Smoking cessation, decline in pulmonary function and total mortality: a 30 year follow up study among the Finnish cohorts of the Seven Countries Study

Transcription

1 Thorax 2001;56: Departmet of Public Health ad Geeral Practice, Uiversity of Kuopio, Kuopio, M Pelkoe M Tervahauta Departmet of Pulmoary Diseases, Kuopio Uiversity Hospital, Kuopio, M Pelkoe H Tukiaie Populatio Research Uit, Departmet of Sociology, Uiversity of Helsiki, Helsiki, I-L Notkola Departmet of Epidemiology ad Health Promotio, Natioal Public Health Istitute, Helsiki, J Tuomilehto A Nissie Correspodece to: Dr M Pelkoe, Uiversity of Kuopio, Departmet of Public Health ad Geeral Practice, P O Box 1627, FIN Kuopio, Margit.Pelkoe@uku.fi Received 9 Jauary 2001 Retured to authors 26 March 2001 Revised versio received 1 Jue 2001 Accepted for publicatio 20 Jue 2001 Smokig cessatio, declie i pulmoary fuctio ad total mortality: a 30 year follow up study amog the Fiish cohorts of the Seve Coutries Study M Pelkoe, I-L Notkola, H Tukiaie, M Tervahauta, J Tuomilehto, A Nissie Abstract Backgroud Permaet smokig cessatio reduces loss of pulmoary fuctio. Less is kow i the log term about idividuals who give up smokig temporarily or quitters with lower iitial pulmoary fuctio. Little is kow also about the relatioship betwee declie i pulmoary fuctio ad mortality. We examied these aspects ad the associatio betwee smokig, declie i pulmoary fuctio, ad mortality. Methods Two middle aged male Fiish cohorts of the Seve Coutries Study ad their re-examiatios o five occasios durig a 30 year period of follow up were aalysed. Results Durig the first 15 years (=1007) adjusted declie i forced expiratory volume i 0.75 secods ( ) was 46.4 ml/year i ever smokers, 49.3 ml/year i past smokers, 55.5 ml/year i permaet quitters, 55.5 ml/year i itermittet quitters, ad 66.0 ml/year i cotiuous smokers (p<0.001 for tred). Quitters across the etire rage of baselie had a slower declie i tha cotiuous smokers. Amog both cotiuig smokers ad ever smokers, o-survivors had a sigificatly (p<0.001) more rapid declie i tha survivors. The adjusted relative hazard for total mortality was 1.73 (95% cofidece iterval (CI) 1.41 to 2.11) ad 1.24 (95% CI 1.02 to 1.52) i the lowest ad middle tertiles of declie i. Never smokers, past smokers, ad quitters had sigificatly lower total mortality tha cotiuous smokers, partly because of their slower declie i. Coclusio These results highlight the positive evect of smokig cessatio, eve itermittet cessatio, o declie i pulmoary fuctio. Accelerated declie i pulmoary fuctio was foud to be a risk factor for total mortality. The beeficial evect of smokig cessatio o mortality may partly be mediated through a reduced declie i pulmoary fuctio. (Thorax 2001;56: ) Keywords: smokig cessatio; lug fuctio; mortality Pulmoary fuctio declies with the process of ageig ad smokig is a major evirometal factor i acceleratig the declie i pulmoary fuctio. 1 9 Givig up smokig permaetly has bee show to reduce loss of pulmoary fuctio, 1 9 but less is kow about declie i pulmoary fuctio i idividuals who give up smokig ad later start to smoke agai Little is also kow about the log term declie i quitters with impaired baselie pulmoary fuctio, although they have beefited from smokig cessatio i short follow up studies. 