Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology.

BACKGROUND: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes. OBJECTIVE: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs). METHODS: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps. RESULTS: We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo. CONCLUSION: Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.

Vía aérea unificada: asociación entre rinosinusitis crónica y asma bronquial / Unified airway: association between chronic rhinosinusitis and bronchial asthma

Bajo la teoría de vía aérea unificada, se ha observado que el asma y la rinosinusitis crónica (RSC) tienen una estrecha relación, con efectos importantes de una enfermedad sobre el control de la otra. El objetivo de esta revisión bibliográfica es clarificar cómo ambas enfermedades se relacionan desde su origen, epidemiología, fisiopatología y tratamiento. Sabemos que la presencia de RSC se asocia con peores resultados del asma, mayor frecuencia de exacerbaciones, hospitalizaciones y mayor uso de corticoides sistémicos. Varios mecanismos parecen tener un rol en la disfunción de la vía aérea inferior en pacientes con RSC, dentro de los cuales se plantea que la respuesta inflamatoria en común de tipo Th2 juega un papel principal. Existe amplia literatura respecto al efecto que tiene el tratamiento de la RSC en el control del asma, en esta revisión se expondrá la evidencia disponible del tratamiento médico con corticoides nasales, montelukast y macrólidos, así como también del tratamiento quirúrgico de la RSC y el uso de biológicos.

Under the unified airway theory, asthma and chronic rhinosinusitis (CRS) have a close relationship, with significant effects of one disease on the control of the other. This bibliographic review aims to clarify how both diseases relate to each other from their origin, epidemiology, pathophysiology, and treatment. CRS is associated with worse asthma outcomes, higher frequency of exacerbations, hospitalizations, and increased use of systemic corticosteroids. Several mechanisms play a role in lower airway dysfunction in patients with CRS, among which the common Th2-type inflammatory response plays a substantial role. There is extensive literature regarding the effect of the treatment of CRS in the control of asthma. We present the available evidence regarding the effect of medical treatment with nasal corticosteroids, montelukast, and macrolides, as well as the surgical treatment and use of biologics.

Dietary Fibre Intake in Relation to Asthma, Rhinitis and Lung Function Impairment-A Systematic Review of Observational Studies.

A high intake of dietary fibre has been associated with a reduced risk of several chronic diseases. This study aimed to review the current evidence on dietary fibre in relation to asthma, rhinitis and lung function impairment. Electronic databases were searched in June 2021 for studies on the association between dietary fibre and asthma, rhinitis, chronic obstructive pulmonary disease (COPD) and lung function. Observational studies with cross-sectional, case-control or prospective designs were included. Studies on animals, case studies and intervention studies were excluded. The quality of the evidence from individual studies was evaluated using the RoB-NObs tool. The World Cancer Research Fund criteria were used to grade the strength of the evidence. Twenty studies were included in this systematic review, of which ten were cohort studies, eight cross-sectional and two case-control studies. Fibre intake during pregnancy or childhood was examined in three studies, while seventeen studies examined the intake during adulthood. There was probable evidence for an inverse association between dietary fibre and COPD and suggestive evidence for a positive association with lung function. However, the evidence regarding asthma and rhinitis was limited and inconsistent. Further research is needed on dietary fibre intake and asthma, rhinitis and lung function among adults and children.

A 70-Year-Old Man With Cough and Recurrent Respiratory Infections.

CASE PRESENTATION: A 70-year-old man was referred for evaluation of recurrent respiratory infections requiring antibiotics and chronic cough over 3 years. Two months prior to presentation, he started to develop blood-tinged sputum but not frank hemoptysis. He otherwise denied any fever, chills, night sweats, or weight loss. He had dyspnea during the respiratory infections but not otherwise. His medical history was significant for chronic rhinitis without sinusitis and a low serum IgM level. He was a never smoker and a farmer but otherwise had no significant or specific exposures or travel history. His family history was significant for alpha-1 antitrypsin deficiency in his mother.

The Effect of Aspirin on Moderate to Severe Asthmatic Patients with Aspirin Hypersensitivity, Chronic Rhinosinusitis, and Nasal Polyposis.

