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CHAPTER 12
Tobacco smoke and respiratory disease
J. Behr*, D. Nowak
#
*Dept of Internal Medicine I, Section for Pulmonary Diseases and
#
Institute and outpatient Clinic for
Occupational and Environmental Medicine, University of Munich, Munich, Germany.
Correspondence: D. Nowak, Institut und Poliklinik fu¨r Arbeits und Umweltmedizin, Klinikum der
Universita¨t Mu¨nchen, Innenstadt, Ziemssenstrasse 1, 80336 Mu¨nchen, Germany.
Although tobacco has been used in Western culture for w400 yrs, inhalative cigarette
smoking is a relatively new development. It was during the 20th century that cigarette
smoking became a mass phenomenon. Interestingly, the evolution of the prevalence of
tobacco smoking in a given population strikingly resembles the evolution of an infective
epidemic [1]. Introduced by "trend-setters" into society, the "smoking epidemic" reached
its maximum in the 1950s in the male population, with considerable geographic variation
in time trends since then. However, the overall prevalence of smoking is determined
by such factors as sex, social status, and age [1]. Currently, the prevalence of smoking
around the world is estimated to be 47% amongst males and 12% amongst females, in
Europe y35% of males and 25% of females are active smokers [2, 3]. There are cross-
sectional and longitudinal studies demonstrating the deleterious effect of smoking on
respiratory health [4–6], but tobacco smoke is also a risk factor for cancer of the digestive
and urinary tract, coronary and vascular disease, as well as a number of nonfatal
conditions. Consequently, tobacco smoking is a major cause of premature death in
Europe. Moreover, throughout the European Union, 32% of deaths in males aged
35–69 yrs and 10% of deaths in females in the same age range are attributable to smoking
[7]. The proportion of deaths from respiratory diseases attributable to tobacco smoking
are even higher: 54% for males and 42% for females [7]. The economic impact of
smoking has been consistently estimated to be approximately 200–300 per capita in
the USA and Europe [8]. Furthermore, since the 1970s there is increasing evidence that
not only active smoking is a risk factor for respiratory diseases, but also environmental
tobacco smoke exposure in nonsmokers, especially in children [9]. Taken together, the
available data clearly demonstrate that active and passive smoking place a significant
burden on public health, especially with regard to respiratory diseases. Extrapolations
of the present data suggest that the proportion of tobacco-associated diseases will
increase in the coming decades with chronic obstructive pulmonary disease (COPD)
and lung cancer becoming the most prevalent causes of death in the year 2020 [10].
Trends in smoking prevalence
Time trends in cigarette consumption vary considerably between regions. During
the last 30 yrs, cigarette consumption per adult was rather stable in Europe, decreased
in America and increased in all other regions, particularly in the Western Pacific region.
The apparent stability of global per capita cigarette consumption, thus, results from
a decreasing consumption in developed countries counterbalanced by increasing
consumption in developing countries. The analysis of temporal trends in 111 countries
Eur Respir Mon, 2002, 21, 161–179. Printed in UK - all rights reserved. Copyright ERS Journals Ltd 2002; European Respiratory Monograph;
ISSN 1025-448x. ISBN 1-904097-24-3.
161
[11] reveals that compared with the 1970s, cigarette consumption per adult increased
in 58 countries and was stable or declining in the other 53 (table 1). The rise in cigarette
consumption, however, includes the world’s most populous countries, such as China.
Reasons for smoking
Smoking status is believed to be largely a function of genetic and sociodemographic
factors, environmental determinants, behavioural factors and specific dimensions of
personality [12, 13].
Genetic factors
Twin studies show a substantial genetic determination of smoking [14]. This is not
surprising since genetic factors substantially contribute to major personality character-
istics as well as to psychiatric dimensions.
Sociodemographic factors
Age is an important determinant for smoking status, since the earlier in life smoking
is started the higher the likelihood of becoming a regular smoker. Moreover, the
likelihood of stopping smoking decreases the earlier the habit is taken up [15, 16]. Gender
differences show geographically and culturally different patterns. Higher smoking
rates in females are frequently found in countries with a "Western lifestyle". Ethnic
background is a major determinant of smoking status, with lower prevalences in Blacks
than in Hispanics [17] and lower relative frequencies of smoking in Northern than in
Southern Europe [11]. Across countries and rather consistently over time, growing up
in intact, two parent families has been demonstrated to be associated with a decreased
prevalence of smoking among children [18]. Parental socioeconomic status is generally
considered to be inversely related to smoking in adolescents [19].
Environmental factors
Children of parents who smoke generally have a higher risk of taking up the habit
themselves as compared to children of nonsmoker parents [20]. Likewise, an influence of
Table 1. Number of countries and consumption of cigarettes per adult aged i15 yrs
WHO regions and countries
1970–1972 to 1990–1992
Increased Decreased Unchanged
WHO regions
African region 15 6 5
Region of the Americas 9 17 0
Eastern Mediterranean region 9 0 3
European region 11 14 1
South-East Asia region 6 2 0
Western Pacific region 8 5 0
More developed countries 12 18 1
Less developed countries 46 26 8
World 58 44 9
Number of countries where consumption of cigarettes per adult aged i15 yrs increased, decreased, or
remained unchanged in the period from 1970 1972 to 1990 1992 (according to the World Health
Organisation (WHO) [11]).
J. BEHR, D. NOWAK
162
sibling smoking on adolescent smoking behaviour has been reported, and the influence
of smoking by siblings may even be stronger than that of smoking by parents [21]. An
authoritative, positive parenting style, positively associated with child competencies
was inversely related to rates of smoking intention, initiation and experimentation in
adolescents [22]. In addition to smoking behaviour in the family, peer smoking is
sometimes even more of a consistent predictor of smoking [23]. Recently, Sargent et al.
[24] demonstrated a dose/response relationship between the number of cigarette
promotional items owned by an adolescent and the likelihood of smoking. The authors
interpreted their findings as support of a causal relationship between tobacco
promotional campaigns and smoking behaviour among adolescents, but they did not
adequately exclude the possibility that the tendency to start smoking may itself enhance
the chance of collecting promotional items.
Behavioural factors
Good academic performance in school is a major predictor for nonsmoking among
teenagers [25]. Risky behaviours such as carrying a weapon [26] and having a high
number of sexual partners [27] are positively associated with smoking statistically,
suggesting that smokers are generally more prone to potentially dangerous habits.
Personal factors
Perceived stress is associated with initiation and maintenance of smoking [28], and
nonsmokers may have healthier coping strategies. Markers of high self-esteem are
generally associated with lower smoking prevalence.
Of course, there are inconsistencies between some of the studies, and many markers
used in these studies may only be proxies for underlying mechanisms, however, the
majority of these findings can be translated into intervention programmes.
Composition of tobacco smoke
Cigarette smoke is a heterogenous aerosol produced by incomplete combustion of
the tobacco leaf. More than 4,000 substances have been identified in cigarette smoke,
including some that are pharmacologically active, antigenic, cytotoxic, mutagenic, and
carcinogenic (table 2).
