Browsing by Author "Black M"

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    Protocol for the INFORM ASTHMA Trial: budesonide–formoterol reliever in adults with asthma on maintenance inhaled corticosteroid
    (European Respiratory Society, 2025-07-07) Noble J; Bean O; Bruce P; Black M; Sayers R; Cullen R; Black B; Holliday M; Kirton L; Perry B; Eathorne A; Pavord I; Weatherall M; Beasley R
    Background International asthma guidelines recommend inhaled corticosteroid (ICS)/formoterol in preference to short-acting β2-agonist (SABA) reliever-based regimens as reliever therapy in adults and adolescents of all asthma severities. A major limitation to this recommendation is the absence of randomised controlled trial (RCT) efficacy and safety data for this approach in patients who continue to use maintenance ICS. The anti-inflammatory effect of ICS/formoterol reliever therapy on airway inflammation is also not well characterised. Objective The objective of the present study is to determine the anti-inflammatory effect, efficacy and safety of budesonide–formoterol reliever therapy versus terbutaline reliever therapy in adults with asthma on maintenance ICS therapy. Fractional exhaled nitric oxide (FENO) will specifically be examined to determine the time-course and magnitude of the anti-inflammatory effect. Methods A 26-week, open-label, parallel-group, 2-arm, phase IV, two-sided superiority RCT will recruit 180 adults aged 16–75 years with a clinical diagnosis of asthma using reliever only therapy, or SABA reliever therapy with maintenance ICS at baseline, and with baseline FENO at screening ≥25 ppb. Enrolled participants will be allocated to maintenance budesonide with the dose based on their baseline treatment step and randomised 1:1 to either budesonide–formoterol or terbutaline reliever therapy. All participants will perform at-home FENO measurements at regular intervals for the first 12 weeks of the study. The primary outcome is FENO at 26 weeks. Key secondary outcomes include FENO time-course, asthma exacerbations, asthma control and spirometry. Conclusion This will be the first RCT comparing ICS/formoterol versus SABA reliever therapy in patients who use maintenance ICS therapy.
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    Recurrent loss of heterozygosity correlates with clinical outcome in pancreatic neuroendocrine cancer
    (Springer Nature in partnership with the Center of Excellence in Genomic Medicine Research at King Abdulaziz University, 2018-07-20) Lawrence B; Blenkiron C; Parker K; Tsai P; Fitzgerald S; Shields P; Robb T; Yeong ML; Kramer N; James S; Black M; Fan V; Poonawala N; Yap P; Coats E; Woodhouse B; Ramsaroop R; Yozu M; Robinson B; Henare K; Koea J; Johnston P; Carroll R; Connor S; Morrin H; Elston M; Jackson C; Reid P; Windsor J; MacCormick A; Babor R; Bartlett A; Damianovich D; Knowlton N; Grimmond S; Findlay M; Print C
    Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Here we report the analysis of gene mutation, copy number, and RNA expression of 57 sporadic well-differentiated pNETs. pNET genomes are dominated by aneuploidy, leading to concordant changes in RNA expression at the level of whole chromosomes and chromosome segments. We observed two distinct patterns of somatic pNET aneuploidy that are associated with tumor pathology and patient prognosis. Approximately 26% of the patients in this series had pNETs with genomes characterized by recurrent loss of heterozygosity (LoH) of 10 specific chromosomes, accompanied by bi-allelic MEN1 inactivation and generally poor clinical outcome. Another ~40% of patients had pNETs that lacked this recurrent LoH pattern but had chromosome 11 LoH, bi-allelic MEN1 inactivation, and universally good clinical outcome. The somatic aneuploidy allowed pathogenic germline variants (e.g., ATM) to be expressed unopposed, with RNA expression patterns showing inactivation of downstream tumor suppressor pathways. No prognostic associations were found with tumor morphology, single gene mutation, or expression of RNAs reflecting the activity of immune, differentiation, proliferative or tumor suppressor pathways. In pNETs, single gene mutations appear to be less important than aneuploidy, with MEN1 the only statistically significant recurrently mutated driver gene. In addition, only one pNET in the series had clearly actionable single nucleotide variants (SNVs) (in PTEN and FLCN) confirmed by corroborating RNA expression changes. The two clinically relevant patterns of LoH described here define a novel oncogenic mechanism and a plausible route to genomic precision oncology for this tumor type.