ABSTRACT

Objective: One of the major issues in the use of spirometry is the evaluation of the values obtained in comparison with standardized reference values. Such reference values should be determined by studying populations similar to the population in which they are intended to be used. Considering the anthropometric differences among races and the effect of regional issues, such as climate and air quality, it is recommended that these standards be set and used regionally. The objective of this study was to measure the spirometric values in residents of the Mazandaran province in Iran, as well as to determine which standardized reference values most closely correlate with the values obtained and to devise predictive equations for the target population. Methods: This was a cross-sectional study of 1,499 volunteers, from whom demographic and anthropometric data were collected. After having been instructed in the correct procedure, each volunteer underwent spirometry. From each volunteer, we obtained three spirometry curves that met the acceptability criteria established by the American Thoracic Society. The test with the highest values of FEV1 and FVC was employed in the analysis. Results: We observed significant correlations between the measured values and the reference values, for both genders. The strongest correlations were with the European Respiratory Society reference values and with the 18-20 year age bracket. The predictive equations devised were based on the regression coefficients obtained and the demographic data collected. Conclusions: Our results show that the European Respiratory Society standard is the most appropriate standard for use in the population studied.

Keywords: Spirometry/statistics  numerical data; Climate effects; Reference values; Iran.

RESUMO

Objetivo: Um dos maiores problemas no uso da espirometria é a avaliação dos valores obtidos em comparação a valores de referência padronizados. Tais valores de referência devem ser determinados pelo estudo de populações semelhantes àquelas que se deseja utilizar. Considerando as diferenças antropométricas entre raças e o efeito de variáveis regionais, como clima e qualidade do ar, recomenda-se que esses padrões sejam definidos e utilizados regionalmente. O objetivo deste estudo foi medir os valores espirométricos em residentes da província de Mazandaran, no Irã; determinar quais valores de referência padronizados se correlacionam de forma mais próxima aos valores obtidos; e produzir equações preditivas para a população alvo. Métodos: Estudo transversal com 1.499 voluntários, dos quais dados demográficos e antropométricos foram coletados. Após terem sido instruídos quanto ao procedimento adequado, cada voluntário foi submetido à espirometria, sendo obtidas três curvas espirométricas de acordo com os critérios de aceitabilidade da American Thoracic Society. O teste com os maiores valores de VEF1 e CVF foram utilizados na análise. Resultados: Houve correlações significativas entre os valores medidos e os valores de referência em ambos os gêneros. As correlações mais fortes ocorreram com os valores de referência da European Respiratory Society e com a faixa etária de 18-20 anos. As equações preditivas produzidas basearam-se nos coeficientes de regressão obtidos e nos dados demográficos coletados. Conclusões: Nossos resultados mostram que os valores de referência da European Respiratory Society são os mais apropriados para a população estudada.

Palavras-chave: Espirometria/ estatística  dados numéricos; Efeitos do clima; Valores de referência; Irã (geográfico).

Introduction

Spirometry is one of the best methods of assessing lung function. It is also used in the diagnosis and follow-up of many pulmonary diseases, as well as providing evidence for use in court cases regarding legal compensation for pulmonary impairment.(1-3) One of the foundations of the use of spirometry is the comparison between the values obtained from an individual and those that are considered the reference (predicted) values. Reference values are based on various factors, including age, gender, height, weight, and race.(1-3) It has been suggested that numerous other factors, such as the type of climate, influence these values and should therefore also be considered.(2,3)

There are significant differences among reference values, depending on the formulas employed. To be generalizable, these values must be obtained by studying representative samples of the general population.(2) It has been recommended that these standards be set by governments.(1) It is currently accepted that referral centers should devise reference values by studying samples of healthy individuals within their region.(2) A study involving 41 male medical students between 23 and 26 years of age, conducted in 1994 in the city of Zanjan, Iran, showed that the mean FVC in the studied population was 90% of the predicted value.(4) Another study, involving 423 children and adolescents, was conducted in 2000 in the city of Isfahan, Iran(5) The authors showed that there is difference between the most widely used reference values and those obtained for the general population of Iran.(5) A study conducted in Spain by Castellsagué et al. in 1998 demonstrated differences among ethnicities in terms of lung volumes.(6) Gore et al. found that the most widely used reference values were applicable to Whites in Australia.(7) In a study conducted by our group in 2006 in the city of Sari, Iran, we found that the spirometric values (FVC, FEV1, and FEF25-75%) for healthy adults (≥ 18 years of age) were more similar to the European Respiratory Society (ERS) standard than to other standards.(8) Common mathematical formulas used for calculating standard spirometric indices are typically based on values obtained for small samples of healthy individuals in Europe or the United States, and those values are then generalized to the population of the world at large, disregarding the fact there are anthropometric differences among races and environmental differences among regions.

