CHAPTER 5

Peptic Ulcer Disease


Contents

Page

Introduction-_-.._- _____ --___-__--__---___--_____________   155
E:pidemiological and Clinical Studies-- _ - - _ _ - - - - _ - _ _ - _ - -_ _ _ _   155
Experimental Studies

Gnslri~ Secretion_-- _______ - ____ -__- ____ -__-___--_--__   157
Pancreatic Secretion---- ____ ---- __..- --____--_-_-__--_-   159
summary of Recent Peptic Ulcer Disease Findings- - _ - _ _ - _ _ _   162
References_---_-- ____ -___-_____ ______ - ___________-_____   163

List of Figures

Figure I.-Gastric ulcer mortality ratios of Japanese (men and
women combined) by age at initiation of cigarette smoking
(1966-70)-----e--e- -__- -_-- ___-_-_ _- __--_-_-__------_   156
Figure 2.-Effect of cigarette smoking on volume of secretin-
stimulated pancreatic secretion in humans-_ --_ __-_ __--_-_   160
Figure 3.-Effect of cigarette smoking on secretin-stimulated
pancreatic bicarbonate output in humans_--- __ _ _ -_ _ - -_ _ - _   161

153


Introduction

Previous epidemiological and csperimental st.udies of the reMion-
ship bctn-ren cigarette smoking and peptic ulcer disease were reviewed
in the 1071 and 1072 reports ou the hea1t.h c,onseqnences of smoking
(17, 18) nnd form the basis of the following summary :
The results of epidemiological studies indicate t.hnt cigarette smok-
ing males hare ml increased prevalence of pept.ic ulcer disease and a
(venter mortality from peptic ulcer as compared to nonsmoking males.
t
.1niong ~nalcs. the association between cigarette smoking and peptic
ulcer disease is stronger for gastric than for duodenal ulcer, but sig-
Axnt for both. For males, cigarette smoking appears to reduce the
ctfectiveness of standard 1)eptic ulcer treatment and to slow the rate of
lqtic ulcer healing. The relationship between cigarette smoking and
the prevalence of and mortality from pept,ic ulcer disease is less clear
for females than for males.

Experimental studies of t.he effect of cigarette smoking in man, and
Of the effect of injection and infusion of nicotine in animals, on gastric
secret,ion and motility have producecl conflicting results. In dogs, an
infusion of nicotine has been found to inhibit. pancreatic and hepatic
l~icnrbouate secretion, t,hus demonstrating a possible link bet.ween
cigarrtte smoking and duodenal ulcer.

Kecemly, additional epidemiological, clinical, autopsy, and esperi-
lllental studies have confirmed the associat.ion bet.we.en cigarette smok-
ing and gastric ulcer mortality and have clarified a mechanism through
nhich cigarette smoking might be linked to duodenal ulcer.

Epidemiological and Clinical Studies

Previous studie.s of the relationship between peptic ulcer disease and
"ixarette smoking have been conducted in predominantl;y IT-hi&, West-
(`1~ populations. X large prospective. epiden~iological studS is current,Iy
t)eing conducted in ,Tapan. From this study, Hiraynma. (6) reported
s;-~ear followup data on 265,118 men and women, aged 46 years and
()lh, representing 91 to 99 percent of the t.otal 1)opnlation in the area
(If the 29 llcalth clistricts in which the study n-as conducted. ISot,h male

155


Figure l.-Gastric ulcer mortality ratios of Japanese (men and women Combined)
     by age at initiation of cigarette smoking (1966-1970).

4.00




3.00




2.00




1.00





0

         Nonsmoker





SOURCE: Hlrayama, T. 16).

:>25        <24        <19
Age at initiation of cigarette smoking (years)

156


Alp, et al. (1) conducted a retrospective survey of 638 pat,ients,
~tlmittecl to two ,Iustralian teaching hospitals between 1954 and 1963,
with chronic gastric ulcer confirmed by roelltgcnogrraphic, cndoscopic,
or swgical examination. The findings in the patients were compared
wit.11 information available about the South Australian population
obtained at census in 1954 and 1961, and with a control group of 233
subjects matched for age and sex with the ulcer patients. Cigarette
use, a family history of peptic ulcer. domestic stress. and aspirin and
:~lcohol intake, occurred significantly ~IOIY~ fruquentl~ among ulcer
patients. Alp, et al. (2) found that after surgical trcatmrnt, recurrence
of the ulcer was significantly more likely to recur amoug those patients
~110 continued to smoke, drink, and use aspirin (P<O.OOl).

Fingerland, et al. (5) compared the autopsy findings from `i65 males
with their smoking history. The atltopsies were performed without
selection during 1965 and 1966 at the I-nivcrsity of Hradec Kr;ilovk:
Czechoslorakia. Peptic ulcer was significantly more frequent among
de es-smokers and male lifelong smokers than among male non-
smokers (P<O.O2). Among males. a close-response relationship was
found between estimated total cigarette consumption and the presence
of peptic ulcer at autopsy.

