Distinct Patterns of Tissue Remodeling and Their Prognostic Role in Chronic Rhinosinusitis

ORL ◽  
2021 ◽  
pp. 1-7
Author(s):  
Ho Yun Lee ◽  
Jung-Soo Pyo ◽  
Su Jin Kim

<b><i>Introduction:</i></b> Tissue remodeling refers to structural changes that occur in damaged tissue and is associated with disease severity in asthma. However, the characteristics of tissue remodeling and its prognostic role in chronic rhinosinusitis (CRS) remain unclear. In this report, we evaluated the clinical implications of tissue remodeling in CRS. <b><i>Methods:</i></b> We performed a retrospective cohort study of adult patients who underwent endoscopic sinus surgery for bilateral CRS. The histopathology of sinus mucosa was determined by evaluating the inflammatory cell count and tissue remodeling markers (squamous metaplasia, subepithelial gland proliferation, basement membrane [BM] thickening, stromal edema, and fibrosis). Eosinophilic CRS (ECRS) was defined as an eosinophil count &#x3e;15/high-power field in the biopsied tissue. Patient characteristics, allergy test grade, preoperative Lund-Mackay score (LMS), and pre- and postoperative Lund-Kennedy scores (LKSs) were analyzed. <b><i>Results:</i></b> Of the identified patients, 59.1% were classified as ECRS and the remaining 40.9% as non-ECRS. Regarding tissue remodeling markers, stromal edema was seen in 90.9%, BM thickening in 63.6%, and stromal fibrosis in 34.1% of patients. In cases with stromal edema and BM thickening, greater tissue eosinophilia was observed, while stromal fibrosis decreased tissue eosinophilia (<i>p</i> &#x3c; 0.05). Prognostically, subepithelial gland proliferation alone was an independent risk factor for poor postoperative endoscopic findings (odds ratio: 8.250, 95% confidence interval: 1.128–60.319, <i>p</i> = 0.038). <b><i>Conclusions:</i></b> Tissue eosinophilia was commonly associated with BM thickening and stromal edema. Subepithelial gland proliferation predicted a poor surgical prognosis in CRS. These findings imply that tissue remodeling provides additional information not only on the CRS endotype but also on the postsurgical prognosis.

2018 ◽  
Vol 32 (2) ◽  
pp. 112-118 ◽  
Author(s):  
Ashley L. Heilingoetter ◽  
Bobby Tajudeen ◽  
Hannah N. Kuhar ◽  
Paolo Gattuso ◽  
Ritu Ghai ◽  
...  

Background Structured histopathology reporting facilitates better understanding of the underlying pathophysiologic mechanisms of chronic rhinosinusitis. The microbiology of chronic rhinosinusitis has been studied extensively; however, distinct histopathologic changes associated with bacteria isolated in chronic rhinosinusitis are largely unknown. Objective The goal of this study is to better understand the relationship between culturable bacteria and histopathology in chronic rhinosinusitis. Methods A structured histopathology report was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery in a group of patients with chronic rhinosinusitis refractory to medical therapy. Patients with cystic fibrosis or ciliary dysfunction were excluded. Histology variables included eosinophil count per high-power field, neutrophil infiltrate, basement membrane thickening, subepithelial edema, hyperplastic/papillary changes, mucosal ulceration, squamous metaplasia, fibrosis, fungal elements, Charcot-Leyden crystals, and eosinophil aggregates. Baseline Lund-Mackay score and Sinonasal Outcome Test 22 score were also collected. The association of culture data with the aforementioned variables was assessed. Results A total of 59 chronic rhinosinusitis patients who underwent functional endoscopic sinus surgery were included. Chronic rhinosinusitis patients with Pseudomonas aeruginosa had significantly increased neutrophil infiltrate (71.4% vs. 26.9%, p = 0.048), subepithelial edema (28.6% vs. 3.8%, p = 0.047), and a trend toward increased fungal elements (28.6% vs. 5.8%, p = 0.071). Chronic rhinosinusitis patients with Staphylococcus aureus had significantly more hyperplastic changes (20% vs. 2.3%, p = 0.050) and a trend toward increased squamous metaplasia (33.3% vs. 14.2%, p = 0.069). Conclusion Distinct histopathologic changes were noted based on sinus culture data for S. aureus and P. aeruginosa. These findings may have important implications on the extent of surgical management and prognosis after surgery.


