Reliever salbutamol use as a measure of exacerbation risk in chronic obstructive pulmonary disease

Christine R Jenkins, Dirkje S Postma, Antonio R Anzueto, Barry J Make, Stefan Peterson, Göran Eriksson, Peter M Calverley, Christine R Jenkins, Dirkje S Postma, Antonio R Anzueto, Barry J Make, Stefan Peterson, Göran Eriksson, Peter M Calverley

Abstract

Background: Debate exists regarding which endpoints most sensitively reflect day-to-day variation in chronic obstructive pulmonary disease (COPD) symptoms and are most useful in clinical practice to predict COPD exacerbations. We hypothesized that short-acting β2-agonist (SABA) reliever use would predict short- and long-term exacerbation risk in COPD patients.

Methods: We performed a retrospective analysis of data from a study (ClinicalTrials.gov registration: NCT00419744) comparing budesonide/formoterol 320/9 μg with formoterol 9 μg (both twice daily) in patients with moderate-to-very-severe COPD; reliever salbutamol 90 μg was provided. First occurrence of reliever use >4 (low), >10 (medium), and >20 (high) inhalations/day was assessed as a predictor of short-term (3-week) exacerbation risk. Mean daily reliever use in the week preceding the 2-month visit was investigated as a predictor of the long-term (10-month) exacerbation risk, using intervals of 2-5, 6-9, and ≥10 inhalations/day.

Results: Overall, 810 patients were included (61 % male; mean age 63.2 years; post-bronchodilator forced expiratory volume in 1 s 37.7 % of predicted). First occurrence of low, medium, or high reliever use was predictive of an exacerbation within the following 3 weeks; exacerbation risk increased significantly with increasing reliever use. Mean reliever use over 1 week was predictive of long-term exacerbation risk. Patients with mean use of 2-5, 6-9, and ≥10 inhalations/day exhibited 21 %, 67 %, and 135 % higher exacerbation rates, respectively, in the following 10 months, compared with <2 inhalations/day. Budesonide/formoterol was associated with lower short- and long-term exacerbation risk than formoterol in all reliever-use groups.

Conclusions: SABA reliever use is a predictor of short- and long-term exacerbation risk in moderate-to-very-severe COPD patients with a history of exacerbations receiving budesonide/formoterol or formoterol.

Figures

Fig. 1
Fig. 1
Short-term (days 0–21) exacerbation risk. Kaplan-Meier plot of patients with occurrence of an exacerbation after they used for the first time >4, >10, or >20 inhalations of salbutamol per day in a) FORM and b) BUD/FORM treatment groups. Data for 16 patients are missing from baseline to day 0. BUD budesonide, COPD chronic obstructive pulmonary disease, FORM formoterol
Fig. 2
Fig. 2
Long-term (months 3–12) exacerbation rate by reliever use thresholds. Long-term (months 3–12) exacerbation rates for patients receiving a) FORM and b) BUD/FORM with a mean number of inhalations less than, and greater than or equal to, reliever use in the range from zero to 12 inhalations/day in the week preceding the 2-month visit. BUD budesonide, FORM formoterol
Fig. 3
Fig. 3
Long-term (months 3–12) exacerbation rate by treatment group. Long-term (months 3–12) exacerbation rate by treatment group, for patients reporting BUD budesonide, FORM formoterol