Cooper and Tolins (4) rrportcd results from a retrospective st,udy
of the relationship between cigarette smoking and postoperative com-
plications among 2,988 males? admitted to 19 Veterans Administration
hospitals, for the surgical treatment of duodenal ulcer. Smoking his-
tory was obtained for 1,441 of the men, and of these 273 were non-
SITlOkers, 1,018 smoked cigarettes only, and 93 smoked cigarettes plus
a pipe and/or cigars. The authors fouud no evidence of an association
between either the number of cigarettes smoked per clay> or the number
of years of cigarette smoking, ant1 postoperative complications, opera-
tire mortality, or length of hospital stay. They emphasized that their
results must be viewed wit11 considerable caution ant1 listecl several
potential sources of bias. In addition. they noted, U* * * that these.
results apply only to the immediate 1)ostopcrativc findings and do not
:lpply to the long-rnugr ctiects of smokiug upon the patient after
surgery for duodenal ulcer disease."

Experimental Studies

IIorales, et al. (10, II) studied the effect of cigarette smoking on
gastric secretion in a group of 312 patients. The patients included 138

157


with duodenal ulcer, 93 with gastric ulcer, and 81 with other gastro.
intestinal disorders, who served as controls. Cigarette smoking was
significant,lv more frequent among the patients with peptic ulcer than
         "
among the controls.

The chronic effect of smoking on gastric secretion was quit.e variable.
Male smokers among the controls and in the group with duodenal
lllcers had a significantly increased baseline acid output as Compared
mit,h nonsmokers in the same groups (P<O.OS). After a subcutaneous
injecbion of histamine, only the group of male smokers with gastric
ulcers had a significant increase in acid output over the values obtained
for nonsmokers in the same group (P<O.OS). Among the smokers in
the control group, the relationship between gastric acid output and the
number of cigarettes smoked daily was dose dependent. pu'o such rela-
tionship was obtained for either of the two groups with peptic ulcers,

In these experiments, the acute effect of smoking on gastric secre-
tion was slight. In one set of experiments, a group of eight smokers
served as its own control. The smoking of two cigarettes prior to
collection of gastric juice had no significant effect on acid output as
compared to baseline value's After smoking two cigarettes and also
receiving a subcutaneous injec,tion of histamine, the patients experi-
enced no significant change in gastric acid output as compared to
baseline values. , 21 male patients, including members from the groups
with ulcers and controls, smoked one cigarette 1 hour after an intra-
venous infusion of histamine. A transient depression of gastric acid
output was noted as compared with the values obtained from nine
patients who did not smoke.

Kontllrek, et al. (8) studied the effect of intravenous infusion of
nicotine on the formation of acute, experimental duodenal ulcers in
cats. The authors infused nicol-ine intravenouslyv in doses comparable
to the smoking of four, eight. and 16 cigarettes per hour into cats in
whom near maximal gastric acid output had been stimulated with
intravenous pcntagastrin. The jnvrstigators found that nicotine in the
two lowr doses had no effect upon the gastric acid output stimulated
by pentagastrin. bllt that thr highest dose produced a significant. de-
crease in wspo~me. due to a fall in both \-olume and acid concentration.
Sicotine nlonc failed to alter :t negligible basal gastric secretion. In
control animals ( pcntagastrin alone), duodenal ulcers were found in
eight of 10 animals. Sicotine at the two lower doses, in rombination
with pentagastrin, prodnccd ulcers in all 26 animals. .1t the inter-
mediate dose of nicotine, the mean ulcer area was twice that found in

156


the control group. ,1t the highest dose of nicotine. peptic ulcers ap-
pearecl in only two of six animals and the area of ulcer was reduced
compared to controls.

Shaikh, et al. (14) studied the acute and chronic effects of sub-
cutaneously injected nicotine on gastric secretion in rats. I-r&r basal
conditions, the volume of gastric sccrrtion x-as initinllx depressed,
then stimulatrd, and deprcsstvl again as the dose of nicotine was
increased. A4cid output KM dccrcnsctl over the entire range of nicotine
dosage. Pepsin output rrflrctrtl a similar triphasic response to in-
creasing nicot.ine doses as did gastric secretory volume. In the absence
of nicotine. pentngastrin stimulated gastric volume, acid, and pepsin
output. The injection of nicotinr. in increasing doses. administered
simultaneously with pentngastl~iii. resulted in a pradual decrease in
response for all parameters. I-olunw of gastric juice, acid output, and
pepsin output x-rre all increased sipiificantly by chronic exposure to
nicotine alone. Based 011 an a\-ernqe smoking dose of nicotine. the dose
of nicotine rmploycd in the chronic csprrinwnts corresponded to the
smoking of three to five cigarettes lwr. day.

Thoml)son. et al. (16) extended the study of rats clcscribed above
by studying the effects of chronic nicotine injections in wgotomized
rats and rats with cliscr.etcJ lesions in the hypothalanlus. In sham-
operated animals, chronic, nicotine injections significantly increased
baseline volume of gastric juice? acid output, aud pepsin output. Fol-
lowing vagotonry, tlw nicotine reslm~w was completely suppressed.
Caudal hypothalamic lesions did not influence the response to nicotine
in the preseilce of intact vagus nerves . -Interior hypothalamic lesions,
ranging from the anterior hypothalamic area to the ventromedial
hypoth&amus, blocked the nicotine-induced gastric secretory stimula-
tion in the presence of intact vagi. The authors concluded that chronic
nicotine-induced gastric secretory stimulation is mediated via anterior
hypothalamic activation and intact vagus nerves. `I% imp0rtanc.e of
local effects remained uncertain.

