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Published in: Allergy, Asthma & Clinical Immunology 1/2014

Open Access 01-12-2014 | Research

Thiazolidinediones and the risk of asthma exacerbation among patients with diabetes: a cohort study

Authors: Seppo T Rinne, Laura C Feemster, Bridget F Collins, David H Au, Mark Perkins, Christopher L Bryson, Thomas G O’Riordan, Chuan-Fen Liu

Published in: Allergy, Asthma & Clinical Immunology | Issue 1/2014

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Abstract

Background

Thiazolidinediones are oral diabetes medications that selectively activate peroxisome proliferator-activated receptor gamma and have potent anti-inflammatory properties. While a few studies have found improvements in pulmonary function with exposure to thiazolidinediones, there are no studies of their impact on asthma exacerbations. Our objective was to assess whether exposure to thiazolidinediones was associated with a decreased risk of asthma exacerbation.

Methods

We performed a cohort study of diabetic Veterans who had a diagnosis of asthma and were taking oral diabetes medications during the period of 10/1/2005 – 9/30/2006. The risk of asthma exacerbations and oral steroid use during 10/1/2006 – 9/30/2007 was compared between patients who were prescribed thiazolidinediones and patients who were on alternative oral diabetes medications. Multivariable logistic regression and negative binomial regression analyses were used to characterize this risk. A sensitivity analysis was performed, restricting our evaluation to patients who were adherent to diabetes therapy.

Results

We identified 2,178 patients who were on thiazolidinediones and 10,700 who were not. Exposure to thiazolidinediones was associated with significant reductions in the risk of asthma exacerbation (OR = 0.79, 95% CI, 0.62 – 0.99) and oral steroid prescription (OR = 0.73, 95% CI 0.63 – 0.84). Among patients who were adherent to diabetes medications, there were more substantial reductions in the risks for asthma exacerbation (OR = 0.64, 95% CI 0.47 – 0.85) and oral steroid prescription (OR = 0.68, 95% CI 0.57 – 0.81).