In Iran, there is a lack of regional and even national spirometric standards, as well as a lack of comprehensive studies on the subject. Therefore, the objective of this study was to determine whether the spirometric values in our population are similar to any of the standard reference values, as well as to use the values obtained in order to devise predictive equations specifically for use in the population of Iran.

Methods

This was a cross-sectional study of healthy adults (≥ 18 years of age) residing in the Mazandaran province of Iran. Volunteers were randomly recruited from urban and rural health centers in every city in the province. The study was approved by the Institutional Review Board and Research Ethics Committee of the Mazandaran University of Medical Sciences. All volunteers gave written informed consent.

Assuming a sample composed of both genders and distributed throughout four age brackets, we calculated the appropriate sample size by using information obtained from previous studies of FVC and FEV1, together with the following formula:

N = 7 = 0/S  = 0.05 d = ./1

where S is the standard deviation,  is the probability threshold, and d is the effect size. Using these calculations, we estimated the sample size required to be 1,500 individuals.

For the individuals selected, we collected demographic data (age and gender) using a questionnaire and anthropometric data (height and weight) through direct measurement with the appropriate tools (scale and stadiometer). Those data were entered into the computer program provided with the self-calibrating spirometer employed (Spirolab , Medical International Research, Rome, Italy). After each volunteer had been instructed in the correct procedure, the spirometry tests were conducted with the individual in a standing position. From each volunteer, we obtained three spirometry curves that met the acceptability criteria established by the American Thoracic Society. The test with the highest values of FVC and FEV1 was used in the analysis.(9,10)

We applied the following exclusion criteria: having upper or lower respiratory symptoms; having dyspnea; being a smoker or former smoker; being a passive smoker; having been exposed to occupational hazards such as dust and irritating gases; using beta blockers; having heart disease, musculoskeletal disorders, or any other disabling chest disease; being unable or unwilling to participate in the study; and producing spirometry curves that did not meet the acceptability criteria. It is notable that 39 individuals were excluded because they were uncooperative or produced unacceptable spirometry curves.

The values obtained for our sample were compared with the reference values established by the ERS, the Intermountain Thoracic Society (ITS), the European Community for Coal and Steel (ECCS), Knudson, and Morris.(2) Using the values obtained, we also devised predictive equations specifically for use in the population of Iran.

The statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA). Differences between means were determined with paired t-tests, correlations were identified with Pearson's correlation coefficient, and the prediction model was constructed by regression analysis.

Results

We evaluated 1,499 individuals (795 males and 704 females), all between 18 and 60 years of age. We found that the mean spirometric values were higher in males than in females (Table 1). As expected, spirometric values showed a strong positive correlation with height (Table 2). The correlation between spirometric values and weight was weaker but still significant for certain parameters. As was also expected, there was an inverse correlation between age and spirometric values.








Table 3 shows the mean values of FVC, FEV1, and FEF25-75% obtained in our sample. As can be seen in Table 4, the values obtained correlated significantly with all of the established reference values, regardless of gender (p < 0.001 for all). Among the male volunteers, the mean FVC did not differ significantly from the Knudson reference value (p = 0.193, T = −1.302); and the mean FEF25-75% did not differ significantly from the ERS reference value (p < 0.961, T = 0.049). Among the female volunteers, the mean FVC did not differ significantly from the ERS reference value (p = 0.783, T = 0.275); the mean FEV1 did not differ significantly from the ERS or Knudson reference values (p = 0.733, T = 0.341 and p = 0.169, T = 1.38, respectively); and the mean FEF25-75% did not differ significantly from the ITS or Morris reference values (p = 0.33, T = −2.138 and p = 0.431, T= −0.788, respectively). We also found that the values obtained for FVC correlated significantly with the established reference values across all age brackets (Table 5).











On the basis of the regression coefficient values obtained and the demographic data collected, we devised the following predictive equations:

For males
FVC = 5.6H × 10−2 − 2.5A × 10−2 − W × 10−3 − 4.067
FEV1 = 3.9H × 10−2 − 2.6A × 10−2 − 1.94
FEF25-75% = 1.6H ×10−2 - 3.2A × 10−2 + 7W × 10−3 + 2.306

For females
FVC = 3.7H × 10−2 − 2.5A × 10−2 + 3W × 10−3 − 2.034
FEV1 = 2.8H × 10−2 − 2.5A × 10−2 − 3W × 10−3 − 0.942
FEF25-75% = 1.6H × 10−2 − 3.5A ×10−2 − 6W × 10−3 + 1.774

where H is height (in cm), A is age (in years), and W is weight.

