Bronchiectasis Treatment Goals, Unmet Needs, and Emerging Therapies: A Podcast

00:00:00: You are listening to an ADIS Journal podcast.

00:00:06: Hello, and welcome to this podcast publication on the current and future treatment landscape for the inflammatory airway disease bronchiectasis.

00:00:15: My name is Dr.

00:00:15: Patrick Flume.

00:00:17: I'm a pulmonologist and a professor of medicine and pediatrics at the Medical University of South Carolina, where I specialize in cystic fibrosis, bronchiectasis, and nontuberculosis micro-bacterial infection.

00:00:31: Joining me today is Dr.

00:00:32: Diego Macelli.

00:00:34: Thank you, Dr.

00:00:35: Flume.

00:00:35: My name is Diego Macelli.

00:00:37: I'm the Chief of the Division of Pulmonary Diseases and Critical Care at UT Health in San Antonio.

00:00:42: And I specialize in severe asthma, non-CF bronchiectasis, and COPD.

00:00:49: Today, we'll be discussing treatment options, treatment goals, unmet needs, and emerging therapies for patients with bronchiectasis.

00:00:58: Before we begin, I want to let everyone know that this podcast is sponsored by Insmed Incorporated.

00:01:04: However, any opinions expressed today by myself and Dr.

00:01:08: Maselli are our own.

00:01:10: With that, let's get started.

00:01:13: To understand the current treatment landscape for patients with bronchiectasis, we first need to talk about what bronchiectasis is and starting with how patients present.

00:01:24: Bronchiectasis is a chronic progressive and heterogeneous inflammatory airway disease.

00:01:31: The list of diseases that are known to cause or are associated with bronchiactasis is quite long and it ranges from congenital genetic conditions to autoimmune diseases to acute injury with improper repair.

00:01:46: And this means that the way that these patients present is also rather heterogeneous, which has historically led to delays in diagnosis.

00:01:56: Dr.

00:01:56: Macelli, would you say this is consistent with what you see in the clinic?

00:02:00: Yes, this aligns what we will observe in our practice.

00:02:04: We make every effort to identify the underlying etiology and provide the treatment when available.

00:02:10: The causes are indeed very heterogeneous, and in a subset of patients, we are unable to determine the cause despite extensive workups.

00:02:18: There's ongoing debate about how much testing should be performed for each patient and how frequently.

00:02:24: We continue to rely heavily on patient history and physical examination to guide our diagnostic approaches.

00:02:30: Thanks, Dr.

00:02:31: Maselli.

00:02:32: Ultimately, patients with bronchiectasis have two key features.

00:02:36: First, bronchiectasis is best defined by dilated airways, which requires a computed tomography or a CT scan to view and diagnose.

00:02:46: Second, these patients have a common feature of impaired mycociliary clearance of the airways.

00:02:52: which is really a key part of host defense.

00:02:56: This impairment creates the opportunity for retention of mucus and other material in the airway, which creates a ripe environment for the development of infection.

00:03:05: Once infection is established, the inflammatory response, which is largely driven by neutrophils, worsens the problem by leading to more material in the airway and further injury, in particular the weapons that these neutrophils use to attack the bacteria.

00:03:21: called neutrophil-serine proteases or NSPs, such as neutrophil-elastase.

00:03:27: They can overwhelm our defenses that keep the inflammatory reaction in check, which then leads to even greater injury to the airways and disease progression.

00:03:37: Traditionally, we have described the pathophysiology of bronchiectasis as a vicious cycle, where one step leads to the next step.

00:03:44: That is, Impaired mucosalary clearance leads to retention of airway phlegm.

00:03:48: This is followed by infection, then inflammation, which in turn causes further injury to the airways.

00:03:55: But what we have come to learn is that each aspect of this cycle contributes to all of the others.

00:04:00: And we have now deemed this the vicious vortex of these interconnected components.

00:04:06: So the approach to therapy would then target each and all aspects of the vortex.

