This webinar was recorded on June 14th

There can be many overlapping symptoms with asthma and COPD. How do you know if it’s asthma, COPD, or asthma-COPD overlap?


  • Dr. Gailen Marshall

CNE for nurses, and CRCE’s for Respiratory Therapists is available through Allergy & Asthma Network’s Online Learning HQ

CME is available through ACAAI for this webinar.

Sponsored by the American College of Allergy, Asthma and Immunology

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Transcript: While this transcript is believed to be accurate, errors sometimes occur. It remains your responsibility to evaluate the accuracy and completeness of the information in this transcript. This transcript is not intended to substitute for professional medical advice.

>> Good afternoon and thank you for joining us. I am Andrea Jensen education specialist for the allergy and asthma network and a certified asthma educator. All participants will be on beautiful today’s webinar. We are recording this, so if we go through information you want to go back and review, we will post it on our website within a few days. Find any of our recorded webinars and any upcoming webinars on our website, Scroll down to the bottom of the page to find any recorded webinars and upcoming webinars. This webinar will be one hour and we will allow time for questions at the end of the webinar. You can put your questions in the Q&A TAB at any time. The tapas at the bottom of your screen on the left. — TAB is at the bottom of your screen on the left. Sometimes questions in the chat get missed. Please, use the Q&A TAB and we will get to those at the end of the program. We do offer CEU for this webinar. It’s part of our webinar series “Advances in Allergy and Asthma” in partnership with the American College of allergy asthma and immunology. The allergy and asthma network offers CNE for nurses and CRCE for respiratory therapists. It offers CME. If you are a member of the college there is no feed to get it for the program. You will receive an email in a few days after the webinar. We will have all the resources from the webinar and links to access to continuing education credits and you will have a link to get your certificate of attendance. Asthma and COPD can have many overlapping symptoms and treatments. How do you tell the difference? Dr. Marshall will help us learn about that today. Allergy and asthma networks is a grassroots organization started over 35 years ago by a mom that knew other mothers like her needed resources and support. Our mission is to end the needless death and suffering through allergy and asthma and related conditions through outreach, advocacy, education and research. It is my pleasure to introduce our speaker Dr. Gailen D. Marshall. Dr. Marshall is the The R Faser Triplett Sr MD Chair of Allergy and Immunology, Professor of Medicine, Pediatrics , Pathology and Population Health Science, Executive Director of the Mississippi Clinical Research and Trials Center, Medical Director of the UMMC Clinical Research Support Program, Vice Chair for Research in the Department of Medicine, Director of the Division of Allergy, Asthma and Clinical Immunology , Chief, Laboratory of Behavioral Immunology Research at the University of Mississippi Medical Center in Jackson He received both his PhD in Immunology and MD from the University of Texas Medical Branch in Galveston, did internal medicine training at the University of Iowa, and completed his internal medicine residency, chief residency, and Allergy-Immunology fellowship at the University of Tennessee at Memphis. He’s an active clinician, educator, and research investigator. His major research interests focus on the clinical effects and underlying mechanisms of psychological stress (in the context of genomics, environmental factors, and lifestyle choices) on dysfunctional immune responses involved in allergic rhinitis, asthma, COVID-19, etc. He also studies the immune-modula-tory effects of new therapeutic agents for allergy and asthma. And the effectiveness of an integrative approach to allergy and asthma care using botanicals and natural products. He has published over 250 peer reviewed articles, reviews, and book chapters. He is an active speaker in regional, national, and international venues. He has extensive editorial experience and recently completed his 16 year term as Editor-in-Chief of the Annals of Allergy, Asthma, and Immunology. That is quite a feat. Thank you for your work in that area. He is President-Elect of the American College of Allergy, Asthma, and Immunology and will start his term as President in November 2023. And for those of you that wish to attend the conference, the annual conference will be in Anaheim, California, right near a certain amusement park that has a mouse as its mascot. Dr. Marshall is married and has 3 children and 5 grandchildren. Dr. Marshall enjoys amateur radio, astrophotography, and fly fishing and is active in church and community activities. Thank you, Dr. Marshall, so impressive. The time is yours.