Asthmatic patients may have aspirin-exacerbated respiratory disease and experience acute dyspnea and nasal symptoms within 3 hours after the ingestion of aspirin. This study aimed to evaluate the effect and outcome of daily low-dose aspirin in the treatment of moderate to severe asthma in patients with concomitant aspirin hypersensitivity and chronic rhinosinusitis with nasal polyposis (CRSwNP). This clinical trial was conducted from February 2014 to February 2015 on 46 adult patients with moderate to severe asthma accompanied by CRSwNP. Patients with a positive aspirin challenge were blindly randomized in three groups receiving placebo/day (A); aspirin 100 mg/day (B); and aspirin 325mg/day (C), respectively. Clinical findings, FEV1 and ACT scores were recorded and compared before, during, and after treatment for 6 months. Of 46 participants at baseline, 30 patients completed this 6-month trial study. The level of asthma control was significant; based on Asthma Control Test (ACT) when comparing the results in groups A and C and also groups B and C, but it was not significant when comparing ACT scores between groups A and B. FEV1 before and after treatment was significant when comparing groups A and B, groups A and C, and groups B and C. To conclude, aspirin desensitization with a daily dose of 325 mg aspirin resulted in the improvement of long-term control of asthma. A daily aspirin dose of 100 mg was not associated with such an increase in ACT score.

Association of Sinonasal Inflammation With Functional Brain Connectivity.

Importance: In recent years, there have been several meaningful advances in the understanding of the cognitive effects of chronic rhinosinusitis. However, an investigation exploring the potential link between the underlying inflammatory disease and higher-order neural processing has not yet been performed. Objective: To describe the association of sinonasal inflammation with functional brain connectivity (Fc), which may underlie chronic rhinosinusitis-related cognitive changes. Design, Setting, and Participants: This is a case-control study using the Human Connectome Project (Washington University-University of Minnesota Consortium of the Human Connectome Project 1200 release), an open-access and publicly available data set that includes demographic, imaging, and behavioral data for 1206 healthy adults aged 22 to 35 years. Twenty-two participants demonstrated sinonasal inflammation (Lund-Mackay score [LMS] ≥ 10) and were compared with age-matched and sex-matched healthy controls (LMS = 0). These participants were further stratified into moderate (LMS < 14, n = 13) and severe (LMS ≥ 14, n = 9) inflammation groups. Participants were screened and excluded if they had a history of psychiatric disorder and/or neurological or genetic diseases. Participants with diabetes or cardiovascular disease were also excluded, as these conditions may affect neuroimaging quality. The data were accessed between October 2019 and August 2020. Data analysis was performed between May 2020 and August 2020. Main Outcomes and Measures: The primary outcome was the difference in resting state Fc within and between the default mode, frontoparietal, salience, and dorsal attention brain networks. Secondary outcomes included assessments of cognitive function using the National Institutes of Health Toolbox Cognition Battery. Results: A total of 22 patients with chronic rhinosinusitis and 22 healthy controls (2 [5%] were aged 22-25 years, 26 [59%] were aged 26-30 years, and 16 [36%] were aged 31-35 years; 30 [68%] were men) were included in the analysis. Participants with sinonasal inflammation showed decreased Fc within the frontoparietal network, in a region involving bilateral frontal medial cortices. This region demonstrated increased Fc to 2 nodes within the default-mode network and decreased Fc to 1 node within the salience network. The magnitude of these differences increased with inflammation severity (dose dependent). There were no significant associations seen on cognitive testing. Conclusions and Relevance: In this case-control study, participants with sinonasal inflammation showed decreased brain connectivity within a major functional hub with a central role in modulating cognition. This region also shows increased connectivity to areas that are activated during introspective and self-referential processing and decreased connectivity to areas involved in detection and response to stimuli. Future prospective studies are warranted to determine the applicability of these findings to a clinical chronic rhinosinusitis population.

A Systematic Review and Meta-Analysis of Taste Dysfunction in Chronic Rhinosinusitis.

