Tobacco Documents Online

'.. •' 1026 •^(tY iC1r) itRITIStI AtEIriCAt. JDUNNAI. 27 OC7OOER 11 Verification of ,moking his-tory in pat.ients after infarction using urinary nicotine and. cotinine measurements 1voTrst • Thts elatkial rtl~y R G WILCOX, J HUGHES,. J ROLAND . . Eno;eetcd by eapyt;l Briria+i M4rlicallnrn.1,1979, 2, 1028-1028 Summary and conclusions Urinary concentrations of nicotine and Its major rttctabolitc catinine were measured In volunteers whose smoking habits were known to test the reliability of the measurements as Indicators of current smoking. In the non-smokers detectable concentrations were always below the confidence limits set for the method, while in smokers the concentrations were always above these limits. After subjects stopped smoking cotinine appeared in the urine for longer than nicotine and was still deteet- able at least 36 hours after the last cigarette had been smoked. «'hen this method was used to verify the smoking histories given by patients attending an infarction clinic it was estimated that 46-53 0 of previous smokers had actually stopped smoking compared with the 63% who said that they had done so. It is suggested that simultaneous assays of urinary nicotine and cotinine may be a useful means of verifying patients' current smoking habits. hw (Tjtk 11 US,C(>d 4 Subjects and methods We collected random samrks of urine fnr nicosiine and cotin nteasunrnents from 104 voluntrers (46 non-smokers and 58 smoke whe+se smoking history we eonsidered to be reiiabk. To study the tin pattern of nicotine and'cotinine exeretion we also collected samples urine at about 0800, 1200, 1tM, and 2200 from 13 habitual smoke who continued to smokc normally for the frrst 24 hours and th attempted to sbuain during the next 36 hou.rs. We then rnilect urine sampla from RS paticnts who ottended our infarction clir during the sttialy period, and at that riat we rccorded the patien dct:l•rrrJ current sttn.king hahits. 'lltcr lmtl:all smoked retularly up the time of their illness. We compared the previous and curic smoking state of 305 consecutive paticnts attcndin= the infarcti clinic as part of secondar•r prevention drug trials. The smok4 among them had been strongly adviscd to stop smoking during th initial admission. This advice was rciterated at each clinic risit those who continued to smoke, whereas those who said thcy'1t stopped were commended and advised never to start smoking aga The concentrations of nicotine and its rnetabolite eotinine in t urine samples were measured by )II using a modification of t method described by kivela'• an vtthout knowing the srnoki history of the ratients from tvhnnt the samples derived. The ass: were done in batches within one week after collecting 'the specimc To 20 Ir>u j,ot; was added 4 mal sodium hcdroxidell and 0-5 intcrnat standard snlution containing 0•02 mr rnethyprylone chloroform. Chloroform, 7 ml, was thcn added and mixed -for minutes. The layers were separated by ccntrifuRinC lightly for o Introduction The health hazards attributed to smoking and the hcnc6ts that accrue from giving up have received considerable attcntiC4t.'-' Unfortunately, patients may not alazys be tzuthfisI in declaring their current smoking habits,' so the real ralue of stopping smokins may he underestimated. Objective methods nf vaiitlating patients' smoking histories have been sought. Determining plasma concentration•s of thinc}•anatc, which has a long haif lifc and is relatively easily measured, is currently a favourcd 'method, although there is considcrablc overlap t+etwccn non- smokers and those smoking less than 10 cigarettes a day.r Blood carboxyhacmnglobin concentrations have proved to be not sufficicntiy discriminating, and urinary nicotine measurements have been suggested as providing a rnore accurate asscssment.' Nicotine is rapidly absorbed through the lungs and reaches a peak concentration in the urine within 15 minutes after a cigarette has been smoked. Thr amount of unchanged nicotine excreted, however, is small, most of the cxcretinn hcinF in the form of its major mt.