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  • Journal article
    Jackson C, Stewart ID, Plekhanova T, Cunningham PS, Hazel AL, Al-Sheklly B, Aul R, Bolton CE, Chalder T, Chalmers JD, Chaudhuri N, Docherty AB, Donaldson G, Edwardson CL, Elneima O, Greening NJ, Hanley NA, Harris VC, Harrison EM, Ho L-P, Houchen-Wolloff L, Howard LS, Jolley CJ, Jones MG, Leavy OC, Lewis KE, Lone NI, Marks M, McAuley HJC, McNarry MA, Patel BV, Piper-Hanley K, Poinasamy K, Raman B, Richardson M, Rivera-Ortega P, Rowland-Jones SL, Rowlands AV, Saunders RM, Scott JT, Sereno M, Shah AM, Shikotra A, Singapuri A, Stanel SC, Thorpe M, Wootton DG, Yates T, Gisli Jenkins R, Singh SJ, Man WD-C, Brightling CE, Wain LV, Porter JC, Thompson AAR, Horsley A, Molyneaux PL, Evans RA, Jones SE, Rutter MK, Blaikley JF, PHOSP-COVID Study Collaborative Groupet al., 2023,

    Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

    , The Lancet Respiratory Medicine, Vol: 11, Pages: 673-684, ISSN: 2213-2600

    BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended
  • Journal article
    Naghilou A, Peter K, Millesi F, Stadlmayr S, Wolf S, Rad A, Semmler L, Supper P, Ploszczanski L, Liu J, Burghammer M, Riekel C, Bismarck A, Backus EHG, Lichtenegger H, Radtke Cet al., 2023,

    Insights into the material properties of dragline spider silk affecting Schwann cell migration

    , INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, Vol: 244, ISSN: 0141-8130
  • Journal article
    Guillen-Guio B, Paynton ML, Allen RJ, Chin DPW, Donoghue LJ, Stockwell A, Leavy OC, Hernandez-Beeftink T, Reynolds C, Cullinan P, Martinez F, CleanUP-IPF Investigators of the Pulmonary Trials Cooperative, Booth HL, Fahy WA, Hall IP, Hart SP, Hill MR, Hirani N, Hubbard RB, McAnulty RJ, Millar AB, Navaratnam V, Oballa E, Parfrey H, Saini G, Sayers I, Tobin MD, Whyte MKB, Adegunsoye A, Kaminski N, Shwu-Fan M, Strek ME, Zhang Y, Fingerlin TE, Molina-Molina M, Neighbors M, Sheng XR, Oldham JM, Maher TM, Molyneaux PL, Flores C, Noth I, Schwartz DA, Yaspan BL, Jenkins RG, Wain LV, Hollox EJet al., 2023,

    Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis.

    , medRxiv

    INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Due to the important role that the Human Leukocyte Antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk. METHODS: We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case-control studies of IPF (comprising a total of 5,159 cases and 27,459 controls, including the prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold p<4.5×10-4 and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reported HLA-DQB1 association in the subset of studies independent of the original report. RESULTS: The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. The HLA-DQB1 association was not replicated in the independent IPF studies. CONCLUSION: Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.
  • Journal article
    Shelton JMG, Rhodes J, Uzzell CB, Hemmings S, Brackin AP, Sewell TR, Alghamdi A, Dyer PS, Fraser M, Borman AM, Johnson EM, Piel FB, Singer AC, Fisher MCet al., 2023,

    Citizen science reveals landscape-scale exposures to multiazole-resistant Aspergillus fumigatus bioaerosols.