2019 ◽  
Vol 34 (3) ◽  
pp. 331-335 ◽  
Author(s):  
Ashwin Ganti ◽  
Hannah J. Brown ◽  
Hannah N. Kuhar ◽  
Paolo Gattuso ◽  
Ritu Ghai ◽  
...  

Background A subset of chronic rhinosinusitis (CRS) patients demonstrates tissue eosinophilia on structured histopathology. Prior studies have suggested that these patients are at increased risk for recurrent disease. The goals of this study are to identify histopathologic features of CRS patients with tissue eosinophilia and compare the influence of tissue eosinophilia to the effects of age and revision surgery on histopathology. Methods A structured histopathology report was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery. Binomial logistic regression analysis was conducted to evaluate the association of age at diagnosis, tissue eosinophil count, and history of revision surgery with histopathology variables. Results A total of 281 CRS patients were included, of which 106 had tissue eosinophilia. Regression analysis demonstrated that tissue eosinophilia was associated with degree of inflammation (odds ratio [OR] 5.744; P <  .001), neutrophilic infiltrate (OR 1.882; P =  .020), basement membrane thickening (OR 3.561; P <  .001), squamous metaplasia (OR 3.315; P <  .001), fibrosis (OR 2.246; P =  .002), presence of Charcot–Leyden crystals (OR 20.700; P =  .004), and eosinophilic aggregates (OR 34.172; P <  .001). Age and history of revision surgery were not significant predictors of histopathology variables on multivariate analysis. Conclusion Tissue eosinophilia appears to be the predominant driving factor of histopathologic changes irrespective of previous sinus surgery or age at diagnosis. These findings may have important implications for postsurgical management and prognosis for patients with tissue eosinophilia presenting for revision surgery.


2020 ◽  
pp. 014556132096035
Author(s):  
Gian Luca Fadda ◽  
Andrea Galizia ◽  
Giuseppe Galizia ◽  
Paolo Castelnuovo ◽  
Maurizio Bignami ◽  
...  

Introduction: Previous studies have reported a diverse range of threshold values for blood eosinophilia. In addition, a single predictive biomarker for eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (ECRSwNP) has not yet been identified. Objectives: The aim of this study is to compare the clinical characteristics of ECRSwNP and non-ECRSwNP to evaluate the preoperative risk of tissue eosinophilia of chronic rhinosinusitis with nasal polyps (CRSwNP) through a multiparametric statistical analysis. Methods: One hundred ten patients with evidence of chronic polypoid rhinosinusitis were included in this study and clinical records were retrospectively reviewed. Eosinophilic CRSwNP was diagnosed based on the presence of at least 10 eosinophils per high-power field. The demographic and clinical features of ECRSwNP and non-ECRSwNP are described. The values of blood eosinophilia as predictors of tissue eosinophilia have been identified using receiver operating characteristic curves. As the predictive value of the identified cutoff through regression analysis was low, we evaluated whether other risk factors could be statistically associated with ECRSwNP, and from this, a new predictive model was proposed for the identification of eosinophilic nasal polyps before surgery. Results: We found that the best method for predicting ECRSwNP is based on a model having asthma, blood eosinophil percentage, posterior ethmoid value in Lund-Mackay score, and modified Lund-Kennedy score as explanatory variables. Conclusions: This study provides new data for a better understanding of the polypoid CRS endotypes, and the proposed model allows the endotype to be identified preoperatively.