-taMlitc ctxinine. Aftrr smtiking thc peak urinary ctttininc czcrctiun occurs at about tw'o hours and its clcarance is slo.r.' We have investigated the valuc of mca•uring both urine nieotine and eutinine concentrations as an indcx nf eurrcitt smoking and harc used nicotine and cntininc mcasurt.•mcnts to verify the smoking histories given by patients attending a post- infarction clinic. L'nivenit7 Itnspital, Nattlneham NG7 2UH R G WILCOX. a,ar.r, lccturer in medicine j 1-IUGHL•S, ttMU, chief inedical laboratory uientifce offieer,depantncnrof clinical chemistry City llnspitrrl, Nnttineham J ROLANn, MRCr, medical r:gistru minute. Tbr chlotnform attract was transfcrred to a tal+crcQ crntrifu tube and evaporated down to apprnximatrly 50 µ1 at room temperattL under vacuum, and 3 ra of the concentratcd extraet w-as injccted intt Pyc 10•t~acli r~i lchrttmatnerar+hlittcdwithattameionisationdsttrv The column was lU^, human chorionic gona otr-p tn (Apiczon tm Diatonite CQ 80-100 mcsh (Pyc Unicani), column tertperatt. '_'00 C, carrier gas (nitrogen) flow rate 70 ml;min. Quantitative rrsu were obtained by comraring the peak hciFht ratios of nicotine:irtterr stan.fardoreotinine: internal standard atainst thoscofaqueous standar treated as urine. The sensitivity of the method was established usi standard solutions of decrcasing concentratinn, Theronfidence detc tion coneentrations for nicotine and rotininc were found to (I• 12 ;emol!I (2 ;eF1)0t1 mi) and 0•57 .mol!1(J0 ;cg,+100 ml) respeeti. c The creatinine toncentration of cach urinc satnpic was also nxasur in order to eotnpare eotinine:crntinine ratios between indixidu smoking the same number of cigarettes each day. Results , rAU1sATItW Ofr Mti7ttqn • Qe cnllccacd b`i rattalntn urine satnpk•s fts+m the 46 non-srnol3 volunteers (never smoked, 42; not srs>.+ked for at least one year; foo Nene of the samples contained any nicotine, and -Ithouth fous (o' contained entininc, the concrntratinns were btlour the confiden linsit af nor methotL lltus no nun-snroker had either a urina nicotine or a eotinine eonecntration above the conAde•neeIimiis set our e.aluation of the method. We collected 1RR urine samples fiont the 58 volunteers vo- smcsked regularly-. Of thesc, _9, smoked a constant number of ciiarett each day, ranging from three to 45 (mran 27 ciFa:ettes/'uv). T other =a voluntecra .vcrc trying to reduce their intake and smolcec varying number of cigarettes each day. All thc urine samples contain cntinine in ennccntratinns detcetahle with con6dcnce by our methc the mean (;ESE of mcan) value being b•t}i:E0-73 pmoi!I (1t16:h pg 11tt/ mi). Similarly they 311 contained nicotine in e:eeess of t ennfcdcncc level for nur mcthud, the rncan value being 7 96 ~ 1• ;Lmol 1(173 f 19 r.p'IM ml). In this tn,ol•int group as a a•hole th: aas no cnrrelation between titr declared numh:r of eitarettes smok and the urinary nictnine and cotinine concentrations. In the subgro•

