Raj Parikh, MD, MPH - phaware® interview 517

Dr. Raj Parikh from Hartford Hospital discusses the development of the PH-ILD Detection tool, a screening tool designed to help detect pulmonary hypertension (PH) in patients with interstitial lung disease (ILD) at an early stage. Early detection is critical, as there is often a significant delay in diagnosis of PH in ILD patients, leading to worsened outcomes.

This Special Edition episode is sponsored by Liquidia.

My name is Raj Parikh. I'm the Director of the Pulmonary Hypertension Center at Hartford Hospital in Hartford, Connecticut. I did a lot of my training kind of all over. I went to medical school in New Orleans, Chicago, ended up in Boston, and then made my way back home to Connecticut where I grew up. I've been at Hartford Hospital for the last four years. I started the Hartford Hospital's Pulmonary Hypertension Program from scratch, and I've been building it up since then.

I got involved in Pulmonary Hypertension really during my fellowship at Boston. I really wanted to get involved in the rare disease space of PH, where patients are far and few between, but the ones that are there, they have pretty significant morbidity, mortality, and a poor prognosis. There's limited treatment options and there's limited specialty care for these patients. I really wanted to come back home to my state of Connecticut and build up a program in sort of the area that I grew up in.

Today, I want to talk to you about the PH‐ILD Detection tool that Hap Farber, MD and I have been working on for a couple years. Now, it's in the community. We're encouraging all interstitial lung disease, ILD specialists, general pulmonary docs who see ILD patients to really use this as a way to work on early detection of pulmonary hypertension in interstitial lung disease patients. The reason behind developing the PH‐ILD Detection tool was to really focus on early detection and early screening for pulmonary hypertension that's associated with ILD. The impetus behind that was the development of the first and only FDA approved therapy for PH-ILD, which is inhaled Treprostinil. That was FDA approved back in 2021 after the INCREASE clinical trial.

The PH-ILD Detection tool, the real spirit behind it is patients with interstitial lung disease that develop pulmonary hypertension carry extremely poor prognosis. They need more oxygen. Their quality of life is worse. Their longevity of life and their mortality is worse, as well. These are things we know. We've studied the PH-ILD population for years and years. This is well-established stuff. The key now that we have a therapy that can A, improve the patient's walk distance and therefore their quality of life. B, keep them from having any sort of clinical worsening like ending up in the hospital or having more right heart failure. These are all findings based on the INCREASE trial. So the key really is to detect the pulmonary hypertension as soon as possible in ILD, not just screen for it once a year, or test for it when you meet the patient for the first time and then test for it again every five years.

This is not like colon cancer screening or lung cancer screening. This is active assessment every time you see an ILD patient, you should be thinking, “Okay, do they now have signs of pulmonary hypertension? Should I now be concerned about pulmonary hypertension or should I not be?" There is no standard protocol or standard practice when it comes to screening and detecting for pulmonary hypertension in ILD patients.

Back in 2022, Hap and I really developed eight parameters for PH-ILD detection. We base these parameters off of things that you should routinely already be using to assess a patient's interstitial lung disease. We're talking about 6 minute walk tests, physical exam, pulmonary function testing, assessing whether the ILD patient needs oxygen or not, blood tests, CAT scans, and their prior history and comorbidities. If we take these eight parameters and we assess, okay, which parameters have a higher weight compared to lower parameters that have maybe not as much of a weight in terms of predicting for pulmonary hypertension? We took these eight parameters and basically created a 12 score tool. The score can be anywhere from zero to 12. Four parameters have a weighted score of two points. Four parameters have a weighted score of one point, therefore equaling a max score of 12 points.

Basically, depending on what you score from zero to 12, you are stratified into either low risk for pulmonary hypertension ILD, intermediate risk for PH-ILD, or high risk for PH-ILD. A score of three or below is low risk. A score of four to five is an intermediate risk. A score of six or higher is actually high risk for PH-ILD. What does that mean? What does it mean if you're low versus intermediate or high? Well, that should really dictate what are your next steps. 

If you're low risk, you should reassess the patient at your follow-up visit, whether that's at three months or six months or whatever. If you're intermediate risk, you should get a screening echocardiogram for that patient to make sure there's no signs or development of pulmonary hypertension or right ventricular disease on that echo. If you're high risk, that's a score of six or higher on the PH-ILD Detection tool, you should not only order an echocardiogram, but you should be calling your nearby your local pulmonary hypertension specialist or pulmonary hypertension center and say, "I have a patient with interstitial lung disease. I have a high suspicion for pulmonary hypertension, can you get them into your clinic? Can you get them in for a right heart catheterization for a definitive diagnosis?" 

