Risk factors of COPD

Cigarette smoking

Cigarette smoking is overwhelmingly the most important risk factor for the development of COPD. Indeed, this is reflected in the GOLD and NICE guidelines’ definition of the disease.Although COPD can occur in non-smokers, about 90% of cases are thought to be a direct result of cigarette smoking.

Lung function declines after the age of 30–35 years as part of the ageing process

In normal, healthy non-smokers the rate of decline of FEV1 is about 25–30ml a year.

In ‘at-risk’ smokers the rate of decline may be double that, at about 50–60ml a year.

Why some smokers are at risk of this accelerated decline and others are not has been the subject of considerable research. Involvement of genetic factors is suggested by the ‘clustering’ of COPD cases in some families. Although some of this increased risk may be due to shared environmental factors, studies of diverse populations
suggest that shared environment does not provide a full Pathology and pathophysiology explanation. The search for a ‘COPD gene’ has revealed a number
of possible candidates, but has so far been inconclusive. What is known is that lung function declines steadily over the years of smoking but the FEV1 often drops below 50% of predicted before symptoms appear. Patients usually present with symptoms of
COPD between the ages of 50 and 70 years. Although lost lung function is not regained when smoking is stopped, the rate of decline returns to that of a non-smoker or nonsusceptible smoker. This highlights the importance of the early detection of such high-risk smokers and persuading them to stop smoking. If they can be persuaded to stop, they may never suffer from severe, disabling and symptomatic COPD.

Even when a smoker has developed symptomatic disease, stopping smoking will still result in worthwhile salvage of lung function and improved life expectancy.The main message for patients is: It is never too late to stop!

Increasing age

COPD is a slowly progressive disorder, so increasing age is another risk factor. Symptoms appearing in someone under the age of 40 years should be regarded with suspicion and investigated fully. The decline in lung function as part of the normal ageing process and as accelerated by cigarette smoking.

Gender

COPD is currently more common in men than women in the UK.A 1997 study of physician-diagnosed COPD showed a prevalence rate of:

1.7% of men,

1.4% of women.

However, the bad news is that, although the prevalence increased in men by 25% between 1990 and 1997, the increase in women during the same period was 69%. In men the prevalence of COPD levelled out in the mid-1990s but is continuing to rise in women.

It is also well recognised that physician-diagnosed COPD rates are an under-estimate of the true prevalence.A national study of ventilatory function in British adults in the mid-1980s – probably a truer picture of the prevalence of COPD – found reductions in lung function in the following proportions of people aged 40–65 years:

18% of male smokers,

7% of male non-smokers,

14% of female smokers,

6% of female non-smokers.

A population study from the USA, conducted in the mid-1990s, supports this earlier British study. It found prevalence rates of airflow limitation in white males of:

14.2% of current smokers,

6.9% of ex-smokers,

3.3% of non-smokers.
In white females the rates were:

13.6% of current smokers,

6.8% of ex-smokers,

3.1% of non-smokers.

These differences between male and female smokers might be related to the fact that in this age cohort smoking was more common in men than in women.With the increase in the number of
women smokers, the preponderance of males is changing. Some recent work has suggested that female smokers are at even greater risk of developing COPD than their male counterparts.

Airway hyper-responsiveness

Airway hyper-responsiveness (AHR) has been proposed as a risk factor for the development of COPD. Certainly AHR is not the sole preserve of the person with asthma. It has been demonstrated extensively in smokers. Smokers also have raised levels of IgE, the
antibody associated with atopy and asthma.

This observation forms the basis of the so-called Dutch hypothesis. Some doctors in the Netherlands have long regarded COPD and asthma as two aspects of the same process, and believe that atrisk smokers share an ‘allergic’ constitution that, when combined
with smoking, is expressed as COPD. However, this hypothesis iscontroversial and it has been argued that raised levels of IgE and increased AHR in COPD patients could be the result of smoking rather than a pre-existing factor.

Lower socio-economic status

The prevalence of COPD is highest among people in lower socioeconomic groups. Smoking rates are higher in these groups, but this may not be the sole causative factor. Low birth weight is associated with a reduced FEV1 in adult life. Airways develop in the first 16 weeks of gestation, and alveoli mature and increase in number in the last six weeks of gestation and
first three years of life.The number of alveoli reaches adult levels of about 300 million by the age of 8 years. Thus, malnutrition of the fetus and serious lower respiratory tract infection (LRTI) in infancy during these periods of lung development may result in lung function failing to reach full potential.This may be an independent risk factor for reduced lung function in adult life and increased risk of COPD.

Maternal smoking has been extensively linked with low birth weight and recurrent LRTI in infancy, as have poor housing and social deprivation.

Poor diet

It has been suggested that antioxidants in the diet protect against the harmful effects of smoking and that a low dietary intake of antioxidant vitamins, such as vitamin C, is associated with decreased lung function and increased risk of COPD. Poor diet is also associated with socio-economic deprivation.

Occupation

Certain jobs have been linked with COPD. Coal mining is probably the most well-recognised occupational risk factor, but cotton processing, farming and other dusty occupations may also be relevant,particularly when added to the effects of smoking.Welding fumes are highly toxic, and welding, particularly in confined spaces, is suspected of being a risk factor. However, in the UK at present the only occupational cause of COPD for which compensation may be paid is coal mining.

Air pollution

Air pollution is often blamed by COPD sufferers for their disease.Before the Clean Air Acts of the 1950s, urban dwelling was associated with an increased risk: the air was polluted with heavy particles, soot and sulphur oxides. The pollution now experienced is mainly from vehicle exhaust emissions and photochemical pollutants such as ozone, produced by the action of sunlight on exhaust fumes. It is seldom disputed that these are respiratory irritants and that episodes of high pollution are associated with increased hospital admissions for respiratory problems.The role of these irritants as a cause of COPD, however, is more controversial. Nowadays, urban dwelling in the UK does not seem to pose a greater risk of COPD than rural dwelling.

Outdoor and indoor air pollution may, however, be significant in Third World countries. Indoor air pollution from biomass fuels, such as charcoal burned for cooking and heating, may carry a risk for the development of COPD.

Deficiency of alpha-1 antitrypsin

A rare, but well-recognised, risk factor for COPD is the inherited deficiency of alpha-1 antitrypsin. This is a protective enzyme that counteracts the destructive action of proteolytic enzymes in the lung. Deficiency of it is associated with the early development –
between the ages of 20 and 40 years – of severe emphysema (see also the section ‘Emphysema’, below).The deficiency is inherited in a homozygous fashion with a frequency of 1:4000 of the population. Both parents will be carriers but the possession of a single abnormal chromosome does not seem to cause severe disease.There is usually a strong family history of COPD. Family members should be tested for alpha-1 antitrypsin deficiency and, if affected, must be very strongly advised never to smoke.

Genetics

Alpha-1 antitrypsin deficiency is an extensively studied genetic risk factor for COPD. It is now believed that many other genetic factors increase (and decrease) an individual’s risk of developing COPD. Why there seem to be familial clusters of COPD cases and why some smokers develop COPD and others do not has intrigued many researchers.The genetics of COPD is being investigated intensively.