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Journal articleDe Wachter E, Davies JC, Simmonds NJ, et al., 2023,
Letter to the editor: Risk of false newborn screening after intra-uterine exposure to ETI.
, J Cyst Fibros -
Journal articleShelton JMG, Rhodes J, Uzzell CB, et al., 2023,
Citizen science reveals landscape-scale exposures to multiazole-resistant Aspergillus fumigatus bioaerosols.
, Science Advances, Vol: 9, Pages: 1-9, ISSN: 2375-2548Using 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.
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Journal articleKondor A, Burnett DJ, Bismarck A, et al., 2023,
Correct specific retention volume determination in inverse gas chromatography
, JOURNAL OF CHROMATOGRAPHY A, Vol: 1700, ISSN: 0021-9673 -
Journal articleDavies J, Southern KW, Barben J, et 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 articleWainwright C, McColley SA, McNally P, et 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: 1073-449XRationale: 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
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Journal articleSandhu D, Redmond JL, Smith NMJ, et 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: 1522-1601This 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
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Journal articleNolan CM, Schofield SJ, Maddocks M, et 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: 1323-7799BACKGROUND 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.
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Journal articleOldham JM, Johnson KW, Albers GJ, et al., 2023,
Airway soluble CSF1R predicts progression in patients with idiopathic pulmonary fibrosis
, ERJ OPEN RESEARCH, Vol: 9 -
Journal articleSass G, Martinez M, Kotta-Loizou I, et al., 2023,
AfuPmV-1-Infected <i>Aspergillus fumigatus</i> Is More Susceptible to Stress Than Virus-Free Fungus
, JOURNAL OF FUNGI, Vol: 9 -
Journal articleAndrade EDQ, Bailey B, Davies JCC, et al., 2023,
Reply to migration is not the perfect answer: Optimized methodology to assess LCI agreement between corrected legacy multiple breath nitrogen washout data and that directly collected on updated software
, PEDIATRIC PULMONOLOGY, Vol: 58, Pages: 1861-1863, ISSN: 8755-6863
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