    , Science Advances, Vol: 9, Pages: 1-9, ISSN: 2375-2548

    Using a citizen science approach, we identify a country-wide exposure to aerosolized spores of a human fungal pathogen, Aspergillus fumigatus, that has acquired resistance to the agricultural fungicide tebuconazole and first-line azole clinical antifungal drugs. Genomic analysis shows no distinction between resistant genotypes found in the environment and in patients, indicating that at least 40% of azole-resistant A. fumigatus infections are acquired from environmental exposures. Hotspots and coldspots of aerosolized azole-resistant spores were not stable between seasonal sampling periods. This suggests a high degree of atmospheric mixing resulting in an estimated per capita cumulative annual exposure of 21 days (±2.6). Because of the ubiquity of this measured exposure, it is imperative that we determine sources of azole-resistant A. fumigatus to reduce treatment failure in patients with aspergillosis.
  • Journal article
    Kondor A, Burnett DJ, Bismarck A, Williams DRet al., 2023,

    Correct specific retention volume determination in inverse gas chromatography

    , JOURNAL OF CHROMATOGRAPHY A, Vol: 1700, ISSN: 0021-9673
  • Journal article
    Wainwright C, McColley SA, McNally P, Powers M, Ratjen F, Rayment JH, Retsch-Bogart G, Roesch E, Ahluwalia N, Chin A, Chu C, Lu M, Menon P, Waltz D, Weinstock T, Zelazoski L, Davies JCet al., 2023,

    Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in children aged ⩾6 years with cystic fibrosis and at least one F508del allele: a phase 3, open-label clinical trial.

    , American Journal of Respiratory and Critical Care Medicine, Vol: 208, Pages: 68-78, ISSN: 1073-449X

    Rationale: A 24-week, phase 3, open-label study showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in children aged 6-11 years with cystic fibrosis (CF) and one or more F508del-CFTR alleles. Objectives: To assess long-term safety and efficacy of ELX/TEZ/IVA in children who completed the pivotal 24-week phase 3 trial. Methods: In this phase 3, two-part (part A and part B), open-label extension study, children aged ⩾6 years with CF heterozygous for F508del and a minimal function CFTR mutation (F/MF genotypes) or homozygous for F508del (F/F genotype) who completed the 24-week parent study received ELX/TEZ/IVA based on weight. Children weighing <30 kg received ELX 100 mg once daily/TEZ 50 mg once daily/IVA 75 mg every 12 hours, whereas children weighing ⩾30 kg received ELX 200 mg once daily/TEZ 100 mg once daily/IVA 150 mg every 12 hours (adult dose). The 96-week analysis of part A of this extension study is reported here. Measurements and Main Results: Sixty-four children (F/MF genotypes, n = 36; F/F genotype, n = 28) were enrolled and received one or more doses of ELX/TEZ/IVA. Mean (SD) period of exposure to ELX/TEZ/IVA was 93.9 (11.1) weeks. The primary endpoint was safety and tolerability. Adverse events and serious adverse events were consistent with common manifestations of CF disease. Overall, exposure-adjusted rates of adverse events and serious adverse events (407.74 and 4.72 events per 100 patient-years) were lower than in the parent study (987.04 and 8.68 events per 100 patient-years). One child (1.6%) had an adverse event of aggression that was moderate in severity and resolved after study drug discontinuation. From parent study baseline at Week 96 of this extension study, the mean percent predicted FEV1 increased (11.2 [95% confidence interval (CI), 8.3 to 14.2] percentage points), sweat chloride
  • Journal article
    Davies J, Southern KW, Barben J, Goldring S, Kneen R, Southward S, Rajeev Y, Bush Aet al., 2023,

    Raised intracranial pressure in three children with cystic fibrosis receiving elexacaftor-tezacaftor-ivacaftor modulator therapy

    , American Journal of Respiratory and Critical Care Medicine, Vol: 208, Pages: 103-105, ISSN: 1073-449X
  • Journal article
    Nolan CM, Schofield SJ, Maddocks M, Patel S, Barker RE, Walsh JA, Polgar O, George PM, Molyneaux PL, Maher TM, Cullinan P, Man WD-Cet al., 2023,

    Change in gait speed and adverse outcomes in patients with idiopathic pulmonary fibrosis: a prospective cohort study

