Kevin Kunzmann

Artificial intelligence (AI) and deep machine learning, previously theoretical proposals of the future of industries, are making a real-time impact in pockets of medicine. In the case of advancing care and diagnostics for a collection of rare, chronic lung diseases, these rapidly evolving tools may make a world of difference today.

, American Lung Association (ALA) chief medical officer Albert Rizzo, MD, discusses the advancement of AI and data learning in the 200-plus 

 including idiopathic pulmonary fibrosis (IPF). 

He’s joined by Simon Walsh, MD, a consultant thoracic radiologist and clinician scientist with the National Heart and Lung Institute at Imperial College in London, and Elizabeth Estes, executive director of the Open Source Imaging Consortium (OSIC).

Walsh and Estes walk Rizzo through the founding of OSIC, and the role itself and fellow data networks are providing to the various clinicians and researchers looking for an upperhand on the burdensome and elusive effects of ILDs on patients.

Prior to their conversation, Rizzo also reviews the centuries-long history of applied AI, beginning with the illustrious career of mathematician Alan Turing.

Lungcast is a monthly respiratory health podcast series from the ALA produced by 

Subscribe or listen to Lungcast on your favorite platforms:

https://open.spotify.com/show/1F3u1hKrwxi9snSQ0q3nti

https://podcasts.apple.com/us/podcast/lungcast/id1524712350

Articles

Simon Walsh, MD, and Elizabeth Estes join Lungcast to discuss advancements in biomarker and treatment option deliberation for the rare disease through data.

How AI, Machine Learning Are Providing an Edge on Interstitial Lung Disease

New late-breaking data presented this month at the European Academy of Dermatology and Venerology (EADV) 2022 Meeting showed distinct inflammatory characteristics in adult-onset atopic dermatitis relative to standard, child-onset 

The data, presented by Paola Facheris, PhD, a post-doctoral fellow at the Laboratory of Inflammatory Skin Diseases at Icahn School of Medicine at Mount Sinai, contributes to an evolving understanding of how increasing rates of adult-onset atopic disease is activating—and how clinicians may potentially tailor treatment for it.

 during EADV 2022, Facheris discussed her lab’s research into atopic dermatitis pathology, these latest findings, and the implication of recent clinical drug development as it relates to the growing disparity between child-onset and adult-onset atopic dermatitis.

 First and foremost, could you help us define our known history and interpretation of TH1 and TH2 activation in atopic dermatitis?

 In our lab, we wanted to first explore the different phenotypes and endotypes of atopic dermatitis. Our lab is well known for this kind of research. Before talking about TH2 and TH1 pathways, I would like first to define what kind of disease we're talking about. We're talking about atopic dermatitis, but in this case, we are considering atopic dermatitis in the adult populations. So classically, atopic dermatitis is known to be a childhood disease. However, about 7% of the adult population suffers from atopic dermatitis. But, we can make a distinction between the age of onset of atopic dermatitis in the adults. 

So, it was thought until 20 years ago that most of the forms of atopic dermatitis that we see in the adult patients are the ones that start in childhood, and they are persistent or remitting in the adult age. But about 20 years ago, for the first time we used the term "adult-onset atopic dermatitis," meaning that there are patients with atopic dermatitis that have symptoms for the first time after 20 years of age. So after that, for about 20 years, there has been a lot of reports about this kind of atopic dermatitis, and what it looks is this subtype is different from the one that's started at childhood, in terms of risk factors and clinical appearance. There are typical forms, where we have involvement of the head and neck area, the hands and feet, and we have atypical forms, in terms of clinical appearance. 

So our lab started from the questions, "Is this form of atopic dermatitis similar to the one that started in childhood or is it different? What is the molecular profile of these 2 diseases?" So we started from these questions, and we analyzed the transcriptomic profile in skin of these patients and we analyzed the proteomic expressions in serum of the patients. So, atopic dermatitis is known to be a TH2 and TH22 disease, meaning that we have a hyper activation of all the cytokines and interleukins related to this pathway—like IL-4, IL-5, and IL-13. 

And what we found out is that both diseases share these common upregulations. They both have a strong TH2 and TH22 upregulations. However, the magnitude of these changes is higher in the form since childhood, and we have a modulation of the other immune pathways. So the form of atopic dermatitis that we call pediatric-onset atopic dermatitis is not only TH2 and TH22, but it's also TH17. And on the opposite side, the form of atopic dermatitis with adult onset is more of a TH1 component that we don't see in the pediatric one. And this TH1 component is present in lesional skin, in no lesional skin, and also in the serum of these patients. And we have a very nice correlation between the TH1 markers in serum and skin of these patients, meaning that this pathway is contributing to this disease and is something atypical of this form of atopic dermatitis.