2008 ◽  
Vol 22 (6) ◽  
pp. 602-605 ◽  
Author(s):  
Robert G. Mynatt ◽  
Jennifer Do ◽  
Christine Janney ◽  
Raj Sindwani

Background The significance of squamous metaplasia (SM) in chronic rhinosinusitis (CRS) is unknown. The objectives of this study were to determine the prevalence of SM in histopathological specimens from patients with CRS and to correlate these histological findings with clinical features. Methods We reviewed the clinical records and pathological slides from 87 consecutive patients who underwent endoscopic sinus surgery for CRS. Demographic and clinical data, preoperative Chronic Sinusitis Survey (CSS) scores, and sinus CT stage were evaluated. Pathological slides were graded by a pathologist to characterize the degree of inflammation and SM, when present. CRS patients with and without SM were compared using student's t-test and χ2 test. Results Evaluation of the pathology slides revealed that 18.4% of specimens had SM present, whereas only 2.2% of pathology reports noted this. Histological grading of chronic inflammation showed significantly greater severity in specimens with SM (n = 16) when compared with the cohort without SM (n = 75; 100.0% versus 77.5%, respectively; p = 0.016). There was no difference in preoperative CT stage or the presence of hyperostosis on imaging, CSS scores, duration of CRS symptoms, or other clinical features between those with SM and those without SM (p > 0.05). Immunodeficiency was the only comorbidity more prevalent in the metaplastic group (12.5% versus 0%, respectively; p = 0.003). Conclusion SM is present in ∼18% of routine CRS specimens. It has a positive correlation with the severity of inflammation noted histologically in CRS but does not correlate with disease severity or chronicity, clinically.


2002 ◽  
Vol 16 (3) ◽  
pp. 131-134 ◽  
Author(s):  
Eva Szucs ◽  
Saied Ravandi ◽  
Anita Goossens ◽  
Mieke Beel ◽  
Peter A.R. Clement

Background The aim of this study was to analyze histopathologically mucosal inflammation in patients with chronic rhinosinusitis. In addition, we assessed tissue eosinophilia in relation to the severity of inflammation and to the computer tomographic (CT) findings. Methods Forty-eight pathological sinus mucosa specimens obtained during functional endoscopic sinus surgery were stained by hematoxylin and eosin. Total inflammatory cells and eosinophils were quantified. The preoperative CT scans were scored by the staging system of Lund-MacKay. Results The grade of the eosinophilic infiltration in the diseased sinus mucosa correlated significantly with the severity of the mucosal inflammation. Allergy or asthma had no effect on the proportion of the eosinophilic infiltrate. The CT scan scores assessed by the Lund-MacKay system correlated significantly with the severity of the inflammatory cellular infiltrate. The correlation between the CT scan scores and the eosinophilic infiltrate of the mucosa was close to significant. Conclusion Eosinophilic mucosal inflammation represents the most severe inflammatory changes of the mucosa. Twenty to forty percent of the patients with chronic rhinosinusitis had no eosinophilic inflammation of the mucosa. The CT-staging system of Lund-Mackay correlated with the extent of mucosal inflammation.


2019 ◽  
Vol 129 (5) ◽  
pp. 512-516 ◽  
Author(s):  
Ashwin Ganti ◽  
Hannah N. Kuhar ◽  
Michael Eggerstedt ◽  
Mahboobeh Mahdavinia ◽  
Paolo Gattuso ◽  
...  

Background: Prior studies have demonstrated associations between serum eosinophilia and chronic rhinosinusitis (CRS) pathogenesis. However, the association of serum eosinophilia with histopathology profiling in CRS has not been fully delineated and may help better characterize CRS disease burden prior to surgery. Methods: A structured histopathology report of 13 variables was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). Complete blood count (CBC) with differential was drawn within 4 weeks prior to FESS. Serum eosinophilia was defined as >6.0% (>0.60 th/μL). Histopathology variables were compared among patients. Results: A total of 177 CRS patients (37 with serum eosinophilia and 140 with normal serum eosinophilia) were analyzed. Compared to CRS patients with normal serum eosinophil counts, CRS patients with serum eosinophilia demonstrated increased polypoid disease (67.6% vs 35.0%, P < .001), eosinophil aggregates (45.9% vs 20.7%, P = .003), and eosinophils per high-power field (>5/HPF) (67.6% vs 40.7%, P = .003). Conclusion: CRS patients with serum eosinophilia demonstrated severe disease burden on histopathology with high levels of polypoid disease and tissue eosinophilia. However, a considerable number of patients without serum eosinophilia demonstrated eosinophilic disease on histopathology, indicating that preoperative serum eosinophilia alone could not be reliably used to predict eosinophilic CRS. Level of evidence: 4


