How is chronic hypersensitivity pneumonitis (cHP) different from IPF?

If you read my last blog, you’ll recall hypersensitivity pneumonitis (HP) is caused by exposure to an aerosolized organic antigen; that is, from inhaling a living organism or a protein that comes from a living organism. The “culprit” antigens are most often mold, mildew, bacteria or bird proteins. There are three forms of HP: acute, subacute and chronic. Chronic HP is believed to be the result of chronic, repeated exposure to an aerosolized organic antigen, and cHP is a form of pulmonary fibrosis.
 
Two key points:
  1. Most people with chronic, repeated exposure to aerosolized organic antigens DO NOT develop cHP…or any other lung disease for that matter. Our current understanding is that only susceptible individuals (those with a certain genetic make-up) develop disease in response to such an exposure. We have a lot of work to do in figuring out what that genetic make-up is.
  2. People diagnosed (correctly) with IPF could have had significant exposure to mold, mildew, bacteria or birds at some point in their life, but the available clinical data that were used to make the diagnosis of IPF (that is, the medical history and exam, biopsy specimens and high-resolution CAT scan [HRCT] images) showed no convincing evidence that such exposure (or any other exposure for that matter) played a significant role in producing the fibrosis.
For this discussion, I would like to focus on the pathology (I know, I know…BO-RING! BO-RING!…hang with me) and HRCT findings. Before we really dig, I think it will be helpful to see HRCT images from a person with subacute HP…and before we jump in to that with both feet, I want to be sure that you know what we’re going to be looking at.
 
Let me set this up for you. When we look at images (what we call slices) from a HRCT, we view them on a computer screen. And we look at the slices as if we’re sitting at the patient’s feet looking up at the structures from below…like this.
 
 
Note: I am not a graphic designer, so cut me a little slack!
 
Now, let’s have the CT scanner make a slice…like this…
 
 
What you have to imagine as you look at a slice on the computer screen is that the body below the slice is completely removed…like this….
 
 
Can you imagine how things would be oriented on the computer screen if you were looking at this particular slice? It would be like this…
 
 
Now, let’s apply that to an actual image. Here’s an actual image of a slice taken from an actual patient (instead of a stick figure). Remember, you’re sitting at the patient’s feet looking up from below, and this slice is taken from the upper chest. As we saw above, the body below the slice is gone.
 
 
Here are some of the structures that you’re looking at in this slice.
 
 
No, I haven’t forgotten about the most important structures: the lungs are the large dark gray/black areas (with the small airways and blood vessels in them). Look between the airways and blood vessels…that shade of gray/black is NORMAL for the lungs. Keep that in mind as we continue our discussion and look at other images.
Ok, so now that you’re comfortable with HRCT images, let’s get on with our discussion. Remember I was going to show you a HRCT slice from a patient with subacute HP? Here it is, right next to the slice from the patient with normal lungs.
 
 
Compared with normal, do you notice how much lighter the shade of gray is in the lungs with HP? That shade of gray is called ground glass (more on that in another blog).
Now let’s look at a slice from a patient with cHP. Here’s one right next to the slice from the patient with subacute HP.
 
 
What’s different between the two images? Well, what I see in the image on the left (the cHP image) are patches of webs or networks of white lines outlining vaguely round, black circles. I don’t see those on the right. Here’s a close-up of what I’m talking about.
 
 
This web or network of white lines makes up what we call honeycombing, and that marks fibrosis. Notice there is no honeycombing in the image from the patient with subacute HP…that’s because there is no fibrosis.
 
Here’s a really important point or two: honeycombing is not specific for IPF; honeycombing is specific for fibrosis…so, if you see honeycombing, you can be certain there is fibrosis in that area. This is absolutely true whether we’re talking about pulmonary fibrosis in the setting of cHP or IPF or rheumatoid arthritis…or any other cause of pulmonary fibrosis. HOWEVER, the kicker is that there can be significant fibrosis present in the lung, even if there is no honeycombing whatsoever on the HRCT images.
 
