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Introdução à Medicina 2006/2007 Class 3, First Year João Almeida Lopes Fonseca

A Meta-analysis on the Sensitivity and Specificity of Exhaled Nitric Oxide and Induced Sputum Eosinophilia for the Diagnosis of Asthma. Introdução à Medicina 2006/2007 Class 3, First Year João Almeida Lopes Fonseca Altamiro Manuel Rodrigues da Costa Pereira. Introduction Current Tests

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Introdução à Medicina 2006/2007 Class 3, First Year João Almeida Lopes Fonseca

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  1. A Meta-analysis on the Sensitivity and Specificity of Exhaled Nitric Oxide and Induced Sputum Eosinophilia for the Diagnosis of Asthma Introdução à Medicina 2006/2007 Class 3, First Year João Almeida Lopes Fonseca Altamiro Manuel Rodrigues da Costa Pereira

  2. 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 Summary

  3. Introduction • 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

  4. IntroductionCurrent Tests Tests Parameters GINA. 2006 Nov Dundas I. Thorax. 2005 Jan Busse WW. Am J Respir Crit Care Med. 2005 Oct

  5. Introduction Inflammatory Biomarkers Tests Parameters Lemiere Cet 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

  6. Introduction Aim To evaluate the sensitivityand the specificity of Fe(NO) and induced sputum eosinophilia in asthma diagnosis

  7. Methods Study Design A meta-analysis of the published studies on the sensitivityand specificity of measurements of Fe(NO)andinduced sputum eosinophilia.

  8. 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*))

  9. 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)))

  10. 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)

  11. Methods Study Selection Inclusion criteria • Studies the use of exhaled nitric oxide or eosinophil levels in induced sputum for the diagnosis of asthma in humans • Reports original data on the sensitivity and specificity of the application of inflammatory biomarkers Exclusion criteria • Not written in English, Portuguese, French or Spanish • Full text not available via Medline, Scopus, FMUP library or through contact with authors • 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

  12. MethodsWhy Were Articles Not Included? Criteria • Does not study the use of exhaled nitric oxide or eosinophil levels in induced sputum for the diagnosis of asthma in humans • Does not report original data on the sensitivity and specificity of the application of inflammatory biomarkers • Not written in English, Portuguese, French or Spanish • Full text not available via Medline, Scopus, FMUP library or through contact with authors • Does not describe the criteria used for the diagnosis of asthma • Article repeated in both data bases

  13. MethodsSearch Results MEDLINESCOPUS 1671 articles 732 articles 1st stage: 284 articles included 2nd stage: 18 articles included 4 5 4 After applying inclusion and exclusion criteria, 9 articles from Medline and 9 from Scopus were included. However, 5 articles were repeated

  14. 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 1.4andSPSS 14.0to 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

  15. MethodsAgreement Between Reviewers Agreement Between Reviewers 2nd Reviewer Total Excluded Included Excluded 2382 3 2385 1st Reviewer Included 1 18 19 Total 2383 21 2404 Kappa = 0,899

  16. ResultsDescription of Included Studies 10 2 1

  17. ResultsQuality Assessment

  18. ResultsData Analysis – Fe(NO) Summary sensitivity There is no evidence of heterogeneity

  19. ResultsData Analysis – Fe(NO) Summary specificity There is evidence of heterogeneity

  20. ResultsData Analysis – Induced Sputum Eosinophilia Summary sensitivity There is no evidence of heterogeneity

  21. ResultsData Analysis – Induced Sputum Eosinophilia Summary specificity There is no evidence of heterogeneity

  22. Discussion • 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% Tests Parameters

  23. Discussion Sensitivity and specificity for both biomarkers were: • High • Similar Therefore other characteristics may be relevant for the choice

  24. DiscussionLimitations • 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

  25. Conclusion • 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

  26. 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 Authors Class 3

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