Brensocatib ‘a game changer’ in treatment of bronchiectasis
The Irish Thoracic Society Annual Scientific Meeting took place from 20-22 November 2025 at the Galway Bay Hotel. Throughout the meeting, attendees heard from international and national experts in respiratory medicine about the latest developments and advances in the field.
The first guest lecture was delivered by Prof James Chalmers from the University of Dundee, Scotland, and chief editor of the European Respiratory Journal. Prof Chalmers, a renowned consultant respiratory physician, runs a specialist clinic for patients with complex respiratory infections, particularly bronchiectasis, at Ninewells Hospital, Dundee.
In his talk, ‘Big news for bronchiectasis’, he highlighted bronchiectasis research as a rapidly advancing and dynamic field, encouraging early-career attendees to consider it as a focus within the specialty. The meeting heard that patients with bronchiectasis face a significant symptom burden and frequent exacerbations, with around 25 per cent requiring hospitalisation for an exacerbation each year across Europe.
“This is not a mild disease,” Prof Chalmers said, adding the condition was “incredibly heterogeneous”.
He said that the condition is his passion, having worked in the area for the last 20 years, and, for him, a “major driver” of clinical trials has been to discover improved treatment options. “There is a lot happening in bronchiectasis. But this was a field where historically there hasn’t been a lot going on,” he said. “In the last one to two years, it really has been transformed.”
Previously, Prof Chalmers noted that bronchiectasis had long been neglected and viewed as a condition of limited significance. “It was [believed to be] rare. It was predominantly caused by tuberculosis (TB), and in places like western Europe, where TB rates were going down, bronchiectasis [was thought to] disappear,” he said.
“[But] we now know that bronchiectasis rates have been rocketing in the last 20 to 30 years, as we recognised these cases with the advances in CT.”
This recent surge in activity has led to a dramatic rise in bronchiectasis clinical trials, increasing from a single study in the early 2000s to more than 10 randomised controlled trials completed or reported last year.
Regarding treatments, he noted that long-term macrolides are highly effective, yet only 17 per cent of patients across Europe currently receive them. “We know they reduce exacerbations, but for some reason they don’t get used as a preventative therapy for most of those frequent exacerbators,” he said.
He added that significant work was required to provide a common, high standard of care for people with bronchiectasis, and “a lot of that starts with trials”.
Prof Chalmers said that earlier this year, the US Food and Drug Administration approved 10mg and 25mg doses of brensocatib, while the European Medicines Agency (EMA) approved the 25mg dose in November, marking the first ever licensed therapy for bronchiectasis. He added that clinical trial data showed brensocatib reduced exacerbations by 20 per cent at both doses.
He noted that the 25mg dose offers the same efficacy in reducing exacerbations, while also providing additional benefits for lung function and symptoms. “I think the EMA has made the right decision,” he said. “And there is much more to come – there are trials opening up everywhere because of the success of brensocatib and the availability of data.”
Prof Chalmers concluded that the new guidelines encourage clinicians to take a proactive approach in managing bronchiectasis patients. He reiterated that macrolides are often the first-line treatment and, while not suitable for everyone, they are very effective, adding that “brensocatib is going to be a game changer”.
Prof Chalmers urged the meeting to also address other treatable aspects of bronchiectasis, including exercise, bronchodilators, and additional supportive therapies. “There is a lot we can do for these patients, and we should be aiming to improve everyone’s outcomes.”
More robust diagnostic strategy for asthma needed
A more robust diagnostic strategy for confirming asthma in patients would be valuable for clinicians, the recent Irish Thoracic Society (ITS) 2025 Annual Scientific Meeting heard.
Dr Cara Gill, a respiratory specialist registrar and research fellow at Beaumont Hospital, Dublin, presented a talk titled ‘Asthma untangled: Standardising expert clinician judgement with a structured multi-modal approach’.
Dr Gill and colleagues recently completed a prospective cohort study, with the primary objective of demonstrating the efficacy of the AZTEC score. She explained that the study aimed to answer the question: ‘Do patients in clinic actually have asthma to begin with?’