with a constant J.rilrrisarvttc cwtwtnptiun, lwwc..r, 11K nuntivr of ciractia srnokad t•orrclatcd stronCly with the uriitary etsininc: ereatininc ratio (fit I). -' Thinc•en:of the smokinf coluntccrs with conat. nwking habits then attempt.d to abstain from smokin= fur the nest 3n huurs, hut only nine stwti•ecJc.1. 1clSure 2 sbwts theu rttcxn urinary• nicutine and c- 'x etuseanratiom for the 24-hour p.•rioJ of numW smoking ! sf by the next 36 hours of ahstin.-ssrs. This iltdicates the rc.- re7y slower rate of Jiopp.aranee of cotininc frotn the urinr in J.•,;Ln.J1 .x-snwk.•rs were still s,nuking, a dccaptiun ntc of! about Of the hJ5 aatst•cutii-e p-''nts (254 men, 51 women) attending tlic infmcliwt clinic Jurinr . survey, _t11t (G!1'•") lud hccn rcpular snwkcrs up to the tintc of thnr illness, tli(,.1(";) haJ nv.•cr smokedi and 12 (3°„) had nut smokc.d for at la•ast onc 1•ar befurt thcir illness. eompasison witb nieetinalS>t11i~6ni~a•nrse r s a s>a '-p""'Y•' i'+'aakr"l k-bift +I 2011 +mokm dt:r h.~.rt erraci ,u:.afiwj rr iwt ..wv../rir. or~asrt^^~~1it ae~v' x +. " .~iotat~5uo16 11 z7 y~ ~ I~staJ!iisvtiite was fuutttd in the urinc in only Irro subi.•en tv~ "anJ in onc suF;c.t at t1:IW on Jay 1. iuAlr"-'on•"Ja" p s•s 30 • _-5 • ~ C e I•0 • Y 1-S C 71 o t-0 Y r •o-40 0'6 • 0 ~ r 0 S 1D 1S IO 7S n 3S s0 t~qoranesleyr rttt I-•Cortatatier betaen uriaary awiniae es+r+tinise (,.enol: taswt) rait.s aad'auatber of ei(peertes smoileJ in 29 regular smoka6 --~...t.+wr.nea M : W •,, _1C -a,t 7,,. ~rrf Iww.w.. w r-) +•++rwiw. s~wilnR At u 071 'A 2007) ). 12 pU 31 ts t+tll 25 U21 a4.. ~«,.t.u..ata:,,tnnntr .rri.J Jar s 9 tt R 19 . wr.t+WM•.Jr++sSt1)) atan 271b)~ t./S2t tT.(Ml TAat.t 11-Clw.ter ir rrw&rX i.iiU wwr.LW rn rfr.• aua l:Jq .urdek t:.w d.r.r/n arts.hwl wtat. .TWW -3 -9 .1a ~+.+f (.ricia+ At a: 1u 7oS t4('J -O++.riat pr.-y++lr +s :!7) _ A1 ITit M/AC) :01/ iwt~Jwlwu tWl 171A1/ i31661 1)1 1! (31) 2otA! 2!(ril A0 ta+(-.7iea•Iriwwdh.erratft.(7) altr tr R'lten asked about their currret smoking habits 131 (63"„) of the preriouslY regular snwkers said that tfler had now swpprd, and this reply was irnik-pt•ntksst of th.ti previous eonsump•.ion of eitan-ttes (tahk 1) or the timing of the survey in r¢laline to the heart attaek : (ubk 11). If the Jeoeluiua rale ataonL this larger group of sntokers is simiLu to that in the group whose urine was tested, howeeer. the true prreearaOC of previous sri+olrers trlte aetwJly haJ stopped smoking is likely to be between 46 and 53;.. a 2 t 0 otlta t1rG ltip 22rD 0lCA ,200 1im = 0[Itp Doyt Dar1 Doy3 stC 2-Disappeary+= of niowine and tvtininc fnra urine ia nine patients wl+o stot.prd snwkint; at ab.wt ".-OOwt J+y 1. Value are mans t SL of mr+n; a-9. USl\G AtET11OD TO OIEt2 M1t7K(XG H1S7ORY IX P.1TIt:.\•TSAPTEII L`1fJtRCTIOa Of the IIS subjects attsmdinS the infarction clinic who haP ub•cn repular smokcrs up to the tunc of dKtir illnazs. 3tl (a2'») saiJ rhatthcp - still smoking anJ' all of these baJ casily J.trc•t>thk utinrrg inc and cotininc .tiuw.•nrr.ttibns. 'Il/c ranaininS {v (Stt*_) ,_..cnts said that the}"haJ stu(+(+al snnJ:utr, and in MI •,f thew we could not J.a•tt citUcr nicutin.• ur eotiuine in tht•ir wdn. In eiSht paticnts, however, both nientina andI .otininc could he .%+n1;J.•rule Jttectcd in thc urine, while in thc remaining five Latiu•nts tutiniiu• and nieotinc wrre J.•tcaahle hut in cuneentr.niuns IxG•w thc oadi.kMKt limits of our mrthoJ. This sncr.ws tlut right to 13 of tli..e •lo Discussion T7ar answer to the question "1rc you still slnokin= ciearctre•s and if so how many?" is hksdy ttt be influcnccd by tlle manner and circumstances in which it is asked. Bun a aI" gave a group of rattents N•h0had had an lnfarctit#t"IntCnSlvC advice" with a "furecful approach" and fintnd that 63", of previous smokers said they had stuppcd•as compared with 27"„ who tt•crc given eunveruional advim We Oave our patients eonventional.but uncwnprumising advice to stop smoking and also founl': that 63";, uf prcvi/tus smokers said they had done so, irf.slseetit•e of pnwiuus cigsr>.