Dr Louie: I have been tasked with this session here. I actually would like to dispute the title. I think it should be clinician-directed diagnosis and assessment. You can probably guess I am not an advocate for artificial intelligence.

[00:29:34]

What Is Severe Asthma?

It is very important to remember that medicine is a practice. This really becomes very important when we talk about severe asthma, because all of you have experience and expertise. You know that regular asthma, as Jennifer referred to, is over-diagnosed and therefore overtreated. In other words, a third of people who have this diagnosis of asthma do not have asthma.

They are receiving none of the benefits of inhaled corticosteroids. On the other hand, severe asthma, which we will try and define now, is underdiagnosed and undertreated, and it is a specific asthma phenotype. We know that asthma is not a single disease today in 2025. Back in the 1970s, we were under the assumption that asthma was either allergic or non-allergic.

There is so many different types of asthma. For our discussion here, severe asthma is asthma that remains uncontrolled despite correct use of high-dose inhaled steroids together with a long-acting beta two agonist. We are talking about treatment plan failure, not the patient's failure or your failure. The plan has failure. You can recognize this when patients have more than one exacerbation a year, 70% of exacerbations are usually triggered by respiratory viruses. It is not COVID. It is not the flu. It is not RSV. It is the rhinovirus.

Repeated need for prednisone or even a hospitalization, or status asthmaticus, or near-fatal asthma when in ICU. Do not assume that asthma is the correct diagnosis. It is the wrong diagnosis third of the time. Do not assume inhaled steroids and together with a LABA long-acting beta two agonists therapeutic when the treatment plan fails when you assess the patient, which is why it needs to be clinician-directed into the assessment.

The need for oral corticosteroids or high-dose inhaled steroids, in my opinion, is evidence of treatment failure. That is based on the evidence. Again, high-dose inhaled steroids is equivalent to 7.5 or 10 milligrams of prednisone. For that so happy to tell you at this conference.

[00:32:02]

Determining Asthma Severity

What about severity? Does it mean anything? This table is actually taken from the GINA guideline update for this year. As you can see, going from left to right, you have component severity intermittent, mild, moderate, and severe.

I am not sure if asthma severity is something we need to assess, but it is a consequence of how we practice medicine that we let people become severe, become moderate. If you look at the column under intermittent, this is what we want patients to have less than two days a week, having symptoms less than two times, waking up at night. No interference with normal activity. Really reduced need for albuterol, and a normal FEV1, if possible.

Heretofore, we basically have let patients have exacerbations, not understanding that it is not a single disease. One size does not fit all. You can, in fact, use this framework that was actually designed back in 1989, but I think it comes back to really being more patient-centric, understanding the symptoms, and really embracing the concept of asthma control.

[00:33:19]

Assessing Asthma Control

Actually, asthma control. That is a concept that was discovered created on a napkin at Starbucks Coffee by Dr Stuart Stoloff. I think Professor Stoloff is now retired. He practiced in Carson City, Nevada. We have him to thank. He is not a pulmonologist. He was a family practitioner, so thank you, Stuart, if you are listening in.

How do you assess asthma control? There are many tests, but the test that we use at UC Davis is to assess control test. The reason why is because it is very simple. There are five questions. This test is free. It is available in 34 different languages. You can basically remember that if you have an asthma control test score less than 20, all hands on deck, fire and hope, you have a patient at risk, not only for poor quality of life, as Jennifer outlined for us, but having exacerbations.

We now know that exacerbations can be the match that can light a stick of dynamite. That can lead to cardiovascular problems, just like in COPD, stroke, heart attack. Again, it is really important to recognize when asthma is not controlled. Most patients will not tell you this. They will say I am fine. The ladies are listening in. Fine is one of the five or six deadly words you use in conversation every day. More men are using it. You really have to take the time to assess.

