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. 2004 May;59(5):396–400. doi: 10.1136/thx.2003.012856

Familial aggregation of FEF25–75 and FEF25–75/FVC in families with severe, early onset COPD

D DeMeo 1, V Carey 1, H Chapman 1, J Reilly 1, L Ginns 1, F Speizer 1, S Weiss 1, E Silverman 1
PMCID: PMC1747013  PMID: 15115866

Abstract

Background: The Boston Early-Onset COPD study showed that current or ex-smoking first degree relatives of severe early onset COPD probands have significantly lower forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) values than current or ex-smoking control subjects, which suggests the existence of genetic risk factors for the development of COPD in response to cigarette smoking. We hypothesised that first degree relatives of early onset COPD probands may also have lower values of spirometric parameters such as forced expiratory flow at the mid-portion of forced vital capacity (FEF25–75) and FEF25–75/FVC.

Methods: Using generalised estimating equations, FEF25–75 and FEF25–75/FVC were analysed in 333 first degree relatives of probands with severe early onset COPD and 83 population based controls; analyses were also performed on data stratified by smoking status. Narrow sense heritability estimates were calculated using a variance component approach.

Results: Significantly lower FEF25–75 and FEF25–75/FVC were observed in smoking (FEF25–75: ß –0.788 l/s (95% CI –1.118 to –0.457), FEF25–75/FVC: ß –20.4% (95% CI –29.3 to –11.6, p<0.0001 for both phenotypes) and non-smoking (FEF25–75: ß –0.357 l/s (95% CI –0.673 to –0.041, p = 0.0271), FEF25–75/FVC: ß –9.5% (95% CI –17.1 to –1.9, p = 0.0145)) first degree relatives of early onset COPD probands. Narrow sense heritability estimates for FEF25–75 (h2 = 0.38) and FEF25–75/FVC (h2 = 0.45) were similar to those for FEV1 and FEV1/FVC.

Conclusion: Lower values of FEF25–75 and FEF25–75/FVC in non-smoking first degree relatives of early onset COPD probands than in controls suggest a genetic susceptibility to develop obstructive lung disease, independent of smoking, which is magnified by exposure to deleterious environments as suggested by the further decrements in FEF25–75 and FEF25–75/FVC seen in smoking first degree relatives. FEF25–75 and FEF25–75/FVC have high heritability and are important intermediate phenotypes for inclusion in genetic epidemiological studies of COPD.

