Pediatricians have considered tobacco smoke exposure in the
troubled allergic child an identifiable problem to be faced. McGovern
and coworkers (70) emphasized that allergic disease represents a major
school health problem because children with hay fever, allergic rhinitis,
and asthma account for about one-third of all chronic conditions
reported under age 17. A survey is cited in which it was noted that
asthma accounted for 11.4 percent of all chronic conditions in children
and for 22.9 percent of days lost from school (8). These. clinical
investigators have, therefore, emphasized the need and value of
removing the allergic child from all environmental sources of tobacco
smoke exposure as a valid preventive measure.

Since the chances for progression of disease are more likely to occur
in the face of continued and uncontrolled presence of causative factors,
the potential for chronicity among adults is evident. The magnitude of
the problem can be appreciated by noting the large population surveys
in the United States which estimate that as many as 15 to 17 percent of
the population suffers from asthma or hay fever (97). Thus, to
whatever extent tobacco and/or tobacco smoke play a causal or
contributory role in allergy, if they are ultimately shown to be
allergens, it would be important for allergic patients of all age groups
to take appropriate precautions to avoid exposure.

Effects of Cigarette Smoking on the Immune System

That cigarette smoking can affect the immune system has been well
documented in both animals and humans. For purposes of discussion,
these alterations in immune function can be classified as local and
systemic. The local host defense system is comprised of the mucociliary
mechanisms and functionally specialized cells, such as the macrophages
and lymphocytes. Systemic defense mechanisms divide conveniently
along the lines of cellular and humoral immunity.

Microscopic examinations of the respiratory tract mucosa demon-
strate that chronic smoking leads to denuding of the ciliated
epithelium, an increased number of goblet cells, and squamous
metaplasia (89). On the other hand, studies attempting to quantify
toxicity of cigarette smoke to cilia have been difficult to evaluate
because of variation of mucus transport rates both among and within
species studied, differences in techniques used to measure ciliary
activity, and variations in methods and periods of exposure employed.

Studies on the short-term effects of smoke on ciliary function in
vitro and in vivo generally show decreased function. Ciliostasis has
been produced by in vitro exposure of the epithelium of the human
respiratory tract to smoke residue passed through an aqueous medium
(7) and, along with decreased rates of mucus transport, has also been
observed in many anima] models (1, 26, 50, 55). However, the effects of
short-term smoking on mucociliary function in man have been

10—14
contradictory. In studies by Yeates, et al. (128) which measured
mucociliary tracheal transport rates, some smokers showed slower
bronchial clearance rates, while others showed little or no change over
nonsmokers. Camner and coworkers (17), on the other hand, found
mucociliary transport to be significantly increased during periods of
intensive smoking (to the point of discomfort) compared to non-
smoking periods.

Studies of long-term exposure have also been undertaken and, again,
both animal and human studies are contradictory. Two studies were
carried out in dogs exposed to forced smoke inhalation. One showed no
change in tracheobronchial clearance (6) while the second, by different
methodology, showed that tracheal mucus velocity was 30 percent of
that found in controls (718).

In a study of 10 pairs of identical twins, discordant with regard to
smoking (16), five of the smoking twins had decreased clearance rates
while the other five demonstrated no differences over controls.
Similarly, Albert, et al. (2) found bronchial clearance impaired in 8 out
of 14 cigarette smokers tested. Lourenco and coworkers (65) found
delayed clearance of particles, particularly in the central airways, at 1
hour after inhalation in nine smokers when compared to controls. On
the other hand, Pavia, et al. (82) found no decrease in the efficiency of
removal of particulate matter in the lungs of smokers compared to
nonsmokers. However, the evidence indicates an adverse effect of
long-term smoking on the mucociliary transport mechanisms and
mucus composition (58).

It is necessary to understand the functions of alveolar macrophages
and lung phagocytic cells as well as the population of immunocompe-
tent lymphocytes in pulmonary tissue in order to appreciate how these
elements and their modification can affect the processing of tobacco
antigen and the resultant production of antibody and cell-mediated
immunity. Since hypersensitivity phenomena are products of the
immune system, these cellular elements can serve as determinants of
allergic inflammation as well as of immunity.

Alveolar macrophages are important to lung function because of
their role as phagocytes, engulfing and digesting particulate matter in
the lung. Also, these cells process antigens and interact with
lymphocytes in immune and allergic processes.