00:04:12: US treatment guidelines are forthcoming.

00:04:15: but there are none in place currently, but we do have updated European guidelines that offer some treatment recommendations for adult patients.

00:04:23: Generally, when I evaluate patients with bronchiectasis, there are two essential questions that I'm trying to answer.

00:04:29: First, why do they have bronchiectasis?

00:04:33: If there is an identifiable cause, such as immune deficiency or allergic bronchopulmonary aspergillosis or ABPA, then there may be specific therapies to address the underlying problem.

00:04:46: The second question is, well, what are we trying to make better?

00:04:50: And this is where knowledge of symptoms and test results, such as imaging, cultures at respiratory specimens, they can be of great help.

00:04:59: And if we consider the basic problems in these patients to be, number one, airway obstruction, number two, infection, and number three, inflammation, Then we can look at the various treatment options available to intervene in the different parts of the vortex.

00:05:14: Dr.

00:05:14: Macelli, how do you approach initial treatment and conversations around treatment goals with your patients?

00:05:21: Our initial approach for patients with bronchiectasis involves diagnostic testing to determine potential etiologies and underlying diseases, as you mentioned before.

00:05:30: Most patients undergo an evaluation for our immune conditions and immune deficiency.

00:05:34: In addition, sputum samples are obtained for microbiological analysis.

00:05:39: Because these patients are at risk for a broad range of infections, we typically send cultures for bacteria, fungi, and nontobreclose macobacteria.

00:05:47: Omonary function testing is also essential, very important, to assess the degree of impairment and to establish a baseline.

00:05:54: Depending on the clinical context, additional tasting may be warranted, including an evaluation for GERD or gastroesophageal reflux disease, primary axillary dyskinesia, cystic fibrosis, and chronic rhinocinositis.

00:06:08: The overall goals of therapy are to improve symptoms and quality of life.

00:06:12: This is very important.

00:06:14: Slow the disease progression and prevent potential complications.

00:06:18: For an individual patient, we need to consider what symptoms are trying to improve.

00:06:22: We're trying to improve.

00:06:23: Is it a cough?

00:06:25: Is it like the sputum production that they have?

00:06:27: Hemoptysis?

00:06:28: Is it a reduction in exacerbations?

00:06:31: Some patients will have progression of lung disease, so they are progressively losing forced expiratory volume in one second, or FEB-I.

00:06:39: Understanding the goals and priorities of patients living with this condition is essential.

00:06:44: While clinicians often focus on clinical outcomes such as lung function, conservation rates, disease progression, patients may have different concerns.

00:06:54: Many patients are more focused on improving their day-to-day quality of life, such as being more active, reducing sputum production and coughing, and participating in social and family activities.

00:07:06: Because of this, it is critical to incorporate quality of life metrics into care planning and engage in shared decision making.

00:07:14: During conversations with patients, we emphasize the importance of preventing exacerbations, effectively treating their infections, and slowing the disease progression and lung function decline.

00:07:24: It is helpful to explain that improvements in these clinical outcomes often align with what patients value the most.

00:07:31: Greater physical activity, social participation, and improved overall well-being.

00:07:37: By aligning therapeutic goals between clinicians and patients, hair becomes more meaningful and effective in both parties.

00:07:45: Exhalstervations are a common complication of bronchiectasis.

00:07:49: Accessorvations are defined as a worsening of three or more respiratory symptoms lasting at least forty-eight hours, along with a declination decision to modify treatment, typically by initiating antibiotics.

00:08:02: Symptoms may include increased cough, sputum volume, and or purulence, dyspnea, fatigue, or malaise, and haemoptysis.

00:08:12: Accessorvations can for patients to take time off at work and potentially lead to hospitalization.

00:08:18: And we also learned that although patients may recover from their respiratory symptoms rather quickly, oftentimes it takes them a full six weeks to recover their functional status.

00:08:28: Moreover, exacerbations are associated with an increased risk of future exacerbations, lung function decline, and increased mortality risk.

