Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: a pooled analysis

Paul W Jones, James F Donohue, Jerry Nedelman, Steve Pascoe, Gregory Pinault, Cheryl Lassen, Paul W Jones, James F Donohue, Jerry Nedelman, Steve Pascoe, Gregory Pinault, Cheryl Lassen

Abstract

Background: Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively. We examined whether changes in trough forced expiratory volume in 1 second (FEV(1)) are correlated with changes in patient-reported outcomes.

Methods: Pooled data from three indacaterol studies (n = 3313) were analysed. Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St. George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV(1). Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.

Results: With increasing positive ΔFEV(1), TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001). Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95. At 26 weeks, a 100 ml increase in FEV(1) was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease). Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV(1) and outcomes.

Conclusions: These results suggest that larger improvements in FEV(1) are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.

Trial registration: ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286.

Figures

Figure 1
Figure 1
Outcome means in ΔFEV1 categories versus category midpoint value. Plots show data with Loess smooth curves superimposed. ΔFEV1, change from baseline in trough forced expiratory volume in 1 second; TDI, Transition Dyspnoea Index; ΔSGRQ, change from baseline in St George's Respiratory Questionnaire.
Figure 2
Figure 2
Outcomes versus ΔFEV1: curves fitted from model-based analysis. SGRQ and TDI data is for Week 24/26. Exacerbations are reported counts normalised to 1 year. Rescue medication use is reported numbers of puffs normalised to 1 day. For plotting predicted curves, 'moderate' refers to baseline FEV1 1.595 l (third quartile of observed values) and GOLD 2 (moderate or less [19]); 'severe' refers to baseline FEV1 0.95 l (first quartile of observed values) and GOLD 3 (severe or greater [19]). For TDI, 'moderate' and 'severe' refer to BDI at quartiles 2 and 1, respectively. For ΔSGRQ, 'moderate' and 'severe' refer to baseline SGRQ at quartiles 31.3 and 58.13, respectively; ΔFEV1, change from baseline in trough forced expiratory volume in 1 second; ΔSGRQ, change from baseline in St George's Respiratory Questionnaire; TDI, Transition Dyspnoea Index; GOLD, Global initiative for chronic Obstructive Lung Disease; BDI, Baseline Dyspnoea Index; ICS, inhaled corticosteroid.