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Selected References

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  1. Almasy L., Blangero J. Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet. 1998 May;62(5):1198–1211. doi: 10.1086/301844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brooks L. J., Byard P. J., Helms R. C., Fouke J. M., Strohl K. P. Relationship between lung volume and tracheal area as assessed by acoustic reflection. J Appl Physiol (1985) 1988 Mar;64(3):1050–1054. doi: 10.1152/jappl.1988.64.3.1050. [DOI] [PubMed] [Google Scholar]
  3. Chen Y., Dosman J. A., Rennie D. C., Lockinger L. A. Major genetic effects on airway-parenchymal dysanapsis of the lung: the Humboldt family study. Genet Epidemiol. 1999;16(1):95–110. doi: 10.1002/(SICI)1098-2272(1999)16:1<95::AID-GEPI8>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  4. Cohen B. H., Ball W. C., Jr, Bias W. B., Brashears S., Chase G. A., Diamond E. L., Hsu S. H., Kreiss P., Levy D. A., Menkes H. A. A genetic-epidemiologic study of chronic obstructive pulmonary disease. I. Study design and preliminary observations. Johns Hopkins Med J. 1975 Sep;137(3):95–104. [PubMed] [Google Scholar]
  5. Cohen B. H., Ball W. C., Jr, Brashears S., Diamond E. L., Kreiss P., Levy D. A., Menkes H. A., Permutt S., Tockman M. S. Risk factors in chronic obstructive pulmonary disease (COPD). Am J Epidemiol. 1977 Mar;105(3):223–232. doi: 10.1093/oxfordjournals.aje.a112378. [DOI] [PubMed] [Google Scholar]
  6. Cosio M., Ghezzo H., Hogg J. C., Corbin R., Loveland M., Dosman J., Macklem P. T. The relations between structural changes in small airways and pulmonary-function tests. N Engl J Med. 1978 Jun 8;298(23):1277–1281. doi: 10.1056/NEJM197806082982303. [DOI] [PubMed] [Google Scholar]
  7. Dockery D. W., Ware J. H., Ferris B. G., Jr, Glicksberg D. S., Fay M. E., Spiro A., 3rd, Speizer F. E. Distribution of forced expiratory volume in one second and forced vital capacity in healthy, white, adult never-smokers in six U.S. cities. Am Rev Respir Dis. 1985 Apr;131(4):511–520. doi: 10.1164/arrd.1985.131.4.511. [DOI] [PubMed] [Google Scholar]
  8. Hankins D., Drage C., Zamel N., Kronenberg R. Pulmonary function in identical twins raised apart. Am Rev Respir Dis. 1982 Jan;125(1):119–121. doi: 10.1164/arrd.1982.125.3P2.119. [DOI] [PubMed] [Google Scholar]
  9. Hankinson J. L., Odencrantz J. R., Fedan K. B. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179–187. doi: 10.1164/ajrccm.159.1.9712108. [DOI] [PubMed] [Google Scholar]
  10. Kueppers F., Miller R. D., Gordon H., Hepper N. G., Offord K. Familial prevalence of chronic obstructive pulmonary disease in a matched pair study. Am J Med. 1977 Sep;63(3):336–342. doi: 10.1016/0002-9343(77)90270-4. [DOI] [PubMed] [Google Scholar]
  11. Larson R. K., Barman M. L., Kueppers F., Fudenberg H. H. Genetic and environmental determinants of chronic obstructive pulmonary disease. Ann Intern Med. 1970 May;72(5):627–632. doi: 10.7326/0003-4819-72-5-627. [DOI] [PubMed] [Google Scholar]
  12. Lewitter F. I., Tager I. B., McGue M., Tishler P. V., Speizer F. E. Genetic and environmental determinants of level of pulmonary function. Am J Epidemiol. 1984 Oct;120(4):518–530. doi: 10.1093/oxfordjournals.aje.a113912. [DOI] [PubMed] [Google Scholar]
  13. Litonjua A. A., Sparrow D., Weiss S. T. The FEF25-75/FVC ratio is associated with methacholine airway responsiveness. The normative aging study. Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1574–1579. doi: 10.1164/ajrccm.159.5.9803063. [DOI] [PubMed] [Google Scholar]
  14. McCloskey S. C., Patel B. D., Hinchliffe S. J., Reid E. D., Wareham N. J., Lomas D. A. Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airflow obstruction. Am J Respir Crit Care Med. 2001 Oct 15;164(8 Pt 1):1419–1424. doi: 10.1164/ajrccm.164.8.2105002. [DOI] [PubMed] [Google Scholar]
  15. Mead J. Dysanapsis in normal lungs assessed by the relationship between maximal flow, static recoil, and vital capacity. Am Rev Respir Dis. 1980 Feb;121(2):339–342. doi: 10.1164/arrd.1980.121.2.339. [DOI] [PubMed] [Google Scholar]
  16. Nishimura M., Kusaka T., Kobayashi S., Yamamoto M., Akiyama Y., Kawakami Y. [Analysis of dysanapsis in healthy twins and sons of patients with chronic obstructive lung disease]. Nihon Kyobu Shikkan Gakkai Zasshi. 1991 Jan;29(1):40–45. [PubMed] [Google Scholar]
  17. Petty T. L., Silvers G. W., Stanford R. E. Functional correlations with mild and moderate emphysema in excised human lungs. Am Rev Respir Dis. 1981 Dec;124(6):700–704. doi: 10.1164/arrd.1981.124.6.700. [DOI] [PubMed] [Google Scholar]
  18. Petty T. L., Silvers G. W., Stanford R. E. Small airway disease is associated with elastic recoil changes in excised human lungs. Am Rev Respir Dis. 1984 Jul;130(1):42–45. doi: 10.1164/arrd.1984.130.1.42. [DOI] [PubMed] [Google Scholar]
  19. Petty T. L., Silvers G. W., Stanford R. E. The morphology and morphometry of small airways disease (relevance to chronic obstructive pulmonary disease). Trans Am Clin Climatol Assoc. 1983;94:130–140. [PMC free article] [PubMed] [Google Scholar]
  20. Redline S., Tishler P. V., Rosner B., Lewitter F. I., Vandenburgh M., Weiss S. T., Speizer F. E. Genotypic and phenotypic similarities in pulmonary function among family members of adult monozygotic and dizygotic twins. Am J Epidemiol. 1989 Apr;129(4):827–836. doi: 10.1093/oxfordjournals.aje.a115197. [DOI] [PubMed] [Google Scholar]
  21. Silverman E. K., Chapman H. A., Drazen J. M., Weiss S. T., Rosner B., Campbell E. J., O'DONNELL W. J., Reilly J. J., Ginns L., Mentzer S. Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease. Risk to relatives for airflow obstruction and chronic bronchitis. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1770–1778. doi: 10.1164/ajrccm.157.6.9706014. [DOI] [PubMed] [Google Scholar]
  22. Silverman E. K., Weiss S. T., Drazen J. M., Chapman H. A., Carey V., Campbell E. J., Denish P., Silverman R. A., Celedon J. C., Reilly J. J. Gender-related differences in severe, early-onset chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000 Dec;162(6):2152–2158. doi: 10.1164/ajrccm.162.6.2003112. [DOI] [PubMed] [Google Scholar]
  23. Tager I. B., Rosner B., Tishler P. V., Speizer F. E., Kass E. H. Household aggregation of pulmonary function and chronic bronchitis. Am Rev Respir Dis. 1976 Sep;114(3):485–492. doi: 10.1164/arrd.1976.114.3.485. [DOI] [PubMed] [Google Scholar]
  24. Tager I. B., Weiss S. T., Muñoz A., Welty C., Speizer F. E. Determinants of response to eucapneic hyperventilation with cold air in a population-based study. Am Rev Respir Dis. 1986 Sep;134(3):502–508. doi: 10.1164/arrd.1986.134.3.502. [DOI] [PubMed] [Google Scholar]
  25. Webster P. M., Lorimer E. G., Man S. F., Woolf C. R., Zamel N. Pulmonary function in identical twins: comparison of nonsmokers and smokers. Am Rev Respir Dis. 1979 Feb;119(2):223–228. doi: 10.1164/arrd.1979.119.2.223. [DOI] [PubMed] [Google Scholar]

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