American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2023
Genetic Modifiers of Cystic Fibrosis Lung Disease Severity: Whole Genome Analysis of 7,840 Patients.
Rationale: Lung disease is the major cause of morbidity and mortality in persons with cystic fibrosis (pwCF). Variability in CF lung disease has substantial non-CFTR (CF transmembrane conductance regulator) genetic influence. Identification of genetic modifiers has prognostic and therapeutic importance. ⋯ Multilocus effects at chr5p13 (SLC9A3/CEP72) and chr11p13 (EHF/APIP) were identified. Variant effect size estimates at associated loci were consistently ordered across the cohorts, indicating possible age or birth cohort effects. Conclusions: This premodulator genomic, transcriptomic, and pathway association study of 7,840 pwCF will facilitate mechanistic and postmodulator genetic studies and the development of novel therapeutics for CF lung disease.
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Am. J. Respir. Crit. Care Med. · May 2023
Impact of Ambient Ultrafine Particles on Cause-Specific Mortality in Three German Cities.
Rationale: Exposure to ambient air pollution has been associated with adverse effects on morbidity and mortality. However, the evidence for ultrafine particles (UFPs; 10-100 nm) based on epidemiological studies remains scarce and inconsistent. Objectives: We examined associations between short-term exposures to UFPs and total particle number concentrations (PNCs; 10-800 nm) and cause-specific mortality in three German cities: Dresden, Leipzig, and Augsburg. ⋯ UFP effects were independent of PM2.5 in two-pollutant models. Conclusions: We found delayed effects for respiratory mortality within 1 week after exposure to UFPs and PNCs but no associations for natural or cardiovascular mortality. This finding adds to the evidence on the independent health effects of UFPs.