Smoking: relationship to chronic bronchitis, chronic obstructive

pulmonary disease and mortality

Margit Pelkonen
Department of Pulmonary Diseases, Kuopio University
Hospital, Kuopio, Finland
Correspondence to Margit Pelkonen, MD, Department
of Pulmonary Diseases, Kuopio University Hospital,
Puijonlaaksontie 2, PO Box 1777, 70210 Kuopio,
Finland
Tel: +358 400 576 222; fax: +358 17 172683;
e-mail: Margit.Pelkonen@kuh.fi

Current Opinion in Pulmonary Medicine 2008,

14:105109

Purpose of review
To describe the recent findings concerning the relationship between smoking, chronic
bronchitis, chronic obstructive pulmonary disease and mortality.
Recent findings
During their lifetime, over 40% of smokers develop chronic bronchitis. Chronic
bronchitis is associated with an accelerated decline in lung function a risk of
developing chronic obstructive pulmonary disease and mortality. Approximately onequarter of smokers can be affected by clinically significant chronic obstructive
pulmonary disease. The incidence of chronic obstructive pulmonary disease is also
substantial in young adults. Smokers may reduce their risk of developing chronic
obstructive pulmonary disease by physical activity and increase their survival by smoking
reduction. In adults and the elderly population, severe chronic obstructive pulmonary
disease is associated with the most rapid decline in lung function, which is, in turn,
associated with chronic obstructive pulmonary disease-related hospitalization and
mortality. Using a fixed forced expiratory volume in 1 s/force vital capacity ratio (0.7) to
define obstruction in chronic obstructive pulmonary disease at old age is acceptable. In
chronic obstructive pulmonary disease patients, the disease is still underreported on
death certificates. Chronic mucus production and being a female are associated with
chronic obstructive pulmonary disease mentioned on death certificates.
Summary
Chronic bronchitis is a marker identifying high-risk individuals. With respect to chronic
obstructive pulmonary disease and mortality, interventions to promote smoking
cessation are important to reduce these risks.
Keywords
chronic bronchitis, chronic obstructive pulmonary disease, mortality, pulmonary
function, smoking
Curr Opin Pulm Med 14:105109
2008 Wolters Kluwer Health | Lippincott Williams & Wilkins
1070-5287

Introduction
Smoking is an important risk factor for chronic bronchitis,
chronic obstructive pulmonary disease (COPD) and
mortality [13]. The present review focuses on recent
articles published in 20062007 that study the associations between smoking, chronic bronchitis, COPD and
mortality (Fig. 1). In this review, cumulative incidences
of chronic bronchitis and COPD in different smoking
categories are calculated in longitudinal studies with
follow-up times varying from 7 to 30 years [4
6
,7

].
Cumulative analysis estimates the risk of developing
chronic bronchitis/COPD during the observation period
compared with prevalence studies which reflect the
existing cases at a certain point of time. The possible
pathway from smoking through the symptoms of chronic
bronchitis to an accelerated decline in pulmonary function and increased risk of developing COPD is examined
by some of the recent articles [4
,5
,7

]. Finally, the
excess mortality caused by chronic bronchitis, a rapid

decline in pulmonary function and COPD is studied in a

few of the articles [4
,8
,9
,10,11
,12].
COPD is known to be underreported on death certificates
[13]; therefore, the validity of mortality statistics in
COPD was considered by one reviewed article [11
].
The use of a fixed forced expiratory volume in 1 s/force
vital capacity ratio (FEV1/FVC 0.7) to define COPD
and at-risk patients at old age was studied in one paper
[14
]. One recent paper examined if the risk of developing COPD could be reduced by physical activity [15

].
The effect of smoking reduction on subsequent mortality
was studied by two long-term follow-ups [4
,16].

Smoking and its relationship to chronic

bronchitis
Chronic bronchitis is a disorder characterized by chronic
mucus production from airways for at least 3 months in
each of 2 successive years, provided that there are no

1070-5287 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins

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106 Obstructive, occupational and environmental diseases

Figure 1 Focus of the present review

Table 1 Description of the GOLD categories

Category

Descriptiona

GOLD stage 1

FEV1/FVC < 70% and FEV1  80%

predicted
FEV1/FVC < 70% and 80 > FEV1  50%
predicted
FEV1/FVC < 70% and 50 > FEV1  30%
predicted
FEV1/FVC < 70% and FEV1 < 30%
predicted or FEV1 < 50% predicted
plus chronic respiratory failure

GOLD stage 2
GOLD stage 3
GOLD stage 4

a
Based on the postbronchodilator FEV1.
GOLD, Global Initiative on Obstructive Lung Disease; FEV1, forced
expiratory volume in 1 s; FVC, forced vital capacity.
Table based on [27].

