CLASS 1 Regent: Altamiro Pereira, MD PhD Adviser: Tiago Jacinto, MD INTRODUCTION TO MEDICINE 2009/2010 SPIROMETRY REFERENCE VALUES: - A SYSTEMATIC REVIEW OF PUBLISHED ARTICLES FROM 1998 TO i.How many and how good are the studies published in the last decade? Are they different in terms of methodological quality? ii. Are they different in terms of methodological quality? Research Questions Reference values provide a point of reference to help to interpret and determine a patients 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 Introduction Spirometry is an exam that allows to assess a patients 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, Miller, 2007 Different People have Different Values Pre-calculated values Inappropriate reference values can lead to bad diagnostics 1,3,5,6 1 Baur, Garcia-Rio, Ip, 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 statement Aims Methods Key words: Systematic review, Spirometry, Reference Values, Forced Expiratory Volume, Forced Vital Capacity Study design: Systematic review ; Data Sources (online databases): 7 Liberati, 2009 Procedure: 1. Search for articles 2. Select and layout articles that meet the criteria 3. Rate using the STROBE checklist 4. Conclusion General Methods Criteria Inclusion CriteriaExclusion Criteria Articles that calculate new FEV1 and FVC spirometric reference values Published from 1998 to 2008 o Articles whose full text can not be achieved for free; o Study subjects with occupational exposure to inhalable materials; 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; o Articles in languages other than Portuguese or English; o Studies conducted in animals; o Articles that dont refer the equipment used; o Participants under 18 years old; o Not 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")) (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 Research Method Schematic representation of our work plan 1. Search for articles 2. Select and layout articles that meet the criteria Procedure Title and abstract1 (a) Indicate the studys 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 Objectives3State specific objectives, including any prespecified hypotheses Modified STROBE check-list Methods Study design4Present key elements of study design early in the paper Setting5 Describe the setting, locations, and relevant dates, including periods of recruitment, exposure, follow-up, and data collection Participants6 (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 caseNA Variables7 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 Bias9Describe any efforts to address potential sources of bias Study size10Explain 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 addressedNA (e) Describe any sensitivity analyses Results Participants 13 * (a) Report numbers of individuals at each stage of studyeg 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 results16 (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 analyses17 Report other analyses doneeg analyses of subgroups and interactions, and sensitivity analyses Discussion Key results18Summarise key results with reference to study objectives Limitations19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias Interpretation20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence Generalisabilit y 21Discuss the generalisability (external validity) of the study results Other information Funding22 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 Variable Extraction Smolej, N. et al, New reference equations for forced spirometry in elderly persons 20080,93CroatiaYes Jagers Pneumoscreen, Wurtzburg, Germany 261 (154/ M. Susan Marion et al. Spirometry Reference Values for American Indian Adults: Results From the Strong Heart Study 20010,88 United States of America Yes Mijnhart S&M Instruments 3167 (1972/1195) A. Langhammer et al. Forced spirometry reference values for Norwegian adults: the Bronchial Obstructi 20010,75NorwayYes 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 20020,72IranYes Model ST90, Fukuda Sangyo 572 (246/326)18-65 Gutierrez, Carlos et al. Reference values of pulmonary function tests for Canadian caucasians 20040,69CanadaYes 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 20060,69 New Zealand Yes Jaegar Master Screen Body 266 (156/110)18-70 Roca, J. et al. References values for forced spirometry 19980,67EnglandNo Sensor Medics 2130; Jaeger Pneumolab Vitalograph; Morgan Spirograph DS12; Sensor Medics Pne 12050; Spirotech S500; Hewlett Packard (6419/6479) Falaschetti, E. et al. Prediction equations for normal and low lung function from the Health Survey for 20040,6EnglandYes Vitalograph Escort Spirometer 3053 (556/2497) Muhammad Asif Memon et al. Spirometric reference values in healthy, non- smoking, urban Pakistani