CLASS 1
Regent: Altamiro Pereira, MD PhDAdviser: Tiago Jacinto, MD
INTRODUCTION TO MEDICINE 2009/2010
SPIROMETRY REFERENCE VALUES:
- A SYSTEMATIC REVIEW OF PUBLISHED ARTICLES FROM 1998 TO 2008 -
i.How many and how good are the studies published in the last decade?
ii. Are they different in terms of methodological quality?
Res
earc
h Q
uest
ions
Reference values provide a point of reference to help to interpret
and determine a patient’s condition: a test result is normal if it falls within
the range predicted for the age, sex and height of the patient, based on
large population studies 4
Reference values are important statistical parameters
to obtain medical relevant information
It is crucial to have adequate reference values when
performing a test, in order to avoid misdiagnosis;
4 Hughes, 2007
Intr
oduc
tion
Spirometry is an exam that allows to assess a patient’s pulmonary function using a spirometer:
Two reference values are commonly used: the FVC (total
amount of exhaled air) and FEV1 (exhaled air during the first second) 6,7
The spirometer measures the volume and flow of the forced exhaled air during a period of
time 2
2 Enright, n.d.
6 Kuster, 2008
8 Miller, 2007
Different People have Different Values Pre-calculated values
Inappropriate reference values can lead to bad diagnostics 1,3,5,6
1 Baur, 1999
3Garcia-Rio, 2004
5 Ip, 2006
6 Kuster, 2008
SYSTEMATIC REVIEW AND QUALITY ASSESSMENT
i. Summarize data published in the last decade;
iii. Propose the most suitable values for Portugal or suggest the conduction of a study
ii. Analyze and rate the obtained information using the STROBE checklist 9;
9 STROBE statementAim
s
Methods
Key words: Systematic review, Spirometry, Reference Values, Forced Expiratory Volume, Forced Vital Capacity
Study design: Systematic review;
Data Sources (online databases):
7Liberati, 2009
Procedure:
1. Search for articles
2. Select and layout articles that meet the criteria
3. Rate using the STROBE checklist
4. Conclusion
Gen
eral
Met
hods
Crit
eria
Inclusion Criteria Exclusion Criteria
Articles that calculate new FEV1 and FVC spirometric reference valuesPublished from 1998 to 2008
oArticles whose full text can not be achieved for free;
oStudy subjects with occupational exposure to inhalable materials;
oArticles about studies with missing data (reference equations, FEV1 or FVC values);
oStudy subjects with history of pulmonary disease, smoking or current disease;
oArticles in languages other than Portuguese or English;
oStudies conducted in animals;
oArticles that don’t refer the equipment used;
oParticipants under 18 years old;
oNot cross-sectional;
ONLINE DATABASE QUERY USED: ARTICLES
FOUND (N)
("1998"[Publication Date] : "2008"[Publication Date]) AND("Spirometry"[tiab] AND ("Reference values"[mh] OR "Reference
equations"))218
814
(TITLE-ABS-KEY(spirometry) AND TITLE-ABS-KEY(“reference values” OR “reference equations” OR “normal values” OR “normative values”)) AND
(LIMIT-TO(PUBYEAR, 2008) OR LIMIT-TO(PUBYEAR, 2007) OR LIMIT-TO(PUBYEAR, 2006) OR LIMIT-TO(PUBYEAR, 2005) OR LIMIT-TO(PUBYEAR,
2004) OR LIMIT-TO(PUBYEAR, 2003) OR LIMIT-TO(PUBYEAR, 2002) OR LIMIT-TO(PUBYEAR, 2001) OR LIMIT-TO(PUBYEAR, 2000) OR LIMIT-
TO(PUBYEAR, 1999) OR LIMIT-TO(PUBYEAR, 1998))
276
QUERY APPLICATION ON MARCH 5TH, 2010
Res
earc
h M
etho
d
Schematic representation of
our work plan
Start
Search
Read title by two reviewers considering the inclusion
criteria
Read title by a “third reviewer”
Read abstract by a “third reviwer”
Finish
Exclude article
Both approve?
Read full text by two reviewers
Include article
Read abstract by two reviewers considering the exclusion criteria
No
No
Extract variables and score using STROBE checklist
Include articleYes
Fulfills the inclusion criteria?
Exclude article Include article
No Yes
Both approve?
Include article
YesNo
Fulfills any exclusion criteria?
