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Published in: Respiratory Research 1/2014

Open Access 01-12-2014 | Research

Quantifying the real life risk profile of inhaled corticosteroids in COPD by record linkage analysis

Authors: Rob W Flynn, Thomas M MacDonald, Adrian Hapca, Isla S MacKenzie, Stuart Schembri

Published in: Respiratory Research | Issue 1/2014

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Abstract

Background

Inhaled corticosteroids (ICS), especially when prescribed in combination with long-acting β2 agonists have been shown to improve COPD outcomes. Although there is consistent evidence linking ICS with adverse effects such as pneumonia, the complete risk profile is unclear with conflicting evidence on any association between ICS and the incidence or worsening of existing diabetes, cataracts and fractures. We investigated this using record linkage in a Dundee COPD population.

Methods

A record linkage study linking COPD and diabetes datasets with prescription, hospitalisation and mortality data via a unique Community Health Index (CHI) number. A Cox regression model was used to determine the association between ICS use and new diabetes or worsening of existing diabetes and hospitalisations for pneumonia, fractures or cataracts after adjusting for potential confounders. A time dependent analysis of exposure comparing time on versus off ICS was used to take into account patients changing their exposure status during follow-up and to prevent immortal time bias.

Results

4305 subjects (3243 exposed to ICS, total of 17,229 person-years of exposure and 1062 non exposed, with a follow-up of 4,508 patient-years) were eligible for the study. There were 239 cases of new diabetes (DM) and 265 cases of worsening DM, 550 admissions for pneumonia, 288 hospitalisations for fracture and 505 cataract related admissions. The hazard ratio for the association between cumulative ICS and outcomes were 0.70 (0.43-1.12), 0.57 (0.24-1.37), 1.38 (1.09-1.74), 1.08 (0.73-1.59) and 1.42 (1.07-1.88) after multivariate analysis respectively.

Conclusion

The use of ICS in our cohort was not associated with new onset of diabetes, worsening of existing diabetes or fracture hospitalisation. There was however an association with increased cataracts and pneumonia hospitalisations.
Appendix
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Literature
1.
go back to reference Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, et al: Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012, 380: 2095-2128. 10.1016/S0140-6736(12)61728-0.PubMedCrossRef Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, et al: Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012, 380: 2095-2128. 10.1016/S0140-6736(12)61728-0.PubMedCrossRef
2.
go back to reference Chronic Obstructive Pulmonary Disease: National clinical guideline on management of adults with chronic obstructive pulmonary disease in primary and secondary care. NICE guideline 12. Thorax. 2004, 59 (I): 1-232. Chronic Obstructive Pulmonary Disease: National clinical guideline on management of adults with chronic obstructive pulmonary disease in primary and secondary care. NICE guideline 12. Thorax. 2004, 59 (I): 1-232.
3.
go back to reference Godtfredsen NS, Lam TH, Hansel TT, Leon ME, Gray N, Dresler C, Burns DM, Prescott E, Vestbo J: COPD-related morbidity and mortality after smoking cessation: status of the evidence. ERJ. 2008, 32: 844-853. 10.1183/09031936.00160007.CrossRef Godtfredsen NS, Lam TH, Hansel TT, Leon ME, Gray N, Dresler C, Burns DM, Prescott E, Vestbo J: COPD-related morbidity and mortality after smoking cessation: status of the evidence. ERJ. 2008, 32: 844-853. 10.1183/09031936.00160007.CrossRef
4.
go back to reference Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet. 1981, 1: 681-686. Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet. 1981, 1: 681-686.
5.
go back to reference Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J: Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007, 356: 775-789. 10.1056/NEJMoa063070.PubMedCrossRef Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J: Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007, 356: 775-789. 10.1056/NEJMoa063070.PubMedCrossRef
6.
go back to reference British National Formulary. 2014, BMJ Group and Pharmaceutical Press, London British National Formulary. 2014, BMJ Group and Pharmaceutical Press, London
7.
go back to reference Kew KM, Seniukovich A: Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014, 3: Kew KM, Seniukovich A: Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014, 3:
8.
go back to reference Garbe E, Suissa S, LeLorier J: Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA. 1998, 280: 539-543. 10.1001/jama.280.6.539.PubMedCrossRef Garbe E, Suissa S, LeLorier J: Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA. 1998, 280: 539-543. 10.1001/jama.280.6.539.PubMedCrossRef
9.
go back to reference Lipworth BJ: Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med. 1999, 159: 941-955. 10.1001/archinte.159.9.941.PubMedCrossRef Lipworth BJ: Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med. 1999, 159: 941-955. 10.1001/archinte.159.9.941.PubMedCrossRef
10.
go back to reference Kelly HW, Nelson HS: Potential adverse effects of the inhaled corticosteroids. J Allergy Clin Immunol. 2003, 112: 469-478. 10.1016/S0091-6749(03)01870-0.PubMedCrossRef Kelly HW, Nelson HS: Potential adverse effects of the inhaled corticosteroids. J Allergy Clin Immunol. 2003, 112: 469-478. 10.1016/S0091-6749(03)01870-0.PubMedCrossRef
11.
go back to reference Suissa S, Kezouh A, Ernst P: Inhaled corticosteroids and the Risks of Diabetes Onset and Progression. Am J Med. 2010, 123: 1001-1006. 10.1016/j.amjmed.2010.06.019.PubMedCrossRef Suissa S, Kezouh A, Ernst P: Inhaled corticosteroids and the Risks of Diabetes Onset and Progression. Am J Med. 2010, 123: 1001-1006. 10.1016/j.amjmed.2010.06.019.PubMedCrossRef
14.
go back to reference Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ: Effect of β blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ. 2011, 342: d2549-10.1136/bmj.d2549.PubMedPubMedCentralCrossRef Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ: Effect of β blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ. 2011, 342: d2549-10.1136/bmj.d2549.PubMedPubMedCentralCrossRef
15.
go back to reference Wei L, Parkinson J, MacDonald TM: The Tayside Medicines Monitoring unit (MEMO). Pharmacoepidemiology. Edited by: Strom BL. 2005, John Wiley and Sons, Chichester, 323-336. 4 Wei L, Parkinson J, MacDonald TM: The Tayside Medicines Monitoring unit (MEMO). Pharmacoepidemiology. Edited by: Strom BL. 2005, John Wiley and Sons, Chichester, 323-336. 4
16.
go back to reference Sheng X, Murphy MJ, MacDonald TM, Schembri S, Simpson W, Winter J, Winter JH, Wei L: Effect of statins on total cholesterol concentrations, cardiovascular morbidity, and all-cause mortality in chronic obstructive pulmonary disease: a population-based cohort study. Clin Ther. 2012, 34: 374-384. 10.1016/j.clinthera.2011.12.014.PubMedCrossRef Sheng X, Murphy MJ, MacDonald TM, Schembri S, Simpson W, Winter J, Winter JH, Wei L: Effect of statins on total cholesterol concentrations, cardiovascular morbidity, and all-cause mortality in chronic obstructive pulmonary disease: a population-based cohort study. Clin Ther. 2012, 34: 374-384. 10.1016/j.clinthera.2011.12.014.PubMedCrossRef
17.
go back to reference Morris AD, Boyle DI, MacAlpine R, Emslie-Smith A, Jung RT, Newton RW, MacDonald TM: The diabetes audit and research in Tayside Scotland (DARTS) study: electronic record linkage to create a diabetes register. DARTS/MEMO Collaboration. Br Med J. 1997, 315: 524-528. 10.1136/bmj.315.7107.524.CrossRef Morris AD, Boyle DI, MacAlpine R, Emslie-Smith A, Jung RT, Newton RW, MacDonald TM: The diabetes audit and research in Tayside Scotland (DARTS) study: electronic record linkage to create a diabetes register. DARTS/MEMO Collaboration. Br Med J. 1997, 315: 524-528. 10.1136/bmj.315.7107.524.CrossRef
18.
go back to reference International classification of diseases, related health problems. 1992, World Health Organization, Geneva International classification of diseases, related health problems. 1992, World Health Organization, Geneva
19.
go back to reference Tabular List of the Classification of Surgical Operations and Procedures Fourth Revision. 1990, Her Majesty's Stationery Office, London Tabular List of the Classification of Surgical Operations and Procedures Fourth Revision. 1990, Her Majesty's Stationery Office, London
20.
go back to reference Suissa S, Patenaude V, Lapi F, Ernst P: Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013, 68: 1029-1036. 10.1136/thoraxjnl-2012-202872.PubMedPubMedCentralCrossRef Suissa S, Patenaude V, Lapi F, Ernst P: Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013, 68: 1029-1036. 10.1136/thoraxjnl-2012-202872.PubMedPubMedCentralCrossRef
21.
go back to reference McMahon M, Gerich J, Rizza R: Effects of glucocorticoids on carbohydrate metabolism. Diabetes Metab Rev. 1988, 4: 17-30. 10.1002/dmr.5610040105.PubMedCrossRef McMahon M, Gerich J, Rizza R: Effects of glucocorticoids on carbohydrate metabolism. Diabetes Metab Rev. 1988, 4: 17-30. 10.1002/dmr.5610040105.PubMedCrossRef
22.
go back to reference Dendukuri N, Blais L, LeLorier J: Inhaled corticosteroids and the risk of diabetes among the elderly. Br J Clin Pharmacol. 2002, 54: 59-64. 10.1046/j.1365-2125.2002.01610.x.PubMedPubMedCentralCrossRef Dendukuri N, Blais L, LeLorier J: Inhaled corticosteroids and the risk of diabetes among the elderly. Br J Clin Pharmacol. 2002, 54: 59-64. 10.1046/j.1365-2125.2002.01610.x.PubMedPubMedCentralCrossRef
23.
go back to reference Blackburn D, Hux J, Mamdani M: Quantification of the risk of corticosteroid-induced diabetes mellitus among the elderly. J Gen Intern Med. 2002, 17: 717-720. 10.1046/j.1525-1497.2002.10649.x.PubMedPubMedCentralCrossRef Blackburn D, Hux J, Mamdani M: Quantification of the risk of corticosteroid-induced diabetes mellitus among the elderly. J Gen Intern Med. 2002, 17: 717-720. 10.1046/j.1525-1497.2002.10649.x.PubMedPubMedCentralCrossRef
24.
go back to reference Caughey GE, Preiss AK, Vitry AI, Gilbert AL, Roughead EE: Comorbid diabetes and COPD: impact of corticosteroid use on diabetes complications. Diabetes Care. 2013, 36: 3009-3014. 10.2337/dc12-2197.PubMedPubMedCentralCrossRef Caughey GE, Preiss AK, Vitry AI, Gilbert AL, Roughead EE: Comorbid diabetes and COPD: impact of corticosteroid use on diabetes complications. Diabetes Care. 2013, 36: 3009-3014. 10.2337/dc12-2197.PubMedPubMedCentralCrossRef
