Jennifer Keeley, DPN and Mary Whittenhall, MSN - phaware® interview 550

Jennifer Keeley and Mary Whittenhall, experienced nurse practitioners in the field of pulmonary hypertension, discuss the management of cough in patients receiving inhaled therapies for pulmonary hypertension and interstitial lung disease. #GossamerBioPartner #sponsored

This Special Edition episode is sponsored by Gossamer Bio.

Jennifer Keeley, DPN:
My name's Jennifer Keeley. I'm a nurse practitioner and I practice in a large academic institution in Pittsburgh, Pennsylvania, Allegheny Health Network, specifically Allegheny General Hospital. I am a nurse practitioner there and have been in the clinic over 10 years, and in the PH space as a nurse practitioner for over 15 years, as a registered nurse for almost 20 years. So, I have a lot of experience and I'm really excited to be here today to talk about inhaled therapies and cough.

Mary Whittenhall, MSN:
My name is Mary Whittenhall. I'm also a nurse practitioner. I am currently an advanced practice provider at Pulmonary and Sleep Associates in East Providence, Rhode Island. I've been in pulmonary hypertension for about 11 years now. In that time, I have worked in a variety of settings, both inpatient and outpatient, managing patients with pulmonary vascular disease, and have also touched upon patients with interstitial lung disease and pulmonary hypertension. 

I get very excited when I hear about new opportunities for our PH patients. I think a lot about even when I started in pulmonary hypertension and the therapies that were available to our patients. Many of these therapies had been around for a little bit of time. But also something that I think is extremely exciting is that there's just been a rapid progression in development of therapies. And now, with the focus of looking at these therapies as potentially disease modifying, not necessarily slowing the progression of disease.

With the advent of all of these new therapies, there become more options for our patients, as well. Often, patients can't tolerate some of the medications that we have due to side effects and despite lots of work to manage these side effects, the patients are not always successful. One of the great things being involved in an academic center is that we have the ability to help link patients to cutting edge research, particularly looking at a new drug that is an inhaled therapy that has shown significant promise in improving the lives of patients with pulmonary hypertension.

As a part of the PH community, we all do quite a bit of networking with each other, as well as with our patients and other colleagues in the space. In that time, we did network regarding the study and have participated in some activities where we're looking at the data from the Phase 2 part of this trial and then also looking at some of the side effect management related to the medication, which seemingly is well tolerated. However, for some patients it may not come extremely easy.

I think that's where the role of the nurse or the advanced practice provider really comes in this space is that we have a real strong dedication to helping educate patients about ways to manage these side effects. We want patients to be able to continue with therapies. We don't want them to say, "Well, this isn't working for me, it's time to move on." I think that we have a lot of strategies and a lot of experience with trying to help patients really figure out the best way to manage these things and to be confident that they can continue on with obviously the biggest benefit of improving their pulmonary vascular disease.

Jennifer Keeley, DPN:
We actually met at an advisory board last year. It was an advisory board consistent of registered nurses and nurse practitioners who, just like Mary and myself, have vast experience with patients and therapies, not just in the inhaled space, but more conventional pulmonary vasodilator medications that have been used in our patients for many, many years. As Mary had suggested before, when we start to think about newer agents, many, many of them are not the conventional pulmonary vasodilator medications, but disease modifying agents. Now, we've acquired an armamentarium of medications. So, inhaled delivery is just a really great option to avoid systemic side effects on top of each other.

Our PH patients today, many of them are on more than three therapies, many of them are on four or even more therapies, so the delivery of the medication is just one aspect. When we talk about cough and side effects, I like to think about it and explain to my patient when we talk about side effects, particularly cough, to imagine a Venn diagram with cough being in the middle and what affects cough. You see this outward circle, how we deliver it, what kind of device we deliver it in. The drug, how small, large are the particle size? Is it easy enough to use for our patients? The formulation, is it dry powdered versus inhaled aerosolized?

And then finally, just the patient themselves. What's their background? What type of PAH do they have? So, we can talk a little bit more about this, but just to get us started, this is how this developed and we had a lovely advisory board meeting with seralutinib and Gossamer Bio, and this was the outcome of it. We produced a lovely poster. This is a conversation if you will, that Mary and I are going to have based on what we talked about and the poster production, that came out of that wonderful advisory board.

