Search

Background: Environmental exposures have been postulated to play an important role in the pathophysiology of chronic rhinosinusitis (CRS). Particulate matter (PM) is one of the most widely studied ambient air pollutants, but its peri-operative impact on CRS is unknown. Objective: To determine the effect of acute, peri-operative PM exposure on outcomes after endoscopic sinus surgery (ESS). Methods: Participants with CRS who self-selected ESS were prospectively enrolled. The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility values scores were recorded. Using residence zip codes, a secondary analysis of patient exposure to PM <2.5 μm and <10 μm (PM2.5 and PM10, respectively) was performed for the month of surgery utilizing data from Environmental Protection Agency air quality monitors. Spearman's correlation coefficients (ρ), 95% confidence intervals (CIs), and effect estimates (β) were used to determine the magnitudes of association. Simple, multivariate regression analysis was also completed. Results: One hundred and seven patients from four geographically unique institutions across the US were enrolled with a follow-up of 6 months. Patients with higher peri-operative PM2.5 exposure had less improvement in their SNOT-22 scores after ESS compared to those with less exposure using both univariate analysis (ρ = 0.26, 95% CI: 0.08, 0.43; P =.01) and after covariate adjustment with multivariate analysis (B = 1.06, 95% CI: 0.001, 2.14, P =.05). Similar associations were not found with SF-6D outcomes or with PM10 as an exposure of interest. No significant correlations were found between peri-operative PM levels and Lund-Kennedy endoscopy scores post-operatively. Conclusion: Preliminary data from this pilot study reveal that PM exposure at the time of ESS may negatively associate with post-operative improvement in sinonasal quality-of-life. Larger, population-based studies with more standardized PM exposure windows are needed to confirm the clinical significance of the present findings. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to investigate otolaryngologists' knowledge, trust, acceptance, and concerns with clinical applications of artificial intelligence (AI). Methods: This study used mixed methods with survey and semistructured interviews. Survey was e‐mailed to American Rhinologic Society members, of which a volunteer sample of 86 members responded. Nineteen otolaryngologists were purposefully recruited and interviewed until thematic saturation was achieved. Results: Seventy‐six respondents (10% response rate) completed the majority of the survey: 49% worked in academic settings and 43% completed residency 10 or fewer years ago. Of 19 interviewees, 58% worked in academic settings, and 47% completed residency 10 or fewer years ago. Familiarity: Only 8% of survey respondents reported having AI training in residency, although 72% had familiarity with general AI concepts; 0 interviewees had personal experience with AI in clinical settings. Expected uses: Of the surveyed otolaryngologists, 82% would use an AI‐based clinical decision aid and 74% were comfortable with AI proposing treatment recommendations. However, only 44% of participants would trust AI to identify malignancy and 53% to interpret radiographic images. Interviewees trusted AI for simple tasks, such as labeling septal deviation, more than complex ones, such as identifying tumors. Factors influencing AI adoption: 89% of survey participants would use AI if it improved patient satisfaction, 78% would be willing to use AI if experts and studies validated the technologies, and 73% would only use AI if it increased efficiency. Sixty‐one percent of survey respondents expected AI incorporation into clinical practice within 5 years. Interviewees emphasized that AI adoption depends on its similarity to their clinical judgment and to expert opinion. Concerns included nuanced or complex cases, poor design or accuracy, and the personal nature of physician‐patient relationships. Conclusion: Few physicians have experience with AI technologies but expect rapid adoption in the clinic, highlighting the urgent need for clinical education and research. Otolaryngologists are most receptive to AI "augmenting" physician expertise and administrative capacity, with respect for physician autonomy and maintaining relationships with patients. Level of Evidence: Level VI, descriptive or qualitative study. [ABSTRACT FROM AUTHOR]

In chronic rhinosinusitis (CRS), a complex pathophysiology results from varied pro-inflammatory stimuli but is consistently characterized by classic cellular, molecular, and microbial alterations. Normally, endogenous specialized pro-resolving mediators (SPM) actively promote resolution of inflammation through numerous pathways, including those involved in host antimicrobial defense. However, these pathways appear to be disrupted in CRS. This paper describes features of CRS in the context of chronic tissue inflammation, and potential mechanisms by which specialized pro-resolving mediators promote active resolution of tissue inflammation. Temporal phases of resolution must be tightly regulated to successfully resolve inflammation in CRS while preserving tissue functions such as barrier maintenance and special sensory function. Dysregulation of SPM enzymatic pathways has been recently shown in CRS and is associated with disease phenotypes and microbial colonization patterns. Current research in animal models and in vitro human cell culture, as well as human dietary studies, demonstrate relevant changes in cell signaling with lipid mediator bioavailability. Further clinical research may provide insight into the therapeutic value of this approach in CRS. [ABSTRACT FROM AUTHOR]

Objective: Despite extensive research into chronic rhinosinusitis (CRS) epidemiology, presentation, and outcomes, there is scant knowledge on sex‐specific differences. The objective of this study was to identify differences between male and female patients with CRS in baseline disease severity at presentation, choice for surgery vs continued medical treatment, and postoperative response. Study Design: We evaluated data on demographic and health characteristics, clinical objective disease measures, and sinus‐specific and general health patient‐reported outcome measures. Setting: Secondary analysis of prospective multicenter outcome study. Methods: Comparison of cohort characteristics and baseline and postoperative measures was performed with a t test, chi‐square test of independence, or Fisher exact test. Within‐subject improvement was compared between sexes with a linear mixed model. Results: Females reported worse quality of life on presentation and postsurgery, despite experiencing less severe disease by standard clinical measures. Overall, females and males showed similar within‐subject improvement after surgery. However, certain quality of life domains and disease measures showed sex‐specific improvement. Females demonstrated greater within‐subject improvement in SF6D‐derived health utility and the SNOT‐22 ear and facial, psychological, and sleep subdomains, although this did not reach statistical significance for the overall cohort. Conclusion: Incorporating data on sex‐specific differences may be important to personalize CRS treatment decision making. The discordance between patient‐reported and clinical measures in CRS has been demonstrated in other pathologies and appears to be exaggerated by sex. Biological and psychological bases for sex‐specific differences in CRS manifestations are an intriguing topic for further research. [ABSTRACT FROM AUTHOR]

