Nasal Lavage Research Articles

Infectivity and immunogenicity of live-attenuated respiratory syncytial virus vaccines in HIV-exposed uninfected children

Abstract Background Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory illness among young children. HIV-exposed uninfected (HEU) children experience a higher burden of RSV disease and have immune abnormalities that may influence their responses to live-attenuated RSV vaccines. Methods In a pooled analysis of clinical trials of seven live-attenuated, intranasal RSV vaccines conducted by the IMPAACT Network among children 6 to <25 months of age with serum RSV-neutralizing titers of <1:40, the infectivity and immunogenicity of these vaccines were compared among HEU and HIV-unexposed uninfected (HUU) children. Nasal washes were collected during the first 28 days after vaccination. Serum RSV-neutralizing and anti-RSV F glycoprotein IgG antibodies were measured prior to and 56 days after vaccination, and before and after the following winter season. Results Of 156 children, 90 (58%) were HUU and 66 (42%) were HEU. Seventy-six (84%) HUU and 63 (95%) HEU participants were infected with vaccine (shed vaccine virus and/or had a ≥4-fold rise in serum RSV antibodies at 56 days after vaccination). HUU children had higher serum RSV-neutralizing and anti-RSV F IgG titers prior to vaccination. Compared to HEU children, lower percentages of HUU children had ≥4-fold rises in RSV-neutralizing (67% vs. 88%) and anti-RSV F IgG (70% vs. 89%) titers at 56 days after vaccination. Conclusions Live-attenuated RSV vaccines are highly immunogenic in HEU children. Given their increased burden of RSV disease and higher early-childhood mortality in some settings, HEU children should be prioritized for vaccination against RSV as these vaccines become available.

Characterization of H5N1 avian influenza virus isolated from bird in Russia with the E627K mutation in the PB2 protein

Currently A(H5Nx) avian influenza viruses are globally widespread and continue to evolve. Since their emergence in 2020 novel highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b reassortant viruses have become predominant in the world and caused multiple infections in mammals. It was shown that some of A(H5N1) viruses mostly isolated from mammals contain an E627K mutation in the PB2 protein which can lead to adaptation of influenza viruses to mammalian cells. In 2023 in Russia we have isolated two highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b viruses from birds one of which contained an E627K mutation in the PB2 protein. This virus had increased virulence in mice. Limited airborne transmission of the virus with the PB2-E627K mutation was observed between ferrets, in which infectious virus was detected in the nasal washings of the three of the twelve recipient ferrets, and clinical symptoms of the disease were observed in one case. Both viruses showed dominant binding to avian-type sialoside receptors, which was most likely the reason for the limited transmissibility. Thus, this study indicates a possible limited increase in the pandemic potential of A(H5N1) 2.3.4.4b viruses and highlights the importance of continuous avian influenza surveillance for pandemic preparedness and response.

Abducens nerve palsy secondary to allergic fungal sinusitis

Abstract Allergic fungal rhinosinusitis (AFRS) stands out as the predominant form of fungal sinusitis, primarily attributable to a hypersensitive response to fungal invasion. AFRS Characterized by symptoms of rhinosinusitis. The expanding mass in the disease leads to bony restructuring and implicating adjacent anatomical structures. AFRS may extend beyond the sinus cavities, leading to compression of nearby structures like the orbit, optic and abducens nerves which leads to many complications such as nerve palsies and proptosis. Diagnosis of AFRS typically necessitates radiographic assessment initially, with histopathological examination serving as the confirmatory modality. The management of AFRS typically entails a multifaceted approach integrating surgical intervention alongside medical therapy. This case report illustrates a distinctive manifestation of abducens nerve palsy secondary to allergic fungal sinusitis which had dramatic improvement and resolution of the diplopia after the Endoscopic sinus surgery. Steroids and nasal saline irrigation have been prescribed post operatively to prevent the recurrence.