2020 ◽  
pp. 194589242094382
Author(s):  
Aykut A. Unsal ◽  
Camilo Reyes ◽  
Paul Biddinger ◽  
Stilianos E. Kountakis

Objective The presence of tissue eosinophilia is a determinate of disease severity in patients with chronic rhinosinusitis (CRS). The impact of eosinophilic mucin (EM) as an independent variable has not yet been elucidated. Study Design Retrospective review. Setting Tertiary academic clinic. Subjects Methods: CRS patients who failed medical therapy were classified by tissue eosinophilia, presence of polyps and EM. Tissue eosinophilia count per high power field (HPF) as well as the presence of EM were determined by pathologic examination of sinus tissue removed during surgery. Sinonasal Outcomes Test (SNOT-22), Lund-Mackay (LM), and Lund-Kennedy (LK) scores were compared between all groups preoperatively and postoperatively up to two and a half years (30 months). Results 192 patients with CRS were included in the study. 87 were diagnosed with eosinophilic CRS with polyps, 58 with eosinophilic CRS without polyps, 14 with noneosinophilic CRS with polyps, and 33 with noneosinophilic CRS without polyps. Only patients with eosinophilia had EM on pathology. Of eosinophilic CRS, 50% of patients with polyps and 12% of cases without polyps demonstrated EM, respectively. EM presence portended more severe disease in patients with eosinophilia on subjective and objective scores preoperatively (P < 0.005). Postoperatively, EM patients experienced a greater improvement of symptoms, but continued to have worse endoscopy scores until 1.5 years. A tissue eosinophil count of 30 or greater per HPF was identified as a potential marker for the development of EM. Conclusions The presence of eosinophilic mucin predicts overall worse disease severity in patients with eosinophilic CRS.


2020 ◽  
Vol 34 (6) ◽  
pp. 775-783 ◽  
Author(s):  
Hannah N. Kuhar ◽  
Ashwin Ganti ◽  
Hannah J. Brown ◽  
Paolo Gattuso ◽  
Ritu Ghai ◽  
...  

Background Smoking status has been established as a known irritant of the upper and lower respiratory tracts, leading to inflammation throughout the respiratory system. Tobacco smoking is one comorbidity encountered among chronic rhinosinusitis (CRS) patients. The histopathologic features of CRS and comorbid smoking status have yet to be determined by structured histopathology and may have important implications on disease management. Methods Retrospective study of structured histopathology reports analyzing sinus tissue removed during functional endoscopic sinus surgery. Histopathology variables were compared among patients with CRS who were reported as never smokers, former smokers, or current smokers. Results A total of 285 CRS patients were included: 173 never smokers, 85 former smokers, and 27 current smokers. When compared with former smokers, current smokers demonstrated increased basement membrane thickening (88.9% vs 67.1%, P <.020). Compared with never smokers, former and current smokers collectively demonstrated increased hyperplastic changes (14.3% vs 6.9%, P < .035), increased squamous metaplasia (26.8% vs 17.3%, P < .040), and trends toward increased basement membrane thickening (72.3% vs 65.3%, P < .124) and increased fibrosis (47.3% vs 40.5%, P < .154). Conclusion Smoking status may influence histopathologic tissue-level changes in CRS disease. Interestingly, former and current smokers maintained few differences in histopathology. However, former and current smokers collectively demonstrated increased chronic inflammatory changes compared with never smokers. These findings suggest that the timing of smoking exposure has limited effect on the tissue level, rather exposure overall influences inflammatory change. These findings may have important implications on medical and surgical management of CRS disease and comorbid smoking status.


