Diversity & Equality in Health and Care Open Access

What is COPD?

Chronic obstructive pulmonary disease (COPD) is a growing problem worldwide and a major cause of disability, hospital admission and premature death (Pauwels and Rabe, 2004). It is projected to become the third most common cause of death by the year 2020 (Murray and Lopez, 1996). From the patient’s perspective, it is also a disease that has a profound effect on quality of life (Rennard et al, 2002).

COPD is an umbrella term used to describe a number of lung conditions that obstruct airflow and make breathing difficult. COPD is multifactorial (stemming from a number of different causes or influences) and multigenic (genes may also play a significant role in why some people who smoke develop COPD). It is a progressive disease process which becomes more severe with time although signs and symptoms vary greatly between individuals. It is characterised by an abnormal inflammatory response which leads to irreversible structural and functional changes within the lungs and airways resulting in chronically poor airflow.

Key point: Chronic bronchitis and emphysema are common types of COPD. Asthma, which results in chronic airway obstruction, is traditionally recognised as a distinct disease from COPD although there are shared overlapping features.

A brief summary of chronic bronchitis

There are several key events which lead to a productive cough, a symptom characteristic of the disease.

• Recurrent injury to the airways caused by inhaled irritants causes inflammation and narrowing of the bronchi, tubes carrying air to and from the lungs.

• Membranes lining the bronchial airways become inflamed. These membranes are responsible for secreting a sticky substance called mucus, essential for trapping foreign particles and bacteria entering the lungs.

• Impairment of cilia, small hair-like waving projections in the upper airways. Cilia are responsible for removing the sticky mucus in the airways. Poor removal of the mucus can lead to subsequent lung infections caused by bacteria such as Streptococcus pneumonia and Haemophilus influenzae.

A brief summary of emphysema

This disease is characterised by a gradual loss of elasticity of lung tissue often caused by exposure to toxic chemicals or long-term exposure to tobacco smoke. Destruction of the elastic fibres in the alveoli leads to their collapse when breathing out. Consequently, air becomes trapped in the lungs. As the disease worsens, alveoli walls become permanently damaged. This reduces the surface area of the lungs and, in turn, the amount of oxygen that reaches the bloodstream.

Key points: Some individuals may have a heightened susceptibility to emphysema due to inherited genetic factors. Bronchitis is frequently a complication in emphysema.

How does COPD affect respiratory function?

COPDis characterised by physiological changes which develop in a particular order over the course of the disease. These changes include excessive mucus production, impairment of cilia, reduction in airflow, and gas exchange abnormalities (Blackler et al, 2007). These physiological changes can be categorised into three separate, often interconnected, disease processes:

• thickening and narrowing of airways (airflow obstruction)

• mucus hypersecretion (chronic phlegm and cough production)

• emphysema (dilation of distal airspaces with destruction of alveolar walls).

Key point: The obstruction to airflow does not revert either in response to bronchodilators, antiinflammatory treatment, or spontaneously (GOLD, 2013).

These disease processes result in airway obstruction (narrowing) and reduced lung compliance (elasticity) which requires an increased effort to exhale and empty the lungs. Consequently, more air will be retained within the lungs, impacting on the rate of respiratory gas exchange. Blood oxygen levels can fall, depriving cells and tissues of this essential gas required for energy (ATP) production. In addition, as the disease progresses, levels of carbon dioxide, an acidic gas, may build up within the body leading to hypercapnia.

Smoking as a risk factor of COPD

Whilst there is overwhelming evidence that tobacco smoking is the major cause of COPD, it is also clear that only a fraction of smokers develop the disease, suggesting that inherited genetic variation modulates susceptibility to the development of COPD. Although tobacco smoking is the primary cause of this inhalation injury, repeated exposure to passive smoking (Eisner et al, 2005), and many other environmental pollutants and occupational exposures (e.g. grain, flour, coal) contribute to the pathology of COPD (GOLD, 2013).

