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FENO: INFLUENCE OF ALLERGIC RHINITIS AND ATOPY ON ITS VALUES Systematic Review Faculdade de Medicina da Universidade do Porto Subject: Introdução à Medicina Professor: Dr. Altamiro Pereira Under the guidance of: Prof. Dr. João Fonseca and Dr. Luís da Silva Date: 28st May 2008

Feno : Influence of allergic rhinitis and atopy on its values

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Faculdade de Medicina da Universidade do Porto Subject: Introdução à Medicina Professor: Dr. Altamiro Pereira Under the guidance of : Prof. Dr. João Fonseca and Dr. Luís da Silva Date: 28st May 2008. Systematic Review. - PowerPoint PPT Presentation

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Page 1: Feno : Influence of allergic rhinitis and  atopy  on its values

FENO: INFLUENCE OF ALLERGIC RHINITIS AND ATOPY ON ITS VALUES

Systematic Review

Faculdade de Medicina da Universidade do PortoSubject: Introdução à MedicinaProfessor: Dr. Altamiro PereiraUnder the guidance of: Prof. Dr. João Fonseca and Dr. Luís da SilvaDate: 28st May 2008

Page 2: Feno : Influence of allergic rhinitis and  atopy  on its values

Index

Introduction Work’s Background Methods and Results Main Results Discussion

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Page 3: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Introduction

FeNO (Fractional Exhaled Nitric Oxide) is one of the tools used for asthma diagnosis. However, its use as a diagnostic test requires a standardized measurement technique due to the many confusion factors that can affect its values.

These alterations have been recorded in literature but were never summarized.

As such, the aim of our systematic review is to collect an analyze all the information on the influence of allergic rhinitis and atopy on FeNO and reach a conclusion about how their presence can modify its values in asthma diagnosis.

Page 4: Feno : Influence of allergic rhinitis and  atopy  on its values

Index

Introduction Work’s Background Methods and Results Main Results Discussion

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Page 5: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Work’s Background

Establish our systematic review’s aims Improve the interpretation of FeNO values as a diagnostic

test for asthma. Assess how atopy and how allergic rhinitis affect exhaled nitric

oxide values.

Define research questions: How does atopy influence FeNO values? How does allergic rhinitis influence FeNO values?

Search for an adequate query This was used in the article search

(Exhaled nitric oxide OR Nitric oxide OR FeNO OR eNO) AND (“Allergic Rhinitis” OR Atopy OR “Skin prick test” OR “Prick test” OR “Ig E” OR “Specific Ig”)

Page 6: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Work’s Background

• Define the inclusion and exclusion criteria• Define our variables for data extraction• Define how statistical analysis will be made

Page 7: Feno : Influence of allergic rhinitis and  atopy  on its values

Index

Introduction Work’s Background Methods and Results Main Results Discussion

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Page 8: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

METHODS AND RESULTS

Page 9: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Methods and Results

Articles Search Collecting Articles Distributing the Articles

Selection phase Read Title and Abstracts Read Full Texts

Data Extraction Process Results

Statistical Analysis

Page 10: Feno : Influence of allergic rhinitis and  atopy  on its values
Page 11: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Methods and Results

Articles Search Collecting Articles Distributing the Articles

Selection phase Read Title and Abstracts Read Full Texts

Data Extraction Process Results

Statistical Analysis

Page 12: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Methods and Results

Articles Search Collecting

Articles Distributing the

Articles

Page 13: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Collecting articlesArticle search: Articles were searched in Scopus, Pubmed

and ISI Web of Knowledge. Limits used: published since 2001language: English, Spanish or Portuguese

Articles Organization Data base creation with single articles copy Total: 616 articles

Methods and Results – Articles Search

Page 14: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Distributing the articles

Article Distribution: Random attribution of articles between the reviewers and double read

Methods and Results – Articles Search

Page 15: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Methods and Results

Articles Search Collecting Articles Distributing the Articles

Selection phase Read Title and Abstracts Read Full Texts

Data Extraction Process Results

Statistical Analysis

Page 16: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Selection Phase

Inclusion/Exclusion of Titles and Abstracts

Inclusion/Exclusion of full-texts

Methods and Results – Selection Phase

Page 17: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Inclusion/Exclusion of Titles and Abstracts

Page 18: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Inclusion/Exclusion of Titles and Abstracts

Methods and Results – Selection Phase

Double reading of title and abstracts

Applying exclusion criteria

Data collection using a Google Docs form

Reaching the final conclusion

616 Articles

128 Included

358 Excluded

130 Divergences

39 Included

84 Excluded

7 Divergences

1 Included

6 Excluded

Discussion between the reviewers

3 rd Reviwer

K = 0.4215 ± 0,22K (ratio) =0.55 ± 0.30PC (Yes) = 0,4401 ± 0,21PC (No)= 0,7118 ± 0,15