Many studies have examined the effect of smoking on macrophage
function and metabolism. Even though most of these are im vitro
studies, comparison is difficult because of differences inherent in the
human and animal models used. In addition, in some cases, human
subjects or animals were exposed to the smoke before the cells were
harvested, while in others, cells were exposed directly to the smoke.
Other variables included serious differences in amounts and lengths of
exposures, filtration of smoke, and different methods of harvesting

10—-15
cells. Nevertheless, it is clear from these studies that profound
alterations in macrophages result from smoke exposure.

One consistent finding concerning the effect of smoking on
macrophages is that the total number is increased in smokers. Keast
and Holt (57) used a special apparatus simulating human smoking in
exposed mice. They found initial and sustained elevations in macro-
phage populations. Other workers (56) also found increased macro-
phage numbers after only 2 weeks of cigarette smoking in humans.
Studies by Pratt, et al. (88) and Harris, et al. (44) showed that smokers
had strikingly increased numbers of macrophages when compared to
nonsmokers and, furthermore, that macrophages accounted for 90 to
95 percent of lavaged lung cells found in smokers. The authors (44)
speculate that increased alveolar macrophages in smokers might play
an important role in pulmonary defense against toxic components of
cigarette smoke. Also important is the possibility that macrophage
accumulations could contribute to the pathogenesis of chronic pulmo-
nary disease by the release of lysosmal enzyme content.

Changes in ultrastructure of macrophages have also been reported in
smokers. Pratt and associates (88) observed that macrophages obtained
in lung fluids of smokers were filled with cytoplasmic inclusions, and
Martin (67) identified multinucleated giant cells in some smokers but
none in nonsmokers. Martin (67) also noted that crystalloid refractile
cytoplasmic inclusions were more common among the smokers. Harris,
et al. (44) found the most salient feature of the macrophages from
smokers to be larger and more numerous lysosomal bodies.

The study by Holt and Keast (47) demonstrated that the immediate
toxic effects of tobacco smoke in vitro were greater in macrophages
than fibroblasts, with surviving macrophages showing an increase in
measured protein synthesis. Keast and Holt (57) also found that the
macrophages from mice exposed to smoke for many weeks were no
longer as susceptible to the untoward effects of smoke and had
apparently adapted to the toxic conditions in a fashion similar to that
seen in the tissue culture experiments.

Enzyme systems have also been shown to be affected by smoking.
Martin (67) demonstrated that increased macrophage acid hydrolase
directly correlated with daily cigarette consumption. Meyer, et al. (72)
examined the effect of various concentrations of nicotine on the
ATPase activity of sheep pulmonary alveolar macrophages and showed
significant inhibition of this activity. Additionally, lower concentra-
tions of this alkaloid stimulated cell respiration while higher concentra-
tions were inhibitory. Kasemir and Kerp (56) recorded decreased
oxygen uptake in sheep macrophages in contact with tobacco extracts.
The in vitro studies of Harris and coworkers (44) on human alveolar
macrophages demonstrated increased glucose utilization in smokers.

In pertinent studies, macrophage function has been measured by
several methods. Green and Carolin (34), using an in vitro system to

10—16
measure phagocytosis, showed that added cigarette smoke had a
depressant effect on the phagocytic activity of alveolar macrophages
for Staphylococcus albus. The studies by Maxwell, et al. (69) on lung
macrophages from guinea pigs exposed to tobacco prior to cell harvest
showed that, although these alveolar cells phagocytosed bacteria at
normal rates, their capacity for bacterial inactivation was impaired.

Laurenzi, et al. (61) demonstrated a 50 percent reduction in clearance
of staphylococci from the lungs of smoke-exposed mice. In two human
studies (22, 44) which measured phagocytic properties of alveolar
macrophages, no significant differences were found between smokers
and nonsmokers. Other studies of in vitro function of macrophages
after in vive exposure to smoke (employing rat alveolar macrophages)
revealed no impairment of bactericidal inactivation of S. albus (49).

In the studies of Warr and Martin (119, 120), macrophages of
smokers demonstrated an impaired response to an immune effector,
MIF, paralleling those situations characterized by the absence of cell-
mediated delayed hypersensitivity as well as acquired resistance to
aggregate under in vitro conditions.

Though more work is needed to define the total qualitative and
quantitative influences of tobacco smoking on alveolar macrophages,
there is sufficient evidence in these studies to indicate measurable
degrees of physiological impairment. Since interference with phagocy-
tosis, endocytosis, and antigen processing can be anticipated as a
consequence, there is the potential diminution of specific immune
functions by these cells. In turn, the impairment of local immune
processes as the first line of host defense exerts its toll on the
dependent development of systemic immunity and influences emerging
allergic inflammation.