12 Few previous studies have examied the associatio betwee the declie i pulmoary fuctio ad mortality The associatio betwee smokig cessatio ad mortality is better described, but research ito the questio of whether reductio i the declie i pulmoary fuctio is a itermediate lik i the chai of causatio betwee smokig cessatio ad mortality is lackig. The Seve Coutries Study provides data o pulmoary fuctio for 30 years i a geeral populatio of middle aged Fiish me. This has give us a opportuity to examie the log term ifluece of cigarette smokig ad smokig cessatio, both permaet ad temporary, o the declie i pulmoary fuctio across the etire rage of baselie pulmoary fuctio. I mortality aalysis we examied the evects of smokig cessatio ad declie i pulmoary fuctio o all cause mortality ad attempted to clarify the possible itermediate role of the declie i pulmoary fuctio i the associatio betwee smokig cessatio ad mortality. Methods SUBJECTS I 1959 all me (=1711) aged years from two rural areas i were ivited to participate i a iteratioal logitudial study called the Seve Coutries Study (the details of the Fiish study populatio have bee described previously 16 ). Re-examiatios of the Fiish cohorts were performed i 1964, 1969, 1974, 1984, 1989 ad the latest i 2000 (which does ot iclude a measuremet of pulmoary fuctio). All deaths betwee 1959 ad 1994 are kow; the collectio of death certificates was performed as described previously. 16 I this study those me with complete data o smokig habits ad declie i pulmoary fuctio betwee 1959 ad 1974 (=1007) ad betwee 1959 ad 1989 (=411), respectively, were icluded i the aalyses. Whe aalysig the associatio betwee the declie i pulmoary fuctio

2 704 Pelkoe, Notkola, Tukiaie, et al ( ) ad total mortality ( ) oly those me with the full data eeded for multivariate aalyses were icluded (=932). LUNG FUNCTION MEASUREMENTS AND CALCULATION OF RATE OF CHANGE Betwee 1959 ad 1974 forced expiratory volume i 0.75 secods ( ) derived from spirometric tests was used as a measuremet of pulmoary fuctio. The spirometric test was performed usig the McKerrow spirometer ad the techique has bee described before i detail. 16 I 1984 ad 1989 spirometric recordigs were performed with the Vitalograph. I these years the best value from the two acceptable recordigs that is, withi 200 ml of each other i the stadig posture was take as. These values were, as before, corrected to BTPS ad recorded i litres. The umber of spirometric recordigs was 1614, 1504, 1341, 1084, 646, ad 410 i 1959, 1964, 1969, 1974, 1984, ad 1989, respectively. (The umber of me examied (alive) was 1675 (1711), 1558 (1595), 1393 (1428), 1174 (1225), 716 (770), ad 470 (526) i 1959, 1964, 1969, 1974, 1984 ad 1989, respectively.) The adjustmet of values for height was achieved by dividig observed values by the square of each subject s stadig height ad the multiplyig these figures by the square of the mea sample height. 4 The aual chage i height adjusted values was calculated by usig withi-perso liear regressio for each subject havig at least three acceptable measuremets. Of the me with both complete data o smokig habits ad a liear regressio durig (=1007), 92 had three ad 915 had four measuremets of pulmoary fuctio. Forty six me were excluded from the study because they had oly two measuremets betwee 1959 ad Of those measured betwee 1959 ad 1974, 411 survived util 1989 ad had a liear regressio durig (of these, seve had three pulmoary fuctio measuremets, 12 had four, 77 had five, ad 315 had all six measuremets). OTHER MEASUREMENTS The recordig of smokig habits has bee explaied i detail previously. 16 For this study the me were classified as ever smokers, past smokers at baselie, those who quitted smokig permaetly (betwee 1959 ad 1974) or itermittetly, ad cotiuous smokers. Subjects who were termed itermittet quitters were either baselie past smokers who reported smokig i at least oe of the subsequet re-examiatios or baselie smokers who relapsed back to smokig after givig up. Those smokers who did ot give up smokig util the latter half of the follow up period were icluded as cotiuous smokers. The duratio of smokig was measured at baselie i 1959 by askig the years of smokig. Weight, height, blood pressure, electrocardiography (ECG), ad total cholesterol measuremets have bee described elsewhere. 