Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) are characterised by relentless fibrotic progression resistant to standard therapy. Purinergic signalling is poorly defined in IPF and PPF, and in this study we performed gene and protein expression analysis of immune and epithelial cells to better characterize P2X and P2Y receptor subtypes in patients with progressive fibrotic interstitial lung diseases (ILD). Patients with ILD (n = 11), bronchoscopy patient controls (n = 6) or healthy control subjects (n = 11) were recruited. ILD nasal epithelial cells and bronchoalveolar lavage (BAL) immune cells showed significantly elevated protein expression levels of P2X7 (P = 0.0064) and P2Y4 receptors (P = 0.004 and P = 0.0145), with ILD monocytes additionally demonstrating increased P2X4 (P = 0.0022). Levels of the receptor agonist, extracellular ATP (eATP), were 13-fold higher in ILD compared to controls (P < 0.0001). eATP inversely correlated with lung function (P = 0.001), and associated with increased receptor expression in vitro (P = 0.0313). In addition, cytokines downstream of ATP purinergic receptor signalling including IL-β (P < 0.0001), TNFR1 (P = 0.0002), TGF-β (P = 0.002) and VEGF (P = 0.0048), were higher in BAL or plasma of ILD patient samples. These findings suggest eATP–P2 receptor signalling as a potential contributor to inflammation and fibrosis across IPF and PPF, highlighting this pathway as a promising therapeutic target.

Background: Interstitial lung diseases (ILDs) or diffuse parenchymal lung diseases are general terms for a group of over 200 conditions that result from the destruction of cells neighbouring the alveoli, leading to extensive inflammation and fibrosis of the lungs. Although different types of ILD have distinct pathophysiology, clinical display, and advancement, many forms drive irreversible pulmonary fibrosis (PF), leading to progressive functional impairment, respiratory failure, and mortality. Summary: Key components of innate immunity include proteases and their cognate inhibitors, which are involved in respiratory homoeostasis. Alterations to the protease-antiprotease balance can lead to pulmonary disease and fibrotic scarring of the lungs, and over the past two decades, there has been a surge in research exploring their effect on the pathogenesis of ILDs. We have evaluated relevant studies regarding these enzymes in the context of lung fibrosis and have discussed prospects for developing novel treatments. This review will place greater emphasis on the overall effect of proteases and antiproteases to the development of PF, as studied using both in vivo and in vitro models. Key Message: Considering the limited therapeutic interventions, continued research on proteolytic enzymes and their inhibitors is required for the development of novel effective treatments for PF.

BACKGROUND:2-Deoxy-2-[18F]fluoro-d-glucose (FDG)-PET/CT imaging has utility in identifying sites of active sarcoidosis. However, the role of FDG-PET/CT imaging in predicting treatment response and guiding therapy outside of cardiac disease is yet to be completely understood. RESEARCH QUESTION:Do physicians agree on the utility of FDG-PET/CT imaging in sarcoid cases, and do they agree on the appropriate treatment response, based on the associated reports? STUDY DESIGN AND METHODS:Physician respondents were presented with a series of anonymized sarcoidosis case vignettes. The perceived utility of FDG-PET/CT imaging in each case, as well as the ultimate treatment decision following provision of FDG-PET/CT results, was assessed. Interrater agreement was assessed overall and per-case vignette specialty, using the Gwet agreement coefficient (AC1). RESULTS:Respondents (n = 215) were predominantly respiratory physicians (86.78%) experienced in sarcoidosis management (94.39%), and one-third of whom had > 20 years of experience (32.66%). Pulmonary sarcoidosis case vignettes had the lowest rates of FDG-PET/CT endorsement among surveyed subspecialties (38%-64%). Overall interrater agreement was assessed among physicians who positively endorsed FDG-PET/CT imaging. Treatment rationalization based on FDG-PET/CT report approached near-chance agreement for pulmonary cases (AC1 = 0.178) (n = 217; 95% CI, 0.125-0.234; P = .07) and multisystem cases (AC1 = 0.296) (n = 168; 95% CI, 0.066-0.477; P = .41), whereas agreement was highest for cases of cardiac sarcoidosis (AC1 = 0.797) (n = 374; 95% CI, 0.759-0.838; P < .05). INTERPRETATION:Our results indicate low agreement between physicians regarding their management of pulmonary sarcoidosis following FDG-PET/CT imaging. This highlights a need for further research and clarity concerning the role of FDG-PET/CT imaging in the therapeutic management of pulmonary sarcoidosis.