OBJECTIVES: Patients with chronic rhinosinusitis (CRS) often describe alterations in sense of taste. These complaints have historically been attributed to olfactory dysfunction; however, there is evidence of direct, objective, gustatory disturbances in the setting of CRS that are not thoroughly characterized. This study sought to investigate and summarize gustatory dysfunction experienced by patients with CRS. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases were reviewed following PRISMA guidelines. English language, original studies investigating objective taste in adult patients with CRS were included. A meta-analysis with inverse variance, random-effects model was performed. RESULTS: Of 2750 studies screened, 11 articles with 471 unique patients were included. Patients with CRS exhibit worse gustatory function compared to healthy controls (standardized mean difference 0.94 [95% CI, 0.44-1.45]). Hypogeusia was identified in 32/95 (33.7%) patients from three studies that used methods with a validated definition of hypogeusia. Older age, male gender, and smoking history were associated with taste dysfunction, while objective gustatory and olfactory dysfunction were not correlated. Subjective taste and quality of life measures were also not associated with objective taste. The impact of sinus surgery on objective taste is unclear. CONCLUSION: Approximately 34% of patients with CRS experience hypogeusia. Neither olfactory function nor subjective taste were associated with objective gustatory function. Given the substantial prevalence of taste dysfunction patients with CRS, there is significant potential for growth in understanding of pathogenesis, impact on quality of life, and potential treatment strategies of taste impairment in the CRS patient population. LEVEL OF EVIDENCE: 1 Laryngoscope, 131:482-489, 2021.

Long-Term Clinical Follow-Up of Patients With Chronic Rhinosinusitis.

OBJECTIVE: This study comprised a long-term follow-up of a cohort of patients with chronic rhinosinusitis (CRS) regarding clinical features and symptomatology. METHODS: Data from 42 patients with CRS were available from a previous study. Forty of these patients were alive and were contacted for inclusion after approximately 10 years. Patients completed a questionnaire about disease and symptoms, and underwent a clinical examination. RESULTS: Thirty-four patients (85%) responded and could be included and evaluated. For the participants in this follow-up study median length of time between initial inclusion (C1) and follow-up (C2) was 11 years (range: 8-15). In some patients the CRS shifted phenotype over time, from CRS with nasal polyposis to CRS without nasal polyposis or vice versa. The median total visual analogue score for combined sinonasal symptoms for all patients was statistically significantly reduced at follow-up. For individual patients, scores for nasal congestion, nasal discharge, facial pressure, and hyposmia were also statistically significantly reduced. The most frequently reported symptom-relieving treatments were nasal steroids and saline rinsing of the nose. Self-reported general quality of life was statistically significantly improved at C2 compared to C1. CONCLUSION: At long-term follow-up, symptoms were generally reduced and patients reported an improved quality of life. Patients can be given hope for eventual symptom relief. CRS is a chronic condition that seems to harbor the ability to alter its phenotype after several years. Topical corticosteroids and saline rinsing of the nose should be emphasized, since patients consider these treatments to be of high value.

Can computational fluid dynamic models help us in the treatment of chronic rhinosinusitis.

PURPOSE OF REVIEW: The aim of this study was to review the recent literature (January 2017-July 2020) on computational fluid dynamics (CFD) studies relating to chronic rhinosinusitis (CRS), including airflow within the pre and postoperative sinonasal cavity, virtual surgery, topical drug and saline delivery (sprays, nebulizers and rinses) and olfaction. RECENT FINDINGS: Novel CFD-specific parameters (heat flux and wall shear stress) are highly correlated with patient perception of nasal patency. Increased ostial size markedly improves sinus ventilation and drug delivery. New virtual surgery tools allow surgeons to optimize interventions. Sinus deposition of nasal sprays is more effective with smaller, low-inertia particles, outside of the range produced by many commercially available products. Saline irrigation effectiveness is improved using greater volume, with liquid entering sinuses via 'flooding' of ostia rather than direct jet entry. SUMMARY: CFD has provided new insights into sinonasal airflow, air-conditioning function, the nasal cycle, novel measures of nasal patency and the impact of polyps and sinus surgery on olfaction. The deposition efficiency of topical medications on sinus mucosa can be markedly improved through parametric CFD experiments by optimising nasal spray particle size and velocity, nozzle angle and insertion location, while saline irrigation effectiveness can be optimized by modelling squeeze bottle volume and head position. More sophisticated CFD models (inhalation and exhalation, spray particle and saline irrigation) will increasingly provide translational benefits in the clinical management of CRS.

Trajectories of early-onset rhinitis in the Singapore GUSTO mother-offspring cohort.