Our interpretation and valuation into these inflammatory pathways as they're impacting patients with atopic disease, such as adults with atopic dermatitis, is hugely implicated given the state of available, emerging and investigative biologics in the space right now. Is this something that there's any potential agents within consideration or for proposal that could address this pathway more directly?

 I mean, we are in a lucky period for atopic dermatitis. There are a lot of agents that are in the pipeline, about to be released on the market or under investigation. So this is a good moment for atopic dermatitis. I would say dupilumab—we know it's the first biologic that was approved for atopic dermatitis, and is targeting mainly the TH2 pathway. So in this case, dupilumab is indicated for older dose form with TH2 upregulations. But, in case of adult-onset atopic dermatitis, ideally, you would want a drug that is able to target also the TH1 pathway. So, something that has a more broad effect—like for example, JAK inhibitors could be good drug, or those drivers that are able to impact the T cells regardless of the pathway they belong to, for example, OX40, it's a good target for these patients or CCR4 can also be another good target.

Speaking of dupilumab, they had a very significant indication achieved within treating atopic dermatitis earlier this year: the youngest eligible pediatric population, aged 6 months to 5 years, received FDA approval in the US. Obviously, with these findings, it would probably elucidate the question of whether we would see greater benefit nonetheless for our adult-onset atopic dermatitis patients. 

Would these findings begin to better influence guidance, even guidelines and recommendations, for treatment and care strategies within atopic dermatitis as these drugs become available across all the age populations?

 Yeah, exactly. That's exactly the point. We will have a lot of drugs on the market, and being able to characterize the disease, being able to choose the right molecule for the right patients will be the goal. Dupilumab, exactly like what you were saying, is a great drug. It's safe, it is suitable for all ages. That's what we have learned. However, when it comes to difficult populations, like adult-onset atopic dermatitis it's possible that dupilumab won't be able to cover this TH1 activation. So that's the main reason why we need to stratify the patients and we need to find the right target for each of them.

As we understand it, pediatric allergic and atopic disease is increasing annually. It really warrants the need for such expansion of availability—obviously, better diagnostics, better interpretation of biomarkers and observable risks. We stay focused so much on the inherent and developed risk at early stages for atopic disease. 

Is it something that we're also seeing increasing in adults as well? Is adult-onset atopic dermatitis on the rise?

 It is exactly like you are saying. We see an increase not only in the pediatric population, but also in the adult population. In the United States 26% of all the adult patients that suffer from atopic dermatitis report an adult onset of the disease. But in other countries like Italy, up to 60% of patients report this kind onset of symptoms after 20 years of age. So it's something that we need to pay attention to. We need to ask the patient, to investigate their story, to see if they have any had any risk factors or any personal history of atopic dermatitis. But apparently, this is something that is emerging and increasing. I think dermatology should be more aware of this form of atopic dermatitis.

New EADV data suggest clinicians may need to uniquely treat patients with adult-onset eczema based on inflammatory pathways.

Paola Facheris, PhD: Distinctions in Adult-Onset and Pediatric Atopic Dermatitis

The US Food and Drug Administration (FDA) has approved aprepitant injectable emulsion (APONVIE) for the prevention of 

The new approval makes the Heron Therapeutics agent the first and only intravenous (IV) form of aprepitant indicated for preventing nausea and vomiting in patients who underwent surgery. The single, 30-second, 32 mg IV injection dose has been shown to provide therapeutic plasma concentrations for ≥48 hours, according to Heron—providing an efficient response to increased risk of post-operative nausea and vomiting associated with 36 million surgeries conducted annually in the US.

Heron’s application to the FDA was supported by the results from a pair of multicenter, randomized, double-blind clinical trials comparing oral aprepitant to standard-care IV ondansetron injection, in patients at risk of post-operative sickness following open abdominal surgery. In the 48 hours following surgery, aprepitant was associated with 50% fewer patients vomiting than ondansetron. The oral form of the drug was also associated with a favorable tolerability and safety profile.

Approximately 3 in every 10 patients receiving general anesthesia experience post-operative sickness, which is among the greatest drivers of patient dissatisfaction with surgical procedures. It’s also associated with increased hospital stays and prolonged procedure recovery, Ashraf Habib, MBBCh, MSc, MHSc, chief of the division of women’s anesthesia at Duke University Hospital, said in a 

“Oral aprepitant has been used to prevent postoperative nausea and vomiting for more than 16 years and it is exciting to see that, with the approval of APONVIE, physicians can now offer patients a more convenient IV injection that delivers the same effective treatment, with a 48-hour duration of effect, in a rapid, consistent and reliable way, ensuring a better experience for patients postoperatively,” Habib said.

