Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and no curative therapies. Fibroblast activation by transforming growth factor β1 (TGFβ1) and disrupted metabolic pathways, including the arginine–polyamine pathway, play crucial roles in IPF development. Polyamines are agonists of the calcium/cation-sensing receptor (CaSR), activation of which is detrimental for asthma and pulmonary hypertension, but its role in IPF is unknown. To address this question, we evaluated polyamine abundance using metabolomic analysis of IPF patient saliva. Furthermore, we examined CaSR functional expression in human lung fibroblasts (HLFs), assessed the anti-fibrotic effects of a CaSR antagonist, NPS2143, in TGFβ1-activated normal and IPF HLFs by RNA sequencing and immunofluorescence imaging, respectively; and NPS2143 effects on polyamine synthesis in HLFs by immunoassays. Our results demonstrate that polyamine metabolites are increased in IPF patient saliva. Polyamines activate fibroblast CaSR in vitro, elevating intracellular calcium concentration. CaSR inhibition reduced TGFβ1-induced polyamine and pro-fibrotic factor expression in normal and IPF HLFs. TGFβ1 directly stimulated polyamine release by HLFs, an effect that was blocked by NPS2143. This suggests that TGFβ1 promotes CaSR activation through increased polyamine expression, driving a pro-fibrotic response. By halting some polyamine-induced pro-fibrotic changes, CaSR antagonists exhibit disease-modifying potential in IPF onset and development.

In idiopathic pulmonary fibrosis (IPF) breathing pattern changes with disease progress. This study aims to determine if unsupervised hierarchal cluster analysis (HCA) can be used to define airflow profile differences in people with and without IPF. This was tested using 31 patients with IPF and 17 matched healthy controls, all of whom had their lung function assessed using spirometry and carbon monoxide CO transfer. A resting tidal breathing (RTB) trace of two minutes duration was collected at the same time. A Euclidian distance technique was used to perform HCA on the airflow data. Four distinct clusters were found, with the majority (18 of 21, 86%) of the severest IPF participants (Stage 2 and 3) being in two clusters. The participants in these clusters exhibited a distinct minute ventilation (p < 0.05), compared to the other two clusters. The respiratory drive was greatest in Cluster 1, which contained many of the IPF participants. Unstructured HCA was successful in recognising different airflow profiles, clustering according to differences in flow rather than time. HCA showed that there is an overlap in tidal airflow profiles between healthy RTB and those with IPF. The further application of HCA in recognising other respiratory disease is discussed.

Background: Idiopathic pulmonary fibrosis (IPF) is a disease with very poor prognosis and no curative therapies. The G protein-coupled, calcium/cation-sensing receptor (CaSR) is activated by environmental pollutants and by arginine-derived polyamines, which are thought to play a role in IPF. Whether the CaSR is involved in the pathogenesis of pulmonary fibrosis is unknown. Objective: To investigate the CaSR as a novel drug target for the treatment of pulmonary fibrosis (PF). Methods and results: CaSR protein expression is found in the airway epithelium in the neuroepithelial bodies of the healthy and IPF human lung. Expression of arginine pathway-linked polyamines is increased in PF patient saliva samples compared to non-PF patients. Arginine pathway metabolites, ornithine and spermine, activate the CaSR in primary normal human lung fibroblasts (NHLF), effects prevented by CaSR antagonism using the calcilytic NPS2143. In NHLF calcilytic also reversed the pro-fibrotic effects of exogenous TGFβ1 administration on Rho kinase and αSMA expression, proliferation, collagen production and IL-8 secretion. Targeted CaSR ablation from fibroblasts and smooth muscle cells protects mice from spontaneously occurring, age-related lung fibrosis. Conclusions: Sustained CaSR activation in the lung drives pro-fibrotic processes, which can be reversed by calcilytic. Pharmacological and genetic CaSR blockade reduce both TGFβ1-induced and naturally occurring pro-fibrotic changes. This work provides the scientific rationale for developing inhaled calcilytics as novel therapeutics for IPF. KEY MESSAGES: Key question: How does the calcium/cation-sensing receptor (CaSR) promote pulmonary fibrosis? Bottom line: The CaSR is expressed in human IPF and experimental models of PF where receptor inhibition prevents pro-fibrotic changes and pulmonary remodeling. Why read on: CaSR blockers, calcilytics, represent a novel treatment for IPF.

