Chronic Rhinosinusitis: Potential Role of Microbial Dysbiosis and Recommendations for Sampling Sites.

Chronic rhinosinusitis (CRS) is an inflammatory condition that affects up to 12% of the human population in developed countries. Previous studies examining the potential role of the sinus bacterial microbiota within CRS infections have found inconsistent results, possibly because of inconsistencies in sampling strategies. The aim of this study was to determine whether the sinus microbiome is altered in CRS and additionally if the middle meatus is a suitable representative site for sampling the sinus microbiome. Swab samples were collected from 12 healthy controls and 21 CRS patients, including all eight sinuses for CRS patients and between one and five sinuses for control subjects. The left and right middle meatus and nostril swabs were also collected. Significant differences in the sinus microbiomes between CRS and control samples were revealed using high-throughput 16S rRNA gene sequencing. The genus Escherichia was over-represented in CRS sinuses, and associations between control patients and Corynebacterium and Dolosigranulum were also identified. Comparisons of the middle meatuses between groups did not reflect these differences, and the abundance of the genus Escherichia was significantly lower at this location. Additionally, intra-patient variation was lower between sinuses than between sinus and middle meatus, which together with the above results suggests that the middle meatus is not an effective representative sampling site

Frontal sinus surgery: indications and outcomes in chronic rhinosinusitis.

The research described in this PhD thesis follows an extensive literature review of the role of the medical and surgical management of CRS. Despite the utilization of surgery to alleviate the symptoms of CRS refractory to medical therapy, there are clear deficiencies in our understanding of what type of surgery to perform, and how extensive this surgery should be so as to maximize long-term symptom alleviation and control. Particular controversy exists regarding addressing the frontal sinus with a wide variety of philosophies employed, but with limited scientific rationale to support such approaches. Chapter two describes a prospective study to validate a quality of life tool, the Adelaide Disease Severity Score. This study showed a simple 5 question tool directly related to sinus symptoms and visual analogue quality of life score correlated very highly with other more complex rhinological quality of life tools – the SNOT 20/22. It further correlated with radiological disease burden (Lund Mackay CT score) and endoscopic disease (Lund Kennedy endoscopic score) burden. This study validated our use of this tool to measure quality of life and symptom improvement in patients undergoing surgery. Chapter three describes a detailed retrospective study of the outcomes of primary frontal sinus surgery. This is the largest study in the literature of primary frontal surgery and forms the basis to support an approach where the diseased frontal sinus should be addressed surgically to optimize long-term outcomes. It also identified that certain anatomical factors such as a narrow frontal ostium seemed to play a role in persistence of symptoms. This raised questions as to whether these outcomes were as successful for revision and extended frontal sinus surgery. Were there identifiable risk factors for success and failure? The fourth chapter describes the outcomes of primary and revision standard frontal sinus surgery and investigates which patient, anatomical and disease factors were poor prognostic factors for failure. It identified a select cohort of patients that would benefit not just from frontal sinus surgery, but extended frontal sinus surgery (EMLP) in the first instance. The final chapter investigates the outcomes of extended frontal sinus surgery (EMLP) and seeks to determine the risk factors for its success and failure. This study found that the EMLP had excellent outcomes in the majority of patients, but there was a significant minority of patients that had persistence of symptoms. The relevance of the host immune system response to sinonasal microorganisms, and anatomical risk factors was also explored and lays open the basis for further study.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201

Outcomes of modified endoscopic Lothrop in aspirin-exacerbated respiratory disease with nasal polyposis

Patients with aspirin-exacerbated respiratory disease (AERD) and chronic rhinosinusitis with nasal polyps (CRSwNP) are often reported to be recalcitrant to standard medical and surgical intervention. Failure rates of standard endoscopic sinus surgery in these patients are reported to be as high as 90%. We review the outcomes for our cohort of AERD patients undergoing endoscopic sinus surgery and endoscopic modified Lothrop procedure (EMLP).Data was collected prospectively between January 2001 and December 2013. Information including demographics, asthma status, aspirin sensitivity, 22-item Sino-Nasal Outcome Test (SNOT-22), Lund-Mackay scores, and endoscopic ostium assessment were collected for up to 5 years. Minimum follow-up was 6 months.A total of 31 AERD patients underwent complete sphenoethmoidectomy, maxillary antrostomy and EMLP during the study period with an average follow-up of 36 months. Polyp recurrence was seen in a total of 18 patients (58%). Seven patients required revision EMLP following initial surgery demonstrating a failure rate of 22.5%. AERD patients had a statistically significant increased risk of both nasal polyps recurrence and need for revision surgery. Revision EMLP was needed due to recurrence of nasal polyps in 6 cases and frontal ostium stenosis in a single case. Time to revision EMLP was similar between the groups.Complete sphenoethmoidectomy, maxillary antrostomy, and EMLP is successful in a significant majority of patients with AERD and CRSwNP. It is well tolerated with a low complication rate and facilitates successful ongoing medical management of the condition in patients with AERD