Dr. Marshall: Thank you, Andrea. I also get some sleep every once in a while. Thank you everybody for joining. The video is not working. So, you just have the pictures of the slides, trust me, that’s better anyway. I just got back from a meeting in Germany and I am suffering from jet lag and I look my age. I think you will enjoy the slides very much more. We will talk about obstructive lung disease today. If there is a subtitle of this, this is obstructive lung disease for the asthma providers. I grew up in internal medicine training. I decided to be this relatively — a pulmonologist late in my trading — training. I saw a lot of COPD and interstitial lung disease. Asthma was trivialized as I begun to do this for a living. I recognized it was not trivial at all. Now what is happening its full circle again. The obstructive lung disease spectrum is amenable to many of the therapies. In the next 35 minutes or so my hope is to get you sort of used to or comfortable with some of the vernacular, some of the terminology, similarities and distinctions, specifically for the purpose of better diagnosis, better predictors of prognosis for patients, and, more effective therapeutic development. If I do that, I have been very successful in what I am going to do today. Think of obstructive lung disease. Really, you can define it as opposed to interstitial lung disease as decreased airflow due to diminished airway patency. It is typically perceived as exhalation al dyspnea. Pressure increases as air flows in. But, exhalation in a normal individual is a passive process. It’s relaxed and air is squeezed out like squeezing toothpaste from a tube. As the airway diameter diminishes there is an increase in effort to get air in and out. The increased effort on top of the already active inhalation all process is early on not perceived as a problem. Now, because of the delay in the exhalation, the diameter the body begins to perform work to squeeze the air out. That is dyspnea typically related to exhalation. As airway trapping occurs and the onus progresses, be it asthma, COPD, or some combination, that can change to become more of a cycle. Early on it is exhalation oh. — exhalation. There are multiple causes. Foreign body. An acute occlusion of the airway either partial or complete. Infections, typically bronchitis things, and less so, pneumonia. There can certainly be dyspnea pneumonia but you are more likely to see this in airway infections and then systemic mass cell activity that affects the lungs in a condition we would call anaphylaxis. Asthma, COPD that we will talk about today, and other conditions like cystic fibrosis, and even certain types of tumors, even those that might be Indo bronchial and cause a fixed mechanical obstruction are those in the lung three, or surrounding tissues that externally compress the airway and the end result is the same, decreased patency. Obstructive lung disease is decreased airway patency. I am old enough now, coming up on my 40th anniversary of graduation from medical school that I remember very distinctly in medical school and residency a discussion about asthma and COPD in the context of it being silos. Asthma was one disease. COPD was another disease. There was not much in common with them. Even though, historically, we recognize there were obstructive lung diseases, there were differences in risk factors. Asthma was considered a disease of children and young adults primarily and considered an allergic problem. COPD was smoker’s. People smoked, they would get COPD. There was not a consideration of the overlap that could occur. Local manifestations, asthma is reversible, COPD is irreversible. So if it is reversible if it — it is asthma and if it is irreversible it is COPD. Asthma, fairly early on, even in my residency, it became clear asthma was an inflammatory disease with bronchospasm, not just a Broncos fast it could disease. So treating the underlying information as a controller resulted in the resulting reliever was necessary for rescue as opposed to COPD where the main process, at least until later in disease was airway patency, trying to maintain it as best you can. Bronchodilators where the primary therapy for COPD. Then the long-term outcomes, very few people relatively speaking died from asthma. Whereas, it was — COPD was considered fatal. If you have it long enough, 100% of the people will die. What came to pass is a further study revealed either asthma had or developed irreversibility. We used to call it airway remodeling. It is still called that to some degree. COPD can have a reversible component that is usually more pronounced early to mid disease and in very advanced disease. Within developed was the idea that this was instead of being a silo, would actually be a spectrum and there was overlap that was possible. When you classified asthma versus COPD, commonly, again, we knew both were obstructive lung diseases. Over him and bronchospasm associated with them. Both had influence — inflammation. Distinction historically and classically, the nature of the inflammation in asthma was called eosinophilic. I am old enough to remember when eosinophilic was caused and asthma cell. COPD was considered to be a neutrophil look disease. There was the issue in bronchospasm whether the bronchospasm was from an adrenergic deficiency or a cholinergic access. Remembering, the natural tone of the airway in healthy individual is under cholinergic control. But in asthma and to a degree in COPD it’s considered that they have an android nurture deficiency. Classically, in COPD it was considered the head of cholinergic access. Anti-cholinergic was used in COPD and beta and were nurtured was used in asthma. Then obstruction was largely reversible in asthma and largely irreversible in COPD. While that is generally true, there is a middle ground in that that has not been considered before. If you get nothing else out of today you will hear me refer over and over again to what the middleground is that it exists. I cannot tell you what it is because I do not know. But that it does exist and exists along a spectrum that has importance for not only prognosis, for therapeutic choices. In COPD, if you are someone that does not take care of patients with COPD, and until 55 and seven years ago, if I saw a patient in clinic with COPD I would send them to pulmonary and not mess with them. I am an asthma doctor. I am not a COPD doctor. Now the recommendation is that there are a lot of COPD patients in my practice. The place to learn about this is the global initiative chronic obstructive lung disease, or, the gold initiative. Here is the URL that you can go and download this pocket guide. It can teach you a huge amount. It’s really not difficult reading. It is amazing the great job that has been done on this publication. The basics in COPD is there are two major components. One in the middle to larger airway. There is excess inflammation with resulting fibrosis