This is something very difficult to do via telehealth. It is not that easy in my experience, so maybe better than I doing it, but I would rather have the patient in front of me because there is so much you can learn, and there is more questions to ask when they are in person.

[00:35:05]

Spirometry (PFT) and Flow Volume Loops

Spirometry is not that important at all in confirming the diagnosis. It is more helpful, in my experience, in making sure I have not missed something else. You had a session on interstitial lung disease. This is why I look at the flow volume loops. In the case of asthma, I always look for vocal cord dysfunction, which you can see basically in the far right diagram with the little warning and exclamation mark. Always think of that.

The flow-volume can tell you so much. A picture is worth a thousand words, but it is important more so in COPD.

Why do we have to wait for patients to lose lung function before we help them? Unlike in asthma, where we think about treating them with their children. I think there is a another disparity. There is a professional bias treating people with asthma versus COPD or even to overlap syndrome.

Again, spirometry is helpful, but most of the patients that I see, in my experience. I would like to hear what Jennifer's experience. By the time they see a specialist like Jennifer or me, they have lost about 30% to 40% of their lung function.

How did they do that? They probably had exacerbations, and what is never recorded are the mild exacerbations, the moderate and severe ones that lead to hospitalization. They trigger an insurance claim. It is so important to get this information.

We are going to talk about biomarkers. Just like you heard in the ILD talks. Biomarkers need to be much more pervasive in the way we practice medicine.

[00:36:38]

Fraction of Exhaled Nitric Oxide (FeNO)

Probably the two that you will remember from this session here is exhaled nitric oxide and the blood eosinophil count. Exhaled nitric oxide is a test we use. It is expensive in the eyes of the clinic administrators. The reimbursement is about $24. The mouthpiece is about $8, and they do not get very much money. This is where we have to again become patient advocates.

The GINA guidelines have stated that if you actually do this test and if your measurement is greater than 50 parts per billion, that is almost like a slam dunk. That is almost diagnostic.

Now, I will say for the record, there is no pregnancy test for asthma. Still a clinical diagnosis, but when you have an elevated exhaled nitric oxide, it is more likely. You have to make sure that there are not other confounding factors. Other diseases can actually do this, like chronic rhinosinusitis with nasal polyps. If you take too much arginine. And again, this is allowed us to talk about endophenotypes, so confirm the diagnosis of asthma, phenotype the patient with asthma. It is a severe asthma, then endotype is a type 2 high or type 2 low. This is where we bring in the ugly word immunology into our conversation.

Immunology is how we have really opened a new era for addressing those patients who continue to fail with their treatment plan. Again, for children, if it is greater than 35 parts per billion, asthma is very likely. The GINA guidelines basically has said that if you have a measurement greater than 20 parts per billion, that that is a measurement indicating a biomarker for type two inflammation.

[00:38:38]

Basic Labs for Asthma (Biomarkers)

Now I mentioned blood eosinophil count. I was one of those skeptics back in 2015, just to show you how stupid I was. As a pulmonologist, I like phlegm. I read a look at phlegm and see how many eosinophils in phlegm because there is no place for eosinophils to be in the airway, not unless they are trying to kill worms or you live in Sacramento.

The blood eosinophil has since been proven to be a very good biomarker. It is not perfect, but it does make us begin to target. Now, severe asthma is frequently uncontrolled using the Asthma Control Test or Asthma Control Questionnaire, whatever test you decide. The majority of patients who have severe asthma have the eosinophilic phenotype.

We are going to define that. I will do it right now. It is 150 eosinophils per microliter or greater in a patient. Now, back in 2015, it was 300. But you know and I know in clinical practice, the laboratory medicine does not declare the blood eosinophil count to be abnormal unless it exceeds 500 according to some laboratories or 400.