A schematic illustration of the associations between smoking, pulmonary

function, chronic bronchitis, chronic obstructive pulmonary disease and
mortality.

other causes of chronic cough [17]. Smoking is a major

risk factor for chronic bronchitis, e.g. by causing airway
inflammation and inducing hyperproduction of mucus
[18]. The prevalence of chronic bronchitis has been
shown to increase with age [2] and with the pack-years
of smoking [19]. Recently, in a 30-year follow-up in rural
Finnish middle-aged men (n 1711 at the baseline), by
the age of 75 years the cumulative incidence of chronic
bronchitis was 42% in continuous smokers, 26% in
ex-smokers and 22% in never-smokers [4
]. Persistent
symptoms of chronic bronchitis developed in 22% of
continuous smokers compared with 11% of ex-smokers
and 9.8% of never-smokers. Symptoms of chronic bronchitis appeared at the approximate median age of 55 years
(in never-smokers at the median age of 60 years) [4
].
Chronic bronchitis has, in turn, been associated with
accelerated decline in FEV1 [4
,20,21], although it was
first believed that chronic mucus production as such has
little relevant impact on the longitudinal decline in
pulmonary function [1,22]. In the Finnish 30-year
follow-up, the additional effect of chronic bronchitis on
the longitudinal decline in FEV1 was approximately
13 ml/year [4
], similar to that presented previously
[21]. Chronic bronchitis was associated with accelerated
decline in FEV1, especially in smokers and those with
persistent symptoms [4
]. In addition, a significant interaction between chronic bronchitis and airflow obstruction
on FEV1 was found [4
].

Smoking and its relationship to chronic

obstructive pulmonary disease
When airways become gradually obstructed with or without the presence of chronic bronchitis, the disorder is
called COPD [17]. The definition of airways obstruction
in COPD has been variable [17,2327]. The GOLD

(Global Initiative on Obstructive Lung Disease) definition

for COPD is FEV1/FVC < 70% (postbronchodilator
FEV1) (Table 1) [26,27]. In the Finnish 30-year followup, by the age of 75 years the cumulative incidence of
COPD was 32% in continuous smokers compared with
14% in ex-smokers and 12% in never-smokers [4
]. In a
recent 7-year follow-up (between 1996 and 2000) in the
Obstructive Lung Disease in Northern Sweden (OLIN)
studies (n 963), the 7-year cumulative incidence of
COPD in middle and old age was six times higher in
smokers than in never-smokers [5
]. It was estimated to
be 4.9 and 11.0%, respectively, according to the spirometric criteria of GOLD stage 2 (FEV1/FVC < 70%
and FEV1 < 80% predicted) and GOLD stages 14
(FEV1/FVC < 70%) [5
]. In smokers the corresponding
incidences were 10.6 and 18.8% (in nonsmokers 1.6 and
7.6%).
In the Copenhagen City Heart Study, 8045 men and
women aged 3060 years with normal lung function at
baseline were followed-up for 25 years (between 1976
1978 and 20012003) [6
]. Altogether 2422 subjects
participated in the first and fourth and 2022 subjects
participated in all four examinations during the followup. During the observation period 25% of smokers without initial disease had clinically significant COPD
(GOLD stage 2 or worse). On the other hand, none of
the early quitters with a complete follow-up developed
severe COPD. No clear differences in developing COPD
were found between men and women; however, a
detailed measure of tobacco consumption was not used,
only a classification to different smoking categories.
The development of COPD has been associated with
chronic mucus production [4
,5
,7

]. In the European
Community Respiratory Health Survey (ECRHS) an international cohort of young adults, aged 2044 years at the
baseline in 19911993, were followed-up until 19992002
[7

]. In this young cohort (n 5002), the 10-year cumulative incidence of COPD was 2.8% (in heavy smokers
5.7%). In both nonsmokers and ever-smokers, subjects
with persistent cough/phlegm production had a nearly

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Smoking Pelkonen 107

three-fold risk of developing COPD with respect to asymptomatic subjects [7

]; however, chronic bronchitis has
been a stronger risk factor for COPD in smokers than in
never-smokers [4
]. For example, in the Finnish 30-year
follow-up, half of smokers with chronic bronchitis later
developed COPD, but less than a fifth of never-smokers
with chronic bronchitis went to develop COPD [4
]. In
general, in addition to smoking and chronic bronchitis,
there are also other factors that affect the development of
COPD such as airway hyperresponsiveness, genetic
factors, gender, respiratory infections, work exposure to
noxious agents, air pollution, diet and alcohol consumption
[2835]. On the contrary, physical activity has been associated with a slower decline in pulmonary function in all
smoking categories [36]. The effect of regular physical
activity on the risk of developing COPD was assessed in
the Copenhagen City Heart Study [15

] where physical
activity was measured by a questionnaire at the baseline
in 19811983 and during the follow-up in 19911994
(n 6790). Active smokers with moderate or high levels
of physical activity reduced their risk of COPD compared
with low physical activity group. The prevented fraction of
COPD in smokers attributable to physical activity was
21%.