The B and T lymphocytes are involved respectively in the humoral
and cell-mediated arms of the immune system that functions both
locally and systemically. It is therefore pertinent to examine the effect
of smoking on these elements that provide the immunologic basis of
hypersensitivity.

Of the immunoglobulins, secretory IgA is known to be predominant
in bronchial mucus (29) (although the IgG/IgA ratio is increased in
smokers (90)) and presumably plays a role in first-line defense against
microbial invasion. Soutar’s (101) studies on the distribution of plasma
and other immunoglobulin-containing cells in the respiratory tract
indicated more IgA-containing cells then those of other immunoglobu-
lin classes. However, the only differential finding between smokers
and nonsmokers was localized to the lobar bronchi of smokers where
significant increases in IgA-containing cells were identified. Smoking
was found to have significant suppressive action on salivary secretory
IgA levels in normals, but not in patients with chronic diseases whose
IgA levels were already elevated above normal (63). While these

10—17
studies show alterations in the expressions of local humoral immunity,
the clinical significance of these changes is unknown.

Investigations have also been done to determine the effect of
smoking on systemic humoral immunity. An assay which reflects
antibody production is the plaque-forming cell (PFC) response.
Thomas, et al. (108) examined PFC responses in samples of immuno-
competent lung cells from mice exposed to fresh cigarette smoke and
found progressive impairment of these responses over the exposure
period of up to 10 months. In the studies of Holt, Keast, Nulsen, and
Thomas (76,106,108,109,110) concerning the long-term effects of
smoking on mice, PFC responses to intratracheally or intraperitoneally
introduced antigens were shown to be initially enhanced and then
depressed by chronic smoking (108,109). The direct measurement of
serum hemolytic and hemagglutinating antibodies also showed depres-
sion, but the humoral response to a T cell-independent immunogen was
unaffected (109). The secondary PFC response reflecting another
aspect of humoral immunity was unaffected by smoking (109). PFC
response depression was found to be reversible in a group when
smoking was discontinued for 16 weeks (110). Other measurements of
humoral immunity in mouse models exposed to tobacco also demon-
strated impairment of the production of hemagglutinating antibodies,
including those raised in response to the influenza virus (66), although
some degree of suppression was reversible (28). Tar content of
cigarettes may also play an important role (46).

Roszman, et al. (93, 94, 95), investigating several aspects of smoking
and immunity in rabbits, found suppression of mitogen-induced
blastogenesis and suppression of the immunoglobulin M and G
antibody responses which correlated directly with the concentration
either of nicotine or of the water-soluble fraction from cigarette smoke
that was added to cultures.

Several surveys have attempted to address the issue of whether
smoking influences serum immunoglobulin levels. Vos-Brat and
Ruemke (116) found significant depression of IgG in smokers,
Kosmider, et al. (59) also found a decreased IgG but increased IgM and
IgA, while Wingerd and Sponzilli (127) found a decrease in the entire
gamma globulin fraction. A decrease in lymphocytotoxic antibodies
among smokers has also been demonstrated in pregnant women (77).
On the other hand, no reported differences in mean concentrations of
immunoglobulins were found when smokers were compared to
nonsmokers by geographic location (71).

While these reports suggest that humoral antibody responses are
influenced by cigarette smoke in a variety of ways, critical to this issue
is a consideration of possible biologic impact in humans. Whether
susceptibility to infection may be the end result of smoking effects on
constituent elements of the immune system should be addressed. Thus,
especially pertinent are the influenza vaccination studies of Waldman,

10—18
et al. (117), indicating that smoking more than one-half pack of
cigarettes per day increased the risk of influenza-like illness, although
the duration of the illness was unaltered. Finklea and associates (32)
showed that the incidence of clinical influenza was 21 percent higher
among smokers than nonsmokers. Serological data from this study
suggested that smokers also had more frequent subclinical influenza.
In pursuing this observation, Finklea, et al. (31) showed that, while
serologic response to vaccination did not significantly differ between
smokers and nonsmokers, the persistence of antibody titers after either
natural infection or vaccination with Az antigens was significantly
decreased among smokers. Nymand (77), examining histories of
pregnant women, found that urinary tract infections and viral illness
were observed more often in smokers than nonsmokers.

That elements indicative of immune function appear in the lung is
evidenced by the identification of both T and B cells in fluid samples
recovered from this site (121). Of interest is the finding of both an
increased number of T and B cells and an increase in the T/B ratio in
smokers.

