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COPD-related morbidity and mortality after smoking cessation: status of the evidence

N. S. Godtfredsen, T. H. Lam, T. T. Hansel, M. E. Leon, N. Gray, C. Dresler, D. M. Burns, E. Prescott, J. Vestbo
European Respiratory Journal 2008 32: 844-853; DOI: 10.1183/09031936.00160007
N. S. Godtfredsen
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T. H. Lam
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T. T. Hansel
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M. E. Leon
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N. Gray
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C. Dresler
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D. M. Burns
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E. Prescott
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J. Vestbo
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  • Fig. 1—
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    Fig. 1—

    Forced expiratory volume in one second (FEV1) decline expressed as a percentage of the decline in 100% of continuing smokers in those studies for which this measure was available. All but one of these studies show a relative reduction in FEV1 decline.

  • Fig. 2—
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    Fig. 2—

    Relative risk (RR)/hazard ratio (HR)/mortality rate (MR) ratio of mortality due to chronic obstructive pulmonary disease after smoking cessation (▪) compared with continuing smoking (▴; RR 1.0).

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    Fig. 3—

    Risk of all-cause mortality after smoking cessation expressed as a percentage of the risk in 100% of continuing smokers. The majority of these studies show a reduction in risk. #: females alone.

Tables

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  • Table 1—

    Effects of smoking cessation on chronic obstructive pulmonary disease(COPD) morbidity

    First author [ref.]StudySubjects nAge yrsFollow-up# yrsΔFEV1 mL·yr−1Summary effectComments
    Clinically based
     Fletcher 15London, UK792 working M30–598-80 (heavy smokers), -62 (light smokers), -37 (ex-smokers) with mild obstruction+Spirometry was performed every 6 months
     Hughes 13London, UK56 M with emphysema45–633–13-58 (smokers), -15 (ex-smokers; p<0.001)+Greater VC decline in smokers than ex-smokers
     Anthonisen 12NIH (USA)985 COPD Pts (FEV1 < 60% pred)53–683-44 (smokers, ex-smokers)0Spirometry was performed every 3 months.
     Postma 14Groningen, NL81 moderate–severe COPD Pts39–572–21-85 (smokers), -49 (ex-smokers; p<0.05)+
     Kessler 20Strasbourg, FR64 moderate–severe COPD Pts57–722.5ND0No difference in COPD exacerbation hospitalisation risk for ex- and current smokers (univariate analysis)
     Garcia-Aymerich 21Barcelona, ES86 Cs (hospitalised, COPD exacerbation); 86 C (stable COPD)60–78Cross-sectionalND-Current smoking associated with less hospitalisation than ex-smoking (OR 0.30)
     Kanner 18LHS (USA)5887 mild–moderate COPD Pts35–605Greater decline in smokers, but not ex-smokers, with more than one LRTI annually (p = 0.0001)+Ex-smokers had fewer self-reported LRTI episodes than current smokers (p = 0.0003)
     Anthonisen 8LHS (USA)5887 mild–moderate COPD Pts35–6011-66 (M smokers), -30 (M ex-smokers), -54 (F smokers), -22 (F ex-smokers)+
     Anthonisen 17LHS (USA)5887 mild–moderate COPD Pts35–605ND0No difference between treatment groups or smokers versus ex-smokers in hospitalisation rate for respiratory causes
     Makris 19Heraklion, GR102 moderate–severe COPD Pts60–70374 (decline faster in current than ex-smokers; p = 0.004)+Both current and ex-smokers with frequent COPD exacerbations had faster FEV1-decline
    Population-based
     Tashkin 27Los Angeles, CA, USA2401 (Gen Pop sample)25–645Same unquantified decline in current/ex-smoking M with COPD0/+Ex-smoking F with COPD had smaller declines than current smokers (p<0.002)
     Sherrill 28Tucson, AZ, USA3805 M/F (random cluster)≥1817M quitters in lowest FEV1/FVC quartile had similar decline to current smokers0/+F quitters in the lowest FEV1/FVC quartile had slower decline than current smokers
     Burchfiel 22Honolulu Heart Program (USA)4451 Japanese–American M45–686-18.8 (quitters with COPD, n = 64), -31.4 (smokers with COPD, n = 199; p = 0.024)+Adjusted for baseline FEV1 and amount smoked
     Pelkonen 23Helsinki, FI1711 M from two rural areas40–5915-62.9 (smokers), -48.4 (ex-smokers; p<0.001) in lowest FEV0.75 tertile+
     Godtfredsen 29Copenhagen, DK19709 (Gen Pop sample, three pooled studies)20–9314ND+Risk of hospitalisation for COPD lower in long-term ex-smokers (HR 0.30) and quitters (HR 0.53) than current smokers.
     LØkke 31Copenhagen DK8045 M/F from CCHS30–6025ND+OR for developing COPD showed increasing trend with shorter duration of smoking cessation compared to never-smokers
     Mannino 25Lexington, KY, USA15536 M/F from ARIC study44–663ND+OR for rapid FEV1 decline not higher in ex- than never-smokers (1.0); OR in current smokers 1.3 (95% CI 1.2–1.5)
     Lindberg 24Luleå, SE1109 M/F with RS36–6710-43/-35 (M/F smokers), -35/-27 (M/F ex-smokers; p<0.05)+Equal decline in never- and long-term ex-smokers; similar in quitters, re-starters and smokers
    • Δ: change; FEV1: forced expiratory volume in one second; NIH: National Institutes of Health; NL: the Netherlands; FR: France; ES: Spain; LHS: Lung Health Study; GR: Greece; FI: Finland; DK: Denmark; SE: Sweden; M: male; Pt: patient; % pred: % predicted; Cs: cases; C: controls; Gen Pop: general population; CCHS: Copenhagen City Heart Study; ARIC: Atherosclerosis Risk in Communities; RS: respiratory symptoms; ND: not determined; LRTI: lower respiratory tract illness; FVC: forced vital capacity; FEV0.75: forced expiratory volume in 0.75 seconds; VC: vital capacity; OR: odds ratio; F: female; HR: hazard ratio; CI: confidence interval; +: ex-smokers/quitters showed benefits over current smokers; -: current smokers showed benefits over ex-smokers/quitters; 0: no difference between the two groups. #: after smoking cessation.

