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. 2003 Aug;58(8):654–658. doi: 10.1136/thorax.58.8.654

Prednisolone response in patients with chronic obstructive pulmonary disease: results from the ISOLDE study

P Burge 1, P Calverley 1, P Jones 1, S Spencer 1, J Anderson 1
PMCID: PMC1746769  PMID: 12885977

Abstract

Background: A trial of corticosteroids has been recommended for all patients with chronic obstructive pulmonary disease (COPD), with the subsequent "response" determining the treatment selected. This approach assumes that patients can be reliably divided into responder and non-responder groups. We have assessed whether such a separation is statistically valid, which factors influence the change in forced expiratory volume in 1 second (FEV1) after prednisolone, and whether the prednisolone response predicts 3 year changes in FEV1, health status, or number of exacerbations during placebo or fluticasone propionate treatment.

Methods: Oral prednisolone 0.6 mg/kg was given for 14 days to 524 patients with COPD before randomised treatment for 3 years with fluticasone propionate or placebo. Factors relating to change in FEV1 after prednisolone were investigated using multiple regression. The response to prednisolone was entered into separate mixed effects models of decline in FEV1 and health status during the 3 years of the study.

Results: The post-bronchodilator FEV1 increased by a mean 60 ml (CI 46 to 74) after prednisolone with a wide unimodal distribution. Current smoking was the factor most strongly associated with the change in FEV1 after prednisolone, with an increase of 35 ml in current smokers and 74 ml in confirmed ex-smokers (p<0.001). There was no relationship between the change in FEV1 after prednisolone and the response to inhaled bronchodilators, baseline FEV1, atopic status, age, or sex. The response to prednisolone, however expressed, was unrelated to the subsequent change in FEV1 over the following 3 years on either placebo or fluticasone propionate. Regression to the mean effects explained much of the apparent prednisolone response. The significant effect of treatment on decline in health status was not predicted by the prednisolone response.

Conclusion: Patients with COPD cannot be separated into discrete groups of corticosteroid responders and non-responders. Current smoking reduces the FEV1 response to prednisolone. Prednisolone testing is an unreliable predictor of the benefit from inhaled fluticasone propionate in individual patients.

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Selected References

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

  1. 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]
  2. Callahan C. M., Dittus R. S., Katz B. P. Oral corticosteroid therapy for patients with stable chronic obstructive pulmonary disease. A meta-analysis. Ann Intern Med. 1991 Feb 1;114(3):216–223. doi: 10.7326/0003-4819-114-3-216. [DOI] [PubMed] [Google Scholar]
  3. Jones P. W., Quirk F. H., Baveystock C. M., Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis. 1992 Jun;145(6):1321–1327. doi: 10.1164/ajrccm/145.6.1321. [DOI] [PubMed] [Google Scholar]
  4. Lam W. K., So S. Y., Yu D. Y. Response to oral corticosteroids in chronic airflow obstruction. Br J Dis Chest. 1983 Apr;77(2):189–198. doi: 10.1016/0007-0971(83)90027-x. [DOI] [PubMed] [Google Scholar]
  5. Pedersen B., Dahl R., Karlström R., Peterson C. G., Venge P. Eosinophil and neutrophil activity in asthma in a one-year trial with inhaled budesonide. The impact of smoking. Am J Respir Crit Care Med. 1996 May;153(5):1519–1529. doi: 10.1164/ajrccm.153.5.8630596. [DOI] [PubMed] [Google Scholar]
  6. Prescott E., Bjerg A. M., Andersen P. K., Lange P., Vestbo J. Gender difference in smoking effects on lung function and risk of hospitalization for COPD: results from a Danish longitudinal population study. Eur Respir J. 1997 Apr;10(4):822–827. [PubMed] [Google Scholar]
  7. 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]
  8. Sunyer J., Antó J. M., Kogevinas M., Barceló M. A., Soriano J. B., Tobías A., Muniozguren N., Martínez-Moratalla J., Payo F., Maldonado J. A. Risk factors for asthma in young adults. Spanish Group of the European Community Respiratory Health Survey. Eur Respir J. 1997 Nov;10(11):2490–2494. doi: 10.1183/09031936.97.10112490. [DOI] [PubMed] [Google Scholar]
  9. Weir D. C., Gove R. I., Robertson A. S., Burge P. S. Corticosteroid trials in non-asthmatic chronic airflow obstruction: a comparison of oral prednisolone and inhaled beclomethasone dipropionate. Thorax. 1990 Feb;45(2):112–117. doi: 10.1136/thx.45.2.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Weir D. C., Gove R. I., Robertson A. S., Burge P. S. Response to corticosteroids in chronic airflow obstruction: relationship to emphysema and airways collapse. Eur Respir J. 1991 Nov;4(10):1185–1190. [PubMed] [Google Scholar]

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