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Background: Intranasal corticosteroids (INCSs) are well established in the treatment of allergic rhinitis, chronic rhinosinusitis, and nasal polyposis. Although reversible atrophy of keratinized skin is seen with corticosteroids, the respiratory mucosa is histologically very different and but concerns remain among patients and some health-care professionals over local side effects on nasal respiratory mucosa. A systematic review and meta-analysis were performed of the available evidence for nasal mucosal atrophy as an adverse effect of INCSs in patients with sinonasal disease. Methods: A systematic search of Embase (1974-) and Medline (1946-) databases to September 27, 2013 was performed. Inclusion criteria selected any study where the histopathology of nasal mucosa was assessed in patients with sinonasal disease using intranasally administered corticosteroids with or without a control group. Results: Twenty-three hundred sixty-four publications were retrieved with a subsequent full text review of 149 publications for 34 articles that met the selection criteria. These articles included 11 randomized controlled trials, 5 cohorts, and 20 case series. Duration of treatment varied from 5 days to 5.5 years. 'Mucosal atrophy' as an outcome was reported in 17 studies. The definition of 'mucosal atrophy' was highly variable with a definition given in only 10 studies. One hundred thirty-six patients were represented in controlled studies of atrophy with only one study reporting the event in both groups with an odds ratio of 'mucosal atrophy' at 0.51 (95% CI, 0.09-3.11; p = 0.47). Conclusion: The concept of nasal mucosal atrophy is poorly defined and there is no histological evidence for deleterious effects from INCS use on human nasal mucosa. [ABSTRACT FROM AUTHOR]

Background Although remodeling changes of the lower airway are well described, similar changes in the upper airway are less well known. Remodeling changes of the upper airway in chronic rhinosinusitis (CRS) relevant to different phenotypes and endotypes and their clinical characteristics are investigated. Methods A cross-sectional study of adult patients with CRS was performed. Mucosal samples were taken during endoscopic sinus surgery (ESS). Histopathological analysis included eosinophil count, eosinophil activation (eosinophilic mucin), and remodeling changes. Mucosal damage was defined as ulceration, edema, and hypertrophic changes. Patient-reported outcomes (PROMs) were assessed using a Nasal Symptom Score (NSS) and Sino-Nasal Outcome Test (SNOT-22). Patients were subgrouped by presence of polyps (CRSwNP/CRSsNP) or tissue eosinophilia (>10/high power field). Subgroup analysis was performed when both eosinophilic chronic rhinosinusitis (eCRS) and eosinophil activation (eCRSwEA) were coexistent. Analysis between subgroups, pathology, and PROMs was also performed. Results A total of 259 patients (age 48.5 ± 15.6 years, 45% female) were recruited; 53% CRSwNP, 51% eCRS. Remodeling changes were present in 85%, higher in both CRSwNP (90%, p = 0.006) and eCRS (91%, p = 0.004). Mucosal damage changes were common in eCRS (ulceration 18%, p = 0.003; edema 98%, p < 0.001; hypertrophic changes 25%, p = 0.007). NSS was worse in CRSwNP compared to CRSsNP (2.84 ± 1.1 vs 2.29 ± 1.1, p < 0.001) and eCRSwEA (2.95 ± 0.16 vs 2.51 ± 0.11, p = 0.04). 'Loss of sense of smell or taste' was worse in patients with evidence of mucosal damage ( p = 0.006). Conclusion Remodeling features are present in CRS. Tissue eosinophilia and evidence of eosinophil activation is closely associated with remodeling features of CRS, associated mucosal damage and clinical symptoms. [ABSTRACT FROM AUTHOR]

Background The histological features of osteitis in chronic rhinosinusitis (CRS) in animal studies induced by bacterial inoculation into maxillary sinuses revealed inflammatory involvement of the underlying bone matrix and/or the Haversian system; however, human studies do not mention these findings. The objective of this study was to investigate the inflammatory characterization of osteitis in CRS. Method A prospective study of primary CRS patients undergoing sinus surgery was conducted (August 2012 to April 2013). Bone-mucosa samples were taken from a predetermined site that correlated to a computed tomography location. Radiological bone thickness was measured. A blinded histopathological assessment included inflammatory infiltrate of bone, periosteal reaction, presence of osteoblasts or osteoclasts, fibrosis, and the percentage of new woven bone to total bone thickness, together with an overall opinion of whether neo-osteogenesis was present. Results Twenty-two primary CRS patients (age 45.8 ± 15.6 years; 59.1% female) were recruited. CRS with polyps accounted for 59.1% of patients. The bony thickness measured radiologically was a median 1.72 (interquartile range [IQR], 2.38; range, 0.3-12.14) mm. No samples (0%) had evidence of inflammatory infiltrate of bone; 90.9% had both osteoblasts present and new woven bone formation. Woven bone was greater with periosteal reaction (80.83% ± 9.25% vs. 47.50% ± 29.37%; p = 0.006), greater with osteoclasts present (80.00% ± 12.58% vs 59.00% ± 28.52%; p = 0.03), and greater when fibrosis was present (69.75% ± 24.14% vs 25.00% ± 7.07%; p = 0.003). Conclusion Most primary CRS patients demonstrated evidence of new woven bone formation. True 'osteitis' with inflammatory infiltrate of the bone was not observed. 'Osteitis' is likely a process of neo-osteogenesis and bone remodeling, rather than bone inflammation in primary CRS. [ABSTRACT FROM AUTHOR]

Background The influence of the microbial community on inflammatory subtype in chronic rhinosinusitis (CRS) has been proposed. Superantigen mechanisms potentially create a T helper 2 (Th-2)/eosinophilic dominated inflammation as a product of local flora rather than an intrinsic mucosal process. The associations between culturable bacteria and the histopathology and clinical features of CRS patients are described. Methods A cross-sectional study involving patients with CRS undergoing surgery was undertaken. Middle meatal swabs were performed at surgery for microbiological evaluation. Mucosal biopsies were taken and a blinded histopathological profile was performed. Disease specific quality of life and nasal symptom scores were recorded. The presence of culturable organisms and particular pathogens were compared with histopathology and clinical outcomes. Results A total of 95 patients were assessed (48.4% female, mean age 45.6 ± 14.0 years), of which 47.3% had a culturable organism. Tissue eosinophilia (>10/high-power field [HPF]) was found in 46.1% of these patients and 30.3% had neutrophilic infiltrate, with the presence of neither Gram-positive organisms, Gram-negative organisms, nor species correlating to pathology subtype. A culturable pathogen was a predictor of subepithelial fibrosis (χ2 = 6.36, p = 0.04) and Gram-negative bacteria had the strongest association (χ2 = 18.82, p < 0.01). There were no other significant associations with other clinical outcomes. Conclusion The culturable bacterial community has little impact on histopathology in CRS. While more sensitive tests may detect bacteria in the sinuses, the impact of the simple 'culturable' bacteria on the underlying pathologic process is limited. Changes, such as subepithelial fibrosis, suggest colonization may lead to undesirable local mucosal damage and remodeling. [ABSTRACT FROM AUTHOR]