Keywords: chronic rhinosinusitis; infection; inflammation; sinusitis; upper airway EN chronic rhinosinusitis infection inflammation sinusitis upper airway 1566 1569 4 12/02/22 20221201 NES 221201 INTRODUCTION Despite ongoing study into chronic rhinosinusitis (CRS) disease mechanisms, the origins of chronic inflammation are somewhat elusive.[1] CRS is defined by 3 months of symptoms with evidence of disease, either radiographically or endoscopically.[2] Interestingly, pathologic correlates of inflammation are not required for diagnosis, but are well described. Control samples had enriched RNA processing GO pathways but no KEGG pathways reaching statistical significance. [Extracted from the article]

Objective: Sex discrepancies have been reported in chronic rhinosinusitis (CRS), but limited data exist exploring sex-specific biological processes and sinonasal quality of life. Study Design: Prospective cohort. Setting: Academic medical center. Methods: Demographics, clinical data, and sinonasal mucus were collected from patients with CRS presenting for surgical consideration over a 5-year period. A random forest model and linear regression were used to assess predictor variables for the 22-item Sino-Nasal Outcome Test (SNOT-22) and subdomains. Enzyme-linked immunosorbent assays were used to measure substance P and tryptase in a subset of mucus samples to explore biological differences by sex. Results: In total, 520 patients were studied (mean age 48.3 years, 50.9% female). Males were older (50.1 vs 46.6 years, P =.008), had more polyp disease (48.2% vs 35.5%, P =.004), and had higher mean Lund-Mackay CT score (11.3 vs 9.5, P =.004). Females had a higher overall mean SNOT-22 (40.9 vs 46.9, P =.001) and higher scores in ear/facial, psychological, and sleep domains (P <.01). Age, objective disease measures, and sex were top predictors for total SNOT-22. Neither mucus substance P or tryptase, alone or paired with sex, correlated with total SNOT-22. Analysis of mucus biomarkers by sex revealed correlation between mucus tryptase in females with the extranasal subdomain (P =.01). Conclusion: Sex differences exist in CRS disease manifestations and presentation for surgical consideration. Detection of mucus (substance P and tryptase) was reliable, but in this exploratory study, we were not able to establish neurogenic or allergic inflammatory processes as a large source of differential disease features between sexes. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a complex, heterogenous condition that is likely associated with infectious and inflammatory causative factors. Renewed interest in the role that microbes play in this condition has stemmed from advancements in microbe identification and parallel research implicating the microbiome as having a role in other chronic inflammatory conditions. This clinical commentary provides a review of the current literature relevant to chronic rhinosinusitis. Particular focus is placed on factors specific to investigation of the sinonasal microbiome, evidence for the role of dysbiosis in the disease state, and influences that may affect the microbiome. Possible mechanisms of disease and therapeutic implications through microbial manipulation are also reviewed, as are deficiencies and limitations of the current body of research. [ABSTRACT FROM AUTHOR]

Objectives: Prior studies have indicated that olfactory cleft (OC) opacification correlates with olfaction in patients with chronic rhinosinusitis (CRS). However, the results have been unclear in patients without polyps. The purpose of this study was to further explore the relationship between OC opacification, sinus opacification, and olfactory function in patients with CRS.Methods: One hundred and forty-eight patients with CRS were prospectively enrolled across five institutions. Olfactory function was evaluated using the Sniffin' Sticks tests (Burghardt, Wedel, Germany) and the 17-item Questionnaire of Olfactory Disorders (QOD-NS). Computed tomography (CT) scans for each patient were acquired and Lund-Mackay scores recorded. Opacification of the OC was determined using OsiriX MD (Pixmeo, Bernex, Switzerland) and correlated with olfaction scores.Results: A total of 148 CRS patients, 73 CRS without nasal polyps (CRSsNP) and 75 CRS with nasal polyps (CRSwNP), as well as 30 control subjects were enrolled. Overall OC opacification averaged 63.7% in CRS patients and 47.1% in control subjects (P < 0.001). In the overall cohort, OC opacification significantly correlated with threshold, discrimination, and identification (TDI) (r = -0.520; P < 0.001) and QOD-NS scores (r = 0.374; P < 0.001). CRSwNP patients demonstrated a significant correlation between OC opacification and TDI scores (r = -0.464; P < 0.001) but not the CRSsNP group (r = -0.143; P = 0.229). Lund-Mackay score correlated with TDI in both the CRSsNP (r = -0.300; P = 0.010) and CRSwNP (r = -0.271; P = 0.019) groups.Conclusion: CT opacification is associated with olfactory dysfunction differentially based on nasal polyp status. Smell loss in CRSwNP correlated with both OC opacification and Lund-Mackay score, whereas CRSsNP correlated only with Lund-Mackay score, indicating different relationships between olfactory function and local inflammatory processes in these disorders.Level Of Evidence: 2 Laryngoscope, 130:2311-2318, 2020. [ABSTRACT FROM AUTHOR]