BACKGROUND: The natural history of childhood rhinitis is not well described. OBJECTIVE: This study aimed to identify different rhinitis trajectories in early childhood and their predictors and allergic associations. METHODS: Rhinitis symptoms were ascertained prospectively from birth until 6 years using standardized questionnaires in 772 participants. Rhinitis was defined as one or more episodes of sneezing, runny and/or blocked nose >2 weeks duration. Latent trajectories were identified using group-based modelling, and their predictive risk factors and allergic associations were examined. RESULTS: Three rhinitis trajectory groups were identified: 7.6% (n = 59) were termed early transient rhinitis, 8.6% (n = 66) late transient rhinitis, and 6.6% (n = 51) persistent rhinitis. The remaining 77.2% (n = 596) were classified as non-rhinitis/reference group. Early transient rhinitis subjects were more likely of Indian ethnicity, had siblings, reported childcare attendance, early wheezing and eczema in the first 3 years of life. Late transient rhinitis was associated with antenatal exposure to smoking, higher maternal education levels, and wheezing at age 36-72 months. Persistent rhinitis was associated with male gender, paternal and maternal history of atopy, eczema, and house dust mite sensitization. CONCLUSIONS & CLINICAL RELEVANCE: Risk factors for early transient rhinitis involve a combination of genetic and early environmental exposures, whereas late transient rhinitis may relate to maternal factors and early respiratory infections independent of atopy. In contrast, persistent rhinitis is strongly associated with atopic risk and likely represents the typical trajectory associated with allergic disorders. Allergic rhinitis symptoms may commence as early as the first year of life and may inform development of early interventive strategies.

Exosomal miR-22-3p Derived from Chronic Rhinosinusitis with Nasal Polyps Regulates Vascular Permeability by Targeting VE-Cadherin.

BACKGROUND: The abnormal vascular permeability is associated with the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). Previously, our study demonstrated that the nasal lavage fluid- (NLF-) derived exosomes from CRSwNP can promote the vascular permeability of human umbilical vein endothelial cells (HUVECs). miR-22-3p, a specific differentiated miRNA, is reported to regulate microvessels in some diseases. This study is purposed to explore the impact of exosomal miR-22-3p derived from CRSwNP on vascular permeability and identify the underlying targets. METHODS: Exosomes were extracted from NLF of 26 CRSwNP patients and 10 control patients. Quantitative real-time PCR (qRT- PCR) was applied to evaluate the relative level of exosomal miR-22-3p. The impact of exosomal miR-22-3p on HUVECs was assessed by permeability assays in vitro. The potential molecular targets of miR-22-3p were investigated by applying such technologies as dual-luciferase reporter assay and western blot. RESULTS: miR-22-3p was upregulated in NLF-derived exosomes from CRSwNP. Exosomal miR-22-3p derived from CRSwNP enhanced the tubule permeability of HUVECs. Vascular endothelial- (VE-) cadherin (CDH5) was identified as a direct target of miR-22-3p. miR-22-3p regulated the vascular permeability by targeting VE-cadherin in HUVECs. CONCLUSIONS: Exosomal miR-22-3p derived from NLF of CRSwNP plays an important role in regulating vascular permeability by targeting VE-cadherin.

Effects of Wnt signaling on epithelial to mesenchymal transition in chronic rhinosinusitis with nasal polyp.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP). Wnt signaling is causative for EMT, whereas the mechanism in CRSwNP is not fully understood. OBJECTIVE: We sought to evaluate the role of Wnt signaling in EMT of CRSwNP using a murine nasal polyp (NP) model and human tissues. METHODS: Inflammatory markers and EMT-related molecules were evaluated in NP models using adenomatosis polyposis coli (Apc)Min/+ mice with activated Wnt signaling and NP models treated with Wnt signaling inhibitor, indocyanine green-001 (ICG-001). EMT markers and Wnt signaling-associated mediators were analysed using human sinonasal tissues from control subjects and CRSwNP patients. RESULTS: ApcMin/+ mice-induced NPs exhibited more frequent polypoid lesions and upregulation of Wnt-related molecules, including nuclear ß-catenin, WNT3A and cyclin D1. Markers of EMT were significantly overexpressed in the ApcMin/+ NP mice (p<0.001 for E-cadherin and α-smooth muscle actin), and interleukin (IL)-17A+ cells and neutrophilic infiltration were increased in ApcMin/+ NP mice (p<0.001). Inhibition of Wnt signaling via ICG-001 resulted in significantly decreased nasal polypoid lesions (p<0.001), EMT-related markers (p=0.019 for E-cadherin and p=0.002 for vimentin) and the mRNA levels of IL-4 (p<0.001) and IL-17A (p=0.004) compared with the positive control group. Finally, nuclear ß-catenin (p=0.042) was significantly increased compared with the control, and the expression levels of Wnt ligands and receptors were upregulated in human NP tissues (p=0.045 for WNT3A and p=0.042 for FZD2), suggesting increased Wnt signaling and EMT in CRSwNP. CONCLUSION: Wnt signaling may contribute to the pathogenesis of NPs through EMT. Therefore, inhibition of Wnt signaling may be a potential therapeutic strategy for patients with CRSwNP.