Ulcerative colitis (UC) is a clinicopathologically challenging diagnosis that greatly impacts patients’ quality of life. The recently developed Inflammatory Bowel Disease-Distribution, Chronicity, Activity (IBD-DCA) scoring system offers histopathologists a consistent template to report colonic biopsies from UC patients in a standardised manner. We reviewed the rate of uptake of the IBD-DCA system within our department since its inception in 2022, and statistically correlated our histological findings with the corresponding UC Endoscopic Index of Severity (UCEIS). Of the 449 cases of IBD biopsies reported, 291 were established UC cases. The uptake of the IBD-DCA reporting format reached beyond 95

Abstract Background Histological assessment is not currently recognised as an independent parameter to guide personalised treatment for patients with ulcerative colitis (UC). The development of the Inflammatory Bowel Disease – Distribution, Chronicity, Activity (IBD-DCA) score allows a pragmatic approach to quantitatively evaluate mucosal injury and healing in UC, compared with other pre-existing histological scores (Lang-Schwarz et al., J Crohns Colitis, 2021). This scoring system facilitates a template-based reporting to produce consistent reports with information representing UC severity. Each domain of the IBD-DCA is scored as one of 0 (normal), 1 (mild), or 2 (moderate to severe) based on the presence of established histological UC findings (Figure 1). This project aims to prospectively validate the IBD-DCA score for routine clinical deployment and correlate with endoscopic scores – UC Endoscopic Index of Severity (UCEIS) and Mayo Endoscopic Score (MES). Methods Colonoscopic biopsies from patients with a previously confirmed diagnosis of UC attending one of four hospitals in a single healthcare group from August 2022 to January 2023 were reported using the IBD-DCA histological score, and the corresponding, clinician-reported UCEIS and MES scores were recorded. The histopathology reports were assessed based on the completeness of information in their respective D, C, and A domains. The proportion of reports with information fully represented by the IBD-DCA reporting template and the distribution of biopsy sites were described. The correlation between IBD-DCA with UCEIS and MES was quantified via Kendall’s tau (τ) using the R statistical package v4.3.2. Results Of the 151 cases reported, 70 (46.4%) patients were female and 81 (53.6%) were male. 12 patients (7.9%) had full colonic biopsies, while the remaining cases were assessed with selective biopsies. Rectal biopsy was most often performed (83.4%). The IBD-DCA components were reported for every biopsied sites in 133 (88.1%) cases. Notable correlations included UCEIS vascular pattern with histological chronicity (τ = 0.3891), UCEIS erosions/ulceration with histological activity (τ = 0.3252), and histological activity with the total UCEIS score (τ = 0.3450). MES showed the strongest correlation with histological disease distribution (τ = 0.3450)(Table 1). All p-values < 0.001. Conclusion These data show encouraging uptake of this simple histological reporting template in UC in daily routine use. The findings suggest that the IBD-DCA score may be a useful addition in the clinical management in patients with UC.

Background: Interstitial lung diseases (ILD) are poorly understood disorders characterised by diffuse damage to the lung parenchyma, with inflammation and fibrosis. Some manifest a progressive fibrotic phenotype with high fatality and limited treatment options, such as idiopathic pulmonary fibrosis. Summary: The degree to which inflammation plays a role in fibrosis progression is unknown. However, wound healing and fibrosis are intricate processes influenced by various inflammatory factors. Extracellular nucleosides and nucleotides, including adenosine triphosphate, activate pro-inflammatory responses to innate immunity and are widely implicated in tissue fibrosis across different organs. The pro-inflammatory effects of extracellular nucleotides occur via P1 and P2 purinergic receptors, expressed across the lung and immune system, and have been implicated in various pulmonary diseases including pulmonary fibrosis. This review amalgamates available data on the complex role of P1 and P2 purinergic receptor signalling in pulmonary fibrosis and discusses perspectives for novel treatments. Key Messages: Purinergic signalling plays a complex and pivotal role in pulmonary fibrosis, warranting further study. The intricate interplay between P1 and P2 receptor pathways necessitates a comprehensive approach to understand their collective impact. While evidence from preclinical models is promising, human studies are essential for further understanding of pulmonary fibrosis. Advances in receptor-specific agonists and antagonists provide novel avenues for research and may ultimately lead to new therapies for patients.