Again, you have to remember, you cannot find trouble unless you look for it. If you have a patient who you are sure the diagnosis is asthma. They are uncontrolled. The blood eosinophil count is 160. You can bring not only your experience and expertise, you can bring your empathy in. You can bring your integrity, and you can bring your accountability. You can basically advance the patient's care. You got to make sure you have the right diagnosis. Which is why it is also helpful to assess if they have an immunological response to their environment. IgE is very helpful, particularly if you are considering escalating the patient's treatment by adding a biologic that targets IgE.

[00:40:40]

Imaging for Asthma

Now imaging. I used to get an X-ray on everybody. I thought that is not very helpful. Remember, about 21% of people who have asthma smoke cigarettes. That is more than the general population. The CT scan may be very helpful in those who are frequent flyers, those frequent exacerbators, because you may discover interstitial lung disease. You may have been fooled for years and decades that the diagnosis was correct. You may discover emphysema, which basically goes together with COPD. COPD is a chronic bronchitis, and it can be complicated in patients with emphysema.

Those patients typically delay their recognition, they delay their treatments by a good 10 to 15 years compared to asthmatics. But what I want to leave you with is bronchiectasis. Bronchiectasis can complicate asthma or be a part of the progression of asthma in 20% to 30% of patients. This is where you really have to talk about airway hygiene and about mucus plugging.

As I said earlier, I love phlegm. Again, you may want to do a simple examination of the nose and look for nasal polyps, and those that mucosal should be pink.

With fire engine red, and you see something hanging out, it is not a tumor. More likely it is a polyp, or you can get a sinus CT scan to confirm that. Again, you are looking for comorbidities that can complicate the clinical picture of asthma. The comorbidities, in addition to chronic rhinosinusitis with nasal polyposis that you and I need to be concerned about, must include COPD, bronchiectasis, but do not forget GERD. Do not forget those patients, particularly adults who take a lot of nonsteroidal anti-inflammatory drugs.

[00:42:30]

Differentiating Asthma Endotypes and Phenotypes*

Again, the sequence is confirm the diagnosis, phenotype the patient. According to the GINA guidelines from years past, there are only five phenotypes: allergic, non-allergic, asthma with fixed airway obstruction, asthma late onset. I forgot the other one, asthma, something else. Now we accept that there can be eosinophilic and non-eosinophilic asthma.

Now we can explain how these phenotypes can arise. That is the appreciation that there may be an underlying disease mechanism. When we talk about asthma, you cannot escape talking about type two inflammation, or type two inflammation that is a little bit lower. Now again there is three branches to our cell-mediated immunity.

Type one is what you and I use to kill off viruses and tuberculosis, intracellular organisms. Type two is how you get rid of parasites like worms, and type three cell-mediated immunity is what you and I use to fend off and fight and kill pneumococcus, staph or whatever.

When we talk about type two inflammation high in asthma, we are talking about dysregulated immune response. There is no turn-offs.

There is also amplification because these eosinophils in particular, they find a way to the airways or other tissues like the sinuses. They establish residency. Even progenitor cells can go from the bone marrow and live in the airways. Once they are in the airway, particularly when they start releasing to themselves the type two cytokines that you all have heard about interleukin 4, interleukin 5, interleukin 13, they live for weeks, if not nearly a month.

They usually do not last more than a day or so in the blood. Once they are in the tissues, they have a party. This table maybe is an oversimplification because it does not include eosinophilic and non-eosinophilic phenotypes. Again, type two high is usually recognized by your clinical assessment, but you can also assess it using exhaled nitric oxide. I just do not understand administrators. Oh, it is too expensive. What price do you put on the patient safety?

[00:44:59]

When to Consider Referrals to Specialist or
Severe Asthma Clinic

This is probably my favorite slide in the deck. When to consider referral? A lot of times, you have to look in the mirror. You may be the asthmatologist for that patient. If you are too far away from an allergist or pulmonologist or too far away from Yale and Jennifer, you are going to have to basically take on the responsibility of being that person that is going to make the difference for your patient.

