Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 2003 Dec;58(12):1020–1026. doi: 10.1136/thorax.58.12.1020

Predictors of mortality in α1-antitrypsin deficiency

P Dawkins 1, L Dowson 1, P Guest 1, R Stockley 1
PMCID: PMC1746543  PMID: 14645964

Abstract

Methods: Over a 5 year period, 256 patients with α1-antitrypsin deficiency (PiZ phenotype) were assessed, of whom 254 underwent lung function testing and 197 had thoracic CT scans. Lung function, CT scans, health status (St George's Respiratory Questionnaire, SGRQ), and other clinical data of survivors and non-survivors were compared and these parameters were applied to survival analyses.

Results: There were 22 deaths in this patient cohort, 10 of which were classified as "respiratory" deaths. Baseline lung function parameters (forced expiratory volume in 1 second (FEV1), carbon monoxide transfer coefficient (KCO)), and CT scores were significantly lower in the non-survivors than in the survivors. 170 of the 256 patients had complete data for entry into multiple regression analyses (Cox proportional hazards model). In the univariate analysis, upper zone expiratory scan had the best association with all cause (p = 0.001) and respiratory mortality (p<0.001), whereas FEV1 (p = 0.158 all cause, 0.015 respiratory) and KCO (p = 0.002 all cause, 0.012 respiratory) had poorer associations with mortality. Only age gave further independent predictive information regarding all cause or respiratory mortality when the CT scan was entered into the survival analyses.

Conclusions: CT scanning predicts respiratory and all cause mortality in α1-antitrypsin deficiency and appears to be superior to lung function parameters, especially FEV1.