ByJIUI~, et al. (3) studied the effect of cigarette smoking upon pan-
rreatic secretion in 23 ltealthy JYN~~ males and females. Five control
nlale nonsmokers were compare"d with seven male and tv;o female light
snlokrrs (less than one pack of cigarettes per day for less than 3 years)
UKYI eight male and one female heart qnlokers (more than one pack of

159


cigarettes per day for more than 3 years). Pancreatic secretion was
n~rasur~d by the double secretin test, using Boots secretin. The experi.
ment was divided into two 1)arts for the smokers: A basal collection
period and an experimental period during which the subject,s smoked
seven nonfiltered cigarettes at the rate of four per hour. Light smokers
had basal values for pancreatic secretory volume and bicarbonate out-
put in response to secretin wllich were not significantly different from
controls. After the subjects had smoked, s&r&cant depression of both
pancreatic volume and bicarbonate output was noted (P<.OOl).
Heavy smokers ha.d basal values that \vere significantly less than in the
control subjects (P<O.Ol). Smoking, however! did not further depress
the response to sccretin (figs. i! and 3).

Solomon and ,Jacobsen (15) reviewed some possible mechanisms
whereby the increased prevalence and mortality from duodenal ulcer
among cigarette smokers might be produced. They concluded that
evidence from studies in animals, coupled with the findings of Bynum.
et al. (.3), supported the hypothesis that the mechanism active in
humans involves impaired neutraliza.tion of acid secondary to tIlc
inhibition of pancreatic bicarbonat'e secretion.

Figure 2.- Effect of cigarette smoking on volume of secretin-stimulated pancre.
       atic secretion in humans.

MeanDvp'ume
pancreatic
fluid in
milliliters
per kilogram
body weight

3.0

2.5


2.0

1.5


1.0

0.5

a

1 Significantly different from nonsmoking test within group of light smokers (P <O.oOl)
3 Significantly different from nonsmoking controls (P <O.Ol).

SOURCE: Bynum. et al. Qb

160


Figure 3. -Effect of cigarette smoking on secretin-stimulated pancreatic bicar.
     bonate output in humans.

Mean hourly 8
output of
bicarbonate 6

   in
milliequiva. 4
lents per hour

J

`Significantly different from nonsmoking test within group of light smokers (P <O.OOl).
`Significantly different from nonsmoking controls (P 10.01).

SOURCE: Bynum. et al. (3).

STUDIES IN bUMALS

Konturek, et al. (7) extended his research on the mechanism of
nicotine-induced inhibition of pancreatic secretion in the dog, using
the design previously employed (9). Infused secretin alone led to a
sustained increase in pancreatic bicarbonate output. Intravenous nico-
Cne, at all four doses of infused secretin, produced a significant in-
llibition of pancreatic. volume and bicarbonate out.put (P <0.05).
Infused nicotine appeared to inhibit compet.itively the effect of secre-
tin on pancreatic secretion of fluid and bicarbonate. Topical (intSraduo-
denal) nicotine failed to affect significantly the response to infused
secretin. Stimulation of endogenous secretin by an acid infusion into
the duodenum produced the expected pancreatic secretory response.
Nicotine either applied to the duodenal mucosa or injected intra-
venously significantly inhibit.ed the pancreatic secretory response to
%dogenous secret.in. n'icotine had no significant effect, on total pancrea-
tic protein output. Nicotine did not alter the cholecystokinin-induced
3timulation of pancreatic secretion. The authors concluded that nico-
&le may inhibit pancreatic secretion of fluid and bicarbonate both

161


by a direct effects on pancreatic secretory mechanisms, acting as a corn-
petit ive inhibitor of secretiq and by a secondary effect on the duodenal
mucosa. depressing the endopenous release of secretin by acid.

Robert (I,?) studied the Ilotentiation of active duodenal ulcers by
nicaotine administration in the rat. Subcutaneous infusion of pentagas-
trin and ca.rbachol resulted in the dose-dependent formation of duo-
denal ulcers within 24 hours. Nicotine alone produced no ulcers.
Increasing closes of subcut.aneously infused nicotine, in combination
with the other two agents, resulted in a steadily increasil:gdose-related
incidence and severity of the duodenal ulcers. Robert noted that
Roaturek, et al. (9) found that nicotine inhibited pancreatic and
biliary bicn&onate secretion in dogs, and that Thompson, et al. (16)
found that acute doses of nicotine in rats either depressed or did not
alter gastric secretion. He concluded that the most probable mechanism
11y which nicotine potentiated acute duodenal ulcer formation in t.he
rat, w-as via a sui)pression of pancreatic secretion.

Robert, ct al. (I.?) further tested this hypothesis by infusing acid
via the esophagus of rats in doses found to cause duodenal ulcers in
one-third of the experimental animals. One group of rats also received
a sulwutallcous infusion of nicotine. Another received nicotine, but
only l\.:ltcr was infused via the esophagus; 31 percent of the animals
rcwit-ing :lvitl but no nicotine had duodenal ulcers; 93 percent of the
[kicutiw-wit1 group had duodenal ulcers, rvhile none of the nicotine-
\v:ltt'r c~`oult Ilad ulcers. The. ulcers in the nicotine-acid group were
n1ow I~~~~WL'OIIJ, extensive, and deeper than those in the animals which
wwivcd acrid alt~nt'.