In cigarette smoke particulate matter is dispersed in the gas phase. During puffing,
mainstream smoke emerges from the mouthpiece, whereas sidestream smoke is emitted
between the puffs at the burning cone and from the mouthpiece. Of the mainstream
smoke, 92–95% is in the gas phase and contains 0.3–3.3 billion particles?mL
-1
. The mean
particle size is 0.2–0.5 mm and therefore within the respirable range. Of special interest
is the fact that cigarette smoke contains a high concentration of reactive organic radicals
(RORs) and substances capable of producing RORs. Free radicals are formed in
high amounts at the tip of the cigarette due to the high temperatures of up to 900uC.
However, the lifetimes of these radicals are too short to allow inhalation by the smoker.
Consequently, fresh mainstream smoke contains only low concentrations of radicals,
whereas the concentration of RORs increases in the gas phase of cigarette smoke as it
ages, with maximal concentrations reached after 1–2 min [29]. This implies that highly
reactive free radicals are formed continuously within the smoke by chemical processes
during inhalation [30]. An important source for radical production is the relatively stable
nitric oxide (NO) radical that is found in cigarette smoke in high concentrations of
TOBACCO SMOKE AND RESPIRATORY DISEASE
163
up to 400 parts per million. NO is oxidised to the more reactive nitrogen dioxide radical
by dioxygen. This radical reacts with isoprene that has been demonstrated in high
concentrations in cigarette smoke to form various biologically active RORs [29].
Moreover, aqueous extracts of tar catalyse the formation of superoxide (O
2
?
-
), hydrogen
peroxide (H
2
O
2
), and the highly toxic hydroxyl radical (?OH) in the presence of oxygen.
These reactions are probably due to the presence of redox-cycling systems within
cigarette tar [29, 31]. Today, many of the adverse effects of cigarette smoke on respiratory
health are thought to be directly or indirectly associated with the high amount (1610
14
10
16
) of highly reactive free radicals inhaled by the smoker with each puff.
Mechanisms of tobacco smoke-induced lung disease
Among the effects that tobacco smoke exerts on the respiratory tract, two main
mechanisms can be differentiated: 1) induction of inflammation; and 2) mutagenic/
carcinogenic effects. The inflammatory reactions are composed of a variety of different
effects that include ciliotoxicity, increased mucous secretion, and accumulation of
activated inflammatory cells in the respiratory tract. Some of the constituents of tobacco
smoke are irritants, others exert toxic effects on the airway epithelium by virtue of their
chemical structure, e.g. acids, ammonia, aldehydes and, therefore, may cause cell damage
or death as well as local inflammation. Moreover, the normal clearance function of the
epithelium is impaired by ciliotoxic effects of these substances (table 2). Together with
goblet cell hyperplasia and increased mucous production, reduced clearance induces
mucous retention in the airways, a relevant predisposition for bacterial colonisation
and infection, ultimately causing inflammatory exacerbations. In addition to these
unspecific irritative and/or toxic effects caused by tobacco smoke constituents due to
their physicochemical properties, another more specific lesion is linked to the inhalation
of RORs. These RORs are either present in tobacco smoke or produced by tobacco
smoke constituents within the lungs after solution of tar constituents in the epithelial
lining fluid (ELF). Furthermore, oxidants in cigarette smoke have been shown to
induce sequestration of neutrophils and monocytes in the lungs that also penetrate the
endothelium and can be found in increased numbers in the bronchoalveolar lavage
(BAL) fluid [32]. These cells, predominantly neutrophilic granulocytes, are able to
produce large amounts of O
2
?
-
anions by the membrane bound reduced nicotinamide-
adenine dinucleotide phosphate-oxidase. O
2
?
-
anions are transformed into more
Table 2. Selected constituents of cigarette smoke
Particulate phase Main effects Gas phase Main effects
Tar Mutagenic/carcinogenic Carbon monoxide Impairment of oxygen binding to
haemoglobin
Nicotine Dose-dependent stimulator
or depressor of
parasympathetic
N-cholinergic receptors
Oxides of nitrogen Irritant, pro-inflammatory, ciliotoxic
Aromatic
hydrocarbons
Mutagenic/carcinogenic Aldehydes Irritant, pro-inflammatory, ciliotoxic
Phenol Irritant, mutagenic/carcinogenic Hydrocyanic acid Irritant, pro-inflammatory, ciliotoxic
Cresol Irritant, mutagenic/carcinogenic Acrolein Irritant, pro-inflammatory, ciliotoxic
b-Naphthylamine Mutagenic/carcinogenic Ammonia Irritant, pro-inflammatory, ciliotoxic
Benzo(a)pyrene Mutagenic/carcinogenic Nitrosamines Mutagenic/carcinogenic
Catechol Mutagenic/carcinogenic Hydrazine Mutagenic/carcinogenic
Indole Tumour acceleration Vinyl chloride Mutagenic/carcinogenic
Carbazole Tumour acceleration
J. BEHR, D. NOWAK
164
aggressive oxidants like H
2
O
2
, ?OH and, in the presence of myeloperoxidase, hypohalides
are formed (fig. 1). These oxidants may cause oxidative damage to a variety of different
substrates (fig. 2) and will ultimately result in alterations or destruction of cells and
constituents of the extracellular matrix of the lungs.
A special relationship exists between oxidants and the protease/antiprotease balance
Oxidative tissue destruction
e
-
O
2
NADPH-
oxidase
O
2
·
-
NO·
ONOO
-
·OH
H
2
O
2
SOD
Fenton's
reaction
Fe
2+
Cu
2+
e
-
2H
+
2 Cl
-
MPO
2 HOCl
Fig. 1. Overview of the metabolism of reactive organic radicals (ROR). NADPH: reduced nicotinamide-adenine
dinucleotide phosphate; O
2
?
-
: superoxide; SOD: superoxide dismutase; H
2
O
2
: hydrogen peroxide; MPO:
myeloperoxidase; NO?: nitrosyl; ? OH: hydroxyl radical; ONOO
-
: peroxynitrite.
Redox/signalling
Lipid mediators/
peroxidation
Cooperative effects
with proteases
Nonspecific
oxidative lesions
Proteins
Lipids
DNA
Injury/death,
of cells
Proteolysis
Tissue
destruction
Prostaglandins
Thromboxane
Leukotrienes
Vascular tone,
endothelial dysfunction
Transcription-
factors,
e.g
.
NF-
κ
B, AP-1
etc
.
Cytokines,
proliferation
apoptosis,
etc
.
ROR
Activated phagocytes
Cigarette smoke
mucus retention, infection
Fig. 2. Mechanisms of cell injury and tissue destruction by reactive organic radicals (RORs). DNA:
deoxyribonucleic acid; NF: nuclear factor; AP: activator protein.
TOBACCO SMOKE AND RESPIRATORY DISEASE
165
within the lungs: oxidants may inactivate important antiproteases, such as a
1
-proteinase
inhibitor, and secretory leukoprotease inhibitor [33, 34]. Other proteases are activated
by oxidation. Taken together, these effects of oxidants result in a protease/antiprotease
imbalance in favour of proteolytic activity likewise inducing tissue damage and inflam-
mation. This interaction between oxidants and the protease/antiprotease system is
referred to as the "cooperative effect".
Another important aspect of oxidant injury induced by cigarette smoke is the
damage of the antioxidant screen of the lung. Physiologically, oxidants are completely
counterbalanced by antioxidants within the lungs. The highly active antioxidants in
the lungs include scavengers, enzymes, and enzyme systems (table 3), which prevent
oxidative damage.