Key point: Risk for COPD is related to an interaction between genetic factors and many different environmental exposures, which could also be affected by comorbid disease. Some individuals may have a heightened susceptibility to COPD due to inherited genetic factors (Higgins et al, 1984).

Tobacco smoke contains in excess of 4000 chemicals in each puff and greater than 70 cancer-causing chemicals or carcinogens (Table 1) (Pryor, 1997). Aside from nicotine, heavy metals, and carcinogens, tobacco smoke exposes cells and tissues to high concentrations of damaging oxidants and free radicals (forms of oxygen that damage our health) which are present in both the gas and tar phase of cigarette smoke (Jones et al, 1980). Oxidants, including reactive oxygen species and reactive nitrogen species, result in oxidative stress, an imbalance in the damaging oxygen species and protective antioxidant defences. This oxidative stress can induce the inflammatory process in the airways and lung tissue (Saetta, 1999), and lead to subsequent tissue damage and cell death (Eiserich et al, 1995).

All cigarette smokers have some inflammation in their lungs and airways. However, smokers who develop COPD have an enhanced or abnormal response to inhaling toxic agents. Our bodies, under normal circumstances, are able to recover well from injury by initiating an in-built healing process known as the inflammatory response. This is important for tissuerepair and remodelling. Irritants entering the airway cause body defence cells such as neutrophils, macrophages and T lymphocytes (CD8/CD4) to accumulate in the airway. Here, they initiate the inflammatory response resulting in the arrival of inflammatory mediators at the site which destroy and remove the inhaled irritant (foreign debris). The inflammatory response will switch off once the foreign body has been removed.

In COPD however, the airways are continuously bombarded and exposed to the vast array of noxious substances in cigarette smoke. This results in a continuous and amplified cycle of inflammation that increases mucus production (chronic bronchitis); tissue destruction (emphysema); and disruption of normal repair and defence mechanisms. Excessive mucus production and the inability of the airway cilia to remove it, due to ciliary dysfunction caused by tobacco smoke, result in the chronic cough and wheezing characteristic of COPD. In addition, the mucus provides a warm, moist, and nurturing medium for bacterial growth leading to the exacerbations common in progressive COPD (Tetley, 2005). It is therefore unsurprising that COPD originates in the epithelial lining of the airway which is exposed to the initial brunt of inhaled cigarette smoke and its cocktail of damaging chemicals (Yoshida and Kaper, 2006).

Key point: It is this continued inflammatory response that results in the progressive structural changes to the lungs and associated airways even after smoking cessation.

Pathogenesis of COPD caused by tobacco smoke – a summary

The effect of tobacco smoke on COPD pathogenesis, that is, the production and development of the disease can be summarised as:

• Induces a continuous and abnormal inflammatory response (Weathington et al, 2006)

• Leads to the generation of tissue-damaging oxidants and subsequent oxidative stress (Seimetz et al, 2011)

• Reduces levels of protective antioxidants (Tsuchiya et al, 2002)

• Reduces other important protective molecules (e.g. antiproteinases) in the cells increasing susceptibility to alveolar cell death and development of emphysema (Rangasamy et al, 2004)

• Induces cell death (apoptosis) (Shoshani et al, 2002).

WANT TO KNOW MORE?

British Lung Foundation website: www.blf.org.uk/Conditions/ Detail/COPD

Education for Health website: www.educationforhealth.org

Devereux G (2006) ABC of chronic obstructive pulmonary disease. Definition, epidemiology, and risk factors BMJ 332(7550):1142–4.

Lee D (2009) Understanding COPD. Poole. Family Doctor Publications Ltd & British Medical Association.