Several aspects of cell-mediated immunity have been studied in
animal models, including the ability of immunocompetent lymphocytes
to proliferate after mitogenic stimulation by phytohemagglutin
(PHA), pokeweed (PW), and Concanavalin A (Con-A). In mice, initial
increases of PHA responses in blood and regional lymph node
lymphocytes were found after brief exposure to cigarette smoke, but
decreases were found after prolonged exposure (107). Another study
(18) demonstrated inhibition of proliferation of mouse lymphocytes to
both PHA and pokeweed mitogen by an aqueous fraction of tobacco. In
the rabbit (94), both nicotine and water-soluble fractions from whole
cigarette smoke diminished peripheral lymphocyte blastogenic re-
sponse to lectin stimulation.

Because of variation in methodology, data from human studies are
difficult to compare. While increased numbers of T cells in peripheral
blood lymphocytes and enhanced PHA response were noted among
younger smokers, responses of older smokers or of those with a history
of heavier cigarette consumption did not differ from normals (100). In
examining peripheral bloods, Suciu-Foca, et al. (103) found no
differences in percent of T lymphocytes, PHA responses, or behavior in
mixed lymphocyte cultures between smokers and nonsmokers. In
another study (125), samples of blood taken from humans after
smoking showed no differences in PHA responses even when
physiologic levels of nicotine were added directly to the cultures. In
contrast, Neher (74) found decreased DNA synthesis in response to
PHA in the presence of nicotine. Desplaces, et al. (27) showed that
smoke inhibited lymphocyte transformation by PHA yet stimulated
lymphocytes in the absence of PHA. The clinical significance of this
single aspect of T-cell function has yet to be determined.

10—19
Effects on other cellular elements of the immune system have also
been described. Vos-Brat and Ruemke (176) and Silverman, et al. (100)
demonstrated increased granular leukocytic levels in smokers. Others
(54,79,98,129) have shown that smokers have hypereosinophilia. In two
studies (79,98) the hypereosinophilia was reversible with abstinence
from smoking. Similar lymphocytic and eosinophilic increases among
smokers have been noted in patients’ post-myocardial infarctions (129).

Serum abnormalities also have been described in smokers, including
increased C-reactive (45) protein and an abnormal seroflocculant in
smokers. Effects of smoking on manifestations of immune hyperres-
ponsiveness add further evidence to the purported suppressive action
of tobacco. Of interest are the reports of diminution of amyloid
formation in the hamster model (123) and the inexplicable increase in
survival of cardiac transplants in patients who resumed smoking
postoperatively (35).

Target Organs of the Allergic Response

Despite the limitations, as previously noted, in appropriate materials
and methods to define any possible effects of tobacco and smoking on
allergic people, studies dealing with their roles in affecting various
organs are noteworthy. A variety of clinical conditions have been
ascribed to allergic manifestations to tobacco leaf or smoke, including
asthma, rhinitis, hives, dermatitis, migraine headaches, cardiac and
other vascular disturbances, as well as gastrointestinal disorders. The
respiratory system has been the most widely studied.

Allergic rhinitis, typified by hay fever due to seasonal pollens and
molds, is caused by exposure to a wide range of ubiquitous allergens.
Apart from investigations of tobacco workers, there are no available
studies to date to suggest that tobacco smoke or tobacco allergens are
in fact a cause of allergic rhinitis in the general population. Many
studies, however, have been reported showing that rhinitis patients
suffer exacerbation of symptoms upon exposure to smoke. Speer (102)
reported that 67 percent of allergic persons noted aggravation of nasal
symptoms upon exposure to smoke, compared to 29 percent of
nonallergic persons similiarly exposed. Broder, et al. (11) found that
most symptoms of allergic rhinitis could be attributed to other
definable allergens with smoking or smoke exposure playing only a
minor role. Allergic rhinitis believed to be related specifically to
hypersensitivity to tobacco leaf products was reported to occur in 14.6
percent of 355 tobacco plantation workers and 8.7 percent of 722
tobacco factory workers (114).

Another study (86) among tobacco workers demonstrated that
allergic rhinitis thought to be related to tobacco leaf occurred in
approximately 4 percent of cases. However, possible contamination of

10—20
tobacco by molds or other allergens or irritants was not excluded in
these studies.