Sunmn~y of Recent Peptic I-leer Disease Findings

TIL :t~l~lition to the findings wlnting cigarette smoking to peptic ulcer
,li -I~:I;c . slullnlarize~l in previotla reports on the health consequences of
.51il,,f~i1l:, ( I;. IR) :in~l cited in the introduction to this chapter, recent
at Il'liC'i LA;-c cwlltrilrlitetl fri1thcr to our understanding of the
:I,s.,cr~~iatii)l~:

1. `1 11t\ tillililq of n 5ignitic:illt dose-related escess mortality from
,2:1-t I ii, t11~~rs ;1111011g Imth 1na1c and female Japanese cigarette
>III~J~`I 5'. in a large proqwtiw stud-, ant1 in the context of the
~t,llc~t ic, :IIII~ c\lltur:ll tlitf~lrenccs be.t\veen the Japanese and pre-
l-ilJ:~-lF in\-& igated IVesi-cm l)opulations, confirms and extends
t 11~ association Iwtv.ecn cigarette smoking and gastric ulcer
m0rtalit.y.

162


2. Data from experiments in several different animal species sug-
gest t.hat nicotine potentiates acute duodqlal ulcer formation by
means of inhibition of pancreatic bicarbonate output.
8. Cigarette smoking has been demonstrated to inhibit pancreatic
bicarbonate secretion in healt.hy young men and women.

Peptic Ulcer Disease References

(1) BLP, 31. H., HISLOP, I. G., GRAST, A. K. Gastric ulcer in South Australia,
  1954-63. 1. Epidemiological factors, Medical Journal of Australia 2(24) :
  1128-1132, Dec. 12,197o.

12) ALP, %I. H., HISLOP, I. G., GRAST, A. K. Gastric ulcer in South Australia,
  195463. 2. Symptomatology and resljonse to treatment. Medical Journal
  of Australia 1 (i ) : 3712-374, Feb. 13, 1971.
(S) BYKUM, T. E., SOLOJLON, T. E., JOHSSON, L. R., JACOBSOX, E. D. Inhibition
  of pancreatic secretion in man by cigarette smoking. Gut 13(5) : 361-365,
   May 1972.

(4, COOPER, P'., TOLISS, S. H. Relationship between smoking histor)- and compli-
  cations immediately following surgery for duodenal ulcer. JIount Sinai
   Journal of Medicine 3Q t 3) : ?87-2QL', May-June lQi2.
(5) FIXGE~LAXD, A., HUSAIC, T., BEXDLOVA, J. Contribution to the investigation
  of the effect of cigarette smoking. Sbornik VedeckFch Praci Lekarske
  Fakulty Karlovy University v Hradci Kralove l+i(2) : 22'1-234, 1971.
(6) HIRAYANA, T. Smoking in relation to the death rates of 265,118 men and
  women in Japan. A report of 5 years of followup. Presented at the Amer-
  ican Cancer Society's 14th Science Writers' Seminar, Clearwater Beach,
  Fla., Mar. 27, 1972, 15 pp.

(1) KOXTUREK, Y. J., DALE, J., JACVBSON, E. D., JOHNBON, I.. R. Mechanisms of
  nicotine-induced inhibition of pancreatic secretion of bicarbonate in the
  dog. Gastroenterology 62 (3) : 42%429, 1972.
(8) KOXTUREK, 8. J., RADECKI, T., THOB, P., DEMBISSKI, a., JACOBSON, E. D.
  Effects of nicotine on gastric secretion and ulcer formation in cats. Pro-
  ceedings of the Society for Experimental Biology and Xedicine 138(2) :
   6i4-67 4, November 1971.

!9) KOSTOBEK, 8. J., SOLOS~ON, T. E., &CRUeH'r, W. G., Joassox, L. R.,
   JACOBSOX, E. D. Elfects of nicotine on gastrointestinal secretions. Gastro-
   enterology W(6) : lOW-1103, June 1971.
(1s) MOBALES, a., HILVA, S., -~LCALIJE, J., WAISSBLUTII, J., RAWX, J., BEY, H.,
   SASZ, R. Cigarrillo y secretion gastrica. I. Analisis de la swrecidn
   gtistrka en I)acientes digestives fumadores y no fumadores. (Cigarettes
   and gastric secretion. I. Analysis of gastric secretion in smoking and non-
   smoking ulcer patients. J Rerista Nedicu de Chile W(4) : Z'l-274, April
    1971.

(11) &~OR.~LES, A., SILvA, S., OSORIO, G., QLC.ILDE, a., U'AISSBLUTII, J. Cigarrillo y
   secretion gastrica. II. Efecto de1 cigarrillo sobre la secreci6n gastrica.
   (Cigarettes and gastric secretion. II. I%&& of cigarettes on gastric secre-
   tion.) Rerista Xedica de Chile QQ(4) : Zi%2i9, Agril 19il.

