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Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting., Methods: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey., Results: 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD., Conclusion: We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting., Competing Interests: Conflict of interest: A.J. Simpson has received funding to his institution from Boehringer Ingelheim (BI) to undertake an educational meeting. A. West has received support from BI for speaking at or chairing educational events, and attendance and travel to educational meetings; and is part of an advisory board for BI and Avalyn Pharmaceuticals. A. John has received funding from BI to attend an educational event. A.M. Wilson has received grants from Aseptika, Brainomix and BASF, has received speakers’ fees from BI, has received support for attending meetings by Chiesi, and has institutional interests with Celgene Corporation, GSK and Insmed Inc. A. Crawshaw has received speakers’ fees from BI and AstraZeneca (AZ). A.U. Wells has undertaken advisory board activity and consultant work for BI, Roche and Veracyte. C.C. Huntley has received an honorarium for educational content from BI and sponsorship for conference attendance. D. Dosanjh has received a speaker's fee from BI, meeting attendance costs from AZ and is part of the advisory board for AZ, Gilead, BI and Synairgen. E. Renzoni has received institutional funding, honoraria for educational events and funding for conference attendance from BI, and is member of the advisory board for BI and Roche. F. Chua has received consulting fees, honoraria, support for conference attendance and is an advisory board member for BI. G. Saini has received institutional payment for educational presentation from BI. G. Dixon, H. Stone, L.M. Nicol and I.A. Forrest have received support for educational event attendance from BI. J.C.L. Rodrigues has received grant funding from NIHR, consulting fees from NHSx and HeartFlow, honoraria from Sanofi, Aidence and 4-C Research market research, meeting attendance support from Aidence and HeartFlow, leadership role in Heart and Lung Imaging LTD (HLH), stock in Radnet and shares in HLH. K. Tsaneva-Atanasova has financial support from EPSRC grant. M. Naqvi has received a grant from NHS Digital, honoraria from BI, AZ and Roche, support for meeting attendance from BI and advisory board membership for BI, and is ILD Pharmacist Network Chair and ILD-IN Co-chair. M.G. Jones has received grants from Royal Society, BI, NC3Rs, MRC, AAIR Charity and the British Lung Foundation. P.M. George has received an institutional grant from BI, honoraria from BI, Roche, Teva, Cipla and Brainomix, meeting attendance support from BI and Roche and has stock in Brainomix. P. Molyneaux has grant funding from AZ, consulting fees from Roche, BI, AZ, Trevi and Qureight, and honoraria from BI and Roche; and is an associate editor of this journal. P. Rivera-Ortega has received grant funding from MRC, institutional grant funding from BI, Roche, CSL Behring, Fibrogen, Vicore Pharma AB, Gilead Sciences and Galecto, consulting fees from BI and Roche, honoraria from BI, Roche and Respiratory Effectiveness Group (REG), support for meeting attendance from BI and REG, is a chair of the REG and member of the Global Writing Group Committee for REMAP-ILD. R.K. Coker has received honoraria from BI. S. Agnew has received honoraria from BI, support for meeting attendance from BI and is member of the BTS ILD registry advisory board. S.L. Barratt has received consulting fees and honoraria from BI. S. Hart has received research grant from BI, consulting fees from Trevi Therapeutics, honoraria and support for meeting attendance from BI and Chiesi, was Chair of the BTS Standard of Care Committee 2019–2022, and is a Trustee of Action for Pulmonary Fibrosis and an associate editor of this journal. S. Barth received honoraria from BI for educational meeting facilitating. T. Garfoot received support to attend the ILD IN annual conference. T. Gatheral has received speakers’ fees from BI. Conflict of interest: The remaining authors have no competing interests., (Copyright ©The authors 2024.)

Introduction: Polycystic ovary syndrome (PCOS) seems to be associated with increased ovarian sympathetic nerve activity and in rodent models of PCOS reducing the sympathetic drive to the ovary, through denervation or neuromodulation, improves ovulation rate. We hypothesised that sympathetic nerves work with gonadotropins to promote development and survival of small antral follicles to develop a polycystic ovary phenotype., Methods: Using a clinically realistic ovine model we showed a rich sympathetic innervation to the normal ovary and reinnervation after ovarian transplantation. Using needlepoint diathermy to the nerve plexus in the ovarian vascular pedicle we were able to denervate the ovary resulting in reduced intraovarian noradrenaline and tyrosine hydroxylase immunostained sympathetic nerves. We developed an acute polycystic ovary (PCO) model using gonadotrophin releasing hormone (GnRH) agonist followed infusion of follicle stimulating hormone (FSH) with increased pulsatile luteinising hormone (LH). This resulted in increased numbers of smaller antral follicles in the ovary when compared to FSH infusion suggesting a polycystic ovary., Results: Denervation had no effect of the survival or numbers of follicles in the acute PCO model and did not impact on ovulation, follicular and luteal hormone profiles in a normal cycle., Discussion: Although the ovary is richly inervated we did not find evidence for a role of sympathetic nerves in ovarian function or small follicle growth and survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Duncan, Nicol, O’Hare, Witherington, Miranda, Campbell, Thomas and Rae.)