Background: Earlier studies have suggested that patients with chronic rhinosinusitis (CRS) report worse sleep quality than population norms. What remains unknown is whether these patients are actually experiencing measurable changes in objective sleep parameters. The goal of this study was to prospectively evaluate objective sleep measures in a cohort of patients with CRS. Methods: A prospective, multi‐institutional, case‐control study was designed to compare patients with CRS to nondiseased controls. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (EpSS). Home sleep studies were administered across all subjects and a battery of objective sleep measurements were recorded using a portable sleep diagnostic device. Regression models were used to control for any factors that differed across groups. Results: A total of 108 subjects were enrolled across 4 institutions, including 52 patients with CRS and 56 controls. Total PSQI scores were worse in patients with CRS when compared with controls (10.1 ± 4.3 vs 4.7 ± 2.5; p < 0.001). Similarly, daytime somnolence, as measured by the EpSS, was greater in patients with CRS (9.1 ± 5.3 vs 6.5 ± 3.7; p = 0.006). On home sleep studies, patients with CRS were found to have an increased number of awakenings during a night's sleep (8.6 ± 4.8 vs 6.3 ± 3.0; p = 0.004), lower average overnight oxygen saturation (93.2 ± 2.6% vs 94.3 ± 2.1%; p = 0.042), increased rapid eye movement sleep (REMS) latency (93.0 ± 67.1 vs 66.7 ± 35.3; p = 0.016), and spent a greater portion of the night snoring at >40 dB (24.7 ± 27.4% vs 14.6 ± 19.7%; p = 0.034). All differences except mean oxygen saturation remained significant after controlling for baseline differences. Conclusion: Differences in both patient‐reported and objective sleep measures exist between patients with CRS and controls. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) is a multifactorial inflammatory airway disorder in which bacteria are implicated in the initiation and/or sustenance of disease in some patients. The sinuses are colonized by bacteria even in health, and the potential for sinus-specific niches harboring unique microbial consortia raises questions for clinical and research investigation. The objective was to determine the degree to which resident upper airways microbiota differ between individuals and anatomic sites, in order to determine the optimal site of microbial sampling for study in CRS. Methods Eight CRS patients undergoing primary surgery were sampled bilaterally at the anterior nares, middle meatus, nasopharynx, maxillary sinus, frontal sinus, and sphenoid sinus for investigation using broad-range bacterial 16S ribosomal RNA (rRNA) sequencing. Results Between-subject variability in bacterial microbiota was substantially greater than within-subject variability. The middle meatus was fairly representative of the underlying sinuses, although corynebacteria were detected at higher abundances in the middle meatus, relative to the maxillary ( p < 0.1), frontal ( p < 0.05), or sphenoid ( p < 0.1) sinuses. Conclusion Interpersonal variation of the upper airway microbiome greatly outweighs niche-specific differences. The middle meatus is a fair representation of the underlying sinuses and may be considered for use as a simple single site for sampling in longitudinal studies or in subjects who have not undergone sinus surgery. [ABSTRACT FROM AUTHOR]

Background: Small colony variants (SCVs) are a metabolically inactive form of bacteria that can be difficult to eradicate. To examine whether SCVs contribute to Staphylococcus aureus persistence in chronic rhinosinusitis (CRS), we compared the prevalence of S. aureus SCVs in CRS patients and healthy controls. Methods: Endoscopically guided middle meatus samples were collected from 23 CRS patients and 12 controls. Samples were cultured and screened for the presence of phenotypically small colonies. Candidate SCV isolates were classified by 16S rRNA gene sequencing. To further characterize the capacity of S. aureus isolates to form SCVs when stressed, colonies underwent a gentamicin exposure assay. Results: Among CRS patient samples, 15 were culture positive for S. aureus (65.2%), and of those, two grew putative SCVs on selective media (8.7%). However, neither was genetically confirmed to be S. aureus upon sequencing. In healthy controls, eight specimens were culture positive for S. aureus (66.7%), and of these, two grew putative S. aureus SCVs on selective media (16.7%); but again, neither was confirmed to be S. aureus by 16S analysis. None of the four patients colonized with SCVs had evidence of sinonasal disease at a mean follow-up of eight months. S. aureus isolates from CRS patients and controls were equally likely to form SCVs with gentamicin exposure. Conclusion: S. aureus SCVs were not associated with CRS in the current study. Their role in refractory CRS remains theoretical, and further research is warranted to determine whether S. aureus SCVs may reside in the intracellular compartment. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Currently, little is known about possible underlying distinguishing factors between these inflammatory differences. Our aim was to interrogate differences in CRSwNP disease between White/non-Asian patients and Japanese patients by using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs). We performed whole transcriptome RNA sequencing with endotype stratification of NPs from 8 White patients (residing in the United States) and 9 Japanese patients (residing in Japan). Reproducibility was confirmed by quantitative PCR in an independent validation set of 46 White and 31 Japanese patients. Single-cell RNA sequencing (scRNAseq) was used to stratify key cell types for contributory transcriptional signatures. Unsupervised clustering analysis identified 2 major endotypes that were present within both cohorts of patients with NPs and had previously been reported at the cytokine level: (1) type 2 endotype and (2) non–type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct subgroups with NPs (P =.03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells. NPs from both racial groups harbor the same 2 major endotypes, which we have determined to be present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed. [ABSTRACT FROM AUTHOR]