The essential oils from Asarum sieboldii Miq. alleviate allergic rhinitis by regulating tight junction and inflammation; Network analysis and preclinical validation

Ethnopharmacological relevanceEssential oils from herbs, including those from Asarum sieboldii Miq., are readily absorbed through mucous membranes, explaining their widespread use in inhalation formulations. Asarum sieboldii Miq. has a long history of traditional use for various medicinal purposes, attributed to its anti-inflammatory, antiallergic, and antioxidant properties. Despite research on Asarum sieboldii Miq. for allergic inflammation in respiratory diseases, detailed mechanistic studies are still lacking. Aim of the studyWe utilized bioinformatics and network pharmacology to identify the effectiveness of Asarum sieboldii Miq. in treating allergic rhinitis (AR). Our aim is to elucidate the potential therapeutic effects of essential oil derived from Asarum sieboldii Miq. (ASO), which is recognized for its diverse pharmacological properties, on AR. Materials and methodsCommon genes associated with the active compounds of ASO and AR were utilized to construct a related network and predict their mode of action. AR was induced in BALB/c mice by exposing them to ovalbumin (OVA) and particulate matter 10 (PM10; airborne particles <10 μm). With induction, aerosolized ASO (0.0002% and 0.02%) were administered via nebulizer for 5 minutes per day, three times a week for 7 weeks. Mice were examined for histopathological changes in the nasal tissue, nasal epithelial inflammation, the production of allergen-specific cytokine response in vitro and in vivo. ResultsThe common genes of ASO and AR were predicted to include 'Tight junction', 'Apoptosis', and 'TGF-beta signaling', which are the main pathways of pathogenesis in AR. Consistent with network prediction, nebulized ASO treatment effectively improved the expression of tight junction-related factors, zonula occludens-1, claudin-1, occludin and junction adhesion molecule A, in OVA+PM10 induced mice. Additionally, it reduced hyperplasia of nasal epithelial thickness, goblet cell counts, and inflammatory cell infiltration (eosinophils, neutrophils, macrophages, and lymphocytes) in nasal lavage fluid, while also alleviating allergic symptoms such as sneezing, rubbing, and serum IgE level when compared to the AR-induced group. The levels of mRNA and protein expression related to tight junctions were restored to normal levels by ASO, as confirmed in immunofluorescence analysis in nasal epithelial cells RPMI2650. Furthermore, treatment of ASO on PM10-treated nasal epithelial cells significantly reduced ROS production, recovered mitochondria membrane potential, and inhibition of the production of proinflammatory cytokines (TNF-α, IL-4, and IL-13) and inflammatory mediators linked to the MAPK/NF-κB signaling pathways. ConclusionIntranasal nebulization of ASO improves TJs and alleviates allergic nasal inflammation in AR. It supports the potential pharmaceutical application of ASO treatment for AR.

Profile of immune response during nasal challenge with dermatophagoides pteronyssinus in subjects with allergic airway diseases

BackgroundT lymphocyte helper (Th) 2 plays the main role in pathogenesis of allergic airway diseases (AAD). Recent studies showed that interleukin (IL) 33, Th17 and Th22 also may be involved in allergic inflammation. The aim is to evaluate cytokine level before and after nasal challenge with Dermatophagoides pteronyssinus in patients with AAD.MethodsPatients with persistent allergic rhinitis (AR) with or without allergic asthma (AA) allergic to house dust mite and healthy individuals underwent nasal challenge with Dermatophagoides pteronyssinus. Measurements of IL-13, IL-17, IL-22 and IL-33 in serum and nasal lavage were performed before, 2 and 22 h after nasal challenge by ELISA.Results. Ten patients with AR only, 6 patients with AR and AA and 7 healthy individuals were involved in the study. Serum IL-22 level significantly increased in patients with AR and AA and nasal lavage IL-22 tended to increase in patients with AAD after nasal challenge. Serum IL-13 level tended to increase in patients with AR and AA. IL-13 level in nasal lavage fluid decreased at 22 h after nasal challenge in patients with AR only. IL-17 level in serum and nasal lavage decreased in patients with AAD. Serum IL-33 tended to increase after nasal challenge whereas IL-33 in nasal lavage significantly decreased.ConclusionCytokine profile differs between local and systemic compartments and between patients with allergic rhinitis only and patients with allergic rhinitis and asthma after nasal challenge.