“The first question we had to ask is how do we actually decide what was asthma and what wasn’t asthma,” she said.
Dr Gill added that a cohort of patients referred from primary care, or other clinics in the hospital, had symptoms suggestive of asthma or the label of asthma. “They were already on inhaled corticosteroid therapy and they remained symptomatic,” she said. “We know that the guidelines don’t really tell us what to do with these patients to confirm that they have asthma,” she said.
The team assigned a score to features that suggested that patients had asthma or another condition. Patients attended the clinic five times over six months, and investigations, including questionnaires and home FEV1 (forced expiratory volume in one second) monitors, were performed.
“After the end of that [period], we were able to provide a template that assigned up to 16 features that suggested someone had asthma or did not have asthma,” she said.
A total of 222 people completed the study, with asthma confirmed in 60 per cent of participants. Among the 40 per cent who did not have asthma, other conditions included allergic rhinitis, gastro-oesophageal reflux disease, and chronic obstructive pulmonary disease (COPD). She said that the study highlighted the need for a more robust diagnostic strategy in confirming asthma.
The ITS meeting also heard from Prof Breda Cushen, HSE National Respiratory Clinical Lead, who delivered a guest lecture on the changing face of COPD care in Ireland. Prof Cushen said that clinical outcomes are better when comprehensive multidimensional approaches are used to inform clinical decision-making in complex conditions like COPD.
Although she admitted there were regional disparities, Prof Cushen said Ireland has taken a “visionary approach” to COPD care.
PCD more common than currently recognised
Primary ciliary dyskinesia (PCD) is much more common than currently recognised, the Irish Thoracic Society 2025 Annual Scientific Meeting heard. An inherited disorder, PCD is a clinically and genetically heterogeneous condition, caused by pathogenic variants in at least 50 genes, but likely many more.
The variants result in the congenital impairment of mucociliary clearance due to a defect in the cilia. Clinically, PCD is variably characterised by bronchiectasis, chronic rhinosinusitis, recurrent otitis media, laterality defects, and infertility.
Dr James O’Hanlon, University Hospital Galway (UHG), gave a presentation on ‘A view of PCD in a tertiary referral centre in Ireland’ to the meeting. Dr O’Hanlon told attendees that PCD prevalence “is likely grossly underestimated”, with only 1,236 people with genetically-diagnosed PCD known to the European Reference Network (ERN)-LUNG registry and 698 included in the US registry.
He added that a 2022 Lancet study looked at the frequency of disease-causing variants in 29 PCD genes in 182,000 individuals worldwide. The study estimated the global prevalence of PCD to be one in 7,500.
“We know that at least 50 genes are associated with PCD, with 37 deemed definitely associated,” he said.
Another 2022 study from the European Respiratory Journal found that motile ciliopathy associated genes were identified in 12 per cent of the 142 patients recruited for whole-genome sequencing who had a diagnosis of idiopathic bronchiectasis.
“The bottom line is that most people with PCD remain undiagnosed,” Dr O’Hanlon said. He added that different mutations can affect different parts of the axoneme, resulting in variable clinical manifestations.
“The resultant lung disease is heterogeneous across all ultrastructural and genotype groups and some are more severe than others,” he said. They are worse in those with inner dynein arm, central apparatus, and microtubular disorganisation ultrastructural defects, Dr O’Hanlon noted.
“When we compare this to [cystic fibrosis], which is a monogenic disease, we can see that comparatively there is a huge variety in what can go wrong in PCD and how that can present.”
Traditionally, guidelines have recommended using a combination of tests to diagnose PCD. In Ireland, however, the requirement for patients to travel abroad for these investigations has likely led to their under-utilisation, resulting in a greater reliance on clinical features for diagnosis.
This year, the European Respiratory Society and American Thoracic Society published consensus guidelines for the diagnosis of PCD for the first time. The diagnosis can be confirmed either by genetic testing or by transmission electron microscopy (TEM), but other methods can support a diagnosis in the correct clinical context.
High-speed video microscopy is the only diagnostic test that allows direct visualisation of ciliary dyskinesia. It can identify abnormalities in cilia affected by pathogenic mutations in DNAH5, the most common gene associated with PCD. Immunofluorescence is another valuable tool, particularly for clarifying genetic uncertainty related to variants of unknown significance, such as HYDIN.
“The guidelines recommend that PCD patients would have all of these investigations performed, but a more practical approach is possible where access is limited,” he said. “Immunofluorescence is much easier to analyse and perform than TEM, so we will likely see a more prominent role in diagnosis going forward.”
He emphasised the importance of obtaining a clear diagnosis, noting that patients with confirmed PCD gain access to specialised, multidisciplinary care provided through dedicated PCD referral centres. Following diagnosis and the initiation of appropriate management, stabilisation of the condition and improvements in lung function can also be achieved.
He noted that delayed diagnosis in adults with PCD is associated with reduced ‘forced expiratory volume’ at the time of diagnosis, as well as an increased likelihood of Pseudomonas aeruginosa colonisation.
“Now there are specific therapies in development targeting known pathogenic mutations, which will hopefully be a future therapy option for our patients,” he said.
While genetic diagnosis is strongly encouraged whenever possible, it is negative in about 30 per cent of cases, so often further testing is needed, the meeting heard. TEM is the only way to confirm a diagnosis where there is no pathogenetic phenotype identified. TEM is 99 per cent specific in confirming a PCD diagnosis when performed within specialist centres.
Nasal nitric oxide (nNO) testing can also support a diagnosis and is easily performed in clinic. It can be measured during velum closure or tidal breathing, with velum closure providing greater accuracy and less variability.
Dr O’Hanlon explained that in UHG, a search was carried out on a clinic letter database for mention of PCD or related terms. Patients who had been given PCD as a primary diagnosis were identified.
Patients were further analysed with regard to previous diagnostic evaluation, clinical features, co-morbidities, and sputum microbiology. The aim of the study was to identify patients with suspected PCD, and assess their previous diagnostic evaluation. A diagnosis would then be made and formal multidisciplinary care would be instituted.
A total of 25 patients were identified, 60 per cent of whom were female, with a median age of 38. Four of these patients had a diagnosis confirmed by genetic testing or TEM.
“So, despite having typical clinical features, the vast majority of patients with suspected PCD had not had the required diagnostic work-up to confirm the diagnosis.”
Following these findings, clinicians continued to actively case-find while also identifying cases opportunistically. Once identified, these patients were referred to the specialist bronchiectasis clinic for comprehensive evaluation and management.
“Now we have five new confirmed diagnoses of PCD by genetic analysis,” he said. nNO has been performed in 12 patients and was positive in nine. One patient was referred to the UK for TEM.
Regarding the most common causative genes, five were identified, with HYDIN being by far the most frequent. The HYDIN gene encodes a protein essential for ciliary motility, but it does not affect the overall ciliary ultrastructure, meaning that TEM results appear normal.
“These patients often have preserved lung function,” he said. He also highlighted that the majority of these patients are within the Traveller community.
In terms of take-home messages, Dr O’Hanlon emphasised that clinicians should maintain a high index of suspicion for PCD in patients with typical features, as a confirmed diagnosis has important implications for care. Certain causative genetic mutations, such as HYDIN, may be more prevalent in Ireland than in other populations.
When asked why HYDIN may be more common here than elsewhere, Dr O’Hanlon said it was known to be more common in closed ethnic groups, with consanguinity a big risk factor.
“But we would still not expect to see it as prevalent in Ireland as compared to the rest of Europe. Most of the people we have seen are members of the Traveller community, but some are not, and don’t have any risk factors. So there is more to it than that as well.”
He stated that UHG, along with other sites in Ireland, will be designated as a PCD centre as part of the ERN-LUNG International PCD Registry.
“We then will be able to centralise care and establish a nationwide diagnostic pathway for adult and paediatric medicine, which will hopefully have important implications for these patients.”
Pricing on obesity medications must be addressed
The dominant intervention for patients presenting with severe and complicated obesity remains surgery, the Irish Thoracic Society 2025 Annual Scientific Meeting was told by a leading expert
in the field. “There’s no equivocation about that,” Prof Francis Finucane, Consultant Endocrinologist, University Hospital Galway, and Professor of Medicine, University of Galway, informed attendees.
During a talk entitled, ‘A two-pronged approach to obesity’, Prof Finucane explained that surgery was safe and more effective “than even the best drugs still”. “And importantly, it is very cost-effective, especially against drug therapy,” he said.
However, Prof Finucane added that new medications have “totally changed our thresholds for certain interventions, the ambitions we have for patients, and their expectations”.
Regarding drug therapy, Prof Finucane explained that progress had been slow for many years, until the recent development of glucagon-like peptide (GLP)-1 receptor agonists, which have significantly changed treatment options and patient outcomes.
“GLP-1 is a ubiquitous molecule in the sense that it is produced all along the gastrointestinal tract,” he said. “It has numerous actions on lots of different tissues.”
However, Prof Finucane added that these medications’ actions are predominantly felt in the centres in the brain that influence appetite, satiety, and reward centres associated with eating. “That’s how these drugs work. We talk about ‘weight loss’ drugs, but really we want to reframe that,” he said. “These aren’t so much ‘weight loss’ drugs as ‘eat less’ drugs.”
He added that the medications can have side effects, including pancreatitis, which occurs in approximately one in 500 patients, gallbladder disease in nearly 4 per cent, and more common issues such as constipation, vomiting, and nausea. “There are a lot of things we need to think about when we prescribe them.”
While they can be very effective, Prof Finucane stressed that there is a variation in the response of patients to the medication in terms of weight loss. “It is not a reflection of their intelligence or motivation – it’s a reflection of their biology,” he said.
“We don’t know and the big challenge is trying to figure out the variation in response to these drugs.”
Answering this question would save patients from “futile treatment” and the health service considerable funds. “There are a significant minority, even with the best drugs, who don’t lose any weight,” he said.
Prof Finucane said people with obesity who need treatment “ought to be getting the drugs provided by the healthcare system, according to the same rules we provide drugs for other conditions”.
“Why is that not happening in Ireland? The biggest challenge we face is that our patients can’t afford these drugs. I might see 20 patients on a morning, and we might offer 10 of those patients obesity medications, and half of them will say ‘I can’t afford them’. It is heartbreaking. And I think it is unique in medicine, where you have a situation where you’d like to offer a patient a safe, efficacious treatment and you can’t because they can’t pay for it. That is a huge challenge.”
He said that these medications are too expensive and this was “a nettle that needed to be grasped” by society. “We’re aligned with drug companies 99 per cent of the time, but when it comes to the cost of medications, our interests and our patients’ interests are diametrically opposed to the commercial interests of drug companies, which by law have to make a profit and have to maximise the return for their shareholders.”
He said that companies need to be encouraged to “do the right thing by society” in terms of pricing.
Prof Finucane also urged Ireland to adopt a similar approach to unhealthy, ultra-processed foods as it did with smoking, describing the recent series of Lancet articles on obesity as a “blueprint for government action”.
“We have to emulate what you have done over the last 30 years in respiratory public health. We are way behind,” he said. “Voluntary codes around the marketing and advertising of unhealthy food to children are toothless, unenforceable, and tend to go around in circles… There is complete policy inertia when it comes to obesity and yet we think we are doing great.”
Prof Finucane highlighted the work of the new HSE National Clinical Programme for Obesity in providing a positive framework of care for patients with severe and complicated obesity. He also praised the 2013 Healthy Ireland strategy.
“Then by 2015/2016, they had the obesity policy and action plan, and it was clear that industry had time to get its ducks in a row and influence that very strongly.”
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