Background Bronchiectasis is an uncommon disease of the lower airways characterized by bronchial wall destruction and permanent bronchiolar dilation. Several etiologic categories exist, and patients with bronchiectasis often complain of symptoms suggestive of chronic rhinosinusitis (CRS). The present study investigates the association between bronchiectasis and CRS using radiologic and bacteriologic data. Methods Retrospective chart review from a tertiary care respiratory hospital was performed. Sinus computed tomography (CT) scans were examined for extent of disease and relationship to pulmonary disease severity. Statistical analysis was performed with Student t test and linear regression. Upper and lower airway cultures from patients with both bronchiectasis and CRS were compared using the chance adjusted agreement. Results Patients with bronchiectasis were found to have a significantly higher Lund-Mackay score when compared to patients with allergic rhinitis ( p = 0.047). Lund-Mackay CT score did not correlate with forced expiratory volume in 1 second (FEV1) and FEV1:forced vital capacity (FVC), or presence of Pseudomonas aeruginosa. Correlation of upper and lower airway bacterial cultures in patients with both bronchiectasis and CRS was noted (kappa = 0.294, p = 0.004), particularly when P. aeruginosa was present (kappa = 0.49, p < 0.0001). Conclusion The current study suggests that the upper and lower airways may be linked in CRS and bronchiectasis from both an objective radiologic standpoint and a bacteriologic perspective. This finding carries implications for disease pathogenesis, clinical care, and future research. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) is an idiosyncratic and multifactorial disease process. Bacteria play a role in some patients, by infection or stimulation of inflammation. Staphylococcus aureus (SA) appears to be implicated in a number of infectious and inflammatory mechanisms, and may be particularly relevant in CRS patients with nasal polyps and asthma. Methods Middle meatus swabs from control and CRS patients collected during endoscopic sinus surgery were analyzed by quantitative polymerase chain reaction (QPCR). Total bacterial count, SA prevalence, and SA abundance were examined with respect to patient demographics and disease characteristics. Results Total bacteria, as measured by QPCR, was not statistically different between controls, CRS without nasal polyps (CRSsNP), CRS with nasal polyps (CRSwNP), or CRS with asthma groups ( p < 0.09). Total bacterial counts did not correlate with disease severity as measured by Lund-Mackay computed tomography (CT) scores ( p = 0.65). The prevalence of SA was similar between groups (15-25%); however, the abundance increased in CRS patients with allergic rhinitis, nasal polyps, and asthma. Conclusion The paranasal sinuses are not sterile. SA is implicated in a subset of CRS patients with nasal polyps and/or asthma. Further study is required to predict this subset of patients, and to define the mechanisms of SA pathogenesis. [ABSTRACT FROM AUTHOR]

Background Nasal polyps in patients with cystic fibrosis (CF) are believed to be phenotypically different than polyps affecting non-CF patients. The aim of this study was to investigate differences in cell cycle regulatory mechanisms between these 2 groups. In this prospective study at a tertiary care academic medical center, multiple techniques were used to confirm the upregulation of antiapoptotic Bcl-2 family proteins in CF polyps. Methods Nasal polyps were prospectively obtained from CF and non-CF patients. The Sigma Panorama Protein Microarray for Cell Signaling was used to identify differences in protein expression between the 2 polyp groups. Western blot analysis confirmed altered expression of a subset of these proteins. Immunohistochemical staining was performed on archived tissue to further investigate B-cell lymphoma 2 protein (Bcl-2) expression. Following review by a pathologist, slides were digitized using an Aperio™ ScanScope XT system and staining intensity was quantified with the Positive Pixel Count algorithm. The mean staining intensity for each polyp group was compared. Results The protein microarray suggested a greater than 2-fold upregulation of Bcl-xl in CF polyps relative to non-CF polyps. Western blot analysis confirmed the upregulation in CF polyps of Bcl-2, a more commonly studied protein analog of Bcl-xl. The CF polyp group was noted to have a higher quantitative intensity of immunohistochemical staining for Bcl-2 compared to the non-CF group ( p < 0.05). Conclusion Through multiple modalities of protein investigation, we have demonstrated an upregulation of Bcl-2 family proteins in CF polyps relative to polyps from non-CF patients. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to identify the incidence of atypical Mycobacterium identified by routine sinus cultures and review the recent literature on management. Methods: A retrospective case series was performed in a tertiary academic hospital. A retrospective case series of all patients treated with atypical Mycobacterium rhinosinusitis from 2005 to 2010 was performed. Cases were identified from a prospective database of 676 endoscopically guided sinus cultures. Results: Eight patients with atypical Mycobacterium sinusitis were identified. There were five women and three men. Median age was 63 years (range, 55-71 years). All patients had prior endoscopic sinus surgery a median of 14 months (range, 0.8-162 months) before a positive culture result. Species identified included Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium abscessus, and Mycobacterium avium complex. Chief presenting symptoms were postnasal discharge (88%), followed by decreased smell and taste (63%), and facial pain/pressure (38%). Patients were treated based on sensitivity results with long-term oral antibiotics for at least 2 months based on improvements on endoscopy. Median follow-up for patients in this study after treatment was 1.3 years (range, 0.6-4.6 years). Conclusion: In this study, atypical mycobacteria were identified in <1% of sinus cultures. Prolonged, culture-directed antibiotic therapy remains the mainstay of treatment when there is clinical evidence of infection. Previous endoscopic sinus surgery may represent a risk factor for colonization and subsequent infection. Further research is necessary to determine the optimal treatment duration and management to prevent disease relapse [ABSTRACT FROM AUTHOR]

Key Points AI‐based CT sinus analysis may have advantages over visual based systems, for example, Lund–Mackay score. Here, we show multi‐institutional validation of an AI algorithm using novel OMC classification. Significant, robust correlations are seen between algorithm outputs and clinical outcomes. AI‐based CT sinus analysis may have advantages over visual based systems, for example, Lund–Mackay score.Here, we show multi‐institutional validation of an AI algorithm using novel OMC classification.Significant, robust correlations are seen between algorithm outputs and clinical outcomes. [ABSTRACT FROM AUTHOR]