4!KGcl"b o--73--12

163


(12) ROBERT, A. Potentiation, h.v nicotine, of duodenal ulcers in the rat. Pro-
   ceedings of the Society for Experimental Biology and Medicine 139( 1) :
   319-322, January 1972.
(13) ROBERT, A., STOWE. D. F., NEZAMIS, J. E. Possible relationship between
    smoking and peptic ulcer. Nature 233(5X0) : 497-498, Oct. 16, 1971.
(14) SHAIKH, M. I., TBOMPSON, J. H., AUBES, D. Acute and chronic effects of
    nicotine on rat gastric secretion. Proceedings of the Western Pharma-
    cology Society 13 : 178-184, 1970.
(15) Solomon, T. E., JACOBSOK, E. D. Cigarette smoking and duodenal-ulcer dis-
    ease. New England Journal of >Iedicine 286(2'1) : 1212-1213, June 1, lQ72.
(16) T~rou~som, J. II., GEORGE, R., ANGULO, M. Some effects of nicotine on gastric
   secretion in rats. Proceedings of the Western Pharmacology Society
    14 : li3-177, 1971.
(17) U.S. PUBLIC HEALTH SEIKICE. The Health Consequences of Smoking. A Re
   port of the Surgeon General : 19'71. U.S. Department of Health, Education,
   and Welfare. \Vashington, DHEW Publication No. (HSM) 71-7513,
    1971, 458 pp.
(18) U.S. PUBLIC HEALTH SERVICE:. The Health Consequences of Smoking. A
   Report of the Surgeon General : 1972. U.S. Department of Health, Educa-
   tion, and Welfare. Washinglon, DHEW Publication No. (HSM) 72-6516,
    1972, 158 pp.


CHAPTER 6

Pipes and Cigars


Contents

Introduction ___-____-__ --- _____ --_-_-- _____ -_-_--- _-_--_-
The Prevalence of Pipe, Cigar, and Cigarette Usage-----__---
The Definition and Processing of Cigars, Cigarettes, and Pipe
Tobaccos___-___-___------------------~---------------
Chemical Bnalysis of Cigar Smoke----_ _ _ _ ___- _ _ _ _ __ ____ ___
Mortality

List of Figures

Figure I.--Inhalation among pipe smokers by age- ~- - --~ - -- -
Figure Z.-Inhalation among cigar smokers by- age--I&m-
mond_-___-----__--~~--____________________~~------~
Figure S.-Depth of inhalation among cigarette smokers by
age-IIamrnond-___________________________-----------
Figure J.-Percent distribution of 130 brands of cigarettes and
25 brands of little cigars by tar content- _ - - _ _ _ - _ _ - _ _ _ _

Page
171
173

175
177

179

180
183
189
189
190
191
193
197
203
210
210
215
216
222
222
229
230

184

185


185

225

167


Fig~rc 5.--Percent distriblttion of 130 brands of cigarettes and
25 brands of little cigars by nicotine content,-- - _ - - - - - - - _ _ _

List of Tables

Table I.-Percent, distribution of U.S. males aged 21 and older
by type of tobacco used for the years 1964, 1966, and 1970--
Table 2.-Percent distribution of U.S. males b>- type of tobacco
wed and agefor 1970_--.._-----_--_-----~-~------~- ____
Table S.-Percent distribution of British males aged 2.5 and
older by tJ.pe of tobacco used for the J-ears 1965, 196S, and
1971---_-_-._--_--_---.------~-----------------~~-~-~
Table 4.-Amounts of several components of 1 gram of par-
ticulate material from mainstream smoke of tobacco prod-
ucts ---_- --~--~---_~--~- -__. -----_---_------_-_-_____
Table 5.-A compariqon of Iseveral chemical compounds found
in the mainstream smoke of cigars;, pipes, and cigarettes--_-
Table 6.--AIortalit)- ratios for total denth~ b>- type of smoking
(males onl~-)~_-~_-_.~__-_--_--~--~-------~.~--~- ___.__
Table T.--bIortality ratios for total deaths of cigar and pil)e
smokers by amount smoked-~~~arutnontl and IEorn- _ - _ - -- _
Table S.--;\Iortalit\- ratios for total deaths of cigar and pipe
smokers by amount smoked---Best--_- - - - - - - - _ - - _ - - - - _ _
Table 9.-Jlortality ratios for total deaths of cigar and pipe
smokers by age and amoltnt smoked-Kahn- - - - _ - - _ - _ - - _ -
Table IO.-IIortnlit>- ratios for total deaths of cigar and pipe
smokers by amount smokt~d-~Iammond- - _ - - - - - - _ - - - - _ -
Table 11 .-The extent of inhaling pipes, cigars, and cigarettes
by British males aged 16 and over in 1968 and 1971_ - - - _ _ _
Table 12.--Inhalation among cigar, pip, and cigarette smokers
b\- age--Doll and )Iill---~-.--~-.._-_~-_~-_--_-__-.--_-. -
Table 15.-1lortalit.v ratios for total deaths of cigar and pipe
smokcr~ by- ape and inhnla tion-~ItlmIllond-~ _ - _ - _ _ _. - _ _ -
Table l-2..-Prrcrntage of British mnlc cigar smokers who rc-
ported inhaling a lot or a fair amount b)- type of product
rrnoked__~______~__-~_-._-~--_--~--_-~--------_----_~
Table lj.p-Percentagc of ir~divitluals reporting inhalation of
"almost every p~iff" of tobacco smoke by current and pre-
Gous tobacco usapc and t:+-pc of tobacco used - - - - - - _ _ _
Table 16.-Percentage of British males I\-ho reported inhaling a
lot or fair amount of cigar smoke by current and previous
tobacco usage and tylw of tobacco previously smoked
(196S)--_~_~__~-_~ ____ -._-__-_--_--_-_--_--~--~------

226

173


174

li4

177


17s


is0


1Sl


181


182


152


1%


IS6


1s;

