Reference: April 2025 | Issue 4 | Vol 11 | Page 3
The 2024 Irish Thoracic Society Annual Scientific Meeting in Derry welcomed respiratory experts from both sides of the Irish border, and beyond, to a diverse programme of lectures, evidence-based practice updates, and professional collaboration.
The three-day event began with specialist registrar training updates in nasal disease, inducible laryngeal obstruction, sleep, and asthma, followed by a case study forum.
Several distinguished national and international specialists delivered guest lectures during the second and third days of the conference, which also boasted a range of parallel poster presentations, oral sessions, and clinical discussions.
Specialist affiliate forums that also took place during the event included meetings of the Respiratory Nurses Association of Ireland, the Irish Institute of Clinical Measurement Physiology, the Pleural Group, and a paediatric forum.
Among myriad highlights, Dr Kerri Johannson, Associate Professor, Departments of Medicine and Community Health Sciences, and member of the Snyder Institute for Chronic Diseases at the University of Calgary, Canada, delivered a comprehensive clinical update on hypersensitivity pneumonitis.
Prof Cecilia O’Kane, Professor of Respiratory Medicine at Queen’s University, Belfast, discussed the latest advances in non-TB mycobacteria, and Prof Gisli Jenkins, Consultant Respiratory Physician, Guy’s and St Thomas’ NHS Foundation Trust, London, UK, explored the role of biomarkers in diagnosing and managing interstitial lung disease.
Altering the trajectory of COPD
The meeting heard an engaging and evidence-based talk on altering the trajectory of COPD from Dr Alexander Mathioudakis, incoming Chair of the European Respiratory Society Airways Pharmacology and Treatment Group.
Dr Mathioudakis, from the UK National Institute for Health and Care Research (NIHR), is also a clinical lecturer in respiratory medicine at the University of Manchester and Manchester University NHS Foundation Trust. Dr Mathioudakis’ own research focuses on personalised medicine and airways disease phenotypes, much of which he shared during the presentation.
COPD patients experience “an unacceptable disease burden despite optimal treatment”, Dr Mathioudakis told the conference. He noted that the heterogenous nature of the disease is a major challenge for clinicians. “Patients do not respond to the same treatment,” he said, adding that grouping this cohort into phenotypes has not provided a solution since patients often overlap across these groups.
Dr Mathioudakis told delegates that carefully identifying, characterising, and targeting treatable traits which contribute to, or cause, COPD exacerbations, such as bacterial or viral infections, airway eosinophilic inflammation, poor adherence to treatment, air pollution, mucus plugging, and others, can achieve more personalised interventions.
Attendees heard that effective management of these treatable traits can help to improve patient outcomes and reduce the unnecessary use of medications – “primarily antibiotics and steroids that can have severe adverse effects”. Dr Mathioudakis also said that identifying traits which contribute to long-term deterioration will lead to treatments that can “prevent lung function decline and salvage lung tissue after exacerbations”.
Dr Mathioudakis proceeded to discuss the characterisation of COPD exacerbations –those caused by the presence of bacteria, viruses, and eosinophilic inflammation, or those that lack a notable eosinophilic response. He acknowledged the “significant overlap” among these categories.
“It is estimated that up to 50 per cent of exacerbations are associated with bacterial infection, however and unfortunately, we treat a significantly higher proportion with antibiotics,” he said. Dr Mathioudakis described this situation as “problematic” in view of risks like antimicrobial resistance and microbial dysbiosis.
Moving on to explore the benefits and limitations of common biomarkers to guide antimicrobial prescribing, Dr Mathioudakis said that using sputum purulence as an indicator results in around 60 per cent of COPD exacerbations being treated with antibiotics. “Purulence is not a sensitive biomarker,” he concluded, before presenting the empirical data from the CATCH study, PACE trial, and others that examined C-reactive protein (CRP) to guide antimicrobial prescribing in COPD exacerbations.
“CRP seems to be a good biomarker,” he outlined, “but we have a few limitations” such as the lack of a universally accepted threshold and non-specificity of the test. He also detailed data indicating that procalcitonin is a more specific biomarker than CRP, which can also reduce the use of antibiotics, but noted that evidence to support its implementation is lacking, that the test is expensive, and not widely accessible.
Delegates then received a comprehensive overview of existing knowledge to guide steroid prescribing in COPD exacerbations. “There is emergent evidence that eosinophil levels can predict response to steroids,” Dr Mathioudakis said, and described findings to suggest that it is “safe not to give steroids for patients with low blood eosinophils”. He did note that further data is needed to reach definitive conclusions regarding systemic corticosteroid administration, before discussing viral exacerbations of COPD and the substantial burdens associated with comorbidities like pulmonary embolism and heart failure. Dr Mathioudakis said “it’s really important to be more vigilant” about assessing for comorbid conditions.
He acknowledged that many of the treatable traits associated with COPD exacerbations, such as infections, chronic inflammation, comorbidities, reflux, ongoing smoking, and poor treatment adherence, are already addressed in clinical practice. He then noted that 20-40 per cent of patients have an eosinophilic phenotype, meaning they have ongoing inflammation.
He discussed the conflicts and evidence base underpinning inhaled corticosteroid (ICS) prescribing in COPD. “Data shows that ICS increases the risk of pneumonia,” stated Dr Mathioudakis, who described the complexity surrounding ICS administration and associated risks.
Delegates heard that although serum eosinophil levels can predict which patients will respond to ICS administration, clinicians “need to assess several variants over time”, as these biomarkers are reduced in 40 per cent of patients who benefit from ICS therapy, remain stable in another 40 per cent of patients who experience neither benefit nor harm from ICS therapy, and increase in 20 per cent of patients who are harmed by ICS and face a “significantly higher risk of exacerbation and accelerated lung function decline”.
“Instead of looking at patients with high eosinophils, it might be smarter to look for patients that have recurrent chest infections and try discontinuation of ICS,” Dr Mathioudakis suggested.
“Measure blood eosinophils, stop ICS, and measure eosinophils two weeks later. If eosinophils were suppressed on ICS, it’s likely that these are the people who are benefitting from therapy and we probably need to restart ICS. But if the blood eosinophils are not suppressed by ICS, it is probably a good decision to stop the treatment.”
Dr Mathioudakis went on to present research showing that current smokers do not gain as much benefit from ICS therapy as ex-smokers, before exploring the role of biologics in COPD. He described findings from the BOREAS and NOTUS trials that showed a decreased risk of exacerbations and improved lung function in COPD patients that resulted in the recent US Food and Drug Administration and European Medicines Agency approval of dupilumab for the disease.
Data was also discussed from trials evaluating the effects of benralizumab and mepolizumab in COPD. Dr Mathioudakis concluded his talk with “exciting findings”, potential new treatment options with biologics, and a bright outlook in the area of eosinophilic subtypes for managing the disease in future.
Obstructive sleep apnoea
A technologically- and clinically-grounded talk on advances in the diagnosis and management of obstructive sleep apnoea (OSA) was presented by Dr John Garvey, Consultant Respiratory Physician and Sleep Laboratory Director at St Vincent’s University Hospital, and Adjunct Assistant Clinical Professor, University College Dublin.
Dr Garvey acknowledged that there is “very little data from an Irish perspective” regarding OSA prevalence. He referenced a recent cross-sectional national survey of validated questionnaires regarding sleep-related issues and disorders that showed a symptom profile “very suggestive of undiagnosed OSA” in around 15 per cent of the Irish population, as well as a high prevalence of restless leg syndrome, diagnosed OSA, and diagnosed insomnia.
“It does appear that sleep conditions are prevalent. We seem to have an association within the Irish population with cardio-metabolic conditions and respiratory conditions. There’s also a high association with musculoskeletal disorders. Morbidity and mortality are even worse for these patients when they have OSA too.” He also emphasised that falling asleep at the wheel is more likely, and occurs more frequently, among people with OSA.
Dr Garvey introduced delegates to a range of “new diagnostic modalities that have the capacity to move away from polysomnography” in the diagnosis of OSA, including the French-made Withings smartwatch and sleep mat that are now approved by the US Food and Drug Administration for the detection of the disorder, as well as the detection of atrial fibrillation and the measurement of oxygen saturations.
“They have a remote patient monitoring programme, called Withings RPM, and in that they have weighing scales, blood pressure monitors, these sleep devices such as the mat, and thermometers, and it all feeds in and gives feedback on your health.”
Dr Garvey admitted that he could not verify the accuracy of the Withings devices, but to demonstrate the watch’s capabilities he used a light-hearted example of his own haemodynamic readings while watching the All-Ireland hurling final, during which he received repeated alerts about his heart rate.
An overview was provided of various other devices that Dr Garvey termed “wearable and nearables”, including commercial technology like Apple and Android smartwatches, and clinically focused tools. “It doesn’t tell you that your apnoea-hypopnoea index is 50,” Dr Garvey said about the technology, “it gives an alert saying you are at risk of OSA”.
“They do seem to be reasonably accurate in terms of what they are presenting,” stated Dr Garvey, who described the capabilities of these devices. He added that the majority of patients internationally are still going through traditional diagnostic pathways, such as polysomnography and home apnoea tests, despite the recent approval of several technologies.
Delegates heard that a total of nine devices have now been FDA-approved for the detection of OSA, with some being introduced and used in Ireland and the UK. The meeting received an overview of the mechanisms by which the various devices operate and how they utilise “the potential of artificial intelligence” for optimal results.
Moving from technology to pharmacology, Dr Garvey said that “conventionally, we think of OSA as an obesity-related collapsibility of the upper airway, but there’s a lot more involved”. He told delegates that until very recently, noradrenergic and anti-muscarinic agents have been the primary focus of pharmacological OSA management, before presenting the emerging evidence for the use of incretin-based therapies.
Dr Garvey talked about the “multiple physiological effects” of glucagon-like peptide-1 (GLP-1) in the body and presented data from the STRIFE trial, which evaluated the efficacy of daily liraglutide in people with obesity. He told attendees that he had referred several of his patients to the trial, and that they experienced “dramatic results” beyond merely weight loss. “The first patient lost one-third of his body weight. His chronic back pain, his OSA with an AHI (apnoea-hypopnoea index) of 70, his diabetes, and hypertension all resolved,” Dr Garvey said.
He went on to present positive data from various randomised control trials investigating the effects of other GLP-1 agents such as semaglutide and tirzepatide, referencing trials in which patients with moderate to severe OSA were treated with tirzepatide and achieved a “dramatic fall in weight” as well as a significant reduction in AHI.
“The effects are profound,” Dr Garvey told delegates. He presented findings demonstrating a range of additional benefits from using these drugs, as well as the advantages of bariatric surgery in both OSA and overall health.
Proceeding to an overview of non-pharmacological interventions for OSA, Dr Garvey described hypoglossal nerve stimulation, noting that several versions are available. “It seems to have benefits for patients, with clinically meaningful improvements in AHI,” he said.
The conference also heard that day-time training of tongue muscles is a technique used by some practitioners. “The idea is to strengthen muscle tone of the tongue and that patients will have a residual effect overnight,” he explained, adding that the technique is “unlikely effective in supine REM sleep due to the physiological drop in muscle tone” during that phase.
Concluding his talk, Dr Garvey said: “There is a little bit more happening, things are progressing. We’re struggling with the numbers of referrals that we have. If you have wearables and nearables that are giving messages like ‘you might have moderate or severe OSA’, more patients will be seeking referral. To use these new modalities, we’re going to have to look at integrating with platforms and AI to try to improve things. Maybe GLP-1 agonists will improve things dramatically over the next few years.”
Tackling chronic cough
Chronic cough, defined as a cough lasting more than eight weeks, affects up to one in 10 adults, according to Prof Jacky Smith, NIHR Senior Investigator, Director of the NIHR Manchester Clinical Research Facility, and Respiratory Theme Lead in the NIHR Manchester Biomedical Research Centre. She shared her knowledge and insights into the mechanisms of refractory chronic cough and developing management strategies.
Prof Smith described an increased prevalence of chronic cough in people who smoke, women, and older people, noting that “patients with no obvious cause are tricky to treat”. She presented a typical case history to demonstrate the complexity of managing the condition, and discussed associated demographics and clinical features. “It’s incredibly disruptive and really impacts quality of life,” she said.
Healthy people cough typically 10-15 times per day, Prof Smith told delegates, and went on to differentiate between coughing in health vs coughing in disease. She described an array of mechanical and chemical triggers, and presented neuroanatomical diagrams depicting somatosensory vagal fibres to explain the sensory disturbances felt by patients in the throat.
Delegates heard that many patients are commonly experiencing asthma, nasal disease, gastro-oesophageal reflux disease, and eosinophilic bronchitis, and that challenges arise when a cough persists despite treatment of these underlying conditions.
“There must be some kind of different pathology going on here, and the best way to think about this is to look at innervation of the airways and how cough might be being evoked,” said Prof Smith, who detailed the neuro-physical pathways controlling cough.
“C-fibres characteristically respond to capsaicin, the pungent extract of chilli pepper,” Prof Smith said about the unmyelinated nerve fibres, and described this as “an important tool” in the study of chronic cough.
“[Capsaicin] acts through a receptor known as TRPV1 to evoke action potentials and produce coughing. It’s also temperature sensitive, as is the channel next to it, which is the TRPA1 sensor, and that also responds to lots of irritant chemicals. These C-fibres also express a very large number of receptors that will respond to inflammatory mediators, including P2X3, which responds to ATP, and that has turned out to be quite an important receptor,” she said.
Prof Smith elaborated further on various other chemo- and mechano-sensitive pathways, and explained that tonicity also activates these nerve fibres. “Hypotonicity is the release of ATP through activation of TRPV4, that’s activating the nerves, and that’s subsequently able to cause cough,” she explained.
“In our human hypotonic challenges, this occurred in our chronic refractory cough patients and not the healthy volunteers, which is why P2X3 antagonists are effective in this patient group and may be effective in subgroups of patients with other diseases.”
Prof Smith said there is “quite a bit of evidence to support the concept that the airways are hypersensitive and inhibitory mechanisms are impaired” in chronic cough.
She said standard therapies such as low-dose morphine and gabapentin “have been shown in studies to be effective, but have side effects and significant abuse potential”. Prof Smith noted that speech and language therapy can also benefit some patients, but is not always widely available. “There’s a number of ways in which these pathways are abnormal, so there are a number of ways to address treatment,” she said.
“You can try to reduce airway nerve activation, reduce conduction in those vagal afferent fibres, and try to interfere with upregulation of inhibitory pathways in the central nervous system,” Prof Smith told delegates, highlighting that most CNS-targeting drugs are associated with multiple side effects. “Most efforts have been focusing on peripheral mechanisms, and we see the most success in blocking P2X3 ion channels that are activated by ATP.”
Prof Smith presented an overview of findings from her own research using the oral P2X3 receptor antagonist gefapixant to treat chronic cough. “The drug at 45mg had quite a dramatic effect on cough from baseline, reducing the amount of coughing by about 60-65 per cent, but it also had a substantial placebo effect.
The drug has been licensed in Europe and the UK, but was not licensed by the FDA (US Food and Drug Administration) because they were unconvinced that this placebo effect was clinically meaningful, and were concerned about the taste side effects, which were much milder than what we saw in previous studies.” The treatment has not yet been funded in Ireland and is only available on private prescription.
Prof Smith concluded by saying that “hyperexcitability of the neuronal pathways is the main problem” in refractory chronic cough, and that blocking peripheral pathways is making “substantial differences” to patients. “Hopefully these therapies will be available to prescribe in clinic for our patients soon,” she said.
