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Chronic rhinosinusitis (CRS) is a heterogeneous disease of the paranasal sinuses. Anatomic variation, genetic mutation, viral infection, and allergic response, are all considered to play etiological roles in CRS. Contributors to pathogenesis include immune dysfunction, impaired mucociliary clearance, increased mucus production and stasis, and bacterial virulence mechanisms, however their importance and order of occurrence is not well understood. Microbiological surveys have implicated Staphylococcus aureus as one of the most frequent bacteria in the CRS sinuses. Paradoxically, S. aureus asymptomatically colonizes the nasal passages of ~50% of healthy adults. This work aimed to further describe the diversity of bacterial communities in the paranasal sinuses of patients with CRS using genomic and bioinformatic methods, and reveal new insights into the balance between S. aureus commensalism and pathogenesis. CRS is particularly prevalent in people with the genetic disorder cystic fibrosis (CF). Bacterial infection of the upper airways is thought to be a focus for pulmonary infection, which accounts for the majority of morbidity and mortality in this population. Using 16S rRNA gene sequencing, we described highly similar bacterial communities between sinus mucus and lung sputum in CF patients. CF patients exhibited high interindividual variation, and several instances where a canonical CF pathogen (e.g. S. aureus, Pseudomonas aeruginosa) was seen in the sinus mucus, but not sputum, suggesting this is a location of initial pathogen colonization and adaptation. Further investigation of the bacterial communities in sinus mucus revealed that diversity of the bacterial community was significantly greater in communities with S. aureus as the dominant organism. In contrast, Pseudomonas dominated communities were less diverse, and associated with both increased patient age, and decreased lung function, though not significantly. These results contribute to a growing body of research suggesting a temporal progression of bacterial diversity in the CF airways towards a community characterized by P. aeruginosa dominance. We further hypothesized that the presence of other bacterial taxa could have differential effects on S. aureus physiology in the non-CF CRS. Using 16S rRNA gene sequencing, the bacterial communities were characterized in CRS and non-CRS patient sinus mucus accessed through endoscopic sinus surgery. Compared to the bacterial communities observed in non-CRS mucus, CRS was characterized by an increased proportional abundance of facultative and obligate anaerobic bacterial genera including Streptococcus, Prevotella, and Fusobacterium, and a decrease in Actinobacteria compared. Guided by taxonomy, we computationally predicted the metagenomic content of CRS-associated communities, which suggested an increased functional capacity for the degradation of mucin-glycoproteins - a highly abundant constituent of mucus responsible for its many biological and physical characteristics. Using anaerobic enrichment of CRS sinus mucus bacterial communities on mucins in a minimal medium, we demonstrated a mucin-degradation phenotype, and further described the bacterial communities to include anaerobic genera such as Streptococcus, Prevotella, Veillonella, and Fusobacterium. This work shows that mucins are not efficiently used as a growth substrate by S. aureus, however, mucin degradation and fermentation by CRS-derived bacterial consortia produced metabolites that could augment S. aureus growth. Furthermore, transcriptomic analysis suggests mucin degradation and fermentation products affect S. aureus metabolic state and virulence potential. This work presents high-resolution molecular characterization of the bacterial communities associated with CRS, demonstrates mucin-degradation as a bacterial phenotype carried out by these communities, and suggests a role for mucin-degradation in supporting the growth and virulence of S. aureus.

Introduction: Chronic rhinosinusitis (CRS) is a highly prevalent pathology in our society. Due to the prevalence of this condition and to the persisting symptoms despite an appropriate medical treatment, surgical techniques are often required. Lately, minimal invasive techniques have been described, such as lacrimal diversion devices (LDDs). This technique offers a fast and convenient choice for delivery of sinus irrigation and topical medication. Objective: We aimed to describe our experience with LDDs and evaluate the safety and effectiveness of the procedure in patients with moderate to severe CRS without nasal polyposis (CRSsNP) and persistent symptomatology despite medical therapy. Methods: A total of 7 patients underwent bilateral lacrimal stents placement in the operating room. A retrospective observational study was conducted. The Sino-Nasal Outcome Test-20 (SNOT-20) survey was performed and the score obtained was compared before and 1 month after the procedure. Results: The LDDs were used for an average of 80 days. During the follow-up, only three patients had a mild complication with the device (granuloma in the punctum, obstruction, and early extrusion). The mean baseline SNOT-20 score dropped significantly (p ¼ 0.015) from 25.85 to 11.57 (mean: - 14.29) 1 month after the procedure. Conclusion: According to our experience and results, the use of LDD is a novel, feasible, and less invasive technique to treat refractory CRS. It reduces the risk of mucosal stripping, provides short-term outcomes, and the surgical procedure does not require advanced training in endoscopic sinus surgery. Moreover, it can be performed in-office under local anesthesia or sedation.

Background. Chronic rhinosinusitis is a highly prevalent condition estimated to affect 9% of the adult population in Australia. It is responsible for a significant burden of disease at a population level and imparts considerable morbidity and reduced quality of life to affected individuals. Recent American data has suggested an $8.6 billion annual direct healthcare cost associated with chronic rhinosinusitis. Few medical options for treating chronic rhinosinusitis exist and there is a paucity of evidence in support of a best medical treatment. Currently available treatments confer a modest benefit. The hallmark of chronic rhinosinusitis is chronic inflammation of the nasal and sinus mucosa lasting in excess of twelve weeks and resulting in typical symptoms. Chronic rhinosinusitis is a multi-factorial disease for which there are many postulated contributory factors. Although the aetiology of the disease is yet to be fully elucidated, current literature suggests the primacy of immune dysfunction in its pathogenesis and treatment recalcitrance. Characteristic inflammatory cell infiltrates and cytokine response have been identified for chronic rhinosinusitis subtypes. Inflammatory mediators with altered activity and/or expression in chronic rhinosinusitis represent potential therapeutic targets. Aims and Objectives. This study sought to investigate the anti-inflammatory and immune modulating activity of xylitol, an agent that has anecdotal utility in CRS and established antibacterial and antibiofilm actions. In order to achieve this aim inflammatory mediator targets were identified and the activity of xylitol against their production was examined relative to that of established anti-inflammatory agents. A further objective in this study was to establish a cell-based in-vitro model that best resembled the clinical condition of CRS and considered the effect of xylitol on epithelial and immune cells likely to be encountered in-vivo.

The author worked with the World Trade Center Medical Monitoring and Treatment Program to create part of a public health education campaign to advertise the existence of the program and to explain World Trade Center health effects. World Trade Center Dust contained particles of many sizes, and it caused irritation to the body's tissues resulting in aerodigestive disorders like World Trade Center Cough, Sinusitis, Bronchitis, Rhinitis and Tracheo-Laryngitis. At the completion of this project, 2 posters, 1 brochure, 4 fact sheets and an interactive web site were created. One of the posters designed was used to promote program awareness amongst Ground Zero volunteers and workers. The second poster created was geared for use in clinics and doctor's offices, especially waiting areas. The author created a series of four patient education fact sheets that explain some of the most frequently seen respiratory diseases amongst World Trade Center volunteers and workers. Also designed was a brochure that included information about the diseases featured in the fact sheets, but in a more condensed form. The educational literature created needed to be simple in design and content, and it had to be presented in a medium that could be easily and cheaply reproduced and distributed to patients by health clinics and the Medical Monitoring and Treatment Program.