1Pi

IS8

1%


Page

Table 17.-Extent of reported inhalation of cigar smoke by
British male cigar smokers who jvere es-cigarette smokers in
1968, analyzed by extent of reported inhalation of cigarette
smoke when lxcrioud?- smoking cigarettes_-_- _ - - - - - _ - - _ - - -
Table lrj.-Jlortality ratios for total cancer deaths in cigar and
pipe smokers. A summary of prospective epidemiological
~tuclies---_--_-__-~~-~~-~~-~-----~----~------------~--
Table lg.-Relative risk of lip cancer for men, comparing cigar,
pipe, and cigarette smokers vith nonsmokers. A summary of
retrospectivest~~dies---_--__--__--~-----~-----~-~--~---
Table 20.--1\Iortality ratios for oral cancer in cigar and pipe
smokers. A summary of prosl)ectivc epidemiological studies- _
Table 21.-Relative risk of oral cancer for men, comparing
cigar, pipe, and cigarette smokers n-ith nonsmokers. A sum-
mar). of retrospective studies- - - - - _ - - _ - - - - - _ - - _ - - _ - - _ - - _
Table 22.--?\lortality ratios for cancer of the larynx in cigar
and l)ipe smokers . A summary of prospective epidemiological
studies__-__-__-__-_____________________--------------
Table 2X.-Relative risk of cancer of the laq-ns for men, com-
paring cigar, pipe, and cigarette smokers with nonsmokers.
A summary of retrospective studies-_- _ _ - _ -_ _ _ - _ - - _ _- _ __ _
Table 24.--?\lortality ratios for cancer of the esophapu; in
cigar and pipe smokers. A summary of prospective epidernio-
logical studies-_- ____________ -------------_------------
Table 25.-Relative risk of cancer of the esophagus for men,
comparing cigar, pipe, and cigarette smokers with non-
smokers. A summary of retrospective studies..- _ _ - _ _ _- _ - -_ -
Table 26.-Mortality ratios for lung cancer deaths in male
cigar and pipe smokers. A summary of prospective studies__--
Table 27.-Lung cancer death rates for cigar and pipe smokers
by amount smoked-Doll and Hill__----- ____ -__--_--_--
Table 28.-Lung cancer mortality ratios for cigar and pipe
smokers by amount smoked-Kahn ____ _ _ - _ _ _ - _ _ _ _ - _ _ - _ _ -
Table 29.-Relative risk of lung cancer for men, comparing
cigar, pipe, and cigarette smokers with nonsmokers. A
summary of retrospective studies__----_--_-_-___________
Table :30.--Changes in bronchial epithelium of male cigar,
pipe, and cigarette smokers as compared to nonsmokers- _ - -
Table 31.-Tumorigenic activity of cigar, pipe, and cigarette
smoke condensates in skin painting experiments on animals-
Table 32.--Mortality ratios for cardiovascular deaths in male
cigar and pipe smokers. A summary of prosI>ective epi-
demiological studies-------_-_-_----------~------------

189

189

192


193

194

196

198

200

201

204


204

205

206

209

213

216

169


TabIf, :3:3.-Ilortality ratios for chronic obstructive pulmonary
tlfv~ths in male cigar and pil)c smokers. A summary of pros-
pectirc c~~itlcmiologica1 studies- - _ - - _ - _ - _ - _ _ - _ _ _ - _ - _ - _ - _ _
Table :H-Preralrncc of respiratory symptoms and illness by
type of smoking-..--------.-------_-__--__-___-_-__--__
Table 35.-Pulmonnr>- function values for cigar and pipe
smokers as compared to nonsmokers - - - - . - _ _ - _ - _ - _ _ _ _ - - _ _
Table 36.--?\lortality ratios for peptic ulcer disease in male
cigar and pipe smokers. Summary of prospective studies- _ _
Table 37.~Shipment of small and large cigars destined for
domestic consuml)tion (1970, 1971, 1972)-----.. -____--____
Table :%.--Sclcctetl (*otnl)ounds in mainstream smoke_-- _ - _ - _
Table :39.-The 1111 of the mainstream smoke of selected
tobacco products---~-_----_-_____________________--~--

219

220


221


2?!


227
221


22x

170


Introduction

This chapter is a review of the epidemiologic,al, pathological, and
~spcrimental data on the health consequences of smoking cigars and
pipes, alone, together, and in rarious combinations with cigarettes.
Prel-ious rerie& on the health consequences of smoking have dealt
primarily with cigarette smoking. hlthouph some of the material on
pipes and cigar-s presented in this chapter has been presented in preri-
DUS reports of the Surgeon General. this is the first attempt to summa-
rize what is known about, the health effects of pipe and cigar smoking.
since the use of pipes and cigars is limited almost exclusively to men
in the United States! only data on men are included in this review.
The influence of pipe and cigar smoking on health is determined
11~ examining the overall and specific mortality and morbidity ex-
perienced by users of these forms of tobacco compared to nonsmokers.
Epidemilogical eridcnce suggests that individuals who limit their
smoking to only pipes or cigars have overall mortality rates that are
Flightly higher"than nonsmokers. For certnin specific causes of death,
i~owever, pipe and cigar smokers experience mortalitv rates that are
as great as or exceed those experienced by cigarette smokers. This
analysis becomes more complex when combinations of smoking forms
we examined. The overall mortality rates of those ~1~9 smoke pipes,
$jars, or both in combination with cigarettes appear to be inter-
IMiate between the high mortality rat& of cigarette smokers and
the lower rates of those who smoke only pipes or cigars. This might
Qeln to suggest, that smoking pipes or cigars in combination with ciga-
rettes diminishes the harmful effects of cigarette smoking. However,
an analysis of mortalitv associated with smdking combinations of ciga-
rettes, pipes, and cigars should be standardized for the level of con-
sumption of each of the products smoked in terms of the amount
B"loked, duration of smoking, and the depth and degree of inhalation.
For example, cigar smokers ITho also smoke a pack of cigwettes a day
might. be expected to have mortality rates some\\-hat higher than those
Iho smoke onlr cigarettes at the level of a pack a day, assuming that
both groups smoke their cigarettes in the same may. Mixed smokers
Rho inhale pipe or cigar smoke in a mannrr similar to the gag they
"make cigarettes might be expected to halye higher mortality rates
than mixdd smokers \vho do not inhale their cigars and pipes and also