Mary Whittenhall, MSN:
Inhaled therapies are unique in a way in that they actually have direct access to the lungs. So, when you think of an oral medication, an oral medication needs to be digested in the gut and sometimes that systemic digestion takes a while. Additionally, it's also often that we see patients that have more systemic side effects when we're using an oral formulation. Intravenous or subcutaneous formulations of these medications tend to cause pretty strong systemic side effects for patients, and there tends to be a lot of management that we need to do to help make these side effects more tolerable. For most of our patients, I say to them, "You're going to think I'm cruel because I don't really want these side effects to go away." In a way, we look at them almost as if you have a cup and your cup is full of water and after the top of the water hits the rim of the cup, then the water starts to spill over onto the sides of the cup.

I think of other medications that we typically prescribe for patients in that way that when we get that spill over, so to speak, it's an indication that we've actually targeted all of those receptors that we want to help with vasodilation. Now that we're looking at other medications that don't really necessarily look at vasodilation, we're looking more at treating the blood vessels in a different way or affecting the process for which those blood vessels become diseased. I think that the side effects become different and I think they become less.

In working with inhaled therapies, as you can imagine, the number one side effect that most patients will complain of is cough. Sometimes we have patients who have an underlying cough already, and that's usually not related to PAH, but in PH-ILD where we now have an FDA indication to use another inhaled therapy, we've seen in treating these patients that baseline cough is something that is extremely problematic for them before they even start therapies. So, trying to find ways to improve that baseline cough, treat any underlying symptoms, things like acid reflux as well, that may cause that, treating seasonal allergies, et cetera, and then, obviously, managing any additional overlapping side effects that may occur because of the new therapy that they're on.

Jennifer Keeley, DPN:
I think that's a really important part, is to talk with the patient, educate the patient on these inhaled therapies. First and foremost, that cough is almost an expected side effect. These are patients particularly with our interstitial lung disease patients that have PAH, cough is a part of their daily life. It's important to document and ascertain what these patients' baseline cough is. In many, many clinics, particularly pulmonary PAH clinics, and I'm sure much like Mary's, many of my colleagues have recommended using validated cough questionnaires so that we can get a really, really good baseline of what that patient's baseline cough is.

Are you coughing at night? Do you have mucus? How long have you been coughing? Does it interfere with the quality of your life? Do you cough at night? Does it keep you up? Does it interrupt your sleep? Those kinds of things that help differentiate acute cough versus chronic cough. Many of these patients cough every day. They also have other inhaled therapies such as our ILD patients that are also on corticosteroids, many of them on inhaled corticosteroid therapy that can thin the oral pharynx, the posterior pharynx, and really affect the degree of nerve innervation in the posterior pharynx in the mouth.

So, just really understanding what the patient's baseline cough is and educating them on the fact that cough is likely going to be a side effect with the use of this inhaled therapy. Certainly, as we continue to use the therapy, we would hope that the cough can be mitigated either through some lifestyle modifications, some natural remedies, and even some medical remedies such as bronchodilators. But really teaching the patient about the medication and inherently that this is likely going to induce a cough, but that we have mitigation strategies to help dissipate the cough.

I always like to tell my patients also in the clinical trials, particularly the Phase 2 clinical trials that are out there that patients had a lot of cough. The patients on drug that were in most of the Phase 2 clinical trials for seralutinib and even for treprostinil inhaled, 30 to 40% of them experienced cough. But at the same token, the placebo-based patients that did not receive drug in these Phase 2 clinical trials also had a lot of cough. So, what that's telling you is yes, you're going to get probably some more cough, but it's likely not going to be that much or more far advanced than the cough that you're already experiencing.

I also think it's important to tell these patients, many, many patients that experienced cough did not stop the medication. Actually, in these Phase 2 clinical trials, very few stop the medication. So, that gives you a really good big picture that we are pretty good at educating our patients how to mitigate cough, and if we aren't, then we should learn how to do so.

Mary Whittenhall, MSN:
I think it's important for us to set some expectations for patients when we're talking about cough. We've already discussed a bit that cough can happen for people from other things outside of their lung disease, but it's important to also look at what may be causing the cough when we are giving a patient an inhaled therapy. So, any type of inhaled therapy, whether that be a dry powder, a mist, whether that's nebulized or through in actuated inhaler, there are particles inside of that medication as it's going in and those little particles, when your lungs inhale that medication, those particles are penetrating your lungs and your lungs are not accustomed to them being there.

It's almost as if your lungs are saying, "I don't recognize this. I don't know why this is here," and it may feel like it's an irritant, so you may start coughing as a result of that, but the cough is not necessarily a bad thing. Those particles are there, and the job is to essentially help deliver the medicine to penetrate that lung tissue and then for your body then to absorb the medicine. Your airways and your blood vessels inside of your lungs are extremely close to each other. So, when you inhale that medication, those little blood vessels are also right next to where those airways are, and then that is how those blood vessels then absorb that medication, because they're so close to the site at which those particles come into your lungs.

