Pneumoconiosis: Clinical Manifestations

00:00 So the clinical manifestations of all of this, if you imagine that the alveolar wall has thickened, obviously you're not getting good gas exchange.

00:08 There's going to be progressive exertional dyspnea.

00:11 You're just not going to be getting as much oxygen in with every breath, or carbon dioxide out with every breath, as you did previously.

00:20 You're going to have ongoing inflammation.

00:22 So there may be a dry cough or even a productive cough with increased mucus production.

00:27 They're going to be increased vascular permeability because of all those inflammatory mediators.

00:35 And so you will have fluid that is getting into the alveoli as well that may be manifested as respiratory rouse and crackles.

00:42 In very advanced cases you get a hypertrophic pulmonary osteoarthropathy and that basically will give you digital clubbing.

00:51 The fingers become very prominently kind of clubbed at the periphery.

00:57 So those are some of the immediate and subacute kind of manifestations.

01:03 There are going to be more long-term manifestations as well.

01:08 Again, looking at our four common forms of pneumoconiosis, silicosis, asbestosis, co-workers pneumoconiosis, and borreliosis.

01:17 The onset of more chronic conditions can take decades, one to two decades.

01:25 Borrelium is the exception in that it may have a shorter acute onset because of the higher activation levels of macrophages in the setting of borrelium particles.

01:38 What's shown here on the diagram is an x-ray of the chest showing the nodular fibrosis associated with silicosis.

01:44 We'll revisit this when we look at some of the pathology later on.

01:50 But what's being shown on the right hand side is what should be air spaces in a lung that's been completely obliterated with fibrosis.

02:00 The little white shiny things and you see the red arrow, those are silica particles.

02:05 Around them are macrophages that have been trying to ingest them but ultimately have only made a lot of inflammation and fibrogenic factors.

02:15 The interstitial fibrosis will impact the ability of blood to be pumped through the lungs.

02:22 That interstitial fibrosis will make it much more difficult for the right heart to pump.

02:28 So there is pulmonary hypertension and over a long period of time, while there may be adaptation with right ventricular hypertrophy, there eventually will be corpulmonale.

02:39 So right heart failure associated with the pulmonary hypertension that's associated with the interstitial fibrosis.

02:48 Besides the right-sided heart failure, there will also be primary respiratory failure as we completely obliterate air spaces within the lungs.

02:58 Let's talk about the special case of asbestosis.

03:01 So what I've described so far is what happens with any of the particulates if you have sufficient exposure.

03:10 Asbestos has an interesting set of relatively unique features.

03:16 Like any of the other pneumoconiosis, when asbestos is inhaled, it cannot be metabolized by the macrophages.

03:22 And so will accumulate in the macrophages and in the alveolar ducts and alveolar sacs.

03:31 The particles are very small and they can reach the alveoli where they will then cause all the inflammation and fibrosis that we've discussed previously.

03:41 But asbestos is not all created equal.

03:44 There are two basic fiber types.

03:46 One is chrysotile, which is the majority or 90% of asbestos when we find it in nature.

03:54 It's a serpentine, so it's curly.

03:57 And that curliness actually makes it much more likely to not get all the way out to the alveoli.

04:05 When we inhale the serpentines, they tend to kind of spiral and get caught up in the mucus in the more proximal bronchioles.

04:15 So they're not as pathogenic.

04:18 On the other hand, this other form, the cruxidilide, which is an amphibole, it is a straight needle-like form of asbestos.

04:28 And it's less common form.

04:30 It's only about 10%, but it is much more dangerous and has a greater pathogenicity.

04:34 That's because those sharp little short fibers can act like a javelin and get all the way into the distal alveoli that can also go right through the alveolar wall and can accumulate in the pleural space where they can then impact mesothelium.

04:53 What happens when we get those asbestos fibers in various spaces? They can drive fibrosis not only in the parenchyma of the lung, giving us interstitial fibrosis, but they can also cause pleural fibrosis.

05:10 Asbestos plaques are a very common sequela of getting those, the amphibole little spears, all the way out into the pleural space where they induce dense fibrosis.

05:23 That's not malignancy, but it can impede the excursion of the lungs.

05:30 It can cause a restrictive pattern.

05:32 Also, the asbestos, when it gets into the airways, can drive a very profound macrophage activation with release of the reactive oxygen species.

05:44 Those reactive oxygen species will cause mutations in the various cells within the lung parenchyma or in the lining of the lung into mesothelium.

05:56 There are also pro-inflammatory cytokines that are driving proliferation of those cells.

06:01 So we are getting cellular proliferation at the same time we're causing mutations, and that's a substrate by which we can develop malignancy.

06:12 Asbestos is also a very potent driver of bronchogenic carcinoma.

06:18 In fact, squamous cell carcinoma of the lung is the most common neoplastic complication developing 10 to 15 years after initial exposure.

06:29 And if you happen to be a smoker and exposed to asbestos, you have a much greater risk of developing bronchogenic carcinoma.

06:36 The other entity though is mesothelioma.

06:41 Because those little javelins, those little spears, can go right through the lung and accumulate in the pleural space, all those reactive oxygen species driving mutations, all those proliferative pro-inflammatory mediators driving proliferation are acting on the mesothelial lining, the visceral or the parietal mesothelial lining in that pleural space, which will drive the development of mesothelioma.

07:07 This has a very long kind of prior exposure history before you develop it, but it is absolutely the number one driver, asbestos is a number one driver for mesothelioma, malignant tumor of the mesothelium.