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Chronic Obstructive Pulmonary Disease

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Chronic respiratory disorders characterized by differing grades of dyspnoea, cough, phlegm expectoration and functional respiratory impairment are included in the general category of chronic non-specific lung disease (CNSLD). The original definition of CNSLD, accepted at the Ciba Symposium in 1959, covered chronic bronchitis, emphysema and asthma. Subsequently, the diagnostic terminology of chronic bronchitis was redefined according to the concept that disabling airflow limitation represents the final stage of the ever-progressing process which starts as a benign expectoration caused by prolonged or recurrent inhalation of bronchial irritants (the “British Hypothesis”). The concept was thrown into question in 1977 and since then hypersecretion and airflow obstruction are regarded as unrelated processes. The alternative hypothesis, known as the “Dutch Hypothesis,” while accepting the role of smoking and air pollution in the aetiology of chronic airflow limitation, points to the key and possibly causative role of susceptibility of the host, manifesting itself as, for instance, an asthmatic tendency. Subsequent studies have shown that both hypotheses can contribute to the understanding of the natural history of chronic airways disease. Although the conclusion about the insignificant prognostic value of hypersecretory syndrome has generally been accepted as well-grounded, the recent studies have shown a significant association between hypersecretory disorder and the increased risk of the development of airflow limitation and respiratory mortality.

Currently, the term CNSLD combines two major categories of chronic respiratory disorders, asthma (discussed in a separate article of this chapter) and chronic obstructive pulmonary disease (COPD).

Definition

In a document published by the American Thoracic Society (ATS) (1987), COPD is defined as a disorder characterized by abnormal tests of expiratory flow that do not change markedly over periods of several months’ observation. Taking into account functional and structural causes of airflow limitation, the definition includes the following non-asthmatic airways disorders: chronic bronchitis, emphysema and peripheral airways disease. The important common characteristics of COPD are pronounced pathophysiological abnormalities mostly exhibited as a varying degree of chronic airflow limitation (CAL). Chronic airflow limitation can be found in a subject with any disease included under the rubric of COPD.

Chronic bronchitis is defined as an abnormal condition of the respiratory tract, characterized by persistent and excessive productive cough, which reflects the mucous hypersecretion within the airways. For epidemiological purposes, the diagnosis of chronic bronchitis has been based on answers to the set of standard questions included in the Medical Research Council (MRC) or ATS questionnaire on respiratory symptoms. The disorder is defined as cough and phlegm expectoration occurring on most days for at least three months of the year, during at least two successive years.

Emphysema is defined as an anatomical alteration of the lung characterized by abnormal enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of acinar architecture. Emphysema often coexists with chronic bronchitis.

The term peripheral airways disease or small airways disease is used to describe the abnormal condition of airways less than 2 to 3 mm in diameter. Inflammation, obstruction and excess mucus production in this part of the bronchial tree has been observed in a variety of clinical entities, including chronic bronchitis and emphysema. The pathological evidence of local structural abnormalities and the concept that the observed changes can represent an early stage in the natural history of chronic disease of airways, have stimulated in the late 1960s and the 1970s a rapid development of functional tests designed to examine physiological properties of peripheral airways. Consequently, the term peripheral airways disease is generally understood to refer to structural abnormalities or functional defect.

CAL is a functional hallmark of COPD. The term refers to an increased resistance to airflow, resulting in a persistent slowing during forced expiration. The definition thereof and the underlying clinical and pathophysiological knowledge imply two important diagnostic clues. First, the condition must be shown to have a chronic course, and the early recommendation of 1958 required the presence of CAL for more than one year to fulfil the diagnostic criteria. The time frame suggested recently is less rigorous and refers to the demonstration of a defect over the period of three months. In surveillance of work-related CAL, the standard spirometric evaluation provides sufficient means of identification of CAL, based on the reduction in the forced expiratory volume in one second (FEV1) and/or in the ratio of FEV1 to forced vital capacity (FVC).

Usually, CAL is diagnosed when the FEV1 value is reduced below 80% of the predicted value. According to the functional classification of CAL recommended by the American Thoracic Society:

  1. mild impairment occurs when the value of FEV1 is below 80% and above 60% of the predicted value
  2. moderate impairment occurs when FEV1 is in the range of 40% to 59% of the predicted value
  3. severe impairment occurs when FEV1 is below 40% of the predicted value.

