Chronic Obstructive Pulmonary Disease (COPD): Overview

00:00 So, for this second lecture on airways disease, I'm going to talk about Chronic Obstructive Pulmonary Disease, COPD. Now, COPD, is the second commonest chronic lung disease after asthma. There's an estimated 65 million people in the world who have moderate to severe COPD, it's incredibly common, and there's even an estimate that 6% of the US population have COPD, although that's scarcely believable. It's very undiagnosed. About 25% of the patients with COPD actually have the diagnosis, the rest having mild disease, which they just put down to aging and making them more breathless, and therefore don't actually seek doctors to get the diagnosis made. In general, COPD is commoner in men, although women, with their increased smoking, as it has occurred in women, it is also very common in women as well, and is largely a disease of the middle aged and the elderly. What's the pathogenesis? Well, in COPD, an inhaled agent, cigarette smoking, most patients in industrialized countries causes chronic inflammation of the airways, which over a long time leads to a variety of pathological changes. These include mucous hypersecretion, increased numbers and expansion of their secretory capacity of the mucous glands leading to a lot of chronic mucous production.

01:22 Inflammation of the small airways, the bronchioles, and that eventually leads to small airways obstruction.

01:28 And then, sometimes you get alveolar destruction. Now, that's called emphysema, where the alveoli, instead of forming a large number of small units are destroyed and form one larger unit.

01:41 And with that, you get something called dynamic airways collapse, which I'll describe in a bit more detail later on. The upshot of these pathologies is that you have a largely irreversible, slowly progressive airways obstruction occurring, largely in the small airways. And, unlike asthma, where the inflammation in asthma responds well to corticosteroid therapy, the inflammation that occurs in COPD, responds very poorly to corticosteroid therapy. Which of the three major pathologies the patient has actually varies, and the ratio between them varies between patients. So, you do get patients who have emphysema as the dominant problem with very little record of airways obstruction elsewhere. You have patients where in fact the main problem is mucous gland hyperplasia or chronic bronchitis and very little airways obstruction, and you get a mix of all three. This leads to the sort of the variation in the phenotype that the patient might present with. What's the cause of the airways inflammation? Well, cigarette smoking. It causes almost all of the disease that you may see in industrialized countries. However, there are inhaled agents that occur elsewhere in the world, which may be relevant. So, use of solid fuel fires is thought to be a very big driver for developing COPD in sub-Saharan Africa for example. In addition, coal workers breathing coal dust that can lead to airways obstruction, purely from the coal dust by itself without smoking.

03:12 Although many coal workers have smoked as well, so it's quite hard to tease out the combination of the two. And then recreational drugs, crack, cocaine, or injected drugs such as heroine. They also contribute and lead to airways obstruction.

03:26 Though, again, many of those patients do smoke cigarettes as well. An important point here, is that not everybody who smokes will develop airways disease. And it's thought to be 1 in 4 patients who smoke will develop COPD, and that suggests there must be other genotypic and phenotypic predispositions in those quarter of smokers that allows the airways inflammation to progress to airways obstruction. So other predisposing factors that were recognized is low birth weight and poor lung development, that will make your overall lung volume smaller, and therefore loss of lung volume will precipitate symptoms at a faster rate, than perhaps somebody who has well developed lungs. Low socioeconomic status is also related to airways obstruction, as is poor nutrition, and there are the occasional rare patients with genetic and inherited deficiencies or alpha-1-antitrypsin. Now what that means is that alpha-1-antitrypsin is an enzyme that prevents trypsin, an enzyme released by neutrophils from digesting lung tissue. So what happens in these patients is that the smoking promotes neutrophil infiltration into the lungs, the neutrophils release their trypsin, that starts to digest the lung. But there is no balancing alpha-1-antitrypsin around to prevent that. And therefore, those patients with alpha-1-antitrypsin deficiency who smoke, will end up with very rapidly progressive early onset basal emphysema.

05:07 This diagram is a sort of overview of what may happen with lung function with age and smoking. So for example, you start off with a certain level of FEV1, and this diagram is not entirely accurate, because in fact you reach peak FEV1 around age 20. It then gradually falls with age in normal people. And somebody who smokes cigarettes who's not susceptible to the development of COPD, it will fall at a similar rate. However, if you smoke cigarettes and you have the susceptibility to developing COPD, then the rate at which the FEV1 falls over time will increase.

05:47 And that means the gradient of this deterioration will be more rapid, it will be steeper.

05:53 And the patient will end up developing disease, symptoms of airways obstruction, and then eventually, if it carries on with the deterioration in the FEV1, they'll get severe respiratory disease with respiratory failure and death potentially. In theory, if the patient stops smoking, that accelerated decline in FEV1 stops, and the patient achieves a lower decline in their FEV1 and that will prolong their stage of disease in the milder stages and hopefully prevent them developing respiratory failure and death. The normal loss of FEV1 each year with age is about 30 mls. If you smoke, that is often increased to 50 mls, and in many patients can go up as far as 100 mls. You can see how that can rapidly lead to a fall, so if you have an FEV1 of 3 Litres for example and you're losing a 100 mls a year, in 10 years your FEV1 will be 2 Litres, in 10 years more it will be 1 Litre, and you won’t have another 10 years because your FEV1 will fall to a level where it doesn't sustain life.

07:12 And this is how airways disease behaves overtime. And it is also why FEV1 is one of the main measures that we use for monitoring patients to seeing how they are doing. So how do patients with