Jennifer Keeley, DPN:
I think this is an important concept to understand. They choose the form of delivery based on the goal of delivering the most medication efficiently to the distal bronchioles. That's where the disease is. It's in the distal arteries. So, trying to formulate how we get these very powerful, oftentimes disease modifying agents into the periphery of the lungs can be very challenging. Dry powdered inhaler is one form that the variability of delivery is not as dispersed as an aerosolized. So, it's more efficient delivery to the place where the medication needs to work the best, and that's in the distal periphery of the lungs.

Unfortunately, one thing you have to deal with is that oftentimes these medications, dry powdered medications, not just in the PH space, but there's a lot of other dry powdered inhalers in the COPD space, as well. Oftentimes, what happens is these powdered particles get dispersed extra thoracically. So, they get dispersed in the oral mucosa, in the posterior pharynx, on the way down into the stomach. That's wherein we have to deal with mitigating side effects. The biggest side effect of these particles, even though they're very small, is cough. So, technique comes into play. Mitigating things to coat the posterior pharynx come into play. Re-education comes into play. Show me again how you're doing this inhalation, because I don't think that you're holding this okay.

In one instance, I had a patient that was inhaling dry powdered inhaler with the medication right out of the refrigerator. So, the medication was cold. It was clumping at the back of her throat. All of these things really take into consideration how we most efficiently get the medicine to these pulmonary arterial hypertension patients where their disease is oftentimes very difficult to get to, and other forms of medications that are systemic, orals, parenterals that have first pass metabolism, and so you're going to get more side effects from those medications. So, I always teach my patients, "Hey, we're a couple steps ahead because we're bypassing the type of metabolism that you get with orals and even parenterals."

Mary Whittenhall, MSN:
There are so many challenges that these patients face. Oftentimes, patients have never been sick before they develop this, and now we're putting them on multiple therapies, multiple modalities, telling them that there's going to be side effects and they need to learn how to manage them. It's certainly a lot to handle. But I think one of the best things that we have in our PH community is that we really work so hard to partner with the patients and their loved ones and forming this relationship, fostering that relationship as time goes on, I believe that these patients really do trust us and that what we're telling them is things are going to be okay. We are going to be there by your side. We're not going to give you this medicine and then say, "See you in six months. Hope everything goes well." We're really going to be working with them.

In some cases in my specialty clinic, we have nurses, we have a pharmacist, a pharmacy tech, and then our advanced practice providers that check in with these patients quite regularly. We are actually taking the initiative to reach out to them versus the patient who may be having trouble advocating for themselves or feeling like, "Really, I don't want to be a pain, but this is challenging for me." We are really in touch with them, and that connection also helps to keep patients on therapy.

So, what are some of the specific techniques to manage or mitigate cough? This is something that was a real hot topic at our last advisory meeting. We put together a bunch of folks in the room who deal with other inhaled therapies and patients that have cough and said, "Well, what do you tell patients to do?" First and foremost is to look at any other potentially underlying conditions that may be causing cough and ensure that treatment of those underlying conditions is optimized. I think cough is actually the number one referral for any type of pulmonary practice, but it is a really, really broad differential when it comes down to it.

We obviously look first at things like environmental factors. If this could be seasonal allergies, then we try treating patients with antihistamines. Perhaps some of those are intranasal, as well, that may help with some things like rhinorrhea or post nasal drip. Acid reflux is actually a huge, huge reason for cough. Many patients say, 'Well, I don't get acid reflux. I don't feel that burning in my chest after I eat," but come to find out that it can actually be a silent trigger. So, treating patients with medicines that help to reduce acid or suppress acid will oftentimes help with that cough.

On top of that, when we're dealing with patients that are on inhalers and now we're adding another inhaled therapy. I find that for some patients that are on actual inhalers that sometimes they do better with nebulized treatments. The nebulized treatments are slower, and may have a bit of a better penetration into the lungs and the patients tend to like it. It is one of those things that you do need to be compliant with in order to really see the benefits to it. I will say that oftentimes, again, partnering with the patient, giving them specific instructions about how to do all of this, we can really see some improvement to those symptoms.

Then, there's just basic over-the counter measures and precautions, things like making sure that when you're eating that you're not laying down at least for 60 minutes after you've been eating. If you do have acid reflux, trying to sleep with two pillows or a wedge pillow, that can help to keep the head of your bed elevated. Some of our patients have those really fancy adjustable beds that are also quite helpful for that. I think that sometimes things like basic cough drops actually can be quite wonderful and helpful. Drinking very cold or very warm water or tea, adding some honey to that if a patient isn't diabetic, things like that tend to really help with cough. We reinforce these measures when we start therapies like this.