Relationship between smoking, chronic

bronchitis, chronic obstructive pulmonary
disease and mortality
Smoking is the major environmental factor in accelerating the decline in pulmonary function [1,35,3740].
Impaired pulmonary function and an accelerated decline
in pulmonary function have, in turn, been associated
with increased mortality in several population-based
longitudinal studies [4046]. In the Atherosclerosis Risk
in Communities study, the decline in FEV1 over 3 years
was examined in a study population (n 13 756) consisting of adults aged 4466 years [8
]. Study subjects in the
most negative category were classified as rapid decliners
based on the annual percentage decrease from the
baseline FEV1. The strongest risk factor for being a
rapid decliner was having GOLD stage 3 or 4 COPD
(FEV1/FVC < 70% and FEV1 < 50% predicted) or
GOLD stage 2 COPD at the baseline, although being
50 or older, female and of black race were also significant
risk factors. Over the subsequent 8 years, a rapid decline
in FEV1 was a significant predictor of death [hazard ratio
(HR) 1.4; 95% confidence interval (CI) 1.21.7)] and the
effect was strongest in subjects with restricted lung
function at the baseline (FEV1/FVC  70% and FVC
< 80% predicted). A rapid decline in FEV1 was also a
predictor of COPD-related hospitalization (HR 1.4; 95%
CI 1.21.8) and this effect was strongest in subjects with
GOLD stage 0 (presence of respiratory symptoms in the
absence of lung function abnormality). Similar analyses
were also done in the Cardiovascular Health Study among

the participants aged 65 years and older at baseline

(n 3388) [9
]. Overall, 26% of the participants had
GOLD stage 2 or worse at the baseline. Participants with
GOLD stages 3 and 4 COPD at baseline were more likely
to have a rapid decline in FEV1 over 4 years. Subjects
with a rapid decline in FEV1 were at higher risk of death
(HR 1.5; 95% CI 1.21.7) and COPD-related hospitalization (HR 1.6; 95% CI 1.32.0).
Chronic bronchitis has also been associated with increased
all-cause mortality [4
,41,47,48], although earlier the
relation between chronic phlegm production and all-cause
mortality had not remained significant after controlling for
initial pulmonary function [49]. In the Finnish study, in
subjects with chronic bronchitis all-cause mortality was
increased by a HR of 1.30 (95% CI 1.021.65) [4
]. During
a 26-year follow-up in a Norwegian occupational male
cohort (n 1623, age range 4059 years at baseline in
19721975), phlegm production in winter mornings
significantly predicted all-cause mortality with a HR of
1.30 (95% CI 1.061.59, P 0.01) after adjusting for
physical fitness, and known cardiovascular and other risk
factors (such as smoking and lung function) [10].
In the Finnish 30-year follow-up, smokers with chronic
bronchitis lived approximately 2.4 years longer by
decreasing the daily number of cigarettes smoked (the
decrease was on average slightly more than half a pack)
[4
]. In another longitudinal study examining the effect
of smoking reduction on mortality [16], study subjects
were screened for risk factors of cardiovascular disease in
the mid-1970s, screened again 313 years later and
followed-up throughout 2003. In this study, smoking
reduction in heavy smokers did not result in decreased
mortality; however, of the 475 reducers, 271 attended the
third examination and of these 271 subjects, 165 subjects
(61%) had actually increased their smoking by the
third examination.
Severe and moderate COPD have been associated with
increased mortality in ever-smokers [13]. In the Copenhagen City Heart Study, there was a clear pattern of
decreasing survival with increasing severity of COPD
[11
]. In a Canadian study, study subjects (n 11 493)
were 40 years or older (three-quarters were 65 years or
older), had COPD diagnosed during 19972000 and
received two or more prescriptions for bronchodilators
within 6 months of diagnosis [12]. Each subject had age
and sex-matched controls without COPD or asthma. The
follow-up lasted to the end of 2001. In the COPD group
the risk ratio for all-cause mortality was 2.82 (95% CI
2.613.05) and for cardiovascular mortality was 2.07 (95%
CI 1.822.36).
Fewer than half of those who have had severe or moderate COPD have later had COPD listed anywhere on