The role of epithelial alarmins and Th2 cytokines in the inflammatory response in allergic rhinitis

Allergic rhinitis (AR) occupies a leading position among the causes of morbidity throughout the world, to date, it has been diagnosed in 400 million people. In the formation and progression of AR, a significant role is assigned to cytokines associated with the second type of immune response, in particular, IL-4, IL-5, IL-9, IL-13, IL-25, IL-33, thymic stromal lymphopoietin (TSLP). This literature review provides information on the influence of the listed mediators on the structural cells of the nasal cavity and blood immune cells (T- and B-lymphocytes, eosinophils, macrophages, dendritic cells), and discusses their association with the manifestation of AR symptoms and the severity of the disease. The results of studies aimed at establishing the level of IL-4, IL-5, IL-9, IL-13, IL-25, IL-33 and TSLP in biological fluids (blood serum, nasal lavage) and their expression in nasal epithelial cells in patients with AR compared to healthy people are assessed.

Ameliorative Potency of Iridoid Glucoside Compound Catalpol on Inhibiting NF-κB-mediated Inflammation in Allergic Rhinitis-induced Mice

Background Over time, the prevalence of allergic rhinitis (AR) has surged due to various risk factors, notably attributed to global urbanization, rendering heightened levels of pollutants, including traffic-related emissions and particulate matter. About 25% of the global children population and 40% of the adult population were reported with AR. Even though AR is recognized as a systemic inflammatory disease, it often results in diverse other comorbidities, such as dermatitis, sinusitis, conjunctivitis, and otitis, requiring extensive and expensive treatment. Purpose We assessed the effectiveness of iridoid glucoside catalpol against AR in a mouse model. Catalpol is recommended in traditional Chinese medicine to treat diverse acute and chronic diseases. Methods AR was induced in mice with an ovalbumin-sensitized AR model and treated with 10 and 20 mg of catalpol. Nasal severity scoring was performed to confirm the AR induction in mice. Allergic mediators immunoglobulin E (IgE) and histamine were quantified in the serum to assess the anti-allergic response of catalpol. In nasal lavage fluid (NALF), the inflammatory mediators IgE Ab, prostaglandin D2, leukotriene C4, eosinophil cationic protein (ECP), and pro-inflammatory cytokines were measured to analyze the anti-inflammatory potency of catalpol. The binding capacity of nuclear factor-kappa B (NF-κB) to DNA was evaluated to assess the catalpol inhibitory potency against NF-κB-mediated inflammation in AR mice. To confirm the ameliorative potency of catalpol in AR mice, a histopathological analysis of nasal mucosa was performed. Results Catalpol treatment significantly decreased the nasal symptoms and reduced the allergic mediators in the serum of experimental animals. It effectively inhibited the synthesis of inflammatory mediators, ECP, and pro-inflammatory cytokines in the NALF, and also suppressed the NF-κB DNA-binding activity in AR mice. The decrease in ciliary loss, goblet cells, eosinophil infiltration, and vascular congestion observed with our nasal mucosa histopathological analysis confirmed the ameliorative potency of catalpol. Conclusion Our findings have proven catalpol inhibits NF-κB-mediated inflammatory response in AR mice. With further analysis, a potent natural compound, catalpol, can be formulated as a drug to treat AR.

