Primary ciliary dyskinesia (PCD) is a genetic disorder associated with recurrent and chronic respiratory infections due to functional defects of motile cilia. In this study, we aimed to elucidate inflammatory and proliferative responses in PCD respiratory epithelium and evaluate the effect of Azithromycin (AZT) on these responses. Airway basal cells (BCs) were isolated from nasal samples of Wild-type (WT) epitope of healthy donors and PCD donors with bi-allelic mutations in DNAH5, DNAH11 and CCDC39. Cells were expanded in vitro and stimulated with either Lipopolysaccharide (LPS) or vehicle control. Post stimulation, cells were treated with either Azithromycin (AZT) or vehicle control. Cell proliferation was imaged in real-time. Separately, BCs from the same donors were expanded and grown at an air-liquid interface (ALI) to generate a multi-ciliated epithelium (MCE). Once fully mature, cells were stimulated with LPS, AZT, LPS + AZT or vehicle control. Inflammatory profiling was performed on collected media by cytokine Luminex assay. At baseline, there was a significantly higher mean production of pro-inflammatory cytokines by CCDC39 BCs and MCEs when compared to WT, DNAH11 and DNAH5 cells. AZT inhibited production of cytokines induced by LPS in PCD cells. Differences in cell proliferation were noted in PCD and this was also corrected with AZT treatment.

• MeSH
• azithromycin * farmakologie   MeSH
• cytokiny MeSH
• epitelové buňky MeSH
• lidé MeSH
• lipopolysacharidy toxicita   MeSH
• poruchy ciliární motility * MeSH
• proliferace buněk MeSH
• zánět farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azithromycin * MeSH
• cytokiny MeSH
• lipopolysacharidy MeSH

INTRODUCTION: In primary ciliary dyskinesia (PCD) impaired mucociliary clearance leads to recurrent airway infections and progressive lung destruction, and concern over chronic airway infection and patient-to-patient transmission is considerable. So far, there has been no defined consensus on how to control infection across centres caring for patients with PCD. Within the BEAT-PCD network, COST Action and ERS CRC together with the ERN-Lung PCD core a first initiative has now been taken towards creating such a consensus statement. METHODS: A multidisciplinary international PCD expert panel was set up to create a consensus statement for infection prevention and control (IP&C) for PCD, covering diagnostic microbiology, infection prevention for specific pathogens considered indicated for treatment and segregation aspects. Using a modified Delphi process, consensus to a statement demanded at least 80% agreement within the PCD expert panel group. Patient organisation representatives were involved throughout the process. RESULTS: We present a consensus statement on 20 IP&C statements for PCD including suggested actions for microbiological identification, indications for treatment of Pseudomonas aeruginosa, Burkholderia cepacia and nontuberculous mycobacteria and suggested segregation aspects aimed to minimise patient-to-patient transmission of infections whether in-hospital, in PCD clinics or wards, or out of hospital at meetings between people with PCD. The statement also includes segregation aspects adapted to the current coronavirus disease 2019 (COVID-19) pandemic. CONCLUSION: The first ever international consensus statement on IP&C intended specifically for PCD is presented and is targeted at clinicians managing paediatric and adult patients with PCD, microbiologists, patient organisations and not least the patients and their families.

• Publikační typ
• časopisecké články MeSH