population 20070,6PakistanYes Micromedical, Microloop and Microrint (airway resistant) in Conjunction with spida 5 PC software 504 (183/321)15-65 AuthorTitleYearScoreCountry ATS/ERS criteria Spirometer Number of Participants Age Range Table 2: Data extraction from the articles Number of participants total (female/male) Author Equation FEV1 Male Equation FVC Male Equation FEV1 Female Equation FVC Female r2 FEV1 Male r2 FEV1 Female r2 FVC Male r2 FVC Female RSD FEV1 Male RSD FEV1 Female RSD FVC Male RSD FVC Female M.H. Boskaba dya et al (A) (H) (A) H) (Age) (Height) (A) (H) ,810,570,760,430,4220,481 0,54 2 0,612 Gutierrez, Carlos et al (A) (H) (A) (H) (A) (H) (A) (H) ,620,730,560,66N.A. A. Langham mer et al. Exp ( z2.733 ln(H) A^2) Exp ( z2.342 ln(H) A^2) Exp ( z2.189 ln(H) A^ A) Exp (-9.851z2.189 ln(H) A^ A) 0,60,720,630,680,120,13N.A.0,13 M. Susan Marion et al (H) - 0,02420(A) - 5, (H) - 0,0129(A)- 0, (H) - 0,0262 (A)- 1, (H) - 0,0258 (A) ,430,530,390,49N.A. Falaschet ti, E. et al. e^( A - ( A^2) lnH) e^( A + ( A^2) lnH) e^( A + ( A^2) lnH) e^( A + ( A^2) lnH) 0,590,690,520,62N.A. Marsh, S. et al H A H A H A H A ,804 0,801 N.AN.A. Roca, J. et al A+4.47H A+6.73H A+4.47H A+6.73H 0,56 0,520,560,450,320,530,4 Muhamm ad Asif Memon et al [0.030 x Ht] + [ x Age] [0.032 x Ht] + [ x Age] [0.032 x Ht] + [ x Age] [0.042 x Ht] + [ x Age] 0,4780,4670,4290,422N.A. Smolej, N. et al, H A H A A A ,1650,2060,2430,2090,4860,328 0,55 9 0,41 Table 3: Equations and statistical data collected from equations, N.A. means Not Applicable * 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 Statistical Results Median=52% Statistical Results Average=0,73; Range 0,6-0,93 Statistical Results 1. Title/abstract2. Introduction3. Methods4. Results5. Discussion6. FundingOVERALL SCORE Gutierrez, % 63%56%100%0%69% Roca, %100%72%50%100% 67% Marsh, % 50%60%100% 69% Memon, % 64%30%100%0%60% Falaschetti, % 73%20%100% 60% Smolej, % 80%100% 93% Laghammer, % 82%78%75%0%75% Marion, %50%82%78%75%0%72% Boskabady, %50%70%83%75%0%72% Average Scores89%83%73%59%92%33%73% Detailed Score Results Smolej, N. et al, New reference equations for forced spirometry in elderly persons 20080,93CroatiaYes Jagers Pneumoscreen, Wurtzburg, Germany 261 (154/ M. Susan Marion et al. Spirometry Reference Values for American Indian Adults: Results From the Strong Heart Study 20010,88 United 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 20010,75NorwayYes 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 20020,72IranYes Model ST90, Fukuda Sangyo 572 (246/326)18-65 Gutierrez, Carlos et al. Reference values of pulmonary function tests for Canadian caucasians 20040,69CanadaYes 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 20060,69 New Zealand Yes Jaegar Master Screen Body 266 (156/110)18-70 Roca, J. et al. References values for forced spirometry 19980,67EnglandNo Sensor Medics 2130; Jaeger Pneumolab Vitalograph; Morgan Spirograph DS12; Sensor Medics Pne 12050; Spirotech S500; Hewlett Packard (6419/6479) Falaschetti, E. et al. Prediction equations for normal and low lung function from the Health Survey for 20040,6EnglandYes Vitalograph Escort Spirometer 3053 (556/2497)16-75 Muhammad Asif Memon et al. Spirometric reference values in healthy, non- smoking, urban Pakistani population 20070,6PakistanYes Micromedical, Microloop and Microrint (airway resistant) in Conjunction with spida 5 PC software 504 (183/321)15-65 AuthorTitleYearScoreCountry ATS/ERS criteria Spirometer Number of Participants Age Range Table 2: Data extraction from the articles Number of participants total (female/male) 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 Conclusion * 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 Discussion * 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 dont 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): Enright P. Testing your lungs: spirometry [Internet]. European Lung Foundation. Available from:3. Garcia-Rio, F., J. M. Pino, et al. (2004). "Spirometric reference equations for European females and males aged yrs." Eur Respir J 24(3): 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:education.org/media/2009/pdf/ pdfeducation.org/media/2009/pdf/ 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): Kuster, S. P., D. Kuster, et al. (2008). "Reference equations for lung function screening of healthy never- smoking adults aged years." Eur Respir J 31(4): 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-e 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: 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:Information Sources LEITE, Ana; PEIXOTO, Cludia; MOURA, Diana; MARTINS, Diana; FERNANDES, Lus; ALMEIDA, Maria; BRITO, Nuno; ALMEIDA, Pedro; DIOGO, Pedro; MONTEIRO, Sara; PIMENTA, Sofia Class 1; 2009/2010