Label-Free Quantitative Proteomics Analysis of Nasal Lavage Fluid in Chronic Rhinosinusitis with Nasal Polyposis

(1) Background: Chronic rhinosinusitis (CRS) is a common chronic inflammation of the nasal mucosa and the paranasal sinuses. The pathogenesis of chronic rhinosinusitis (CRS) is multifactorial and, as of yet, not well understood. (2) Methods: Nasal lavage fluid samples were collected from patients diagnosed with chronic sinusitis with nasal polyposis (CRSwNP) (n = 10) and individuals without sinusitis (control group) (n = 10) who had no nasal complaints. In the present study, we used an untargeted label-free LC-MS/MS mass spectrometric approach combined with bioinformatics and network pathway analysis to compare the changes in the proteomic profiles of the CRSwNP group and the control group. Data from LC-MS/MS underwent univariate and multivariate analyses. (3) Results: The proteomic analyses revealed distinct differences in the abundances of nasal lavage fluid proteins between the CRSwNP and control groups: a total of 234 proteins, 151 up- and 83 down-regulated in CRSwNP. Functional Gene Ontology (GO) analysis showed that dysregulated proteins were involved in airway inflammatory reaction, immune response, and oxidative stress. The biomarkers were evaluated using the Receiver Operating Characteristic (ROC) curve; an Area Under the Curve (AUC) of 0.999 (95% CI) identified potential biomarkers between the CRSwNP and control group. EMILIN-3 and RAB11-binding protein RELCH were down-regulated, and Macrophage migration inhibitory factor and deoxyribonuclease-1 were up-regulated, in CRSwNP compared to the control group. (4) Conclusions: These differentially expressed proteins identified in CRSwNP are involved in airway inflammatory reaction, immune response, and oxidative stress. In particular, the identification of increased interleukin-36 gamma (IL-36γ), which contributes to inflammatory response, and a decrease in SOD, in this group are notable findings. In the future, several of these proteins may prove useful for exploring the pathogenesis of nasal polyps and chronic sinusitis or as objective biomarkers for quantitatively monitoring disease progression or response to therapy.

Intranasal M2SR and BM2SR Vaccine Viruses Do Not Shed or Transmit in Ferrets

Background/Objectives: Live influenza vaccines are considered to stimulate better overall immune responses but are associated with safety concerns regarding shedding and the potential for transmission or reassortment with wild-type influenza viruses. Intranasal M2SR and BM2SR (M2- and BM2-deficient single replication), intranasal influenza viruses, have shown promise as broadly cross-reactive next-generation influenza vaccines. The replication deficiency, shedding, and transmissibility of M2SR/BM2SR viruses were evaluated in a ferret model. Methods: Wild-type influenza A and B control viruses replicated in upper respiratory organs and transmitted to both direct and aerosol contact ferrets, whereas M2SR and BM2SR influenza vaccine viruses were not detected in any tissues or in nasal washes after inoculation and were not recovered from any direct or aerosol contact ferrets. Mice were simultaneously infected with wild-type influenza A and M2SR viruses to assess reassortment potential. Sequence and PCR analyses of the genome recovered from individual virus plaques isolated from lung homogenates identified the origin of the segments as exclusively from the replicating wild-type virus. Results: These results indicate that M2SR and BM2SR influenza vaccine viruses are attenuated, do not shed or transmit, and have a low probability for reassortment after coinfection. Absence of shedding was further demonstrated in nasal swabs taken from subjects who were inoculated with H3N2 M2SR in a previously described Phase 1 clinical study. Conclusions: These results indicate that M2SR/BM2SR viruses have the potential to be used in a broader population range than current live influenza vaccines.

Protection of Rabbits Against Colonization and Morbidity Associated With Toxigenic Pasteurella multocida by Immunization With Inactivated Heat-labile Toxin.

Pasteurella multocida is a significant cause of morbidity and mortality in rabbits, as well as other species. Some isolates elaborate a heat-labile toxin (PMT) that has been shown to be an important virulence factor. Though previous studies have demonstrated protective immunity can be conferred via immunization of rabbits with heat-inactivated PMT (IPMT), we investigated the ability of immunization to impact colonization of P. multocida. Rabbits were immunized at days 0, 7 and 14 with either phosphate buffered saline (PBS), the mucosal adjuvant cholera toxin (CT), IMPT or IPMT + CT. Male New Zealand white rabbits were used and confirmed to be free of P. multocida prior to experimentation. Serum IgG and nasal lavage fluid IgA responses directed against PMT were found in rabbits immunized with IPMT, with or without CT, but not in those immunized with only PBS or CT; and the addition of CT to IPMT enhanced the response. Significantly more P. multocida CFUs (p≤0.05) were cultured from the lungs of rabbits immunized with IPMT, with or without CT, compared to those administered only PBS or CT, although no differences were observed in nasal lavage fluid samples. Further, immunization IPMT, with or without CT, conferred protection against pleuritis and pneumonia. PMT, in addition to its role as a virulence factor, may serve as a colonization factor for P. multocida in the lungs of rabbits.

