1. 1 The Use of Inflammatory Biomarkers in the Diagnosis of Asthma – a systematic review – Introdução à Medicina 2006/2007 Class 3, First Year João Almeida Lopes Fonseca Altamiro Manuel Rodrigues da Costa Pereira

2. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 2 Summary Introduction Current Tests Inflammatory Biomarkers Aim Methods Study Design First Queries Data source Study Selection Quality Criteria Statistical Analysis Flow Chart Gantt chart

3. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 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). Bronchial biopsy. There is growing interest in exhaled nitric oxide (Fe(NO)) and induced sputum eosinophilia.

4. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 4 Introduction Introduction Current Tests GINA. 2006 Nov Dundas I. Thorax. 2005 Jan Busse WW. Am J Respir Crit Care Med. 2005 Oct Lung function BronchodilatationMethacholine Bronchial Biopsy Safe  Non-Invasive  Quick and Easy  Sensitive  Specific  Tests Parameters

5. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 5 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

6. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 6 Introduction Introduction Aim To evaluate the sensitivity and the specificity of Fe(NO) and induced sputum eosinophilia in asthma diagnosis.

7. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 7 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.

8. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 8 Methods Methods First Queries Inflammatory Biomarkers in diagnosing asthma Without limits - 7 results (4 revision articles) Biological Markers[MeSH] AND Asthma[MeSH] AND Nitric Oxide[MeSH] AND Diagnosis[MeSH] Limits: English, Portuguese, Clinical Trial 29 results (without limits - 126 results (33 revision articles))

9. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 9 Diagnosis[MeSH] AND Eosinophil[MeSH] AND Asthma[MeSH] AND Biological Markers[MeSH] Limits: English, Portuguese, Clinical Trial, Randomized Controlled Trial 42 results (0 revision articles) (without limits - 236 results (20 revision articles)) asthm* AND diagnos* AND sputum AND eosinophil Limits: English, Portuguese, Clinical Trial, Humans 59 results (0 revision articles) (without limits - 294 results; 36 revision articles) Methods Methods First Queries

10. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 10 Methods Methods Data source Research was made using Medline, Scopus and references of used articles. Query was: ((Asthma[MeSH] OR Asthma OR Asthm*) AND ((Nitric Oxide[MeSH] OR feno OR ENO OR exhaled air) OR ((Eosinophil* OR Eosinophil[MeSH] 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*)))

11. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 11 Methods Methods Study Selection Six groups of two reviewers - titles/abstracts Five groups of two reviewers - full text Articles atributted randomly. Checked inclusion and exclusion criteria to select the articles 1st stage: titles/abstracts 2nd stage: full text. Non-agreement solved by: Consensus or A third reviewer (a specialist in the field).

12. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 12 Methods Methods Study Selection Inclusion criteria Asthma diagnosis in adults or children. Assessing Fe(NO) or induced sputum eosinophilia. Reports the sensitivity and specificity of inflammatory biomarkers. Explains the way the diagnosis was done (diagnostic criteria). Exclusion criteria Not in English, Portuguese, French or Spanish. Published before 1991. The sensitivity and specificity of inflammatory biomarkers cannot be determined with the article data. Full text article not accessible (not available via Medline, Scopus, FMUP library or request to authors).

13. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 13 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

14. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 14 Methods Methods Statistical Analysis Meta-Disc 1.4 and/or SPSS 14.0 - Relevant information extracted from the chosen articles was registered. SensitivitySpecifity Main parameters - Sensitivity and Specifity of inflammatory biomarkers: Nitric oxide Eosinophils Kappa Statistics - compares the agreement against that which might be expected by chance.

15. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 15 Flow chart

16. Use of inflammatory biomarkers in the diagnosis of asthma Class 3; 2006-7 16 Gantt chart