• Distinct lipidomic signatures in CRS offer new therapeutic targets for each subtype. • Pro-resolving mediators RvD2 and LXA 4 are elevated in CRSwNP compared to CRSsNP. • Sinonasal RVD1 and RvD2 are decreased in cigarette smokers compared with never-smokers. • Upper airway microbiota are associated with lipid mediators in underlying tissue. Current literature implicates arachidonic acid-derived leukotrienes and prostaglandins in the pathogenesis of chronic rhinosinusitis. However, other omega-3 and omega-6 derived lipid mediators, such as specialized pro-resolving mediators (SPMs), may also be important in chronic inflammatory disorders of the upper airway. We hypothesize that SPMs differ among CRS subtypes compared to controls and in relation to sinonasal microbiota. Ethmoid sinus tissue and middle meatal swabs were collected from a convenience sample of 66 subjects, including non-CRS controls, CRS with polyps (CRSwNP), and CRS without polyps (CRSsNP). Lipid mediator pathways were analyzed by liquid chromatography/tandem mass spectrometry. Bacterial taxa were profiled in parallel by 16S rRNA gene sequencing. Resolvin D2 was elevated in both CRSwNP (p = 0.00076) and CRSsNP (p = 0.030) compared with non-CRS controls. Lipoxin A 4 was significantly increased in CRSwNP compared with CRSsNP (p = 0.000033) and controls (p = 0.044). Cigarette smoking was associated with significantly lower concentrations of several 15-lipoxygenase metabolites including resolvin D1 (p = 0.0091) and resolvin D2 (p = 0.0097), compared with never-smokers. Several of the lipid compounds also correlated with components of the sinonasal mucosal microbiota, including bacterial pathogens such as Pseudomonas aeruginosa. These data suggest that dysfunctional lipid mediator pathways in CRS extend beyond the traditional descriptions of leukotrienes and prostaglandins and include SPMs. Furthermore, dysregulated SPM signaling may contribute to persistent inflammation and bacterial colonization in CRS. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether chronic rhinosinusitis (CRS) endotypes show a differential response to endoscopic sinus surgery (ESS). We explored patient mucous inflammatory cytokine expression and associations with patient‐reported and clinically measured post‐operative outcome measures. Methods: Patients with CRS were prospectively recruited between 2016 and 2021 into a national multicenter, observational study. Mucus was collected from the olfactory cleft preoperatively and evaluated for 26 biomarkers using cluster analysis. Patient‐reported outcome measures included the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and Questionnaire of Olfactory Dysfunction (QOD). Additional clinical measures of disease severity included threshold, discrimination, and identification (TDI) scores using "Sniffin' Sticks" testing and Lund–Kennedy endoscopic score (LKES). Results: A total of 115 patients were clustered into type 2 inflammatory, non–type 2 inflammatory, noninflammatory, and two indeterminate clusters based on individual protein levels. Overall, the type 2 inflammatory cluster was found to have the highest mean improvement in both SNOT‐22 (−28.3 [standard deviation, ±16.2]) and TDI (6.5 [standard deviation, ±7.9]) scores 6 months after ESS. However, on average, all endotype clusters demonstrated improvement in all outcome measures after ESS without statistically significant between‐group differences in SNOT‐22 (p = 0.738), QOD (p = 0.306), TDI (p = 0.358), or LKES (p = 0.514) measures. Conclusions: All CRS endotype clusters responded favorably to surgery and showed improvements in patient‐reported and objective outcome measures. Thus, ESS should be considered a more generalized CRS therapy, and benefits appear to not be limited to specific endotypes. [ABSTRACT FROM AUTHOR]