    , Respirology, Vol: 28, Pages: 649-658, ISSN: 1323-7799

    BACKGROUND AND OBJECTIVE: Gait speed is associated with survival in individuals with idiopathic pulmonary fibrosis (IPF). The extent to which four-metre gait speed (4MGS) decline predicts adverse outcome in IPF remains unclear. We aimed to examine longitudinal 4MGS change and identify a cut-point associated with adverse outcome. METHODS: In a prospective cohort study, we recruited 132 individuals newly diagnosed with IPF and measured 4MGS change over 6 months. Death/first hospitalization at 6 months were composite outcome events. Complete data (paired 4MGS plus index event) were available in 85 participants; missing 4MGS data were addressed using multiple imputation. Receiver-Operating Curve plots identified a 4MGS change cut-point. Cox proportional-hazard regression assessed the relationship between 4MGS change and time to event. RESULTS: 4MGS declined over 6 months (mean [95% CI] change: -0.05 [-0.09 to -0.01] m/s; p = 0.02). A decline of 0.07 m/s or more in 4MGS over 6 months had better discrimination for the index event than change in 6-minute walk distance, forced vital capacity, Composite Physiologic Index or Gender Age Physiology index. Kaplan-Meier curves demonstrated a significant difference in time to event between 4MGS groups (substantial decline: >-0.07 m/s versus minor decline/improvers: ≤-0.07 m/s; p = 0.007). Those with substantial decline had an increased risk of hospitalization/death (adjusted hazard ratio [95% CI] 4.61 [1.23-15.83]). Similar results were observed in multiple imputation analysis. CONCLUSION: In newly diagnosed IPF, a substantial 4MGS decline over 6 months is associated with shorter time to hospitalization/death at 6 months. 4MGS change has potential as a surrogate endpoint for interventions aimed at modifying hospitalization/death.
  • Journal article
    Sandhu D, Redmond JL, Smith NMJ, Short C, Saunders CJ, Couper JH, Fullerton CJ, Richmond G, Talbot NP, Davies JC, Ritchie GAD, Robbins PAet al., 2023,

    Computed cardiopulmonography and the idealized lung clearance index, iLCI2.5, in early-stage cystic fibrosis.

    , Journal of Applied Physiology, Vol: 135, Pages: 205-216, ISSN: 1522-1601

    This study explored the use of computed cardiopulmonography (CCP) to assess lung function in early-stage cystic fibrosis (CF). CCP has two components. The first is a particularly accurate technique for measuring gas exchange. The second is a computational cardiopulmonary model where patient-specific parameters can be estimated from the measurements of gas exchange. Twenty-five participants (14 healthy controls, 11 early-stage CF) were studied with CCP. They were also studied with a standard clinical protocol to measure the lung clearance index (LCI2.5). Ventilation inhomogeneity, as quantified through CCP parameter σlnCl, was significantly greater (P < 0.005) in CF than in controls, and anatomical deadspace relative to predicted functional residual capacity (DS/FRCpred) was significantly more variable (P < 0.002). Participant-specific parameters were used with the CCP model to calculate idealized values for LCI2.5 (iLCI2.5) where extrapulmonary influences on the LCI2.5, such as breathing pattern, had all been standardized. Both LCI2.5 and iLCI2.5 distinguished clearly between CF and control participants. LCI2.5 values were mostly higher than iLCI2.5 values in a manner dependent on the participant's respiratory rate (r = 0.46, P < 0.05). The within-participant reproducibility for iLCI2.5 appeared better than for LCI2.5, but this did not reach statistical significance (F ratio = 2.2, P = 0.056). Both a sensitivity analysis on iLCI2.5 and a regression analysis on LCI2.5 revealed that these depended primarily on an interactive term between CCP parameters of the form σlnCL*(DS/FRC). In conclusion, the LCI2.5 (or iLCI2.5) probably reflects an amalgam of different underlying lung changes in early-stage CF that would require a multiparameter approach, such as potentially CCP, to resolve.NEW & NOTEWORTHY Computed cardiopulmonography is a new technique comprising a highly accurate sensor for measuring respiratory gas exchange coupled with a cardiopulm
  • Journal article
    Oldham JM, Johnson KW, Albers GJ, Calamita E, Mah J, Ghai P, Hewitt RJ, Maher TM, Molyneaux PL, Huang M, Byrne AJet al., 2023,

    Airway soluble CSF1R predicts progression in patients with idiopathic pulmonary fibrosis

    , ERJ OPEN RESEARCH, Vol: 9

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