Extended nitric oxide analysis in patients with chronic rhinosinusitis with nasal polyps, with or without associated asthma.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease highly impacting patient's quality of life, and associated with lower airway inflammation often evolving into asthma. Exhaled nitric oxide (FENO) is a non-invasive tool to assess Type 2 airway inflammation and its extended analysis allows to differentiate between alveolar concentration (CalvNO) and bronchial output (JawNO). It is also possible to assess the sino-nasal production of nitric oxide (nNO). We studied extended nitric oxide production in patients with CRSwNP with or without associated asthma. Consecutive adult patients with CRSwNP, with or without asthma, and 15 healthy controls were enrolled. Exclusion criteria were: smoking, uncontrolled asthma, recent upper or lower airway infections and oral corticosteroid therapy in the 4 weeks preceding clinical evaluation. Patients' demographic and clinical data were collected; patients underwent pulmonary function tests and extended nitric oxide analysis including nasal nNO assessment. A total of 125 subjects were enrolled (15 healthy controls; 69 with CRSwNP and asthma, and 41 with CRSwNP only). FENO, JawNO and CalvNO values were higher, while nNO was lower, in all patients with CRSwNP compared to healthy controls; no difference was found in CalvNO between patients with concomitant asthma and non-asthmatic subjects; in asthmatic patients, FENO and JawNO were significantly higher, while nNO values was lower, compared to patients with CRSwNP only. These results suggest that CRSwNP could be the first manifestation of a more complex systemic inflammatory pathology driven by Type 2 inflammation. An 'inflammatory gradient' hypothesis could describe a pattern of inflammation in CRSwNP patients that starts distally in the alveoli. Finally, our study indirectly reinforces the concept that novel biological drugs could become valid therapeutic options for nasal polyposis.

Influence of nasal mucosa irritants on the occurrence of chronic rhinosinusitis without /and with polyps.

<b>Introduction: </b>The aim of the study was to assess the effect of nasal mucosa irritants on the occurrence of chronic rhinosinusitis without/and with nasal polyps. <br><b>Material and methods:</b> The study involved 100 adult participants, including 39 women and 61 men, aged 21-68, diagnosed and treated at the Department of Otolaryngology, ENT Oncology, Audiology and Phoniatrics at the University Clinical Hospital WAM in Lódz. Based on the otorhinolaryngological and imaging (CT) tests they were divided into two groups: I - 50 patients, including 23 women and 27 men, aged 21-64 - with chronic rhinosinusitis without nasal polyps, II - 50 patients, including 16 women and 34 men, aged 22-68 - with chronic rhinosinusitis with nasal polyps. The control group consisted of 50 people (group III), including 25 women and 25 men, aged 18-30, students of the Faculty of Military Medicine at the Medical University of Lodz. All respondents completed a prepared questionnaire consisting of 17 questions addressed in the form of an anonymous interview among patients treated in the Department of Otolaryngology, ENT Oncology, Audiology and Phoniatrics. <br><b>Results:</b> The conducted surveys indicate the impact of the following factors in pathogenesis of chronic rhinosinusitis without/ with nasal polyps: exogenous factors (viruses, bacteria, fungi, drugs, injuries, toxic substances, environmental pollution), general endogenous factors (allergy, hypersensitivity to acetylsalicylic acid and its derivatives, hormonal disorders, supraesophageal reflux disease, granulation disease, immunity disorders, local endogenous factors. <br><b>Conclusions:</b> In the examined material, patients with chronic rhinosinusitis without/and nasal polyps in most cases are in the age range 51-60 years and over 60 years, they most often live in large cities over 250 thousand inhabitants, suffer from allergic rhinorhinitis in 38.0% in group I and 36.0% in group II, rapid temperature changes and dry air have a negative impact on comfort of breathing. The conducted surveys confirm that the cause of chronic rhinosinusitis with polyps is multifactorial, but a significant factor affecting typical tissue remodeling in this disease is long-term breathing of polluted atmospheric air.