Women with polycystic ovary syndrome (PCOS) are more likely to be obese and have difficulty in losing weight. They demonstrate an obesity-independent deficit in adaptive energy expenditure. We used a clinically realistic preclinical model to investigate the molecular basis for the reduced postprandial thermogenesis (PPT) and develop a therapeutic strategy to normalize this deficit. Sheep exposed to increased androgens before birth develop the clinical features of PCOS. In adulthood they develop obesity and demonstrate an obesity-independent reduction in PPT. This is associated with reduced adipose tissue uncoupling protein expression and adipose tissue noradrenaline concentrations. These sheep are insulin resistant with reduced insulin signaling in the brain. Increasing brain insulin concentrations using intranasal insulin administration increased PPT in PCOS sheep without any effects on blood glucose concentrations. Intranasal insulin administration with food is a potential novel strategy to improve adaptive energy expenditure and normalize the responses to weight loss strategies in women with PCOS., Competing Interests: Declarations of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease, with high mortality. Currently, the aetiology and the pathology of IPF are poorly understood, with both innate and adaptive responses previously being implicated in the disease pathogenesis. Heat shock proteins (Hsp) and antibodies to Hsp in patients with IPF have been suggested as therapeutic targets and prognostic biomarkers, respectively. We aimed to study the relationship between the expression of Hsp72 and anti-Hsp72 antibodies in the BAL fluid and serum Aw disease progression in patients with IPF., Methods: A novel indirect ELISA to measure anti-Hsp72 IgG was developed and together with commercially available ELISAs used to detect Hsp72 IgG, Hsp72 IgGAM, and Hsp72 antigen, in the serum and BALf of a cohort of IPF ( n = 107) and other interstitial lung disease (ILD) patients ( n = 66). Immunohistochemistry was used to detect Hsp72 in lung tissue. The cytokine expression from monocyte-derived macrophages was measured by ELISA., Results: Anti-Hsp72 IgG was detectable in the serum and BALf of IPF ( n = 107) and other ILDs ( n = 66). Total immunoglobulin concentrations in the BALf showed an excessive adaptive response in IPF compared to other ILDs and healthy controls ( p = 0.026). Immunohistochemistry detection of C4d and Hsp72 showed that these antibodies may be targeting high expressing Hsp72 type II alveolar epithelial cells. However, detection of anti-Hsp72 antibodies in the BALf revealed that increasing concentrations were associated with improved patient survival (adjusted HR 0.62, 95% CI 0.45-0.85; p = 0.003). In vitro experiments demonstrate that anti-Hsp72 complexes stimulate macrophages to secrete CXCL8 and CCL18., Conclusion: Our results indicate that intrapulmonary anti-Hsp72 antibodies are associated with improved outcomes in IPF. These may represent natural autoantibodies, and anti-Hsp72 IgM and IgA may provide a beneficial role in disease pathogenesis, though the mechanism of action for this has yet to be determined.

Introduction: Oral curcumin decreases inflammatory cytokines and increases muscle regeneration in mice., Purpose: To determine effects of curcumin on muscle damage, inflammation and delayed onset muscle soreness (DOMS) in humans., Method: Seventeen men completed a double-blind randomized-controlled crossover trial to estimate the effects of oral curcumin supplementation (2.5 g twice daily) versus placebo on single-leg jump performance and DOMS following unaccustomed heavy eccentric exercise. Curcumin or placebo was taken 2 d before to 3 d after eccentric single-leg press exercise, separated by 14-d washout. Measurements were made at baseline, and 0, 24 and 48-h post-exercise comprising: (a) limb pain (1-10 cm visual analogue scale; VAS), (b) muscle swelling, (c) single-leg jump height, and (d) serum markers of muscle damage and inflammation. Standardized magnitude-based inference was used to define outcomes., Results: At 24 and 48-h post-exercise, curcumin caused moderate-large reductions in pain during single-leg squat (VAS scale -1.4 to -1.7; 90 %CL: ±1.0), gluteal stretch (-1.0 to -1.9; ±0.9), squat jump (-1.5 to -1.1; ± 1.2) and small reductions in creatine kinase activity (-22-29 %; ±21-22 %). Associated with the pain reduction was a small increase in single-leg jump performance (15 %; 90 %CL ± 12 %). Curcumin increased interleukin-6 concentrations at 0-h (31 %; ±29 %) and 48-h (32 %; ±29 %) relative to baseline, but decreased IL-6 at 24-h relative to post-exercise (-20 %; ±18 %)., Conclusions: Oral curcumin likely reduces pain associated with DOMS with some evidence for enhanced recovery of muscle performance. Further study is required on mechanisms and translational effects on sport or vocational performance.

Background: Silicosis is one of the oldest occupational lung diseases, but it continues to cause significant morbidity and mortality worldwide., Aims: To report cases of silicosis presenting to two specialist respiratory clinics., Methods: A retrospective analysis of prospectively collected data of cases of silicosis in workers referred to specialist respiratory clinics., Results: Over the course of 6 years, six cases were identified. The patients were all male with an age range between 24 and 39 years. The duration of silica exposure ranged between 7 and 20 years (mean 13 years). Four cases were entirely asymptomatic at presentation, and two cases described minimal shortness of breath on exertion. Pulmonary function tests were normal in three cases, and a mild restrictive ventilatory defect was documented in the other cases. All had a low apparent predicted probability of pneumoconiosis based on health questionnaires, spirometry and duration of silica exposure. The initial chest X-ray was abnormal in all six cases with radiological evidence of silicosis (International Labour Office profusion category ≥1/1) on imaging, and all had evidence of silicosis on high-resolution computed tomography (HRCT). Three patients had already progressed to progressive massive fibrosis on HRCT scanning at the time of referral to specialist respiratory services., Conclusions: The appearances of these six cases of silicosis in young, asymptomatic construction workers emphasizes the importance of enforcing effective exposure control and comprehensive surveillance programmes. Our observations highlight the importance of having a low threshold for early radiological screening to promote early and effective detection of this disease., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)