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
Index
Introduction Work’s Background Methods and Results Main Results Discussion
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.
Index
Introduction Work’s Background Methods and Results Main Results Discussion
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”)
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
Index
Introduction Work’s Background Methods and Results Main Results Discussion
FeNO: Influence of Allergic Rhinitis and Atopy on its values
FeNO: Influence of Allergic Rhinitis and Atopy on its values
METHODS AND RESULTS
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
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
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Methods and Results
Articles Search Collecting
Articles Distributing the
Articles
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
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
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
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
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Inclusion/Exclusion of Titles and Abstracts
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
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
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Inclusion/Exclusion of Full Texts
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
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
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
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Data ExtractionMethods and Results – Data Extraction
Process Results
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Data Extraction - Process
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
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Data Extraction - Results
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
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
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Statistical Analysis
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
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
Index
Introduction Work’s Background Methods and Results Main Results Discussion
FeNO: Influence of Allergic Rhinitis and Atopy on its values
FeNO: Influence of Allergic Rhinitis and Atopy on its values
MAIN RESULTS
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
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Main Results - General
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
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
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Main Results – Qualitative Analysis
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Qualitative Analysis – Factors Studied
AllergicRhinitis
9Atopy
2Both6
Main Results – Qualitative Analysis
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
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
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
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Main Results - Meta-analysis
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
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Meta-analysis: Allergic Rhinitis
Causes for heterogeneity:- Age groups?
Main Results – Meta-analysis
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Meta-analysis: Allergic Rhinitis Child
Main Results – Meta-analysis
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Meta-analysis: Allergic Rhinitis Adults
Main Results – Meta-analysis
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Meta-analysis: Atopy
Causes for heterogeneity:- Age Group?
Main Results – Meta-analysis
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Meta analysis: Atopy
Child
Adults
Main Results – Meta-analysis
Index
Introduction Work’s Background Methods and Results Main Results Discussion
FeNO: Influence of Allergic Rhinitis and Atopy on its values
FeNO: Influence of Allergic Rhinitis and Atopy on its values
DISCUSSION
FeNO: Influence of Allergic Rhinitis and Atopy on its values
Discussion
General Results Limitations Our Study Other Studies Future Prespectives
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
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
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
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
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
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
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
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]