Conclusions

Thiazolidinediones may provide a novel anti-inflammatory approach to asthma management by preventing exacerbations and decreasing the use of oral steroids.
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Literature
1.
go back to reference Barnett SB, Nurmagambetov TA: Costs of asthma in the United States: 2002–2007. J Allergy Clin Immunol. 2011, 127 (1): 145-152.CrossRefPubMed Barnett SB, Nurmagambetov TA: Costs of asthma in the United States: 2002–2007. J Allergy Clin Immunol. 2011, 127 (1): 145-152.CrossRefPubMed
3.
go back to reference Expert Panel Report 3 (EPR-3): Guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol. 2007, 120 (5 Suppl): S94-S138. Expert Panel Report 3 (EPR-3): Guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol. 2007, 120 (5 Suppl): S94-S138.
4.
go back to reference Gamble J, Stevenson M, McClean E, Heaney LG: The prevalence of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2009, 180 (9): 817-822.CrossRefPubMed Gamble J, Stevenson M, McClean E, Heaney LG: The prevalence of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2009, 180 (9): 817-822.CrossRefPubMed
5.
go back to reference Chung KF, Godard P, Adelroth E, Ayres J, Barnes N, Barnes P, Bel E, Burney P, Chanez P, Connett G, Corrigan C, de Blic J, Fabbri L, Holgate ST, Ind P, Joos G, Kerstjens H, Leuenberger P, Lofdahl CG, McKenzie S, Magnussen H, Postma D, Saetta M, Salmeron S, Sterk P: Difficult/therapy-resistant asthma: the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies: ERS Task Force on Difficult/Therapy-Resistant Asthma: European Respiratory Society. Eur Respir J. 1999, 13 (5): 1198-1208.PubMed Chung KF, Godard P, Adelroth E, Ayres J, Barnes N, Barnes P, Bel E, Burney P, Chanez P, Connett G, Corrigan C, de Blic J, Fabbri L, Holgate ST, Ind P, Joos G, Kerstjens H, Leuenberger P, Lofdahl CG, McKenzie S, Magnussen H, Postma D, Saetta M, Salmeron S, Sterk P: Difficult/therapy-resistant asthma: the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies: ERS Task Force on Difficult/Therapy-Resistant Asthma: European Respiratory Society. Eur Respir J. 1999, 13 (5): 1198-1208.PubMed
6.
7.
go back to reference Spiegelman BM: PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998, 47 (4): 507-514.CrossRefPubMed Spiegelman BM: PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998, 47 (4): 507-514.CrossRefPubMed
8.
go back to reference Dubuquoy L, Dharancy S, Nutten S, Pettersson S, Auwerx J, Desreumaux P: Role of peroxisome proliferator-activated receptor gamma and retinoid X receptor heterodimer in hepatogastroenterological diseases. Lancet. 2002, 360 (9343): 1410-1418.CrossRefPubMed Dubuquoy L, Dharancy S, Nutten S, Pettersson S, Auwerx J, Desreumaux P: Role of peroxisome proliferator-activated receptor gamma and retinoid X receptor heterodimer in hepatogastroenterological diseases. Lancet. 2002, 360 (9343): 1410-1418.CrossRefPubMed
9.
go back to reference Spears M, McSharry C, Thomson NC: Peroxisome proliferator-activated receptor-gamma agonists as potential anti-inflammatory agents in asthma and chronic obstructive pulmonary disease. Clin Exp Allergy. 2006, 36 (12): 1494-1504.CrossRefPubMed Spears M, McSharry C, Thomson NC: Peroxisome proliferator-activated receptor-gamma agonists as potential anti-inflammatory agents in asthma and chronic obstructive pulmonary disease. Clin Exp Allergy. 2006, 36 (12): 1494-1504.CrossRefPubMed
10.
go back to reference Hammad H, de Heer HJ, Soullie T, Angeli V, Trottein F, Hoogsteden HC, Lambrecht BN: Activation of peroxisome proliferator-activated receptor-gamma in dendritic cells inhibits the development of eosinophilic airway inflammation in a mouse model of asthma. Am J Pathol. 2004, 164 (1): 263-271.PubMedCentralCrossRefPubMed Hammad H, de Heer HJ, Soullie T, Angeli V, Trottein F, Hoogsteden HC, Lambrecht BN: Activation of peroxisome proliferator-activated receptor-gamma in dendritic cells inhibits the development of eosinophilic airway inflammation in a mouse model of asthma. Am J Pathol. 2004, 164 (1): 263-271.PubMedCentralCrossRefPubMed
11.
