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Aspects of Staphyloccus aureus in Chronic Rhinosinusitis

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Aspects of Staphyloccus aureus in

Chronic Rhinosinusitis

av

Ulrica Thunberg

Akademisk avhandling

Avhandling för medicine doktorsexamen i medicinsk vetenskap; inriktning kirurgi,

som kommer att försvaras offentligt fredagen den 9 oktober 2020 kl. 8.00, hörsal C3, Campus USÖ, Örebro Universitet

Opponent: Professor Johan Hellgren Sahlgrenska akademin, Göteborgs Universitet

Örebro universitet

Institutionen för medicinska vetenskaper 701 82 ÖREBRO

(2)

Abstract

Ulrica Thunberg (2020): Aspects of Staphylococcus aureus in Chronic Rhinosinusitis. Örebro Studies in Medicine nr 219

Chronic rhinosinusitis (CRS) affects about 10% of the European population, and is considered a great scourge. Its cause is not clear. Findings of Staphylo-coccus aureus in the maxillary sinus are common in CRS patients, but are usu-ally regarded as insignificant due to the bacterium’s attribute as a commensal elsewhere. S. aureus has the ability to cause both mild disease and serious con-ditions, due to its wide armoury of secreted components such as staphylococcal enterotoxins and cell-surface-associated virulence components.

This thesis focuses on the clinical features and importance of S. aureus in CRS, including a long-term perspective on the disease, through studying a cohort of CRS patients.

S. aureus was found to be highly prevalent in the maxillary sinus and nares of CRS patients, which might indicate an impact on the disease. A sheltered sampling technique for maxillary sinus culture reduced the con-tamination rate but did not significantly improve the diagnostic reliability. Whole genome sequencing showed that 95% of paired S. aureus isolates collected simultaneously from the nares and maxillary sinus were from identical lineages, indicating colonization of the maxillary sinus from the nares as one joint milieu. A decade-long persistence of S. aureus in the nares and maxillary sinus was established in 20% of CRS patients. The vast ma-jority of S. aureus isolates were susceptible to all tested antibiotics, includ-ing the strains that had persisted for a decade. No significant differences in the prevalence of gene determinants were seen for selected virulence factors and MSCRAMMs in S. aureus isolates sampled from CRS patients and healthy controls. The overall alterations of anti-staphylococcal antibodies over time showed great variability and minor support for an impact of S. aureus on CRS. At the long-term follow-up, symptoms were generally re-duced and VAS quality of life in terms of fatigue was improved. The sub-group of CRS patients without nasal polyposis had a greater chance of symptom relief than their counterparts with nasal polyposis in this long-term perspective. There was no correlation between severity of symptoms for CRS patients and S. aureus growth in the maxillary sinus to support a role for S. aureus in CRS.

Keywords:: Chronic rhinosinusitis, Staphylococcus aureus, enterotoxins, immune response, SNP, clinical features

Ulrica Thunberg, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden, ulrica.thunberg@regionorebrolan.se

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