Now, again, if you do have access to an institution where they have consultants, and yes, some patients who are difficult to diagnose, you are not sure. If you are worried about a systemic eosinophilic vasculitis first described in 1951 as Churg-Strauss, but today, in 2025, you and I know it as EGPA by its initials, eosinophilic granulomatosis with polyangiitis.

Again, it is very important to remember teamwork makes the dream work and make friends before you need them. Do try and find an asthmatologist nearby that you can at least talk to. I am really one of the few who really want to give all of you the power and the privilege to begin to prescribe biologics. We are held hostage by the current business model for healthcare that require that patients see a specialist. It just does not make any common sense whatsoever. Everybody is treating obesity. What is the difference?

[00:46:36]

Skill Building and Feedback II

Tyler, I think I will hand it over to you. Maybe Jennifer and I can help Devon here.

Tyler Kuhk: Sounds good. Thanks, Dr Louie. Always a pleasure to hear you speaking. It is quite clear you have a big passion for this. I think we all appreciate that energy. Devon is this 33-year-old ICU nurse who reports frequent wheezing despite using multiple medications. He uses a high-dose ICS/LABA, and he is still experiencing symptoms.

His spirometry shows an FEV1 of 60% predicted with 12% reversibility. He denies missing doses and has correct technique. Dr Louie talked about inhaler technique. He is concerned about work absences and wants to finally get control of his disease. I want us to think, as we move into the question next is what is the next step to confirm that his disease truly meets the criteria for severe asthma.

[00:47:30]

Poll 5

A question to the audience is, which evaluation step best aligns with current guideline recommendations? For a patient like Devon, would we:

1. Add an oral corticosteroid and reassess in four weeks;
2. Evaluate for asthma mimics, adherence, and comorbidities;
3. Confirm the diagnosis based on spirometry data; or at this point,
4. Initiate a biologic therapy and discontinue the ICS/LABA.

We will give you a few moments to answer that, and we will jump into some discussion after that. 67% of you chose B, to evaluate for asthma mimics, adherence, and comorbidities. I want to open it up to discussion. We will follow up on that question, Dr Louie, and then Jennifer, if you have anything to add. How would you answer to that question and so forth?

[00:48:32]

Faculty Discussion

Dr Louie: Tyler, the first answer is what people do when they go to the emergency room. Take prednisone, but good luck if you can see your doctor or advanced practice provider in four weeks. I already said earlier, the answer is C. Spirometry is not that helpful in confirming the diagnosis of asthma. It is very helpful when you are looking for a comorbidity like vocal cord dysfunction. This is where you have to look at all the flow-volume loops. The bottom of the flow-volume loop looks like it has been scissored off by a child. It is flat.

Again, treating with a biologic may be appropriate, but please do not stop the inhaled corticosteroid, because if you do, the insurance company will penalize the patient and you. They hurt the patient by denying the patient three months of a biologic if the patient is actually responding favorably. We talked about the importance of the correct diagnosis. A third of people with asthma, as a diagnosis, do not have asthma.

Tyler Kuhk: Jennifer, did you have anything you wanted to add to that?

Jennifer Weber: Absolutely. I cannot agree with Dr Louie more. I think it is so important, before escalating therapies, to really be sure we are confident about that asthma diagnosis. Devon is a really interesting case because he is like the perfect patient. He is a healthcare worker. He has some health literacy. At least we can assume so. He is using his inhalers correctly and consistently and reporting to us that he has symptoms and is concerned. Really this is a dream. A lot of the times, it is a lot more complicated than that.

What is standing out a lot here, is that there is wheezing. Exactly to Dr Louie's point, not all that wheezes is asthma. We really have to make sure that upper airway looks okay by looking at flow-volume loops. Something I like to do a lot in my practice, if there is a lot of wheezing, we are not entirely sure if it is just asthma.