20 Body mass idex (BMI) was calculated as weight (kg) divided by height (m) squared. The presece of coroary heart disease at each examiatio was defied as electrocardiographic evidece of old myocardial ifarctio that is, a major Q wave o the ECG sca or a smaller Q wave with ST segmet chages correspodig to Miesota code items 1:1 or 1:2 ad 5: a history of myocardial ifarctio verified i a hospital, or defiite or probable agia pectoris assessed by a stadard questioaire. 20 The presece of respiratory disease (physical or history of brochial asthma, pulmoary emphysema, chroic brochitis, pulmoary tuberculosis, brochiectasis, pulmoary fibrosis, ad thorax deformity) was evaluated each time by the examiig physicia. STATISTICAL METHODS Statistical aalyses were performed usig SPSS for Widows. The divereces i the mea aual declie i betwee smokig groups were evaluated by ANCOVA ad the results are preseted with a adjustmet for age ad iitial level of pulmoary fuctio. Oly those me who had a withi-perso liear regressio ad complete data o smokig habits durig the follow up period were icluded i ANCOVA aalyses (=1007 ad =411 i ad , respectively). Cox s proportioal hazards regressio model was used to examie the evects of smokig status ad aual declie i durig o total mortality i after adjustig for other potetial risk factors. To clarify the possible itermediate role of declie i pulmoary fuctio i the associatio betwee smokig status ad mortality, two models were fitted, oe without declie i pulmoary fuctio (model 1) ad oe i which declie i pulmoary fuctio was icluded (model 2). A total of 932 me were icluded i the mortality aalyses. For these aalyses the declie i betwee 1959 ad 1974 was divided ito three tertiles. Iitial pulmoary fuctio ad values (i 1974) of diastolic blood pressure ad total cholesterol were icluded i the models as cotiuous variables, the presece of coroary heart disease betwee 1959 ad 1974 was icluded as a dichotomous variable, ad BMI (i 1974) was icluded as a variable with three categories (<18.99, , >25.00). Smokig status was classified ito five categories o the basis of smokig data from (ever, past, permaet ad itermittet quitters, ad cotiuous smokers). A additioal adjustmet for smokig was made usig the baselie duratio of smokig as a cotiuous variable ad the baselie amout of smokig as a dichotomous variable (<20 ad >20 cigarettes/day). Additioal adjustmet was also made for the presece of respiratory disease betwee 1959 ad 1974 (a dichotomous variable). Results The adjusted declie i durig the first 15 years was sigificatly slower i ever

3 Smokig cessatio, pulmoary fuctio ad mortality 705 Table 1 Smokig status Mea aual declie* i durig the first 15 years Mea age (years) Baselie (ml) Declie p Value Never <0.001 Past at the baselie <0.001 Permaet quitters <0.001 Itermittet quitters Cotiuous For tred <0.001 *Adjusted for age ad baselie pulmoary fuctio. Cotiuous smokers are referece group. At baselie. At baselie, adjusted for age ad height. Table 2 Mea aual declie* i durig the first 15 years by smokig status ad baselie tertile of Tertile of baselie Quitters Baselie (ml) Declie Cotiuous Baselie (ml) Declie Low Middle High *Adjusted for age; p<0.001 for smokig, p=0.044 for tertile of baselie, p=0.003 for age, p= for duratio of smokig, p=0.765 for smokig*tertile of (all ANCOVA). Tertile limits are <3019 ml, ml, ad >3478 ml achieved by dividig height adjusted baselie values of 1007 study subjects ito three tertiles. Icludig baselie past smokers ad permaet quitters. At baselie, adjusted for age ad height. Table 3 Smokig status Mea aual declie* i durig the whole 30 years Mea age (years) Baselie (ml) Declie p Value Never <0.001 Past at the baselie <0.001 Permaet quitters <0.001 Itermittet quitters <0.001 Cotiuous For tred <0.001 *Adjusted for age ad baselie pulmoary fuctio. Cotiuous