 

When the degree of impairment is assessed by the value of the FEV1/FVC ratio, a mild defect is diagnosed if the ratio falls between 60% and 74%; moderate impairment if the ratio ranges from 41% to 59%; and severe impairment if the ratio is 40% or less.

Prevalence of COPD

Accumulated evidence indicates that COPD is a common problem in many countries. Its prevalence is higher in men than in women and increases with age. Chronic bronchitis, a well-standardized diagnostic form of COPD, is two to three times more prevalent in men than in women. Large surveys document that usually between 10% and 20% of adult men in the general population meet the diagnostic criteria of chronic bronchitis (Table 18). The disease is much more frequent among smokers, both in men and in women. Occurrence of COPD in occupational populations is discussed below.

Table 1. Prevalence of COPD in selected countries-results of large surveys

Country Year Population Males Females
  SMK (%) CB (%) COPD/CAL (%) SMK (%) CB (%) COPD/CAL (%)
USA 1978 4,699 56.6 16.5 n.r. 36.2 5.9 n.r.
USA 1982 2,540 52.8 13.0 5.2 32.2 4.1 2.5
UK 1961 1,569   17.0 n.r. n.r. 8.0 n.r.
Italy 1988 3,289 49.2 13.1 n.r. 26.9 2.8 n.r.
Poland 1986 4,335 59.6 24.2 8.5 26.7 10.4 4.9
Nepal 1984 2,826 78.3 17.6 n.r. 58.9 18.9 n.r.
Japan 1977 22,590 n.r. 5.8 n.r. n.r. 3.1 n.r.
Australia 1968 3,331 n.r. 6.3 n.r. n.r. 2.4 n.r.

Legend: SMK = smoking habit; CB = chronic bronchitis; COPD/CAL = chronic obstructive pulmonary disease/chronic airways limitation; n.r. = not reported.

Modified with permission from: Woolcock 1989.

 

Risk factors of COPD, including effect of occupational exposures

COPD is a disorder of multifactorial aetiology. Numerous studies have provided evidence for a causative dependence of COPD on many risk factors, categorized as host and environmental factors. The role of occupational exposures among environmental risk factors in the genesis of COPD has been recognized following accumulation of epidemiological evidence published in the period 1984 to 1988. Recently independent effects of smoking and occupational exposures have been confirmed, based on the results of the studies published from 1966 to 1991. Table 2 summarizes the current state of knowledge on multifactorial aetiology of COPD.

Table 2. Risk factors implicated in COPD

Factor
related to
Established Putative
Host Sex Age Antitrypsin deficiency Atopy Familial factors Increased airway reactivity Past health
Environment Tobacco smoke (personal) Tobacco smoke
(environmental) Air pollution Occupational exposure

Reproduced with permission from: Becklake et al. 1988.

 

The occurrence of chronic bronchitis in occupational populations is a potential marker of significant exposure to occupational irritants. A significant effect of exposure to industrial dust on the development of chronic bronchitis has been documented in workers employed in coal mining, the iron and steel industry, as well as in textile, construction and agricultural industries. In general, more dusty environments are associated with higher prevalence of the symptoms of chronic expectoration. The prevalence studies, however, are subject to “healthy worker effect”, a bias that results in underestimation of health impact of harmful occupational exposures. More conclusive, yet less available, are data on the disease’s incidence. In certain occupations the incidence rate of chronic bronchitis is high and ranges from 197-276/10,000 in farmers to 380/10,000 in engineering workers and 724/10,000 in miners and quarryworkers, compared with 108/10,000 in white-collar workers.

This pattern, and the causative effect of smoking as well, are in line with a concept that chronic bronchitis presents a common response to chronic inhalation of respiratory irritants.

A deleterious effect of lung dust burden is thought to result in chronic non-specific bronchial wall inflammation. This type of inflammatory response has been documented in workers exposed to organic dust and its constituents, such as for example grain and endotoxin, both responsible for neutrophillic inflammation. The role of individual susceptibility cannot be ruled out and known host-related factors include past respiratory infections, the efficiency of clearance mechanisms and poorly determined genetic factors, whereas cigarette smoking remains a single most potent environmental cause of chronic bronchitis.