EDP-938 Has a High Barrier to Resistance in Healthy Adults Experimentally Infected with Respiratory Syncytial Virus.

EDP-938 is an oral once-daily RSV nucleoprotein (N) inhibitor with potent antiviral activity. In a human RSV challenge trial, EDP-938 significantly reduced viral load and symptom severity. During antiviral development, it is critical to understand the propensity for resistance to develop. In vitro studies of EDP-938 suggest a higher barrier to resistance as compared to RSV fusion inhibitors. We evaluated the development of viral resistance to EDP-938 in a human challenge trial. A subset of the 124 participants with RSV infection were chosen for genetic analysis; 159 nasal wash samples from 48 participants were analyzed using next-generation sequencing of the N gene of RSV. Of the 48 participant sampled, 37 were from EDP-938-treated and 11 were placebo-treated participants, representing 45% and 26% of the participants, respectively. The effects of treatment-emergent mutations on viral load, EDP-938 efficacy, and viral fitness were evaluated. Two of the 37 EDP-938-treated participants with samples sequenced had treatment-emergent mutations: N:L139I and N:E112G. From in vitro analysis, N:L139I reduced sensitivity to EDP-938 by approximately 10-fold, while N:E112G had no effect. However, N:L139I was associated with a reduction in viral fitness, suggesting clinical resistance is associated with fitness costs. Neither of these variants were associated with reduced viral clearance. In human RSV infections treated with EDP-938, emergence of RSV variants with reduced sensitivity to EDP-938 occurred in only 1 participant and was associated with reduced viral fitness. EDP-938's high barrier to resistance highlights its robust mechanism of action. NCT03691623.

Transforming Nasal Irrigation Experience of Children and Families with Therapeutic Instructional Plays.

In Brazil, nasal irrigation is a common procedure for children hospitalized with respiratory conditions. However, it often causes stress for both the child and their family. Nurses need to rethink their approach to care, and the use of therapeutic play can be an ally in transforming the stressful context. To understand the family perceptions of nasal irrigation in hospitalized children after an educational intervention mediated by instructional therapeutic play (ITP). This descriptive, exploratory, and qualitative study was conducted from the perspective of Herbert Blumer's Symbolic Interactionism in a hospital in São Paulo, Brazil. The study included family members of hospitalized children aged 3-6 years who participated in an ITP intervention and remained for 6 hours afterward. Participants self-reported literacy with preserved cognition and verbal communication. This study was conducted between March 2023 and January 2024 using semi-structured interviews with 38 family members. Data were analyzed using Bardin's thematic content and lexical analysis with IRAMUTEQ® software. The interaction of families with ITP for nasal irrigation in children led to a redefinition of the procedure from distressing to enjoyable. ITP was evaluated as an essential and stimulating method that familiarized the child with the procedure, facilitating the understanding process for both the child and the family. ITP is a caregiving technology that nurses can use to assist with nasal irrigation, re-signifying the experiences of children and their families during the procedure.