Impaired small airway function in non-asthmatic chronic rhinosinusitis with nasal polyps.

BACKGROUND: There is clinical evidence for impaired lung function in chronic rhinosinusitis with nasal polyps (CRSwNP) patients, which may be due to a high incidence of asthma comorbidity. The lung function characteristics of non-asthmatic CRSwNP patients are not known. Small airway dysfunction (SAD) is involved in the pathogenesis of asthma. However, whether SAD is detected in non-asthmatic patients with CRSwNPs remains unclear. OBJECTIVE: This study analysed the lung function of non-asthmatic patients with CRSwNPs and evaluated its clinical relevance in CRSwNPs. METHODS: The clinical data for 191 consecutive CRSwNP patients (73 asthmatic and 118 non-asthmatic) and 30 control subjects were prospectively collected. The patients were followed up for at least 3 years (mean [standard deviation], 42.47 ± 8.38 months). Serum and tissue total IgE levels were measured in 95 and 93 patients, respectively. Tissue eosinophil counts were documented in 63 patients. RESULTS: Non-asthmatic CRSwNP patients had decreased forced expiratory flow at 75% of the FVC (FEF75 ) and FEF50 compared to the control subjects, and this difference was related to the severity of CRSwNP. The risk factors for impaired lung function in asthmatic and non-asthmatic patients were duration of asthma and smoking. A multivariate logistic analysis showed that decreased FEF50 was associated with the recurrence of non-asthmatic CRSwNPs. The lung function of CRSwNP patients negatively correlated with the degree of type-2 inflammation, which was defined by the levels of Eos and IgE in polyp tissues and blood. The SAD of non-asthmatic CRSwNP patients was related to serum IgE levels. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides evidence that non-asthmatic CRSwNP patients may have SAD, which correlated with the severity and recurrence of CRSwNP. The decreased lung function of patients with CRSwNP was related to the degree of type-2 inflammation.

Chronic rhinosinusitis in COPD: A prevalent but unrecognized comorbidity impacting health related quality of life.

INTRODUCTION: Unified airway disease where upper respiratory tract inflammation including chronic rhinosinusitis (CRS) affects lower airway disease is known from asthma, bronchiectasis, cystic fibrosis and primary ciliary dyskinesia but little is known about CRS and health related quality of life in COPD. We investigate firstly, the prevalence of CRS in COPD. Secondly the impact of CRS on HRQoL. Thirdly, risk factors for CRS in COPD. METHODS: cross-sectional study of CRS in 222 COPD patients from 2017 to 2019 according to EPOS2012/2020 and GOLD2019 criteria. Patients completed the COPD assessment test (CAT), Medical Research Council dyspnea scale and Sinonasal outcome test 22 (SNOT22) and questions on CRS symptoms. They then had a physical examination including flexible nasal endoscopy, CT-sinus scan and HRCT-thorax. RESULTS: 22.5% of COPD patients had CRS and 82% of these were undiagnosed prior to the study. HRQoL (CAT, SNOT22 and the SNOT22-nasal symptom subscore) was significantly worse in COPD patients with CRS compared with those without CRS and healthy controls. Multiple logistic regression analysis suggests that the most likely candidate for having CRS was a male COPD patient who actively smoked, took inhaled steroids, had a high CAT and SNOT22_nasal symptom subscore. DISCUSSION: the largest clinical study of CRS in COPD and the only study diagnosing CRS according to EPOS and GOLD. This study supports unified airway disease in COPD. The SNOT22_nasal symptoms subscore is recommended as a standard questionnaire for COPD patients and patients at risk should be referred to an otorhinolaryngologist.

Type 1/type 2 inflammatory cytokines correlate with olfactory function in patients with chronic rhinosinusitis.