00:08:36: Going back to the aspects of the vortex, we have a number of therapies to address obstruction by enhancing clearance of airway secretions.

00:08:45: And these range from different breathing techniques to devices to help move this material up and out of the airways.

00:08:51: In some patients, we'll use concentrated hypertonic saline.

00:08:55: Some use three percent up to seven percent to hydrate the airway flam to make them more fluid and easier to clear from the airways.

00:09:03: And the hypertonic saline also provokes coughing and enhanced mucosal clearance.

00:09:08: Airweed clearance is one of the cornerstones of therapy in bronchiectasis.

00:09:13: Initial therapy depends, typically, on the patient's symptoms.

00:09:17: Rocko dilator, airway clearance devices, and hypertonic saline have been found to be helpful in managing respiratory symptoms.

00:09:25: We also encourage all patients to perform breathing exercises and increase physical activity to enhance airway clearance.

00:09:32: Certain devices can be incorporated into the airway clearance routine for patients with bronchiectasis, including flutter valves, high-frequency chest wall oscillation, and others.

00:09:41: These advice help in mobilizing secretions and we encourage all of our patients to use these therapies daily as much as possible.

00:09:49: All patients with bronchiectasis should engage in some form of airway clearance therapy, especially and very importantly those that have frequent exacerbations or events of mucus ploughing or chest CT.

00:10:02: Ultimately no single method of airway clearance has been proven to be better than any other for addressing obstructions so It is important to introduce the patient to the various choices in order to find which therapy is best for them.

00:10:16: The one that they will actually do or use is also the one most likely to be effective.

00:10:22: Dr.

00:10:22: Macelli, in terms of dealing with infection, what is your approach with patients?

00:10:27: We remain highly vigilant for signs of active infection in patients with bronchiectasis.

00:10:32: At each visit, we assess symptoms such as fever, pure in sputum, hemoptysis, rigors, and night-time dysphoresis.

00:10:41: We also place close attention to nonspecific symptoms, including fatigue, malaise, loss of appetite, and weight loss, as these may indicate an ongoing infection.

00:10:52: Sputum samples are obtained regularly to evaluate for bacterial, fungal, and nonturricular macrobacterial infections.

00:10:59: We also closely monitor symptoms for signs suggestible and active infections, such as three embot opacities on imaging, worsening cavitar lesions, or mucus plugging.

00:11:10: In patients who are unable to produce adequate sputum, bronchoscopy may be necessary to obtain bronchial samples and do a proper diagnostic evaluation.

00:11:20: Once we identify a pathogen in the right clinical context, we may initiate therapy.

00:11:26: Pseudomonas aerogenosis is among the most common pathogen isolated in patients with bronchiectasis.

00:11:32: In these, Pseudomonas infection is associated with poorer clinical outcomes, including lung function decline and all-cause mortality, and bronchiectasis alone.

00:11:43: Treatment for chronic Pseudomonas infection may not eradicate infection, so inhaled delivery of antibiotics to suppress the bacteria is another option.

00:11:52: Now, with respect to treating the inflammation, We've had far fewer options.

00:11:57: One frequently used therapy is macrolides.

00:12:00: Trials have demonstrated the beneficial effects of macrolides, but there remains controversy as to whether they work by an anti-inflammatory effect or because they're an antibiotic.

00:12:11: Nonetheless, macrolides are primarily used for patients who have frequent exacerbations and they have had good success in reducing these exacerbations in this population.

00:12:20: We typically reserve the use of macrolides.

00:12:22: for patients who experience at least three exacerbations per year or more.

00:12:27: Although generally well-tolerated, macrolites can cause several side effects that should be carefully considered before initiating therapy.

00:12:35: This class of medications may lead to gastrointestinal symptoms such as nausea, vomiting, and diarrhea.

00:12:41: Additionally, macrolites have been associated with QT prolongation and should be used with caution in patients with underlying cardiac diseases.

00:12:49: They can also cause liver toxicity and ototoxicity.

