Inhaled corticosteroid use in patients with chronic obstructive pulmonary disease and the risk of pneumonia: a retrospective claims data analysis

Barbara P Yawn, Yunfeng Li, Haijun Tian, Jie Zhang, Steve Arcona, Kristijan H Kahler, Barbara P Yawn, Yunfeng Li, Haijun Tian, Jie Zhang, Steve Arcona, Kristijan H Kahler

Abstract

Background: The use of inhaled corticosteroids in patients with chronic obstructive pulmonary disease (COPD) has been associated with an increased risk of pneumonia in controlled clinical trials and case-control analyses.

Objective: Using claims databases as a research model of real-world diagnosis and treatment, to determine if the use and dose of inhaled corticosteroids (ICS) among patients with newly diagnosed COPD are associated with increased risk of pneumonia.

Patients and methods: This was a retrospective cohort analysis of patients diagnosed with COPD between January 01, 2006 and September 30, 2010, drawn from databases (years 2006-2010). Patients (aged ≥45 years) were followed until first pneumonia diagnosis, end of benefit enrollment, or December 31, 2010, whichever was earliest. A Cox proportional hazard model was used to assess the association of ICS use and risk of pneumonia, controlling for baseline characteristics. Daily ICS use was classified into low, medium, and high doses (1 μg-499 μg, 500 μg-999 μg, and ≥1000 μg fluticasone equivalents daily) and was modeled as a time-dependent variable.

Results: Among 135,445 qualifying patients with a total of 243,097 person-years, there were 1020 pneumonia incidences out of 5677 person-years on ICS (crude incidence rate, 0.180 per person-year), and 27,730 pneumonia incidences out of 237,420 person-years not on ICS (crude incidence rate, 0.117 per person-year). ICS use was associated with a dose-related increase in risk of pneumonia, with adjusted hazard ratios (versus no use; (95% confidence interval) of 1.38 (1.27-1.49) for low-dose users, 1.69 (1.52-1.88) for medium-dose users, and 2.57 (1.98-3.33) for high-dose users (P < 0.01 versus no use and between doses).

Conclusion: The use of ICS in newly diagnosed patients with COPD is potentially associated with a dose-related increase in the risk of pneumonia.

Keywords: COPD; ICS; LABA; pneumonia.

Figures

Figure 1
Figure 1
Patient selection. Note: *COPD diagnosis was not made during the 12-month baseline period. Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid.
Figure 2
Figure 2
Kaplan–Meier pneumonia-free survival estimates during follow up period by inhaled corticosteroid dose level. Abbreviation: ICS, inhaled corticosteroid.
Figure 3
Figure 3
Adjusted hazard ratio for risk of pneumonia according to inhaled corticosteroid dose. Pairwise comparisons between the three ICS dose levels were all significantly different at P < 0.01. The hazard ratios were from multivariate Cox proportional hazards model, with ICS use and dose level as time-dependent variables. Abbreviations: CI, confidence interval; ICS, inhaled corticosteroid.