Background: Poor air quality increases the risk of developing chronic rhinosinusitis (CRS) and other airway diseases. However, there are limited data on air pollutants and CRS‐specific disease severity. We assessed the impact of air pollutants on sinonasal‐specific and general quality‐of‐life (QOL) measures in a multi‐institutional cohort of patients with CRS. Methods: Participants with CRS were prospectively enrolled in a cross‐sectional study and self‐selected continued appropriate medical therapy or endoscopic sinus surgery (ESS). The 22‐item SinoNasal Outcome Test (SNOT‐22) and Medical Outcomes Study Questionnaire Short‐Form 6‐D (SF‐6D) health utility value scores were recorded. Patient exposure to air pollutants was determined using residence zip codes. Unadjusted group differences were compared, and correlation coefficients were evaluated to identify the magnitude of bivariate association. Results: A total of 486 patients were enrolled and followed for a mean of 6.9 (standard deviation [SD] ± 2.3) months. Pollutant exposure did not significantly correlate with baseline SNOT‐22 or SF‐6D scores. Revision ESS was associated with higher median fine particulate matter (PM2.5; Δ = 0.12, [95% confidence interval {CI}: 0.003, 0.234]; p = 0.006) compared with primary surgery. PM2.5, PM10, and nitrogen dioxide concentrations (μg/m3) did not correlate with change in total SNOT‐22 or SF‐6D scores after treatment. Nevertheless, sulfur dioxide (SNOT‐22: ρ = –0.121 [95% CI: –0.210, –0.030]; p = 0.007; SF‐6D: ρ = 0.095 [95% CI: 0.002, 0.186]; p = 0.04) and carbon monoxide (SNOT‐22: ρ = ‐0.141 [95% CI: –0.230, 0.050]; p = 0.002) exposure did correlate with these outcome measures. Conclusion: Air pollutants may contribute, at least in part, to disease severity in CRS; future investigation is needed to further elucidate the nature of this relationship. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Socioeconomic status (SES) is linked to health outcomes but has not been well studied in patients with chronic rhinosinusitis (CRS). The area deprivation index (ADI) is a comprehensive measure of geographic SES that ranks neighborhood disadvantage. This investigation used ADI to understand the impact of neighborhood disadvantage on CRS treatment outcomes.A total of 642 study participants with CRS were prospectively enrolled and self‐selected endoscopic sinus surgery (ESS) or continued appropriate medical therapy as treatment. The 22‐item SinoNasal Outcome Test (SNOT‐22) and Medical Outcomes Study Questionnaire Short‐Form 6‐D (SF‐6D) health utility value scores were recorded pre‐ and post‐treatment. Using residence zip codes, national ADI scores were retrospectively assigned to patients. Spearman's correlation coefficients (Rs) and Cramer's V effect size (φc) with 95% confidence interval (CI) were calculated.A history of ESS was associated with significantly worse ADI scores compared to no history of ESS (φc = 0.18; 95% CI: 0.10, 0.25; p < 0.001). Baseline total SNOT‐22 (Rs = 0.14; 95% CI: 0.06, 0.22; p < 0.001) and SF‐6D values (Rs = −0.20; 95% CI: −0.27, −0.12; p < 0.001) were significantly negatively correlated with national ADI rank. No significant correlations between ADI and within‐subject improvement, or achievement of >1 minimal clinically important difference, in SNOT‐22 or SF‐6D scores after treatment were found.Geographic socioeconomic deprivation was associated with worse baseline disease severity and history of prior surgical intervention. However, ADI did not correlate with improvement in disease‐specific outcomes. The impact of socioeconomic deprivation on outcomes in CRS requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Poor sleep quality is common in chronic rhinosinusitis (CRS). Prior studies have demonstrated improvements in patient‐reported measures of sleep quality following endoscopic sinus surgery (ESS). The purpose of this study was to evaluate the effect of ESS on objective sleep parameters and identify any associations between specific objective measures and patient characteristics, comorbidities, and patient‐reported outcome measures (PROMs). Methods: Adults with CRS undergoing ESS were prospectively enrolled from 4 centers across North America. Any subject previously diagnosed with a known primary sleep disorder was excluded. Objective sleep indices were recorded using a portable sleep diagnostic device preoperatively and postoperatively. Patient‐reported outcome instruments were completed including the Pittsburgh Sleep Quality Index (PSQI) and the 22‐item Sino‐Nasal Outcome Test (SNOT‐22). Results: Thirty‐six patients (mean age 47 years, 56% male) completed baseline and postoperative sleep studies with mean ± standard deviation (SD) follow‐up 9.6 ± 7.7 months. Mean PSQI and SNOT‐22 before and after ESS was 10.2 ± 3.9 vs 7.8 ± 4.4 (p = 0.001); and 54.6 ± 14.6 vs 28.5 ± 15.3 (p < 0.001), respectively. Total sleep time, sleep latency, and awakenings after sleep onset did not change following ESS (all p > 0.5) despite improvements in PSQI and SNOT‐22. Changes in PSQI did not correlate with comorbidities or objective sleep indices (all p > 0.1). Conclusion: In this multicenter prospective cohort, objective sleep indices were not improved following ESS for CRS despite significant improvements in patient‐reported sleep quality and CRS‐specific QOL. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) is a prevalent multifactorial disease process in which bacteria are believed to play a role in the propagation of inflammation. Multiple subtypes of CRS have been described based on clinical and pathologic features, but a detailed examination of the sinus microbiota in patients with CRS and its clinical subtypes has yet to be performed. Objective We sought to examine the resident microbiota of CRS subtypes and determine whether bacterial diversity is a predictor of disease outcomes. Methods Sinus swabs from patients with CRS and healthy subjects collected during endoscopic sinus surgery were analyzed by means of molecular phylogenetic analysis of 16S rDNA pyrosequences. Results Fifty-six patients with CRS and 26 control subjects were studied. Biodiversity was similar between the CRS and control groups. Among the CRS subtypes examined, only 2 conditions (presence of purulence and comorbid condition of asthma) were associated with significant alterations in microbial community composition. In 27 patients with CRS who were followed postoperatively, those with better outcomes had more diverse bacterial communities present at the time of surgery, along with higher relative abundances of Actinobacteria. Conclusion Analysis of microbiota in a large cohort reveals that particular CRS phenotypes (asthma and purulence) are characterized by distinct compositions of resident bacterial communities. We found that bacterial diversity and composition are predictors of surgical outcome, promoting the concept of community ecology in patients with CRS. [ABSTRACT FROM AUTHOR]

Background Nasal polyps (NPs) are hallmark inflammatory lesions of sinusitis. Despite the spectrum of NP conditions, cellular differences between NPs from patients with chronic rhinosinusitis with NPs (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) are poorly understood. NPs are associated with abundant eosinophils; the contributions of neutrophil and basophil granulocytes are less defined. We therefore sought to assess granulocyte subpopulations, and differential effects following prednisone pretreatment, within NPs of CRSwNP and AERD patients. Methods NPs, adjacent ethmoid sinus tissue, and peripheral blood mononuclear cells (PBMCs) were obtained from patients undergoing endoscopic sinus surgery. Samples from 5 cohorts: CRSwNP ± prednisone (n = 6 each), AERD ± prednisone (n = 6 each), and controls (n = 9), were analyzed by high-dimensional flow cytometry to gate granulocyte populations. Specimens were also assessed using immunohistochemistry (IHC) staining. Results Systemic prednisone administration was associated with a lower frequency of eosinophils ( p < 0.0001, n = 6) in NPs in both CRSwNP and AERD patients, whereas a decrease in neutrophils ( p = 0.0070, n = 6) in NPs was only observed in CRSwNP patients after prednisone treatment. In contrast, steroids do not alter basophil proportions ( p = 0.48, n = 6) within NPs from either group. No significant shift in granulocyte subsets after steroid treatment was identified in the adjacent ethmoid mucosa or PBMCs from the same patients. Immunohistochemistry (IHC) staining supported these findings. Conclusion Granulocyte subpopulations are focally affected within NPs by systemic steroid exposure, without notable granulocyte alterations in the surrounding regional tissues. These data provide direct insights into the cellular effects of routine prednisone exposure in CRS patients, and highlight a unique microenvironment present within NP lesions. [ABSTRACT FROM AUTHOR]

