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.

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.

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.

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.

Sleep Dysfunction is an Independent Predictor of Productivity Losses in Patients with Chronic Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is known to have a significant impact on economic productivity. Sleep dysfunction is associated with staggering productivity losses and is highly prevalent in patients with CRS. The effect of sleep dysfunction on productivity in CRS has not been elucidated. The objective of this study was to determine the relationship between sleep dysfunction and lost productivity in patients with CRS. METHODS: Eighty-two adult patients with CRS were prospectively enrolled into a cross-sectional cohort study. Patients with obstructive sleep apnea were excluded. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Presenteeism (reduced work efficiency), absenteeism (missed work days), and lost work, household, and overall productivity were analyzed. The primary aim was assessing the correlation between PSQI and productivity. Regression analyses were performed to account for disease severity, pain, and depression. RESULTS: Sleep dysfunction is significantly correlated with overall lost productivity (R2 = 0.397, P < .05). Presenteeism is the most strongly affected by sleep dysfunction (R2 = -0.441, P < .001). Higher PSQI scores were significantly associated with productivity losses, whereas lower scores were not. Sleep remained an independent predictor of productivity when regression analysis accounted for disease severity, depression, and pain. CONCLUSION: Sleep dysfunction has a significant association with lost productivity in patients with CRS, particularly with worsening PSQI scores. More clearly defining those components of CRS that most impact a patient's daily function will allow clinicians to more optimally manage and counsel patients with CRS.

The Sinonasal Outcome Test (SNOT-22) Is a Poor Diagnostic Tool for Chronic Rhinosinusitis.

BACKGROUND: The SNOT-22 is a validated and widely used outcomes tool in chronic rhinosinusitis (CRS). We hypothesized that SNOT-22 scores and response patterns could be used as a diagnostic tool to differentiate between patients with CRS and those who present with CRS-like symptoms but prove not to have CRS. METHODOLOGY/PRINCIPAL: SNOT-22 measurements were collected from 311 patients who presented with a chief complaint of sinusitis to a tertiary rhinology practice. Following a full diagnostic evaluation, patients were diagnosed with CRS or determined to have non-CRS diagnoses. A response pattern "heatmap" of the SNOT-22 scores for each group was compared. An optimal cutoff point for total SNOT-22 score in predicting CRS was sought using a receiver operating characteristic (ROC) curve. RESULTS: A total of 109 patients were diagnosed with CRS and 202 patients were assigned to non-CRS. The non-CRS SNOT-22 total score histogram had lower overall scores compared to the CRS group, although there was substantial overlap. The CRS SNOT-22 heatmaps had a distinctive pattern compared to the non-CRS group. As individual measures, 3 of the 4 cardinal symptoms of CRS (nasal congestion, loss of smell, and rhinorrhea) were found to be significantly different between the 2 groups (P < .002). However, the ROC analysis showed the total SNOT-22 score to be a poor instrument to differentiate CRS from non-CRS patients. CONCLUSIONS: Our results cause us to reject our hypothesis and conclude that, while an effective outcomes tool, the SNOT-22 (using total score and response pattern) is a poor differentiator between CRS and non-CRS patients.

The real-world "ControL'Asma" study: a nationwide taskforce on asthma control in children and adolescents.

BACKGROUND: Asthma control is the goal of asthma management. A nationwide study on this aspect was launched by the Italian Society of Paediatric Allergy and Immunology (ControL'Asma study). OBJECTIVE: To define variables associated with different asthma control grades in a nationwide population of asthmatic children and adolescents. METHODS: This cross-sectional real-world study included 480 asthmatic children and adolescents (333 males, median age 11.2 years) consecutively enrolled in 10 third level pediatric allergy clinics. According to the Global Initiative for Asthma (GINA) document, history, medication use, perception of asthma symptoms assessed by visual analog scale (VAS), clinical examination, lung function, childhood asthma control test (cACT)/asthma control test (ACT), and asthma control level were evaluated. RESULTS: Considering GINA criteria, asthma was well controlled in 55% of patients, partly controlled in 32.4%, and uncontrolled in 12.6%. Regarding cACT/ACT, asthma was uncontrolled in 23.2%. Patients with uncontrolled asthma had the lowest lung function parameters and VAS scores, more frequent bronchial obstruction and reversibility, and used more oral and inhaled corticosteroids (CS). CONCLUSIONS: The ControL'Asma study, performed in a real-world setting, showed that asthma in Italian children and adolescents was usually more frequent in males. Asthmatic patients had an early onset and allergic phenotype with very frequent rhinitis comorbidity. Uncontrolled and partly controlled asthma affected about half of the subjects, and the assessment of asthma symptom perception by VAS could be a reliable tool in asthma management.

Data Science-Based Analysis of Patient Subgroup Structures Suggest Effects of Rhinitis on All Chemosensory Perceptions in the Upper Airways.

Viral rhinitis contributes significantly to olfactory dysfunction, but it is unclear how many patients have other chemosensory symptoms in addition to olfactory loss. This was addressed in the present reanalysis of data previously published in Pellegrino R, Walliczek-Dworschak U, Winter G, Hull D, Hummel T. 2017. Investigation of chemosensitivity during and after an acute cold. Int Forum Allergy Rhinol. 7(2):185-191, using unsupervised and supervised machine-learning methods. Fifty-eight patients with acute rhinitis and 59 healthy controls were assessed for orthonasal and retronasal olfactory function, taste, and intranasal trigeminal sensitivity. Unsupervised analysis showed that during rhinitis, clinical scores of olfactory function, expressed as threshold, discrimination, identification (TDI) values, were trimodally distributed. Two minor modes were separated from the main mode at TDI = 30.5, which corresponds to the established limit of hyposmia. This trimodal distribution was not observed after the rhinitis subsided. Olfactory function was not significantly impaired in 40% of all rhinitis patients, whereas it was transiently impaired in 59%. For this group, supervised machine-learning algorithms could be trained with information on retronasal olfactory function, gustatory function, and trigeminal sensitivity to assign patients to subgroups based on orthonasal olfactory function with a balanced classification accuracy of 64-65%. The ability to recognize patients with olfactory loss based on retronasal olfactory function as well as gustatory function and trigeminal sensitivity suggests in turn that these modalities are affected by rhinitis. However, the only modest accuracy at which this information allowed to reproduce the olfactory diagnosis indicated they are involved in the symptomatology of rhinitis to a lesser extent compared with the orthonasal olfactory function.