25.
go back to reference O'Byrne PM, Rennard S, Gerstein H, Radner F, Peterson S, Lindberg B, Carlsson LG, Sin DD: Risk of new onset diabetes mellitus in patients with asthma or COPD taking inhaled corticosteroids. Respir Med. 2012, 106: 1487-1493. 10.1016/j.rmed.2012.07.011.PubMedCrossRef O'Byrne PM, Rennard S, Gerstein H, Radner F, Peterson S, Lindberg B, Carlsson LG, Sin DD: Risk of new onset diabetes mellitus in patients with asthma or COPD taking inhaled corticosteroids. Respir Med. 2012, 106: 1487-1493. 10.1016/j.rmed.2012.07.011.PubMedCrossRef
26.
go back to reference Janson C, Larsson K, Lisspers KH, Ställberg B, Stratelis G, Goike H, Jörgensen L, Johansson G: Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting β2 agonist: observational matched cohort study (PATHOS). BMJ. 2013, 346: f3306-10.1136/bmj.f3306.PubMedPubMedCentralCrossRef Janson C, Larsson K, Lisspers KH, Ställberg B, Stratelis G, Goike H, Jörgensen L, Johansson G: Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting β2 agonist: observational matched cohort study (PATHOS). BMJ. 2013, 346: f3306-10.1136/bmj.f3306.PubMedPubMedCentralCrossRef
27.
go back to reference Ek A, Larsson K, Siljerud S, Palmberg L: Fluticasone and budesonide inhibit cytokine release in human lung epithelial cells and alveolar macrophages. Allergy. 1999, 54: 691-699. 10.1034/j.1398-9995.1999.00087.x.PubMedCrossRef Ek A, Larsson K, Siljerud S, Palmberg L: Fluticasone and budesonide inhibit cytokine release in human lung epithelial cells and alveolar macrophages. Allergy. 1999, 54: 691-699. 10.1034/j.1398-9995.1999.00087.x.PubMedCrossRef
28.
go back to reference Ferguson GT, Calverley PM, Anderson JA, Jenkins CR, Jones PW, Willits LR, Yates JC, Vestbo J, Celli B: Prevalence and progression of osteoporosis in patients with COPD: results from the TOwards a Revolution in COPD Health study. Chest. 2009, 136: 1456-1465. 10.1378/chest.08-3016.PubMedCrossRef Ferguson GT, Calverley PM, Anderson JA, Jenkins CR, Jones PW, Willits LR, Yates JC, Vestbo J, Celli B: Prevalence and progression of osteoporosis in patients with COPD: results from the TOwards a Revolution in COPD Health study. Chest. 2009, 136: 1456-1465. 10.1378/chest.08-3016.PubMedCrossRef
29.
go back to reference Yang IA, Clarke MS, Sim EH, Fong KM: Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012, 11: 7-CD002991 Yang IA, Clarke MS, Sim EH, Fong KM: Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012, 11: 7-CD002991
30.
go back to reference Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, Wachtel A, Martinez FJ, Barnhart F, Sanford L, Lettis S, Crim C, Calverley PM: Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials. Lancet Respir Med. 2013, 1: 210-223. 10.1016/S2213-2600(13)70040-7.PubMedCrossRef Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, Wachtel A, Martinez FJ, Barnhart F, Sanford L, Lettis S, Crim C, Calverley PM: Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials. Lancet Respir Med. 2013, 1: 210-223. 10.1016/S2213-2600(13)70040-7.PubMedCrossRef
31.
go back to reference Vestbo J, Sørensen T, Lange P, Brix A, Torre P, Viskum K: Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 1999, 353: 1819-1823. 10.1016/S0140-6736(98)10019-3.PubMedCrossRef Vestbo J, Sørensen T, Lange P, Brix A, Torre P, Viskum K: Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 1999, 353: 1819-1823. 10.1016/S0140-6736(98)10019-3.PubMedCrossRef
32.
go back to reference Jebrak G, Initiatives B: COPD routine management in France: are guidelines used in clinical practice?. Rev Mal Respir. 2010, 27: 11-18. 10.1016/j.rmr.2009.08.002.PubMedCrossRef Jebrak G, Initiatives B: COPD routine management in France: are guidelines used in clinical practice?. Rev Mal Respir. 2010, 27: 11-18. 10.1016/j.rmr.2009.08.002.PubMedCrossRef
Metadata
Title
Quantifying the real life risk profile of inhaled corticosteroids in COPD by record linkage analysis
Authors
Rob W Flynn
Thomas M MacDonald
Adrian Hapca
Isla S MacKenzie
Stuart Schembri
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2014
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-014-0141-y

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