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?

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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

od

uct

ion

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

Meth

od

s

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

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ds

Cri

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a

Inclusion Criteria Exclusion Criteria

Articles that calculate new FEV1 and FVC spirometric reference values

Published 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

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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

Pro

ced

ure

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

2Explain the scientific background and rationale for the investigation being

reported

Objectives 3 State specific objectives, including any prespecified hypotheses

Modified STROBE check-list

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

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

Var

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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

YesMijnhart 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 Yes

MasterScope 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

caucasians

2004 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 population

2006 0,69New

ZealandYes

Jaegar Master Screen Body

266 (156/110) 18-70

Roca, J. et al.References values for

forced spirometry1998 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 YesVitalograph Escort

Spirometer3053

(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 CountryATS/ERS criteria

SpirometerNumber of

ParticipantsAge

Range

AuthorEquation FEV1

MaleEquation FVC Male

Equation FEV1 Female

Equation FVC Female

r2 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

0,542

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) - 1.0910,62 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 - 2.8250,804 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 + 2.553

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 0,3280,55

90,41

Exp

ected R

esults

* Few recent studies with new reference equations;

* Expose the necessity for these kind of studies

* Heterogeneous concerning the methodological quality

Sta

tist

ical

Res

ult

s

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 20080

1

2

Number of Articles by Year

Median=52%

Sta

tist

ical

Res

ult

s

0102030405060708090

100

Boskabad

y

Gutierrez

Langh

ammer

Marion

Falasch

ettiMars

h

Roca

Memon

Smolej

% of Female Participants

% of FemaleParticipants

•S

tati

stic

al R

esu

lts

Continent of Studies

0

1

2

3

4

Africa America Asia Europe Oceania

Average=0,73; Range 0,6-0,93

Sta

tist

ical

Res

ult

s

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

ult

s

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

YesMijnhart 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

YesJaegar Master Screen

Body266 (156/110) 18-70

Roca, J. et al.References values for

forced spirometry1998 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 YesVitalograph Escort

Spirometer3053 (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 CountryATS/ERS criteria

SpirometerNumber 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

Co

ncl

usi

on

* 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

Discu

ssion

* There is a limited number of studies of this type published each year

Discu

ssion

* 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

*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

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

So

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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