR Sputum))) AND ((sensitiv*[Title/Abstract] OR sensitivity and
specificity[MeSH Terms] OR diagnos*[Title/Abstract] OR diagnosis[MeSH:noexp]
OR diagnostic * [MeSH:noexp] OR diagnosis,differential[MeSH:noexp] OR
diagnosis[Subheading:noexp] OR (Diagnosis[MeSH] OR Diagnosis OR Diagnos*))
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 99
Methods Methods Data source
• Query of Scopus was:
(((asthma OR asthm) AND ((nitric oxide OR feno OR eno OR exhaled air) OR (eosinophil
OR eosinophilia) AND sputum)) AND
(((sensitiv OR sensitivity) AND specificity) OR (diagnostic OR differential diagnosis OR
diagnosis)))AND PUBYEAR AFT 1991
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 1010
Methods Methods Study Selection
• Six groups of two reviewers - titles/abstracts• Six groups of two reviewers - full text
• Articles atributted randomly using excel
• Checked inclusion and exclusion criteria to select the articles
1st stage: titles/abstracts 2nd stage: full text.
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 1111
Methods Methods Study Selection
• Non-agreement on 1st stage: The article is included
• Non-agreement on 2nd stage solved by: Consensus
or A third reviewer (a specialist in the field).
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 1212
Methods Methods Study Selection
Inclusion criteria
1. Studies the use of exhaled nitric oxide or eosinophil levels in induced sputum for the diagnosis of asthma in humans.
2. Reports original data on the sensitivity and specificity of the application of inflammatory biomarkers
Exclusion criteria
3. Not written in English, Portuguese, French or Spanish.4. Full text not available via Medline, Scopus or FMUP library.5. Does not describe the criteria use for the diagnosis of
asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 1313
Methods Methods Quality Criteria
The articles included were evaluated regarding their methodological quality using a scale based on
STARD.
1. http://www.consort-statement.org/stardstatement.htm
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 1414
Methods Methods Statistical Analysis
• Meta-Disc 1.4 and SPSS 14.0 - Relevant information extracted from the chosen articles was registered.
• Main parameters - SensitivitySensitivity and SpecifitySpecifity of inflammatory biomarkers:
Nitric oxide Eosinophils
• Kappa Statistics - compares the agreement against that which might be expected by chance.
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 1515
Flow chartFlow chart
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 1616
ResultsResultsProportion of Inclusion/Exclusion – Pubmed and Scopus
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 1717
ResultsResultsDegree of Concordance-Titles/Abstracts and Full Texts
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 1818
ResultsResultsExclusion Criteria – Titles/Abstracts and Full Texts
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 1919
Data extractionData extraction
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 2020
Data extractionData extraction
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 2121
Quality AssessmentQuality Assessment
The first three articles with the better quality evaluation:
• Pijnenburg, MW - Thorax – 2005 – 23,5 pts
• Hefflera, E - Respiratory Medicine – 2006 – 19,5 pts
• Efthimiadis, A - The Journal of Allergy and Clinical Immunology – 2000 – 18,5 pts
Highest pontuation – 23,5 points
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 2222
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The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma
Class 3; 2006-7 2323
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