Tobacco Documents Online

' 156 1 1 , T[-rE LAnICET, It71s 19, 1986 LOW-TAR CIGARETIES PUT TO THE TEST stated incorrectly that a smoking research project directed from St Thomas' Hospital had collapsed after its condemnation as "unethical" by the (71ief Medical Officer for Wales. The feasibility of this ptoject~ double-blind randontised study of the effect on respiratory symptoms of changing from middle to low tar ©garettes-has been investigated' and a large-scale trial, instigated by the Independent Scientific Committee on Smoking andHealth, is underway. This committee strongly urges smokers to stop and non-smokets not to start. However, without a ban on cigarette sales or politically unacceptable tobacco duties many people will continue to smoke and ofiers will start, despite all the wamings. So, while no clgarette can ever be regarded as safe, there is a need to assess'9ess harmful" products. The tar, nicotine, and carbon monoxlde yields of cigarettes have been falling' but the effect of these product modifications on health is notknown. Lung cancer mortality in the UK in men under 70 and women under 55 years has been falling but the interpretatiop of this trend in terms oftarcontent is confounded by the accompanying fall in cigarette constunption! The relation between tar delivery and deadls from chronic bronchitis (on the decline in the UK5) and coronary heart disease (staticb) are even less well defined. Another difficulty is compensatory smoking: Peach et al' compared urinary nicotine merabolite levels in people who had changed from high to lower tar cigarettes with those in smokers who had not changed and found similar levels. An international workshop in 1985s concluded that further evaluation of the lower tar policy was needed. The difficulties should not be underestimated. Smokers tend to report that they smoke lower tar brands than they actually do and are hazy about brands in earlier years? Thus questionnaires on smoking habits need objective validation. Colorimetric assays of urinary nicotine metabolites are cheap, simple, and, for large groups, give a reasonably good indication of amount smoked.10 Becsuse smokers with incipient disease may switch to lower tar brands'l' an experimental design, with random allocation of cigarette type, is essential to test the effect of cigarette modification on health. In the feasibility study' participants were invited to retut'n an empty packet of their usual cigarette brand. Men aged 20-44 who smoked middle tar cigarettes were sent information on the dangers of smoking and those who had no intention of stopping were invited to take part in the trial in which they would b e randomly allocated to middle tar/tniddle nicotine or low tar/low nicotine cigarettes in anonymous packets sold at discount to encourage participation. Participants were asked to collect their cigarette buns and provide urine specunens at 0, 3, and 5 weeks. Drop-outs were similar in the two groups and cigarette price didnotappear m affect consumption. Of some 19 000 individuals sent the questionnaire, only 140 satisfied the selection criteria and agreed to participate. About 270 000 individuals will need to be sent questionnaires to rectuit sufficient participants for the full trial. Participants will be randomly allocated to middle tar/middle nicotine, low tar(low, nicotine, or low tar/middle nicotine cigarettes, to be sold at wholesale price; cigarette uptake will be monitored in a 20% subsample. Smoking habits will be monitored for 6 months and the prevalence of and change in respiratory symptoms will be compared with a control group of non-smokers and ex-smokers. The ethical aspects hade been carefully considered. Those who smoke middle tar cigarettes will receive postal advice from an independent source catcoumgipg them to stop smoking. 3 months later, only thosewho continueto smoke middle tar cigarettes will be invited to participate in the trial. An independent research instimre' will undertake the fieldwork. One problem for epidemiologists undertaking large-scale national studies is the need to approach a large number of ethical committees. Some central guidance or, even better, one authorimtive ethical body to which epidemiologists involved in national studies could turn would be welcome. Despite some adverse publicity, of the 30 district health authorities approached, 8 -acoepted the St Thomas' Hospital ethical committee's approval and 1$ had the study protocol approved by their local ethical Committees; 4 etltical committees refused permission