•ttc consumption or the timc since infarttion. IIuw is the acwrrey nf such statements best cstahlished? When mczstuing the carhnxyhacmu0luhin (COl ih) : conccn- tratiuns in vc-nuus hlaKf Sfllcts er o!' found that ?3-10": of alk•Ot•d et-snwkcss had amc.mratitms above 1•7",,, thrir critical value hasctl on mcasurcmcnts obtained in 161 known ntm- srntkcrs. No general aprc•emcnt e.xists, htmvv~•r, on tlsis criiinl' taluc, and in that study 5vc nut of S6 patients who said they t • still sma(tint had COHb cunccntr;ttigas-+^lo.r 1•7^'.. _ ~~sryyl~ ~~,;,~Ll'Sll~{i1[1~L•Atr3(h~lK•~ L.t•' a• il~~,'~t~rtllt(t'71 ~~ C(rS7RY1371c~!]1 j+it1l:.ZS~TS~i.7Tt3IDS?* P nnary ^nicutinc mt•asurcrnentsi too, arc intlucnccd byy ra..itK urrokin0 under c.titrcnnc cslxrimcntal: cxpl>,un„hut, byy u.inx a m.th.rl similar tu that dcscribcd here and incorr--ratint a nitn+rcn Jetct,aur,.vhich int•rcaxs the srnsiti.tity a+n.iilcr.tblv, Ru...ll!:u+.l hcy.rahcnJ• f,Mtnd nu.n•crl•rp Fx•t.r.-en.rn.-k.n and mnl-unukcrs tmFlcr rnmnali tomditiuns. In uur stu.ly•nu nun- >m~d cr ha.l any dctcl.•tahk ninltinc, althuuy;h fuur ha.l tktcctahll+ crnininc hut at vcxtc.ntrui.a» l.clu.v thc tti+nfitl.ncc limii vf,rur a..:q: In all Ihc currrnt smok.rs lwnh nicotine and cutininc c.mid Ix rcaJill° .lctcat.J in thcir urine. r'

1028 In future studies we shall note t trand of ciprettc smula:di for this will determine the nicntinc yield , cr cigarette. This clearly will influence the correlation bctr<cen urinary cotinine: txeatininc ratios and the numbcr of cigarettes smoked cach day and, in the ewrt:nt study, may explain some of the scattcr. We suggest that simultaneous assays of urinary nicotine and cotinine could be a useful index of current smoking habits and that the slower disappearance of cotinine from the urine will facilitate idcntifyine smokers who attempt to conceal their habit by abstaining from smokin6 on the day of their clinic visit. We should ltlte to thank Mr E J C.oilin, of John Player and Sena, Nottinghany for arranging the supplies of cotininc; btr A RridM principal bioehettsiu, University Hos(+ital, Nottingham, for technical guidance; Prokssor J R A MitcJsell for his helpful criticism; and Mrs Jayne Webster for typing the tnatruscript. • RRIT1SIt N/:DIUtL JOUR%AL 27 OcTOntrR 197~ References t I1,dI. R, and 11i11, A n, ,\utiorw/ Cwun Innirutr AfemTr,rp/n, 1966, 19 :cn. ~/lantm.rnd. I': C, and earftnkel, L, ArcAirtt 4 r:wt;.r.Mrtwrol xteirh 1'Nr9, 1!, 167. a(irrrdius, T, Kannel, W It, and L1cGee, U, LoNcrt, 1976, ?. 1345. s R'illsclinwm, C, et o1, IrMcn, 1975, 1, I IS. s Uoil, R, snd Cetn, R, liritish A(tdie,rl )wannl, 1976, 2, 1525. `Sillcrt, R R',ct./,1Jriridl,ttcJicolJnureal, 1978, 2, 11t+S. r Vugt, 7 At, tr .l, Awnicoa Tornael~ ~nj IhrNit lltulth', 1977, 67, 545. ' r Russell, M A H, and itcl•crabend, .., 1'A/Krt, 1975, 1, 179. ' Heckttt, A H, and'frius, E J, A'eh,rt, 1966, 211, 1415. sa Ki.•ela, E lf'r, in.1lonnnl e/ Tsicehyy, cd l Sunshine, p 252. Oe.eland Ohin, CRC Ptess Inc. 1971. rs Bwt, A, tr al. Lurttt, 197•1, 1, 304. " st Jnnes, R U, Cmtntins, Il 'r, and Cerniiy A A, Lnntn, 19'!2, 2, 302. ta Russell, M A H, Cok, r V, and 13tovrn, E, Lsnttt, 1973, 1, 576. (AcuPtrd 14 Ausurt 19i9) Return to work and quality of life after surgery for coronar~ ) ) artery disease STEPHEN WESTABY, RALPH N SAPSFORD, HUGH •H BENTALL Dririili btad.nl~wrwrl,1979, 2, 1028-1031 Summary and conclusions Changes in work capability and quality of life were assessed retrospectively in 130 patients with ischaemic