It is relevant to note that symptoms of nasal congestion and excess
mucous gland secretion, which may mimic those of allergic rhinitis or
hay fever, can be caused by the nonspecific irritant or pharmacologic
effects of vapor from the constituents of tobacco smoke. Thus,
although it is not known whether allergy to tobacco or tobacco smoke
plays a primary etiologic role in the usual case of allergic rhinitis,
tobacco smoke per se is known to aggravate this condition via an
irritant effect.

It is well known (102) that eye irritation manifested by itching,
burning, swelling, and lacrimation occurs commonly among both
allergic nonsmokers and nonallergic nonsmokers. To date, no studies
are available suggesting that this manifestation is due to anything
other than the nonspecific irritating effect of cigarette smoke.

Many studies have attempted to assess the relation between tobacco
or smoking and asthma. Early investigators, using a variety of skin
test materials (64, 91), inferred that allergy to tobaeco could be
causally related to asthma. Subsequent reports have examined the
possible role of passive smoking in asthma. Speer (102) found that
wheezing occurred more frequently in allergic people than in
nonallergic people upon exposure to smoke. O’Connell and Logan (78),
in studying the effects of parental smoking, found that smoke
aggravated attacks of asthma in 26 percent of asthmatic children of
nonsmoking parents, in contrast to 67 percent of asthmatic children of
smoking parents. Importantly, they assessed the effects upon
asthmatic children whose parents stopped smoking and reported
improvement in 18 of 20 children. In contrast, only 4 of 15 asthmatic
children improved when parents continued to smoke. Cameron and
coworkers (15) concluded that asthmatic children of smoking parents
were more often ill with respiratory disease but that this was related
to nonspecific irritation rather than hypersensitivity. On the other
hand, Rosen and Levy (92) published a case report of an infant who
developed bronchial asthma associated with exposure to smoke. In this
study, reaginic antibody to tobacco extract was documented by passive
cutaneous transfer. More conclusive studies that tobacco may be
causally related to asthma are reported among tobacco workers.
Among 286 persons exposed to raw or fermented tobacco, the incidence
of allergic manifestations was 8 percent, of which 17 percent had
asthma (86). The possible role of tobacco additives has also been
considered. Burge, et al. (13) reported the occurrence of occupationally-
related asthma in a group of 21 industrial workers where colophony or
pine resin, a substance also present in cigarettes as adhesives and filter
fillings, was implicated.

The consequences of cigarette smoking in the asthmatic patient have
also been examined. Townley and coworkers (112) reported similar

10—21
bronchial airway responses to lung function tests by methacholine
inhalation in both smoking and nonsmoking asthmatics. Pimm and
associates also reported that passive exposure of asthmatics to
cigarette smoke resulted in no consistent significant effect on lung
volumes and expiratory flow rates when compared with parallel room
air exposure (84). On the other hand, Burrows, et al. (14), in a study of
smoking and tests of lung function, found that an allergic predisposi-
tion, asthma or allergic rhinitis, as defined by positive skin reactivity,
were associated with an increased susceptibility to bronchoconstrictor
effects of cigarette smoking and to recurrent chest infections. That
smoking can adversely effect an asthmatic patient in an indirect
manner is illustrated by the finding of Powell, et al. (87) demonstrat-
ing interference with normal metabolism of the bronchodilator agent,
theophylline, in smokers.

The concept that hyperreactive airways in asthmatics are due to a
regulatory dysfunction of the autonomic nervous system is pertinent to
this discussion (30). In addition to the effects of specific allergens
inducing responsible mediators of bronchoconstriction, it is appreciated
that nonspecific irritants (for example odors, temperature extremes,
exercise, chemicals) can also act upon the affected cell receptors to
precipitate asthmatic attacks.

Thus, apart from any putative allergenic effects of tobacco in a
specifically sensitized patient, inhaled tobacco smoke carries the
irritant potential to trigger or to aggravate asthmatic symptoms in the
patient so affected. Hence, there is further support offered for both
cessation of smoking and the following of avoidance procedures of
passive exposure in the asthmatic individual.

Allergic effects of tobacco on the cardiovascular system have also
received considerable attention. It is well documented that cardiac
abnormalities occur in association with allergic phenomena, for
example, anaphylaxis or allergic shock (5, 25, 73). However, whether
tobacco may play a role in cardiovascular alterations apart from known
pharmacologic effects is still not clear. Harkavy’s series of observa-
tions (36, 37, 38, 39, 40, 42, 48) would support the concept that allergy to
tobacco leaf may have important implications in a variety of cardiac
and vascular diseases. In these he would include cardiac arrythmias,
intensification of coronary artery insufficiency, thromboangiitis
obliterans, migrating phlebitis, and some forms of allergic vasculitis.
Although acknowledging the pharmacologic effects of nicotine on the
cardiovascular system, Harkavy also suggests that it may act as a
hapten in inducing allergic responses. Recent observations by Becker
and coworkers (10), using a partially characterized antigenic compo-
nent of tobacco, led them to hypothesize that circulating tobacco
antigens in sensitive individuals might react with corresponding
antibody to produce focal injury of blood vessels. If this hypothesis is
corroborated, design of further studies of potential adverse conse-

10—22
quences of possible tobacco allergy on the cardiovascular system will be
possible.