Outcomes of revision endoscopic modified Lothrop procedure

Endoscopic modified Lothrop procedure (EMLP) is used to treat patients who fail conventional sinus surgery. The failure rate of a primary EMLP is reported to be between 5% and 32%. The failure rate of revision EMLP has not been reported. We present our institutions data regarding the outcome of patients requiring revision EMLP.Data was collected prospectively. Patients undergoing primary EMLP between January 2001 and December 2013 with a minimum follow-up of 6 months were included. Information related to demographics, asthma status, aspirin sensitivity, 22-item Sino-Nasal Outcome Test (SNOT-22) score, Lund-Mackay scores, intraoperative findings, and endoscopic ostium assessment were collected.There were 213 primary EMLPs completed with average follow-up of 36 months. The failure rate of primary EMLP was 8.9% (19/213), whereas the failure rate of revision EMLP was 21% (4/19). Risk factors for failure of primary EMLP included the presence of intraoperative pus, more than 5 previous sinus operations and aspirin-exacerbated respiratory disease (AERD). Revision of EMLP was undertaken primarily due to recurrence of nasal polyps or ostium stenosis. Those patients who underwent revision EMLP experienced symptomatic improvement and no major complications following the procedure.The failure rate of revision EMLP is 21% in our series. The majority of revisions were for nasal polyp recurrence. Revision EMLP is a safe and well-tolerated procedure in the small group of patients that require further surgery. Patients with intraoperative pus present at their initial EMLP, more than 5 previous sinus operations, or AERD are at increased risk of failure

Image4.TIFF

<p>Chronic rhinosinusitis (CRS) is an inflammatory condition that affects up to 12% of the human population in developed countries. Previous studies examining the potential role of the sinus bacterial microbiota within CRS infections have found inconsistent results, possibly because of inconsistencies in sampling strategies. The aim of this study was to determine whether the sinus microbiome is altered in CRS and additionally if the middle meatus is a suitable representative site for sampling the sinus microbiome. Swab samples were collected from 12 healthy controls and 21 CRS patients, including all eight sinuses for CRS patients and between one and five sinuses for control subjects. The left and right middle meatus and nostril swabs were also collected. Significant differences in the sinus microbiomes between CRS and control samples were revealed using high-throughput 16S rRNA gene sequencing. The genus Escherichia was over-represented in CRS sinuses, and associations between control patients and Corynebacterium and Dolosigranulum were also identified. Comparisons of the middle meatuses between groups did not reflect these differences, and the abundance of the genus Escherichia was significantly lower at this location. Additionally, intra-patient variation was lower between sinuses than between sinus and middle meatus, which together with the above results suggests that the middle meatus is not an effective representative sampling site.</p

DataSheet2.docx

<p>Chronic rhinosinusitis (CRS) is an inflammatory condition that affects up to 12% of the human population in developed countries. Previous studies examining the potential role of the sinus bacterial microbiota within CRS infections have found inconsistent results, possibly because of inconsistencies in sampling strategies. The aim of this study was to determine whether the sinus microbiome is altered in CRS and additionally if the middle meatus is a suitable representative site for sampling the sinus microbiome. Swab samples were collected from 12 healthy controls and 21 CRS patients, including all eight sinuses for CRS patients and between one and five sinuses for control subjects. The left and right middle meatus and nostril swabs were also collected. Significant differences in the sinus microbiomes between CRS and control samples were revealed using high-throughput 16S rRNA gene sequencing. The genus Escherichia was over-represented in CRS sinuses, and associations between control patients and Corynebacterium and Dolosigranulum were also identified. Comparisons of the middle meatuses between groups did not reflect these differences, and the abundance of the genus Escherichia was significantly lower at this location. Additionally, intra-patient variation was lower between sinuses than between sinus and middle meatus, which together with the above results suggests that the middle meatus is not an effective representative sampling site.</p