BACKGROUND: Olfactory dysfunction secondary to chronic rhinosinusitis (CRS) has been highly associated with impaired quality of life. Asian CRS patients showed a distinct inflammatory profile, with less type 2 endotype compared with European and North American. This study aimed to explore the pattern of the inflammatory cytokines in CRS patients from China and their association with olfactory function. METHODS: Institutional review board-approved prospective study in which the olfactory function of 71 CRS patients was assessed with Sniffin' Sticks before the nasal endoscopic surgery. A set of cytokines and inflammatory mediators including type 1 and type 2 inflammatory cytokines were measured in nasal mucus by using a multiplex flow cytometric bead assay (CBA). Baseline characteristics in CRS patients were collected and the Spearman r statistic was performed to assess the association of olfactory function with cytokines and inflammatory mediators. RESULTS: A total of 71 nasal mucus samples of CRS patients, including 25 chronic rhinosinusitis without nasal polyposis (CRSsNP) patients and 46 chronic rhinosinusitis with nasal polyposis (CRSwNP) patients, were evaluated in this study. The nasal mucus levels of type 1 inflammatory cytokine IFN-γ (interferon-γ), type 2 inflammatory cytokines including IL-4, IL-5 and GM-CSF (granulocyte-macrophage colony-stimulating factor) and anti-inflammatory cytokine IL-10 were significantly and inversely correlated with olfactory function in total patients with CRS (r = -0.308, p = 0.009; r = -0.250, p = 0.036; r = -0.399, p = 0.001; r = -0.269, p = 0.023; r = -0.273, p = 0.021, respectively). In CRSsNP, the olfactory function was inversely correlated with levels of type 1 inflammatory cytokine TNF-α (tumor necrosis factor-α) (r = -0.637, p = 0.001) and IL-10 (r = -0.468, p = 0.018). Nevertheless, the olfactory function in CRSwNP was inversely correlated with type 2 inflammatory cytokines including IL-4 (r = -0.303, p = 0.041) and IL-5 (r = -0.383, p = 0.009). CONCLUSION: Both type 1 and type 2 inflammatory cytokines may contribute to the pathogenesis of CRS-associated olfactory dysfunction in the Chinese population.

Rinosinusitis crónica en niños: revisión de la evaluación y manejo actual / Chronic rhinosinusitis in children: review of the evaluation and current management

La rinosinusitis crónica (RSC) en niños corresponde a la inflamación de la mucosa de la cavidad nasal y senos paranasales, presentando síntomas como obstrucción nasal, descarga nasal, presión o dolor facial y tos, presentes por más de 12 semanas. Conlleva una gran carga de morbilidad para quienes la padecen, y un alto costo económico. Su diagnóstico constituye un desafío debido a la sobreposición de síntomas con infecciones respiratorias altas y otras condiciones no infecciosas. En los últimos años se han dilucidado nuevos factores contribuyentes como los biofilms , disfunción del microbioma, y el creciente papel de mecanismos inflamatorios no infecciosos. El estudio imagenológico de elección es la tomografía computarizada, preferentemente en casos de duda diagnóstica, falta de respuesta a tratamiento o sospecha de complicaciones. El tratamiento de primera línea es el manejo médico, basado en irrigación nasal, posible uso de antibióticos prolongados y corticoides nasales. Para casos refractarios se plantean intervenciones quirúrgicas, siendo la adenoidectomía la primera elección, principalmente en niños menores; otras intervenciones incluyen la cirugía endoscópica de cavidades paranasales. Nuevas terapias biológicas están siendo estudiadas basadas en los mecanismos inflamatorios no infecciosos de la RSC y su relación con comorbilidades como el asma.

Chronic rhinosinusitis (CRS) in children is the inflammation of the nasal and sinus mucosa, presenting symptoms such as obstruction, nasal discharge, pressure or facial pain and cough, which extends for more than 12 weeks. It represents a great burden for those affected, with high economic cost. Its diagnosis constitutes a challenge due to the overlap of symptoms with other upper respiratory infections and other non-infectious conditions. In recent years, new contributing factors have been elucidated, such as biofilms, microbiome dysfunction, and the growing role of noninfectious inflammatory mechanisms. Diagnosis depends on the recognition of characteristic symptoms and their duration. The imaging study of choice is computed tomography, especially in cases of diagnostic doubt, lack of response to treatment or suspicion of complications. First-line treatment of is based on nasal irrigation, possible use of prolonged antibiotics and nasal corticosteroids. For refractory cases, surgical intervention is proposed, with adenoidectomy being the first choice, mainly in younger children; other interventions include endoscopic sinus surgery. New biological therapies are being studied based on noninfectious inflammatory mechanisms of CRS and its comorbidities such as asthma.

Voice-Related Quality of Life in Patients with Chronic Rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis (CRS) has long been associated with vocal dysfunction. However, studies quantifying the presence of voice dysfunction in CRS patients or the effects of functional endoscopic sinus surgery (FESS) are sparse. The goal of this study was to determine the voice-related quality of life in patients undergoing FESS for CRS using the validated Voice Related Quality of Life Survey (VRQL). We correlated the preoperative VRQL scores to the Sino-Nasal Outcome Test (SNOT-22) scores, and we determined the effect of FESS on postoperative VRQL scores. METHODS: Consecutive patients undergoing FESS were preoperatively administered both the VRQL and the SNOT-22 surveys. Spearman (ρ) and Pearson (r) correlation coefficients were calculated. The VRQL was mailed to patients postoperatively between 3 and 6 months. The paired t-test was used to compare pre- and post-FESS scores. RESULTS: A total of 102 patients were enrolled, and 81 patients completed the two surveys. A total of 51 (62.9%) patients had raw VRQL score ≥ 10, signifying presence of significant vocal symptoms. The mean ± standard deviation (SD) raw VRQL score of the entire study population was 12.4 ± 4.6, and the mean SNOT-22 score was 37.8 ± 19.2. The Spearman correlation coefficient between VRQL and the total SNOT-22 score was 0.34 (P =.002), and the Pearson correlation coefficient was 0.36 (P = .001). Both correlations were similar, demonstrating that increasing severity of CRS symptoms correlates with decreasing voice-related quality of life (QOL). Seventy patients completed the postoperative survey for an 86% retention rate. Thirty-six of these patients had abnormal preoperative VRQL scores, and these patients improved significantly after FESS. The mean preoperative versus postoperative raw scores were 15.2 ± 5.6 versus 12.5 ± 4.1, respectively (P = .003). CONCLUSION: This study demonstrates the increasing presence of vocal complaints with increasing severity of CRS. It also demonstrates that VRQL scores improve after FESS in those patients with preoperative vocal complaints. LEVEL OF EVIDENCE: IV.

Comparison of olfactory and taste functions between eosinophilic and non-eosinophilic chronic rhinosinusitis.

OBJECTIVE: Most patients with chronic rhinosinusitis (CRS) complain of olfactory and/or taste dysfunctions. However, olfactory and taste dysfunctions depending on the subtype of CRS, classified as eosinophilic CRS (ECRS) and non-eosinophilic CRS (NCRS), have not been clearly reported. Therefore, the purpose of this study was to investigate the clinical features in olfactory and taste functions according to the subtype classified as ECRS and NCRS. METHODS: We retrospectively analyzed the electronic medical records of patients who underwent endoscopic sinus surgery and were diagnosed with CRS. The patients were divided into ECRS and NCRS groups, according to their Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scores. We analyzed demographic characteristics, Sino-Nasal Outcome Test findings, Lund-Mackay score, and the results of previously-validated tests, including the Korean Version of Sniffin' Stick test and chemical gustatory function test. RESULTS: Patients with ECRS and NCRS had decreased olfactory and taste functions compared to the control group. In particular, the olfactory score of ECRS patients was lower than that of NCRS patients (18.1 ± 9.5 vs 23.7 ± 8.5, respectively, p <0.001). On the other hand, taste scores of ECRS patients were not statistically different compared to NCRS patients (19.1 ± 4.7 vs. 18.3 ± 4.7, respectively, p = 0.166). Olfactory score decreased with increase in JESREC score (r=-0.203, p = 0.002), but it had no correlation with taste score (r = 0.072, p = 0.276). CONCLUSION: We found a difference in olfactory function but no difference in taste function between patients in ECRS and NCRS groups. These results may provide valuable clinical features in terms of olfactory and taste functions according to the subtypes of CRS.