171


resist inhaling their c.igarett'es. I-nfortunately, little of the published
material on mixed cigarette, pipe, and cigar smoking contains these
types of analyses or controls.

A paradox seems to exist b,etween the mortality rates of ex-smokers
of pipes and cigars and es-sntokers of cigarettes. Ex-cigarette smokers
experience a relative decline in overall and certain specific causes of
mortality following cessation. This decline is important but indirect
evidence that cigarette smoking is a major cause of the elevated mor-
tality rates experienced by current cigarette smokers. In contrast to
this finding! several prospective epidemiological investigations,
Hammond and Horn (40)) Best (9), Kahn (50)) and Hammond (38))
have reported higher death rates for ex-pipe and ex-cigar smokers
than for current pipe and cigar smokers. This phenomenon was ana-
lyzed by Hammond and Garfi.nkel (39). The development of ill health
often results in a cigarette smoker giving up the habit, reducing his
daily tobacco consumption, switching to pipes or cigars, or choosing
a cigarette low in tar and nicotine. In many instances, a smoking-
related disease is the cause of ill health. Thus, the group of ex-smokers
includes some people who.are ill from smoking-related diseases, and
death rates are high among persons in ill health.

As a result', ex-cigarette smokers initially have higher overall and
specific mortality rates than continuing cigarette smokers, but be-
cause of the relative decrease in mortality that occurs in those who
quit smoking for reasons other than ill health, and because of the
dwindling number of ill ex-smokers, a relative decrease in mortality
is observed (w-ithin a few years) following cessation of cigarette
smoking. The beneficial effects of cessation would be obvious sooner
were it not for the high mortality rates of those who quit smoking
for reasons of illness. A similar principle operates for ex-pipe and cx-
cigar smokers, but because of the lower initial risk of smoking these
forms and therefore the smaller margin of benefit following cessation,
t,he effect produced by the ill ex-smokers creates a larger and more
persistent, impact on the mortality rates than is seen in cigarette
smoking.

For the above reasons a bias is introduced into the mortality rates
of current smokers and ex-smokers of pipes and cigars, so that a more
accurate picture of mortality might be obtained by combining the
ex-smokers with the current smokers and looking at the resultant
mortality experience.

Because of a lack of data that would allow a prec.ise analysis of
mortality among ex-pipe and ex-cigar smokers, a detailed analysis
of these groups could not be undertaken in this review.
For each specific, cause of death, tables have been prepared which
summarize the mortality and relative risk ratios reported in the major

172


prospective and ret,rospective studies \Thich contained information
:lbout pipe and cigar smokers. The smoking categories used include:
\-igur only, pipe only, total pipe and cigar, cigarette only, and mixed.
The total pipe and cigar category includes: those who smoke pipes
only, cigars only, and pipes and cigars. The mixed category includes:
tllose who smoke cigarettes and cigars; cigarettes and pipes; and
cigarettes, pipes, and cigars. Mortality and relative risk ratios were
calculated relative to nonsmokers.

The Prevalence of Pipe, Cigar, and Cigarette Usage

The prevalence of pipe, cigar, and cigarette smoking in the United
States was estimated by the National Clearinghouse for Smoking and
Health from population surveys conducted in 1964,1966, and 1970 (98,
39, 200). In each survey, about 2,500 interviews were conducted on a
l\ational probability sample stratified by type of population and
geographic area. The use of these products among adults aged 21 and
older is summarized in tables 1 and 2. The prevalence of pipe, cigar,
and cigarette smoking in Great Britain for the years 1965, 1968, and
1971 is presented in table: 3.

TABLE I.-Percent distribution qf U.S. male smokers aged 21 and older
  by type of tobacco used for the years 1964, 1966, and 19YO

Forms used

1970
(percent)

6. 8      5. 5       5. 6
1. 7      3. 0       3. 6
3. 9      4. 9       4. 4
28. 6     31. 2     25. 9
11. 3      9. 9       6. 6
5. 3      4. 9       5. 3
7. 7      6. 3       4. 6
34. 7     34. 3      44. 0

   Total-_--_-__-____-________________    100. 0    100. 0     100. 0

Number of persons in sample- - _ _ _ __-_ -. - _. _   2, 389    2, 679    2,861
Total pipe users (2+3+6$7) ___._ - ____..___    18. 7     19. 2     17. 9
Total cigar users (1+3+5+7)------ .___.___     29. 9     26. 7      21. 2
Total cigarette users (4+5+6+7) ___.__.-_--     52. 9     52. 4      42. 3

Source: U.S. Department of Health, Education, and Welfare (98, 99,100).