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108 Obstructive, occupational and environmental diseases

their death certificate [11
,13]. In the Copenhagen City

Heart Study, in subjects with COPD, chronic mucus
production and being a female were associated with
COPD mentioned on the death certificate HR 3.6
(95% CI 1.77.7) and HR 2.7 (95% CI 1.35.6), respectively [11
]. On the other hand, in almost half of the deaths
where COPD was listed as the cause of death, the subject
had a normal FEV1/FVC ratio at baseline. Thus, it was
presented that some of the deaths recorded as due to
COPD in subjects with a restrictive spirometry pattern
may have been misclassified (cardiac disease causing
breathlessness).
Finally, there has been a concern that using a fixed FEV1/
FVC < 0.7 to define COPD might result in overdiagnosis
of COPD at old age. This might happen because during
ageing FVC declines less rapidly than FEV1 [37,50]. The
issue was examined in the Cardiovascular Health Study
in adults aged 65 years and older at the baseline and
followed-up for up to 11 years (n 4965) [14
]. Altogether
54% of those 2090 study subjects who met the current
GOLD threshold for COPD (74.9% of those with
GOLD stage 1, 38.6% of those with GOLD stage 2
and 2.4% of those with GOLD stage 3 or 4) would not
have been identified as having COPD using the lower
limit of normal of the FEV1/FVC ratio. These study
subjects, however, had an increased risk of both death
(HR 1.3; 95% CI 1.11.5) and COPD-related hospitalization (HR 2.6; 95% CI 2.03.3). These risks were
though greater in subjects with FEV1 < 80% predicted
(GOLD stage 2 or worse) than in those above this
threshold.

Conclusion
During their lifetime, over 40% of smokers develop
chronic bronchitis [4
] and approximately one-quarter
of smokers can be affected by clinically significant COPD
[6
]. Thus, the statement that only 1015% of smokers
develop COPD is an underestimate and the longer
people smoke, the higher the risk of developing COPD
[6
]. One of the most important factors determining the
prevalence of COPD is the age distribution in the study
population [6
]. According to the results from the
ECRHS study, however, COPD can be a major health
problem in young adults [7

]. Overall, smoking is a
preventable cause of chronic bronchitis and COPD.
Thus, interventions to prevent initiation of smoking
and promote smoking cessation are important.
Chronic bronchitis does not seem to be an innocent
symptom, as it was though earlier [1,49]. Chronic bronchitis is rather a marker helping to identify high-risk
individuals who are at risk of developing COPD [5
,7

]
and increased mortality [4
]. In particular, smokers with
chronic bronchitis went on to develop COPD [4
]. More

studies are, however, needed to define whether chronic

bronchitis affects pulmonary function with the same
pathological mechanisms in never-smokers and smokers.
Recent studies did not find any difference between the
incidence of COPD in men and women [5
,6
], although
tobacco consumption was not examined in detail in these
studies. As smoking is becoming more common in women,
further studies could also be performed to examine
the gender differences in the development of COPD.
On the contrary, regular physical activity could counteract
the smoking effects, possibly through an anti-inflammatory and antioxidant mechanism, and could reduce COPD
risk in smokers [15

].
According to the recent results, using a fixed FEV1/
FVC < 0.7 seems to identify at-risk patients, even at
old age. On the other hand, examining epidemiological
trends based on mortality statistics only can produce
biased results because of the lack of COPD diagnosis
on death certificates [11
,13].
A rapid decline in FEV1 was a predictor of COPD-related
hospitalizations and death in adults and older people
[8
,9
]. Previously, smokers who have given up smoking
have had lower all-cause mortality over the entire range
of baseline pulmonary function [43]. On the other hand,
in smokers who have given up smoking about a third of
the reduction in total mortality can be explained by the
subsequent slower decline in pulmonary function [40].
Thus, smoking cessation is critical to reduce all-cause
mortality. Smokers may also benefit from smoking
reduction [4
]; however, the effect of smoking reduction
on the decline in pulmonary function and mortality
should be examined further. Overall, a periodic
spirometric re-evaluation in middle and old age (especially in smokers) is an important way to detect individuals
who will most likely need medical attention in the
future.

References and recommended reading

Papers of particular interest, published within the annual period of review, have
been highlighted as:


of special interest


of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (pp. 148149).
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4

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