00:12:53: We recommend obtaining both an electrocardiogram and baseline geometry for all patients prior to starting this therapy.

00:13:01: Importantly, if there is no significant chronic improvement after two to three months, the treatment should be discontinued.

00:13:08: There remains concern in the field about the potential for long-term antibiotic or macrolide use selecting out resistant bacteria.

00:13:16: particularly with non tuberculosis mycobacteria, which are frequently found in our patients with Marquisectasis.

00:13:23: In general, the advice that we give is to test for evidence of mycobacteria before initiating the macrolides, but to also continue monitoring for mycobacteria while the patient is taking them.

00:13:34: In terms of other anti-inflammatories, corticosteroids are commonly used for pulmonary disease, whether by oral systemic therapy or inhalation.

00:13:43: Dr.

00:13:44: Maselli, how do you generally approach prescribing corticosteroids?

00:13:47: Inhaled corticosteroids or ICS are sometimes used in patients with bronchiectasis with mixed results.

00:13:54: Some studies suggest that ICS are prescribing more than fifty percent of bronchiectasis cases.

00:14:00: They may be appropriate in patients with overlapping conditions such as asthma or COPD coexisting with bronchiectasis.

00:14:08: However, because ICS have been associated with an increased risk of infection in certain patient populations, a careful risk-benefit assessment should be performed before initiating therapy.

00:14:19: Phenotyping these patients, particularly using blood eosinophil counts, for example, may provide some clinical guidance, though further studies are needed to support definitive recommendations.

00:14:32: Existing guidelines do not routinely recommend ICS for bronchi-actas as patients.

00:14:37: Beyond the vortex, it's also important to understand whether there are comorbidities that might worsen the patient's condition, such as esophageal reflux or a nutritional deficit.

00:14:47: Maybe they have mental health issues like depression or anxiety.

00:14:51: Trying to find ways to address all these things is important for the patient's quality of life.

00:14:56: There are many factors that can influence the underlying drivers of disease in bronchiectasis, making a multimodal approach often necessary and very important.

00:15:06: In many cases, multiple specialties are involved to address specific comorbidities and complications.

00:15:13: For example, an evaluation by gastroenterologist may be needed for refractory GERD or cervical reflux disease.

00:15:20: A ENT specially may be needed or consulted for complex sinus conditions.

00:15:25: A dietician can ensure adequate nutrition to meet increased caloric needs.

00:15:30: And an infectious disease specialist may assist with managing difficult to treat infections.

00:15:34: This multidisciplinary approach enhances the quality and effectiveness of care provided by patients with bronchiectasis.

00:15:41: I agree, Dr.

00:15:42: Maselli, and despite all the therapies we've outlined here, there remain clear unmet needs.

00:15:48: Although available therapies provide some symptom relief and address infections, they don't fully address the neutrophilic inflammation that drives this condition.

00:15:56: We can see this with the continued exacerbations that patients have with some patients suffering from multiple events each year, every year.

00:16:04: Patients do not want to miss the opportunity to engage in their daily activities.

00:16:08: They want to be able to work, spend time with their families, and maintain the sense of normalcy.

00:16:14: While available therapists can help support these goals, a significant number of patients continue to experience daily symptoms and very importantly frequent exacerbations.

00:16:23: Additionally, many patients are concerned about the burden of treatment.

00:16:27: They need to use multiple devices.

00:16:30: Enabilized various medications throughout the day can be time-consuming and overwhelming, contributing to a high treatment burden.

00:16:38: Ultimately, as clinicians, we unfortunately can't do much about lung tissue that's already damaged, but we can try to prevent progression of disease.

00:16:47: We have therapies that target the impaired, make us lay a clearance in infection, although we still remain concerned about selection for antimicrobial resistance.

00:16:55: Therefore, the treatment opportunity that remains is to address the inflammation.

00:17:00: or more specifically, the dysregulated neutrophilic inflammation.

00:17:04: We know that there is an excessive quantity of neutrophils and NSPs in the airways and speedings of patients with bronchiectasis.

00:17:12: We also now have reasonably good data that demonstrate that high levels of neutrophils and NSPs are associated with worse clinical outcomes, worse lung function, more frequent hospitalizations, and increased mortality.

00:17:26: So this drives the interest in trying to tame that inflammatory response.

00:17:31: This treatment approach has proven challenging, however.

00:17:34: An effort to block neutrophil migration into the lung space was tested in patients with cystic fibrosis, but this was associated with a greater rate of adverse events, perhaps showing us that some inflammation is a good thing, so we must be careful about reducing it too much.

00:17:50: Another approach is to block the effect of the excess NSPs.

00:17:55: The presence of alpha-one antitrypsin is one host defense mechanism.

00:17:59: It just becomes overwhelmed.

00:18:02: However, nebulizing alpha-one antitrypsin into the airways was not successful, primarily because we just couldn't get enough into the airspace to have the desired clinical effect of inhibiting neutrophililastase.

00:18:14: A novel approach is based on the discovery that NSPs are activated in the bone marrow by a canzyme Dipeptidilpeptidase I or DPP I. This led to the development of DPP-I inhibitors, which essentially reduced the amount of activated NSPs.

00:18:31: DPP-I inhibitors are now being tested in clinical trials, some of which have been completed, and are demonstrating clinical benefit in patients with bronchiectasis.

00:18:41: One example is Brentzacatab.

00:18:43: In the Phase II Willow trial, Brentzacatab reduced the activity of NSPs, and it prolonged the time to the first pulmonary exacerbation in patients with bronchiectasis.

00:18:53: who had a history of frequent pulmonary exacerbations.

00:18:57: Medication was well-tolerated, had a similar rate of adverse events leading to discontinuation for subjects with benzocatab or placebo.

00:19:05: Dental and skin adverse events, which were adverse events of special interest, they occurred more frequently with the ten and the twenty-five milligram benzocatab doses compared with placebo, yet none of those events were considered to be serious by the investigators.

00:19:21: Dr.

00:19:22: Maselli Results from the phase three Aspen trial have been published.

00:19:26: What did they show?

00:19:27: The Aspen trial enrolled over seventeen hundred patients with bronchiectasis and a history of frequent exacerbations, including a small cohort of adolescents.

00:19:37: The patients were randomized to placebo or one of two doses of Prince Ocata, ten milligrams or twenty-five milligrams, or a year-long treatment with a primary endpoint being the annualized rate of pulmonary exacerbations.

00:19:51: The trial demonstrated an important and clinically relevant twenty percent reduction in the frequency and exacerbations with both doses of benzocatal compared to placebo.

00:20:01: Additionally, the time to first exacerbation was significantly longer and a greater proportion of patients remained exacerbation free with both doses of benzocatal compared to placebo.

00:20:13: Other important clinical endpoints include a significantly reduced lung function decline, seen with a higher perinsocative dose, which is the twenty-five milligrams, and a nominally significantly improved patient-reported symptoms, as measured by respiratory symptoms, scores, and the quality of life.

00:20:31: bronchiectasis questionnaire.

00:20:33: Subgroup analysis indicated a treatment benefit of perinsocative when exacerbations across most subgroups evaluated.

00:20:40: which is an important observation in a heterogeneous disease like bronchiectasis.

00:20:45: Regarding the overall safety profile, both doses of Brensocatib had similar rates of adverse events as placebo.

00:20:51: The most common events that were more frequently with Brensocatib than placebo were COVID-IX, nasopharyngitis, cough, and headache.

00:21:02: Again, hypercarotosis was more frequent with Brensocatib than placebo.

00:21:07: but most cases were mild to moderate and resolved during the study.

00:21:12: With these results, Bransocative is a welcome addition to the treatment armamentarium for bronchiectasis, particularly due to its ability to reduce exacerbation, a very important outcome.

00:21:22: Since exacerbations are associated with worse clinical outcomes, increased risk of future exacerbations, and disease progression, reduction in their frequency is again a critical goal.

00:21:34: Rensocative is also easy to administer and has a favorable safety profile, which may support better patients adherence.

00:21:42: Dr.

00:21:42: Froome, what are your thoughts on the Aspen trial data?

00:21:45: Overall, I thought the results are of great importance and highly encouraging.

00:21:51: This is the first successful phase to re-study embryoectasis.

00:21:55: Also, the results support our goal to not only try to improve our patient's symptoms and quality of life, but also to change the course of disease.

00:22:04: The observation in Aspen that the twenty-five milligram dose reduced the rate of decline of lung function as measured by post bronchodilator FEV-I is very intriguing.

00:22:14: If we see this in patients in the real world setting, this would suggest that perhaps modulating the inflammatory response can in fact change the trajectory of disease.

00:22:24: Yes, the lung function data are very thought provoking.

00:22:27: Evidence suggests that perhaps by reducing the trophillic inflammation, disease progression may also be slowed.

00:22:33: This effect may result from a reduction in exacerbations through inflammation control and from a direct decrease in airway-level inflammation.

00:22:42: Patients often worry about declining lung function, but this data provides some reassurance that regular use of this drug may help delay that decline.

00:22:51: Similarly, there are two other phases to studies of additional DPP-I inhibitors.

00:22:56: The air-leave trial for veriducatib and the save BE trial for HSK- Three-One-Eight-Five-Eight.

00:23:03: Both demonstrated early success in patients with bronchiectasis, further supporting this mechanism of action and treatment strategy.

00:23:11: Both of those drugs are now being studied in phase three trials, with treatments going out to seventy-six weeks for the BI drug and fifty-two weeks for the HACCO drug.

00:23:21: Based on the positive results from Aspen, Brinsecadab has recently been approved in the U.S.

00:23:25: for the treatment of non-cystic fibrosis bronchiectasis in adult and pediatric patients, twelve years of age and older.

00:23:33: Both of these doses used in the Aspen trial, ten milligrams and twenty-five milligrams, have been recommended.

00:23:40: They are taken orally once daily, with or without food.

00:23:44: There are no contraindications in place, but warnings and precautions have been given for dermatologic adversary actions.

00:23:51: gingival and periodontal adverse reactions, as well as the use of live attenuated vaccines.

00:23:58: I should add that Brent's Academy has been approved irrespective of the number of exacerbations patients have.

00:24:05: There currently aren't any requirements for patients to have frequent exacerbations.

00:24:10: Since the ass control results were published, we've already begun to identify which patients would be good candidates for Brent's Academy.

00:24:18: We are obviously considering those patients who have a history of frequent exacerbations, but we are also considering those who have a high symptom burden because they are suffering day to day.

00:24:28: We also believe that CT scans are useful to identify the extent of ongoing inflammation in the airways, as might be suggested by features such as increased airway wall thickening and mucus plugs.

00:24:41: In Aspen, as in all trials, the patient population was highly selected, so now we need to look at its effectiveness in the real world.

00:24:49: Obviously, when we start new therapies, we first care about tolerability, which I don't really worry about so much with this drug, but we also want to assess patient response and have some objective numbers, whether it's quality of life, cough scores, other symptom scores, or lung function data.

00:25:06: Dr.

00:25:07: Maselli, how would you measure response to Brinsecata in your patients?

00:25:11: Response to therapy will be assessed over several months following initiation.

00:25:16: While our primary focus will be on exacerbation rates, we're equally interested in quality of light metrics and lung function.

00:25:23: We will be interested in getting patients' perceptions on their day-to-day symptoms and the impact of their overall treatment burden.

00:25:30: We will also be closely following the safety profile of these novel medications.

00:25:35: Here we've been focusing on targeting the neutrophils, but there is also great interest in eosinophils and their role in the disease process, because some patients that you see with bronchiectasis have elevated levels of eosinophils as well.

00:25:50: So people are interested in whether that could be an indication of where steroids or one of the more recently developed biologic agents that target eosinophilic inflammation might be useful.

00:26:00: Interestingly, a subgroup analysis from Aspen showed that Brinsecata was associated with clinical benefit regardless of patient's baseline blood eosinophil level, whether it was low, meaning less than three hundred cells or high, greater than three hundred cells per microliter.

00:26:16: And that suggests that treating underlying neutrophilic inflammation is effective regardless of eosinophilic inflammation.

00:26:23: Yes, and more broadly, there are other drugs in development such as phosphodiesterase PDE.

00:26:29: three-four inhibitor and sephendrine and the anti-interleukin-thirty-three monoclonal antibody itepachymab.

00:26:37: And sephendrine is an inhaled drug approved for the use in patients with COPD for its anti-inflammatory and bronchodilatory effects.

00:26:44: And itepachymab is an injectable biological that has anti-inflammatory effects.

00:26:50: Both of these drugs are being investigated in ongoing phase two trials.

00:26:54: This leads as to what's next.

00:26:56: I see two big things.

00:26:58: First, the future is bright in the space of bronchiectasis.

00:27:02: It has been a long neglected condition where patients were underdiagnosed or diagnosis was substantially delayed, but I think that has been improving.

00:27:11: There is greater awareness of this disease and greater use of high-resolution CT scanning for the diagnosis.

00:27:17: Almost every center that I'm aware of is seeing an increased number of referrals for evaluation.

00:27:23: In the

00:27:23: U.S.,

00:27:24: the bronchiectasis and NTM association was established with the goal of cultivating a clinical network where patients affected by bronchiectasis can be seen and evaluated throughout the country in a thorough and timely manner, which can only help to push this disease further into the spotlight.

00:27:42: Second, there is great need to have long-term data to understand the disease course, and as new interventions are introduced to determine how these might best be used.

00:27:52: There's also need for long-term data to help design clinical trials and post-marketing analyses to assess clinical benefit or adverse effects.

00:28:00: Registries are the way to track these data, and there are several that are ongoing, including MBARC in Europe, which is also expanding into Asia, and the bronchiectasis research registry in the US.

00:28:14: Dr.

00:28:14: Massili, what are your thoughts on the future of bronchiectasis?

00:28:18: I agree that the future is very promising for patients with bronchiectasis.

00:28:22: In recent years, there has been a significant increase in our understanding of the disease pathophysiology, along with greater awareness of its impact on various clinical outcomes.

00:28:31: I believe that we are now at the next frontier where targeted anti-inflammatory therapies hold the potential to alter the disease trajectory and ultimately improve patients' prognosis and quality of life.

00:28:44: This is an exciting time in the management of bronchiectasis, and I look forward to the results of the ongoing studies.

00:28:51: Great.

00:28:52: Thank you so much, Dr.

00:28:53: Moselle.

00:28:55: I'd like to close by saying that although we describe bronchiectasis as a single condition, it is the result of many, many different conditions.

00:29:05: It's important that we should be using a holistic approach to patient care since Beyond the airway disease that many need education and care around nutrition, mental health, and other issues that are associated with the disease to receive the most benefit.

00:29:20: That concludes our podcast.

00:29:22: Thank you, Dr.

00:29:23: Maselli, for joining me today for this robust discussion on the current and future treatment landscape for patients with bronchiectasis.

00:29:30: We hope our listeners have found this discussion useful, and thank you for listening.

00:29:39: You can listen to more podcasts

00:29:41: by subscribing

00:29:42: to ADIS Journal Podcasts with your preferred

00:29:45: podcast provider

00:29:46: or by visiting the journal website.

00:29:49: For a full list of declarations, including funding and author disclosure statements and copyright information,

00:29:55: please visit the

00:29:57: article page on the journal website.

00:29:59: The link to the

00:30:00: article page can be found

00:30:02: in the podcast description.