The contribution of occupational exposures to the aetiology of emphysema is not clearly understood. The putative causative factors include nitrogen oxide, ozone and cadmium, as suggested by experimental observations. The data provided by occupational epidemiology are less convincing and may be difficult to obtain because of usually low levels of occupational exposures and a predominant effect of smoking. This is particularly important in case of so-called centriacinar emphysema. The other pathological form of the disease, panacinar emphysema, is considered hereditary and related to alpha1-antitrypsin deficiency.

Bronchiolar and peribronchiolar inflammation, accompanied by progressive narrowing of the affected segment of the bronchial tree (peripheral airways disease or constrictive bronchiolitis) can be seen in a variety of conditions underlying symptoms of COPD, at different stages of natural history. In the occupational setting, the disease usually follows acute lung injury due to inhalation of toxic fumes, such as sulphur dioxide, ammonia, chlorine and nitrogen oxides. However, the occupational epidemiology of constrictive bronchiolitis largely remains unclear. Apparently, its early stages are difficult to identify because of non-specific symptomatology and limitation of diagnostic procedure. More is known about the cases following industrial accidents. Otherwise, the disease can go undetected until the development of overt symptomatology and objective respiratory impairment (i.e., chronic airflow limitation).

CAL is not infrequently found in various occupational groups and, as documented by controlled studies, its prevalence in blue-collar workers can exceed that of white-collar workers. Due to the complex aetiology of CAL, including the effect of smoking and host-related risk factors, early studies on the association of chronic airflow limitation with occupational exposure were inconclusive. Modern occupational epidemiology, employing goal-oriented design and modelling of exposure-response relationships, has provided evidence on association of airflow capacity with exposure to both mineral and organic dusts, fumes and gases.

Workforce-based longitudinal studies conducted in workers exposed to mineral and organic dusts, and to fumes and gases show that lung function loss is associated with occupational exposures. The results summarized in table 3 prove a significant effect of exposures to dust in coal and iron mining, the asbestos-cement industry, steel and smelter workers and pulp mill workers. A number of analysed exposures is composed of exposure to dust and fumes (such as non-halogenated hydrocarbons, paints, resins or varnishes) as well as gases (such as sulphur dioxide or the oxides of nitrogen). According to the results of a comprehensive review, restricted to the most valid and systematically analysed articles on COPD and occupational dust exposure, it can be estimated that 80 of 1,000 non-smoking coalminers could be expected to develop at least 20% loss of FEV1 following 35 years of work with a mean respirable dust concentration of 2 mg/m3, and for non-smoking gold miners the respective risk could be three times as large.

Table 3. Loss of ventilatory function in relation to occupational exposures: results from selected longitudinal workforce-based studies

Country (year) Subjects and exposures Test used Annual loss of function*
      NE E NS S
UK (1982) 1,677 coalminers FEV ml 37 41 (av)
57 (max)
37 48
USA (1985) 1,072 coalminers FEV ml 40 47 40 49
Italy (1984) 65 asbestos cement workers FEV ml 9 49 Not given Not given
Sweden (1985) 70 asbestos cement workers FEV% 4.2 9.2 3.7 9.4
France (1986) 871 iron miners FEV% 6 8 5 7
France (1979) 159 steel-workers FEV% 0.6 7.4 Not given Not given
Canada (1984) 179 mine and smelter workers FEV/FVC% 1.6 3.1 2.0 3.4
France (1982) 556 workers in factories FEV ml 42 50
52 (dust)
47 (gases)
55 (heat)
40 48
Finland (1982) 659 pulp mill workers FEV ml No effect No effect 37 49
Canada (1987) 972 mine and smelter workers FEV ml   69 (roaster)
49 (furnace)
33 (mining)
41 54

* Table shows the average annual loss of lung function in the exposed (E) compared to the non-exposed (NE), and in smokers (S) compared to non-smokers (NS). Independent effects of smoking (S) and/or exposure (E) shown to be significant in the analyses carried out by the authors in all studies except for the Finnish study.

Modified with permission from: Becklake 1989.

 

Selected studies performed with grain workers show the effect of occupational exposure to organic dust on longitudinal changes in lung function. Although limited in number and the duration of follow-up, the findings document an independent relationship of smoking with annual lung function loss (vis à vis exposure to grain dust).

Pathogenesis

The central pathophysiological disorder of COPD is chronic airflow limitation. The disorder results from narrowing of the airways—a condition that has a complex mechanism in chronic bronchitis—whereas in emphysema the airways obstruction results mainly from low elastic recoil of the lung tissue. Both mechanisms often coexist.

The structural and functional abnormalities seen in chronic bronchitis include hypertrophy and hyperplasia of submucosal glands associated with mucous hypersecretion. The inflammatory changes lead to smooth muscle hyperplasia and mucosal swelling. The mucous hypersecretion and airways narrowing favour bacterial and viral infections of the respiratory tract, which may further increase the airways obstruction.

The airflow limitation in emphysema reflects the loss of elastic recoil as a consequence of the destruction of elastin fibres and collapsing bronchiolar wall due to high lung compliance. The destruction of elastin fibres is considered to result from an imbalance in the proteolytic-antiproteolytic system, in a process known also as protease inhibitor-deficiency. Alpha1-antitrypsin is the most potent protease inhibiting the elastase effect on alveoli in humans. Neutrophils and macrophages that release elastase accumulate in response to local inflammatory mediators and inhalation of various respiratory irritants, including tobacco smoke. The other, less powerful inhibitors are a2-macroglobulin and low-weight elastase inhibitor, released from submucosal glands.

Recently, the antioxidant-deficiency hypothesis has been examined for its role in the pathogenetic mechanisms of emphysema. The hypothesis contends that oxidants, if not inhibited by antioxidants, cause damage to the lung tissue, leading to emphysema. Known oxidants include exogenous factors (ozone, chlorine, nitrogen oxides and tobacco smoke) and endogenous factors such as free radicals. The most important antioxidant factors include natural antioxidants such as vitamins E and C, catalase, superoxide dysmutase, glutathion, ceruloplasmin, and synthetic antioxidants such as N-acetylcysteine and allopurinol. There is an increasing body of evidence about synergism regarding antioxidant-deficiency and protease inhibitor-deficiency mechanisms in the pathogenesis of emphysema.

Pathology

Pathologically, chronic bronchitis is characterized by hypertrophy and hyperplasia of the glands in the submucosa of large airways. As a result, the ratio of the bronchial gland thickness to the bronchial wall thickness (the so-called Reid index) increases. Other pathological abnormalities include metaplasia of the cilliary epithelium, smooth muscle hyperplasia and neutrophillic and lymphocytic infiltrations. The changes in large airways are often accompanied by pathological abnormalities in small bronchioles.

Pathological changes in small bronchioles have been consistently documented as varying degrees of the inflammatory process of airway walls. After the introduction of the concept of small airways disease, the focus has been on the morphology of separate segments of bronchioles. The histological evaluation of the membranous bronchioles, expanded subsequently to the respiratory bronchioles, displays wall inflammation, fibrosis, muscle hypertrophy, pigment deposition, epithelial goblet and squamous metaplasia and intraluminal macrophages. Pathological abnormalities of the type described above have been termed “mineral dust induced airway disease”. An associated condition demonstrated in this segment of the respiratory tract is peribronchiolar fibrosing alveolitis, which is thought to represent the early reaction of pulmonary tissue to inhalation of mineral dust.

Pathological changes in emphysema can be categorized as centriacinar emphysema or panacinar emphysema. The former entity is largely limited to the centre of the acinus whereas the latter form involves changes in all structures of the acinus. Although panacinar emphysema is thought to reflect a hereditary protease inhibitor deficiency, both forms may coexist. In emphysema, terminal bronchioles show signs of inflammation and distal airspaces are abnormally enlarged. The structural destruction involves alveoli, capillaries and may lead to the formation of large abnormal airspaces (emphysema bullosum). Centriacinar emphysema tends to be located in the upper lung lobes whereas panacinar emphysema is usually found in the lower lung lobes.