smokers are referece group. At baselie. At baselie, adjusted for age ad height. smokers, past smokers, permaet ad itermittet quitters tha i subjects who cotiued to smoke (table 1). The test for a liear tred betwee smokig categories was also sigificat. The duratio of baselie smokig was sigificatly (p<0.001) shorter i past smokers, permaet ad itermittet quitters tha i cotiuous smokers (17.8, 24.9, 21.8, ad 27.1 years, respectively). Adjustig for the duratio of smokig did ot, however, chage the divereces i declie i betwee smokig categories, or did adjustmet for the baselie umber of cigarettes smoked or for a prevalet respiratory disease durig the follow up period (ot show). Smokig cessatio dimiished the declie i across the etire rage of baselie (table 2) with p<0.001 for smokig cessatio ad p=0.044 for tertile of baselie (ANCOVA). Both past smokers ad permaet quitters were icluded i the category of quitters to esure a reasoable umber of me for the aalyses. The iteractio evect betwee smokig cessatio ad tertile of baselie o the declie i was ot sigificat (p=0.765) which meas that the beeficial evect of smokig cessatio o the declie i was similar at all tertiles of baselie. Durig ever smokers, past smokers, permaet ad itermittet quitters lost Average aual declie i (ml/year)( ) Never smokers Cotiuous smokers 0 Survived ( ) Died ( ) Figure 1 Mea aual declie i (ml/year) with stadard error bars i selected smokig groups by survival status adjusted for age, baselie pulmoary fuctio, ad smokig. p<0.001 for age, p<0.001 for baselie pulmoary fuctio, p<0.001 for smokig, p<0.001 for survival, ad p=0.365 for smokig*survival (all ANCOVA). sigificatly less tha subjects who cotiued to smoke (table 3). Adjustig for the baselie duratio of smokig, the baselie amout of smokig, or for a prevalet respiratory disease durig the follow up period did ot chage this result either (ot show). Amog both cotiuig smokers ad ever smokers, o-survivors had a more rapid declie i tha survivors (fig 1). DiVereces i the declie i had a sigificat evect o survival (p<0.001) ad smokig (p<0.001) but there was o sigificat evect of the iteractio of smokig ad survival (p=0.365). The duratio of baselie smokig was sigificatly shorter i survivig tha i o-survivig cotiuous smokers (24.3 ad 26.6 years, respectively). However, amog smokers, additioal adjustmet for the baselie duratio of smokig was ot sigificat (p=0.938, ot show). Durig there were 684 deaths. Accordig to model 2 (table 4), both smokig status betwee 1959 ad 1974 ad aual declie i betwee 1959 ad 1974 predicted sigificatly ad idepedetly the total mortality betwee 1974 ad Additioal adjustmet for the baselie duratio of smokig, the baselie amout of smokig, or for a prevalet respiratory disease durig the follow up period did ot chage the observed associatio betwee accelerated declie i ad icreased all cause mortality (ot show). Figure 2 illustrates the evect of the rate of declie i o survival. The possible itermediate role of declie i pulmoary fuctio i the causal pathway from smokig (ad smokig cessatio) to mortality ca be assessed by comparig the divereces betwee smokig categories based o model 1 which icludes oly cotrol variables ad smokig status ad o model 2 which icludes cotrol variables, smokig status ad declie i pulmoary fuctio. The results show that the itroductio of declie i pulmoary fuctio ito the model clearly reduced the divereces betwee smokig categories. This suggests that part of the evect of smokig habits ad chages i these habits o total mortality is due to their evect o the declie i lug fuctio. For