DataSheet1.DOCX

<p>Chronic rhinosinusitis (CRS) is an inflammatory condition that affects up to 12% of the human population in developed countries. Previous studies examining the potential role of the sinus bacterial microbiota within CRS infections have found inconsistent results, possibly because of inconsistencies in sampling strategies. The aim of this study was to determine whether the sinus microbiome is altered in CRS and additionally if the middle meatus is a suitable representative site for sampling the sinus microbiome. Swab samples were collected from 12 healthy controls and 21 CRS patients, including all eight sinuses for CRS patients and between one and five sinuses for control subjects. The left and right middle meatus and nostril swabs were also collected. Significant differences in the sinus microbiomes between CRS and control samples were revealed using high-throughput 16S rRNA gene sequencing. The genus Escherichia was over-represented in CRS sinuses, and associations between control patients and Corynebacterium and Dolosigranulum were also identified. Comparisons of the middle meatuses between groups did not reflect these differences, and the abundance of the genus Escherichia was significantly lower at this location. Additionally, intra-patient variation was lower between sinuses than between sinus and middle meatus, which together with the above results suggests that the middle meatus is not an effective representative sampling site.</p

Image1.TIFF

<p>Chronic rhinosinusitis (CRS) is an inflammatory condition that affects up to 12% of the human population in developed countries. Previous studies examining the potential role of the sinus bacterial microbiota within CRS infections have found inconsistent results, possibly because of inconsistencies in sampling strategies. The aim of this study was to determine whether the sinus microbiome is altered in CRS and additionally if the middle meatus is a suitable representative site for sampling the sinus microbiome. Swab samples were collected from 12 healthy controls and 21 CRS patients, including all eight sinuses for CRS patients and between one and five sinuses for control subjects. The left and right middle meatus and nostril swabs were also collected. Significant differences in the sinus microbiomes between CRS and control samples were revealed using high-throughput 16S rRNA gene sequencing. The genus Escherichia was over-represented in CRS sinuses, and associations between control patients and Corynebacterium and Dolosigranulum were also identified. Comparisons of the middle meatuses between groups did not reflect these differences, and the abundance of the genus Escherichia was significantly lower at this location. Additionally, intra-patient variation was lower between sinuses than between sinus and middle meatus, which together with the above results suggests that the middle meatus is not an effective representative sampling site.</p

Image2.TIFF

<p>Chronic rhinosinusitis (CRS) is an inflammatory condition that affects up to 12% of the human population in developed countries. Previous studies examining the potential role of the sinus bacterial microbiota within CRS infections have found inconsistent results, possibly because of inconsistencies in sampling strategies. The aim of this study was to determine whether the sinus microbiome is altered in CRS and additionally if the middle meatus is a suitable representative site for sampling the sinus microbiome. Swab samples were collected from 12 healthy controls and 21 CRS patients, including all eight sinuses for CRS patients and between one and five sinuses for control subjects. The left and right middle meatus and nostril swabs were also collected. Significant differences in the sinus microbiomes between CRS and control samples were revealed using high-throughput 16S rRNA gene sequencing. The genus Escherichia was over-represented in CRS sinuses, and associations between control patients and Corynebacterium and Dolosigranulum were also identified. Comparisons of the middle meatuses between groups did not reflect these differences, and the abundance of the genus Escherichia was significantly lower at this location. Additionally, intra-patient variation was lower between sinuses than between sinus and middle meatus, which together with the above results suggests that the middle meatus is not an effective representative sampling site.</p

Image5.TIFF

<p>Chronic rhinosinusitis (CRS) is an inflammatory condition that affects up to 12% of the human population in developed countries. Previous studies examining the potential role of the sinus bacterial microbiota within CRS infections have found inconsistent results, possibly because of inconsistencies in sampling strategies. The aim of this study was to determine whether the sinus microbiome is altered in CRS and additionally if the middle meatus is a suitable representative site for sampling the sinus microbiome. Swab samples were collected from 12 healthy controls and 21 CRS patients, including all eight sinuses for CRS patients and between one and five sinuses for control subjects. The left and right middle meatus and nostril swabs were also collected. Significant differences in the sinus microbiomes between CRS and control samples were revealed using high-throughput 16S rRNA gene sequencing. The genus Escherichia was over-represented in CRS sinuses, and associations between control patients and Corynebacterium and Dolosigranulum were also identified. Comparisons of the middle meatuses between groups did not reflect these differences, and the abundance of the genus Escherichia was significantly lower at this location. Additionally, intra-patient variation was lower between sinuses than between sinus and middle meatus, which together with the above results suggests that the middle meatus is not an effective representative sampling site.</p