  • Table 2—

    Effects of smoking cessation on all-cause and chronic obstructive pulmonary disease (COPD) mortality

    First author [ref.]StudySubjects nFollow-up# yrsMortality outcomeSummary effectComments¶
    Clinically based
     Kanner 33USA140 Utah COPD Pts7–13All-cause+In a case–control design (sex- and age-matched Pop), 12-yr survival probabilities were 86, 79 and 64% in never-, ex- and current smokers, respectively
     Postma 34Groningen, NL129 severe COPD Pts18All-cause+Pts were stratified according to bronchodilator reversibility; relative survival was higher in both current- and ex-smokers with greater reversibility; within each stratum, mortality was lower in ex- than current smokers
     Anthonisen 12USA985 COPD Pts aged 53–68 yrs3All-cause0Overall mortality was 23% (no difference between current and ex-smokers)
     Hersh 36USA139 M severe COPD Pts aged <53 yrs8All-cause+Recent smoking status predicted mortality independently of the effects of lifetime smoking intensity; Pts who were ex-smokers at enrolment had better survival than smokers
     Anthonisen 17LHS (USA)5887 M/F smokers with early COPD (FEV1 55–90%) aged 35–60 yrs5CV?There were 149 deaths during the study, caused largely by lung cancer and CVD; smoking cessation was associated with significant reductions in fatal CVD and coronary artery disease (too few COPD deaths for analysis)
     Anthonisen 35USA5887 M/F smokers with early COPD (FEV1 55–90%) aged 35–60 yrs14.5All-cause/ respiratory+After 14.5 yrs of follow-up, 731 patients had died; all-cause/respiratory MR was significantly lower in the special intervention group than in the usual care group
    Population-based
     Doll 56UK6194 F doctors22COPD+COPD MRs lower in ex- than current smokers (5.0 versus 10.5–32.0% (depending on amount smoked))
     Rogot 32USA∼200000 M US veterans16COPD- to +COPD MRs higher in ex- than current smokers until 10 yrs after smoking cessation; thereafter lower MRs in ex- than current smokers (5.2 versus 12.1%)
     Carstensen 39SE25129 M16COPD+COPD MRs lower in ex- than current smokers (1.8 versus 1.9–5.3% (depending on amount smoked))
     Marcus 41Honolulu Heart Program (USA)11136 Japanese–American M aged 45– 65 yrs at enrolment20COPD- to +Age-specific COPD MRs calculated at 5-yr intervals (1965–1984); after 10 yrs, MRs were higher in ex- than never- and current smokers; after ≥15 yrs, MRs were similar in never- and ex-smokers and lower than current smokers
     Tockman 42USA36110 M/F aged 35–84 yrs from private census Pop, examined in two 6-yr periods884 M with FEV1 measures(subset of above)All-cause/ COPD+M MRs due to both all causes and COPD were greater in ex- than never-smokers, but lower than MRs for current smokers (p<0.05); this applied to both time periods; same trend for F, but too few COPD deaths in ex-smokers for analysis. Normal FEV1: OR 1 (never-smokers), 1.75 (ex-smokers), 4.80 (current smokers); FEV1 <65% pred: OR 3.71 (never-smokers), 6.50 (ex-smokers), 17.80 (current smokers)
     Kuller 40USA12866 M from MRFIT10All-cause+Lower all-cause MR in ex- than current smokers
     Lange 45DK14214 M/F from CCHS13COPD+Compared to never-smokers, RR of COPD mortality in F ex-smokers was 11 (95% CI 2.5–53), current smokers 15 (95% CI 3.1–65); RR in M ex-smokers was 3.0 (95% CI 0.9–10), current smokers 6.4 (95% CI 2.0–20)
     Tverdal 43NO68000 M/F aged 35–49 yrs13 (mean)All-cause+MRs for ex-smokers were intermediate to rates for never-smokers and smokers in both M and F
     Ben-Shlomo 38UK19018 M from Whitehall Study18COPD+Annual COPD MRs in never-, ex- and current smokers were 0.68, 0.95 and 2.2 per thousand study population
     Sunyer 44ES477 M from Barcelona aged >65 yrs8COPD0There were similar prevalences of self-reported respiratory illness in ex- and current smokers, and similar annual COPD MRs (6.0 versus 1.7 per thousand study population in never-smokers)