Glutathione (GSH) is quantitatively the most important antioxidant of the lung in the
extracellular and intracellular compartment [35]. Moreover, GSH is a scavenger for most
biologically relevant oxidants and can be recycled intracellularly by the GSH redox cycle
or the c-glutamyl cycle, which allows for de novo biosynthesis of GSH using degraded
extracellular GSH or glutathione disulphide as a substrate [35, 36]. It has been
demonstrated that cigarette smoke leads to an acute intracellular drop of GSH but
after several hours GSH production is increased and elevated levels of GSH have
been measured in the ELF from smokers [37]. This may represent an effort of the lung
to counterbalance the increased oxidant burden from smoking. Moreover, antioxidant
enzymes such as catalase and O
2
?
-
dismutase, as well as the antioxidant vitamin C, have
been reported to be elevated in the lungs of smokers. However, due to the increased
amount of oxidation products and decreased plasma antioxidant capacity, a shift of
the oxidant/antioxidant balance towards a more oxidated milieu has been indicated
in smokers [38]. The causes and mechanisms of oxidant lung injury induced by tobacco
smoke are summarised in figure 3. Taken together, smoking poses an increased oxidative
burden on the lungs which is overall not adequately counterbalanced despite an elevated
antioxidant screen.
Chronic obstructive pulmonary disease
In this context, the term COPD is confined to those obstructive respiratory conditions
most closely associated with cigarette consumption, namely, chronic bronchitis and
emphysema. Murray and Lopez [10] predicted that COPD, being the sixth most
common cause of death in 1990, will advance to worldwide third place in 2020. The
population attributable fraction of smoking for the development of COPD has been
estimated to be 0.7–0.8 in males and 0.7 in females [39]. Despite a considerable healthy
smoker effect which tends to mask effects of smoking on spirometric indices [40, 41],
airflow obstruction is more common among smokers than nonsmokers. The increased
longitudinal decline in forced expiratory volume in one second in smokers might be
considerably lowered by smoking cessation even when mild-to-moderate COPD is
already present [42]. Beside cigarette smoking, other less important risk factors for the
development of COPD include those seen in table 4 [43].
Table 3. Antioxidants of the lung
Scavengers Enzymes Enzyme systems
Serum proteins, albumin, transferrin,
coeruloplasmin, etc.
Superoxide dismutase c-Glutamyl cycle
Lactoferrin, taurin Catalase Glutathione redox cycle
Vitamin C and E
Glutathione
J. BEHR, D. NOWAK
166
The pathogenesis of smoking-related COPD includes the protease/antiprotease and
oxidant/antioxidant hypotheses and abnormal repair processes. In short, proteolytic
products from inflammatory cells, if not adequately counterbalanced by protective
antiprotease systems, lead to bronchial injury and destruction of alveolar architecture.
The protease/antiprotease hypothesis is based on the observation of premature
emphysema in patients with severe a
1
-proteinase inhibitor deficiency. Additionally,
the pathogenetic role of neutrophil elastase is compatible with the involvement of
neutrophils in the pathogenesis of COPD. Neutrophil elastase can damage the
respiratory epithelium and enhances mucous production by goblet cells [44]. It increases
interleukin-8 [45], which, in itself, is a potent chemoattractant for neutrophils.
In addition to neutrophils, alveolar macrophages and enzyme macrophage elastase,
a matrix metalloproteinase, play a role in the pathophysiology of emphysema [46].
However, the relative contribution of neutrophils and macrophages and their elastolytic
products for the development of COPD is not fully understood. The oxidant/antioxidant
hypothesis of COPD which has already been introduced in this article is based on a huge
amount of data indicating that oxidative stress contributes to COPD [47, 48]. In smokers
Cigarette smoke
Impaired ciliary
clearance
Oxidants
Aromatic hydrocarbons
Nitrosamines
etc.
Growth signals
Chromosomal damage
and DNA adducts
Oncogene expression
Carcinogenesis
Lung cancer
Infection
Mucus and toxin
retention
Oxidants
Aldehydes
Acids
Ammonia
etc.
Local irritation of
airway epithelium
Injury/death of cells
Influx of neutrophils
Inflammation
COPD & other inflammatory lung diseases
Fig. 3. Mechanisms of cigarette smoke induced lung disease. DNA: deoxyribonucleic acid; COPD: chronic
obstructive pulmonary disease.
Table 4. Risk factors (other than smoking) for the devlopment of chronic obstructive pulmonary disease
Genetic predisposition Host factors Environmental factors
a
1
-Proteinase inhibitor deficiency Female sex Childhood respiratory infections
Other familial predispositions Atopy and BHR Low socioeconomic status
Eosinophilia Alcohol consumption
Industrial exposures
Exposure to ETS
Air pollution
BHR: bronchial hyperresponsiveness; ETS: environmental tobacco smoke.
TOBACCO SMOKE AND RESPIRATORY DISEASE
167
and subjects with COPD, systemic increases in oxidants [49] and decreases in
antioxidants [38] have been demonstrated. Incomplete repair processes may cause
alterations in subepithelial structures leading to fibrosis of periobronchial tissue as well
as to inhibition of extracellular matrix remodelling [50–52].
Despite cigarette smoking being the most important risk factor for the development
of COPD, only a minority of smokers develop the disease. Therefore, research is
increasingly focusing on the question of which endogenous factors predispose smokers
to COPD [53–55].
Lung cancer
Since the beginning of the 20th century, from being a rare disease, lung cancer has
become the most common type of lethal cancer throughout the world [7]. In a recent
paper, Murray and Lopez [10] estimated lung cancer to be the 10th most common
cause of death today, accounting fory1 million deaths around the world annually. They
also predicted that by the year 2020 lung cancer will advance to the fourth most common
death cause in developed countries and to the fifth most common death cause worldwide
[10].
The causal relationship between lung cancer and cigarette smoking was first reported
in well conducted case-control studies in 1950 [56–59] and later confirmed in large
population-based, prospective, cohort studies [60, 61]. For most developed countries it
is currently estimated that 90% of lung cancer cases in males and 80% in females are
attributable to smoking. The critical risk factors are the early start of smoking during
teenage years and early adulthood, duration of smoking, number of cigarettes smoked
daily, and inhalation practices [62–64]. Amongst the established occupational respiratory
carcinogens, a multiplicative relationship with smoking has been shown for asbestos [65],
radon [66], nickel [67], as well as silica [68], and an overadditive but not multiplicative
relationship was demonstrated for arsenic [69].
As already stated, from a pathogenetic point of view, it is well established that cigarette
smoke contains a mixture of highly toxic compounds like irritants, mutagenic and
carcinogenic substances, including RORs that are fully capable of inducing alterations of
cell proliferation, chromosomal damage, deoxyribonucleic acid (DNA)-adduct forma-
tion, and activation of oncogenes. Recently, Denissenko et al. [70] reported selective
benzo(a)pyrene diol-epoxide adduct formation along exons of p53 in bronchial epithelial
cells, thus, providing a direct mechanistic link between tobacco smoke and lung cancer.