Yes
1. Search for articles
2. Select and layout articles that meet the criteria
Proc
edur
e
Title and abstract 1
(a) Indicate the study’s design with a commonly used term in the title or the abstract
(b) Provide in the abstract an informative and balanced summary of what was done and what was found
Introduction
Background/rationale 2 Explain the scientific background and rationale for the investigation being
reported
Objectives 3 State specific objectives, including any prespecified hypotheses
Modified STROBE check-list
MethodsStudy design 4 Present key elements of study design early in the paper
Setting 5 Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection
Participants 6(a) Give the eligibility criteria, and the sources and methods of case ascertainment and control selection. Give the rationale for the choice of cases and controls
(b) For matched studies, give matching criteria and the number of controls per case NA
Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if applicable NA
Data sources/ measurement 8*
For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group
Bias 9 Describe any efforts to address potential sources of bias
Study size 10 Explain how the study size was arrived at
Quantitative variables 11 Explain how quantitative variables were handled in the analyses. If applicable,
describe which groupings were chosen and why
Statistical methods 12
(a) Describe all statistical methods, including those used to control for confounding
(b) Describe any methods used to examine subgroups and interactions
(c) Explain how missing data were addressed
(d) If applicable, explain how matching of cases and controls was addressed NA
(e) Describe any sensitivity analyses
Results
Participants 13*
(a) Report numbers of individuals at each stage of study—eg numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed
(b) Give reasons for non-participation at each stage
(c) Consider use of a flow diagram
Descriptive data 14*
(a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders
(b) Indicate number of participants with missing data for each variable of interest
Outcome data 15*Report numbers in each exposure category, or summary measures of exposure
Main results 16
(a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision (eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were included
(b) Report category boundaries when continuous variables were categorized
(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time period
Other analyses 17 Report other analyses done—eg analyses of subgroups and interactions, and sensitivity analyses
Discussion
Key results 18 Summarise key results with reference to study objectives
Limitations 19Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias
Interpretation 20Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence
Generalisability 21 Discuss the generalisability (external validity) of the study results
Other information
Funding 22Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based
Varia
ble
Extr
actio
n
Smolej, N. et al,
New reference equations for forced spirometry in
elderly persons2008 0,93 Croatia Yes
Jager’s Pneumoscreen,
Wurtzburg, Germany261 (154/1079 65-86
M. Susan Marion et al.
Spirometry Reference Values for American
Indian Adults: Results From the Strong Heart
Study
2001 0,88United
States of America
Yes Mijnhart S&M Instruments
3167 (1972/1195) 45-74
A. Langhammer
et al.
Forced spirometry reference values for
Norwegian adults: the Bronchial Obstructi
2001 0,75 Norway YesMasterScope
spirometer, version 4.15, Erich Jaeger
GmbH, 908 (546/362) 20-80
M.H. Boskabadya
et al.
Lung Function Values in Healthy Non-Smoking
Urban Adults in 2002 0,72 Iran Yes Model ST90, Fukuda
Sangyo 572 (246/326) 18-65
Gutierrez, Carlos et al.
Reference values of pulmonary function tests for Canadian
caucasians2004 0,69 Canada Yes
Morgan Model USA System; Med Science
wedge spirometer model 570, PK Morgan
Rolling seal spirometer, Stead wells spirometer
627 (327/300) 20-80
Marsh, S. et al.
Complete reference ranges for pulmonary function tests from a
single population2006 0,69 New
Zealand Yes Jaegar Master Screen Body 266 (156/110) 18-70
Roca, J. et al. References values for forced spirometry 1998 0,67 England No
Sensor Medics 2130; Jaeger Pneumolab
Vitalograph; Morgan Spirograph DS12; Sensor Medics Pne 12050; Spirotech
S500; Hewlett Packard
12898 (6419/6479) 20-44
Falaschetti, E. et al.
Prediction equations for normal and low lung
function from the Health Survey for
2004 0,6 England Yes Vitalograph Escort Spirometer
3053 (556/2497) 16-75
Muhammad Asif Memon
et al.
Spirometric reference values in healthy, non-
smoking, urban Pakistani population
2007 0,6 Pakistan Yes
Micromedical, Microloop and
Microrint (airway resistant) in
Conjunction with spida 5 PC software
504 (183/321) 15-65
Author Title Year Score Country ATS/ERS criteria Spirometer Number of
ParticipantsAge
Range
Author Equation FEV1 Male Equation FVC Male Equation FEV1
FemaleEquation FVC
Femaler2
FEV1 Male
r2 FEV1 Female
r2 FVC Male
r2FVC
Female
RSD FEV1 Male
RSD FEV1
Female
RSD FVC Male
RSD FVC
Female
M.H. Boskabadya et al.
-0.0942(A) + 0.0319(H)-3.494
-0.0200(A) + 0.0001508H) - 0.677
-0.0184(Age) + 0.0349(Height) -
3.189
-0.0230(A) + 0.000130(H) -
0.7150,81 0,57 0,76 0,43 0,422 0,481 0,54
2 0,612
Gutierrez, Carlos
et al.-0.030(A) + 0.047(H)
- 2.832-0.025(A) + 0.067(H)
- 5.473-0.024(A) +
0.049(H) - 3.335-0.025(A) +
0.037(H) - 1.091 0,62 0,73 0,56 0,66 N.A. N.A. N.A. N.A.
