1 The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia 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

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; Summary 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 Class 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

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; Introduction Introduction Current Tests GINA Nov Dundas I. Thorax Jan Busse WW. Am J Respir Crit Care Med Oct Lung function BronchodilatationMethacholine 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 Class 3; Introduction Introduction Inflammatory Biomarkers Lemiere C et al. Can J Physiol Pharmacol Jan Joos GF et al. Curr Opin Pharmacol Jun Dinakar C et al. Curr Allergy Asthma Rep Nov Kim CK et al. Ann Allergy Asthma Immunol 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 Class 3; 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 Class 3; 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 Class 3; 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*))

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; 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 Class 3; 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 Class 3; 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 Class 3; 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 Class 3; Methods Methods Quality Criteria The articles included were evaluated regarding their methodological quality using a scale based on STARD. 1.

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; Methods Methods Statistical Analysis Meta-Disc 1.4 and SPSS 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.

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; Flow chart

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; Results Results Proportion of Inclusion/Exclusion – Pubmed and Scopus

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; Results Results Degree of Concordance -Titles/Abstracts and Full Texts

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; Results Results Exclusion Criteria – Titles/Abstracts and Full Texts

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; Data extraction

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; Data extraction

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; Quality 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 Class 3; Site Map

The Use of Exhaled Nitric Oxide and Induced Sputum Eosinophilia in the Diagnosis of Asthma Class 3; Gantt chart