That tobacco may operate through the mechanism of cell-mediated
immunity or delayed hypersensitivity is suggested by case reports of
contact dermatitis caused by tobacco smoke and tobacco smoke residue
(19, 24, 122). Recent surveys among tobacco workers have shown that
contact dermatitis related to tobacco was responsible for 14 percent of
skin eruptions occurring in this industrial sample (3). By. contrast,
however, an earlier survey (96) could not implicate tobacco. as a cause
of dermatitis among cigar factory workers. It has been pointed out
that dermatitis among tobacco workers probably represents a nonspe-
cific response due to injury, moisture, or irritants, especially those
from the chemicals or other fertilizers used in the growing process
(122). To date, therefore, there is little evidence that allergic skin
manifestations due to tobacco occur with any significant frequency.

Summary

1. Tobacco and tobacco smoke extracts have been found to act as
antigens inducing both precipitating and reaginic antibodies in
experimental animals. Tobaceo leaf products ean also sensitize
lymphocytes participating in cell-mediated immune functions.

2. Tobacco and its combustion products are known to be heterogene-
ous mixtures of particulate and gasous materials. Additionally, natural
contaminants and intentional additives increase the array of compo-
nents, presenting a complex of toxic, pharmacologic, irritant, and
inflammatory effects that can complicate interpretation of a precisely
defined role for tobacco in immune and allergic processes.

3. Several tobacco antigens have been isolated by chemical proce-
dures. Of special interest is a glycoprotein common to both tobacco
extracts and smoke antigenically corresponding with reaginic antibody
in humans.

4. Epidemiologic samplings to define the presence of true allergy to
tobacco, either among healthy persons or among those suffering from
known allergic conditions, are inconclusive.

5. Tobacco smokthg exerts a variety of effects on respiratory tract
structures involved in local host defense, and chronic smoking leads to
20nsistent histological changes in the respiratory tract.

(a) There is evidence to indicate an adverse effect of long-term
smoking on the mucociliary transport mechanisms and mucus
composition.

(b) The number of macrophages isolated from lung fluids of smokers
is increased over nonsmokers.

(c) Changes in the ultrastructure of macrophages—most notably the
presence of cytoplasmic inclusions—are found in smokers.

10—23
(d) Alveolar macrophages from smokers have altered metabolism

and measurable degrees of physiologic impairment.

6. Alterations of indicators of humoral immunity have been
demonstrated in the respiratory tracts of smokers, and smoking may
impair systemic humoral immunity both in vitro and in vivo.

7. Alterations in assays of cell-mediated immunity are noted locally
and systemically in smokers.

8. Leukocytosis and reversible hypereosinophilia have been seen in
smokers.

9. The ability to make a definitive diagnosis of tobacco allergy is
complicated by the difficulty of demonstrating a cause and effect
relationship between immunologic events and disease manifestations;
additional evidence is required to establish whether there is a
definitive role for tobacco smoke sensitization in causing allergic
diseases.

10. Studies concerned with the adverse consequences of either active
or passive smoking have shown that allergic individuals, especially
those with rhinitis or asthma, may, in fact, be more sensitive to the
nonspecific noxious effects of cigarette smoke than healthy individu-
als.

Conclusion and Comment

Apart from symptom-relieving drugs, there are no known effective
therapeutic measures to prevent or combat the adverse effects of
smoking on immune function and on allergy-related problems. It is
evident that further studies defining tobacco antigens, determining
the clinical incidence of tobacco allergy, further clarifying the nature
of immune responses to tobacco, and improving the diagnostic agents
and materials should be undertaken. Such studies, however, can not be
expected to have an impact on improving the health of individuals
subject to tobacco’s adverse effects comparable to that which would
result from adhering to the mainstay of management of the allergic
patient—complete avoidance of the incriminated substance.

10—24
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10—32
11. INVOLUNTARY SMOKING.