A. Langhammer et al.
Exp (-12.396z2.733 ln(H)- 0.0000592
A^2)
Exp (-10.556z2.342 ln(H)- 0.0000685
A^2)
Exp (-9.851z2.189
ln(H)- 0.000163A^2 +
0.007237A)
Exp (-9.851z2.189 ln(H)- 0.000143
A^2 + 0.006439A)0,6 0,72 0,63 0,68 0,12 0,13 N.A. 0,13
M. Susan Marion et
al.-0.0599(H) -
0,02420(A) - 5,650-0.0807(H) -
0,0129(A)- 0,840
-0.0358(H) - 0,0262 (A)-
1,774
-0.049(H) - 0,0258 (A) - 3.208 0,43 0,53 0,39 0,49 N.A. N.A. N.A. N.A.
Falaschetti, E. et
al.e^(-9.37674 +
0.00183A - (0.00011A^2) + 2.10839 lnH)
e^(-10.36706 + 0.00334A + (-0.00011A^2) + 2.32222 lnH)
e^(-8.49717 + 0.00422A + (-0.00015A^2) + 1.90019 lnH)
e^(-9.66999 + 0.00837A + (-
0.00017 A^2) + 2.14118 lnH)
0,59 0,69 0,52 0,62 N.A. N.A. N.A. N.A.
Marsh, S. et al. 0.0514H - 0.0216A -
3.9550.0678H - 0.0147A -
6.0550.0326H -
0.0253A - 1.2860.0454H -
0.0211A - 2.825 0,804 0,804 0,801 0,801 N.A N.A. N.A. N.A.
Roca, J. et al.
-2.73+0.57-0.031A+4.47H
-5.87+0.65-0.03A+6.73H
-2.73-0.031A+4.47H
-5.87-0.03A+6.73H 0,56 0,56 0,52 0,56 0,45 0,32 0,53 0,4
Muhammad Asif Memon
et al.-1.440+[0.030 x Ht]
+ [-0.020 x Age]-0.848+[0.032 x Ht]
+ [-0.020 x Age]
-1.866 + [0.032 x Ht] + [-0.019 x
Age]
-3.072 + [0.042 x Ht] + [-0.020 x
Age]0,478 0,467 0,429 0,422 N.A. N.A. N.A. N.A.
Smolej, N. et al, 1.636 H - 0.038 A +
2.5532.825 H - 0.050 A +
2.058 -0.034 A + 4.230 -0.042 A + 5.247 0,165 0,206 0,243 0,209 0,486 0,328 0,559 0,41
* Find at least one study that can be applied to Portugal;
* Gather a set of adequate spirometry reference values for our country;
* Expose the necessity for these kind of studies
Expected Results
Stat
istic
al R
esul
ts
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 20080
1
2
Number of Articles by Year
Median=52%
Stat
istic
al R
esul
ts
0102030405060708090
100
Boskabad
y
Gutierrez
Langh
ammer
Marion
Falasch
ettiMars
h
Roca
Memon
Smolej
% of Female Participants
% of FemaleParticipants
•St
atis
tical
Res
ults
Continent of Studies
0
1
2
3
4
Africa America Asia Europe Oceania
Average=0,73; Range 0,6-0,93
Stat
istic
al R
esul
ts
00,10,20,30,40,50,60,70,80,9
1
Boskabady Gutierrez Langhammer Marion Falaschetti Marsh Roca Memon Smolej
Article Score
1. Title/abstract 2. Introduction 3. Methods 4. Results 5. Discussion 6. Funding OVERALL SCORE
Gutierrez, 2004 100% 100% 63% 56% 100% 0% 69%
Roca, 2008 50% 100% 72% 50% 100% 100% 67%
Marsh, 2006 100% 100% 50% 60% 100% 100% 69%
Memon, 2007 100% 100% 64% 30% 100% 0% 60%
Falaschetti, 2004 100% 100% 73% 20% 100% 100% 60%
Smolej, 2008 100% 100% 100% 80% 100% 100% 93%
Laghammer, 2001 50% 50% 82% 78% 75% 0% 75%
Marion, 2001 100% 50% 82% 78% 75% 0% 72%
Boskabady, 2002 100% 50% 70% 83% 75% 0% 72%
Average Scores 89% 83% 73% 59% 92% 33% 73%
Detailed Score
Res
ults
Smolej, N. et al,New reference equations for forced spirometry in
elderly persons2008 0,93 Croatia Yes Jager’s Pneumoscreen,
Wurtzburg, Germany 261 (154/1079 65-86
M. Susan Marion et al.
Spirometry Reference Values for American Indian Adults: Results From the
Strong Heart Study
2001 0,88United
States of America
Yes Mijnhart S&M Instruments 3167 (1972/1195) 45-74
A. Langhammer et al.
Forced spirometry reference values for
Norwegian adults: the Bronchial Obstructi
2001 0,75 Norway YesMasterScope spirometer,
version 4.15, Erich Jaeger GmbH,
908 (546/362) 20-80
M.H. Boskabadya et
al.