Therefore, toxin-induced injury or death of cells creates an environment of constant
generation of inflammatory and growth signals, including oxidants that finally results
in hyperplasia, metaplasia, mutagenic and carcinogenic transformation of resident cells
of the respiratory tract. Despite increased epidemiological and pathophysiological
knowledge about the links between smoking and lung cancer, it has to be kept in mind
that v20% of smokers develop lung cancer during their lifetime suggesting that host-
related factors are involved. Moreover, epidemiological studies revealed correlations
between familial risk of lung cancer and lung function level of relatives suggestive of the
existence of genetic susceptibility for the deleterious effects of cigarette smoke both as a
carcinogen and as a substance inducing airway obstruction [71, 72]. Genetic influence
may be mediated by various mechanisms like differences in carcinogen metabolism
[73–75], mucociliary clearance [76], efficiency of DNA repair [77], and regulation of
oncogene expression. A number of candidate genes for cancer suceptibility have already
been identified [78]. The new tools of molecular biology like microarray chip systems
may provide new insights into the genetic background of carcinogenesis in the near
J. BEHR, D. NOWAK
168
future. A better knowledge of individuals at risk might increase the efficacy of inter-
vention programmes due to the possibility of focusing on better defined high-risk groups.
Interstitial lung diseases
Interstitial lung diseases (ILDs) represent a heterogenous group of lung disorders,
generally characterised by dyspnoea, dry cough, diffuse interstitial infiltrates, restrictive
lung function pattern, and impaired gas exchange. The most common forms of ILDs
include sarcoidosis, idiopathic pulmonary fibrosis (IPF), pneumoconiosis, and those
ILDs associated with connective tissue diseases. It has recently been suggested that a
number of ILDs are positively linked to tobacco smoking whereas other forms are clearly
inversely related to cigarette smoking (table 5).
Idiopathic pulmonary fibrosis/usual interstitial pneumonia
Reclassification of the interstitial pneumonias by Katzenstein and Myers [79] has
defined usual interstitial pneumonia (UIP) as a clinical and pathological entity, and it is
solely this entity which should be referred to as IPF. The prevalence of IPF/UIP ranges
from 3–29 cases per 100,000 population, with this wide range being due to differences
in definition, study design, and populations [80]. Most importantly for the patient, IPF/
UIP has to be clearly differentiated from other interstitial pneumonias like respira-
tory bronchiolitis-associated (RB)-ILD or desquamative interstitial pneumonia (DIP)
because of its significantly worse median survival time of y3 yrs. The majority of cases
are sporadic with only a few familial forms; there is a slight male preponderance
(1–2:1; male:female), and most patients are w50 yrs of age [80–82]. The prevalence of
current or former smoking varied widely from 41–83% in series of IPF/UIP [83] and
was associated with an increased risk for developing the disease [84–86]. The role of
smoking in the pathogenesis of IPF/UIP is not well understood and there is no evidence
that smoking per se causes IPF/UIP. However, based on the pathogenetic mechanisms of
tobacco smoke already outlined, the underlying inflammatory process in IPF/UIP might
be enhanced by cigarette smoke.
Desquamative interstitial pneumonia
DIP is another form of the idiopathic interstitial pneumonias that is morphologically
characterised by a uniform picture showing accumulation of pigmented macrophages
within the alveolar spaces [79]. The clinical features of DIP are quite different from those
of IPF/UIP; an average age ofy40 yrs,y90% current or previous smokers, and ground-
glass appearance of lung tissue in high-resolution computed tomography (CT) are
characteristic [87, 88]. In contrast to IPF/UIP, most patients with DIP stabilise or
Table 5. Association between interstitial lung diseases (ILD) and cigarette smoking
ILD positively associated with smoking ILD negatively associated with smoking
Usual interstitial pneumonia/idiopathic
pulmonary fibrosis
Exogenous allergic alveolitis
(hypersensitivity pneumonitis)
Desquamative interstitial pneumonia Sarcoidosis
Respiratory bronchiolitis-associated ILD
Connective tissue disease-associated ILD
Pulmonary Langerhans’ cell histiocytosis
TOBACCO SMOKE AND RESPIRATORY DISEASE
169
improve with corticosteroid therapy and complete remission is possible [89]. Overall,
the long-term prognosis of the disease is somewhat better (average survival is 12 yrs).
The role of smoking in the pathogenesis and for the treatment of DIP is unknown,
although smoking cessation is clearly advocated.
Respiratory bronchiolitis-associated interstitial lung disease
RBILD was first described as an incidental autopsy finding in young male smokers
[90]. Whereas respiratory bronchiolitis without accompanying ILD is a common
finding in smokers, usually without any significant clinical implications, some smokers
or exsmokers develop this symptomatic ILD [83, 90, 91]. Similarly to DIP, RBILD is
characterised by intra-alveolar accumulation of pigmented macrophages. In contrast
to DIP, these changes are less diffuse and clearly centred on respiratory bronchioles and
peribronchiolar alveoli, sparing peripheral airspaces. There are only mild interstitial
inflammatory changes in peribronchiolar parenchyma and frank fibrosis is absent.
Clinical presentation is dominated by cough and exertional dyspnoea, there may be
inspiratory cackles and occasionally clubbing is observed. Lung function tests reveal
a mixed restrictive and obstructive impairment of mild-to-moderate degree. On chest
radiographs reticular or reticulonodular changes are frequent, but normal chest
radiographs have been reported in approximately one-third of affected patients [91].
On high-resolution CT areas of ground-glass attenuation are the most common finding
whereas subpleural reticulations and honeycombing, typical findings in UIP, are
distinctly absent. Overall prognosis is good, especially with smoking cessation. In some
cases, corticosteroids have been employed with beneficial results. With respect to the
similarities between DIP and RBILD regarding epidemiology, positive association with
smoking and clinical as well as histopathological presentation, it has been suggested
to use the term "smoking-related ILD" for both disorders.
Pulmonary Langerhans’ cell histiocytosis
Pulmonary Langerhans’ cell histiocytosis (PLCH; also known as histiocytosis X) is
classified as a dendritic cell-related (Langerhans’ cell) disease of variable, nonmalignant
biological behaviour with a wide range of severity from spontaneous remission to
lethality [92]. Rarely, PLCH is observed in the context of a multifocal Langerhans’ cell
histiocytosis affecting multiple organs; most of these diseases occur in children and are
not related to smoking. By contrast, PLCH of the adult patient is observed almost
exclusively in smokers (w90%) and smoking has been demonstrated to be a strong risk
factor for PLCH in a case-control study [93]. Although the pathogenetic role of smoking
has not yet been elucidated, an increase of Langerhans’ cells on the surface of bronchial
epithelium from smokers has been observed [94]. The peribronchial distribution of the
lesions and the fact that Langerhans’ cells are potent antigen-presenting cells suggest
an inhaled antigen within cigarette smoke as the cause of PLCH.
Miscellaneous interstitial lung disease
Epidemiological associations between cigarette smoking and ILDs have been reported
for some disorders with potential pulmonary manifestations. For rheumatoid arthritis
(RA), most [95–100], but not all [101, 102], studies have reported a positive relationship
between cigarette smoking and pulmonary function or radiological abnormalities.
J. BEHR, D. NOWAK
170
Interestingly, in a study of 150 twin pairs discordant for RA, cigarette smoking was a
risk factor for RA itself [103].
Antiglomerular basement membrane antibodies may cause nephritis and/or pulmo-
nary haemorrhage by binding to glomerular and alveolar basement membranes. The
term "Goodpasture’s syndrome" refers to the subset of patients with both nephritis
and pulmonary haemorrhage. Pulmonary haemorrhage, as observed in 60–80% of
antibasal membrane antibody-associated disease, has been consistently found to be
linked to cigarette smoking [104, 105]. However, in none of the reported diseases
has the pathophysiological role of cigarette smoking within the disease process been
clarified beyond the level of speculation.