NICE guideline CG101 on diagnosing, managing and treating COPD. www.nice.org.uk/nicemedia/live/13029/ 49397/49397.pdf

PREVIOUSLY PUBLISHED IN DIVERSITY AND EQUALITY IN HEALTH AND CARE (FORMERLY DIVERSITY IN HEALTH AND CARE)

We note that there has been remarkably little published in this journal on respiratory illness and/ or tobacco control but that the following may be of some relevance to the issue:

Lam KBH, Kurmi OP, Ayres JG (2010) Indoor air pollution: a poorly recognised hazard Diversity in Health and Care 7(1):5–7.

Poureslami I, Nimmon L, Doyle-Waters MMR, FitzGerald JM (2011) Using community-based participatory research (CBPR) with ethno-cultural groups as a tool to develop culturally and linguistically appropriate asthma educational material. Diversity in Health and Care 8(4):203–15.

Shum J, Poureslami I, Cheng N, FitzGerald JM (2014) Responsibility for COPD self-management in ethnocultural communities: the role of patient, family member, care provider, and the system. Diversity and Equality in Health and Care 11(3–4):201–13.

References

1. Blackler L, Jones C, Maloney C (eds) (2007) Managing Chronic Obstructive Pulmonary Disease, pp 6. John Wiley and Sons. Wiley Online Library.
2. Eiserich JP, van der Vliet A, Handelman GJ et al (1995) Dietary antioxidants and cigarette smoke-induced biomolecular damage: a complex interaction. Am J Clin Nutr 62(supplement 6):S1490-S1500.
3. Eisner MD, Balmes J, Katz BP et al (2005) Lifetime environmental tobacco smoke exposure and the risk of chronic obstructive pulmonary disease. Environ. Health Perspect. 4:7–15.
4. Global Initiative for Chronic Obstructive Lung Disease (GOLD): Global Strategy for the Diagnosis, Management, and Prevention of COPD (2013) www.goldcopd.org.
5. HigginsMW,Keller JB, Landis JR et al (1984) Risk of chronic obstructive pulmonary disease. Collaborative assessment of the validity of the Tecumseh index of risk. Am Rev Respir Dis 130: 380–5.
6. Jones JG, Lawler P, Crawley JCW et al (1980) Increased alveolar epithelial permeability in cigarette smokers. Lancet i:66–8.
7. Murray CJ, Lopez AD (1996) The Global Burden of Disease. Boston, Harvard School of Public Health, Harvard University Press.
8. Pauwels RA, Rabe KF (2004) Burden and clinical features of chronic obstructive pulmonary disease (COPD). Lancet 364:613–20.
9. Pryor WA (1997) Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity. Environ Health Perspect 105(supplement 4):875–82.
10. Rangasamy T, Cho CY, Thimmulappa RK et al (2004) Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. J Clin Invest 114(9):1248–59.
11. Rennard S, Decramer M, CalverleyPMet al (2002) Impact of COPD in North America and Europe in 2000: subjects’ perspective of Confronting COPD International Survey. Eur Respir J 20:799–805.
12. Saetta, M (1999) Airway inflammation in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med 160:S17-S20.
13. Seimetz M, Parajuli N, Pichl A et al (2011) Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice. Cell 147(2):293– 305.
14. Shoshani T, Faerman A, Mett I et al (2002) Identification of a novel hypoxia-inducible factor 1-responsive gene, RTP801, involved in apoptosis. Mol Cell Biol 22(7): 2283–93.
15. Tetley TD (2005) Inflammatory cells and chronic obstructive pulmonary disease. Curr Drug Targets Inflamm Allergy 4(6):607–18.
16. Tsuchiya M, Asada A, Kasahara E et al (2002) Smoking a single cigarette rapidly reduces combined concentrations of nitrate and nitrite and concentrations of antioxidants in plasma. Circulation 105(10):1155–7
17. Weathington NM, van Houwelingen AH, Noerager BD et al (2006) A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Nat Med 12(3):317–23.
18. Yoshida T and Tuder RM (2007) Pathobiology of cigarette smoke-induced chronic obstructive pulmonary disease. Physiol Rev 87:1047–82.