heart disease who had undcrgonc aortocoroisary bypass opcrations during 1976-7 because of medically un- controllable angina. • A tnta/ of 85 patients (fiS-S%) reported complete relief from angina six ntonths aftcr operation, though 12 latcr. . suffered a rccurrcncc. Substantially fewer patients needed drugs after the operation. Isefore operation 9 out of 117 men fully employed at the onsct of anbina. were working without restriction or doing lighter, fult- timc work, 38 were at work but seriously incapacitated by angina, and 70 were fisrccd -to stop work. After operation 70wcrc working without restriction or engaged in lighter work, 15 were at work but still restricted by angina, and only V_ were fordcd to stop work. This result was highly significant (P <0•001). These differences were even more pronounced in hca.y manual workers, of whom none could work normaIly before operation, whereas 16 were working without restrietion afternvards. Of patients wishirg to cnl;al;c in hobbies or sports, etscial activity, and sexual intercourse but were restricted before operation, about two-thirds could resume these activities aftcrwards. Coronary artcry surgery providcd dramatic sympto matie relief in up to 90% of patients ana pcrtrsittet rehabilitation and return to gainful cxnploymcn irrespcetivc of type af labour. The degree of sy-mptomati improvcmcnt and increase in exercise tolerance aftc successful surs¢ry is usually far greater tisan occur with any other form of trcattucnt and directly iiapro.e quality of life and work capability. Introduction Cumnan artery di%casc is a major, ccause nf dcath and disabilit in men agrd 35-GS ycars. who are traJitionally rt.~srdcd as th most ccttrnnmictlly pnuluait•c mrmtxrs of socicty: It nt.znif6tatitms include sudden dcath, mytxardial infarctinr .;' heart failurc, and angina lxauris. Althtrugh many patient resl+and to mcdical manaFt:mcnt, the .le.•clurmcstt of aortc :; atrtmary bypass trafting using the saphcnuus vein over th I+ast 101ears offers a new and int;rcacingly acccptal+ic appraich c•p<-tcially fitr the scswrclr handicapped. Many large wrics ha.• shown l•~ncfit in terms nf pain rrlicf,= rrcecntinn of myoeartli: infyraitm,' and iml+mvcm.nt id t•rntricuiar functit+ri.' T'hcr is al.n cci.lencc of increased Innl;cricy.° Althuuch carly rcrort shatcctl fiwcr paticnts working aftcr nlnratitxs than hcfurc,• later reKults trcrc cncnuracing.•' c; Tc have in.c-tij;atctl the qualitr nf ]ifc and ts'tak capabitit uf paticntn c6rrc and after OMr:aiiuns pcrfrrmcd irr th hospital during Iy76-7. RoyaJ Potteraduate Atedical School, ilamancrsnuth Ilo.rital, London 1ti 1Z 01tS STl':rlll':r w1••s'fAnv. esc, tsttt, r.ei.trar in carJinttmracic .urecr;• tm+.e locum scnior r.gistnr in carJintlxtracic aurScrr, ilarcfirld !(iNfital, Harcficld, Atiddkaxl RAi.PII N SA1SFt)RD, ctut„ FKt3, cnn+uttant and acniar kcturcr in cardietMwacic wre.ry MUGii Ft lit:a'CAt.L, an,,rsts, rru(a ua of cardiac surp.ry and h..norarr conauttaat tfaracic surecnn I'aticnts and tucthutis 1'aticnts e•crc .cl.'ctcJ fiN r+hiratir+rt atto failurc to cuntrol tttc angina hc at:,ndarJ m.tilkal traarnnnt anJ climinatien of ri.k factnr :1 u-tal yd 1% r.sticnts unJen.•cnt tr1-nar}• ancrr !F.•pass traftn during the tars v.ars, of %ltmm ninc had h¢cn or¢ratcd on h.for 'lltrec nf thc rati,cnts alws unJ.rucnt r~~svctien of a ltft vcntricut anrurism, Of ttn 1•1 ktnrr.a Jcatha, t+co nccurra•J in hacrital!anJ after wt.U,,.,Nine p:rtr.•ntR ,1ic,1 ttf thrir J'rteaae a•ithr+ut rrtur t.•„rk, rrnc Ji.•J aft.r I+ncurnnnrctump fur carcinorna of the bron.-ht anJ anntl><r died ahcr an aortofctrtoral hcpass orer2tioa for rcriphe: