1 A Meta-analysis on the Sensitivity and Specificity of Exhaled Nitric Oxide and Induced Sputum...

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A Meta-analysis on the A Meta-analysis on the

Sensitivity and Specificity of Sensitivity and Specificity of

Exhaled Nitric Oxide and Exhaled Nitric Oxide and

Induced Sputum Eosinophilia Induced Sputum Eosinophilia

for the Diagnosis of Asthmafor the Diagnosis of AsthmaIntrodução à Medicina 2006/2007

Class 3, First YearJoão Almeida Lopes Fonseca Altamiro Manuel Rodrigues da Costa Pereira

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A Meta-analysis on the Sensitivity and Specificity of Exhaled Nitric Oxide and Induced Sputum Eosinophilia for the Diagnosis of Asthma

Class 3; 2006-7

SummarySummary

Introduction• Current Tests• Inflammatory Biomarkers• Aim

Methods • Study Design• Data source• Study Selection• Why Were Articles Not

Included? • Search Results• Included Articles: Quality

Criteria and Statistical Analysis• Agreement Between Reviewers

Results • Description of Included

Studies• Quality Assessment• Data Analysis

Fe(NO) Induced Sputum

Eosinophilia

Discussion• Limitations

Conclusion

Authors

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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

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IntroductionIntroduction 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

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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

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Introduction Introduction Aim

To evaluate the sensitivity and the

specificity of Fe(NO) and

induced sputum eosinophilia

in asthma diagnosis

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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.

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Methods Methods Data Source

Research 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*))

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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)))

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Methods Methods Study Selection

• Six groups of two reviewers - titles/abstracts• Six groups of two reviewers - full text

• Articles atributted randomly using Microsoft Excel

• Checked inclusion and exclusion criteria to select the articles

1st stage: titles/abstracts (non-agreement: article included)

2nd stage: full text (non-agreement solved by consensus or a third reviewer)

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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 Spanish4. Full text not available via Medline, Scopus, FMUP library or

through contact with authors5. Does not describe the criteria used for the diagnosis of asthma

After the 2nd stage of selection, the articles repeated in both data bases were excluded

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MethodsMethodsWhy Were Articles Not Included?

Criteria

1. Does not study the use of exhaled nitric oxide or eosinophil levels in induced sputum for the diagnosis of asthma in humans

2. Does not report original data on the sensitivity and specificity of the application of inflammatory biomarkers

3. Not written in English, Portuguese, French or Spanish

4. Full text not available via Medline, Scopus, FMUP library or through contact with authors

5. Does not describe the criteria used for the diagnosis of asthma

6. Article repeated in both data bases

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MEDLINE SCOPUS

1671 articles 732 articles

1st stage: 284 articles included

2nd stage: 18 articles included

MethodsMethodsSearch Results

After applying inclusion and exclusion criteria, 9 articles from Medline and 9 from Scopus were included. However, 5 articles were repeated

5 44

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Methods Methods Included Articles: : Quality Criteria and Statistical Analysis

STARD Checklist(1) to evaluate the articles regarding their methodological quality – mean of two reviewers

Meta-Disc 1.4 and SPSS 14.0 to extract relevant information

(1) BOSSYUT, PM, et al; The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. The Standards for Reporting of Diagnostic Accuracy Group;

Croat Med J.; 2003; 44(5):639-50

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MethodsMethodsAgreement Between Reviewers

Kappa = 0,899

Agreement Between Reviewers

2382 3 2385

1 18 19

2383 21 2404

Excluded

Included1st Reviewer

Total

Excluded Included

2nd Reviewer Total

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ResultsResultsDescription of Included Studies

10

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ResultsResultsQuality Assessment

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ResultsResultsData Analysis – Fe(NO)

Summary sensitivity

There is no evidence of heterogeneity

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Summary specificity

There is evidence of heterogeneity

ResultsResultsData Analysis – Fe(NO)

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Summary sensitivity


ResultsResultsData Analysis – Induced Sputum Eosinophilia

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Summary specificity


ResultsResultsData Analysis – Induced Sputum Eosinophilia

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DiscussionDiscussion Fe(NO): The sensitivity is around 83%, the specificity

ranges from 60% to 90%

Induced Sputum Eosinophilia: Although only 3 studies were analysed, the sensitivity was 76% and specificity was 85%

Fe(NO)Induced Sputum

Eosinophilia

Safe Non-Invasive Quick and Easy

Sensitive (83%) ? (76%)Specific ? ? (85%)

Parameters

Tests

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DiscussionDiscussion

Sensitivity and specificity for both biomarkers were:

High Similar

Therefore other characteristics may be relevant for the choice

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DiscussionDiscussionLimitations

Research only in Medline and Scopus databases

Published data not assessed by the queries

Language restriction

Full texts not available

Articles with missing data

Heterogeneity among population and conditions of the studies

Few articles on induced sputum eosinophilia in asthma diagnosis

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Induced Sputum Eosinophilia and ENO are

two sensitive and specific methods

There are few studies concerning Induced

Sputum Eosinophilia

On evaluating the quality of this

biomarkers, other items should be

considered

ConclusionConclusion

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AuthorsAuthors

Ana Luísa Marçal

Andreia Coelho

Carolina Rodrigues

Delfim Duarte

Diogo Costa

Inês Falcão

João Paulo Castro

Mariana Rocha

Marina Eichmann

Pedro Sousa

Sara Ranchordás

Vânia Guedes

João A. Fonseca, PhD MD

Class 3Class 3

1 A Meta-analysis on the Sensitivity and Specificity of Exhaled Nitric Oxide and Induced Sputum...

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