4 706 Pelkoe, Notkola, Tukiaie, et al Table 4 Multivariate adjusted hazard ratios* for all cause mortality durig by selected variables Variable Hazard ratio (95% CI) p Value Model 1 Smokig status <0.001 Never 0.62 (0.50 to 0.77) <0.001 Past at the baselie 0.58 (0.45 to 0.75) <0.001 Permaet quitters 0.73 (0.59 to 0.89) Itermittet quitters 0.73 (0.53 to 1.00) Cotiuous 1.00 Baselie pulmoary fuctio 0.82 (0.72 to 0.94) Model 2 Smokig status Never 0.72 (0.57 to 0.90) Past at the baselie 0.68 (0.52 to 0.88) Permaet quitters 0.80 (0.65 to 0.99) Itermittet quitters 0.80 (0.58 to 1.09) Cotiuous 1.00 Baselie pulmoary fuctio 0.76 (0.66 to 0.87) <0.001 Declie i <0.001 Slow 1.00 Itermediate 1.24 (1.02 to 1.52) Rapid 1.73 (1.41 to 2.11) <0.001 *Cox s proportioal hazards regressio model. Icludig the followig variables: age, baselie pulmoary fuctio, body mass idex, diastolic blood pressure, total cholesterol, smokig status, ad coroary heart disease. Icludig the followig variables: age, baselie pulmoary fuctio, body mass idex, diastolic blood pressure, total cholesterol, smokig status, coroary heart disease, ad the tertile of declie. Cumulative survival probability Declie i Slow Itermediate Rapid Years from Figure 2 Cumulative survival probability curves for i the three tertiles of declie ( ) based o Cox s proportioal hazards regressio model (adjusted for age, baselie pulmoary fuctio, body mass idex, diastolic blood pressure, total cholesterol, smokig status, ad coroary heart disease). example, i model 1, those who had stopped smokig had 30% lower total mortality (HR 0.73 (95% CI 0.59 to 0.89) tha cotiuous smokers; adjustig for declie i reduced the diverece to 20% (HR 0.80 (95% CI 0.65 to 0.99)). Thus, it ca be estimated that about oe third of the evect of smokig cessatio o the declie i total mortality was mediated through its evect o pulmoary fuctio. Discussio I this study ever smokers, past smokers, those who quitted smokig permaetly or itermittetly lost less of their pulmoary fuctio i later adult life tha cotiuous smokers. The beeficial evect of smokig cessatio o declie i was similar i all tertiles of baselie. The rates of declie are cosistet with those published i previous studies. 2 4 Declie i pulmoary fuctio was evaluated i a relatively large sample of me who lived i a o-polluted rural area, most of whom were farmers or forestry workers. Spirometric tests were performed usig stadard criteria durig the same seaso of the year, ad 87 97% provided satisfactory spirometric data i all surveys. The radom variability of the chage i was reduced by restrictig the aalysis to those subjects with at least three measuremets. The umber of me excluded because they had oly two measuremets was low. Sice impaired pulmoary fuctio is a risk factor for failure to perform acceptable spirometric tests later, 22 selective attritio could occur i those subjects with low pulmoary fuctio ad rapid rates of declie 4 23 which would actually atteuate the associatio betwee smokig ad declie i pulmoary fuctio. The results ca be compared with other studies which have used FEV 1 because ca be assumed to measure approximately the same as FEV 1 ( eeds to be multiplied by 1.09 to estimate FEV 1 ). 25 The estimated mea aual declie i betwee examiatios may have bee avected by the chage i the equipmet ad the posture of measuremet durig follow up, ad this may be oe of the reasos why the aual declie i was slower durig the whole follow up period tha at the begiig. However, the chages i the equipmet ad the posture of measuremet do ot disturb the comparisos betwee smokig categories because all participats were measured similarly i each examiatio. Our fidig of a sigificat tred across smokig categories from o-smokers through quitters to cotiuous smokers highlights greater beefits of earlier smokig cessatio. Whe the duratio of smokig is shorter, the evects of smokig are partially reversible that is, the brochocostrictive or iflammatory evects may become ormalised. 