173


TABLE 2.-Percent distribution of C.S. male smokers by type qf tabwe
         co wsed and age for 1.970

21 to 34    35 to 44   45 to 54   55 to 64  65 to 75  _

1. Cigar only ___. -__-_-------_     3. 7    6. 5     4. 7    6. 7     9.
2. Pipeonl3.__-_~----_-_-----~       3                          :j
                            4.      3. 5     3. 0    3. 2     3.
3. Pipe and cigar-_              3.                           6
              _-.- _. - .____       8    3. 3     5. 2     4. 4     6. 0
4. Cigarette onl~---~------~~     28. s    29. 0    27. 1    24. 3    13.
5. Cigarette and cigar_-__                                      6
                   - _. _ . _      6. 8    10. 4     5. 5     5. 2     4.
6. Cigarette and pipe-_-------_                                2
                           6. 6    4. 4    5. 6    4. 0     3. h
7. Cigarette, pipe, and cigar- - - _     .5. 8     4. 8    5. 0    4. 0     1. 4
&  Nonsmoker-__-__-_--.- _.___    40. 2    38. 1    43. 9    48. 2    57. L'

   Total-_-_--_-_-__-_.--~    100. 0   100. 0   100.0   100.0   100. 0
                       ---__--___
                       -------------En=_
                                                    -
Number of persons in sample- _ _   1,009     528     ,523    405     35%
                        :---
Total pipeusers___---_-___~_-.     20. 5    16. 0    18. 8    15. 6    1.5. 7
Total cigar users_--_-------_-_     20. 1    25. 0    20. 4    20. 3    21. F-
Total cigarette  users- - _ - _ - - _ - _    4P. 1    48. 6    43. 3   37. 5    23. r,

Source: U.S. LIepartment of Health, Education, and Welfare (IW)

TABLE S.----Percent distrib?ltion of British male smokers aged % anI/
older by type of tobacco used for the years 1965, 1968, and 1971

Forms used

               --
1965       1968      1971

1. Cigarsonl~~--.--~--~--~--~--~--.-~~-~~~      1. 9      2. 8       3. 3
2. Pipeonly __.__. -..-._-_~-_--_--~-__-_.-     5. 1      5. 6       5. 9
3. Cigarettesonls.-_~-.---~-.--.--.-~-~~.-     46. 8      45. 7      40. h
4. Cigarettesalldpipe---_-_.-_.-_.-__-~_-_     8. 0      7. 0       6. 1
5. ~lixedsmokers-~~-~-~.--.-~~--.-~~--~-~     7. 5      9. 1       8. 4
6. Nonsmokers.-~--~--~~-.~-~--.~-.-..  ___     30. 7     29. 9      35. 4

   Total__.-_---~-~--.~-.~- ~~-.- __._._    100. 0     100. 0     100.0
                                                        -.
Number of persons in sample_--_ .--------~-   3, 576    3, 566    3, !594

Totalpipeusers~...~~.~~-~---.-- .--~-_.~_~-     13. 9     14. 3      13. 3
Totalcigar-~~-.~~..~.-~.--~-~~.---------..     9. 0     11. 7      11. 3
Totalcigarette-.._-_~-.--_--~~..~-.~ _.._._    67. 6     67. 6      61. 6

Source: Todd, Cr. F. (9:)

174


The Definition and Processing of Cigars, Cigarettes, and
          Pipe Tobaccos

Cigarettes

The U.S. Government has defined tobacco products for tax pur-
poses. Cigarettes are defined as " (1) Any roll of tobacco wrapped in
paper or in any substance not containing tobacco, and (`2) any roll of
tobacco wrapped in any substance containing tobacco which, because
of its appearance, the type of tobacco used in the filler, or its packaging
and labeling, is likely to be offered to, or purchased by, consumers as
a cigarette described in subparagraph (1) ." Cigarettes are further
classified by size, but virtually all cigarettes sold in the I-nited States
are "small cigarettes" which by definition weigh "not more than 3
pounds per thousand" which is not more than 1.361 grams per
cigarette (96).
American brands of cigarettes contain blends of different grades of
Virginia, Burley, Maryland, and oriental tobaccos. Several varieties
of cigarette tobaccos are flue-cured. In this process, tobacco leaves are
(wed in closed barns where the temperature is progressively raised
over a period of several days. This results in "color setting," fixing,
und drying of the leaf. The most conspicuous change is the conversion
of starch into simpler sugars and suppression of osidatix-e reactions.
Flue-cured tobaccos produce an acidic smoke of light aroma (35,112).

cigars

Cigars have been defined for tax purposes as: "Any roll of tobacco
`Qapped in leaf tobacco or in any substance containing tobacco (other
than any roll of tobacco which is a cigarette within the meaning of
Qhparagraph (2) of the definition for cigarette)" (112). In order to
Elarify the meaning of %ubstance containing tobacco" the Treasury
`k'par&nent has stated that, "The wrapper must (1) contain a signifi-
(`ant proportion of natural tobacco; (2) be within the range of colors
normally found in natural leaf tobacco; (3) have some of the other
characteristics of the tobaccos from which produced; e.g., nicotine
"`Jnter& pH, taste, and aroma: and (4) not be so changed in the
!`censtitution process that it loses all the tobacco characteristics"
' I@). Further, L`To be a cig ar the filler must be substantially of
                          ,
rohaccos unlike those in ordinary cigarettes and must not have any
"`lded flavoring which would cause the product to hare the taste or
drema genera 11. attributed to cigarettes. The fact that a product does
          y

175