Jennifer Keeley, DPN:
In terms of mitigation, I think it's really important on technique. This is why, as Mary had alluded to, it's so important to follow up closely with these patients, particularly our elderly patients who sometimes don't, if they have connective tissue disease or scleroderma, have a lot of good fine motor coordination. A couple of things that I wanted to touch on with regards to that…

One, these inhalers are typically high resistance, low flow. So, these are not the type of patients that need to be taking in very forceful inhalations with these inhalers and thank goodness, because we're talking about patients that have inflammatory interstitial lung disease, as well as pulmonary vascular disease. So their degree of inspiratory effort is actually minimal to disperse that medication to the distal pulmonary bronchials. It's equivalent to them taking a deep breath in when you ask them to auscultate their lungs. So it's not a big forceful breath.

The other thing is too, a lot of times, sometimes more variability in the disbursement of the drug is better in compliance with some patients. Dry-powdered inhalers, again, do not take a very big forceful effort, but some of them, because they are powder, some of the medication will actually hit the back of the throat as it goes down and can cause some irritation, whereas the nebulized form does have a variability in disbursement and can be more easily tolerated in some.

The other issue is the technique itself. Oftentimes, we ask them in some of the inhaled therapies to lower the device itself so that the tongue doesn't protrude and get in the way, because if medication gets on the tongue, the next swallow that they take, that medication is going to hit their posterior pharynx, and they're going to probably cough pretty aggressively.

I always start off by telling my patients, "Cough is not a bad thing. It's actually a protective reflex and it's involuntary. So, if you cough, don't actually negate it. Don't think it's a bad thing." It's actually a very protective mechanism that avoids irritation in most of our patients probably already irritated mucosa. So, that's how I like to start the conversation. There's so many good techniques that we can share with them over time, and I might add that each patient is different. Each patient needs to have a personalized plan.

When we talk about giving patients warm tea, typically chamomile, chamomile tea in itself is anti-inflammatory. Then, when you add something like honey, which is also a soothing, anti-inflammatory natural remedy, you have to really think to yourself, "They're getting honey. If they're diabetic, we don't want to give them too much honey." But, you have to make sure that their swallowing technique is good. There's no aspiration there, particularly if we give them cough drops. Then, just simple things that actually numb or anesthetize the back of the throat are very, very helpful for elderly patients who do have very friable tissue and mucosa from previous therapies like inhaled corticosteroids, as I had talked about before.

Dairy products, I tend to ask my patients to avoid those. They can produce a lot of mucus, which these coughs that we see in our inhaled therapy patients are typically tend to be dry coughs, but some patients that have concomitant asthma, COPD, along with their ILD that are using these inhaled therapies can actually have more of a congested mucoid cough. So, avoiding dairy before and after use is always very smart. Avoiding alcohol, avoiding acidic drinks like orange juice, also very, very helpful.

Mary Whittenhall, MSN:
The part about technique I think is so, so important here. Oftentimes, when patients start these therapies, when they are approved in that space, the specialty pharmacy has a nurse educator that will come out to the patient's home and provide education not only about the medication, but about the administration of that medication. In many cases, the patients will take their first dose while the nurse is present so that the nurse can then critique whether or not the patient took it appropriately and how they tolerated it.

I'm going to give a shout out to our nurse educators from the specialty pharmacies, because they are also a really crucial set of eyes and ears for us out in the community. They do provide education to the patients in the home. We have had situations where the patient has done well while the nurse is there, and then two weeks later we get a call from the patient saying, "I can't do this. This isn't working for me." And I'll say, "Okay. Well, you have a couple options. We can have you come in to the clinic and I want you to bring your device with you, and I would like to watch you do a treatment, or I can have the nurse come out and see you again and go over that." And they'll say, "I already know what I'm doing. I don't need that." But in many instances, we have found that they have adjusted their technique. They might've gotten into some bad habit since the nurse has left them. So, really reinforcing that is important.

The other thing that I wanted to bring up is that some of our patients with connective tissue disease also have thickness in their tongues. So, their tongues become thicker and more sclerotome as their connective tissue disease progresses. For some of those patients, it is actually hard for them to get their tongue flat enough so that they can get the medication down into their lungs. So, working with those patients to find strategies to help rectify that. I will say that it is not impossible, it just takes maybe a little extra work.