18F-Fluorodeoxyglucose (FDG) PET/CT is emerging as a tool in the diagnosis and evaluation of pulmonary sarcoidosis, however, there is limited consensus regarding its diagnostic performance and prognostic value. A meta-analysis was conducted with PubMed, Science Direct, MEDLINE, Scopus, and CENTRAL databases searched up to and including September 2023. 1355 studies were screened, with seventeen (n = 708 patients) suitable based on their assessment of the diagnostic performance or prognostic value of FDG-PET/CT. Study quality was assessed using the QUADAS-2 tool. Forest plots of pooled sensitivity and specificity were generated to assess diagnostic performance. Pooled changes in SUVmax were correlated with changes in pulmonary function tests (PFT). FDG-PET/CT in diagnosing suspected pulmonary sarcoidosis (six studies, n = 400) had a pooled sensitivity of 0.971 (95

BACKGROUND AND OBJECTIVE:There is increasing interest in the role of lipids in processes that modulate lung fibrosis with evidence of lipid deposition in idiopathic pulmonary fibrosis (IPF) histological specimens. The aim of this study was to identify measurable markers of pulmonary lipid that may have utility as IPF biomarkers. STUDY DESIGN AND METHODS:IPF and control lung biopsy specimens were analysed using a unbiased lipidomic approach. Pulmonary fat attenuation volume (PFAV) was assessed on chest CT images (CTPFAV ) with 3D semi-automated lung density software. Aerated lung was semi-automatically segmented and CTPFAV calculated using a Hounsfield-unit (-40 to -200HU) threshold range expressed as a percentage of total lung volume. CTPFAV was compared to pulmonary function, serum lipids and qualitative CT fibrosis scores. RESULTS:There was a significant increase in total lipid content on histological analysis of IPF lung tissue (23.16 nmol/mg) compared to controls (18.66 mol/mg, p = 0.0317). The median CTPFAV in IPF was higher than controls (1.34% vs. 0.72%, p < 0.001) and CTPFAV correlated significantly with DLCO% predicted (R2 = 0.356, p < 0.0001) and FVC% predicted (R2 = 0.407, p < 0.0001) in patients with IPF. CTPFAV correlated with CT features of fibrosis; higher CTPFAV was associated with >10% reticulation (1.6% vs. 0.94%, p = 0.0017) and >10% honeycombing (1.87% vs. 1.12%, p = 0.0003). CTPFAV showed no correlation with serum lipids. CONCLUSION:CTPFAV is an easily quantifiable non-invasive measure of pulmonary lipids. In this pilot study, CTPFAV correlates with pulmonary function and radiological features of IPF and could function as a potential biomarker for IPF disease severity assessment.

Introduction: St. Vincent9s University Hospital ERN-Lung Centre for Interstitial lung diseases (ILD) reviews over 600 patients annually. The role of an advanced nurse practitioner (ANP) was established in 2021 to facilitate better access for patients to treatment, oxygen assessment, facilitation of transplant referral and appropriate institution of palliative care. THe ILD-ANP coordinates monthly ILD multidisciplinary meetings (MDM) to ensure prompt diagnosis. Objective: To determine the effect of an ILD-ANP on the provision of care in an ILD specialist centre. Methods: To determine the impact of ILD-ANP service two 12-month periods of activity and interventions were compared. A retrospective review of the ILD service was performed for the calendar years 2018 and 2022. Results: Following the introduction of an ILD-ANP service, the number of new patients seen increased 2.7 fold from 79 to 213 new patients respectively. The ILD-MDM saw an increase of 25% in the number of cases discussed from 160 to 200 cases. The ILD-ANP service conducted 1763 consultations/visits in a 12 month period. Moreover, the service handled 767 unscheduled telephone calls and had 631 indirect contacts with ILD patients. 207 oxygen assessments were performed by ILD-ANP and 6 minute walk tests were performed at 85% of initial clinic visits. 95% of patients seeking early review were accomodated within one week and 100% of patients referred for transplant received ILD-ANP reviews monthly. Conclusions: The addition of a specialist ILD-ANP at a busy ILD referral centre, has facilitated increased number of referrals to be adequately accomodated and improved patient care and service metrics.