Changing the burden of COPD mortality

Figures & data

Table 1 Classification of severity of COPD using GOLD criteria (GOLD 2005)

Stage	Characteristic
	FEV1/FVCa	FEV1, % predicteda	Chronic symptomsb
0 (at risk)	Normal	Normal	+
I (mild COPD)	<70%	≥ 80%	±
II (moderate COPD)	<70%	<80% but ≥ 50%	±
III (severe COPD)	<70%	<50% but ≥ 30%	±
IV (very severe COPD)	<70%	<30%; or <50% with chronic respiratory failurec	±

a Classification based on post-bronchodilator FEV₁.

b Cough, sputum production.

c Arterial partial pressure of oxygen (PaO₂) less than 8.0 kPa (60 mmHg) with or without arterial partial pressure of CO₂ (PaCO₂) greater than 6.7 kPa (50 mmHg) while breathing air at sea level.

Abbreviations: FEV₁, forced expiratory volume in one second; FVC, forced vital capacity.

Table 2 Estimated COPD deaths by WHO region in 2000 (Lopez et al 2006)

WHO region	Deaths (000s)
Africa Aa	52
Africa E	65
Americas A	141
Americas B	90
Americas D	10
Southeast Asia B	100
Southeast Asia D	556
Europe A	140
Europe B	45
Europe C	76
Eastern Mediterranean B	15
Eastern Mediterranean D	80
Western Pacific A	21
Western Pacific B	1354
World	2748

a Mortality strata: A, very low child/adult mortality; B, low child/adult mortality; C, low child and high adult mortality; D, high child and adult mortality; E, high child and very high adult mortality.

Figure 1 Change in age-adjusted death rates for COPD and other leading causes of death in the USA from 1965 to1998. Reprinted from Pauwels RA, Rabe KF. 2004. Burden and clinical features of chronic obstructive pulmonary disease (COPD). Lancet, 364:613–20. Copyright © 2004 with permission from Elsevier.

Figure 2 Age-adjusted COPD mortality rates in individuals aged 35–74 years in selected European countries (non-European country data are provided for comparison). Reprinted from Hurd SS. 2000. International efforts directed at attacking the problem of COPD. Chest, 117:S336–8. Copyright © 2000 with permission from CHEST.

Table 3 Summary of data from randomized placebo-controlled clinical trials investigating the effect of pharmacotherapy on mortality in COPD patients

Source of data	Comparison	RRa (95% CI) of mortality	Statistical significance
Clinical trials for ICS
(Burge et al 2000)	FP vs placebo	0.77 (0.54, 1.11)	NS
(Van Der Valk et al 2002)	FP vs placebo	0.98 (0.06, 15.55)	NS
(Lung Health Study Research Group 2000)	Triamcinolone vs placebo	0.79 (0.40, 1.53)	NS
(Vestbo et al 1999)	Budesonide vs placebo	0.80 (0.22, 2.92)	NS
(Pauwels et al 1999)	Budesonide vs placebo	0.81 (0.22, 2.04)	NS
Pooled summary (n=3678) (Sin et al 2003)	ICS vs placebo	0.78 (0.58, 1.05)	NS
Pooled summary (n=5085)(Sin et al 2005)	ICS vs placebo	0.73 (0.55, 0.96)	Significant
Clinical trials for LABA + ICS
(Szafranski et al 2003)	Budesonide+formoterol vs placebo	0.66 (0.24, 1.81)	NS
(Mahler et al 2002)	FP+salmeterol vs placebo	0.16 (0.01, 3.01)	NS
Pooled summary (n=1486) (Sin et al 2003)	ICS+LABA vs placebo	0.52 (0.20, 1.34)	NS

a Hazard ratio.

Abbreviations: CI, confidence interval; FP, fluticasone propionate; ICS, inhaled corticosteroids; LABA, long-acting β₂-agonists; NS, not significant; RR, relative risk.

Table 4 Effect of ICS therapy on COPD mortality in non-randomized cohort studies

Source of data	Comparison	Risk of death (95% CI)	Summary of outcome
(Sin and Tu 2001)	ICS vs no ICS	0.71 (0.65, 0.78)	Significant survival benefit with ICS
(Soriano et al 2002)	FP + salmeterol vs no ICS or LABA	0.48 (0.31, 0.73)	Significant survival benefit with FP and salmeterol
	FP alone vs no ICS or LABA	0.62 (0.45, 0.85)	Significant survival benefit with FP alone
	Salmeterol alone vs no ICS or LABA	0.79 (0.58, 1.07)	Significant survival benefit with salmeterol alone
(Soriano et al 2003)b	ICS + LABA	10.5%	Reduction in risk of rehospitalization or death with ICS and/or LABA
	ICS alone	17.1%
	LABA alone	17.3%
	SABA alone	24.3%
(Sin and Man 2003a)	ICS vs no ICS	0.75 (0.68, 0.82)	Significant survival benefit with ICS overall, and especially for medium- to high-dose ICS
	Low-dosea ICS vs no ICS	0.77 (0.69, 0.86)
	Medium-dosea ICS vs no ICS	0.48 (0.37, 0.63)
	High-dosea ICS vs no ICS	0.55 (0.44, 0.69)
(Suissa 2003)	ICS vs no ICS	0.69 (0.55, 0.86)	No reduction in morbidity or mortality with ICS (after controlling for time dependence)
	Time fixed adjusted rate
	ICS vs no ICS	1.00 (0.79, 1.26)
	Time dependent rate
(Suissa 2004)	ICS vs bronchodilators	0.66 (0.57, 0.76)	No reduction in all-cause mortality with ICS
(Fan et al 2003)	Low-dose ICS vs no ICS	0.75 (0.53, 1.05)	No reduction in mortality or exacerbations with ICS
	Medium-/high-dose ICS vs no ICS	0.91 (0.73, 1.13)
(Kiri et al 2005b)	ICS vs no ICS	0.69 (0.052, 0.93)	Survival benefit with ICS (in both models)
	propensity scores
	ICS vs no ICS	0.71 (0.56, 0.90)
	nested case control