Diseases with decreased incidence or severity in smokers
Hypersensitivity pneumonitis
Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is a chronic
inflammatory lung disease caused by inhalation of organic dust including antigens
typically derived from animal proteins or microbes. Formation of precipitating
antibodies against these antigens is characteristic for patients with HP. Consequently,
a type-III immune response has been implicated in the pathogenesis of the disease but
endotoxin may also be involved [106]. A number of studies report a decreased prevalence
of precipitating antibodies among smokers within antigen-exposed populations [107–
110]. Moreover, smokers are clearly underrepresented among patients with manifest
HP [111–113]. In a prospective study by Arima et al. [114], HP was observed in 65.9%
of the nonsmokers and in only 27.3% of the smokers. Based on these findings, several
hypotheses have been proposed to explain the protective effect of smoking on the
development of HP. Most of them focus on immunomodulatory effects of smoking, e.g.
suppression of antibody production, reduction of T-helper cells in BAL, and impairment
of macrophage function [115–117]. More recently, it has been reported that down-
regulation of pulmonary GSH levels may be associated with disease manifestation
in farmers [118]. Although the reason for these differences has not yet been elucidated,
the observations are suggestive to assume that genetic predisposition may play a role
in disease manifestation.
Sarcoidosis
Sarcoidosis is a systemic granulomatous disease of unknown cause with y90%
pulmonary involvement. It is generally believed that sarcoidosis might be an immuno-
logical disorder. Initiated by a putative inhaled antigen that leads to T-cell activation,
sarcoidosis is characterised by a lymphocytic alveolitis with increased T-helper/
T-suppressor cell ratio and by formation of noncaseating granulomas. As in
hypersensitivity pneumonitis, smokers are underrepresented in patients with sarcoidosis
suggesting that cigarette smoke provides some kind of protection against this disease
[93, 119–121]. Although distinct differences in BAL differential cell counts and T-cell
subsets have been observed between nonsmokers and smokers affected by sarcoidosis,
there is no conclusive pathogenetic concept to explain the reduced incidence of
sarcoidosis in smokers [121]. Smoking-induced alterations of antigen presentation,
macrophage function, and lymphocyte proliferation may be involved.
TOBACCO SMOKE AND RESPIRATORY DISEASE
171
Smoking cessation
There is scientific consensus that cigarette smoking is an addiction to the drug nicotine.
As with any drug addiction, social, economic, personal and political influences play
an important part in determining patterns of smoking prevalence and cessation [122].
Seventy per cent of smokers report that they would like to quit [123]. However, in a USA
survey of exsmokers, respondents acknowledged little assistance in giving up smoking
[124]. Therefore, within the last 10 yrs, particularly in the USA, tremendous public
efforts have been undertaken to promote and spread plans for smoking cessation
[125, 126] (table 6).
Given that the progression of COPD can be slowed down by smoking cessation
[42] and that people who stop smoking even well into middle age avoid most of their
subsequent risk for lung cancer [127], smoking cessation should be a crucial issue in
Table 6. A 5-day plan to quit smoking
The first step to quitting smoking is to decide to quit. Next, make an appointment with your healthcare provider,
or contact a smoking cessation clinic to discuss your options for treatment. Set a quit date.
Quit day minus 5: List all of your reasons for quitting and tell your friends and family about your plan.
Stop buying cartons of cigarettes.
Quit day minus 4: Pay attention to when and why you smoke. Think of new ways to relax or things to hold in your
hand instead of a cigarette. Think of habits or routines you may want to change. Make a list to use when you quit.
Quit day minus 3: Make a list of the things you could do with the extra money you will save by not buying cigarettes.
Think of who to reach out to when you need help, like a smoking support group.
Quit day minus 2: Buy the over-the-counter nicotine patch or nicotine gum, or get a prescription for the nicotine
inhaler, nasal spray, or the nonnicotine pill, bupropion SR. Clean your clothes to get rid of the smell of cigarette
smoke.
Quit day minus 1: Think of a reward you will get yourself after you quit. Make an appointment with your dentist to
have your teeth cleaned. At the end of the day, throw away all cigarettes and matches. Put away lighters
and ashtrays.
Quit day: Keep very busy. Change your routine when possible, and do things out of the ordinary that don’t r
emind you of smoking. Remind family, friends, and coworkers that this is your quit day, and ask them to help
and support you. Avoid alcohol. Buy yourself a treat, or do something to celebrate.
Quit day plus 1: Congratulate yourself. When cravings hit, do something else that isn’t connected with smoking,
like taking a walk, drinking a glass of water, or taking some deep breaths. Call your support network. Find things
to snack on, like carrots, sugarless gum, or air-popped popcorn.
Adapted from the Surgeon General [126].
Table 7. Some of the smoking cessation methods available
Massmedia and community programmes
Self-help
Educational (books and other material, e.g. from the Internet)
Brief clinical interventions (physician advice and counselling)
Clinics and groups
Voluntary agencies
Commercial programmes
Pharmacotherapy
Nicotine replacement
Chewing gum
Transdermal systems
Nasal spray
Inhaler
Bupropion
Behavioural
Hypnosis?
Acupuncture?
Modified from Rennard and Daugton [128].
J. BEHR, D. NOWAK
172
evidence-based health promotion driven by pulmonologists. Available methods are listed
in table 7.
The "baseline rate" of successful quitting on a particular attempt ranges between
0.5–3.0% [128]. Brief clinical interventions can be provided by any clinician and reveal an
increase in the odds of quitting (odds ratio (OR), 1.7; 95% confidence interval: 1.5–2.0),
equal to an absolute difference in the cessation rate ofy2.5% [129]. Pharmacotherapeutic
first-line drugs are nicotine (gum, inhaler, nasal spray, patch) and sustained-release
bupropion hydrochloride [130]. A meta-analysis of 53 randomised controlled trials of
nicotine replacement therapy in individuals motivated to quit smoking showed ORs
for gum of 1.6, for transdermal patch of 2.1, for nasal spray of 2.9, and for inhaled
nicotine of 3.1. These ORs were nonsignificantly higher in subjects with higher levels
of nicotine dependence but were largely independent of the intensity of additional
support provided or the setting in which nicotine replacement therapy was offered [131].
In a recent, randomised controlled study comparing the efficacy of sustained-release
bupropion, a nicotine patch, or both for smoking cessation, the authors reported
12-month point (cumulative) prevalence abstinence rates of 15.6% (5.6%) in the placebo
group compared with 16.4% (9.8%) in the nicotine patch group, 30.3 (18.4%) in the
bupropion group, and 35.5 (22.5%) in the group given nicotine patches and bupropion
[132]. Thus, although smoking cessation is obviously the best strategy for eliminating
the health risks associated with smoking, the outlined strategies are effective only in a
minority of patients. Since smoke-free environments, advertising bans and price increases
have been demonstrated to be effective measures in many countries, primary prevention
and cessation strategies should be combined on a large-scale sociomedico-political scale
in order achieve better health.
Summary
During the 20th century, cigarette smoking has become a mass phenomenon. Within
the last 30 yrs, cigarette consumption per adult has remained stable in Europe,
decreased in America and increased in all other regions, particularly in the Western-
Pacific region. Smoking status is believed to be largely a function of genetic and
sociodemographic factors, environmental determinants, behavioural factors and
specific dimensions of personality.