Hypertonic Saline Nasal Rinse Intervention: Immunomodulatory Effects in Dairy Workers

ABSTRACT Objective Increased risk of occupational exposure to bioaerosols has long been recognized in livestock operations including dairy facilities. Spanning the inhalable fraction (0–100 μm), dairy bioaerosols comprise a wide variety of inflammatory components that deposit in the nasopharyngeal region. The resultant inflammatory response from bioaerosol exposure is likely driving the increased prevalence of respiratory disease observed in dairy workers. It is also thought the microbiome of the upper respiratory system may help mediate this inflammation. We investigated the viability of a low-cost hypertonic saline nasal rinse intervention in modulating inflammatory responses in bioaerosol exposed dairy workers and its impact on microbial diversity. Methods Pre- and post-shift nasal rinses were administered and collected alongside full shift inhalable personal breathing zone (PBZ) samples for each participant for up to 5 consecutive days. Treatment group participants (n = 23) received hypertonic saline rinses while control group participants (n = 22) received normotonic saline rinses. Particulate matter (PM) and endotoxin concentrations were quantified from PBZ samples using gravimetric and enzymatic analytical methods, respectively. Pre- and post-shift rinses were analyzed for pro- and anti-inflammatory markers and microbial diversity using a multiplex assay and 16S rRNA sequencing, respectively. Results PM and endotoxin concentrations were comparable between groups indicating similar exposures. Post-shift pro-inflammatory markers were significantly higher than pre-shift for IL-13 (p = .047), IL-1β (p < .001), IL-6 (p < .001), IL-8 (p < .001), and TNF-α (p = .024). There was no evidence of a difference in log concentrations between intervention group or day among any of the measured inflammatory markers. Anti-inflammatory IL-10 concentrations increased across the 5 sample days, independent of treatment group suggesting tonicity may not be driving the change. However, this result was not significant (p = .217). Nasal microbiome alpha (within sample) and beta (between sample) diversity metrics did not differ significantly between group or day demonstrating no adverse washout intervention effects. Conclusion This study provided encouraging results that warrant future research to further evaluate saline nasal rinses as a workplace intervention.

Cytokines Measured in Nasal Lavage Compared to Induced Sputum in Patients with Mild Cystic Fibrosis

The measurement of cytokines in induced sputum and nasal lavage (NL) samples has been performed for years in people with cystic fibrosis (CF). The aim of this study was to directly compare sputum and NL samples and interpret results based on disease severity in patients who were categorized as having mild or severe lung disease. The categorization was based primarily on structural abnormalities detected on lung computed tomography and secondarily on lung function. The serum inflammatory markers neutrophil elastase (NE), IL-1β, 2, 6, 8, 10 and 17a were measured in each sputum and NL sample. Thirty-two sample pairs from 29 patients were included in this study (13 mild, 19 severe). In the patients classified as severe, many systemic inflammatory markers as well as sputum cytokines were significantly higher compared to those in the mild patients. However, all the markers measured in the NL were higher in the mild patients (p =&lt; 0.05 for NE, IL-6 and IL-8). In addition, many cytokines in the NL correlated negatively with those in the sputum samples. Major differences in the cytokine levels were shown although the samples were obtained at the same time in the same patient. Advanced structural lung disease was closely related to systemic and lower airway inflammation, whereas preserved lung function was associated with higher levels in the NL. We hypothesize that the main part of the immune response takes place in the nasal mucosa in patients with minor pulmonary changes. Our results suggest that inflammation must be interpreted individually depending on the compartment in which it is measured. Further research is needed to accurately understand inflammatory markers measured in NL.

Microplastics in different nasal irrigation options.

We aimed to assess the presence of microplastics in nasal irrigation methods commonly used in the treatment of sinusitis and rhinitis, and to evaluate human exposure. A total of 150 samples were included in the study, consisting of nasal wash bottles containing nasal irrigation solution, seawater spray, syringes for nasal irrigation with isotonic solution. The amount of microplastics per millilitre in the samples and patient exposure during single use were assessed separately for each method and product. All samples were filtered using a stainless steel vacuum filter on filter paper with a pore size of 1.2μm, washed at least three times with distilled water and incubated at 45°C for 24h to prevent mould growth. Identification and counting of microplastics was performed using a Leica Flexacam C1 camera connected to an M80 stereomicroscope. The presence of microplastics was confirmed by the hot needle method and Nile red staining. An average of 6.49 ± 13.08 microplastics/product was detected in all filtered samples. The lowest microplastic count was 0 microplastics/product in syringes and the highest was 92 microplastics/product in nasal wash bottles. Significant differences in the amount of microplastics individuals were exposed to during a single use were found between nasal wash bottles and seawater brands, while no significant differences were found between syringe brands. When nasal wash kits, seawater sprays and isotonic nasal rinses were evaluated separately, significant differences were found in the number of microplastics, the microplastics/ml ratio and the number of microplastics exposed during a single use. The highest microplastic exposure was found in nasal irrigation bottles. The exposure of individuals to microplastics increases with medical support treatments, regardless of intranasal or intravenous administration. Due to the inflammation, oxidative stress and proliferation caused by microplastics, new regulations and inspections of production conditions should be implemented worldwide to reduce exposure.