Page 19: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

It doesn't talks about atopy or similar or allergic rhinitis or similar or ways of diag-

nose them

17%

It doesn't talks about atopy or similar or allergic rhinitis or similar or ways of diag-nose them, It doesn't use

original data1%

It doesn't talks about atopy or similar or allergic rhinitis or similar or ways of diag-nose them, It is about ani-

mals1%It doesn't talks about nitric

oxide or FENO or similar or values or ways of measure

them24%

It doesn't talks about nitric oxide or FENO or similar or values or ways of measure them, It doesn't talks about atopy or similar or allergic

rhinitis or similar or ways of diagnose them

11%

It doesn't talks about nitric oxide or FENO or similar or values or ways of measure them, It doesn't talks about atopy or similar or allergic

rhinitis or similar or ways of diagnose them, It doesn't

use original data2%

It doesn't talks about nitric oxide or FENO or similar or values or ways of measure them, It doesn't use original

data2%

It doesn't use original data30%

It is about animals12%

It is about animals, It doesn't use original data

1%

Titles and Abstracts - Exclusion CriteriaMethods and Results – Selection Phase

Page 20: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Inclusion/Exclusion of Full Texts

Page 21: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Inclusion/Exclusion of full-textsMethods and Results – Selection Phase

Double reading of full texts

Applying exclusion criteria

Data collection using a Google Docs form

Reaching the final conclusion

168 Articles

17Included

94

Excluded

33 Diverge

nces

3 Included

30 Excluded

22No Full

Text Availabl

e

K = 0,3509 ± 0,24K (ratio) =0.46 ± 0,31PC (Yes) = 0,3689 ± 0.18PC (No)= 0,7066 ± 0,12

Discussion between the reviewers

E-mail sent to the authors

Page 22: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

It doesn't talks about atopy or similar or allergic rhinitis or similar or ways of diag-

nose them16%

It doesn't use online FeNO measurments

28%

It doesn't use original data2%

It doesn’t have comparable groups21%

It doesn’t talks about FeNO, eNO, ways of mesure them

or anything similar, It doesn’t measure FeNO val-ues in individuals studied.

2%

It doesn’t talks about FeNO, eNO, ways of mesure them

or anything similar17%

It measure FeNO in individ-uals with confounding fac-

tors13%

Others2%

Full Texts Exclusion ReasonsMethods and Results – Selection Phase

Page 23: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Methods and Results

Articles Search Collecting Articles Distributing the Articles

Selection phase Read Title and Abstracts Read Full Texts

Data Extraction Process Results

Statistical Analysis

Page 24: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Data ExtractionMethods and Results – Data Extraction

Process Results

Page 25: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Data Extraction - Process

Page 26: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Data Extraction - Process

After reading some papers about factors that might confuse FeNO values we decided to extract information that might be relevant for future analysis and discussion.

We use a form for data extraction that summarize all important variables.

Prevent missing values; increase the efficiency

Methods and Results – Data Extraction

Page 27: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Data Extraction - Results

Page 28: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Data Extraction - Results

22 Articles

17 Analyzed

4 Divergences

5 Missing Data

Methods and Results – Data Extraction

Page 29: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Methods and Results

Articles Search Collecting Articles Distributing the Articles

Selection phase Read Title and Abstracts Read Full Texts

Data Extraction Process Results

Statistical Analysis

Page 30: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Statistical Analysis

Page 31: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Statistical Analysis

After extraction, data was transferred to a file were it can be analyzed with the proper tools

We organize the data following the sequence:

1st: Factors Studied 2nd: Age Group 3rd: Allergic Rhinitis Assessment

Methods and Results – Statistical Analysis

Page 32: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Statistical AnalysisArticles that use mean as summary

measure and SD as dispersion measure

Achieve the mean difference between healthy and diseased considering

random effects

Meta-analysis(Revman)

Data from different articles, with different summary and dispersion

measures

Make a qualitative analysis of articles

Analysis of FeNO values variation in the presence of the condition

Methods and Results – Statistical Analysis

Page 33: Feno : Influence of allergic rhinitis and  atopy  on its values

Index

Introduction Work’s Background Methods and Results Main Results Discussion

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Page 34: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

MAIN RESULTS

Page 35: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Main Results

General Qualitative Analysis

Factors Studied Age Groups Condition Assessment

Meta-analysis Articles Selection Allergic Rhinitis Atopy

Page 36: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Main Results - General

Page 37: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Results - General

Data File

Tendency for increased FeNO values, when

comparing to the healthy/control group

AtopyAllergic Rhinitis

Main Results – General

Page 38: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Main Results

General Qualitative Analysis

Factors Studied Age Groups Condition Assessment

Meta-analysis Articles Selection Allergic Rhinitis Atopy

Page 39: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Main Results – Qualitative Analysis