Lung Function Values in Healthy Non-Smoking
Urban Adults in 2002 0,72 Iran Yes Model ST90, Fukuda
Sangyo 572 (246/326) 18-65
Gutierrez, Carlos et al.
Reference values of pulmonary function tests for
Canadian caucasians2004 0,69 Canada Yes
Morgan Model USA System; Med Science
wedge spirometer model 570, PK Morgan Rolling seal spirometer, Stead
wells spirometer
627 (327/300) 20-80
Marsh, S. et al.Complete reference ranges for pulmonary function tests
from a single population2006 0,69 New
Zealand Yes Jaegar Master Screen Body 266 (156/110) 18-70
Roca, J. et al. References values for forced spirometry 1998 0,67 England No
Sensor Medics 2130; Jaeger Pneumolab
Vitalograph; Morgan Spirograph DS12;
Sensor Medics Pne 12050; Spirotech S500;
Hewlett Packard
12898 (6419/6479) 20-44
Falaschetti, E. et al.
Prediction equations for normal and low lung
function from the Health Survey for
2004 0,6 England Yes Vitalograph Escort Spirometer 3053 (556/2497) 16-75
Muhammad Asif Memon et
al.
Spirometric reference values in healthy, non-
smoking, urban Pakistani population
2007 0,6 Pakistan Yes
Micromedical, Microloop and Microrint (airway
resistant) in Conjunction with spida 5 PC software
504 (183/321) 15-65
Author Title Year Score Country ATS/ERS criteria Spirometer Number of
ParticipantsAge
Range
18 Years Old
86 Years Old
20 Years Old
80 Years Old
45 Years Old
74 Years Old
65 Years Old
A. Langhammer et al. 0,75
M. Susan Marion et al. 0,88
Smolej, N. et al. 0,93
Con
clus
ion
* The best scored article (93%) refers to a population with a very limited age
* The second best scored article has a larger range of age but is still limited
* The third best scored article, in spite of having a much lower score than the others has a larger age range
Discussio
n * There is a limited number of studies of this type published each year
* All but one study follow ATS/ERS criteria showing an effort for the standardization of this studies
*There is the need for a study with a good sample size that covered a wide range of ages
We don’t have enough data to affirm that there are equations that can be applied in Portugal: a study should be conducted
Web site Plan
1. Baur, X., S. Isringhausen-Bley, et al. (1999). "Comparison of lung-function reference values." International Archives of Occupational and Environmental Health 72(2): 69-83.2. Enright P. Testing your lungs: spirometry [Internet]. European Lung Foundation. Available from: http://www.european-lung-foundation.org3. Garcia-Rio, F., J. M. Pino, et al. (2004). "Spirometric reference equations for European females and males aged 65-85 yrs." Eur Respir J 24(3): 397-405.4. Hughes, J.M.B.,Interpreting pulmonary function tests [Internet] ERS Education –Your best online source of CME in respiratory medicine [2007] European Respitatory Society. Available from: http://www.ers-education.org/media/2009/pdf/103639.pdf5. Ip, M. S.-m., F. W.-s. Ko, et al. (2006). "Updated Spirometric Reference Values for Adult Chinese in Hong Kong and Implications on Clinical Utilization" Chest 129(2): 384-392.6. Kuster, S. P., D. Kuster, et al. (2008). "Reference equations for lung function screening of healthy never-smoking adults aged 18-80 years." Eur Respir J 31(4): 860-868.7. Liberati, A., D. G. Altman, et al. (2009). "The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration." Journal of Clinical Epidemiology 62(10): e1-e34.8. Miller, Martin R. Interactive Course on Spirometry Training [Internet] ERS Education –Your best online source of CME in respiratory medicine [2007] European Respitatory Society. Available from: http://www.ers-education.org/pages/default.aspx?id=3269. Unknown. STROBE Statement - checklist of items that should be included in reports of observational study [Internet] Strobe Statement: Strengthening the reporting of observational studies in epidemiology. [2009] ISPM - University of Bern. Available from: http://www.strobe-statement.org
Info
rmat
ion
Sour
ces
LEITE, Ana; PEIXOTO, Cláudia; MOURA, Diana; MARTINS, Diana; FERNANDES, Luís; ALMEIDA, Maria; BRITO, Nuno; ALMEIDA, Pedro; DIOGO, Pedro;
MONTEIRO, Sara; PIMENTA, Sofia
Class 1; [email protected] 2009/2010