Update on Bronchiectasis: Diagnosis and Treatment

Additional Info

• Audio File:uab/ua159.mp3
• Doctors:Solomon, George
• Featured Speaker:George Solomon, MD
• CME Series:Clinical Skill
• Post Test URL:https://cmecourses.som.uab.edu/mod/quiz/view.php?id=4375
• Guest Bio:Dr. Solomon's clinical interest centers on the care of CF and non-CF bronchiectasis patients and the pursuit of continued inpatient medicine care of these patients in the acute care setting. 
  
  Learn more about George Solomon, MD 
  
  Release Date: November 11, 2020
  Expiration Date: November 11, 2023
  
  Disclosure Information:
  
  Planners:
  Ronan O’Beirne, EdD, MBA
  Director, UAB Continuing Medical Education
  
  Katelyn Hiden
  Physician Marketing Manager, UAB Health System
  
  The planners have no commercial affiliations to disclose.
  
  Presenters:
  George Solomon, MD
  Assistant Professor in Critical Care Medicine and Pulmonology
  
  Dr. Solomon has the following financial relationships with commercial interests:
  
  Grants/Research Support/Grants Pending - Vertex, Electromed, Bayer, Pro-QR, Insmed, Translate Bio
  Consulting Fee - Electromed, Vertex
  Board Membership - Electromed
  Payment for Lectures, including Service on Speakers' Bureaus - Insmed
  
  Dr. Solomon does not intend to discuss the off-label use of a product. No other speakers, planners or content reviewers have any relevant financial relationships to disclose.
  
  There is no commercial support for this activity.
• Transcription:Introduction: UAB Med Cast is an ongoing medical education podcast. The UAB division of continuing education designates that each episode of this enduring material is worth a maximum of 0.25 AMA PRA category one credit. To collect credit, please visit UABmedicine.org/medcast, and complete the episodes Post-test. Welcome to UAB Med Cast, continuing education podcast for medical professionals, bringing knowledge to your world. Here's Melanie Cole.
  
  Melanie Cole: Welcome to UAB Med Cast. I'm Melanie Cole, and today we're giving an update on bronchiectasis, diagnosis and treatment. Joining me is Dr. George Solomon. He's a Pulmonologist and an Assistant Professor in the Division of Pulmonary, Allergy, and Critical Care Medicine at UAB Medicine. Dr. Solomon, it's a pleasure as always to have you join us on the podcast today. So just give the listeners a little bit of a summary on bronchiectasis. Before we start into our update.
  
  Dr. Solomon: As many of you are aware of bronchiectasis is a condition that's characterized by chronic and recurrent infections. It's oftentimes due to a host of various immune or mucus clearance defects. These are most commonly conditions like cystic fibrosis or secondary to chronic infection or chronic immunodeficiency disorders. One of those chronic infections is nontuberculous mycobacteria, which is covered in another podcast. We have recently learned a bit more about the condition and especially in phenotyping patients who are at risk for worsening outcomes. And I'll tell you about those in just a moment, otherwise in treatment, we're pleased that there's been some development of new therapies. The most important of those is a therapy, which is looking at inflammation and a specific pathway called the neutrophil elastase pathway, which is known to propagate damage to the airway linings and the epithelial surfaces in the cells.  
  
  When that pathway is operative, which is especially in many patients who are sicker with bronchiectasis, we are learning that there's a potential for blocking that pathway in various different levels, and that will prevent clearing of the disease and progression of the disease. And so there are some recent developments of drugs that may be beginning to answer this aspect of care for the patients. So the most promising is one that was released by pharma companies recently completed a phase 2B study, which looks at both safety and early efficacy of the drug that was studied by the inspect corporation study called the Willow study. They have released public information about that, which suggests that in fact, blocking the neutrophil elastase pathway, which is a pathway that pertains to repair in the airways and other parts of the body as well, but especially operative in repairing the airways in response to inflammatory insults like infections, especially chronic infections, tobacco smoke, or other damages that can happen belongs.
  
  And so, when those happen, this pathway gets upregulated into a way that becomes not just for a person, but it also causes damage because of an overly exuberant response that inflammation. Therefore, the pathway, not only overexpresses itself, but it doesn't resolve itself once the inflammation or other cause by which it was activated is resolved. And that's the case in bronchiectasis and has been known for some time. The concept of treating that is one that is brought to bear more recently, and the thought process was can we safely and effectively block aspects of that pathway so that we can shut that down in a way that would make a good clinical outcome. Now, the clinical outcome of interest in that study was resolution of exacerbations or flares of the disease. And that brings us to bear with another important aspect that we've learned in bronchiectasis in recent years is that one of the most important elements of progression of disease has to do with the frequency of exacerbations or flares.
  