and excess consistent mucus production that creates the obstruction. Chronic bronchitis, in the old days the classic individual was someone that had — that was often overweight. A little on the cyanotic side. And later in their disease they puffed a lot and they were called blue loaders because they were really big. The observed major component is the destruction of the alveolar membrane over time at the terminal bronchiolitis and into the Vila themselves with larger sacs producing emphysema. These people were very often underweight, then. They were called pink puffers. They had a lot of trouble breathing. If you are my age you know it a blue boater and a pink puffer is. If you are younger, you have had a little nostalgia for those of us that have been doing this a while. So the gold criteria being the system for classifying severity, therapy, and prognosis for COPD assesses symptoms like dyspnea, cough, wheeze, chest pain. Exacerbations. Hospitalizations. It becomes very important. In these and the PFTs. The major ones used in the diagnosis is that FPV one, SVC ratio. Then the FEV1 is used to classify them in terms of severity. The various stages. Gold stages 1-4. In an established COPD patients with post bronchodilator ratio classified one-for mild, moderate, severe. And very severe. Greater than 80%, 50%-80%, 30%-50% and less than 30% in very severe. These people do not breathe very well and it’s a very real problem for them. Not unlike in asthma where we can go to a major life-threatening exacerbation for someone with mild disease, these people can move through these stages if there is an appropriate insult that occurs there, they continue to smoke heavily, they are exposed to toxic chemicals, they get an upper respiratory viral infection, etc.. I know people don’t like to see all this. Let me just walk you through a couple and if you’re interested in more details the reference is at the bottom for you to come back and look at the slides later on. When insults occur to the airway, and the number one thing in COPD is cigarette smoke and pollution, but it’s not the only thing. There are people that have never smoked a cigarette in their lives who have unfortunately lived around other secondary smoke, or have never lived around cigarette smoke to any degree, but have lived in polluted urban environments or their occupation or they have had recurrent viruses or they have underlying disorders that allow recurrent bacterial infections, the commonality is the damage to the airway epithelium. There are several pathways. Macrophages are scavengers cells that move into the airways, the advent and show airways — areas under the airway. The lambda areas. They move into the areas and become activated by various chemo kinds. They adapt new mechanisms. The ultimate effect is the recruitment of neutrophils. Neutrophils are very, very potent post defense cells full of things used to kill bacteria and other pathogens. Unfortunately, if they accumulate, they themselves again to granulate. They can, the same enzymes used it to be protected, can be very damaging. If they are in the area of the alveolar that alveolar walls can result in the change we are talking about. The other part of this on the others, with the reaction oxygen that occur from pollution, cigarette smoke, and others. Chairs are reprogramming of these cells. They shift from being epithelial shales — cells that characteristically bond together, and hearing one to another providing various, if you will. Then endothelium is for blood vessels. Epithelium usually cover other surfaces, the long being a major one. Missing Comeau transition, there are three types. Malignant changes. Smokers, this is one of the presumed mechanisms where smokers are susceptible to lung cancer. The EMT one cell is producing factors that will activate fibroblast to become a laydown five rent and scar, if you will come of the lung tissue, the long airway. Related to then a permanent decrease in airway latency. The middle part is now there are multiple cytokines. Three of which are commonly referred to interleukins 25, 33,. There is a commercial one we will talk about in a second. A commercial monoclonal antibody used in asthma. These are called alarm ends. When the epithelium is damaged they release alarm it’s. There are types of cells like CD fuel — CD4 positive T cells that are not T cells. They are called innate lymphoid cells. There are three types. Type two will be producing IL-five. IL-five is a recruiter, activator, and life prolonged or. Just as the neutrophil has its own levels of toxins so do eosinophil have their own toxic granules that are important in host defense. When they get out of hand in the airway they create inflammation with ultimate remodeling. The other part is through this cytokine network. Goblet cell activation produces large amounts of mucus. So you have emphysema, lots of mucus, and fibrosis for chronic from Curtis — chronic bronchitis that represents the spectrum of this. What about management? First, make sure like with anything else there is a differential diagnosis. I will not go into all of that. I could spend three hours talking about this easily. The representatives systems, this mute being the most common one. The risk factors are smokers. Working in a polluted environment. They live in an urban area with positive airway pollution. Then spirometry. It shows evidence of FEV1, and have PVC ratio of less than 0.7. Then there is an initial assessment and their gold category escort. Tasha is scored. They also have an assessment of symptoms. They now call it the gold ABE system. They get a history of exacerbation. Are they still smoking, how many packs did they smoke? They measure an alpha one a trypsin level because there is a certain subgroup of COPD patients that have a deficiency. If that can be recognized and treated they will stop smoking. It will slow down the progress of their COPD significantly. Other comorbidities can happen. Our failure, a history — heart failure a history of tuberculosis. They can have diabetes, other comforting things that will make a treating them effectively more challenging. Initial management, smoking cessation. It is important to counsel and not to preach. My experience is not as a smoker, but as a health care provider that has talked to many people about smoking over the years. People respond to suggestions and affirmations more than they do to condescension and mandates. Vaccine status it’s very important for these individuals. Fluvial vaccine as flu vaccines, and pneumonia vaccines, now, COVID vaccines. They keep updating these because there are respiratory infections that for you and me might create a cough or make us feel bad for a week will be a mortality statistic for them. Active lifestyle and exercise. These people quickly become physically deconditioned because it’s difficult to breathe. So they just sit around. When you sit around the body starts to take havoc