As can be seen in Table 5, the mean FVC was most similar to the ERS standard, for both genders. However, the mean FEV1 was most similar to the ERS standard in males and to the ITS standard in females. The mean FEF25-75% was most similar to the ERS standard in males and to the Knudson standard in females.

Discussion

In our sample, the mean spirometric indices were higher in males than in females. This can be attributed, in part, to the influence that height has on these parameters.

A study conducted in 1997 by Pan et al.(11) showed that, in the local population of Taiwan, the mean FVC and FEV1, adjusted for age and height, were lower than the standard reference values established for White populations. The authors found that age and height both had a significant influence on spirometric parameters. The results of the present study also show that spirometric indices decrease in parallel with increasing age. We obtained the highest values for the 18-20 year age bracket, a finding that differs slightly from those of an earlier study conducted by our group,(8) in which the highest values were obtained for the 20-30 year age bracket.

In a study conducted in England and involving 6,053 healthy individuals (16-75 years of age), FVC, FEV1, and the FEV1/FVC ratio were found to be considerably higher than the ERS reference values.(12) However, in the present study, as well as in our earlier study,(8) the mean FVC was lower than the ERS reference value. In addition, we found that the mean FEV1, although higher than the ERS and Knudson reference values, was lower than the ITS and Morris reference values. Furthermore, in our sample, the mean FEF25-75% was lower than the ERS reference value but higher than other standards. A multicenter study involving 12,900 subjects (20-44 years of age) in 14 European countries compared the measured FVC and FEV1 with the ERS reference values and found that the ERS reference values were noticeably lower than the overall mean.(13) Nevertheless, the results of the present study show that the ERS reference values are noticeably higher than the mean values obtained among residents of the Mazandaran province in Iran.

Duarte et al.(14) evaluated FVC and FEV1 in a sample composed of 643 White individuals in Brazil. The authors evaluated the values obtained in comparison with the current (2006) Brazilian standards, as well as in comparison with those established by Knudson and by the ECCS. They showed that the values obtained were most similar to the 2006 Brazilian standards, whereas they differed significantly from the Knudson and ECCS standards, which effectively invalidated the use of those standards in Brazil.(14) However, the values obtained in the present study did not differ significantly from the predicted values established by the ECCS. In another study conducted in Brazil in 2004,(15) the values of FEV1 and FVC were found to exceed those obtained 12 years prior (in 1992), a difference that could be attributable to technical factors.

In 2000, Golshan  Nematbakhsh conducted a study in the city of Isfahan.(16) The authors suggested that the lung volume reference values recommended for American and Europeans are appropriate for use in adults in Isfahan, despite the fact that estimated lung volumes were slightly higher in the last group. In an earlier study conducted in Brazil, spirometric values were obtained in 1,070 individuals.(17) The authors showed that the mean FVC obtained for females was 4% lower than the Knudson standard, leading to a higher rate of diagnosis of restrictive disorders in females, whereas there was no significant difference for males. They also found that mean FEV1 was higher than the Knudson standard for both genders, increasing the sensitivity of FEV1 for the diagnosis of obstructive lung disorders, although there was no significant difference in terms of the mean FEF25-75%.(17)

The results of the present study show that all of the parameters measured correlated significantly with all of the standards evaluated, regardless of gender (p < 0.001 for all). A study of 41 male students (23-26 years of age) at Zanjan University showed that the mean FVC in the studied population was 90% of the predicted value.(4) Sharifian et al.(18) evaluated 1,589 residents of the Kurdistan province in Iran and showed that the mean FVC obtained was lower than the reference value, whereas the mean FEV1 was comparable. In the present study, mean values were > 99% of the ERS reference values, > 93% of the Knudson reference values, and > 98% of the ITS reference values. The predictive equations we have devised make it clear that the values obtained for FVC were most similar to the ERS reference values, for both genders, whereas those obtained for FEV1 were most similar to the ERS reference values in males and to the ITS reference values in females. The mean FEF25-75% correlated most strongly with the ERS reference values in males and with the Knudson reference values in females.

On the basis of our results, taken together with those of previous studies, we can recommended the use of our predictive equations in all spirometry tests conducted in the region under study.


Acknowledgments

We would like to express our appreciation to Mr. Golikani, Industrial Health Engineer at the Sari Health Faculty, for his cooperation and efforts.


References


1. Roy T, Edward P. Pulmonary function testing in industry. In: Zenz C, editor. Occupational Medicine -- Principles and Practical Applications. 3rd ed. St. Louis: Mosby; 1994. p. 229-36.