References

    1. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163–2196. doi: 10.1016/S0140-6736(12)61729-2.
    1. Yeatts KB, Lippmann SJ, Waller AE, Hassmiller Lich K, Travers D, Weinberger M, et al. Population-based burden of COPD-related visits in the ED: return ED visits, hospital admissions, and comorbidity risks. Chest. 2013;144(3):784–793. doi: 10.1378/chest.12-1899.
    1. Postma D, Anzueto A, Calverley P, Jenkins C, Make BJ, Sciurba FC, et al. A new perspective on optimal care for patients with COPD. Prim Care Respir J. 2011;20(2):205–209. doi: 10.4104/pcrj.2011.00041.
    1. Jones PW. Health status measurement in chronic obstructive pulmonary disease. Thorax. 2001;56(11):880–887. doi: 10.1136/thorax.56.11.880.
    1. Westwood M, Bourbeau J, Jones PW, Cerulli A, Capkun-Niggli G, Worthy G. Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review. Respir Res. 2011;12:40. doi: 10.1186/1465-9921-12-40.
    1. Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George’s Respiratory Questionnaire. Am Rev Respir Dis. 1992;145(6):1321–1327. doi: 10.1164/ajrccm/145.6.1321.
    1. Cazzola M, MacNee W, Martinez FJ, Rabe KF, Franciosi LG, Barnes PJ, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J. 2008;31(2):416–469. doi: 10.1183/09031936.00099306.
    1. Landis SH, Muellerova H, Mannino DM, Menezes AM, Han MK, van der Molen T, et al. Continuing to confront COPD international patient survey: methods, COPD prevalence, and disease burden in 2012–2013. Int J Chron Obstruct Pulmon Dis. 2014;9:597–611.
    1. Bateman ED, Reddel HK, Eriksson G, Peterson S, Ostlund O, Sears MR, Jenkins C, Humbert M, Buhl R, Harrison TW. Overall asthma control: the relationship between current control and future risk. J Allergy Clin Immunol. 2010;125(3):600–8. doi: 10.1016/j.jaci.2009.11.033.
    1. Melosini L, Dente FL, Bacci E, Bartoli ML, Cianchetti S, Costa F, et al. Asthma control test (ACT): comparison with clinical, functional, and biological markers of asthma control. J Asthma. 2012;49(3):317–323. doi: 10.3109/02770903.2012.661008.
    1. Revicki D, Weiss KB. Clinical assessment of asthma symptom control: review of current assessment instruments. J Asthma. 2006;43(7):481–487. doi: 10.1080/02770900600619618.
    1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. Updated 2014 []
    1. Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013;187(4):347–365. doi: 10.1164/rccm.201204-0596PP.
    1. Kessler R, Partridge MR, Miravitlles M, Cazzola M, Vogelmeier C, Leynaud D, et al. Symptom variability in patients with severe COPD: a pan-European cross-sectional study. Eur Respir J. 2011;37(2):264–272. doi: 10.1183/09031936.00051110.
    1. Cook D, Guyatt G, Wong E, Goldstein R, Bedard M, Austin P, et al. Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;163(1):85–90. doi: 10.1164/ajrccm.163.1.2004214.
    1. Sharafkhaneh A, Southard JG, Goldman M, Uryniak T, Martin UJ. Effect of budesonide/formoterol pMDI on COPD exacerbations: a double-blind, randomized study. Respir Med. 2012;106(2):257–268. doi: 10.1016/j.rmed.2011.07.020.
    1. Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, et al. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;180(8):741–750. doi: 10.1164/rccm.200904-0492OC.
    1. Donohue JF, Fogarty C, Lotvall J, Mahler DA, Worth H, Yorgancioglu A, et al. Once-daily bronchodilators for chronic obstructive pulmonary disease: indacaterol versus tiotropium. Am J Respir Crit Care Med. 2010;182(2):155–162. doi: 10.1164/rccm.200910-1500OC.
    1. D’Urzo A, Ferguson GT, van Noord JA, Hirata K, Martin C, Horton R, et al. Efficacy and safety of once-daily NVA237 in patients with moderate-to-severe COPD: the GLOW1 trial. Respir Res. 2011;12:156. doi: 10.1186/1465-9921-12-156.
    1. Fuhr R, Magnussen H, Sarem K, Llovera AR, Kirsten AM, Falques M, et al. Efficacy of aclidinium bromide 400 mug twice daily compared with placebo and tiotropium in patients with moderate to severe COPD. Chest. 2012;141(3):745–752. doi: 10.1378/chest.11-0406.
    1. Vogelmeier C, Hederer B, Glaab T, Schmidt H, Rutten-van Molken MP, Beeh KM, et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med. 2011;364(12):1093–1103. doi: 10.1056/NEJMoa1008378.
    1. Buhl R, Kuna P, Peters MJ, Andersson TL, Naya IP, Peterson S, et al. The effect of budesonide/formoterol maintenance and reliever therapy on the risk of severe asthma exacerbations following episodes of high reliever use: an exploratory analysis of two randomised, controlled studies with comparisons to standard therapy. Respir Res. 2012;13:59. doi: 10.1186/1465-9921-13-59.
    1. Tashkin DP, Rennard SI, Martin P, Ramachandran S, Martin UJ, Silkoff PE, et al. Efficacy and safety of budesonide and formoterol in one pressurized metered-dose inhaler in patients with moderate to very severe chronic obstructive pulmonary disease: results of a 6-month randomized clinical trial. Drugs. 2008;68(14):1975–2000. doi: 10.2165/00003495-200868140-00004.
    1. Rennard SI, Tashkin DP, McElhattan J, Goldman M, Ramachandran S, Martin UJ, et al. Efficacy and tolerability of budesonide/formoterol in one hydrofluoroalkane pressurized metered-dose inhaler in patients with chronic obstructive pulmonary disease: results from a 1-year randomized controlled clinical trial. Drugs. 2009;69(5):549–565. doi: 10.2165/00003495-200969050-00004.
    1. Calverley PM, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olsson H. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J. 2003;22(6):912–919. doi: 10.1183/09031936.03.00027003.
    1. Szafranski W, Cukier A, Ramirez A, Menga G, Sansores R, Nahabedian S, et al. Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease. Eur Respir J. 2003;21(1):74–81. doi: 10.1183/09031936.03.00031402.
    1. Make BJ, Eriksson GS, Calverley PM, Jenkins C, Postma DS, Peterson S, et al. A score to predict short-term risk of COPD exacerbations (SCOPEX) Int J Chron Obstruct Pulmon Dis. 2015;10:201–209. doi: 10.2147/COPD.S69589.
    1. Juniper EF, Bousquet J, Abetz L, Bateman ED. Identifying’well-controlled’ and ’not well-controlled’ asthma using the Asthma Control Questionnaire. Respir Med. 2006;100(4):616–21.
    1. Juniper EF, Langlands JM, Juniper BA. Patients may respond differently to paper and electronic versions of the same questionnaires. Respir Med. 2009;103(6):932–934. doi: 10.1016/j.rmed.2008.10.019.

Source: PubMed

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