References

    1. Jones PW, Agusti AGN. Outcomes and markers in the assessment of chronic obstructive pulmonary disease. Eur Respir J. 2006;27:822–832. doi: 10.1183/09031936.06.00145104.
    1. Álvarez-Gutiérrez FJ, Miravitlles M, Calle M, Gobartt E, López F, Martín A. Grupo de Estudio EIME. Impact of chronic obstructive pulmonary disease on activities of daily living: results of the EIME multicenter study. Arch Bronconeumol. 2007;43:64–72.
    1. Anzueto A, Leimer I, Kesten S. Impact of frequency of COPD exacerbations on pulmonary function, health status and clinical outcomes. Int J Chron Obstruct Pulmon Dis. 2009;4:245–251.
    1. de Torres JP, Cote CG, Lopez MV, Casanova C, Díaz O, Marin JM, Pinto-Plata V, de Oca MM, Nekach H, Dordelly LJ, Aguirre-Jaime A, Celli BR. Sex differences in mortality in patients with COPD. Eur Respir J. 2009;33:528–535. doi: 10.1183/09031936.00096108.
    1. Groenewegen KH, Postma DS, Hop WC, Wielders PL, Schlösser NJ, Wouters EF. COSMIC Study Group. Increased systemic inflammation is a risk factor for COPD exacerbations. Chest. 2008;133:350–357. doi: 10.1378/chest.07-1342.
    1. Gudmundsson G, Gislason T, Janson C, Lindberg E, Hallin R, Ulrik CS, Brøndum E, Nieminen MM, Aine T, Bakke P. Risk factors for rehospitalisation in COPD: role of health status, anxiety and depression. Eur Respir J. 2005;26:414–419. doi: 10.1183/09031936.05.00078504.
    1. Gudmundsson G, Gislason T, Lindberg E, Hallin R, Ulrik CS, Brøndum E, Nieminen MM, Aine T, Bakke P, Janson C. Mortality in COPD patients discharged from hospital: the role of treatment and co-morbidity. Respir Res. 2006;7:109. doi: 10.1186/1465-9921-7-109.
    1. Mannino DM, Davis KJ. Lung function decline and outcomes in an elderly population. Thorax. 2006;61:472–477. doi: 10.1136/thx.2005.052449.
    1. McGlone S, Venn A, Walters EH, Wood-Baker R. Physical activity, spirometry and quality-of-life in chronic obstructive pulmonary disease. COPD. 2006;3:83–88. doi: 10.1080/15412550600651263.
    1. Niewoehner DE, Lokhyygina Y, Rice K, Kuschner WG, Sharafkhaneh A, Sarosi GA, Krumpe P, Pieper K, Kesten S. Risk indexes for exacerbations and hospitalizations due to COPD. Chest. 2007;131:20–28. doi: 10.1378/chest.06-1316.
    1. Niewoehner DE. Relation of chronic obstructive pulmonary disease exacerbations to FEV1 - an intricate tango. Respiration. 2009;77:229–235. doi: 10.1159/000162877.
    1. Omata M, Wakabayashi R, Kudoh S, Kida K. Correlation between bronchodilator responsiveness and quality of life in chronic obstructive pulmonary disease. Allergol Int. 2007;56:15–22. doi: 10.2332/allergolint.O-06-431.
    1. Watson L, Schouten JP, Lofdahl CG, Pride NB, Laitinen LA, Postma DS. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. Predictors of COPD symptoms: does the sex of the patient matter? Eur Respir J. 2006;28:311–318. doi: 10.1183/09031936.06.00055805.
    1. Jones PW. Health status measurement in chronic obstructive pulmonary disease. Thorax. 2001;56:880–887. 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. Dahl R, Chung KF, Buhl R, Magnussen H, Nonikov V, Jack D, Bleasdale P, Owen R, Higgins M, Kramer B. on behalf of the INVOLVE (INdacaterol: Value in COPD; Longer Term Validation of Efficacy and Safety) Study Investigators. Efficacy of a new once-daily long-acting inhaled β2-agonist indacaterol versus twice-daily formoterol in COPD. Thorax. 2010;65:473–479. doi: 10.1136/thx.2009.125435.
    1. Donohue JF, Fogarty C, Lötvall J, Mahler DA, Worth H, Yorgancioğlu A, Iqbal A, Swales J, Owen R, Higgins M, Kramer B. for the INHANCE Study Investigators. Once-daily bronchodilators for chronic obstructive pulmonary disease: indacaterol versus tiotropium. Am J Respir Crit Care Med. 2010;182:155–162. doi: 10.1164/rccm.200910-1500OC.
    1. Feldman G, Siler T, Prasad N, Jack D, Piggott S, Owen R, Higgins M, Kramer B. the INLIGHT 1 study group. Efficacy and safety of indacaterol 150 μg once-daily in COPD: a double-blind, randomised, 12-week study. BMC Pulm Med. 2010;10:11. doi: 10.1186/1471-2466-10-11.
    1. Global initiative for chronic Obstructive Lung Disease (GOLD) Global Strategy for the Diagnosis, Management, and Prevention of chronic obstructive pulmonary disease. Date last updated: 2005 [ ]
    1. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CPM, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J. Standardisation of spirometry. Eur Respir J. 2005;26:319–338. doi: 10.1183/09031936.05.00034805.
    1. Jones PW. St. George's Respiratory Questionnaire: MCID. COPD. 2005;2:75–79. doi: 10.1081/COPD-200050513.
    1. Mahler DA, Witek TJ Jr. The MCID of the transition dyspnea index is a total score of one unit. COPD. 2005;2:99–103. doi: 10.1081/COPD-200050666.
    1. Harrell FE. Regression modeling strategies. New York: Springer-Verlag; 2001.
    1. Venables WN, Ripley BD. Modern applied statistics. New York: Springer-Verlag; 2002.
    1. Donohue J. Minimal clinically important differences in COPD lung function. COPD. 2005;2:111–124. doi: 10.1081/COPD-200053377.
    1. Jenkins CR, Jones PW, Calverley PMA, Celli B, Anderson JA, Ferguson GT, Yates JC, Willits LR, Vestbo J. Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study. Respir Res. 2009;10:59.
    1. Vestbo J, Anderson JA, Calverley PMA, Celli B, Ferguson GT, Jenkins C, Yates JC, Jones PW. Bias due to withdrawal in long-term randomised trials in COPD: evidence from the TORCH study. Clin Respir J. 2011;5:44–49. doi: 10.1111/j.1752-699X.2010.00198.x.
    1. Calverley PMA, Pauwels R, Vestbo J, Jones PW, Pride N, Gulsvick A. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease. Lancet. 2003;361:449–456. doi: 10.1016/S0140-6736(03)12459-2.
    1. Calverley PM, Anderson JA, Celli BR, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J. Salmeterol and fluticasone proprionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775–789. doi: 10.1056/NEJMoa063070.
    1. Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M. UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359:1543–1554. doi: 10.1056/NEJMoa0805800.
    1. Di Marco F, Milic-Emili J, Boveri B, Carlucci P, Santus P, Casanova F, Cazzola M, Centanni S. Effect of inhaled bronchodilators on inspiratory capacity and dyspnoea at rest in COPD. Eur Respir J. 2003;21:86–94. doi: 10.1183/09031936.03.00020102.
    1. Global initiative for chronic Obstructive Lung Disease (GOLD) Global Strategy for the Diagnosis, Management, and Prevention of chronic obstructive pulmonary disease. Date last updated: 2010 [ ]

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다