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.

Oxidative stress is associated with atopic indices in relation to childhood rhinitis and asthma.

BACKGROUND: The association between oxidative stress and atopic diseases is uncertain. Several risk factors for atopic diseases have been identified, however, a comprehensive investigation of the relationship between oxidative stress markers and atopic indices related to atopic diseases is currently lacking. METHODS: We investigated 132 children who completed a 7-years follow-up in a birth cohort. Oxidative stress markers including plasma glutathione peroxidase (GPx), myeloperoxidase (MPO), total anti-oxidant capacity (TAC), and urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured. Allergen-specific IgE levels, FeNO levels, and pulmonary function tests were also obtained. RESULTS: The activity of GPx and levels of MPO were inversely correlated to food (shrimp and crab) and house dust mite sensitization respectively. The 8-OHdG levels were strongly negatively correlated with FeNO levels (p < 0.01). A significant positive correlation was found between TAC levels and pre-and post-bronchodilator FVC % and FEV1% predicted (p < 0.05). All oxidative stress markers were not associated with the risk of atopic diseases. However, GPx-related crab sensitization and 8-OHdG related FeNO levels were significantly associated with increased risk of allergic rhinitis, while MPO-related mite sensitization and TAC-related pulmonary function parameters were strongly associated with risk of asthma (p < 0.01). CONCLUSION: Oxidative stress is strongly correlated with allergic indices, potentially playing a role in the modulation of allergic responses contributing to atopic diseases.

Predictive Factors for a New Positive Nasopharyngeal Swab Among Patients Recovered From COVID-19.

INTRODUCTION: As an emerging infectious disease, the clinical and virologic course of COVID-19 requires better investigation. The aim of this study is to identify the potential risk factors associated with persistent positive nasopharyngeal swab real-time reverse transcription‒polymerase chain reaction tests in a large sample of patients who recovered from COVID-19. METHODS: After the acute phase of SARS-CoV-2 epidemic infection, the Fondazione Policlinico A. Gemelli IRCSS of Rome established a post-acute care service for patients discharged from the hospital and recovered from COVID-19. Between April 21 and May 21, 2020, a total of 137 individuals who officially recovered from COVID-19 were enrolled in this study. All patients were tested for the SARS-CoV-2 virus with nucleic acid RT-PCR tests. Analysis was conducted in June 2020. RESULTS: Of the 131 patients who repeated the nasopharyngeal swab, 22 patients (16.7%) tested positive again. Some symptoms such as fatigue (51%), dyspnea (44%), and coughing (17%) were still present in a significant percentage of the patients, with no difference between patients with a negative test and those who tested positive. The likelihood of testing positive for SARS-CoV-2 infection was significantly higher among participants with persistent sore throat (prevalence ratio=6.50, 95% CI=1.38, 30.6) and symptoms of rhinitis (prevalence ratio=3.72, 95% CI=1.10, 12.5). CONCLUSIONS: This study is the first to provide a given rate of patients (16.7%) who test positive on RT-PCR test for SARS-CoV-2 nucleic acid after recovering from COVID-19. These findings suggest that a significant proportion of patients who have recovered from COVID-19 still could be potential carriers of the virus. In particular, if patients continue to have symptoms related to COVID-19, such as sore throat and rhinitis, it is reasonable to be cautious by avoiding close contact, wearing a face mask, and possibly repeating a nasopharyngeal swab.

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.

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.

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.

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.

Patterns of viral pathogens causing upper respiratory tract infections among symptomatic children in Mwanza, Tanzania.

Upper-respiratory tract infections (URTI) are the leading causes of childhood morbidities. This study investigated etiologies and patterns of URTI among children in Mwanza, Tanzania. A cross-sectional study involving 339 children was conducted between October-2017 and February-2018. Children with features suggestive of URTI such as nasal congestion, dry cough, painful swallowing and nasal discharge with/without fever were enrolled. Pathogens were detected from nasopharyngeal and ear-swabs by multiplex-PCR and culture respectively. Full blood count and C-reactive protein analysis were also done. The median age was 16 (IQR: 8-34) months. Majority (82.3%) had fever and nasal-congestion (65.5%). Rhinitis (55.9%) was the commonest diagnosis followed by pharyngitis (19.5%). Viruses were isolated in 46% of children, the commonest being Rhinoviruses (23.9%). Nineteen percent of children had more than 2 viruses; Rhinovirus and Enterovirus being the commonest combination. The commonest bacteria isolated from ears were Staphylococcus aureus and Pseudomonas aeruginosa. Children with viral pathogens had significantly right shift of lymphocytes (73%-sensitivity). Majority (257/339) of children were symptoms free on eighth day. Viruses are the commonest cause of URTI with Rhinitis being the common diagnosis. Rapid diagnostic assays for URTI pathogens are urgently needed in low-income countries to reduce unnecessary antibiotic prescriptions which is associated with antibiotic resistance.

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.

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.