Clinical Symptoms

Chronic cough and phlegm expectoration are two major symptoms of chronic bronchitis, whereas dyspnoea (shortness of breath) is a clinical feature of emphysema. In advanced cases, the symptoms of chronic expectoration and dyspnoea usually coexist. The onset and progress of dyspnoea suggest the development of chronic airflow limitation. According to the symptoms and the physiological status, clinical presentation of chronic bronchitis includes three forms of the disease: simple, mucopurulent and obstructive bronchitis.

In chronic bronchitis, the results of chest auscultation may reveal normal breath sounds. In advanced cases there may be a prolonged expiratory time, wheezes and rales, heard during expiration. Cyanosis is common in advanced obstructive bronchitis.

Clinical diagnosis of emphysema is difficult in its early stage. Dyspnoea may be a single finding. The patient with advanced emphysema may have the barrel-chest and signs of hyperventilation. As a result of lung hyperinflation, other findings include hyperresonance, decrease in diaphragmatic excursion and diminished breath sounds. Cyanosis is rare.

Because of similar causative factors (predominantly the effect of tobacco smoke) and similar presentation diagnosis of chronic bronchitis vis-à-vis emphysema may be difficult, especially if chronic airflow limitation dominates the picture. Table 4 provides some clues that are helpful for diagnosis. The advanced form of COPD can take two extreme types: predominant bronchitis (“blue bloater”) or predominant emphysema (“pink puffer”).

Table 4. Diagnostic classification of two clinical types of COPD, chronic bronchitis and emphysema

Signs/symptoms Predominant bronchitis
(“Blue Bloater”)
Predominant emphysema
(“Pink Puffer”)
Body mass Increased Decreased
Cyanosis Frequent Infrequent
Cough Predominant symptom Intermittent
Sputum Large quantity Rare
Dyspnoea Usually marked during exercise Predominant symptom
Breath sounds Normal or slightly decreased,
adventitious lung sounds
Decreased
Cor Pulmonale Frequent Infrequent
Respiratory infections Frequent Infrequent

 

Chest radiology has a limited diagnostic value in chronic bronchitis and early stages of emphysema. Advanced emphysema shows a radiological pattern of increased radiolucency (hyperinflation). Computerized tomography provides better insight into the location and magnitude of emphysematous changes, including differentiation between centriacinar and panacinar emphysema.

Lung function testing has a well-established position in diagnostic evaluation of COPD (table 5). The battery of tests that are of practical importance in functional assessment of chronic bronchitis and emphysema includes functional residual capacity (FRC), residual volume (RV), total lung capacity (TLC), FEV1 and FEV1/VC, airways resistance (Raw), static compliance (Cst), elastic recoil (PL,el), blood gases (PaO2, PaCO2) and diffusing capacity (DLCO).

Table 5. Lung function testing in differential diagnosis of two clinical types of COPD, chronic bronchitis and emphysema

Lung function test Predominant bronchitis
(“Blue Bloater”)
Predominant emphysema
(“Pink Puffer”)
RV, FRC, TLC Normal or slightly increased Markedly increased
FEV1 , FEV1 /VC Decreased Decreased
Raw Markedly increased Slightly increased
Cst Normal Markedly increased
PL,el Normal Markedly increased
PaO2 Markedly increased Slightly decreased
PaCO2 Increased Normal
DLCO Normal or slightly decreased Decreased

RV = residual volume; FRC = functional residual capacity; TLC = total lung capacity; FEV1 = forced expiratory volume in the first second and VC = vital capacity; Raw = airways resistance; Cst = static compliance; PL,el = elastic recoil; PaO2 and PaCO2 = blood gases; DLCO = diffusing capacity.

 

Clinical diagnosis of peripheral airways disease is not possible. Very often the disease accompanies chronic bronchitis or emphysema or even precedes clinical presentation of both latter forms or COPD. Isolated form of peripheral airways disease can be investigated by means of lung function testing, although the functional status of peripheral airways is difficult to assess. This part of the bronchial tree contributes to less than 20% of the total airflow resistance and isolated, mild abnormalities in small airways are considered to be below the level of detectability of conventional spirometry. More sensitive methods designed to measure the function of peripheral airways include a number of tests, among which the following are in most frequent use: maximal midexpiratory flow rate (FEF25-75), flow rates at low lung volumes (MEF50, MEF25), single breath nitrogen index (SBN2/l), closing capacity (CC), upstream airflow conductance (Gus) and frequency dependent compliance (Cfd). In general, these tests are thought to have a low specificity. On theoretical grounds FEF25-75 and MEF50,25 should reflect calibre-limiting mechanisms first of all, whereas SBN2/l is thought to be more specific to the mechanical properties of airspaces. The former indices are used most frequently in occupational epidemiology.