Full Text

The Full Text of this article is available as a PDF (296.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anthonisen N. R., Connett J. E., Kiley J. P., Altose M. D., Bailey W. C., Buist A. S., Conway W. A., Jr, Enright P. L., Kanner R. E., O'Hara P. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. JAMA. 1994 Nov 16;272(19):1497–1505. [PubMed] [Google Scholar]
  2. Ashley F., Kannel W. B., Sorlie P. D., Masson R. Pulmonary function: relation to aging, cigarette habit, and mortality. Ann Intern Med. 1975 Jun;82(6):739–745. doi: 10.7326/0003-4819-82-6-739. [DOI] [PubMed] [Google Scholar]
  3. Burge P. S., Calverley P. M., Jones P. W., Spencer S., Anderson J. A., Maslen T. K. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ. 2000 May 13;320(7245):1297–1303. doi: 10.1136/bmj.320.7245.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cook D. G., Shaper A. G. Breathlessness, lung function and the risk of heart attack. Eur Heart J. 1988 Nov;9(11):1215–1222. doi: 10.1093/oxfordjournals.eurheartj.a062432. [DOI] [PubMed] [Google Scholar]
  5. Dirksen A., Dijkman J. H., Madsen F., Stoel B., Hutchison D. C., Ulrik C. S., Skovgaard L. T., Kok-Jensen A., Rudolphus A., Seersholm N. A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy. Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1468–1472. doi: 10.1164/ajrccm.160.5.9901055. [DOI] [PubMed] [Google Scholar]
  6. Domingo-Salvany Antònia, Lamarca Rosa, Ferrer Montserrat, Garcia-Aymerich Judith, Alonso Jordi, Félez Miquel, Khalaf Ahmad, Marrades Ramon M., Monsó Eduard, Serra-Batlles Joan. Health-related quality of life and mortality in male patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002 Sep 1;166(5):680–685. doi: 10.1164/rccm.2112043. [DOI] [PubMed] [Google Scholar]
  7. Dowson L. J., Guest P. J., Hill S. L., Holder R. L., Stockley R. A. High-resolution computed tomography scanning in alpha1-antitrypsin deficiency: relationship to lung function and health status. Eur Respir J. 2001 Jun;17(6):1097–1104. doi: 10.1183/09031936.01.00056501. [DOI] [PubMed] [Google Scholar]
  8. Dowson L. J., Newall C., Guest P. J., Hill S. L., Stockley R. A. Exercise capacity predicts health status in alpha(1)-antitrypsin deficiency. Am J Respir Crit Care Med. 2001 Mar;163(4):936–941. doi: 10.1164/ajrccm.163.4.2007048. [DOI] [PubMed] [Google Scholar]
  9. Ebi-Kryston K. L. Respiratory symptoms and pulmonary function as predictors of 10-year mortality from respiratory disease, cardiovascular disease, and all causes in the Whitehall Study. J Clin Epidemiol. 1988;41(3):251–260. doi: 10.1016/0895-4356(88)90129-1. [DOI] [PubMed] [Google Scholar]
  10. Fletcher C., Peto R. The natural history of chronic airflow obstruction. Br Med J. 1977 Jun 25;1(6077):1645–1648. doi: 10.1136/bmj.1.6077.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gevenois P. A., De Vuyst P., Sy M., Scillia P., Chaminade L., de Maertelaer V., Zanen J., Yernault J. C. Pulmonary emphysema: quantitative CT during expiration. Radiology. 1996 Jun;199(3):825–829. doi: 10.1148/radiology.199.3.8638012. [DOI] [PubMed] [Google Scholar]
  12. Gevenois P. A., De Vuyst P., de Maertelaer V., Zanen J., Jacobovitz D., Cosio M. G., Yernault J. C. Comparison of computed density and microscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med. 1996 Jul;154(1):187–192. doi: 10.1164/ajrccm.154.1.8680679. [DOI] [PubMed] [Google Scholar]
  13. Gevenois P. A., de Maertelaer V., De Vuyst P., Zanen J., Yernault J. C. Comparison of computed density and macroscopic morphometry in pulmonary emphysema. Am J Respir Crit Care Med. 1995 Aug;152(2):653–657. doi: 10.1164/ajrccm.152.2.7633722. [DOI] [PubMed] [Google Scholar]
  14. Gould G. A., MacNee W., McLean A., Warren P. M., Redpath A., Best J. J., Lamb D., Flenley D. C. CT measurements of lung density in life can quantitate distal airspace enlargement--an essential defining feature of human emphysema. Am Rev Respir Dis. 1988 Feb;137(2):380–392. doi: 10.1164/ajrccm/137.2.380. [DOI] [PubMed] [Google Scholar]
  15. Guerra Stefano, Sherrill Duane L., Bobadilla Arnel, Martinez Fernando D., Barbee Robert A. The relation of body mass index to asthma, chronic bronchitis, and emphysema. Chest. 2002 Oct;122(4):1256–1263. doi: 10.1378/chest.122.4.1256. [DOI] [PubMed] [Google Scholar]
  16. Hole D. J., Watt G. C., Davey-Smith G., Hart C. L., Gillis C. R., Hawthorne V. M. Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study. BMJ. 1996 Sep 21;313(7059):711–716. doi: 10.1136/bmj.313.7059.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ketelaars C. A., Schlösser M. A., Mostert R., Huyer Abu-Saad H., Halfens R. J., Wouters E. F. Determinants of health-related quality of life in patients with chronic obstructive pulmonary disease. Thorax. 1996 Jan;51(1):39–43. doi: 10.1136/thx.51.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kinsella M., Müller N. L., Abboud R. T., Morrison N. J., DyBuncio A. Quantitation of emphysema by computed tomography using a "density mask" program and correlation with pulmonary function tests. Chest. 1990 Feb;97(2):315–321. doi: 10.1378/chest.97.2.315. [DOI] [PubMed] [Google Scholar]