on that in a very short time. Initial pharmaceutical therapy we will talk about in a moment and self-management education. Shared decision-making is very important in CPD to help individuals manage risk factors and make sure they have good inhaler techniques. Just like asthma management. There used to be one inhaler and they put different medications in the inhalers, different colors, but the mechanics were the same. If you taught them for one, you taught them for all. Now virtually every product has their own inhaler. Dry powder inhaler, metered dose inhaler, etc.. Each one takes a technique and reinforcement of the technique. Helping people understand breathlessness, dyspnea, the perception of dyspnea. In COPD like in asthma there are over perceivers and other perceivers and it’s important for with to help them relate their perception of the briefing to measures with their airway. COPD is probably longer than it is for asthma. It’s still extremely important for the individuals. Managing comorbidity. If a person caring for COPD will not manage this, URC needs to make sure that he or she needs to make sure the patient has somebody that will manage it. A constant consistent review. Over and over. Every time these individuals are seen it is very important. Assessing hazard, disease may progress when they need oxygen. Relative approaches, lung volume reduction, etc.. Updating vaccine status. That falls behind often in these patients. Then adjust both formal — pharmacotherapy unarmed — and non-formal logical therapy. The ABE assessment tool is based on the Spira medically confirmed diagnosis. A post-bronchodilator ratio less than .7. Assessment of airflow goods — obstruction, the goal of classification and assessment of symptoms and risk of acts — exacerbations. In the older version of gold they would have an ABC and D. There are two questionnaires used. And in MRC, a one questionnaire that has a 0-4 score based upon an assessment of dyspnea and a cat score that is 10 questions with a 1-4 for each of them. So a maximum score of 40. A different pulmonologist and COPD people put different rates on this. These are tools commonly used. In this assessment they are both done. There is no reason to not — not to come as we are doing, if you are going to do that cap, a useful tool, the M MRC as one more question. It’s worth doing. So the exacerbation history per year, if there are more than two moderate exacerbations typically requiring courses of systemic steroids or one that leads to hospitalization, they are put into the category — that each category regardless of their symptom category. If they have lower numbers of exacerbations their symptom categories classify them as a or B having to do with prognosis. What you do in group A, B, and eat? Group A is in good shape. Low number of exacerbations or none. And at low numbers on their symptom scores. With the bronchodilator they can have a long acting bronchodilator or an anti-muscular proper dilator. You add a combination of the number goes up to b and if the number goes up to aa you consider adding an inhale closer to it if the blood citizen account is equal to or greater than 300. In almost all clinical labs 300 is still the normal range. The idea is if the account is going up or they are more likely to be responsive. This can give you an idea of factors to consider when adding inhaled corticosteroids to the long-acting. If they have a history of hospitalizations or exacerbations in category e or blood center so counts greater than 300 or a history of or concurrent asthma, then it strongly favors adding an inhaled corticosteroid. There may be some listeners not aware of the big deal. Why would you use it? For the longest time, the pulmonologist’s in particular did not want to use inhaled corticosteroids for COPD management because of the literature that strongly suggested it increased their risk for life-threatening pneumonia. More recent data have compartmentalized that a little better. It is not as much of a global anathema as it used to be. Those that have long-term taking care of COPD patients and those that are more recent to caring for them. Their favorite uses, one moderate exacerbation or blood center for Count 100-300. But, it is appropriate not to use in haired corticosteroids if they have had repeated events of pneumonia. Regardless of the infectious ideology, if there is low blood citizen account or a history of micro bacterial infection. What about using the blood us and fill count for therapeutic decisions? If you have an individual that starts out with laba or lama and they still have exacerbations if the the Senate fill — Nielsen fill count is less than 300, may be switching becomes appropriate. If the the Senate fill — Io center fill count goes up again with triple therapy, and there are not commercial therapies that have all three in it. If the exacerbations still continue, then using PDE antagonists and or antimicrobials becomes important. In this case, RO flew my last — there are two examples in this paper. A very nice paper from Peter Barnes from London. This is a paper worth reading if you are interested in this topic. There is a concomitant to the gold local admission for asthma called Gina. I think everybody that takes care of asthma patients is familiar with Gina. It was updated earlier this year. It has to do with the idea of the normal patency of the airway with bronchospasm and inflammation as a result of various exacerbating factors that make this worse. The classification was again updated in 2023. Assessed by airway function, both obstruction and reversibility as well as hyperresponsiveness. Uncommon and comorbidities. Exacerbation, assessment, and response to therapy. Clarification revisions in 2023 from earlier emergence of Gina. Intermittent eliminated. So there is no more intermittent, MOD, moderate and severe persistent. There are various stages I will show you in a second and therapeutic recommendations revised based upon severity. This is Endo type. Endo type is clinical presentation based on specific mechanisms. There are now four major ones associated with asthma. Common triggers, allergens, pause on — pollens, dust mites, pollution, animal dander, microbes, particularly viruses, and pollutants all impacted the epithelium and other normal inflammatory components that are there. You have the Io synthetic — eosinophilic asthma allergic in nature with the release of mast cell factors from Th2 and the production increasing the eosinophil in terms of recruitment, activity, and perseverance in anti-a pertussis factors stopping the early program death of silly pops that and you’re around longer. A eosinophil in tissue is not something you want unless it is fighting an active investing — infection because it will eventually to granulate and as it do granulate’s all of the major basic proteins and other eosinophil proteins create lots of tissue damage. As well as hyperactivity. Mucus