Cigarette smoke is a heterogenous aerosol produced by incomplete combustion of the
tobacco leaf. More than 4,000 substances have been identified in cigarette smoke,
including some that are pharmacologically active, antigenic, cytotoxic, mutagenic, and
carcinogenic. Out of the different effects that tobacco smoke exerts on the respiratory
tract, this chapter focused on two main mechanisms: firstly, induction of inflamma-
tion; and secondly, mutagenic/carcinogenic effects.
The most relevant tobacco-associated diseases of the respiratory system are chronic
obstructive pulmonary disease (COPD) and lung cancer. COPD, being the sixth most
common cause of death in 1990, will advance to third place worldwide in 2020.
The pathogenesis of smoking-related COPD includes the protease-antiprotease and
oxidant-antioxidant hypotheses and abnormal repair processes. Lung cancer has
become the most common type of lethal cancer throughout the world. By 2020, it will
advance to the fourth most common cause of death in developed countries and to the
fifth most common worldwide. Additionally, it has recently been suggested that a
number of interstitial lung diseases are positively associated with tobacco smoking
(i.e. usual interstitial pneumonia, desquamative interstitial pneumonia, respiratory
TOBACCO SMOKE AND RESPIRATORY DISEASE
173
bronchiolitis-associated interstitial lung disease, connective tissue disease-associated
interstitial lung disease, and pulmonary Langerhans’ cell histiocytosis).
There is scientific consensus that cigarette smoking is an addiction to the drug
nicotine, with 70% of smokers reporting that they would like to quit. Thus, smoking
prevention and smoking cessation should be crucial issues in evidence-based health
promotion driven by pulmonologists. Brief clinical interventions can be provided by
any clinician and reveal an increase in the odds of quitting, and the efficacy of
pharmacotherapeutic intervention with nicotine and bupropion have been consistently
demonstrated. Furthermore, smoke-free environments, advertising bans and price
increases are effective measures in many countries.
Keywords: Chronic obstructive pulmonary disease, interstitial lung disease, lung
cancer, oxidants, smoking cessation, tobacco smoke.
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... Additionally, smoking is associated with cancer in various other organs, including the mouth, pharynx, larynx, esophagus, stomach, pancreas, cervix, kidney, and bladder (see Table 1) [4]. Moreover, CS can contribute to the development of second primary tumors [5,6], promote cancer metastasis [7,8], and contribute to the onset of other lung diseases [9,10] such as chronic obstructive pulmonary disease (COPD) including both emphysema and chronic bronchitis, pulmonary fibrosis, and asthma [11,12]. The findings of comparative studies between smokers and nonsmokers have demonstrated that smokers experience an accelerated decline in lung function [13][14][15] and are at a higher risk of developing both lung cancer and COPD simultaneously [16,17]. ...
... Reduced survival and higher recurrence rates post-esophagectomy. [10] Lung cancer Current smokers Increased risk of second primary lung cancer among smokers. ...
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This review delves into the molecular complexities underpinning the epithelial-to-mesenchymal transition (EMT) induced by cigarette smoke (CS) in human bronchial epithelial cells (HBECs). The complex interplay of pathways, including those related to WNT//β-catenin, TGF-β/SMAD, hypoxia, oxidative stress, PI3K/Akt, and NF-κB, plays a central role in mediating this transition. While these findings significantly broaden our understanding of CS-induced EMT, the research reviewed herein leans heavily on 2D cell cultures, highlighting a research gap. Furthermore, the review identifies a stark omission of genetic and epigenetic factors in recent studies. Despite these shortcomings, the findings furnish a consolidated foundation not only for the academic community but also for the broader scientific and industrial sectors, including large tobacco companies and manufacturers of related products, both highlighting areas of current understanding and identifying areas for deeper exploration. The synthesis herein aims to propel further research, hoping to unravel the complexities of the EMT in the context of CS exposure. This review not only expands our understanding of CS-induced EMT but also reveals critical limitations in current methodologies, primarily the reliance on 2D cell cultures, which may not adequately simulate more complex biological interactions. Additionally, it highlights a significant gap in the literature concerning the genetic and epigenetic factors involved in CS-induced EMT, suggesting an urgent need for comprehensive studies that incorporate these types of experiments.
... It remains unclear how pirfenidone works [4]. The onset of IPF is associated with risk factors such as aging, air pollution, and smoking [5,6]. The exact etiology and detailed pathophysiology of IPF are still not fully understood. ...
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Background Idiopathic pulmonary fibrosis (IPF) is a lethal disease with an unknown etiology and complex pathophysiology that are not fully understood. The disease involves intricate cellular interplay, particularly among various immune cells. Currently, there is no treatment capable of reversing the fibrotic process or aiding lung regeneration. Hepatocyte growth factor (HGF) has demonstrated antifibrotic properties, whereas the adoptive transfer of modified T cells is a well‐established treatment for various malignancies. We aimed to understand the dynamics of T cells in the progression of lung fibrosis and to study the therapeutic benefit of adoptive T cell transfer in a bleomycin‐injured mouse lung (BLM) model. Methods T cells were isolated from the spleen of naïve mice and transfected in vitro with mouse HGF plasmid and were administered intratracheally to the mice lungs 7 days post‐bleomycin injury to the lung. Lung tissue and bronchoalveolar lavage were collected and analyzed using flow cytometry, histology, qRT‐PCR, ELISA, and hydroxyproline assay. Results Our findings demonstrate the successful T cell therapy of bleomycin‐induced lung injury through the adoptive transfer of HGF‐transfected T cells in mice. This treatment resulted in decreased collagen deposition and a balancing of immune cell exhaustion and cytokine homeostasis compared with untreated controls. In vitro testing showed enhanced apoptosis in myofibroblasts induced by HGF‐overexpressing T cells. Conclusions Taken together, our data highlight the great potential of adoptive T cell transfer as an emerging therapy to counteract lung fibrosis.
... The etiology of sinusitis includes both genetic and environmental factors (e.g., viral and bacterial infections, allergies, and pollutants) (Slavin et al., 2005). As air pollutants act as irritants causing inflammation, the role of both indoor and outdoor air pollution is increasingly recognized as a cause of sinusitis, together with overcrowding and tobacco smoke (Behr and Nowak, 2002;Schwarzbach et al., 2020;Wee et al., 2021). Although CMS is generally not considered a life-threatening condition, if the inflammation spreads from the sinuses to the nearby Eustachian tubes (which connect the middle ear to the back of the throat), it can lead to fluid buildup and inflammation in the middle ear, resulting in otitis media. ...
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Objectives: To investigate the prevalence of respiratory disease in several populations from the Netherlands across different time periods and socioeconomic conditions. Materials: We analyzed 695 adult individuals from six different Dutch contexts of urban and rural settlements dating to different time periods (i.e., early-medieval, late-medieval, post-medieval). Methods: For each individual, the presence/absence of chronic maxillary sinusitis, otitis media, and inflammatory periosteal reaction on ribs was recorded macroscopically according to accepted methods. Results: Statistically significant associations were found in the presence of sinusitis diachronically (early-medieval to late-medieval period, and early-medieval to post-medieval period) both in rural and urban environments. Differences in prevalence rates of otitis media were found statistically significant when comparing rural to urban environments in the early-medieval and late-medieval periods. Conclusion: Our results suggest that factors such as increased contact between towns and countryside, higher population densities, and intensification of agricultural production impacted the respiratory health of past populations both in rural and urban settings. Significance: Our study provides new insights into the impact of environmental changes and urbanization on respiratory disease prevalence, shedding light on the relationship between health and changing social and environmental contexts. Limitations: Research limitations included the complex etiology of respiratory diseases, and the impact of uncontrollable factors such as hidden heterogeneity, selective mortality, and rural-to-urban migration. Future research: Further research in different contexts is advised in order to continue exploring urbanization and its impact on human health across both time and space.