  Which are basically periods in the patient's life, in which they have increasing symptoms that are oftentimes due to environmental or infectious insults, and that results in worsening of the disease process, which initially causes increasing cough, mucus production, fevers, and systemic symptoms. And if left unchecked can cause the patient to get quite ill and result in hospitalization and or worst outcomes beyond that. So what we have learned is, is that patients who have a high frequency of those types of exacerbations or flares are at risk for worsening progression of the illness. And so treating that aspect of the disease independent of the underlying cause of their bronchiectasis, we find is important. And we hope that information like the results from the Willow study, if they go on to a phase three study and are efficacious, we hope they will be, that will prove the concept that we can block certain reparative pathways, which become damaging to the airways and progress the disease. And by blocking those, we can prevent poor clinical outcomes like frequency of exacerbations in those patients.
  
  Host: Would you like to tell other providers what those signs of exacerbation are? Is there something that they should be looking out for specifically?
  
  Dr. Solomon: Yeah. And that's something that I think in the field, we have defined a bit more fully. It used to be sort of, well, the physician thinks the patient needs some antibiotics. That's a flare. That's really not the case. The concept of an exacerbation has been well-defined in cystic fibrosis for some time. And only more recently, has there been a better definition put into place for non cystic fibrosis bronchiectasis in which we define a flare as increasing radiographic abnormalities and or decreasing spiral metric function of the lungs companied with systemic symptoms like fever, fatigue, anorexia, and as well as change in their pulmonary symptoms like increasing cough or mucus production or the change in quantity or quality of the mucus that's being coughed up. So basically a well rounded approach to understanding exacerbations through a lot of the clinical studies, which are the looked at the reduction of those as a clinical endpoint has helped us to better define what is a clinically significant exacerbation. And therefore we can better define when to treat it by routine conditions or how to treat it and how to identify it for the purposes of end points for clinical studies. Like the one I just discussed with you guys about the Willow study.
  
  Host: Dr. Solomon, we've discussed this before you and I, but now I'd like to ask you as we're giving this update, what about children and vaccinations? Do we find any link there? Is there any news about that now?
  
  Dr. Solomon: Yeah. So there's long been held some beliefs about various aspects of vaccination causing, as you may be aware the most, the strongest of those was the debunked concept of it causing point psychosocial endpoints like the development of autism. That's been debunked. There's also a concern about giving virus to a patient in the form of a vaccine to elicit an immune response. That's really what's happening in a virus, is you take some level of a virus, you give the patient a safe amount of that. They develop a immune response, which is both protective and, and simulates to the body at low level of infection, to some extent, and thereby the patient experiences that without having significant symptoms or it's a risk of their health, they develop protective immunity. Now, what you should be aware of is that most vaccines we use today are not actually full viruses. They're not live viruses, nor are they complete virus particles. So many have probably learned about that. The most is development of vaccine protocols for the COVID-19 virus. And many of those vaccine protocols that are being developed are, for instance, the ones being developed by Pfizer is an MRNA virus.
  
  So that virus is an MRNA vaccine. That means that only parts of the viruses MRNA are being injected into the human, not the entire virus. So there is no way to get the initial immune response that would be significant enough to cause bronchiectasis, nor would it be propagated by that type of vaccine. And many of the vaccines that are on the market now are that type of vaccine. They're either inactivated virus either by heat killing the virus or dissolving the virus into components, or they're already engineered components of the virus, which are enough to elicit the immune response. And so the concerns which were held years ago about we call live virus vaccines, which are very seldom used today, causing concerns like chronic immune issues, which may result in bronchiectasis, it's really a debunked situation. And so there should be no concern about the development of those types of condition like bronchiectasis from routine immunization in the modern era. Therefore I can recommend to providers to continue routine vaccination in both pediatric and adult patients, both for primary and secondary prophylaxis of infections.
  
  Host: Give us an update on the approach to co-morbidities of bronchiectasis. And tell us a little bit about what you've seen, what your outcomes are?
  
  Dr. Solomon: What we know at this point is that bronchiectasis is a condition that is not just a lung condition. It's definitely a systemic disease, whereby some of the inflammatory pathways I was talking about earlier, which are initially intention for reparative use become deleterious in the lungs. Those are operative and systemic in other organ systems as well. And so as a result, there are probably consequences to development of secondary problems in other areas of the body through vasculature abnormalities, due to abnormal repair or other organs that are directly damaged as a result of infections or antibiotics. So we have learned that in fact, there is an increased risk of various complications to bronchiectasis besides just pulmonary complications. And those include increased risk of stroke, likely an increased risk of malignancy and also a potential risk of other vascular diseases like coronary artery disease and peripheral arterial disease.
  
  There has been a link, especially in patients that get a lot of antibiotic type called amino glycosides and development of chronic kidney disease, as well as hearing loss from those. But that's more of a direct effect of a treatment for bronchiectasis, not the condition itself to bring that full circle. That means that patients that have bronchiectasis have a system type, which is more prone to the effects of chronic inflammation, because inflammation developing from the lungs does spill out into the rest of their organ systems. It doesn't mean per se, there's a direct treatment for that. It just means that we have to be more, it's more important to guarantee screening for certain conditions. And I'll give you an example in the cystic fibrosis bronchiectasis world, we have learned that in fact, the chronic Colonic inflammation due to the direct protein, the CFTR or CF protein defect in the Cola and GI tract is directly responsible for the development of earlier risk of colon cancer.
  
  And so those patients therefore are screened by guidelines at an earlier age with more frequency to prevent the development of precancerous lesions like polyps that may be if unchecked and untreated would lead to cancers that could spread throughout the rest of the body. That's just one example where we've learned that is the case. We are learning more about the vascular changes that happen in non CF bronchiectasis, but at present that is not altered the thought process and a guideline fashion well enough to tell us we should change screening beyond routine screening for adults based on gender and age as we currently do in the primary care world.
  
  Host: Well, as you're talking about non CF bronchiectasis, and as we wrap up, because this has been a fascinating update, are you recommending prophylactic prevention, tell other providers what you'd like them to know about possible prevention and what you'd like them to know as far as what's changed?
  
  Dr. Solomon: I think a couple of things we've learned, one is, is that bronchiectasis is a condition that usually has an antecedent because either they had severe infections as a child. One of those is severe whooping, cough, or certain severe viral infections like varicella or the patient is older and has a predisposition like an immuno deficiency condition, or they have a chronic airway disease like severe asthma or severe chronic obstructive pulmonary disease. Also known as COPD. If the patients have any of those characteristics then really should be assessed at some point for the presence of bronchiectasis, if, and when they develop chronic cough or chronic mucus production. And if they are found to have bronchiectasis, they should also be commonly looked for chronic infections, the most common of those being a pseudomonas infection, which is there's development of treatments for that, including the development in various stages of chronic inhalational antibiotics for treating that condition and that infection, which can complicate bronchiectasis.
  
  As well as looking at looking for nontuberculous mycobacterial conditions, which is strongly associated with concomitant bronchiectasis and is known to progress the underlying disease process. So my biggest recommendation is a patient has a risk factor for bronchiectasis, have a low suspicion for checking for that and getting diagnostics, which are definitive for that, which is really boils down to getting a high resolution CT of the chest to confirm the diagnosis in those patients. And if it's present then the referring, or if you're going to manage the patient primarily in your clinic, that you screen for risky infections that may complicate the illness such as the nontuberculous mycobacterial infections, like a mycobacterium complex. Commonly known as MAI infection and pseudomonas aeruginosa both of which are known to progress the illness. And if left unchecked can cause worsening illness in the patient, if not treated,
  
  Host: Do you have any final thoughts you'd like to share with other providers?
  
  Dr. Solomon: You know, my biggest thought for general providers in thinking about bronchiectasis is it's a diagnosis that's often overlooked. And so if you have a patient with risk factors, please consider screening them or referring to pulmonary so that we can do the appropriate testing, which is pretty simple to make that diagnosis because there are specific treatments are in development for that. And if you're a pulmonologist, it's not with bronchiectasis, please consider this as a differential diagnosis for patients with especially chronic bronchitis or mucus producing asthma or in patients that you're seeing that have immunodeficiency disorders, which may put them at risk for this. And if so, please make sure you have appropriate diagnosis done early so that we can begin treatment for those patients when appropriate.
  
  Host: Great information as always Dr. Solomon, thank you so much. You are a great guest and a community physician can refer a patient to UAB medicine by calling the MIST line at 1-800-UAB-MIST. That concludes this episode of UAB MedCast. For more information on resources available at UAB Medicine, please visit our website at UAB medicine.org/physician. Please also remember to subscribe, rate, and review this podcast and all the other UAB Medicine podcasts. I'm Melanie Cole.
• Hosts:Melanie Cole, MS