  19. Knudson R. J., Standen J. R., Kaltenborn W. T., Knudson D. E., Rehm K., Habib M. P., Newell J. D. Expiratory computed tomography for assessment of suspected pulmonary emphysema. Chest. 1991 Jun;99(6):1357–1366. doi: 10.1378/chest.99.6.1357. [DOI] [PubMed] [Google Scholar]
  20. Krzyzanowski M., Wysocki M. The relation of thirteen-year mortality to ventilatory impairment and other respiratory symptoms: the Cracow Study. Int J Epidemiol. 1986 Mar;15(1):56–64. doi: 10.1093/ije/15.1.56. [DOI] [PubMed] [Google Scholar]
  21. Landbo C., Prescott E., Lange P., Vestbo J., Almdal T. P. Prognostic value of nutritional status in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 Dec;160(6):1856–1861. doi: 10.1164/ajrccm.160.6.9902115. [DOI] [PubMed] [Google Scholar]
  22. Larsson C. Natural history and life expectancy in severe alpha1-antitrypsin deficiency, Pi Z. Acta Med Scand. 1978;204(5):345–351. doi: 10.1111/j.0954-6820.1978.tb08452.x. [DOI] [PubMed] [Google Scholar]
  23. Madani A., Keyzer C., Gevenois P. A. Quantitative computed tomography assessment of lung structure and function in pulmonary emphysema. Eur Respir J. 2001 Oct;18(4):720–730. doi: 10.1183/09031936.01.00255701. [DOI] [PubMed] [Google Scholar]
  24. Marquis Karine, Debigaré Richard, Lacasse Yves, LeBlanc Pierre, Jobin Jean, Carrier Guy, Maltais François. Midthigh muscle cross-sectional area is a better predictor of mortality than body mass index in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002 Sep 15;166(6):809–813. doi: 10.1164/rccm.2107031. [DOI] [PubMed] [Google Scholar]
  25. Miller R. R., Müller N. L., Vedal S., Morrison N. J., Staples C. A. Limitations of computed tomography in the assessment of emphysema. Am Rev Respir Dis. 1989 Apr;139(4):980–983. doi: 10.1164/ajrccm/139.4.980. [DOI] [PubMed] [Google Scholar]
  26. Müller N. L., Staples C. A., Miller R. R., Abboud R. T. "Density mask". An objective method to quantitate emphysema using computed tomography. Chest. 1988 Oct;94(4):782–787. doi: 10.1378/chest.94.4.782. [DOI] [PubMed] [Google Scholar]
  27. Peto R., Speizer F. E., Cochrane A. L., Moore F., Fletcher C. M., Tinker C. M., Higgins I. T., Gray R. G., Richards S. M., Gilliland J. The relevance in adults of air-flow obstruction, but not of mucus hypersecretion, to mortality from chronic lung disease. Results from 20 years of prospective observation. Am Rev Respir Dis. 1983 Sep;128(3):491–500. doi: 10.1164/arrd.1983.128.3.491. [DOI] [PubMed] [Google Scholar]
  28. Prescott E., Almdal T., Mikkelsen K. L., Tofteng C. L., Vestbo J., Lange P. Prognostic value of weight change in chronic obstructive pulmonary disease: results from the Copenhagen City Heart Study. Eur Respir J. 2002 Sep;20(3):539–544. doi: 10.1183/09031936.02.00532002. [DOI] [PubMed] [Google Scholar]
  29. Seersholm N. Body mass index and mortality in patients with severe alpha 1-antitrypsin deficiency. Respir Med. 1997 Feb;91(2):77–82. doi: 10.1016/s0954-6111(97)90071-8. [DOI] [PubMed] [Google Scholar]
  30. Seersholm N., Kok-Jensen A. Clinical features and prognosis of life time non-smokers with severe alpha 1-antitrypsin deficiency. Thorax. 1998 Apr;53(4):265–268. doi: 10.1136/thx.53.4.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Seersholm N., Kok-Jensen A. Survival in relation to lung function and smoking cessation in patients with severe hereditary alpha 1-antitrypsin deficiency. Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):369–373. doi: 10.1164/ajrccm.151.2.7842193. [DOI] [PubMed] [Google Scholar]
  32. Siafakas N. M., Vermeire P., Pride N. B., Paoletti P., Gibson J., Howard P., Yernault J. C., Decramer M., Higenbottam T., Postma D. S. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force. Eur Respir J. 1995 Aug;8(8):1398–1420. doi: 10.1183/09031936.95.08081398. [DOI] [PubMed] [Google Scholar]
  33. Smeeth L., Boulis M., Hubbard R., Fletcher A. E. A population based case-control study of cataract and inhaled corticosteroids. Br J Ophthalmol. 2003 Oct;87(10):1247–1251. doi: 10.1136/bjo.87.10.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tockman M. S., Anthonisen N. R., Wright E. C., Donithan M. G. Airways obstruction and the risk for lung cancer. Ann Intern Med. 1987 Apr;106(4):512–518. doi: 10.7326/0003-4819-106-4-512. [DOI] [PubMed] [Google Scholar]
  35. Tockman M. S., Comstock G. W. Respiratory risk factors and mortality: longitudinal studies in Washington County, Maryland. Am Rev Respir Dis. 1989 Sep;140(3 Pt 2):S56–S63. doi: 10.1164/ajrccm/140.3_Pt_2.S56. [DOI] [PubMed] [Google Scholar]
  36. Traver G. A., Cline M. G., Burrows B. Predictors of mortality in chronic obstructive pulmonary disease. A 15-year follow-up study. Am Rev Respir Dis. 1979 Jun;119(6):895–902. doi: 10.1164/arrd.1979.119.6.895. [DOI] [PubMed] [Google Scholar]
  37. Tsukino M., Nishimura K., Ikeda A., Koyama H., Mishima M., Izumi T. Physiologic factors that determine the health-related quality of life in patients with COPD. Chest. 1996 Oct;110(4):896–903. doi: 10.1378/chest.110.4.896. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES