Innovation, advances, and evidence-based medicine

An abundance of novel research findings from procedural, pharmacological, medical, and other aspects of respiratory care was presented during oral presentations and guest lectures throughout the Irish Thoracic Society Annual Scientific Meeting. The “very common challenge” of unilateral pleural effusion was addressed by Dr Sally Griffiths, Respiratory Registrar at Galway University Hospital (GUH), who presented results from a retrospective 10-year review of medical thoracoscopies at GUH. The review found the procedure offered a safe and effective method of obtaining parietal pleural biopsies to diagnose malignancy in suitable patient groups.

“Thoracoscopy is a safe and highly sensitive procedure in appropriately selected patients. It reduces the need for multiple aspirations or biopsies and shortens time to diagnosis. It remains the gold standard for molecular diagnosis, and has an equal diagnostic yield to surgical VATS [video-assisted thoracic surgery] and, in appropriately selected patients, can be performed in an outpatient or ambulatory setting.”

In pharmacological-based data, attendees heard that the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin may have benefits that extend beyond diabetes management and into lung fibrosis care. Introducing findings from a study at Queen’s University Belfast, Mr Paul Peppard began by describing human epididymis protein 4 (HE4), a mediator linking fibrosis and inflammation that is increased in fibrotic lung conditions, such as systemic sclerosis and interstitial lung disease.

“It suppresses multiple proteases and inhibits their capacity to create type 1 collagen,” Mr Peppard said about HE4, and elaborated on the study that looked specifically at fibrotic and inflammatory pathways in epithelial bronchial cells. Highlighting the urgent “need to develop new anti-fibrotic drugs”, he then explained that the SGLT2 inhibitor significantly reduced hypoxia-induced HE4 and exhibited both anti-fibrotic and anti-inflammatory properties in a model of lung fibrosis.

“We concluded that dapagliflozin significantly reduces HE4, both expression and secretion, in airway epithelial cells,” he said, before acknowledging that the exact mechanisms of action remain unclear. “Further work is needed to establish HE4 as a biomarker of disease and disease progression,” he said.

The meeting also learned that the adenoviral Covid-19 vaccine exhibited extended positive benefits by enhancing monocyte responses to Mycobacterium tuberculosis (TB), and may induce trained immunity. Ms Dearbhla Murphy, who won best oral presentation at the event, said that a quarter of the global population has a latent TB infection, and that the disease is still “a long-term concern”. She then presented evidence from Trinity College Dublin that found expression of HLA-DR, CD40, and CD80 on monocytes was enhanced following a single vaccination dose, that monocytes showed evidence of increased glycolysis, and produced more IL-1b, IL-6, CXCL1, AND MIPa after TB stimulation in the study.

Moving from drugs to diet, Dr Natalia Muñoz-Wolf, Immunologist at Trinity College Dublin, proposed a positive link between fermentable dietary fibre intake and improved outcomes in Streptococcus pneumoniae infection via the gut-lung axis. She described the short chain fatty acid butyrate, a microbiota-derived metabolite with immunomodulatory properties that travels from the gut to the lungs via circulation, before detailing the in vivo study methodology that found butyrate pathways modulated macrophage phenotype and function in Streptococcus pneumoniae infection.

“We were able to demonstrate that butyrate is protective during pneumococcal pneumonia. Butyrate causes infiltration of Ly6C positive monocytes, which contributes to bacterial clearance. Butyrate regulates the capacity of monocytes to phagocytose and kill intracellular bacteria… and it modulates inflammatory cytokine production.”

In immunology, Dr Guy Scadding, Consultant Allergist at the Royal Brompton Hospital, Guy’s and St Thomas’s NHS Trust, and Honorary Senior Clinical Lecturer at Imperial College, London, UK, presented evidence for allergen immunotherapy in managing, and potentially preventing, allergic airway disease. He discussed a wide range of applications, including non-allergic rhinitis, chronic rhinosinusitis, and asthma, as well as food, medication, and insect venom allergies and anaphylaxis, and presented a wealth of supporting empirical data to attendees.

In a lively questions and answers session after the talk, “problems in mainstreaming the treatment in Ireland and the UK” were highlighted and discussed. Dr Scadding said “a number of factors”, such as price, a lack of interest among regulatory authorities, and “head-to-head data” against corticosteroids likely contribute to challenges with mainstreaming the therapies for appropriate patient groups.