a Dose was converted to beclomethasone equivalents and classified as low (≤ 500 μg/day), medium (501–1000 μg/day), and high (>1000 μg/day).

b This study reported one-year mortality rates.

Abbreviations: CI, confidence interval; FP, fluticasone propionate; ICS, inhaled corticosteroids; LABA, long-acting β₂-agonists; NS, not significant.

GOLD2005Global Initiative for Chronic Obstructive Lung Disease [online]Accessed 9 November 2005 URL: www.goldcopd.com

 Google Scholar

LopezADShibuyaKRaoC2006Chronic obstructive pulmonary disease: current burden and future projectionsEur Respir J2739741216452599

 PubMed Web of Science ®Google Scholar

PauwelsRARabeKF2004Burden and clinical features of chronic obstructive pulmonary disease (COPD)Lancet3646132015313363

 PubMed Web of Science ®Google Scholar

HurdSS2000International efforts directed at attacking the problem of COPDChest117S3368

 Web of Science ®Google Scholar

BurgePSCalverleyPMJonesPW2000Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trialBMJ320129730310807619

 PubMed Web of Science ®Google Scholar

van der ValkPMonninkhofEvan der PalenJ2002Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE studyAm J Respir Crit Care Med16613586312406823

 PubMed Web of Science ®Google Scholar

[LHSRG] Lung Health Study Research Group2000Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary diseaseN Engl J Med3431902911136260

 PubMed Web of Science ®Google Scholar

VestboJSorensenTLangeP1999Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trialLancet35318192310359405

 PubMed Web of Science ®Google Scholar

PauwelsRALofdahlCGLaitinenLA1999Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary DiseaseN Engl J Med34019485310379018

 PubMed Web of Science ®Google Scholar

SinDDMcAlisterFAManSF2003Contemporary management of chronic obstructive pulmonary disease: scientific reviewJAMA29023011214600189

 PubMed Web of Science ®Google Scholar

SinDDWuLAndersonJA2005Inhaled corticosteroids and mortality in chronic obstructive pulmonary diseaseThorax60992716227327

 PubMed Web of Science ®Google Scholar

SzafranskiWCukierARamirezA2003Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary diseaseEur Respir J21748112570112

 PubMed Web of Science ®Google Scholar

MahlerDAWirePHorstmanD2002Effectiveness of fluticasone propionate and salmeterol combination delivered via the Diskus device in the treatment of chronic obstructive pulmonary diseaseAm J Respir Crit Care Med16610849112379552

 PubMed Web of Science ®Google Scholar

SinDDTuJV2001Inhaled corticosteroids and the risk of mortality and readmission in elderly patients with chronic obstructive pulmonary diseaseAm J Respir Crit Care Med164580411520719

 PubMed Web of Science ®Google Scholar

SorianoJBVestboJPrideNB2002Survival in COPD patients after regular use of fluticasone propionate and salmeterol in general practiceEur Respir J208192512412670

 PubMed Web of Science ®Google Scholar

SorianoJBKiriVAPrideNB2003Inhaled corticosteroids with/without long-acting beta-agonists reduce the risk of rehospitalization and death in COPD patientsAm J Respir Med2677414720023

 PubMedGoogle Scholar

SinDDManSF2003aInhaled corticosteroids and survival in chronic obstructive pulmonary disease: does the dose matter?Eur Respir J21260612608439

 PubMed Web of Science ®Google Scholar

SuissaS2003Effectiveness of inhaled corticosteroids in chronic obstructive pulmonary disease: immortal time bias in observational studiesAm J Respir Crit Care Med168495312663327

 PubMed Web of Science ®Google Scholar

SuissaS2004Inhaled steroids and mortality in COPD: bias from unaccounted immortal timeEur Respir J23391515065827

 PubMed Web of Science ®Google Scholar

FanVSBrysonCLCurtisJR2003Inhaled corticosteroids in chronic obstructive pulmonary disease and risk of death and hospitalization: time-dependent analysisAm J Respir Crit Care Med16814889414525798

 PubMed Web of Science ®Google Scholar

KiriVAPrideNBSorianoJB2005bInhaled corticosteroids in chronic obstructive pulmonary disease: results from two observational designs free of immortal time biasAm J Respir Crit Care Med172460415901610

 PubMed Web of Science ®Google Scholar