When we developed this score, we not only first developed it internally retrospectively, but once it was initially published, we discussed it and presented it at an oral presentation at CHEST back in Nashville, so that was a couple of years back. We then actually had seven centers used the score prospectively, and we validated the score by doing a multi-center validation cohort study. That study actually upheld a very significant area under the curve, very significant sensitivity and specificity for a score of six or higher to really strongly predict pulmonary hypertension in interstitial lung disease patients.

As a result of this, we've been working on promoting the use of this PH-ILD Detection tool with local ILD specialists, local general pulmonologists. We use this score not only to predict or increase suspicion for pulmonary hypertension, we've done some other data and we actually presented this information at CHEST, this past year at Boston, where the higher the score you have, the worse your right heart cath hemodynamics are, and therefore the worse your prognosis may be. Some of that is almost common sense, but it's nice to kind of see pen to paper and see that correlation, as well.

We've actually been working on seeing if we can create an app for this score. Now, Hap and I are creating an abbreviated version of the PH-ILD Detection tool to take it instead of eight parameters with 12 points, can we make it three parameters? Can we simplify it even further and make it as simple as possible so that the community pulmonary doctor, the community ILD specialist -- all of them can really focus on how simple it can be to detect and screen for pulmonary hypertension. Mostly because we know that once patients develop PH with ILD, the prognosis is so poor that we want to really act fast. We want to get them diagnosed soon. If we can diagnose them quickly, we can treat them with inhaled Treprostinil. We can mirror some of those outcomes that we saw with the INCREASE clinical trial, and get these patients having a better quality of life, better walk distance, lower proBNP scores, keep them out of the hospital, so on and so forth.

We know from PAH pulmonary arterial hypertension and the REVEAL registry, there's almost a three year delay in diagnosis from the time a patient develops cardiopulmonary symptoms to the point B, which is when they actually have a formal PAH diagnosis. Three years. Those three years are met with seeing different specialists, being in and out of the hospital, having a worsening quality of life because they’re always short of breath and overall just poor more prognosis. If we take that, do we have that exact number when it comes to PH-ILD? No, but we do have an extremely wide range of epidemiology when it comes to PH existence with ILD. PH can range anywhere from 12% to 86% in ILD patients. Why do you have such a wide range? That's because we don't know when to look. We don't know how to look. A lot of times we don't even look and we're getting a lot of that data that 86% is sometimes showing up on autopsy results and transplanted patients.

Then, we're looking back at those autopsy or transplanted lungs and saying, "Oh wow, those patients not only had ILD, they actually had PH as well." That's not something to necessarily be proud or happy about. So it kind of is in the same boat as, what is our delay in diagnosis? What is the window of opportunity that we need to really diagnose and intervene so we can make a difference? There will be a point of no return when it comes to ILD patients with PH. The same way there is sometimes a point of no return with PAH where the patients get so advanced that they're meeting them in the intensive care unit and they're meeting them really on what we call rocket fuel. These patients are looking for the Hail Mary to get better. You're not meeting them in the office, you're not trying to do a 6 minute walk test on them these patients can't even do a 6 minute walk test when they're sometimes at that point of no return. So really what is the sweet spot? I think it is trying to mirror what we went through with PAH several years ago. Developing a registry, understanding more of the referral patterns for PAH and we're trying to extrapolate all of that information and bring it now into this PH-ILD space, as well. 

I know I'm speaking to a lot of the providers and doctors who are involved with taking care of ILD patients, but really switching gears and thinking about it from the patient perspective. If you're a patient who has been diagnosed with any of the many subtypes of interstitial lung disease, I think it's important to be aware of this concomitant process that can occur and that can develop, which is pulmonary hypertension. It is difficult to tease out when you have worsening cardiopulmonary symptoms, worsening breathing symptoms. Is that the interstitial lung disease? Or is that something new such as pulmonary hypertension? I think it's important to think about that and be open with your provider, with your specialist, with your pulmonologist and say, "I'm now feeling this way, and I'm now using this much more oxygen, and wasn't my 6 minute walk distance this far last time and now it's down to this time? Could this be something else? Is this just not necessarily worsening interstitial lung disease or is this a second process?" A second process that now we know we can treat and we can make better. I think that's important to sort of think about. You can be your best advocate when it comes to going into your provider's office and really telling them exactly how you're feeling, and what you're feeling, and how it's different from prior.

My name is Dr. Raj Parikh, and I'm aware that my patients are rare.

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