Jennifer Keeley, DPN:
Inhaled therapies in themselves are pretty portable. Mary had alluded to a little bit earlier, our patients with pulmonary vascular disease, PAH, that are on parenteral therapies, delivering the conventional pulmonary vasodilator therapies. As we get into the new disease modifying agents such as seralutinib, which are anti-fibrotic, anti-inflammatory, anti-prolific medications, these are portable therapies that are actually modifying the disease. So they're portable. They're easy to use. They're easy to use for our patients, again, that are elderly or are younger and are still working, they have a professional life, they don't have to wear a pump that's 24/7 oftentimes. They can use these inhaled therapies first to see if they can avoid parenteral therapy with prostacyclins.

Their quality of life is improved immensely. When you can take an inhaled therapy two to four times a day and really improve quality of life, decrease cough, decrease dyspnea, or shortness of breath on exertion. Sometimes, these patients that do very, very well can actually reduce their supplemental oxygen needs. Just improving their walk distances without having to stop or have excessive dyspnea, improves their quality of life. More time spent with loved ones and more time spent in social environments rather than sitting at home. These wonderful inhaled portable therapies have significantly changed our patients' lives and improved their quality of lives.

Mary Whittenhall, MSN:
This community I think is phenomenal. It's made up of so many great people. There are many patients who have been a part of this space for a long time who really want to help other patients who may be newer to the journey than them. I'm a big advocate for support groups. We've had an extremely active support group in our area for a long time, and I often partner some of my patients that have been with me for quite some time with some of the new patients that may need a bit more help. I can tell them things and my colleagues can tell them things. Oftentimes, the same message doesn't resonate. It resonates differently, I think when it comes from a peer, a patient who may have experienced the same thing as them.

One of the things that I really try to drive home with our patients is just that sense of empowerment. Connect with these other folks in the community. They want to help you. They remember what it feels like being newly diagnosed or starting a new therapy or transitioning from another therapy. What that change is like.

One of the other things I tell my patients is that we all sit at the same table. I'm not better than you. Maybe I have this information, but this information is for you. It's for you to take and to improve your life. If that information doesn't work for you, then you come back to me with some feedback and we come up with something else that's going to be more helpful to you.

I really think having an equal playing field with them and having a very open and honest dialogue is what is going to help our patients do the best. If patients don't feel comfortable reaching out to other local patients or connecting with an in-person support group, there are tons of online resources through the PHA, through phaware®, Team Phenomenal Hope, lots of great groups out there that do things virtually. I think in some ways for some patients, anonymity is important, so being able to protect that is an option for them, but to be able to still get what they need so they can become the best advocate for themselves that they can.

Jennifer Keeley, DPN:
I stress so importantly to my patients, we are here today in this great environment and we have the armamentarium of medications to treat because of patients just like you that have contributed to the science of the disease and implemented themselves and engaged in these clinical trials. Right now we have an ongoing clinical trial for seralutinib called PROSERA, that's enrolling as we speak.

Patients are the best advocates, not only for themselves, but for other patients, and they talk. There's a lot of social media out there where patients communicate amongst themselves and they say, "Through the help of my provider and through the help of my family, I was hesitant to start this additional therapy." They do have, at this juncture, and I don't think it's such a bad thing, they do have a little bit of a pharmacy burden now. Again, these aren't our patients that are on one or two therapies. They're on four or more oftentimes. When you take in our ILD patients, they're also on disease modifying agents, as well, for their interstitial lung disease. So again, I think it's really important for patients to communicate amongst themselves and share their ups and downs in the disease, but also share the rewards that come with surviving and living with PAH.

I think one thing that we really do have to understand though is like many other chronic diseases, PH is a personalized disease. You need to have a personalized approach for your patients. That's why it's so very important to do a really good history of your patients and understand not only what their baseline cough is, but who they are, what their personal history is. Are they working? Who's helping to care for them? Who's helping to make that chamomile tea with honey? Who's going to the store to get that? A personalized approach is so important for these patients, I can't stress that enough.

Mary Whittenhall, MSN:
Special thanks to everybody involved in this project. This was extremely exciting. To my co-podcaster, Jennifer Keeley, who is amazing, and all of us in the PH community are extremely lucky to have her. We are all aware that you are all rare, and we are grateful to be able to help you in this journey.

Jennifer Keeley, DPN:
Thank you so much, Mary, and what a pleasure it's been to speak with you about cough and inhaled therapies, and thank you to Gossamer Bio for this opportunity and for the opportunity that led to this podcast, which was a significant advisory board amongst specialists in our field, advanced practice providers and registered nurses who were able to convene in a great open space and talk about this. I think this moves our science forward. It helps us to talk about the disease and take better care of our patients. Again, my name is Jennifer Keeley. It's been such a pleasure to deal with my good friend Mary Whittenhall today, and we're aware that our patients are very rare.

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