Introduction: Respiratory diseases affect millions of people in the UK, with a disproportionately high burden seen among many marginalised communities. They are the third leading cause of death in the UK and a major driver of morbidity, disability and healthcare service use. Many respiratory conditions cause debilitating symptoms and deterioration in patients’ health and quality of life over time, resulting in substantial increases in National Health Service (NHS) expenditure. Social inequalities, including occupational, housing and environmental disparities, have led to a disproportionate burden of respiratory disease among the Black community. For many Black people living in the UK, respiratory conditions have been under-recognised, misdiagnosed or inadequately treated, further contributing to disparities in health outcomes. Despite the need to address these urgent challenges, research in this area is fragmented and rarely informed by the views and opinions of those most affected. Research prioritisation provides a structured methodology to address this unmet need. The Equal Breath Priority Setting Partnership (PSP) aims to identify the 10 most urgent research priorities in respiratory health for people of Black heritage through meaningful collaboration with people with lived experience of respiratory disease, their caregivers and family members and the healthcare professionals caring for them. Methods and analysis: The top 10 research priorities for the Equal Breath PSP will be established using the James Lind Alliance (JLA) method. A steering group comprising approximately 12 people from key stakeholder groups will first be assembled to guide the PSP. Once the context and scope of the PSP has been agreed, the first survey will be developed and disseminated among stakeholder communities to identify evidence uncertainties. Data analysis of the survey responses will create summary questions and critical appraisal of available evidence will verify which of these are evidence gaps. A longlist of approximately 50 summary questions derived from the first survey will be shared with stakeholders in a second shortlisting survey. The highest ranking questions from this survey will be taken into a workshop where the top 10 research priorities will be established through a consensus process. Ethics and dissemination: This PSP employs the JLA methodology, which does not constitute research as defined by the Health Research Authority. Survey respondent data will be stored in accordance with UK General Data Protection Regulation by Asthma+Lung UK. The final 10 research priorities will be shared with funders, policymakers, professional bodies and relevant communities to inform future investment and promote equity in respiratory health.

Introduction: Idiopathic pulmonary fibrosis (IPF) is an incurable disease with very poor prognosis and no curative therapies. The extracellular calcium-sensing receptor (CaSR) has been shown to drive pulmonary remodelling in preclinical models of pulmonary hypertension and inflammatory lung diseases. CaSR activation is induced by endogenous and exogenous polycations (polyamines and positively-charged environmental pollutants, respectively). However, the role of CaSR in IPF requires further investigation. Methods: Immunostaining was used to assess lung CaSR expression in IPF patients and control. CaSR-related metabolites were assessed in patient saliva samples (IPF and control) using high-resolution mass spectrometry. Histology was carried out in old mice with targeted CaSR deletion to assess age-induced lung remodelling. In human lung fibroblasts (HLF), the polyamine, spermine, was used to assess CaSR activation via calcium imaging. Results: Differential CaSR expression was observed in IPF lungs compared to controls. Several CaSR activators (amines and polyamines) were significantly increased in IPF patients compared to control (p<0.05). Selective CaSR deletion protected mice from age-induced fibrosis (p<0.05). CaSR is expressed and functional in human lung fibroblasts; receptor activation was blocked in the presence of calcilytics. Conclusions: This study supports the role of the CaSR in PF, as receptor deletion resulted in reduced fibrosis. Since CaSR activators are elevated in IPF patient saliva, increased levels of these metabolites suggest a role for the CaSR in the pathophysiology of IPF. Although further work is required, our results highlight CaSR as a therapeutic target for IPF.

Objectives: Despite UK targets to reduce stillbirth, there has been comparatively less research focused on stillbirth than on other pregnancy complications. This study aimed to ensure that future research addresses the most important contemporary questions regarding stillbirth by updating the 2015 UK Stillbirth Priority Setting Partnership (PSP), in accordance with the James Lind Alliance (JLA), in collaboration with over 30 professional and stakeholder organizations. Methods: The Stillbirth PSP was accepted by the JLA for a refreshed list of priorities in June 2024, and a steering group was formed. A survey was then developed in English to identify potential research questions regarding stillbirth and perinatal death in the UK. The initial survey was open from 3 February 2025 to 7 April 2025, during which professionals and people affected by stillbirth were invited to submit research questions relating to either the causes, impact, prevention or management of stillbirth or pregnancy loss after 20 weeks' gestation. The questionnaire was publicized via social media and by stakeholder organizations. Participants' responses were analyzed, duplicate or out‐of‐scope questions were removed, and indicative questions were formulated from those submitted. Literature searches were carried out in MEDLINE, EMBASE, CINAHL, Cochrane Library and PsychInfo to identify which of the submitted questions had been answered in previously published work. The remaining unanswered research questions were carried forward into a second prioritization survey, which was hosted online from 15 September 2025 to 16 October 2025. The research questions at the highest priority level were determined by consensus at a face‐to‐face workshop in November 2025, involving participants with lived experience and healthcare professionals. Results: The initial survey received 1261 responses from 525 participants. A further 24 research questions were identified from 10 clinical practice guidelines. Of these 1285 questions, 120 were out of scope. After removing duplicates and combining responses, there were 89 indicative questions. Literature searches determined that 10 questions had been answered previously. The remaining 79 questions were carried forward into the second prioritization survey and were ranked by 441 participants. The top 26 questions were taken to the face‐to‐face workshop, which prioritized 12 research questions by consensus. The prioritized topics for future research included prediction, prevention, understanding of the causes and management of stillbirth. Conclusions: This updated Stillbirth PSP indicates that researchers should prioritize studies addressing the identified research priorities, because these reflect the most important research questions for those affected by stillbirth and frontline professionals. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.