Background: The impact of multiple coexisting medical comorbidities on treatment outcomes in chronic rhinosinusitis (CRS) is unknown. In this study we sought to evaluate the effect of comorbidities on sinonasal quality of life (QOL) and general health utility values by utilizing the Functional Comorbidity Index (FCI) in CRS patients. Methods: Patients with CRS were prospectively enrolled in a cross‐sectional study of medical and surgical therapies. The 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and Medical Outcomes Study Short‐Form 6D (SF‐6D) scores were recorded at enrollment and 6‐month follow‐up; Lund‐Kennedy endoscopy and Lund‐Mackay computed tomography scores were recorded at enrollment. The FCI was calculated using the electronic medical record. The impact of cumulative comorbidity burden on baseline and posttreatment outcomes was assessed using univariate and bivariate correlations. Results: A total of 428 participants with CRS were included. The average (mean standard ± deviation) FCI score was 3.03 ± 2.28 (range, 0‐12). Significant linear correlations were identified between increasing FCI score and baseline SNOT‐22 and SF‐6D scores (R = 0.166, p = 0.001 and R = −0.245, p < 0.001, respectively). There was no correlation between FCI and change in SNOT‐22 or SF‐6D scores after CRS treatment (R = 0.066, p = 0.17 and R = −0.087, p = 0.074, respectively). Achievement of a minimally clinically important difference was also independent of FCI. Conclusion: Although cumulative comorbidity burden, as measured by FCI, is associated with worse baseline SNOT‐22 and SF‐6D scores, it does not appear to limit posttreatment improvement in either outcome measure. On average, patients with high comorbidity burden report substantial improvement in both QOL and health utility after CRS treatment, similar to those with fewer comorbidities. [ABSTRACT FROM AUTHOR]

Background: The Sinus Control Test (SCT) is a 4‐question, patient‐reported questionnaire that assesses disease control in chronic rhinosinusitis (CRS). This prospective, multicenter study examines SCT outcomes following endoscopic sinus surgery (ESS), further validating its use as a control instrument for CRS. Methods: Adults with CRS undergoing ESS were prospectively enrolled from 5 centers across North America. The SCT was administered at baseline and once 6 months after surgery. Quality of life and disease burden were evaluated using the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) and Lund‐Kennedy endoscopy scores. Linear regression was used to determine whether specific demographic, comorbidity, or disease severity measures were independently associated with changes in SCT scores postoperatively. Results: A total of 218 patients, 111 females (50.9%) and 107 males (49.1%), were enrolled, with mean ± standard deviation age of 50.1 ± 15.6 years. Mean SCT score improved from 8.9 ± 3.5 to 4.3 ± 3.7 postoperatively (p < 0.001). Preoperatively, 21.6% were uncontrolled, 71.5% partially controlled, and 6.9% controlled. Postoperatively, 6.0% were uncontrolled, 42.6% partially controlled, and 51.4% controlled (p < 0.001). Change in SCT score correlated independently with change in SNOT‐22 (r = 0.500, p < 0.001) and endoscopy scores (r = 0.310, p < 0.001). Endoscopy scores did not correlate with control status among patients with CRS without nasal polyposis (CRSsNP) nor between uncontrolled and partially controlled patients. Demographics and comorbidities were not associated with changes in SCT. Conclusion: Improvement in disease control following ESS as measured by the SCT correlated with improvements in SNOT‐22 and endoscopy scores. The SCT is an easily administered instrument that provides information complementary to existing patient‐reported and objective measures of disease severity. [ABSTRACT FROM AUTHOR]

Background: Computed tomography (CT) plays a key role in evaluation of paranasal sinus inflammation, but improved, and standardized, objective assessment is needed. Computerized volumetric analysis has benefits over visual scoring, but typically relies on manual image segmentation, which is difficult and time‐consuming, limiting practical applicability. We hypothesized that a convolutional neural network (CNN) algorithm could perform automatic, volumetric segmentation of the paranasal sinuses on CT, enabling efficient, objective measurement of sinus opacification. In this study we performed initial clinical testing of a CNN for fully automatic quantitation of paranasal sinus opacification in the diagnostic workup of patients with chronic upper and lower airway disease. Methods: Sinus CT scans were collected on 690 patients who underwent imaging as part of multidisciplinary clinical workup at a tertiary care respiratory hospital between April 2016 and November 2017. A CNN was trained to perform automatic segmentation using a subset of CTs (n = 180) that were segmented manually. A nonoverlapping set (n = 510) was used for testing. CNN opacification scores were compared with Lund‐MacKay (LM) visual scores, pulmonary function test results, and other clinical variables using Spearman correlation and linear regression. Results: CNN scores were correlated with LM scores (rho = 0.82, p < 0.001) and with forced expiratory volume in 1 second (FEV1) percent predicted (rho = −0.21, p < 0.001), FEV1/forced vital capacity ratio (rho = −0.27, p < 0.001), immunoglobulin E (rho = 0.20, p < 0.001), eosinophil count (rho = 0.28, p < 0.001), and exhaled nitric oxide (rho = 0.40, p < 0.001). Conclusion: Segmentation of the paranasal sinuses on CT can be automated using a CNN, providing truly objective, volumetric quantitation of sinonasal inflammation. [ABSTRACT FROM AUTHOR]

Keywords: adult onset CF; CF sinusitis; CFTR genotyping; CFTR-related disorder; chronic rhinosinusitis EN adult onset CF CF sinusitis CFTR genotyping CFTR-related disorder chronic rhinosinusitis 1135 1137 3 06/30/21 20210701 NES 210701 HISTORY AND CLINICAL FEATURES A 66-year-old female with an 8-year history of worsening chronic rhinosinusitis (CRS) and three prior sinus surgeries presented to the rhinology clinic in 2017 with persistent purulent drainage, sinus pressure, congestion, and olfactory dysfunction. Adult onset CF, CF sinusitis, CFTR genotyping, CFTR-related disorder, chronic rhinosinusitis Highlights CFTR dysfunction in the upper airway Adult-onset CF sinusitis CFTR-related disorder clinical improvement with CF therapy DISCUSSION Diagnosis and clinical course A diagnosis of CFTR-related disorder was made with the patient's sinopulmonary manifestations, intermediate sweat chloride levels, and CFTR testing. [Extracted from the article]