References

    1. Asche CV, Brixner DI, Conoscenti CS, et al. Assessment of physician prescribing for primary care patients with chronic obstructive pulmonary disease (COPD) in a national electronic medical record (EMR) research database. Chest. 2006;130(4):175s. [abstract]
    1. Bourbeau J, Sebaldt RJ, Day A, et al. Practice patterns in the management of chronic obstructive pulmonary disease in primary practice: the CAGE study. Can Respir J. 2008;15(1):13–19.
    1. de Miguel-Díez J, Carrasco-Garrido P, Rejas-Gutierrez J, et al. I nappropriate overuse of inhaled corticosteroids for COPD patients: impact on health costs and health status. Lung. 2011;189(3):199–206.
    1. Cazzola M, Segreti A, Bettoncelli G, et al. Change in asthma and COPD prescribing by Italian general practitioners between 2006 and 2008. Prim Care Respir J. 2011;20(3):291–298.
    1. Mehuys E, Boussery K, Adriaens E, et al. COPD management in primary care: an observational, community pharmacy-based study. Ann Pharmacother. 2010;44(2):257–266.
    1. Smith CJ, Gribbin J, Challen KB, Hubbard RB. The impact of the 2004 NICE guideline and 2003 General Medical Services contract on COPD in primary care in the UK. QJM. 2008;101(2):145–153.
    1. global strategy for diagnosis, management and prevention of chronic obstructive pulmonary disease [homepage on the Internet] Global Initiative for Chronic Obstructive Lung Disease (GOLD) [updated Dec 2011] Available from: Accessed August 20, 2012
    1. Singh S, Loke YK. An overview of the benefits and drawbacks of inhaled corticosteroids in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2010;5:189–195.
    1. Patel AR, Hurst JR. Extrapulmonary comorbidities in chronic obstructive pulmonary disease: state of the art. Expert Rev Respir Med. 2011;5(5):647–662.
    1. Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356(8):775–789.
    1. Kardos P, Wencker M, Glaab T, Vogelmeier C. Impact of salmeterol/fluticasone propionate versus salmeterol on exacerbations in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;175(2):144–149.
    1. Wedzicha JA, Calverley PM, Seemungal TA, et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008;177(1):19–26.
    1. Ernst P, Gonzalez AV, Brassard P, Suissa S. Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia. Am J Respir Crit Care Med. 2007;176(2):162–166.
    1. CG101 Chronic obstructive pulmonary disease (update): full guideline [webpage on the Internet] National Institute for Health and Clinical Excellence [updated May 30, 2012] Available from: Accessed August 20, 2012
    1. Qaseem A, Wilt TJ, Weinberger SE, et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011;155(3):179–191.
    1. Colice GL. Pragmatic research and outcomes in asthma and COPD. Pragmatic Obs Res. 2012;3:11–25.
    1. Crim C, Calverley PM, Anderson JA, et al. Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination: TORCH study results. Eur Respir J. 2009;34(3):641–647.
    1. Walsh LJ, Wong CA, Oborne J, et al. Adverse effects of oral corticosteroids in relation to dose in patients with lung disease. Thorax. 2001;56(4):279–284.
    1. Inhaled steroids approximate dose conversions for adults [webpage on the Internet] Greater Rochester Independent Practice Association (GRIPA)2005Available from: Accessed February 1, 2012
    1. Joo MJ, Au DH, Fitzgibbon ML, Lee TA. Inhaled corticosteroids and risk of pneumonia in newly diagnosed COPD. Respir Med. 2010;104(2):246–252.
    1. Minas M, Hatzoglou C, Karetsi E, et al. COPD prevalence and the differences between newly and previously diagnosed COPD patients in a spirometry program. Prim Care Respir J. 2010;19(4):363–370.
    1. Centers for Disease Control and Prevention (CDC) Chronic obstructive pulmonary disease and associated health-care resource use – North Carolina, 2007 and 2009. MMWR Morb Mortal Wkly Rep. 2012;61(8):143–146.
    1. Spencer S, Karner C, Cates CJ, Evans DJ. Inhaled corticosteroids versus long-acting beta2-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011;12:CD007033.
    1. Yang IA, Clarke MS, Sim EH, Fong KM. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;7:CD002991.
    1. Singh S, Amin AV, Loke YK. Long-term use of inhaled corticosteroids and the risk of pneumonia in chronic obstructive pulmonary disease: a meta-analysis. Arch Intern Med. 2009;169(3):219–229.
    1. Jones PW, Willits LR, Burge PS, Calverley PM, Inhaled Steroids in Obstructive Lung Disease in Europe study investigators Disease severity and the effect of fluticasone propionate on chronic obstructive pulmonary disease exacerbations. Eur Respir J. 2003;21(1):68–73.
    1. Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2003;361(9356):449–456.
    2. Lancet. 2003;361(9369):1660.
    1. Yawn B, Kleerup E, Zhang J, Kianifard F, Williams J. Inhaled corticosteroid use and GOLD severity stage among patients with chronic obstructive pulmonary disease in different regions. Am J Respir Crit Care Med. 2012;185:A2944. [abstract]
    1. Chen S, Plauschinat CA, Wu N, Fraser K, Boulanger L. Economic impact of using inhaled corticosteroids without prior exacerbation among elderly patients with chronic obstructive pulmonary disorder. J Med Econ. 2011;14(4):458–462.
    1. Papi A, Bellettato CM, Braccioni F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med. 2006;173(10):1114–1121.
    1. Seemungal T, Harper-Owen R, Bhowmik A, et al. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;164(9):1618–1623.
    1. Myint PK, Lowe D, Stone RA, Buckingham RJ, Roberts CM. UK National COPD Resources and Outcomes Project 2008: patients with chronic obstructive pulmonary disease exacerbations who present with radiological pneumonia have worse outcome compared to those with non-pneumonic chronic obstructive pulmonary disease exacerbations. Respiration. 2011;82(4):320–327.
    1. Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epi. 1994;47:1246–1261.
    1. Finkelstein J, Cha E, Scharf SM. Chronic obstructive pulmonary disease as an independent risk factor for cardiovascular morbidity. Int J Chron Obstruct Pulmon Dis. 2009;4:337–349.
    1. Dai S, Walsh P, Wielgosz A, Gurevich Y, Bancej C, Morrison H. Comorbidities and mortality associated with hospitalized heart failure in Canada. Can J Cardiol. 2012;28(1):74–79.
    1. Mannino DM, Thorn D, Swensen A, Holguin F. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur Respir J. 2008;32(4):962–969.
    1. Rana JS, Mittleman MA, Sheikh J, et al. Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women. Diabetes Care. 2004;27(10):2478–2484.
    1. Calverley PM, Stockley RA, Seemungal TA, et al. Reported pneumonia in patients with COPD: findings from the INSPIRE study. Chest. 2011;139(3):505–512.
    1. Hogg JC, Chu FS, Tan WC, et al. Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airway pathology. Am J Respir Crit Care Med. 2007;176(5):454–459.
    1. Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(26):2645–2653.
    1. Patterson CM, Morrison RL, D’Souza A, Teng XS, Happel KI. Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella pneumoniae in mice. Respir Res. 2012;13(1):40.
    1. Halpin DM, Gray J, Edwards SJ, Morais J, Singh D. Budesonide/formoterol vs salmeterol/fluticasone in COPD: a systematic review and adjusted indirect comparison of pneumonia in randomised controlled trials. Int J Clin Pract. 2011;65(7):764–774.
    1. Singanayagam A, Chalmers JD, Akram AR, Hill AT. Impact of inhaled corticosteroid use on outcome in COPD patients admitted with pneumonia. Eur Respir J. 2011;38(1):36–41.
    1. Chen D, Restrepo MI, Fine MJ, et al. Observational study of inhaled corticosteroids on outcomes for COPD patients with pneumonia. Am J Respir Crit Care Med. 2011;184(3):312–316.
    1. Restrepo MI, Mortensen EM, Anzueto A. Are COPD patients with pneumonia who are taking inhaled corticosteroids at higher risk of dying? Eur Respir J. 2011;38(1):1–3.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren