SPIROMETRY REFERENCE VALUES:
- A SYSTEMATIC REVIEW OF PUBLISHED ARTICLES FROM 1998 TO 2008 -
CLASS 1
Regent: Altamiro Pereira, MD PhD
Adviser: Tiago Jacinto, MD
INTRODUCTION TO MEDICINE 2009/2010
ii. Are they different
methodological quality?
in
terms
of
Research Questions
i. How many and how good are the studies
published in the last decade?
4
Hughes, 2007
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
performing a test, in order to avoid misdiagnosis;
Reference values are important statistical parameters to
obtain medical relevant information
Introduction
It is crucial to have adequate reference values when
Spirometry is an exam that allows to assess a
patient’s pulmonary function using a spirometer:
The spirometer measures the
volume and flow of the forced
exhaled air during a period of
time
2
Two reference values are commonly used: the FVC (total
amount of exhaled air) and FEV1 (exhaled air during the first
second)
6,7
2
Enright, n.d.
Kuster, 2008
8
Miller, 2007
6
Different People have
Different Values
Pre-calculated values
Inappropriate reference values can lead to bad diagnostics 1,3,5,6
SYSTEMATIC REVIEW
AND QUALITY ASSESSMENT
1
3
Baur, 1999
Garcia-Rio,
2004
5
Ip, 2006
6
Kuster, 2008
9
STROBE statement
Aims
i. Summarize data published in the last decade;
ii. Analyze and rate the obtained information using the
9
STROBE checklist ;
iii. Propose the most suitable values for Portugal or
suggest the conduction of a study
Methods
Study design: Systematic review;
Key words: Systematic review, Spirometry, Reference Values,
Forced Expiratory Volume, Forced Vital Capacity
Procedure:
1. Search
for articles
2. Select
and layout articles that meet the criteria
3. Rate
using the STROBE checklist
4. Conclusion
7
Liberati, 2009
General Methods
Data Sources (online databases):
Inclusion Criteria
Exclusion Criteria
o Articles whose full text can not be
achieved for free;
o Study subjects with occupational
exposure to inhalable materials;
 Articles that calculate
new FEV1 and FVC
spirometric reference
values
o Articles about studies with missing
data (reference equations, FEV1 or FVC
values);
o Study subjects with history of
pulmonary disease, smoking or current
disease;
 Published from 1998 to
2008
o Articles in languages other than
Portuguese or English;
o Articles that don’t refer the
equipment used;
o Participants under 18 years old;
o Not cross-sectional;
Criteria
o Studies conducted in animals;
QUERY APPLICATION ON MARCH 5TH, 2010
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 LIMITTO(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 LIMITTO(PUBYEAR, 1999) OR LIMIT-TO(PUBYEAR, 1998))
276
Schematic
representation of
our work plan
Start
Search
Read title by two reviewers
considering the inclusion
criteria
Both approve?
Yes
Include article
No
Read abstract by two reviewers
considering the exclusion criteria
Fulfills the inclusion
criteria?
No
No
Both approve?
Yes
Yes
Read abstract by a “third
reviwer”
Exclude article
Include article
Include article
Exclude article
Yes
Fulfills any exclusion
criteria?
Read full text by two
reviewers
Extract variables and score
using STROBE checklist
Finish
No
Include article
Research Method
Read title by a
“third reviewer”
2. Select and
layout articles that
meet the criteria
Procedure
1. Search for articles
Modified STROBE check-list
(a) Indicate the study’s design with a commonly used term in the title or the
abstract
Title and abstract
1
(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
Methods
Study 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
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
Variables
(a) Describe all statistical methods, including those used to control for confounding
(b) Describe any methods used to examine subgroups and interactions
Statistical
methods
(c) Explain how missing data were addressed
12
(d) If applicable, explain how matching of cases and controls was addressed
(e) Describe any sensitivity analyses
NA
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
Outcome data
(a) Give characteristics of study participants (eg demographic, clinical, social) and
information on exposures and potential confounders
14
*
(b) Indicate number of participants with missing data for each variable of interest
15
Report numbers in each exposure category, or summary measures of exposure
*
(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
Main results
16
(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
19
Discuss limitations of the study, taking into account sources of
potential bias or imprecision. Discuss both direction and magnitude
of any potential bias
Interpretation
20
Give a cautious overall interpretation of results considering
objectives, limitations, multiplicity of analyses, results from similar
studies, and other relevant evidence
Generalisabilit
y
21
Discuss the generalisability (external validity) of the study results
Limitations
Other information
Funding
22
Give 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
Title
Year
Smolej, N. et
al,
New reference equations
for forced spirometry in
elderly persons
2008
0,93
2001
0,88
M. Susan
Marion et al.
A.
Langhammer
et al.
M.H.
Boskabadya et
al.
Spirometry Reference
Values for American
Indian Adults: Results
From the Strong Heart
Study
Forced spirometry
reference values for
Norwegian adults: the
Bronchial Obstructi
Lung Function Values in
Healthy Non-Smoking
Urban Adults in
ATS/ERS
criteria
Spirometer
Number of
Participants
Age
Range
Croatia
Yes
Jager’s Pneumoscreen,
Wurtzburg, Germany
261 (154/1079
65-86
United
States of
America
Yes
Mijnhart S&M
Instruments
3167
(1972/1195)
45-74
908 (546/362)
20-80
Score Country
2001
0,75
Norway
Yes
MasterScope
spirometer, version
4.15, Erich Jaeger
GmbH,
2002
0,72
Iran
Yes
Model ST90, Fukuda
Sangyo
572 (246/326)
18-65
627 (327/300)
20-80
Gutierrez,
Carlos et al.
Reference values of
pulmonary function tests
for Canadian caucasians
2004
0,69
Canada
Yes
Morgan Model USA
System; Med Science
wedge spirometer
model 570, PK Morgan
Rolling seal
spirometer, Stead wells
spirometer
Marsh, S. et
al.
Complete reference
ranges for pulmonary
function tests from a
single population
2006
0,69
New
Zealand
Yes
Jaegar Master Screen
Body
266 (156/110)
18-70
12898
(6419/6479)
20-44
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
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, nonsmoking, urban Pakistani
population
Yes
Micromedical,
Microloop and
Microrint (airway
resistant) in
Conjunction with spida
5 PC software
504 (183/321)
15-65
2007
0,6
Pakistan
Variable Extraction
Author
Equation FEV1
Female
Equation FVC
Female
r2
FEV1
Male
Female
r2
FVC
Male
Female
RSD
FEV1
Male
RSD
FEV1
Female
RSD
FVC
Male
-0.0200(A) +
0.0001508H) - 0.677
-0.0184(Age) +
0.0349(Height) 3.189
-0.0230(A) +
0.000130(H) 0.715
0,81
0,57
0,76
0,43
0,422
0,481
0,54
2
0,612
-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.
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
-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.
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.
0.0514H - 0.0216A 3.955
0.0678H - 0.0147A 6.055
0.0326H 0.0253A - 1.286
0.0454H 0.0211A - 2.825
0,804
0,804
0,801
0,801
N.A
N.A.
N.A.
N.A.
-2.73+0.570.031A+4.47H
-5.87+0.650.03A+6.73H
-2.730.031A+4.47H
-5.870.03A+6.73H
0,56
0,56
0,52
0,56
0,45
0,32
0,53
0,4
-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.
1.636 H - 0.038 A +
2.553
2.825 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
0,55
9
0,41
Equation FEV1
Male
Equation FVC Male
M.H.
Boskaba
dya et al.
-0.0942(A) +
0.0319(H)-3.494
Gutierrez
, Carlos
et al.
Author
A.
Langham
mer et al.
M. Susan
Marion et
al.
Falaschet
ti, E. et
al.
Marsh, S.
et al.
Roca, J.
et al.
Muhamm
ad Asif
Memon
et al.