 

Center for Disease Control
CONTENTS

 

Introduction ........ccecece ec ec ence eee e een ee neces ee ene eee ee nents ene eee 5

 

Constituents of Tobacco Smoke and Their Absorption by

 

 

 

 

the Nonsmoker ...........:0:cceececeereceeceeeenseneeteeeneneeneseees 6
Carbon Monoxide.............cccceeeeee eee ee ene eee neneeeene erates 15
NiCOCING ...0..ccccccccecceeecceeet esse eesee eres se eeeeeteneenneeenges 24
Other Substances...........--0:ccceeeenec en eceeeeeeeeeeeneeeenees 24

Effects of Tobacco Smoke on the Nonsmoker.............++- 25
General Population .............:::eceseeeeeeeeee eee nee ener ees 25
Effects of Carbon Monoxide in Psychomotor Tests ...28
Special Populations ...............::seeerseeeeeeeet ener eneseee es 29
Cardiovascular Disease ...............ccecseeeeee ene eeeeeneeeene 29
Chronic Obstructive Lung Disease..............::.:eseeeee 31
Hypersensitivity ..........::cceseeeeeeeeseeeeeeseeeneateeenecennes 31
Children .........ccccccceccecc eee eee eee eeeseedenee ena eneeneens ene eeeee 31

SUT 0 ah CECE 33

Recommendations ...........0:ceeceeeeeeeee teens cececeesuseeseeeneees 35

References .....c.ccccccncceseccceeeete ences tees ess eeeeeeea seen eeneeeee eee 36

LIST OF FIGURES

 

Figure 1.—Calculated buildup of CO under varying
conditions of ventilation and smoking.................-..-.6+ 22

11—3
LIST OF TABLES

Table 1.—Constituents of cigarette smoke: ratio of
sidestream smoke to mainstream smoke......-.--serereeeeee 6

 

 

 

Table 2.—Measurement of constituents of tobacco smoke in
experimental conditions ........--s-sssresrertrerretrtre see 7

 

Table 3.—Measurement of constituents of tobacco smoke
under natural conditions.........--::cssssessrereersesersree ee 16

 

Table 4.—Median percent carboxyhemoglobin (COHb)
saturation and 90 percent range for nonsmokers by
JOCAtION. ...cceeeceeceeee seen eee etre ete EEE EET TEESE SEES 23

 

Table 5.—Admission rates (per 100 infants) by diagnosis,
birth weight, and maternal SMOKING....-...ceeeeeeeeeeee reese

 

 

Table 6.—Pneumonia and bronchitis in the first 5 years of
life, by parents’ smoking habit and morning phlegm....34

11—4
Introduction

The effects of smoking on the smoker have been extensively
documented in other chapters of this report. This chapter will review
the effects of tobacco smoke on the nonsmoker, an area in which there
has been increasing concern in the past several years (66a, 76, 77). This
topic has been referred to as “passive smoking” or “secondhand”
smoking as well as “involuntary smoking.” The term involuntary
smoking will be used to mean the inhalation by the nonsmoker of
tobacco combustion products from smoke-filled atmospheres. This type
of exposure is, in a sense, “smoking” because it provides exposure to
many of the same constituents of tobacco smoke that voluntary
smokers experience. It is also “involuntary” because the exposure
occurs as an unavoidable consequence of breathing in a smoke-filled
environment.

The chemical constituents found in an atmosphere filled with
tobacco smoke are derived from two sources—mainstream and
sidestream smoke. Mainstream smoke emerges from the tobacco
product while being drawn through the tobacco during puffing.
Sidestream smoke rises from the burning cone of tobacco. For several
reasons, mainstream and sidestream smoke contribute different
concentrations of many substances to the atmosphere: different
amounts of tobacco are consumed in the production of mainstream and
sidestream smoke; the temperature of combustion for tobacco is
different during puffing than while smouldering; and certain sub-
stances are partially absorbed from the mainstream smoke by the
smoker. The amount of a substance absorbed by the smoker depends on
the characteristics of the substance and the depth of inhalation by the
smoker.

When the smoker does not inhale the smoke into his lungs, the smoke
he exhales contains less than half its original amount of water-soluble
volatile compounds, four-fifths of the original nonwater-soluble
compounds and particulate matter, and almost all of the carbon
monoxide (25). When the smoker inhales the mainstream smoke, he
exhales into the atmosphere less than one-seventh of the amount of
volatile and particulate substances that were originally present in the
smoke, and he also reduces the exhaled CO to less than half its original
concentration (26). As a result, different concentrations of substances
are found in exhaled mainstream smoke depending on the tobacco
product, composition of the tobacco, and degree of inhalation by the
smoker.