2021 ◽  
Vol 9 (6) ◽  
pp. 1182
Author(s):  
Veronica-Elena Trombitaș ◽  
Alina Anda Nagy ◽  
Cristian Berce ◽  
Emoke Pall ◽  
Flaviu Tăbăran ◽  
...  

Objectives/Hypothesis: It is acknowledged that the treatment of chronic rhinosinusitis (CRS) represents an important challenge for rhinology and for social and economic life. At present, one of the most common treatments for CRS is represented by local corticosteroids followed by endoscopic sinus surgery (ESS). Starting from the example of the mesenchymal stem cell’s (MSC) capacity to migrate and to modulate a real response in the nasal mucosa of an allergic rhinitis mouse model, we try to obtain a response in a CRS mouse model, using MSC derived by adipose tissue. The aim of this study is to demonstrate that the MSC can be used in CRS treatment and could change its priorities. Methods: Seventy female mice (6 MSC donor mice) were randomized in two stages of study, 32 Aspergillus fumigatus (Af) exposure mice (20 for histological comparison to 1st control mice and 12 for MSC administration, to CRS/MCS model) and 32 control mice (20 for histological comparison to CRS model and 12 for MSC administration and histological control to MSC model); in the first stage, the Aspergillus fumigatus (Af) CRS mouse model was targeted, in this section were included 64 (n = 32) mice (treated and control group). In order to assess the inflammation level (histological analysis), the animals were euthanized; in the second stage MSCs (1 × 106/animal) were administered intravenously to a total of 24 (n = 24) mice (12 mice from the exposed group and 12 mice from the second control group). Results: After 12 weeks of Af intranasal instillation, the inflammation parameters evaluated indicated a severe diffuse chronic inflammation, associated with diffuse severe hyperplasia and mature diffuse squamous metaplasia. The MSCs’ injection via the ophthalmic vein induced important histopathological changes in the CRS experimental group, starting with the presence of MSCs in all samples and continuing with the important degenerative character of inflammation. Conclusions: MSC administration demonstrated a real improvement of CRS evolution on the CRS mouse model.


2021 ◽  
pp. 000348942098797
Author(s):  
Ashwin Ganti ◽  
Hannah J. Brown ◽  
Paolo Gattuso ◽  
Ritu Ghai ◽  
Peter Papagiannopoulos ◽  
...  

Background: Structured histopathology reporting is increasingly being utilized in rhinology to characterize endotypes in chronic rhinosinusitis and guide management decisions after sinus surgery. Objective: The goal of this investigation is to evaluate inter-observer agreement in structured histopathology reporting. Methods: Two experienced head and neck pathologists independently compiled structured histopathology reports for tissue samples collected during functional endoscopic sinus surgery. Cohen’s standard kappa (κ) coefficients were calculated for each histopathologic variable to assess inter-pathologist agreement. Results: A total of 92 cases were analyzed. Substantial inter-pathologist agreement was reached on tissue eosinophil count (κ = 0.64, P < .001), the presence of eosinophil aggregates (κ = 0.62, P < .001), and the presence of fungal elements (κ = 0.74, P < .001). There was moderate agreement on the degree of inflammation (κ = 0.56, P < .001) and the presence of squamous metaplasia (κ = 0.46, P < .001). There was fair agreement on the presence of neutrophil infiltrates (κ = 0.33, P < .001), the presence of hyperplastic changes (κ = 0.40, P < .001), and the presence of fibrosis (κ = 0.24, P = .022). There was only slight agreement on the degree of subepithelial edema (κ = 0.20, P = .008). The κ coefficients for basement membrane thickening and mucosal ulceration were not statistically significant. Conclusion: High inter-pathologist agreement was demonstrated for several salient histopathologic variables, including tissue eosinophil count and the presence of eosinophil aggregates. However, refining the definitions of certain histopathologic variables may improve the reproducibility of structured histopathology reporting.


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