... Significantly, cancer and respiratory disease are worsening. Earlier studies also showed lung cancer among smokers in Bangladesh [35] and overall respiratory diseases globally [36]. Similarly, pesticides and tobacco processing caused skin diseases and other health problems, significantly worsening the situation. ...
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Tobacco farming in Bangladesh has significant and far-reaching environmental impacts, affecting the land, water, and air. While the country has implemented tobacco control measures, the lack of monitoring and enforcement has resulted in environmental degradation and public health concerns. This study aims to document the environmental impact of tobacco farming in Bangladesh, adopting a qualitative approach to collect and analyze data. The study used focus group discussions, key informant interviews, and a structured questionnaire survey to gather data, assessing the impact of tobacco farming on the environment, socioeconomic conditions, and human health using a five-point impact assessment scale. Results illustrated that tobacco cultivation contributes to the ecosystem and natural resource degradation, leading to a loss of habitat diversity and domestic animal death. Soil erosion, water pollution, and air pollution from excessive plowing and pesticide usage have also been observed, causing skin diseases and other health issues. Despite some economic benefits, social conditions have worsened due to drug addiction and conflicts among tobacco workers. The study will help policymakers and environmentalists by highlighting the need to take action in reducing the environmental and social impacts of tobacco farming in Bangladesh. It also informs the public about the potential tobacco production and consumption risks. This study provides important insights into the adverse effects of tobacco farming in Bangladesh and emphasizes the importance of implementing appropriate measures to reduce environmental and public health impacts.
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Tobacco use remains a leading preventable contributor to serious health conditions in the United States, notably chronic obstructive pulmonary disease (COPD) and severe COVID-19 complications. Within Louisiana's Medicaid population, tobacco use prevalence is particularly high compared to privately insured groups, yet its full impact on long-term outcomes is not fully understood. This study aimed to investigate how tobacco use, in conjunction with demographic and clinical risk factors, influences the incidence of COPD and COVID-19 among Medicaid enrollees over time. We analyzed Louisiana Department of Health data from January 2020 to February 2023. Chi-square tests were conducted to provide descriptive statistics, and multivariate logistic regression models were applied across three discrete waves to assess both cross-sectional and longitudinal associations between risk factors and disease outcomes. Enrollees without baseline diagnoses of COPD or COVID-19 were followed to determine new-onset cases in subsequent waves. Adjusted odds ratios (AOR) were calculated after controlling for socio-demographic variables, comorbidities, and healthcare utilization patterns. Tobacco use emerged as a significant independent predictor of both COPD (Adjusted Odd Ratio= 1.12) and COVID-19 (Adjusted Odd Ratio = 1.66). Additional risk factors -- such as older age, gender, region, and pre-existing health conditions -- also showed significant associations with higher incidence rates of COPD and COVID-19. By linking tobacco use, demographic disparities, and comorbidities to an increased risk of COPD and COVID-19, this study underscores the urgent need for targeted tobacco cessation efforts and prevention strategies within this underserved population.
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The increasing popularity of electronic cigarettes (e-cigarettes) as an alternative to conventional tobacco products has raised concerns regarding their potential adverse effects. The cardiovascular system undergoes intricate processes forming the heart and blood vessels during fetal development. However, the precise impact of e-cigarette smoke and aerosols on these delicate developmental processes remains elusive. Previous studies have revealed changes in gene expression patterns, disruptions in cellular signaling pathways, and increased oxidative stress resulting from e-cigarette exposure. These findings indicate the potential for e-cigarettes to cause developmental and cardiovascular harm. This comprehensive review article discusses various aspects of electronic cigarette use, emphasizing the relevance of cardiovascular studies in Zebrafish for understanding the risks to human health. It also highlights novel experimental approaches and technologies while addressing their inherent challenges and limitations.
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Introduction The World Health Organization reported that one third of global population was tobacco smoker. In countries with a high tuberculosis burden, a big proportion was attributed to tobacco smoking. In the general population of Rwanda, the prevalence of tobacco smoking was higher among males (14%) compared to females (3%). We conducted a second analysis to assess factor associated with tobacco smoking among patient with TB attending Health Facilities. Methodology A retrospective case-control study in Centres of Diagnosis and Treatment of tuberculosis (CDT). Cases were patients with bacteriological TB confirmation; controls were persons with signs and symptoms without TB confirmation. Proportions and logistic regression were used in data analysis. Results The total number of tobacco smokers was 680. Among tobacco smokers, 88.1% tobacco smokers were males, 94.3% tobacco smokers had at least 25 years old and 64.6% were living in union. By education, 84.9% tobacco smokers were illiterate or attained primary school. Almost all tobacco smokers (97.0%) ever drunk alcohol while 67.9% used illicit drugs and 25.3% had low BMI (≤ 18.5) with increased proportion among cases (29.1%). A proportion of 38.3% in tobacco smokers had history of imprisonment. In multivariable logistic regression data analysis, males compared to females (aOR = 3.49[95%CI:1.76–6.94]), ever drunk alcohol compared to never drank alcohol (aOR = 6.39[95%CI:2.67–15.31]) and ever used illicit drugs compared to never used illicit drugs (aOR = 9.89[95%CI:3.87–25.25]) were associated with high odds of tobacco smoking. In addition, illiterate people or people who attained only primary school education level compared to people having primary education level and above (aOR = 0.39[95%CI:0.23–0.69]) were associated with low odds of tobacco smoking. Conclusion Tobacco smoking is common in pulmonary TB patients. Males were more likely using tobacco smoking compared to females. Alcohol drinkers and illicit drug users were associated to tobacco smoking. A campaign on tobacco cessation, focusing on males, should be conducted in the general population starting by people on TB treatment.
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Objetivo: objetivou-se caracterizar a prevalência de hábitos tabágicos entre estudantes de uma IES. Métodos: trata-se de um estudo quantitativo efetuado na cidade de Cajazeiras – PB em uma IES entre fevereiro e dezembro de 2010. A amostra foi composta por 248 discentes dos cursos da área da saúde oferecidos pela instituição de ensino estudada. Os dados foram obtidos através de questionário, após a assinatura do termo de anuência pelos participantes. Resultados: observou-se o seguinte percentual de estudantes tabagistas entre os cursos investigados: enfermagem 5,6%, fisioterapia 4,5% e farmácia 5,6%. A taxa identificada de ex-fumantes entre os estudantes foi: enfermagem 19%, fisioterapia 9,1% e farmácia 17%. Conclusão: o índice de estudantes tabagistas demanda da IES a adoção de estratégias pedagógicas que ilustrem os malefícios oriundos do consumo de tabaco. Descritores: tabagismo, nicotina, educação superior.