The protective effects and mechanisms of essential oil from Chimonanthus nitens Oliv. leaves in allergic rhinitis based on the NF-κB and T-bet/GATA-3 signaling pathways

Ethnopharmacological relevancePreliminary studies showed that Shanlameiye granules are derived from Chimonanthus nitens Oliv. Leaves ameliorate inflammatory responses in mice with Allergic Rhinitis (AR). The essential oil from Chimonanthus nitens Oliv. Leaves (CLO) have been identified as the key active substances in these granules. However, whether CLO constitutes the primary mechanism for the mitigation of AR-related inflammation by these granules has not yet been investigated. Aim of the studyThis experiment was to validate the effects and mechanism of CLO on inflammatory responses in RAW264.7 cells and AR rat model. Materials and methodsAn inflammatory model was induced in RAW264.7 cells by Lipopolysaccharide (LPS) & Interferon-gamma (IFN-γ) stimulation. AR rat model was established using both systemic and local challenges with Ovalbumin (OVA). ResultsIn cell experiments, CLO obviously decreased the secretion of cytokines and inhibited the NF-κB signaling pathway activation. In animal experiments, CLO decreased the number of eosinophils in the blood and lowered the levels of cytokines in nasal lavage fluid (NALF). Additionally, CLO inhibited the expression of STAT6, GATA-3, and p-p65, while increasing the expression of STAT4 and T-bet in the nasal mucosa. ConclusionIn AR rat model, CLO may play an anti-inflammatory role in AR rat model by regulating NF-κB and T-bet/GATA-3 signaling pathways.

Reduced Sense of Smell in Patients with Severe Chronic Rhinosinusitis and its Implications for Diagnosis and Management: A Narrative Review.

Reduced sense of smell is a common symptom in patients with chronic rhinosinusitis (CRS). Although it is often under-diagnosed by healthcare providers, reduced sense of smell can have a substantial negative impact on patient's quality of life as measured by health-related quality of life (HRQoL) assessments and patient-reported outcomes. This narrative review describes current smell loss diagnosis and management guidelines in CRS, and the relationship between smell loss and CRS. Reduced sense of smell can be an indication of CRS disease severity in patients with (CRSwNP) and without nasal polyps (CRSsNP), and recovery of smell can be an indicator of successful CRS treatment. The current first-line therapeutic options for smell loss are intranasal corticosteroids and nasal irrigation, and second-line therapeutic options include systemic steroids and surgery. Shared decision-making between patient, caregiver, and healthcare provider is important when choosing the most appropriate CRS treatment option. Emerging biologic therapies that target type 2 inflammation signaling pathways, such as dupilumab, omalizumab, and mepolizumab, have been shown to improve smell and taste in randomized controlled trials of patients with CRSwNP.A graphical abstract and video abstract are available with this article.