6 I two earlier studies the declie i pulmoary fuctio was faster i those who relapsed back to smokig tha i cotiuous smokers. I cotrast, our data support the fidigs of the Lug Health Study that itermittet quitters also beefit from smokig cessatio, which suggests that cotiuous stimulatio of the iflammatory respose may lead to more profoud fuctioal ad aatomical chages i the lugs. 12 Fletcher et al have reported that smokers ot susceptible to chroic airflow limitatio may have oly a slightly worse declie i pulmoary fuctio tha ever smokers. 7 Thus, logitudial studies may uderestimate the evect of smokig o the declie i pulmoary fuctio because of the survivor evect, particularly amog the elderly I our study survivig ever smokers lost less tha survivig smokers. O the other had, durig the first half of the follow up period survivig smokers had a slower declie i tha those smokers who did ot survive. However, there was a similar but smaller diverece betwee survivig ad o-survivig ever smokers. This result suggests that survivors geerally have a tedecy to a slower declie i. The reasos may be geetic ad iclude, amog other thigs, brochial hyperresposiveess, 27 or they may be behavioural ad

5 Smokig cessatio, pulmoary fuctio ad mortality 707 iclude other protective factors such as higher physical activity 28 or a higher itake of fruit ad vegetables, 29 both factors associated with better pulmoary fuctio. I this study we foud that accelerated declie i was associated with icreased all cause mortality. A few earlier studies have described the associatio betwee the declie i pulmoary fuctio ad mortality I the Hoolulu Heart Program a6yeardeclie i FEV 1 was sigificatly related to all cause mortality i smokers. 13 I the Busselto Health Study a 6 year declie i FEV 1 predicted icreased all cause mortality sigificatly amog wome. 14 I the Baltimore logitudial study of ageig, a accelerated declie i FEV 1 icreased cardiac mortality. 15 I a previous study we foud that quitters had lower total mortality ad lower mortality from cardiovascular disease tha cotiuous smokers, which was probably explaied maily by atherosclerotic ad thrombotic mechaisms. 16 We also foud that me with impaired iitial pulmoary fuctio had a additioal beefit from smokig cessatio o mortality from cardiovascular disease, which we thought resulted from a decrease i the declie i pulmoary fuctio. Our preset results support this hypothesis because we have ow foud that part of the reductio i total mortality amog quitters is explaied by their slower declie i pulmoary fuctio. A icreased declie i pulmoary fuctio ca lead to the developmet of chroic obstructive pulmoary disease 2 5 ad it also seems to be a risk factor for mortality. It is therefore crucial to idetify measures to prevet ay additioal deterioratio. I our study smokig cessatio had a great advatageous evect. However, it has bee show that, for may smokers, the process of quittig requires several attempts before the habit is elimiated. 30 It is therefore ecouragig that itermittet quitters, as well as smokers across all levels of baselie pulmoary fuctio, gai protectio agaist a accelerated loss of pulmoary fuctio. Thus, too much emphasis caot be give to the importace of smokig cessatio. Further studies are eeded to elucidate the other mechaisms which result i a declie i pulmoary fuctio. Supported by grats from the Fiish Academy, the Fiish Ati-Tuberculosis Associatio Foudatio, the Fiish Lug Health Associatio, ad the Natioal Istitute o Agig, USA (grat EDC-1 1 RO1 AGO A1). 