     Knuiman 48AU4277 M/F from the Busselton Health Study20–26All-cause-Per 10% decrease in FEV1, HR of all-cause mortality was 1.195 (95% CI 1.124–1.271) in ex-smokers and 1.167 (95% CI 1.108–1.229) in current smokers compared to never-smokers
     Engstrom 49SE291 smoking M born 191414CV0CV MRs in current- and ex-smokers similar by FEV1 decline tertile
     Pelkonen 46FI1582 middle-aged M30All-cause/ COPD+/-Compared to current smokers, there was lower total mortality in never- smokers, long-term ex-smokers and quitters; RR of COPD mortality in ex-smokers was 2.51 (95% CI 0.65–9.70) compared to current smokers.
     Godtfredsen 47DK19732 M/F from 3 Copenhagen Pop studies15.5 (mean)All-cause/COPD+/0RR of COPD mortality after smoking cessation was 0.77 (95% CI 0.44–1.35) compared to current smokers; HR of all-cause mortality was 0.65 (95% CI 0.56–0.74); no comparison was made with never-smokers
     Mannino 50USA5542 M/F aged 25–74 yrs from NHANES22All-cause+HR of all-cause mortality in a multivariate adjusted model was 1.1 in ex-smokers (95% CI 0.9–1.4), 1.4 in current smokers (95% CI 1.2–1.7)
     Doll 37, 55UK34439 M UK doctors40, 50All-cause/ COPD+COPD MRs in ex-smokers were intermediate between those of never-smokers and current smokers; RR of all-cause mortality lower in ex- than current smokers (1.3 versus 2.2)
    Chinese
     Ho 51HK2030 M/F aged ≥70 yrs3All-cause/COPD0/-Similar all-cause MRs in ex- and current smokers; higher rate of respiratory mortality in F ex-smokers (RR 2.3 (95% CI 1.3–4.0))
     Lam 53HK1268 retired male cadres aged ≥60 yrs12COPD-RR of COPD mortality 2.13 (95% CI 0.55–8.30) in current smokers; 4.10 (95% CI 1.18–14.28) in ex-smokers
     Hsu 52TW4049 M/F aged ≥60 yrs7All-cause/ COPD0No differences between ex- and current smokers for all-cause or cause-specific mortality; this study does not meet standard quality criteria
     Lam 54HK56167 M/F aged ≥65 yrs4 (mean)All-cause/ COPD+/-RR of all-cause mortality in ex-smokers was 1.39 (95% CI 1.23–1.56) in M and 1.43 (95% CI 1.25–1.64) in F; rates were significantly higher in current smokers; COPD MRs were higher in ex- than current smokers
    • NL: the Netherlands; LHS: Lung Health Study; SE: Sweden; DK: Denmark; NO: Norway; ES: Spain; AU: Australia; FI: Finland; HK: Hong Kong; TW: Taiwan; Pt: patient; M: male; F: female; FEV1: forced expiratory volume in one second; Pop: population; MRFIT: Multiple Risk Factor Intervention Trial; CCHS: Copenhagen City Heart Study; NHANES: National Health and Nutrition Examination Survey; CV: cardiovascular; CVD: cardiovascular disease; MR: mortality rate; OR: odds ratio; % pred: % predicted; RR: relative risk; CI: confidence interval; HR: hazard ratio; +: risks lower in ex-smokers than smokers (benefits of quitting); -: risks higher in ex-smokers than smokers; 0: risks similar in ex-smokers and smokers; ?: results not clear. #: after smoking cessation; ¶: RR and HR of never-smokers (reference group) = 1.0.

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COPD-related morbidity and mortality after smoking cessation: status of the evidence
N. S. Godtfredsen, T. H. Lam, T. T. Hansel, M. E. Leon, N. Gray, C. Dresler, D. M. Burns, E. Prescott, J. Vestbo
European Respiratory Journal Oct 2008, 32 (4) 844-853; DOI: 10.1183/09031936.00160007

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COPD-related morbidity and mortality after smoking cessation: status of the evidence
N. S. Godtfredsen, T. H. Lam, T. T. Hansel, M. E. Leon, N. Gray, C. Dresler, D. M. Burns, E. Prescott, J. Vestbo
European Respiratory Journal Oct 2008, 32 (4) 844-853; DOI: 10.1183/09031936.00160007
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