The effects of cigarette smoke on the environment and on the
nonsmoker in the environment will be examined by reviewing data on
the constituents of cigarette smoke measured under various conditions
and on the absorption of these constituents by the nonsmoker. The
physiologic effects of this “involuntary smoking” will then be
considered.

11-5
Constituents of Tobacco Smoke and Their Absorption by the
Nonsmoker

Brunnemann, et al. (14) have recently presented a compilation of the
levels of some of the important substances in mainstream cigarette
smoke and the ratio of sidestream to mainstream levels for these
substances (Table 1). The actual amount of the substance and the
mainstream-to-sidestream ratio will vary with different types of
tobacco tested and the method used to burn the cigarette, but Table 1
gives values generally consistent with those found by others (23, 45,
50). Many of the substances, including nicotine, carbon monoxide, and
ammonia, are found in much higher concentrations in sidestream
smoke than in mainstream smoke. Thus, the total smoke exposure of
nonsmokers is quantitatively much smaller than the exposure of
smokers, but the smoke nonsmokers inhale may be qualitatively richer
in certain compounds than mainstream smoke. This qualitative

TABLE 1.—Constituents of Cigarette Smoke.! Ratio of
sidestream smoke (SS) to mainstream smoke (MS)

 

 

 

 

A. GAS PHASE MS SS/MS MS SS/MS
Carbon Dioxide 20-60 mg 8.1 Nitrogen Oxides (NOx)
Carbon Monoxide 10-20 mg 2.5 Ammonia 30 ug 3
Methane 13 mg 3.1 Hydrogen cyanide 430 pe Og
Acetylene 27 ug 08 Acetonitrile 120 pg 3.9
Propane Propene 05mg 41 Pyridine 32 ug 10
Methylchioride 0.65 mg 21 3-Picoline 24 pg 18
Methylfuran 20 ne 34 3-Vinylpyridine 2 ug 2B
Propionaldehyde 40 pe 24 Dimethylnitrosamine 10-65 ug 52
2-Butanone 80-250 yg 29 Nitrospyrrolidine 10-35 pe 27
Acetone 100-600 ue
. ARTICULATE MS SS/MS MS SS/M:
“Tar” 1-40 mg 17 Quinoline LT ug 1
Water 14 mg 24 Methylquinolines 0.7 pe 1
Toluene 108 pe 5.6 Aniline 360 ng 30
Stigmasterol 53 ue 08 2-Naphthylamine 2ng 39
Total Phytosterols 130 ng «= «08 4-Aminobiphenyl 5 ng 31
Phenol 20-150 pg 26 Hydrazine 32 ng 2
Catechol 130-280 pg 0.7 N'-Nitrosonornicotine 100-500 ng &
Napthalene 28 ug =«16 NNK? 80-220 ng 10
MethyInaphthalene 22 pg 2B Nicotine 1-25 mg 7
Pyrene 50-200 ug 3.6
Benzo(a)pyrene 20-40 pg 3.4

 

‘Nonfilter cigarette
2NNK = 44N-methyl-N-nitrosamino}-143-pyridyl}-1-butanone {tobacco specific carcinogenic nitrosamine)
SOURCE: Adapted from Brunnemann (14).

11—6
LT

TABLE 2.—Measurement of constituents of tobacco smoke in experimental conditions.!

 

 

 

 

Reference, location, Ventilation Amount of Level of Measure of
and dimensions tobacco burned constituent absorption
Anderson and Dalhamn (8).
Room 80 m3 6.4 air changes 46 cig & 45 ppm CO COHb 6%
per hour 3 pipefuls 377 mg/m nicotine
Bridge and Corn (13).
Party room 145 m? 70 air changes 50 cig & 17 7.0 ppm CO
per hour cigars in 1.5 hr
Party room 101 m3 10.6 air changes 63 cig & 10 9.0 ppm CO
per hour cigars in 1.5 hr
Brunnemann, et al. (16).
Box .4 m3 none 10 cig in 1 hr 2.7 ng/| dimethylnitrosamine
15 liters/min 10 cig in 1 hr 29 ng/l dimethy!nitrosamine
Small room 20 m3 none 100 cig in 1 hr 33 ng/| dimethylnitrosamine
none 100 cig in 1 br .23 ng/l dimethylnitrosamine
some 100 cig in 1 hr 1.85 ng/| dimethylnitrosamine