1 Burchfield CM, Marcus EB, Curb JD, et al.evects of smokig ad smokig cessatio o logitudial declie i pulmoary fuctio. Am J Respir Crit Care Med 1995;151: Scalo PD, Coett JE, Waller LA, et al. Smokig cessatio ad lug fuctio i mild-to-moderate chroic obstructive pulmoary disease. Am J Respir Crit Care Med 2000;161: Lage P, Groth S, Nyboe J, et al. EVects of smokig ad chages i smokig habits o the declie of FEV 1. Eur Respir J 1989;2: Xu X, Dockery DW, Ware JH, et al. EVects of cigarette smokig o rate of loss of pulmoary fuctio i adults: a logitudial assessmet. Am Rev Respir Dis 1992;146: Tager IB, Segal MR, Speizer FE, et al. The atural history of forced expiratory volumes. EVect of cigarette smokig ad respiratory symptoms. Am Rev Respir Dis 1988;138: Camilli AE, Burrows B, Kudso RJ, et al. Logitudial chages i forced expiratory volume i oe secod i adults. EVects of smokig ad smokig cessatio. Am Rev Respir Dis 1987;135: Fletcher C, Peto R. The atural history of chroic airflow obstructio. BMJ 1977;1: Hughes JA, Hutchiso DC, Bellamy D, et al. The ifluece of cigarette smokig ad its withdrawal o the aual chage of lug fuctio i pulmoary emphysema. QJ Med 1981;202: Sherill DL, Holberg CJ, Eright PL, et al. Logitudial aalysis of the evects of smokig oset ad cessatio o pulmoary fuctio. Am J Respir Crit Care Med 1994;149: Xu X, Weiss ST, Rijcke B, et al. Smokig, chages i smokig habits, ad rate of declie i FEV 1 : ew isight ito geder divereces. Eur Respir J 1994;7: Sherill DL, Eright P, Clie M, et al. Rates of declie i lug fuctio amog subjects who restart cigarette smokig. Chest 1996;109: Murray RB, Athoise NR, Coett JE, et al. EVects of multiple attempts to quit smokig ad relapses to smokig o pulmoary fuctio. J Cli Epidemiol 1998;51: Rodriquez BL, Masaki K, Burchfiel C, et al. Pulmoary fuctio declie ad 17-year total mortality: The Hoolulu Heart Program. Am J Epidemiol 1994;151: Rya G, Kuima MW, Divitii ML, et al. Declie i lug fuctio ad mortality: the Busselto Health Study. J Epidemiol Commuity Health 1999;53: Tockma MS, Pearso JD, Fleg JL, et al. Rapid declie i FEV 1. A ew risk factor for coroary heart disease mortality. Am J Respir Crit Care Med 1995;151: Pelkoe M, Tukiaie H, Tervahauta M, et al. Pulmoary fuctio, smokig cessatio ad 30 year mortality i middle aged Fiish me. Thorax 2000;55: Jacobs DR, Jr, Adachi H, Mulder I,et al. Cigarette smokig ad mortality risk. Twety-five-year follow-up of the Seve Coutries Study. Arch Iter Med 1999;159: Kawachi I, Colditz GA, Stampfer MJ, et al. Smokig cessatio i relatio to total mortality rates i wome. A prospective cohort study. A Iter Med 1993;119: Karvoe M, Blomqvist G, Kallio V, et al. Me i rural east ad west. Acta Med Scad 1967;460: Keys A. Coroary heart disease i seve coutries. Am Heart Assoc Moogr 1970; Rose GA, Blackbur H. Cardiovascular survey method. Geeva: World Health Orgaizatio, Eise EA, Robis JM, Greaves IA, et al. Selectio evects of repeatability criteria applied to lug spirometry. Am J Epidemiol 1984;120: Va Pelt W, Borsboom GJJM, Rijcke B,et al. Discrepacies betwee logitudial ad cross-sectioal chage i vetilatory fuctio i 12 years of follow-up. Am Rev Respir Dis 1994;149: Sherma CB, Xu X, Speizer FE, et al. Logitudial lug fuctio declie i subjects with respiratory symptoms. Am Rev Respir Dis 1992;146: Cotes JE. Lug fuctio: assessmet ad applicatio i medicie. 3rd ed. Bosto: Blackwell Scietific Publicatios, Ware JH, Dockery DW, Louis TA. Logitudial ad crosssectioal estimates of pulmoary fuctio declie i eversmokig adults. Am J Epidemiol 1990;132: Rijcke B, Schoute JP, Xu X, et al. Airway hyperresposiveess to histamie associated with accelerated declie i FEV 1. Am J Respir Crit Care Med 1995;151: Burchfiel CM, Eright PL, Sharp DS, et al. Factors associated with variatios i pulmoary fuctio amog elderly Japaese-America me. Chest 1997;112: Tabak C, Smith HA, Räsäe L, et al. Dietary factors ad pulmoary fuctio: a cross sectioal study i middle aged me from three Europea coutries. Thorax 1999;54: Raw M, McNeill A, West R. Smokig cessatio guidelies for health professioals. A guide to evective smokig cessatio itervetios for health care system. Thorax 1998; 53(Suppl 5, Pt 1):S1 19.