Severe forms of chronic rhinosinusitis (CRS), a common upper airway inflammatory disorder, are associated with nasal polyps (NPs). NP disease is ameliorated by glucocorticoid (GC) treatment, whose cellular effects are poorly understood. We therefore assessed the influence of GC therapy on NPs in CRS patients, focusing on regulatory T (T reg ) cells. T reg cell populations were analyzed by flow cytometry in NPs and control tissues from GC-treated CRS patients and controls. After GC exposure, selective expansion of T reg cells was seen within NPs, and not blood or adjacent ethmoid tissues. To confirm direct GC effects, NPs from the same patients were biopsied prior to, and following, 1 week of oral GC exposure. Direct expansion of Tregs into the same NP bed was detected in 4/4 CRS patients following GC exposure. T reg cell spikes into NPs were secondary to cellular recruitment given limited Ki67 expression within these regulatory cells. Chemokine gene expression profiling identified several chemokines, notably CCL4, induced within NPs upon GC treatment. Neutralization of chemokine receptor/ligand interactions using CCR4 small molecule antagonists reduced T reg migration towards GC-treated NPs in an ex vivo migration assay. Our findings suggest that the common use of GCs in the treatment of NP disease leads to recruitment of T reg cells from peripheral sites into NP tissues, which may be critical to the anti-inflammatory effect of GCs. Mechanistically T reg expansion appears to be conferred, in part, by chemokine receptor/ligand interactions induced following corticosteroid therapy. [ABSTRACT FROM AUTHOR]

Background Saline nasal irrigation is effective in the treatment of sinonasal disorders, including chronic rhinosinusitis (CRS). Despite bacterial contamination in rinse bottles and reports of infections from contaminated irrigation water, tap water is still used by ∼50% of irrigation users, raising a potential public health concern. This study aimed to determine whether bacteria from the water supply used in sinus irrigations colonizes the paranasal sinuses. Methods Samples were taken from the: (1) water used for irrigation, (2) faucet or container the water originated from, (3) rinse bottle, and (4) postoperative ethmoid cavity from 13 subjects with CRS. Microbiota were characterized using quantitative polymerase chain reaction (qPCR) and 16S ribosomal RNA (rRNA) gene sequencing. The Morisita-Horn beta-diversity index (M-H) was used to assess similarity in microbiota between samples, and genomic analysis was performed to assess clonality of cultured bacteria. Results Of 13 subjects, 6 used distilled water, 6 used tap water, and 1 used well water in this institutional review board (IRB)-approved observational study. Well-water had markedly more bacteria than tap or distilled water. There was a trend toward tap having more bacteria than distilled water. The sinus samples were notably dissimilar to the bottle, faucet, and irrigant (M-H 0.15, 0.09, and 0.18, respectively). There was no difference in postoperative microbiotas between distilled and tap water users. Conclusion The current study suggests that irrigation plays little role in establishing the sinus microbiome. Although rinsing with tap water may never be formally recommended, these data are useful to counsel patients who prefer to do so in non-endemic areas if the municipal water supply is appropriately treated. [ABSTRACT FROM AUTHOR]

Background Endoscopic sinus surgery (ESS) enjoys high success rates, but repopulation with pathogenic bacteria is 1 of the hallmarks of poorer outcomes. There are many hypothesized sources of repopulating bacteria; however, this process remains largely unexplored. This study examined changes in the sinus microbiome after ESS and medical therapies to identify potential sources for postsurgical microbial repopulation. Methods Samples from the anterior nares, ethmoid sinus, and nasopharynx were taken at the time of surgery from 13 subjects undergoing ESS for chronic rhinosinusitis (CRS). Patients were treated postoperatively with 2 weeks of oral antibiotics and saline rinses. The ethmoid sinus was sampled at 2 and 6 weeks postoperatively; microbiota were characterized using quantitative polymerase chain reaction (qPCR) and 16S ribosomal RNA (rRNA) gene sequencing. The Morisita-Horn beta-diversity index (M-H) was used to compare similarity between samples. Results The bacterial burden of the ethmoid was higher 2 weeks postoperatively than 6 weeks postoperatively ( p = 0.01). The 6-week samples most closely represented the anterior nares and ethmoid at surgery (M-H = 0.58 and 0.59, respectively), and were least similar to the nasopharynx (M-H = 0.28). Principal coordinates analysis (PCoA) plots illustrate that the ethmoid microbiota temporarily shifted after surgery and antibiotics but returned toward baseline in many subjects. Conclusion Bacterial communities colonizing the ethmoid 6 weeks postoperatively were most similar to anterior nasal cavity and pretreatment sinus microbial profiles, indicating a high degree of resilience in the sinonasal microbiome of most subjects. Interestingly, surgery and postoperative antibiotic therapy does not appear to reduce bacterial burden, but rather, shifts the microbial consortia. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) is an inflammatory disorder of the paranasal sinuses in which bacteria are implicated. Culture-based assays are commonly used in clinical and research practice; however, culture conditions may not accurately detect the full range of microorganisms present in a sample. The objective of this study was to determine the accuracy of clinical culture of CRS specimens compared with DNA-based molecular techniques. Methods Ethmoid samples from 54 CRS patients collected during endoscopic sinus surgery were analyzed by both clinical culture and 16S ribosomal RNA (rRNA) gene sequencing. The association between 16S relative abundance and detection by culture was determined using logistic regression. Results Each subject had an average of 3 isolates identified by bacterial culture and 21.5 ± 12.5 species identified by 16S sequencing. On average, 1.6 dominant taxa (>10% abundance) per subject were identified using molecular techniques, but only 47.7% of these taxa were identified by culture. Low abundance taxa (abundance <1%) were detected in only 4.5% of cultures. The odds that any organism would be detected by culture were 2.3 times higher with each 10% increase in relative abundance ( p < 0.01). Conversely, only 29.5% of isolates identified by culture represented the dominant species, whereas 40% accounted for species with 1% to 10% abundance. Interestingly, 12% of isolates detected by culture were not identified by 16S pyrosequencing. Conclusion Standard clinical culture is a poor representation of resident microbiota. The incorporation of modern culture-independent techniques into clinical and research practices provides additional information that may be relevant for CRS. [ABSTRACT FROM AUTHOR]