Smolej,
N. et al,
r2
FEV1
r2
FVC
RSD
FVC
Female
* Few recent studies with new reference
equations;
Expected Results
* Heterogeneous concerning the
methodological quality
* Expose
the necessity for these kind
of studies
Number of Articles by Year
1
0
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
Statistical Results
2
100
90
80
70
60
50
40
30
20
10
0
Median=52%
Statistical Results
Bo
sk
ab
Gu ady
La tie
ng rr
ha ez
m
m
M er
Fa ario
la
sc n
he
t ti
M
ar
sh
Ro
M ca
em
o
Sm n
ol
ej
% of Female Participants
% of Female
Participants
Continent of Studies
4
2
1
0
Africa
America
Asia
Europe
Oceania
Statistical Results
3
1
0,9
0,8
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
Boskabady Gutierrez Langhammer Marion Falaschetti Marsh
Roca
Memon
Smolej
Average=0,73; Range 0,6-0,93
Statistical Results
Article Score
Detailed 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%
Spirometer
Number of
Participants
Age
Range
Croatia
Yes
Jager’s Pneumoscreen,
Wurtzburg, Germany
261 (154/1079
65-86
0,88
United
States of
America
Yes
Mijnhart S&M
Instruments
3167 (1972/1195)
45-74
2001
0,75
Norway
Yes
MasterScope spirometer,
version 4.15, Erich
Jaeger GmbH,
908 (546/362)
20-80
2002
0,72
Iran
Yes
Model ST90, Fukuda
Sangyo
572 (246/326)
18-65
627 (327/300)
20-80
Title
Year
Score Country
Smolej, N. et al,
New reference equations
for forced spirometry in
elderly persons
2008
0,93
M. Susan
Marion et al.
Spirometry Reference
Values for American Indian
Adults: Results From the
Strong Heart Study
2001
A. Langhammer
et al.
Forced spirometry
reference values for
Norwegian adults: the
Bronchial Obstructi
M.H.
Boskabadya et
al.
Lung Function Values in
Healthy Non-Smoking
Urban Adults in
Gutierrez,
Carlos et al.
Reference values of
pulmonary function tests for
Canadian caucasians
2004
0,69
Canada
Yes
Morgan Model USA
System; Med Science
wedge spirometer model
570, PK Morgan Rolling
seal spirometer, Stead
wells spirometer
Marsh, S. et al.
Complete reference ranges
for pulmonary function tests
from a single population
2006
0,69
New
Zealand
Yes
Jaegar Master Screen
Body
266 (156/110)
18-70
12898
(6419/6479)
20-44
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
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, nonsmoking, urban Pakistani
population
Yes
Micromedical, Microloop
and Microrint (airway
resistant) in Conjunction
with spida 5 PC software
504 (183/321)
15-65
2007
0,6
Pakistan
Results
ATS/ERS
criteria
Author
Conclusion
20
18 Years
Years Old
Old
A. Langhammer et al.
0,75
Smolej, N. et al.
0,93
M. Susan Marion et al.
0,88
45
Years
Old
65
Years
Old
74
Years
Old
80
Years
Old
86
Years
Old
* 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
Discussion
* The third best scored article, in spite of having a much
lower score than the others has a larger age range
* 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
Discussion
*We don’t have enough data to affirm that there are
equations that can be applied in Portugal: a study
should be conducted
*The average score for methods (73%) and results (59%)
were the lowest. Suggesting that most studies are frail in
the most important topics of the check-list.
Web site Plan
Information Sources
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.org
3. 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.erseducation.org/media/2009/pdf/103639.pdf
5. 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 neversmoking 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=326
9. 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
LEITE, Ana; PEIXOTO, Cláudia; MOURA, Diana; MARTINS, Diana; FERNANDES,
Luís; ALMEIDA, Maria; BRITO, Nuno; ALMEIDA, Pedro; DIOGO, Pedro;
MONTEIRO, Sara; PIMENTA, Sofia
Class 1; turma1intromed@gmail.com
2009/2010