Mannose targeting of poly(lactic-co-glycolic acid): a promising approach for improving sublingual allergen-specific immunotherapy

Objective One of the most effective treatments for allergic respiratory diseases is allergen-specific sublingual immunotherapy (SLIT). While, mannose targeting has been applied in various immunostimulatory approaches, but it has not been investigated in sublingual allergen-specific immunosuppressive treatment. This study assesses mannose targeting for the ovalbumin (Ova) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles(NPs). Methods The emulsion-solvent evaporation method was employed for the synthesis of PLGA NPs containing Ova, and subsequently they attached to D-mannose. Ova-sensitized mice underwent treatment in different ways: subcutaneous administration of 10 µg Ova, sublingual administration of 5 and 10 µg Ova loaded in PLGA NPs, 5 and 10 µg Ova loaded in mannose-targeted PLGA NPs, 10 µg Ova, and 10 µg Ova loaded in dendritic cell-specific aptamer-attached PLGA NPs. Serum Ova-specific IgE and IgG2a levels, as well as IFN-γ, IL-4, IL-10, and IL-17a levels in the supernatant of Ova-stimulated splenocytes were measured. Splenocyte proliferation was assessed using an MTT assay, and also lung histological examinations, and nasal lavage fluid cell counting were performed. Results Ova-specific IgE, IL-4, IL-17a levels, eosinophil cell count, and splenocyte proliferation were remarkably reduced in the mice treated with mannose or aptamer targeted NPs compared to other groups. Also, IL-10 and IFN-γ levels were remarkably increased in the targeted NPs groups. Conclusion Our findings indicated that mannose targeting of PLGA NPs could decrease allergen dose and improve immunomodulatory effects of SLIT. However, this approach suggests an effective formulation for SLIT in the mice model, further studies with common allergens are needed for application in humans.

Assessment of microplastic exposure in nasal lavage fluid and the influence of face masks

Microplastics (MPs) can enter the human body through respiration and pose a hazard to human health. Wearing masks has become a routine behavior during the COVID-19 pandemic. The level of respirational exposure and the influence of wearing masks are currently unknown. We recruited 113 college students and divided them into natural exposure (NE), surgical mask (SM), and cotton mask (CM) groups. Nasal lavage fluid (NLF) was collected and MPs characteristics were analyzed using polarized light microscopy and laser direct infrared system. We found a relatively high abundance of MPs in NLF in the SM group (41.24 ± 1.73 particles/g). The particle size distribution and fibrous MP percentage significantly differed among the three groups. The main components in the NE, SM, and CM groups were polypropylene (58.70 %)，polycarbonate (PC, 49.49 %)，and PC (54.29 %). Components such as polyamide, polyethylene and polyethylene terephthalate were also detected. Wearing surgical masks increased the MP abundance in NLF (β = 0.36, P < 0.01). As the wear time increased, the abundance of MPs also rose (β = 0.28, P < 0.05). However, those who used bedding containing synthetic fibers had lower MP abundance in their NLF. This study highlights the use of NLF to evaluate MP exposure, which is associated with potential health risks.

Allergic rhinitis management: a survey on Italian primary care pediatricians.

Background. Allergic rhinitis (AR) is a widespread condition. The Italian Society of Pediatric Allergology and Immunology (SIAIP) promoted an initiative to update the knowledge on AR in children and adolescents. The present survey directly addressed primary care pediatricians, thus reflecting the real-world management of AR in children and adolescents. The aim was to investigate common practice in managing AR children. Methods. A panel of experts drafted a series of questions concerning the practical management of children with AR in clinical practice. The questionnaire was administered to a large sample of primary care pediatricians (864). Results. 864 primary care pediatricians participated to the survey. Each pediatrician on average follows 94 children with AR; globally 81,231 children. More than 70% of participants follow ARIA guidelines. Accordingly, 42% of children have mild AR and 58% moderate/severe. Asthma, conjunctivitis and adenoid hypertrophy are the most common comorbidity. Most pediatricians autonomously follow their patients. The intensity of treatment (use of medication) is directly proportional to the symptom severity. Intranasal corticosteroids are the most common medication used followed by oral antihistamines and nasal lavages (with hypertonic or isotonic solution). Up to 20% of participants prescribe the fixed association topical corticosteroids plus antihistamine. Conclusions. The present survey demonstrated that Italian primary care pediatricians accomplish ARIA guidelines and adapt treatment on the basis of the intensity of symptoms. Corticosteroids and antihistamines are the most common prescribed medications. Nasal lavages are also popular.