Differential diagnosis

Basic differences between chronic bronchitis and emphysema are shown in tables 4 and 5. However, in individual cases the differential diagnosis is difficult and sometimes impossible to conduct with a fair degree of confidence. In some cases it is also difficult to differentiate between COPD and asthma. In practice, asthma and COPD are not clear-cut entities and there is a large degree of overlap between the two diseases. In asthma, the airway obstruction is usually intermittent, while in COPD it is constant. The course of airflow limitation is more variable in asthma than in COPD.

Case Management

The clinical management of COPD involves cessation of a smoking habit, the single most effective measure. Occupational exposure to respiratory irritants should be discontinued or avoided. The clinical management should focus on the proper treatment of respiratory infections and should involve regular influenza vaccinations. Bronchodilator therapy is justified in patients with airflow limitation and should comprise b2-adrenergic agonists and anticholinergics, given as monotherapy or in combination, preferably as an aerosol. Theophylline is still in use although its role in the management of COPD is controversial. Long-term corticosteroid therapy may be effective in some cases. Bronchial hypersecretion is often dealt with by mucoactive drugs affecting mucus production, mucus structure or mucocilliary clearance. The assessment of the effects of mucolytic therapy is difficult because these drugs are not used as monotherapy of COPD. Patients with hypoxaemia (PaO2 equal to or less than 55 mm Hg) qualify for long-term oxygen therapy, a treatment that is facilitated by access to portable oxygenators. Augmentation therapy with alpha1-antitrypsin can be considered in emphysema with confirmed alpha1-antitrypsin deficiency (phenotype PiZZ). The effect of antioxidant drugs (such as vitamin E and C) on the progress of emphysema is under investigation.

Prevention

Prevention of COPD should begin with anti-smoking campaigns targeting both the general population and occupational groups at risk. In the occupational setting, the control and prevention of exposures to respiratory irritants are essential and always constitute a priority. These activities should aim at effective reduction of air pollution to safe levels, usually defined by so-called permissible exposure levels. Since the number of air pollutants is not regulated or not adequately regulated, every effort to reduce exposure is justified. In circumstances where such a reduction is impossible to achieve, personal respiratory protection is required to diminish the risk of individual exposure to harmful agents.

Medical prevention of COPD in the occupational setting incorporates two important steps: a respiratory health surveillance programme and an employee education programme.

The respiratory health surveillance programme involves regular evaluation of respiratory health; it starts with initial assessment (history, physical examination, chest x ray and standard lung function testing) and continues to be performed periodically over the period of employment. The programme is meant to assess the baseline respiratory health of workers (and to identify workers with subjective and/or objective respiratory impairment) prior to the commencement of work, and to detect early signs of respiratory impairment during ongoing surveillance of workers. Workers with positive findings should be withdrawn from exposure and referred for further diagnostic evaluation.

The employee education programme should be based on the reliable recognition of respiratory hazards present in the work environment and should be designed by health professionals, industrial hygienists, safety engineers and the management. The programme should provide workers with proper information on respiratory hazards in the workplace, potential respiratory effects of exposures, and pertinent regulations. It should also involve promotion of safe work practices and a healthy lifestyle.

 

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Contents

Preface
Part I. The Body
Part II. Health Care
Part III. Management & Policy
Part IV. Tools and Approaches
Part V. Psychosocial and Organizational Factors
Part VI. General Hazards
Part VII. The Environment
Part VIII. Accidents and Safety Management
Part IX. Chemicals
Part X. Industries Based on Biological Resources
Part XI. Industries Based on Natural Resources
Part XII. Chemical Industries
Part XIII. Manufacturing Industries
Part XIV. Textile and Apparel Industries
Part XV. Transport Industries
Part XVI. Construction
Part XVII. Services and Trade
Part XVIII. Guides