Page 40: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Qualitative Analysis – Factors Studied

AllergicRhinitis

9Atopy

2Both6

Main Results – Qualitative Analysis

Page 41: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Qualitative Analysis - Age Groups

Allergic RhinitisAtopy

02468

10

43

10

510

Child AdultChildren and Adults

Main Results – Qualitative Analysis

Page 42: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Qualitative Analysis - Condition Assessment

AtopyAllergic Rhinitis

15

13

10

Medical Diagnosis Questionary/Self ReportedSkin Prick Test or Total IgE

Main Results – Qualitative Analysis

Page 43: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Main Results

General Qualitative Analysis

Factors Studied Age Groups Condition Assessment

Meta-analysis Articles Selection Allergic Rhinitis Atopy

Page 44: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Main Results - Meta-analysis

Page 45: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Meta-analysis: Articles Selection

17 Articles

8 with mean as summary

measure

2 not

used

6 used

8 with median as summary

measure

Not used

1 only with a sample of 3 subjects

Not used

- First: Error in Standart deviation? Errors in FeNO assessment?- Second: Values

grouped by gender

Main Results – Meta-analysis

Page 46: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Meta-analysis: Allergic Rhinitis

Causes for heterogeneity:- Age groups?

Main Results – Meta-analysis

Page 47: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Meta-analysis: Allergic Rhinitis Child

Main Results – Meta-analysis

Page 48: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Meta-analysis: Allergic Rhinitis Adults

Main Results – Meta-analysis

Page 49: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Meta-analysis: Atopy

Causes for heterogeneity:- Age Group?

Main Results – Meta-analysis

Page 50: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Meta analysis: Atopy

Child

Adults

Main Results – Meta-analysis

Page 51: Feno : Influence of allergic rhinitis and  atopy  on its values

Index

Introduction Work’s Background Methods and Results Main Results Discussion

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Page 52: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

DISCUSSION

Page 53: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Discussion

General Results Limitations Our Study Other Studies Future Prespectives

Page 54: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

General Results

Presence of atopy and allergic rhinitis is responsible for raise in FeNO values.

Meta-analysis showed that the difference between its values in healthy and patients was significant (p<0.05)

Atopy Allergic Rhinitis

Child 11.10 (9.13-13.07)

17.45 (14.14-20.46)

Adults 9.50 (9.05-9.93)

9.70 (7.35-12.04)

Both 10.0 (8.45-11.55)

13.84 (10.08-17.60)

Mean Differences (ppb) obtained from meta-analysis. Values presented as mean (95%CI)

Discussion

Page 55: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Limitations

Different ways of assessment of the conditions

Results achieved from articles with: Individuals without asthma FeNO values measured in an online way

Discussion

Page 56: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Limitations

Analyzed the difference between Atopic and Healthy Subjects

FeNO values: elevated in Atopic patients

Atopy influences FeNO values

Analysis of the difference between Allergic Rhinitis

and Healthy Subjects

FeNO values: elevated in Allergic Rhinitis

patients

Is Rhinitis the source of elevation? Or is it the

atopy influence?

New studies comparing

Allergic Rhinitis and non allergic

rhinitis subjects

Discussion

Page 57: Feno : Influence of allergic rhinitis and  atopy  on its values

Limitations: Interpreting Heterogeneity Few articles, with distinct populations Articles don’t refer when values were

assessed: pollen influences were not stated (the only one showing different values: out of season)

Different populations

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Population: Hospital or Clinical

Condition Controlled?

Differences in values?

Population: out of hospital

Condition not controlled?

Discussion

Page 58: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Our Study

Articles without full text: e-mail was sent to the authors asking for the papers (from 22, 11 were obtained)

Articles without values: e-mail was sent to the authors asking for the data (no answer was obtained)

Forms were used -> less time spent and lower probability of errors

Discussion

Page 59: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Other Studies

Kovesi et al: FeNO values are raised in children with allergy

Dressel et al: FeNO values are raised in adults with atopy

Welsh et al: Differences are not significant

Our meta-analysis: significant differences between Healthy and Diseased (p<0.05)

Discussion

Page 60: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Future Prespectives

More homogeneity/accordance in values presentation

More studies directed at FeNO study New meta-analysis exploring the

theme Studies in different age groups

Discussion

Page 61: Feno : Influence of allergic rhinitis and  atopy  on its values

FeNO: Influence of Allergic Rhinitis and Atopy on its values

Developed by

Turma 3 Caeiro, Alexandra; Coelho, Ana

Margarida; Abreu, Ana Teresa; Guedes, Bruna; Linhares, Daniela; Vasconcelos,

Gisela; Pita, Inês; Fonseca, João Alberto; Gomez, Maria de La Salete; Oliveira, Marta Isabel; Abreu, Vitor

Alexandre Contacto: [email protected]