Chronic Obstructive Pulmonary Disease

Overview

COPD is a conceptually difficult disease because it is a mixture of two pathologies: chronic bronchitis and emphysema. The two coexist in patients to different degrees, so patients present with a mixture of different respiratory problems. Indeed, in the past, patients were described simply as being “blue bloaters” or “pink puffers”. These now redundant terms, which were thought to describe patients with predominantly chronic bronchitis or emphysema, respectively, are no longer very useful. Modern CT scanning shows that COPD patients have both pathologies as part of a single disease.

However, the two pathologies of COPD are worth considering separately in order to understand the individual contributions that they make, which can then be reconstructed to form an idealised patient. Don't believe the myth you may find in some (older) texts that some people have only bronchitis and others only emphysema. It’s always a mixture of the two, although clinical presentations do vary.

Chronic bronchitis

Chronic bronchitis affects mainly the conducting airways and consists of chronic inflammation (largely glucocorticosteroid-resistant) and mucus hypersecretion. Excess mucus is the result of hypertrophy (growth) of submucosal mucus glands, as well as the increased number of mucus-secreting goblet cells in the airways epithelium. The impact of increased mucus and mucosal inflammation is the same as is similar to that seen in asthma – a reduction in airway radius and hence an increase in airway resistance. COPD is an obstructive disease that can be difficult to distinguish from asthma and may require a careful differential diagnosis. One of the useful diagnostic criteria is the degree to which airflow limitation is sensitive to bronchodilators such as salbutamol.

Emphysema

Emphysema is the destruction of the airway parenchyma, the alveoli and the extracellular components that maintain their structure. Over time, proteolytic enzymes released by inflammatory cells degrade the extracellular matrix, resulting in a breakdown of the alveolar walls. This leads to large, irregular airspaces and a reduction in the surface area for gas exchange. Eventually, the surface area becomes too small for gas exchange to occur efficiently.

Loss of surface area is just the beginning of the problems though. Because the elastin fibres in the parenchymal extracellular matrix make a large contribution to the elastic recoil of the lungs, the process of inflating the lungs becomes easier: lung compliance increases. This makes the lungs easier to expand because there’s less recoil to work against, but for the same reason they don’t deflate as well of their own accord. This requires more work during exhalation – perhaps even quite forceful expiration. This is where the third problem in emphysema arises.

In a normal lung, the alveoli and small airways are influenced by the surrounding alveoli, which tend to pull against them and keep the open at the end of inspiration. This allows you to perform quite forceful exhalation without collapsing the fine airways, since the elastic fibres of the lung are provide an opposing force. As the architecture of the airspaces in the lung becomes destroyed in emphysema, this network of forces becomes disrupted and it is much easier to compress the small airways. So while it is probably possible for a healthy person to collapse some of their small airways (being suddenly “winded” might be a good example of this), it’s much easier to do in someone with emphysema (Figure 1). Now, because such patients have less recoil (see above), they have to use forceful exhalation, which tends to collapse their finer airways and trap air in the alveoli. Many COPD patients tend to be chronically hyperinflated for this reason, which accounts for the sometimes “bloated” appearance of some patients.

Figure 1: At the end of inspiration in the normal lung (A), the alveoli and terminal bronchioles are kept open by the radial traction provided by the elastic fibres in surrounding tissues (mostly other alveoli). This supporting network usually allows forceful expiration (positive intrapleural pressure) with minimal airway collapse. In emphysema (B), degradation of these important connective tissue fibres allows alveoli to collapse into neightbouring airspaces and fails to support the terminal bronchioles. Applying positive pressure - as in the forced expiration required to compensate for the lack of lung recoil – tends to collapse the terminal bronchioles, trapping air in the distended alveoli.

COPD as both pathologies

Now, imagine a typical COPD patient with a mixture of emphysema and chronic bronchitis. Airways resistance in the conducting airways is increased, making it hard to move air in and out of the lungs. This is mostly due to inflammation and mucus, with a smaller reversible (i.e. β₂-agonist-sensitive) component than you would see in asthma. Unlike typical asthma, the airway obstruction is permanent in COPD, rather than episodic, possibly requiring increased work of breathing all of the time. On top of this airflow problem, there is a reduction in surface area for gas exchange due to destruction of the alveoli, leading to hyperventilation (hence hypocapnia) in order to maintain adequate O₂ levels. (You can read around these problems in the blood gas basics and VQ mismatch entries.) Finally, because radial traction is lost, it is difficult to perform the more forceful expiration required to get air out of the lungs without collapsing small airways and trapping gas in the alveoli. There aren’t many pharmacological solutions to these largely mechanical problems.

Pink Puffers and Blue Bloaters?

While COPD patients can often broadly fit into one category or another as a clinical presentation, the thing to remember is that these phenotypes don’t necessarily relate to the different contributions of different pathologies to their symptoms. Furthermore, many patients don’t fit naturally into either supposed category. It’s probably better to think of COPD patients as those who retain CO₂ (and who are consequently hypercapnic) and those who don’t.

Figure 2: A common and useful analogy for CO₂ retention by any patient who is hypoventilating and CO₂ washout. Think of CO₂ as dirt at the bottom of a vase. If you try to wash this out using a low flow of water, only some of the dirt gets dislodged. By increasing the flow, you remove the muck more readily.

One story goes that because these patients are acclimatised to high PaCO₂, their breathing is driving by hypoxic, rather than hypercapnic drive (which has become desensitised; see reflex control of breathing). The truth is probably more complicated than that, and you shouldn’t withhold supplemental O₂ for fear that it will silence hypoxic drive and stop them breathing. Just be cautious.