production, but, no neutrophil. The eosinophil nonallergic is essentially the same pathway, except, it’s not the activation of the recruitment that will cause a mechanism. It is primarily because of these alarm ends. TSL P as well as AL 35. It activates these to produce a type two environment. The mast cell, the non-IGE mediated mast cell is involved — involved in this as well. There is a mixed granular civic asthma that includes both eosinophil send neutrophils that’s an overlap in asthma of the nonallergic so-called tea low or T-1 five asthma. That is where you have again the alarmists, I’ll 23 being involved in this — IL 23 being involved in this and you are engaged with the lymphoid cell type three, similar to a TH 17 cell having impact on a macrophage that reduces a chemo kind like and that recruits neutrophils. Hide neutrophils damages epithelium. There is a loss of mucus produced. Not as much sickening in the basal membrane. Not as much airway hypertrophy. And it lowers silly pops. The 1 — silly pops. The one no one really knows what to do about is the so-called posse granular acidic — pau cigranulocytic asthma. There is lots of damaged at the file up. This has irreversibility. Allergic asthma, as we have discussed. Exercise-induced asthma. Which is more amenable to treatment. If you are trying modifiers. The eosinophilic asthma. Aspirin exacerbated respiratory diseases fit into that as well. On the other, Th2, it goes along with severity and age of onset. There is a significant influence of genetic background. While we all appreciate that and we know there is family history associated with this, and a lot of Jean candidates, that’s not something that has really been established on the individual patient level get to direct therapy. Give it time. In the next several years I believe there will be data published which will give us who care for asthma as well as COPD as well as overlap, that will give us the ability to modify therapy and therapeutic decisions on the based of genetic information we get. In asthma management the basic idea is to assess confirming the diagnosis if necessary. I get consults multiple times a year. Individuals that have been treated for asthma for years and are just not getting better. It turns out, they are not getting better because they don’t have asthma. There are lots of reasons for that. For the sake of time we will not go into it. Symptom control and modifiable risk factors, comorbidities, inhaler techniques, preferences, both for the patient or the parent if they are a child and the goals they have. Assessment is important at this time. Adjustment of the modifiable risk factors. Nonfarm illogical — non- pharmacological strategies. Asthma medications and education and skills training. Then, reviewing symptoms, exacerbations, side effects, lung function, patient or parent satisfaction. This is what we do in our management principles taking care of asthma in patients. In the major young adult to adult population, first assessment, again, as we talked about, it’s all of these. Then there are two pathways we take. A more recent one, many may have heard of. It is called a smart therapy. That specifically involves the use of form are brought. There are other therapies being investigated called Mark therapy that does not use that. It uses another long acting bronchodilator. This principle uses the argument that the ICS fomoteral with a very rapid onset of action. It is up and running in five or 15 minutes. The inhaler is comparable to a short acting bronchodilator. It is using the same controller medication, the two agent ICS fomoteral as a reliever as well as a controller in the pathway where if there is concern for the individual regularly using their long-acting bronchodilator ICS compilation there is data to show it reduces the risk of dilation. You have different symptoms. Less than four to five days a week. They are in step 1-2. As needed symptoms. Most days waking with asthma one or more times a week they moved to step three on a regular everyday basis. The reliever is as needed low doses form pop, typically one plus — formoteral, typically one puff. Daily symptoms are waking with asthma one day a week or more and low lung function. If it moves up they go to step five for they add on LAMA. This is if they are in the primary care range. Then getting an asthma specialist involved is appropriate considering high-dose for formoteral with or without Biologics. The more classical one more of us are familiar with if we have taken care of asthma for any timeframe is the so-called track two. If you have individuals that are likely to be adherent to therapy. Then it becomes very important to have a good relationship that is candid with these individuals. Will they use it or not? The challenge that can be here is reimbursement. If insurance pays for these combination medicine that are by definition more expensive and they calculate they are using one puff twice a day or two puffs twice a day, whatever it is, calculating the monthly use of this, and you have somebody also using it as a reliever, particularly, if they are using it a lot, that can be a problem. It has to be considered something to look out. In this pathway it is not because they are using a short acting bronchodilator and the symptoms are less than twice a month. So, they use their Bureau inhaler then whatever I CEO’s you have suggested. Now, there is one recently on the market and others undervaluation that are SABA ICS combination medicines released here in the U.S.. There is a thought that this might take that place. That it will already be there when they are using the SABA, they will get theICS automatically because it’s two products instead of one. They stepped up accordingly then out on the Biologics when it’s appropriate. So it is a similar stepwise program but the different is a short acting versus a long acting when the combinations come on. The combination action starts here in start — step three as opposed here — to hear in step one. For kids, younger kids, again, confirming the diagnosis, looking for comorbidities. The symptoms here, twice a month load is ICS, step one. — lodos ICS, step one. They don’t have that combination here for kids in this age category. They move up stepwise here until they potentially have the use of biologicals in the 6-11 category depending on the specific biological. When we say Biologics for obstructive lung disease, currently in the U.S. that’s just for asthma. I think you will see it coming for certain subgroups of COPD. When they say biologicals are typically referring to monoclonal antibodies directed against specific components of the inflammatory chain. IGE is the first one. It’s been around a long time. It is useful in asthma. It has a proven track record. Then the argument is whether you use it only in people with elevated IgE versus not, people that are allergic versus not. The debate rages. It depends on where you are asked what you think about that answer. IL-five. We have already talked about the importance on either role here. Silly pop, chemo toxin, growth factor activation, approved drugs. There have been three. IL-4, IL three. That’s a mistake. It should be IL-13. We will correct that before it’s posted to the web. Mast cell growth factor promote mucus formation. Switch to IgE. Both four and 13 can switch to IGE. 13 is particular important in mucus formation at four is a mast cell — and four is a mast cell growth factor. There is one approved drug for this and IL-4 receptor alpha shared by both receptors. The newest one on the block, and thymic stromal is one of the three alarm ends — alarmins we have already showed you. It was supposed to be a drug that it did not matter it would work. In the eosinophil pour category this one seems to work better than the others, but it still works better in the more eosinophilic asthma. This one is really active and works well in eosinophil rich and it works well in some of the other choices in eosinophil poor asthma. What about the overlap? Asthma is a heterogeneous sender usually Carol — characterized with varying degrees of chronic airway inflammation defined by medical history and presentation that varies over time and intensity with variable airflow obstruction straight from Gina. COPD is heterogeneous characterized by chronic respiratory symptoms due to airway abnormalities and/or alveoli that produce frequent and often progressive airflow obstruction. That’s from the gold criteria. The overlap is collectively described patients who have persistent airflow limitation along with clinical features consistent with both asthma and COPD. The important thing is we try to call this a syndrome. Asthma COPD overlap syndrome. This is not a single disease. There is controversy in — amongst experts now with the difference British and Dutch interpretations. One says it is a distinctive one. The other says it is concomitant illnesses. Other than the argument, what is the value of trying to decide what this is one way or another? I will set this aside for a moment. If somebody has a question I am happy to address it. I will savor the moment for the sake of discussion it does not matter. It does not matter if it is a single entity or a concomitant disease. The patient is in that category and what will we do for her or him? Why is it important getting the right diagnosis? Risk exacerbation, quality of life and mortality risk. Asthma is low. COPD is high. But with asthma COPD overlap the mortality risk is higher than asthma but less than COPD. Here is a study published a couple years ago. A large number of patients, almost 400,000 patients, 65,000 of whom had as — asthma. COPD patients, 45,000 that had COPD, 230,000 that did not. And in overlap group where there were 22,000 of them. They compared the mortality risk for overlap — COPD versus asthma. It was a little higher, 90% higher. A hazard ratio for mortality. When they compared overlap with COPD it was about 11% lower. So you can see that the overlap is somewhere in terms of mortality risk in between that of asthma and COPD. The pathophysiology of asthma overlap with cell activity remodeling Th2 inflammation. Asthma patients smoke and have pollution exposure and biomass fueled this deck — exposure hand on the others I come in COPD, neutrophil, cytotoxic T cells, macrophages. People with COPD have allergies and there is a certain amount of modeling that goes on. Genetic susceptibility we have already talked about. There is a suggestion that early childhood lung disorder might play a role in this overlap as well. Then the epithelial to missing commode transition we mentioned. That might be prominent in ACO. The question is being raised, is it a unique disease? The approach to therapy to this is likely to be asthma, features of both. Likely to be COPD, look at their history. Symptoms over time. Are they more like asthma them like asthma. What about lung function? Do they have various airflow limitations? Good or, do they have mild persistent airflow? So, maybe they have a ratio that is .68. Come about, the ratio will not be .4. And call it asthma. It will just not be that way, OK? The other side of this that you would treat as COPD, dyspnea persistent on most days, later onset in life, more related to a history of smoking. Remember, asthma patients smoke and a some COPD patients never smoked. Bunk function, persistent limitations. The features of both, treating as asthma is of the intermittent middle-of-the-road function. This is the red I want to emphasize. It is you don’t give LBABA or LAMA without ICS two asthma patients. You don’t manage them with bronchodilators if they are at stage two or above. Reserve that for when there are failures. On the other hand, treating as it COPD using the gold report, LABA LAMA< avoiding high-dose ICS unless absolutely necessary much later in disease. Reliever containing ICS is not recommended with the exceptions we discussed before. The middle-of-the-road the big red one is not giving LABA or LAMA without ICS and maintenance corticosteroids is a last result. Then regular follow-up with these. Measurements here. The FEV1 pre-and post is comparable. It’s not consistent with COPD. Reduced, required for the diagnosis of COPD. And the overlap in the bronchodilator greater than 80% is more consistent with asthma. Less than 80% postbronchodilator is more consistent or is necessary — I won’t say more consistent, but necessary with COPD and overlap. An improvement in the 12% and 200 milliliter is more consistent with asthma and it very much more consistent with asthma when you move up to 400 milliliters. Some people do 200. Some people do 400. Then the lung function test DL Seo is normal. Asthma is often reduced. Can be abnormal in COPD. Airway responsiveness is not very useful. Imaging can be useful. But, less so in COPD — I’m sorry, so I asthma down COPD. ATP will increase in asthma. But, it is not — it does not rule out COPD if they have a topy. FeNo is usually normal in COPD unless they are current smokers and can be used for inflammatory versus inflammatory — less inflammatory. Blood for Lipa is more rare than it used to be and the cell analysis is not done in large populations anymore. In summary, asthma and COPD are both obstructive lung diseases. It is a growing problem in our world. It’s been estimated that COPD will be the third leading cause of death globally by 2030. This is not something to be taken lightly. Asthma and COPD represent a spectrum of obstructive lung disease. Both are inflammatory with an overlap in diagnosis, classification, treatment and outcomes in many more patients than we might realize and more precise diagnosis and treatment is important to effectively treat patients and ultimately develop medication and prevention strategies. With that, I thank you for your attention and I will turn it over to Andrea to moderate questions.

Andrea: I know there was a lot of detailed information. For those of you treating patients with asthma, we are recording this webinar. Go on our website was in a day or two to relisten. If there is a part you wanted to review. I was taking him seriously as you were going along. Our first question is are there similarities between viral respiratory distress and either a COPD or asthma exacerbation?

Dr. Marshall: This is particularly relevant in little kids, infants in their first years of life that have smaller airways. Viral bronchitis, even bronchiolitis in infants, small children can move up into adults and create a turbulent airflow. Remember, wheezing is nothing more than turbulent airflow. Back in the old days they would talk about asthmatic bronchitis. That term has been dropped. It’s not used by many people anymore because the term asthma implies a persistence or permanence. But you can certainly, with viral bronchitis, have an asthma like picture. Some individuals, even adults, need airways steroids to help reduce the inflammation that reduces the aeration of their symptoms. Substantially. Sometimes, as much as 50%. The issue is if they get a further 8-12 weeks after the acute episode and you want to assess them with a bronchodilator or meso coding, they would be negative if they don’t have asthma or underlying COPD. Acutely it can mimic it. On a chronic basis, it does not.

Andrea: Someone says, what is your opinion of the recent recommendation of the zoster vaccine for patients with COPD?

Dr. Marshall: I’m a huge believer in that. The COPD patient is almost by definition immuno compromised. At the cellular and tissue-based, we have limited ourselves to the lung in this discussion but systemically, they are both in the nature of the greenest city of the disease, the chronic disease produces stress. I study stress and how it impacts immunity. It’s not only psychological stress because they cannot breathe well. It’s physiological stress as well. Therapies, these COPD patients come as their disease progresses they see more and more steroids. Never let anyone tell you that higher dose inhaled port — corticosteroids don’t have systemic immune effects. They do. They do not have the same systemic immune effects as the equivalent systemic administration, but they are there. If they are using them over a. Of time, yes, there immune system will be copper mice. So, good vaccines including the zoster vaccine should absolutely be recommended to all these patients.

