"Epigenomic partitioning of a polygenic risk score for asthma reveals distinct genetically driven disease pathways." B. Stikker, L. Trap, B. Sedaghati-Khayat, et al. Eur Respir J 2024; 64: 2302059

“哮喘多基因风险评分的表观基因组划分揭示了不同的遗传驱动疾病通路。” B. Stikker、L. Trap、B. Sedaghati-Khayat 等。Eur Respir J 2024; 64: 2302059

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Abstract

BACKGROUND: Difficult-to-treat bacterial infections represent a significant public health issue.(1) Phage therapy is emerging as a promising strategy to be combined with antibiotic treatment for their eradication.(2) In Italy, the demand for this therapy is steadily increasing; however, patients can receive phage therapy only under compassionate use (approval by an Ethics Committee (EC)).(3) METHODS: From January 1, 2021, to September 30, 2024, 47 patients contacted the Bacteriophage Laboratory at the University of Pisa requesting phage therapy. Of these, only 22 patients (46.8%) were supported by a specific request from a specialist physician. RESULTS: The chronic infections to be treated were mainly osteoarticular (n = 8, 36%) and respiratory tract infections (n = 6, 27.27%), followed by soft tissue and cardiovascular infections (n = 3, 13.64% each), post-surgical and abdominal infections (n = 1, 4.55% each). In total, 39 bacterial strains of different species were received: P. aeruginosa (n = 19, 48.7%), S. aureus (n = 5, 12.8%), Achromobacter spp. (n = 3, 7.69%), P. mirabilis, A. baumannii, K. pneumoniae (n = 2, 5.13% each), E. coli, S. pyogenes, S. maltophilia, E. hormachaei, E. faecalis, M. arupense (n = 1, 2.56% each). Each strain was tested for susceptibility to bacteriophages in the Phage Bank (PB). In cases of a positive results, the lytic activity was evaluated using a phagogram, along with the synergistic activity with antibiotics (based on the antibiogram of the tested strain). No phages from the PB were active against only 7 bacterial strains (18%); however, research for specific bacteriophages is ongoing. Among the 17 patients eligible for phage therapy, a personalized treatment protocol has been defined for two cases, and a request for compassionate use has been submitted to the EC. CONCLUSIONS: Although phage therapy currently requires EC approval, slowing down the patient treatment process, our experience is laying the foundation for defining a phage-based therapeutic approach within the precision medicine framework.

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