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Several studies have investigated lung function in patients with rheumatoid arthritis but have reached different conclusions. The main discrepancy has been between airways disease reported in 38–65 per cent of patients and interstitial pulmonary disease reported in 30–41 per cent. These variable results have probably arisen because specific lung disorders have often been diagnosed on the basis of non-specific tests of lung function which, when considered in isolation, are subject to different interpretations. We adopted a combined epidemiological and clinical approach to investigate lung function and respiratory symptoms in patients with rheumatoid arthritis. Epidemiological data showed that rheumatoid arthritis is associated with a mild restrictive lung defect with reductions in mean FEV1 and FVC of 0.261 and 0.291 respectively and a normal FEV1/FVC ratio. The reduction in mean maximum mid-expiratory flow rate of 0.34 l/s could be explained on the basis of lung restriction and there was no evidence of widespread airways dysfunction other than that which could be explained by cigarette smoking. The clinical study showed that abnormal lung function tests in individual patients were caused by a heterogeneous group of conditions which are frequently caused, or exacerbated, by cigarette smoking. Cigarette smoking, and not the rheumatoid process, was the most frequent cause of abnormal lung function in the rheumatoid arthritis.
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BACKGROUND: Health care professionals frequently advise patients to improve their health by stopping smoking. Such advice may be brief, or part of more intensive interventions. OBJECTIVES: The aims of this review were to assess the effectiveness of advice from physicians in promoting smoking cessation; to compare minimal interventions by physicians with more intensive interventions; to assess the effectiveness of various aids to advice in promoting smoking cessation and to determine the effect of anti-smoking advice on disease specific and all cause mortality. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group trials register and the Cochrane Controlled Trials Register. Date of the most recent searches: October 1998. SELECTION CRITERIA: Randomised trials of smoking cessation advice from a medical practitioner in which abstinence was assessed at least six months after advice was first provided. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the setting in which advice was given, type of advice given (minimal or intensive), and whether aids to advice were used, the outcome measures, method of randomisation and completeness of followup. The main outcome measure was abstinence from smoking after at least six months follow-up. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates where available. Subjects lost to follow-up were counted as smokers. Where possible, meta-analysis was performed using a fixed effects model. MAIN RESULTS: We identified thirty-one trials, conducted between 1972 and 1997, including over 26,000 smokers. In some trials, subjects were at risk of specified diseases (chest disease, diabetes, ischaemic heart disease), but most were from unselected populations. The most common setting for delivery of advice was primary care. Other settings included hospital wards and outpatient clinics, and industrial clinics. Pooled data from 16 trials of brief advice versus no advice (or usual care) revealed a small but significant increase in the odds of quitting (odds ratio 1.69, 95% confidence interval 1.45 to 1.98). This equates to an absolute difference in the cessation rate of about 2.5%. There was insufficient evidence, from indirect comparisons, to establish a significant difference in the effectiveness of physician advice according to the intensity of the intervention, the amount of follow-up provided, and whether or not various aids were used at the time of the consultation in addition to providing advice. However, direct comparison of intensive versus minimal advice showed a small advantage of intensive advice (odds ratio 1.44, 95% confidence interval 1.23 to 1.68). In one study which determined the effect of smoking advice on mortality at twenty years, there were no statistically significant differences in death rates in the group receiving advice. REVIEWER'S CONCLUSIONS: Simple advice has a small effect on cessation rates. Additional manoeuvres appear to have only a small effect, though more intensive interventions are marginally more effective than minimal interventions.
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This chapter synthetizes the evidence on the effects of environmental tobacco smoke (ETS) on respiratory health in children and adults, with emphasis on epidemiological studies, and discusses methodological issues and their impact on interpretation of the findings. ETS is a prevalent exposure in many countries and contains several known and probable human carcinogens as well as irritant and toxic substances. In children, there is convincing evidence that parental, especially maternal, smoking increases susceptibility to lower respiratory illness in infants and causes chronic respiratory symptoms in children. Parental smoking causes asthma in children, and the evidence strongly supports its role in aggravating asthmatic symptoms. There is convincing evidence that parental, especially maternal, smoking is related to small lung function deficits in neonates and school children. In adults, there is convincing evidence that ETS causes lung cancer. Recent studies have detected significant effects on the occurrence of chronic respiratory symptoms in adults. A limited number of studies on ETS and asthma in adults suggest that ETS exposure increases the risk of asthma and contributes to poor overall control of asthma. In addition, a limited number of studies link ETS exposure to chronic obstructive pulmonary disease in adults. Several cross-sectional studies in adults provide evidence that ETS exposure is related to small deficits in lung function. Although many interesting challenges are left for the future research, there is definitely enough evidence to justify a high priority for prevention of ETS exposure among both children and adults.
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To the Editor:— Two articles published in the May 27 issue of The Journal "Tobacco Smoking and Bronchogenic Carcinoma," by Ernest L. Wynder and Evarts A. Graham, and "Cancer and Tobacco Smoking" by Morton L. Levin, Hyman Goldstein and Paul R. Gerhardt, represent the past and present clinical approach to the cancer problem but completely miss some of the extremely interesting and basic aspects of the disease. Both articles fail to emphasize the elemental cellular unit, which is the heart of the entire problem. No matter how early cancer is seen clinically, it is biologically late, and the entire philosophy of investigation must move to this level if we ever hope to effect a cure. To illustrate from the two papers noted, in tobacco tar a benzpyrene compound can be readily isolated and, when applied to normal cells, can alter the genetic structure so that a cancer cell can be
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Rheumatoid arthritis (RA) is a systemic disease manifest as a symmetric polyarthritis usually in the setting of elevated autoantibodies (rheumatoid factor). This disease affects 1-2% of the world's population, most frequently in the 25-55 year old age group and has a female predominance (2.5:1). Nearly 50% of patients with RA demonstrate some type of extra-articular manifestation of the disease such as pleuritis, pleuropericarditis, vasculitis, pneumonitis, pulmonary fibrosis, scleritis or nodulosis. Pulmonary involvement in RA is common and can be due to the disease itself as well as to the therapies used to treat it. In fact, lung disease is the second most common cause of death, following infection, for patients with RA and has been reported to effect between 1-40% of patients. RA associated interstitial lung disease (ILD) is often subtle in onset, slowly progressive and of unclear etiology and response to treatment. This article aims to clarify the current clinical, radiographic and pathologic status of RA-ILD.
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Secretory leukoprotease inhibitor (SLPI) and alpha(1)-protease inhibitor (alpha(1)-PI) are powerful antiproteases currently under investigation for their potential to protect the lung from neutrophil elastase (NE). The aim of this study was to determine whether the recombinant form of SLPI (rSLPI) and alpha(1)-PI show different grades of loss of inhibitory activity when exposed to reactive oxygen metabolites. We incubated rSLPI and alpha(1)-PI with N-chlorosuccinimide (NCS), chloramines, activated polymorphonuclear leucocytes (PMNs) and activated alveolar macrophages (AMs). Under all conditions evaluated, both antiproteases were partially inactivated, The resulting anti-NE activity of rSLPI was not significantly different from that of alpha(1)-PI after exposure to NCS (p>0.5), chloramines (p>0.6), activated PMNs (p> 0.07) and activated AMs (p>0.9). In conclusion, recombinant secretory leukoprotease inhibitor and alpha(1)-protease inhibitor lose antineutrophil elastase activity to a similar extent when expressed to conditions that may be present in inflammatory lung disorders.