Barry Quart, PharmD, chairman and chief executive officer of Heron, said the new approval provides clinicians an “easy to use, highly effective option for these patients that fits seamlessly into our acute care franchise.”

The approval is based on data from 2 clinical trials showing the agent improved the rate of post-operation patients avoiding sickness by 50%.

FDA Approves Aprepitant IV Injection for Post-Surgery Vomiting, Nausea Prevention

As the treatment fields for immunologic diseases including 

 continue to broaden, investigators are seeking patient-tailored agents that fill cracks of care and refine current standards of therapy: what treats a patient for longer, better, and with an even greater rate of benefits?

A potentially emerging option in atopic dermatitis may be rocatinlimab, a molecule designed to inhibit OX40 that is currently in mid-phase trials.

 during the European Academy of Dermatology and Venerology (EADV) 2022 Meeting last week, study author Emma Guttman, MD, PhD, System Chair of The Kimberly and Eric J. Waldman Department of Dermatology and Director of the Center of Excellence in Eczema and Laboratory of Inflammatory Skin Diseases at Icahn School of Medicine, discussed her team’s new research into rocatinlimab, the components of the new potential agent, and the importance of their key outcomes in assessment.

HCPLive: Before we go into the clinical data, can you talk a bit more about rocatinlimab, its makeup and composite benefit? What exactly are we hoping to observe from this molecule?

So this is a monoclonal antibody that is exciting, because it's a novel class of drugs. The targeting is a novel way to target atopic dermatitis. OX40 is involved in memory T-cells, and particularly activated in type 2 cells. When this study was designed—and I'm actually happy that I was part of that design, and I think we designed it smartly, I want to say—we already thought about the fact that maybe because of the potential involvement of memory cells, this may lead to long term efficacy. And we thought to design it in a way that will assess disease modification.

What new data were presented at EADV 2022?

So the study has parts 2: Part A, in which the endpoint was at week 16, and part B that started at week 18 in which the patients on placebo were also put on drugs. So the primary endpoint was at week 16 but then the secondary endpoint was at week 36, after the placebo patients also had the drug. At week 36, everybody had started treatment, and then there was another 20 weeks of follow-up to assess for that long-term efficacy. And what we saw is that while the drug achieved in all dosesthe primary endpoint versus placebo, it's a drug that continues to improve over time. There is not a plateau at week 16. In fact, the efficacy was much better at week 36. And the patients who switched to the drug from placebo also improved a lot in that time. But importantly, at week 36, we saw that the highest 2 doses maintained the efficacy in about 90% of the patients, if not a little more than 90%, in the highest dose for about 20 weeks, which is really unusual. We don't see that with other drugs—that maintenance of response. And that is very meaningful because there is this potential for disease modification.

So, it had biopsies at baseline and weeks 8, 16, 36 and most importantly at 56—which is so unusual, because it's after you stop the drug. And then we had blood-based assessment from North America. So first, the biopsy study and the blood study both showed the same thing. They showed very robust manipulation of biomarkers, and continued increase toward the end of the treatments at week 36. There was a very big differentiation between drug and placebo at week 16, very clear-cut not only in lesional skin but also in non-lesional skin. And then we saw that the placebo patients that were put on the drug at week 18 started improving until week 36. But the unique thing about this drug is that the patients that stopped the treatment still maintained efficacy in biopsies. So that, I think is unique to this drug and I'm very excited about this presentation.

What is the rationale behind assessment into head and neck dermatitis with rocatinlimab?

Head and neck (atopic dermatitis) is an area that is very important for patients, and with existing drugs sometimes the head and neck is not fully controlled. And there are some reports also that dupilumab for example, causes head and neck rashes. And the reason being is that dupilumab targets the type 2 immunity, but may not target well type 1 immunity that is involved, for example, in contact dermatitis. And rocatinlimab, from preliminary studies, seems to target both TH2 and TH1 immune pathways. And this is why we think that while it works well on atopic dermatitis, many of the patients with atopic dermatitis may also have contact dermatitis, and it may cover that as well. So what we showed here is that patients that were under studies and have moderate to severe involvement of the face, the drug works very well and there was a delta between improvement in the drug and placebo that was significant and meaningful to the patients. And we believe that this drug may provide a very important avenue for all patients with eczema, but definitely also to patients with facial eczema.

What are next steps with regard assessing rocatinlimab? Are there other regions impacted by atopic dermatitis that you'd consider assessing? Is it a long-term assessment? Where do we go from here?

This drug works very well on the entire party, but sometimes you want to locate areas of special interest. So, the face is a very important thing for patients. Another important place for me is the hands and feet. These are areas that are usually more difficult to treat, but particularly the face, you know, that's your business card, right?

The novel OX40 inhibitor molecule showed significant benefit for patients in new EADV 2022 data. A lead author discusses its potential.