For example, let us say Devon said he was losing his voice. He was getting hoarse often, I would say, let us refer you to ENT for a fiberoptic laryngoscopy. Let us take a look at the vocal folds, see what is going on in there, and see if something like speech language pathology could help, give it three months maybe before escalating therapy. I will say that in the absence of severe asthma exacerbations, which would be defined as recurrent emergency room visits or hospitalization, it is a very different conversation about let us try this and wait. If there is hospitalization, then you may need to step up a little bit sooner.

Dr Louie: Yes, Jennifer, I totally agree. If it was regular asthma that Devon should have responded within a week. He would probably tell you I can go to church, I can go to Costco. I am making vacation plans. It does not take like three months for somebody to respond to inhaled corticosteroids if the diagnosis is correct.

Jennifer Weber: Exactly.

Dr Louie: We are looking, as I said earlier, not the patient's failure. We have taught them how to use their inhaler. We are looking for treatment plan failure.

In other words, the patient is not benefiting from the prescription. We may have to go back to the beginning. And who has time to go back to the beginning? You send them off to consultant. If you want to see me in Sacramento or in Davis, it will take five months. I might as well tell them to head east and find Jennifer at Yale. He or she will probably be seen sooner.

Jennifer Weber: Let us hope so. I am sure you guys feel the same way. Other things I think about with someone like Devon, he is a healthcare worker. A little fun fact about occupational asthma is it is more common in people who are healthcare workers, people who work in hospitals, because of exposure to really irritating chemicals like CaviWipes, and also, they are getting exposed to people with respiratory illnesses, probably a lot more frequently than the general population. These patients are at risk in general. Let us just say this is truly severe asthma.

We are confident about that diagnosis. Is he really eosinophilic? Is he really atopic? Let us look at those biomarkers. I am going to tell Devon time to repeat your biomarkers. Let us get an IgE with an ImmunoCAP. Let us get a CBC with diff, so we can figure out what your eosinophil count is. Let us start thinking about stepping up your therapy if this is truly the case. Let us modify your environment. That might include work as well.

For example, if he is specifically responsible for using really irritating chemicals to clean, I do not know, whatever equipment he is cleaning, we maybe give him an accommodation so he does not have to do that specific task. You have to think outside of the box sometimes to get these patients really on the right track.

Tyler Kuhk: Guys, great discussion, and there is some good questions coming in, and we are going to make some time for them at the end of the presentation.

[00:53:51]

Poll 6

Just in the interest of time, I am going to move on to some of our poll and post-test questions. This is a commitment to practice change question. Just to the audience, what assessment tools will you use in practice? You can select all that apply. That is:

1. An asthma control test,
2. The asthma control questionnaire; or
3. Another assessment tool.

I will give you a couple of minutes to answer that.

[00:53:30]

Poll 7

The next commitment to practice changes. How will you distribute them to your patients? Again another select all that apply. Would you:

1. Mail or email these tools to patients;
2. Give to the patient upon arrival to the appointment;
3. Give to the patient in the exam room;
4. Have staff fill out with the patient;
5. Complete it with the patient yourself; or
6. Do any other method.

Just a couple of moments to answer that.

[00:55:07]

Posttest 2

Then getting to our post-test questions. We have a 55-year-old woman with asthma who presents with persistent wheezing, nocturnal cough, and dyspnea. She uses her budesonide formoterol inhaler as prescribed. She has diffuse expiratory wheezing on exam. Spirometry showing an FEV1 of 62% with less than 10% reversibility. Which of the following is the most appropriate next step in evaluation? Would we:

1. Add oral corticosteroids and reassess reversibility in four weeks;
2. Order bronchial provocation testing;
3. Order biomarker testing to assess for type two inflammation and eosinophilia; or
4. Add a biologic to the patient's current regimen.

We will give you a few moments on that, and we will go through the pre and post-test answer after that.

[00:56:02]

          Posttest 2: Rationale

The correct answer is C. In the pretest was 44% and 70% in the post-test, so good work.