and 3 /authorities did not wish to take pdrt, for a variety of reasons. . It is only by a well-designed randomised controlled trial that ^ `""` '°'r ""'•• ^""""""`• "+"'•"'• ••" `^""`• . eftects on respitatory health ol' cbangmg to lower tar cngarettes mn be assessed. . .. DPemvenr of Conunsvtiry Medidne, Unitcd Mrdical and Dental schools of Guy'sand St Thomas' Hospivls, SrTlwmas'HOVpital, . , __.. I.ondnn Sel ]EH; W. W. HoLtaND Deparwmmf EPitlenuolagy yul Gunmuniry Medicine, UniversiryufHristol Hristo1,H522PR . R. T. (^AILEY DcpemnenrofCUmmuniryMedicine, ~ - UMDS of Guy'sand ScThomas'HOSpirels, St'ILom.v' Hosplyd, London SEl FIONA NORTH 1. Md4e D. Adverdsing and sponsorship by the tobauv industry. Lanrer 1986; i:393. 2. PeaehH, EllmdGA,HaywazdDM,MonisRW,ShxhD. Adoubleblindrandomixd wntrolted ttial of the eR : of a low rcrsus a middle rer rigazette on repisatory symptorrss: Fesibitiry srudy.In: Proceediogs o(Internationxl Meeringon Cenra Canrml Pre.endun: TobacrosMejorlssue(MOSCmv,1985).IARCSa Mmug.( press). 3. Jarvis MD, Phil M, Ruaell MAH. Taz and nimdne yields of UK ciprcna 19]b19fli: Sales-weigptM esvmares from nm,-indvsirysouras. Br,7Addicnon 1985y8U:929-34. 4. Wa1dN7.5rnoking.In: VessryMP,Grey M,eds. Canc¢prevenuon. ONfocd:Oxford Ihuversiry Pcss,1985:946]. -' 5. Holland W W, Gitdadale S. Epidemi°logy of chronic b,oncM1lris. In: Sadding ]G, Cutn,ning G, eds. Respinrary mNicine.Iandan: Hehi.nm,ry 1981; IL2o. 6. Florcy C du V, Metia RJW, Darby SC. Chmging monzliry G°m isrttsemic heaa diseme in Grrn &irefn 1968-]fi. BrMed] 1998; i:635-32 7. Peach H, Hayurerd DM, Ellard DR, Moms RW, Sheh D. Phlegm producrion and lung funcdon zmong tlgaette smol:eis changing mr groups during thc 1910's. 96pidrnuNCrorurwn Heahh 1986; A01to-16. 8. Wa1d N, S,epnry R,Haddow ].Is therc e[umre for lowararyidd dgarmes?tanm y985;ii:11y1-14. 9. Pcazh H, SM1ah D, Motns RW. Validiry of smokecs' mf°,nution about presmr xod pasr <igdretu brerds: Isnp4cadons for swdies of the effetts of fdl"v,g ve yield of agazrrtes an hcddh. Thoraz 1986; 4L 2C6-0]. 10. PeecM1 H, Ellazd GA, Ie+mn P7, Moms RW. A simplr inexpmsivc v,ive mx of smofting. Tlwrax1985,4U:351-5]. l l. Alderson MR, Lee PN, Wan6 R, ltisks of lung emcer, duovic brvncldlis, ischaemic hean diseace, and srtoke in ,eladon of rype of rigarme smoked. 3 Epidmvo! Cormmm Hea(rF 1985; 3928b-93. PROSTAGLANDIN E, DECREASES ACTIVATION OF ARTERIAL SMOOTH-MUSCLE CELLS Sla,-The antiaggregatory prostaglandins PGE, and PGI, (epoprostenol, prostacyclin) have been used to nCat patients with peripheral vascular disease (PVD) but theclinical benefit was much less than had been expected from the very potent in-vitm actions of these compounds. The mechanism was at first thought to be an antiplatelet action, but it now seems unlikely that prostaglandins exert,viatheirantiaggregatoryproperties,aclinicalactionthatlasts much longer than the duration of the infusion. A few genrs ago an antiproliferative effect of prostaglandins and a beneficial effect on vascular wall smooth-muscle cell lipid metabolism was reported in avimals.'•' We wondered if the inhibitory effect on mitotic activity and proliferation of arterial smooth-muscle cells seen in laboratory animalss•° is seen in vivo in man. Surgical specimens from the femoral and popliteal artery have beeninvestigated in 33 patients (24males, 9 females). As a lastreso[t before surgery infusions of PGE, (1 ng/kg/min) (Prostarasin'; Sauol-Schwarz, West Germany) for 6 h a'day for 5 days had been given intra-arterially into the affected leg in 15 patients (11 males, 4 females). Tissue was immediately fixed in glutaraldehyde (phosphate buffered to pH 7•4). Processing for semi-thin sections (periodic-add/Schiff and toluidine-blue staining') and electron microscopyweredoneand thentuubasofactivatedsmooth-musde cells in intima and media were expressed as the peroetttage of the total smooth-muscle cells on the basis of cell chromophilia and the predominance of unspecific cells organelles' The percentage of activated smooth-muscle cells in human arteries is age dependent (table). Intra-arterial PGE, infusions for 5 days significantly decreased rhe numbers of acdvated smooth- muscle cells in intima and media (p <001; t test). No apparent difference between males and females was noted. These data reinforce findings in cultured cells• and laboratory avimals,' demonstrating an antiproliferative action of various prostaglandins. The demonstration of an antiproliferative effect of -PGE, in man supports the interest in alternative routes for PGB, r