go back to reference Lee KS, Park SJ, Hwang PH, Yi HK, Song CH, Chai OH, Kim JS, Lee MK, Lee YC: PPAR-gamma modulates allergic inflammation through up-regulation of PTEN. FASEB J. 2005, 19 (8): 1033-1035.PubMed Lee KS, Park SJ, Hwang PH, Yi HK, Song CH, Chai OH, Kim JS, Lee MK, Lee YC: PPAR-gamma modulates allergic inflammation through up-regulation of PTEN. FASEB J. 2005, 19 (8): 1033-1035.PubMed
12.
go back to reference Mueller C, Weaver V, Vanden Heuvel JP, August A, Cantorna MT: Peroxisome proliferator-activated receptor gamma ligands attenuate immunological symptoms of experimental allergic asthma. Arch Biochem Biophys. 2003, 418 (2): 186-196.CrossRefPubMed Mueller C, Weaver V, Vanden Heuvel JP, August A, Cantorna MT: Peroxisome proliferator-activated receptor gamma ligands attenuate immunological symptoms of experimental allergic asthma. Arch Biochem Biophys. 2003, 418 (2): 186-196.CrossRefPubMed
13.
go back to reference Narala VR, Ranga R, Smith MR, Berlin AA, Standiford TJ, Lukacs NW, Reddy RC: Pioglitazone is as effective as dexamethasone in a cockroach allergen-induced murine model of asthma. Respir Res. 2007, 8: 90-PubMedCentralCrossRefPubMed Narala VR, Ranga R, Smith MR, Berlin AA, Standiford TJ, Lukacs NW, Reddy RC: Pioglitazone is as effective as dexamethasone in a cockroach allergen-induced murine model of asthma. Respir Res. 2007, 8: 90-PubMedCentralCrossRefPubMed
14.
go back to reference Rhee CK, Lee SY, Kang JY, Kim SJ, Kwon SS, Kim YK, Park SH: Effect of peroxisome proliferator-activated receptor-gamma on airway smooth muscle thickening in a murine model of chronic asthma. Int Arch Allergy Immunol. 2009, 148 (4): 289-296.CrossRefPubMed Rhee CK, Lee SY, Kang JY, Kim SJ, Kwon SS, Kim YK, Park SH: Effect of peroxisome proliferator-activated receptor-gamma on airway smooth muscle thickening in a murine model of chronic asthma. Int Arch Allergy Immunol. 2009, 148 (4): 289-296.CrossRefPubMed
15.
go back to reference Trifilieff A, Bench A, Hanley M, Bayley D, Campbell E, Whittaker P: PPAR-alpha and -gamma but not -delta agonists inhibit airway inflammation in a murine model of asthma: in vitro evidence for an NF-kappaB-independent effect. Br J Pharmacol. 2003, 139 (1): 163-171.PubMedCentralCrossRefPubMed Trifilieff A, Bench A, Hanley M, Bayley D, Campbell E, Whittaker P: PPAR-alpha and -gamma but not -delta agonists inhibit airway inflammation in a murine model of asthma: in vitro evidence for an NF-kappaB-independent effect. Br J Pharmacol. 2003, 139 (1): 163-171.PubMedCentralCrossRefPubMed
16.
go back to reference Park SJ, Lee KS, Kim SR, Min KH, Choe YH, Moon H, Chae HJ, Yoo WH, Lee YC: Peroxisome proliferator-activated receptor gamma agonist down-regulates IL-17 expression in a murine model of allergic airway inflammation. J Immunol. 2009, 183 (5): 3259-3267.CrossRefPubMed Park SJ, Lee KS, Kim SR, Min KH, Choe YH, Moon H, Chae HJ, Yoo WH, Lee YC: Peroxisome proliferator-activated receptor gamma agonist down-regulates IL-17 expression in a murine model of allergic airway inflammation. J Immunol. 2009, 183 (5): 3259-3267.CrossRefPubMed
17.
go back to reference Seidel P, Alkhouri H, Lalor DJ, Burgess JK, Armour CL, Hughes JM: Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies. Respir Res. 2012, 13: 90-PubMedCentralCrossRefPubMed Seidel P, Alkhouri H, Lalor DJ, Burgess JK, Armour CL, Hughes JM: Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies. Respir Res. 2012, 13: 90-PubMedCentralCrossRefPubMed
18.
go back to reference Woerly G, Honda K, Loyens M, Papin JP, Auwerx J, Staels B, Capron M, Dombrowicz D: Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation. J Exp Med. 2003, 198 (3): 411-421.PubMedCentralCrossRefPubMed Woerly G, Honda K, Loyens M, Papin JP, Auwerx J, Staels B, Capron M, Dombrowicz D: Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation. J Exp Med. 2003, 198 (3): 411-421.PubMedCentralCrossRefPubMed
19.
go back to reference Richards DB, Bareille P, Lindo EL, Quinn D, Farrow SN: Treatment with a peroxisomal proliferator activated receptor gamma agonist has a modest effect in the allergen challenge model in asthma: a randomised controlled trial. Respir Med. 2010, 104 (5): 668-674.CrossRefPubMed Richards DB, Bareille P, Lindo EL, Quinn D, Farrow SN: Treatment with a peroxisomal proliferator activated receptor gamma agonist has a modest effect in the allergen challenge model in asthma: a randomised controlled trial. Respir Med. 2010, 104 (5): 668-674.CrossRefPubMed