Andrea: Our next question is a little long. So hold on to your seats here for this one. Why not follow what the field of psychiatry has done with the creation of autism spectrum? Move away from asthma and COPD towards the active airway disorder, putting greater focus on treating the individual patient, not the label, thus, more patients can be evaluated for the underlying disease?

Dr. Marshall: I love that idea. I truly believe we are working towards that idea. The problem is, old thoughts die hard. Old traditions die hard. They tried unsuccessfully to try to do this with a cost. C OS developing a disorder like the autism spectrum disorder. The problem is from autism spectrum disorder, the work they done, and there is even some controversy there, there is a therapy based upon the disorder and the individual therapy for patients. That’s the whole principle of precision medicine. I think that’s all they have for this. I love the idea of discarding the term asthma and COPD and calling it an airway obstruction spectrum or something like that. Something like that. I just think we are not there yet. But, I love the idea. And I would be very supportive of it as the data would support.

Andrea: Thank you. The field is always changing, including the terms. I will combine two questions. What does spirometry look like for the asthma COPD overlap? Can you tell if a patient has COPD component without using spirometry?

Dr. Marshall: Wonderful question. That’s actually a question where the ACOS concept fell apart, because it depends. What they were trying to do was if the spirometry was more like asthma with a higher level of reversibility or a higher blood for Lipa County to treat it — eosinophil count to treat it like asthma. Or if it is more neutrophil again permanent treated like COPD. The problem of course is that, again, as I showed in the last slide with the mechanism of the overlap there is again a spectrum there of finding where the patient is on the spectrum. When you have a mixed pattern, you have someone that has an allergic component to it. But their sputum is largely neutrophil it. How do you treat that person? Much of what we do now is still empirical. We look at guidelines. We look at trying to classify them. The gold is doing this pretty well in COPD. Gina has done it very well in asthma. But, there has not been those two groups getting together to say let’s do a similar one for overlap. The reason there is not is there is simply not enough data for studies to defend what they were doing with those unique things. I say, these are the ones that are good to teach us that they call medicine practice for a good reason. We try with each individual patient to discern what is most likely to respond. There COPD effort? There asthma effort? Treat them and monitor them carefully then be willing to adjust accordingly.

Andrea: Someone else is asking about Peak and the Tory force when using drain power inhalers, that I know can be an issue with certain people. Is this a concern for asthma and ACOS or just COPD?

Dr. Marshall: It’s a concern for everyone. It becomes part of the assessment. Now, we have tools. There are commercially available tools to allow the individual, and they are not terribly expensive, really. There are several hundred dollars. They can be used in the office with people that take care of folks with obstructive airway disease and it not only assesses her their inhaler techniques, it assesses their ability to do inhalation, whether for the coordination necessary for a metered dose it had her or the effort necessary for a dry powder inhaler. I would argue if you take care of a number of patients with obstructive airway disease, that is something you should have. It’s useful. It is designed not only for you to know, but for them to know. They got green lights when they are doing it well and red lights when it is not working. It allows them to see firsthand the technique you are teaching them that it works or it does not work.

Andrea: I love the instant feedback patients will get. Often when I coordinated and asthma home visit program people would say, honey, I know how to use my NAR. I have been using it a long time. I could probably teach you a thing or two. You watch their inhaler technique and say, you have not been doing this right all time. I love them having them see the green and the constant over themselves, oh, I thought I was doing it right this time and I am not. The instant feedback is brilliant. We only have time for a couple more. I know everyone is busy and we need to get back to work. This question is about peak flow and if people should use that. It often depends on the provider. What is your opinion about having them do peak flow meters?

Dr. Marshall: Peak flow and spacers are like politics and religion. There are a lot of people with different opinions. There is not as much objective evidence as you would like. I grew up in — in an age where asthma inhalers, particularly controllers, you always used a spacer. It decreased side and improved inhalation delivery. Everybody was a big believer in it. Peak flow meters were what you used. We had paradigms based on that. Those have fallen out of grace because the peak flow tends to be a measurement of a larger airway. Asthma in particular is more a measure for middle and smaller airways. More of a disease of middle and smaller airways. I am not aware again, caring for CBD — CUPD Kaisha — patients is relatively reason for me compared to asthma patients. I am not aware if COPD patients are using peak flow to high degree. I still have some patients that use spacers. Obviously, for PPIs. The effectiveness changed a lot when they moved from so chlorofluorocarbons to HFA’s back 20 something years ago because the delivery is so different. The particle size is different and so on. Having said that, I still have a few people that have a real problem with coordination and either because of insurance reasons or the specific combination of therapy have, they do better with the EPI than the DPI and better with a spacer than without one. It becomes very individualized. It will be hard to get a consensus anytime soon. There are studies that need to be done it that no one will ever find.

Andrea: We are all short on time and funding, correct.

Dr. Marshall: correct.

Andrea: Apologies for all of you that we aren’t able to get to the questions but I want to be respectful of everyone’s time. Dr. Marshall, if you can go forward one more side. This is a — if you have any other ideas for webinars or you want any other feedback, jot them down in our evaluation survey. I look at every comment in there. Another thing is, often, people ask for topics. We have already done a webinar on that. Check our website at Scroll down to the bottom then you can see a lot of recorded webinars. Thank you for joining us. This is Andrea Jensen from the staff of allergy and asthma network. Join us as we work every day to breathe better together. Thank you everyone and thank you Dr. Marshall.

Dr. Marshall: My pleasure.