2. Garay SM. Pulmonary function testing. In: Rom WN, Markowitz S. Environmental and Occupational Medicine. 4th ed. Philadelphia:
Lippincott-Raven; 2007. p. 200-36.

3. Balmes JR, Scannell CH. Occupational lung diseases. In: LaDou J, editor. Occupational Environmental Medicine. 2nd ed., Hightstown: McGraw Hill Professional; 1997. p. 307.

4. Mortazavi N. Comparison of spirometric index function with standards in 23-26 year old male medical students of Zanjan University of Medical Sciences. J Zanjan Univ Med Sci. 2009;17(75):20-7.

5. Golshan M, Nemat Bakhsh M, Masjedi M. Determination of spirometric indices in 423 healthy non-smoking children and youngster in Isfahan. J Kerman Univ Med Sci. 1999;6(3):28-32.

6. Castellsagué J, Burgos F, Sunyer J, Barberà JA, Roca J. Prediction equations for forced spirometry from European origin populations. Barcelona Collaborative Group on Reference Values for Pulmonary Function Testing and the Spanish Group of the European Community Respiratory Health Survey. Respir Med. 1998;92(3):401-7.

7. Gore CJ, Crockett AJ, Pederson DG, Booth ML, Bauman A, Owen N. Spirometric standards for healthy adult lifetime nonsmokers in Australia. Eur Respir J. 1995;8(5):773-82.

8. Alizade A, Etemadinezhad S, Mohammadpor R. Comparison of measured spirometric values in healthy individuals over 18 years of Sari. J Mazandaran Univ Med Sci. 2006;55:65-7.

9. Bellia V, Pistelli R, Catalano F, Antonelli-Incalzi R, Grassi V, Melillo G, et al. Quality control of spirometry in the elderly. The SA.R.A. study. SAlute Respiration nell'Anziano = Respiratory Health in the Elderly. Am J Respir Crit Care Med. 2000;161(4 Pt 1):1094-100.
10. Enright PL, Beck KC, Sherrill DL. Repeatability of spirometry in 18,000 adult patients. Am J Respir Crit Care Med. 2004;169(2):235-8.

11. Pan WH, Chen JY, Haung SL, Liou TL, Lee TK, Wang LY, et al. Reference spirometric values in healthy Chinese neversmokers in two townships of Taiwan. Chin J Physiol. 1997;40(3):165-74.

12. Falaschetti E, Laiho J, Primatesta P, Purdon S. Prediction equations for normal and low lung function from the Health Survey for England. Eur Respir J. 2004;23(3):456-63.

13. Roca J, Burgos F, Sunyer J, Saez M, Chinn S, Antó JM, et al. References values for forced spirometry. Group of the European Community Respiratory Health Survey. Eur Respir J. 1998;11(6):1354-62.

14. Duarte AA, Pereira CA, Rodrigues SC. Validation of new Brazilian predicted values for forced spirometry in caucasians and comparison with predicted values obtained using other reference equations. J Bras Pneumol. 2007;33(5):527-35.

15. Pereira CA, Sato T, Rodrigues SC. New reference values for forced spirometry in white adults in Brazil. J Bras Pneumol. 2007;33(4):397-406.

16. Golshan M, Nematbakhsh M. Prediction equations of ventilatory function in non-smoker adults in Isfahan, Iran. Iran J Med Sci. 2000;25(3-4):125-8.

17. Ladosky W, Andrade RT, Loureiro NG, Gandar JM, Botelho MM. Comparing reference spirometric values obtained from Knudson and Pereira equation adults [Article in Portuguese]. J Pneumologia. 2001;27(6):315-20.

18. Sharifian A, Sigary N, Rahimi A, Yazdanpanah K. Evaluation of normal pulmonary function test in people of Kurdistan Province. Sci J Kurdistan Univ Med Sci. 2007;12:15-20.




* Study carried out at the Mazandaran University of Medical Sciences, Sari, Iran.
Correspondence to: Siavash Etemadinezhad. Mazandaran University of Medical Sciences, Health Faculty and Health Research Center, School of Public Health, Km 18, Khazar Abad Road, Sari, Iran.
Tel. +98 151 354-3085. E-mail: dr.setemadi@yahoo.com
Financial support: This study received financial support from the Research Deputy of the Mazandaran University of Medical Sciences.
Submitted: 28 April 2011. Accepted, after review: 15 August 2011.
** A versão completa em português deste artigo está disponível em www.jornaldepneumologia.com.brOriginal



About the authors

Siavash Etemadinezhad
Assistant Professor. Department of Occupational Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Ahmad Alizadeh
Assistant Professor. Department of Occupational Medicine, Mazandaran University of Medical Sciences, Sari, Iran.