I know it seems like it took forever to get here, but let’s now compare cHP with IPF. First, let’s talk about how they’re the same. As alluded to above, both are forms of pulmonary fibrosis. As such, both are serious diseases.
 
Now, let’s talk about the differences. Since we’ve focused on HRCT so much already, let’s look at the differences between cHP and IPF on HRCT images.
 
Here’s a side-by-side comparison of HRCT slices from a patient with cHP and a patient with IPF. The green line marks from where in the chest the slice was taken.
 
 
You see in the cHP image, we’re high in the chest (at the arch of the aorta), and in the IPF image we’re way down in the chest (toward the bottom of the heart). That’s because the fibrosis of cHP is typically upper lobe predominant (it affects more of the mid and UPPER lungs than the lower); whereas IPF is a lower-lobe predominant fibrosis (it affects more of the mid and LOWER lungs than the upper). Keep in mind, in IPF, there may be fibrosis in the mid and upper lungs, but there’s much more of it in the lowest zones of the lungs.
 
In cHP, we also may see something called lobular air-trapping…little pockets of lung that are over-inflated and appear too dark on the HRCT. These are best seen on expiratory images (we take the picture after the patient has exhaled fully and while he holds his breath in exhalation for a moment). Air-trapping does not occur in IPF. Lobular air-trapping in cHP looks like this…
 
 
Since we’ve whipped the HRCT into submission, let’s move on to the differences in pathology between cHP and IPF. Under the microscope, cHP is classically a peri-bronchiolar (kind of emanating from the airways out into the lung) predominant fibrosis…the worst fibrosis seems to emanate from the air sacs closest to the microscopic airways. That kind of makes sense, right?…the fibrosis is driven by an inhaled antigen, so we’d expect the fibrosis to occur more robustly where the antigen is being inhaled.
 
Under the microscope, IPF occurs as a pattern called usual interstitial pneumonia (or UIP). UIP is a subpleural process…rather than the fibrosis being “centered” around airways, it appears to start immediately beneath the lining of the lung and move inward.
 
Here’s another important point: UIP is a non-specific pattern of fibrosis. The UIP-pattern can occur in a number of different causes of pulmonary fibrosis; IPF is the most common reason for UIP, but UIP may occur in rheumatoid arthritis, drug-induced pulmonary fibrosis, asbestosis, and yes…even cHP.
 
In cHP, within and around the fibrosis, we see things called granulomas…what the heck are those? Granulomas are nothing more than clusters of immune cells that have arranged themselves in loose little balls. They occur in other diseases too; the best example being sarcoidosis (but that’s a topic for another blog). Granulomas do not occur in IPF.
 
You’ve probably noticed that I’ve taken a bit of latitude and been pretty dogmatic with certain statements about what may or may not occur in cHP and IPF. I’ve only done so to try to drive home the key points. In reality, as you all well-know, things are usually not so black and white. That notwithstanding, here’s how we can summarize the differences between cHP and IPF:
  1. cHP is a form of pulmonary fibrosis caused by chronic, repeated exposure to an aerosolized, organic antigen. IPF is a form of pulmonary fibrosis whose cause is unknown.
  2. cHP is an upper-lung-predominant disease, and IPF is a lower-lung-predominant disease.
  3. Lobular air-trapping often occurs in cHP (and is used to distinguish cHP and IPF on HRCT); lobular air-trapping does not occur in IPF.
  4. Under the microscope, the fibrosis in cHP is centered around microscopic airways; the fibrosis in IPF is not. The fibrosis in IPF is most severe and extensive in the lower lobes, immediately under the lining of the lung (called the visceral pleura).
  5. Under the microscope, in cHP, we see granulomas. Granulomas do not occur in IPF.
I better shut this one down. In my next blog I can cover some of the nuances about cHP—e.g., identifying the antigen, treatment, prognosis, etc. After that, we’ll move on to non-specific interstitial pneumonia (NSIP). As always, comments are welcome and encouraged.
 
Thanks for reading.
 
Jeff



Posted: November 05 2013 by Aaron Hoy | with 0 comments


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