20.
go back to reference Sandhu MS, Dimov V, Sandhu AK, Walters RW, Wichman T, Casale T: The use of the peroxisome proliferator-activated receptors gamma agonist rosiglitazone to treat airway hyperreactivity. Ann Allergy Asthma Immunol. 2012, 109 (1): 75-77.CrossRefPubMed Sandhu MS, Dimov V, Sandhu AK, Walters RW, Wichman T, Casale T: The use of the peroxisome proliferator-activated receptors gamma agonist rosiglitazone to treat airway hyperreactivity. Ann Allergy Asthma Immunol. 2012, 109 (1): 75-77.CrossRefPubMed
21.
go back to reference Spears M, Donnelly I, Jolly L, Brannigan M, Ito K, McSharry C, Lafferty J, Chaudhuri R, Braganza G, Bareille P, Sweeney L, Adcock IM, Barnes PJ, Wood S, Thomson NC: Bronchodilatory effect of the PPAR-gamma agonist rosiglitazone in smokers with asthma. Clin Pharmacol Ther. 2009, 86 (1): 49-53.CrossRefPubMed Spears M, Donnelly I, Jolly L, Brannigan M, Ito K, McSharry C, Lafferty J, Chaudhuri R, Braganza G, Bareille P, Sweeney L, Adcock IM, Barnes PJ, Wood S, Thomson NC: Bronchodilatory effect of the PPAR-gamma agonist rosiglitazone in smokers with asthma. Clin Pharmacol Ther. 2009, 86 (1): 49-53.CrossRefPubMed
22.
go back to reference Joish VN, Malone DC, Wendel C, Draugalis JR, Mohler MJ: Development and validation of a diabetes mellitus severity index: a risk-adjustment tool for predicting health care resource use and costs. Pharmacotherapy. 2005, 25 (5): 676-684.CrossRefPubMed Joish VN, Malone DC, Wendel C, Draugalis JR, Mohler MJ: Development and validation of a diabetes mellitus severity index: a risk-adjustment tool for predicting health care resource use and costs. Pharmacotherapy. 2005, 25 (5): 676-684.CrossRefPubMed
23.
go back to reference Ash AS, Ellis RP, Pope GC, Ayanian JZ, Bates DW, Burstin H, Iezzoni LI, MacKay E, Yu W: Using diagnoses to describe populations and predict costs. Health Care Financ Rev. 2000, 21 (3): 7-28.PubMedCentralPubMed Ash AS, Ellis RP, Pope GC, Ayanian JZ, Bates DW, Burstin H, Iezzoni LI, MacKay E, Yu W: Using diagnoses to describe populations and predict costs. Health Care Financ Rev. 2000, 21 (3): 7-28.PubMedCentralPubMed
24.
25.
go back to reference StataCorp: Stata Statistical Software: Release 11.2. College Station. 2012, TX: StataCorp LP StataCorp: Stata Statistical Software: Release 11.2. College Station. 2012, TX: StataCorp LP
26.
go back to reference Bryson CL, Au DH, Young B, McDonell MB, Fihn SD: A refill adherence algorithm for multiple short intervals to estimate refill compliance (ReComp). Med Care. 2007, 45 (6): 497-504.CrossRefPubMed Bryson CL, Au DH, Young B, McDonell MB, Fihn SD: A refill adherence algorithm for multiple short intervals to estimate refill compliance (ReComp). Med Care. 2007, 45 (6): 497-504.CrossRefPubMed
27.
go back to reference Sin DD, Man J, Sharpe H, Gan WQ, Man SF: Pharmacological management to reduce exacerbations in adults with asthma: a systematic review and meta-analysis. JAMA. 2004, 292 (3): 367-376.CrossRefPubMed Sin DD, Man J, Sharpe H, Gan WQ, Man SF: Pharmacological management to reduce exacerbations in adults with asthma: a systematic review and meta-analysis. JAMA. 2004, 292 (3): 367-376.CrossRefPubMed
28.
go back to reference Hanania NA, Chapman KR, Kesten S: Adverse effects of inhaled corticosteroids. Am J Med. 1995, 98 (2): 196-208.CrossRefPubMed Hanania NA, Chapman KR, Kesten S: Adverse effects of inhaled corticosteroids. Am J Med. 1995, 98 (2): 196-208.CrossRefPubMed
29.
go back to reference Blanquart C, Barbier O, Fruchart JC, Staels B, Glineur C: Peroxisome proliferator-activated receptors: regulation of transcriptional activities and roles in inflammation. J Steroid Biochem Mol Biol. 2003, 85 (2–5): 267-273.CrossRefPubMed Blanquart C, Barbier O, Fruchart JC, Staels B, Glineur C: Peroxisome proliferator-activated receptors: regulation of transcriptional activities and roles in inflammation. J Steroid Biochem Mol Biol. 2003, 85 (2–5): 267-273.CrossRefPubMed
30.
go back to reference Daynes RA, Jones DC: Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol. 2002, 2 (10): 748-759.CrossRefPubMed Daynes RA, Jones DC: Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol. 2002, 2 (10): 748-759.CrossRefPubMed
31.
go back to reference Patel HJ, Belvisi MG, Bishop-Bailey D, Yacoub MH, Mitchell JA: Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior anti-inflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapy. J Immunol. 2003, 170 (5): 2663-2669.CrossRefPubMed Patel HJ, Belvisi MG, Bishop-Bailey D, Yacoub MH, Mitchell JA: Activation of peroxisome proliferator-activated receptors in human airway smooth muscle cells has a superior anti-inflammatory profile to corticosteroids: relevance for chronic obstructive pulmonary disease therapy. J Immunol. 2003, 170 (5): 2663-2669.CrossRefPubMed
32.
go back to reference Hashimoto Y, Nakahara K: Improvement of asthma after administration of pioglitazone. Diabetes Care. 2002, 25 (2): 401-CrossRefPubMed Hashimoto Y, Nakahara K: Improvement of asthma after administration of pioglitazone. Diabetes Care. 2002, 25 (2): 401-CrossRefPubMed
33.
go back to reference Lipscombe LL, Gomes T, Levesque LE, Hux JE, Juurlink DN, Alter DA: Thiazolidinediones and cardiovascular outcomes in older patients with diabetes. JAMA. 2007, 298 (22): 2634-2643.CrossRefPubMed Lipscombe LL, Gomes T, Levesque LE, Hux JE, Juurlink DN, Alter DA: Thiazolidinediones and cardiovascular outcomes in older patients with diabetes. JAMA. 2007, 298 (22): 2634-2643.CrossRefPubMed
34.
go back to reference Ferwana M, Firwana B, Hasan R, Al-Mallah MH, Kim S, Montori VM, Murad MH: Pioglitazone and risk of bladder cancer: a meta-analysis of controlled studies. Diabet Med. 2013, 30 (9): 1026-1032.CrossRefPubMed Ferwana M, Firwana B, Hasan R, Al-Mallah MH, Kim S, Montori VM, Murad MH: Pioglitazone and risk of bladder cancer: a meta-analysis of controlled studies. Diabet Med. 2013, 30 (9): 1026-1032.CrossRefPubMed
35.
go back to reference Nissen SE, Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007, 356 (24): 2457-2471.CrossRefPubMed Nissen SE, Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007, 356 (24): 2457-2471.CrossRefPubMed
36.
go back to reference Ray WA: Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol. 2003, 158 (9): 915-920.CrossRefPubMed Ray WA: Evaluating medication effects outside of clinical trials: new-user designs. Am J Epidemiol. 2003, 158 (9): 915-920.CrossRefPubMed
37.
go back to reference Thomson NC, Chaudhuri R, Livingston E: Asthma and cigarette smoking. Eur Respir J. 2004, 24 (5): 822-833.CrossRefPubMed Thomson NC, Chaudhuri R, Livingston E: Asthma and cigarette smoking. Eur Respir J. 2004, 24 (5): 822-833.CrossRefPubMed
38.
go back to reference Fitzpatrick S, Joks R, Silverberg JI: Obesity is associated with increased asthma severity and exacerbations, and increased serum immunoglobulin E in inner-city adults. Clin Exp Allergy. 2012, 42 (5): 747-759.CrossRefPubMed Fitzpatrick S, Joks R, Silverberg JI: Obesity is associated with increased asthma severity and exacerbations, and increased serum immunoglobulin E in inner-city adults. Clin Exp Allergy. 2012, 42 (5): 747-759.CrossRefPubMed
39.
go back to reference Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, Casale TB, Chanez P, Enright PL, Gibson PG, de Jongste JC, Kerstjens HA, Lazarus SC, Levy ML, O'Byrne PM, Partridge MR, Pavord ID, Sears MR, Sterk PJ, Stoloff SW, Szefler SJ, Sullivan SD, Thomas MD, Wenzel SE, Reddel HK: A new perspective on concepts of asthma severity and control. Eur Respir J. 2008, 32 (3): 545-554.CrossRefPubMed Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, Casale TB, Chanez P, Enright PL, Gibson PG, de Jongste JC, Kerstjens HA, Lazarus SC, Levy ML, O'Byrne PM, Partridge MR, Pavord ID, Sears MR, Sterk PJ, Stoloff SW, Szefler SJ, Sullivan SD, Thomas MD, Wenzel SE, Reddel HK: A new perspective on concepts of asthma severity and control. Eur Respir J. 2008, 32 (3): 545-554.CrossRefPubMed
Metadata
Title
Thiazolidinediones and the risk of asthma exacerbation among patients with diabetes: a cohort study
Authors
Seppo T Rinne
Laura C Feemster
Bridget F Collins
David H Au
Mark Perkins
Christopher L Bryson
Thomas G O’Riordan
Chuan-Fen Liu
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Allergy, Asthma & Clinical Immunology / Issue 1/2014
Electronic ISSN: 1710-1492
DOI
https://doi.org/10.1186/1710-1492-10-34

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