Pneumoconiosis: Epidemiology and Pathophysiology

00:00 Welcome.

00:02 With this talk, we're going to be discussing the topic of pneumoconiosis.

00:06 Fundamentally, this is a variety of inhalation and then deposition within the lungs of mineral dusts and other kinds of inorganic particles.

00:16 We typically think of the pneumoconiosis in the setting of occupational exposures, and we'll talk about those.

00:25 But fundamentally, we're all inhaling particulate matter all the time that can deposit and would technically constitute pneumoconiosis.

00:33 The most common causes of kind of occupational exposure include silicosis, which is from silica dust of a very small size, about five microns.

00:46 Asbestos exposure, and where this is coming from in the environment.

00:50 Coal workers' pneumoconiosis due to coal dust inhalation.

00:53 Borreliosis associated with beryllium.

00:56 Those are the most common causes of occupational pneumoconiosis.

01:01 But on this slide, we're also going to just briefly mention that you can have iron oxide inhalation in welders, or tin oxide, or barium sulfate, or cobalt with or without tungsten carbide in a variety of settings.

01:15 Talc powder can also be inhaled and accumulate.

01:20 And typically, this is going to be for workers who work in industries that make or process ceramics, paper, plastics, rubber paint, and cosmetics.

01:31 Theoretically, if you liberally apply talc yourself, you can have some degree of talc inhalation, but usually that's not going to be at the same level as those workers who are constantly in that environment.

01:46 So the epidemiology.

01:48 Let's talk about the four major causes.

01:50 Silicosis is the most common cause of pneumoconiosis.

01:53 It's going to be in individuals who are in the mining, sandblasting, quarry kind of capacity.

02:01 There are roughly 2 million cases worldwide with about 13,000 deaths attributable to silica inhalation each year.

02:12 As we recognize that this is a potential health risk, using masks that can filter out the small silica particles, the incidence is decreasing overall.

02:24 Next up is asbestos.

02:26 There are about 150,000 cases each year, about 3,500 deaths annually.

02:31 This occurs in individuals who are involved in shipbuilding.

02:36 A lot of the boilers onboard ships were previously insulated with asbestos.

02:41 We also see asbestos exposures from those in the roofing industry, plumbing, insulation, and demolition where constructions had a lot of asbestos in them previously.

02:53 It's important that family members of workers in the asbestos industries above can also be at risk and that there have been numerous instances of spouses of individuals who work, say, on shipbuilding developing asbestos-related pathologies.

03:13 Again, as we recognize that this inhalation is pathologic, we're limiting exposure and the overall numbers of cases is declining.

03:27 Importantly, as opposed to the other pneumoconiosis, which tend to induce primarily pulmonary fibrosis, asbestos is also associated with carcinogenesis.

03:38 It will drive the development of bronchogenic carcinoma as well as mesothelioma.

03:45 The next entity is coal workers' pneumoconiosis, very common among coal miners, and they have substantial exposure to particulate carbon, so a very high prevalence of a disease in that setting.

04:01 And again, this is being limited by mask wearing and filtering of what is being inhaled, but is a substantial risk among the coal miners.

04:11 Notably, what they're being exposed to is particulate carbon, but it's also the impurities in the coal.

04:20 And then berylliosis is relatively rare of these four most common entities.

04:26 Even in exposed workers, it has a relatively infrequent prevalence, so 1 to 5 percent.

04:31 Where we encounter beryllium in the occupational environment is in the aerospace industry, ceramics, metallurgy, electronics repair, jewelry making, and dentistry.

04:41 Family members of workers who bring home particulate material on their clothing can also be at risk.

04:47 The path of physiology of what goes on when you inhale particulate material.

04:53 These compounds can be elemental, say in the case of beryllium, it can be larger chemical compounds, but they get inhaled and the pulmonary alveolar macrophages are there.

05:07 And the job of those cells is to gobble up inhaled particulates, bacteria or fungus, that gets into that space and to degrade them if at all possible.

05:19 Well, these compounds, silica, asbestos, are not degradable by macrophages, so they get engulfed by them.

05:28 The macrophages attempt to fuse their lysosomes and degrade the material within the phagosomes, but can't degrade it.

05:39 As a result, there is a pro-inflammatory and pro-fibrotic cytokine release, so we're releasing interleukin-1 and tumor necrosis factor.

05:46 This induces an inflammatory response.

05:51 As a result of that, we are getting increased mucous production in the airways, but also we're fibrosing the alveolar wall because of the pro-fibrotic effects of interleukin-1 and tumor necrosis factor alpha.

06:06 That fibrotic scarring leads to thickening of the airways, so they're no longer as compliant, so you reduce the elasticity.

06:15 The alveolar walls are thickened, so there's impaired gas exchange.

06:19 We're not getting good oxygen out of the alveolus and into the bloodstream, or carbon dioxide out of the bloodstream and into the alveolus.

06:29 Some of these particulates can drive the accumulation of mutations that can lead to malignancy, and asbestos, as I've already mentioned, is going to be a key driver of a particular malignancy called mesothelioma.

06:45 So what we've just said in terms of words, we're going to see now in a diagram.

06:52 So we have the particles getting down into the distal alveoli, where the alveolar macrophages, marauding around looking for things to gobble up, will indeed gobble them up.

07:01 As part of that fusion, you may release oxygen- derived free radicals and proteases that would normally be contained within the phagocytosome.

07:11 So that will cause direct lung injury.

07:14 The macrophages that are ingesting these are also undergoing pro-inflammatory activation.

07:18 So they'll make things like leukotriene B4.

07:23 They will make interleukin 8, which is a CXC chemokine that will recruit neutrophils.

07:29 They'll make interleukin 6, which is going to be a pro-inflammatory mediator, driving acute phase reactant synthesis by the liver.

07:38 They'll make tumor necrosis factor alpha.

07:40 So we're going to recruit and activate additional inflammatory cells.

07:43 And these activated macrophages, not only are they driving inflammation, they're also gonna be making things like tumor necrosis factor alpha, platelet-derived growth factor alpha, insulin-like growth factor 1, fibronectin.

07:56 Those things are going to ultimately recruit fibroblasts and drive collagen production.

08:01 And that's going to give us end-stage fibrosis down in the lungs.