Now, the next slide gets into some of the risk factors for COPD, and as you can see from slide 7, the most important is cigarette smoking. Eighty-five percent to 90% of all COPD patients have COPD because they smoke. Now, the twist on this factor is that only 15% to 20% of smokers develop COPD, so this has some far-reaching concepts when you start to try to determine who has COPD and how to treat this disorder, and that is that because only 1 in 5 smokers gets COPD. It is almost like the Russian roulette phenomenon where smokers say, well, geez, no one in my family has had it, why would I get emphysema? Why would I get chronic bronchitis? And they are right in the fact that COPD does tend to cluster in families, and it often even clusters in families where you'll find evidence of asthma, so there seems to be some not only genetic predisposition for the development of COPD among smokers, but, furthermore, there seems to be an overlap with the genetic predisposition of asthma and COPD.

As we move into some other risk factors on slide 8 for COPD, we see that there is a hereditary form of COPD, which is alpha-1-antitrypsin deficiency, and its other name is alpha-1-antiprotease deficiency. It's kind of like Tony and Anthony, he's still the same kid. This disorder has 2 different names, but it's still the same disorder. This is a congenital lack of the secretory protein for alpha-1-antitrypsin. It stays within the liver, it isn't secreted in secretions, and, as a result, patients lack antineutrophil elastase protection.

As you move to the next slide, you can see some data on this. You can see that alpha-1-antitrypsin is the primary protection against neutrophil elastase. When we think about neutrophil elastase and its function in the lung, neutrophils are increased among smokers, increased during infection, not only the absolute number but also the state of activation. They release more neutrophil elastase, which has a functional component similar to Janitor in a Drum -- it breaks down collagen, elastin, and as a result, unrestrained neutrophil elastase activity can lead to destruction of alveolar septa and premature development of emphysema.

As we see in the next slide, slide 10, the prevalence of alpha-1-antitrypsin deficiency is variable dependent upon where you live in the world or in the United States. You can see it very frequent in Seattle -- I'm sorry, Sweden, 1 out of every 1600. Pretty frequent in Seattle at 1 out of 5000, and fairly frequent in St. Louis, where Ed Campbell actually surveyed all the donors to the St. Louis blood bank and found that 1 out of every 2800 donors were alpha-1 deficient. The importance of this is that we frequently tend to overlook this as a cause. We infrequently test for alpha-1 deficiency, and there is a treatment for this disorder.

So this should be considered in any person who develops emphysema young, in their 30s or 40s. It should be considered in anyone who has asthma with a progressive downhill course in their FEV₁. It should be considered in anyone who has emphysema or COPD but doesn't have much of a smoking history. It should also be considered in key patients who have a distribution of bulla in the bases of the lung.

As you can see, it is a much more common disorder in Caucasians than African Americans, Asians, Native Americans, etc. And so, dependent upon the region in which you live, you may have a higher or lower frequency of this disorder.

Now, other factors that may enhance the development of COPD include exposure to occupational dust. We know, clearly, that exposure to coal can lead to coal worker's pneumoconiosis. We have recently shown that exposure to asbestos on the job can lead to a higher than expected prevalence of airways obstruction. Finally, those factors such as birth weight, as exemplified on slide 11, can lead to low lung function or a low FEV₁ in adulthood.

In this study by Barker et al, there was reliance on nurse practitioners who went out and delivered babies in the early 1900s in Herefordshire County in England. They were meticulous about weighing the babies and keeping records, and so, some 40-50-60 years later, Barker could go back and review those records and summon the men born between 1911 and 1930 and record their lung function.

So as we see on the one axis, the FEV₁, and on the other, the birth weight of these individuals in the early 1900s, and you can see even when patients were stratified according to smoking status -- that is a current smoker, exsmoker, or never smoker -- you can see that the smaller babies, even among never smokers, had equivalent lung function to the big babies who were current smokers.

At this point I think we have the polling questions.