Nasal Barrier Research Articles

Exploring the Intranasal Medication Delivery Methods for the Management of Hypertension

Intranasal drug delivery systems (INDS) have attracted interest as a possible tactic to enhance the bioavailability and absorption of medications. The use of INDS to treat hypertension (HTN), a prevalent cardiovascular ailment, is examined in this review study. The paper describes the ability for medication to cross the nasal barrier and gives a summary of the cellular and structural makeup of the nasal cavity. It talks about many options and strategies to improve the way nasal drugs are delivered, with an emphasis on devices that make use of nanotechnology. The paper also includes a thorough analysis of the various approaches to treating HTN and a discussion of how INDS can enhance medication efficacy and lessen systemic side effects. This review compiles available literature on formulation strategies, relevant in vivo, ex vivo, and in vitro assessment technologies, as well as the advancement of studies concerning the role of the nasal epithelium in the systemic circulation of antihypertensive medications. With intranasal delivery, the first-pass impact is removed, doses are lowered, and drug bioavailability is enhanced. Future research in this area may lead to more effective and patient-friendly HTN therapies.

Mesenchymal stem cell-derived small extracellular vesicles restored nasal barrier function in allergic rhinitis via miR-143–GSK3β in human nasal epithelial cells

BackgroundThe nasal epithelial barrier is the first line of defense against the deep entry of pathogens or aeroallergens, and is more critical in allergic rhinitis (AR). Restoring epithelial barrier dysfunction might be a promising strategy for AR. Recent studies reported that mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEV) potentially inhibit the inflammation response and promote tissue regeneration. However, their effect on nasal epithelial cells remains unknown. ObjectivesThis study sought to describe the therapeutic effect of MSC-sEV on AR, particularly focusing their effect on nasal epithelial cells and underlying molecular mechanisms. MethodsWe utilized an ovalbumin (OVA)-induced mouse model to study AR. Both primary and immortalized human nasal epithelial cells were used to further validate the therapeutic effects of MSC-sEV on epithelial cell function. Then we constructed miR-143 overexpressing and low-expressing HNEpC and MSC-sEV to elucidate molecular mechanisms. Transcriptome analysis was performed to identify the downstream pathways involved. ResultsMSC-sEV successfully maintained nasal barrier integrity in AR mouse model. The MSC-sEV therapeutic effect on the nasal barrier was substantiated in HNEpC. Mechanistically, microRNA (miR)-143 was a candidate mediator of the above effects. Subsequently, transfecting HNEpC with miR-143 partially mimicked the restoring effect of MSC-sEV. MSC-sEV overexpressing miR-143 exerted more therapeutic effects on tight junctions and barrier integrity. Moreover, miR-143 regulated the GSK3β pathway. ConclusionsOur results indicated that MSC-sEV mitigated AR and restored nasal epithelial barrier dysfunction through the miR-143–GSK3β axis, which suggested that MSC-sEV have the remarkable ability to treat AR.

Non-Invasive Techniques of Nose to Brain Delivery Using Nanoparticulate Carriers: Hopes and Hurdles.

Intranasal drug delivery route has emerged as a promising non-invasive method of administering drugs directly to the brain, bypassing the blood-brain barrier (BBB) and blood-cerebrospinal fluid barriers (BCSF). BBB and BCSF prevent many therapeutic molecules from entering the brain. Intranasal drug delivery can transport drugs from the nasal mucosa to the brain, to treat a variety of Central nervous system (CNS) diseases. Intranasal drug delivery provides advantages over invasive drug delivery techniques such as intrathecal or intraparenchymal which can cause infection. Many strategies, including nanocarriers liposomes, solid-lipid NPs, nano-emulsion, nanostructured lipid carriers, dendrimers, exosomes, metal NPs, nano micelles, and quantum dots, are effective in nose-to-brain drug transport. However, the biggest obstacles to the nose-to-brain delivery of drugs include mucociliary clearance, poor drug retention, enzymatic degradation, poor permeability, bioavailability, and naso-mucosal toxicity. The current review aims to compile current approaches for drug delivery to the CNS via the nose, focusing on nanotherapeutics and nasal devices. Along with a brief overview of the related pathways or mechanisms, it also covers the advantages of nasal drug delivery as a potential method of drug administration. It also offers several possibilities to improve drug penetration across the nasal barrier. This article overviews various in-vitro, ex-vivo, and in-vivo techniques to assess drug transport from the nasal epithelium into the brain.

Injectable Hydrogel Mucosal Vaccine Elicits Protective Immunity against Respiratory Viruses.

Intranasal vaccines, eliciting mucosal immune responses, can prevent early invasion, replication, and transmission of pathogens in the respiratory tract. However, the effective delivery of antigens through the nasal barrier and boosting of a robust systematic and mucosal immune remain challenges in intranasal vaccine development. Here, we describe an intranasally administered self-healing hydrogel vaccine with a reversible strain-dependent sol-gel transition by precisely modulating the self-assembly processes between the natural drug rhein and aluminum ions. The highly bioadhesive hydrogel vaccine enhances antigen stability and prolongs residence time in the nasal cavity and lungs by confining the antigen to the surface of the nasal mucosa, acting as a "mucosal mask". The hydrogel also stimulates superior immunoenhancing properties, including antigen internalization, cross-presentation, and dendritic cell maturation. Furthermore, the formulation recruits immunocytes to the nasal mucosa and nasal-associated lymphoid tissue (NALT) while enhancing antigen-specific humoral, cellular, and mucosal immune responses. Our findings present a promising strategy for preparing intranasal vaccines for infectious diseases or cancer.

Transmucosal Delivery of Nasal Nanovaccines Enhancing Mucosal and Systemic Immunity.

Intranasal vaccines can induce protective immune responses at the mucosa surface entrance, preventing the invasion of respiratory pathogens. However, the nasal barrier remains a major challenge in the development of intranasal vaccines. Herein, a transmucosal nanovaccine based on cationic fluorocarbon modified chitosan (FCS) is developed to induce mucosal immunity. In our system, FCS can self-assemble with the model antigen ovalbumin and TLR9 agonist CpG, effectively promoting the maturation and cross-presentation of dendritic cells. More importantly, it can enhance the production of secretory immunoglobin A (sIgA) at mucosal surfaces for those intranasally vaccinated mice, which in the meantime showed effective production of immunoglobulin G (IgG) systemically. As a proof-of-concept study, such a mucosal vaccine inhibits ovalbumin-expressing B16-OVA melanoma, especially its lung metastases. Our work presents a unique intranasal delivery system to deliver antigen across mucosal epithelia and promote mucosal and systemic immunity.

Cigarette Smoke Mediates Nasal Epithelial Barrier Dysfunction via TNF-α.

Extensive data suggest that exposure to cigarette smoke can induce pulmonary epithelial barrier dysfunction. However, the effects of cigarette smoke on the nasal epithelial barrier are still unclear. Here, we investigated the consequence and mechanism of cigarette smoke on the nasal epithelial barrier. Sprague Dawley rats were exposed to cigarette smoke for 3 or 6 months, and changes in inflammatory markers and nasal barrier function were evaluated. Moreover, underlying mechanisms were explored. Finally, normal human bronchial epithelial cells were cultured with or without tumor necrosis factor-alpha (TNF-α) in vitro, and the levels of continuity and tight junction-associated proteins were measured. In vivo experiments showed that the nasal mucosal barrier function of rats exposed to cigarette smoke was disturbed. Indeed, proteins associated with tight junctions were decreased, and the levels of inflammatory factors, such as IL-8, IL-6, and TNF-α, were dramatically increased in comparison to those of control animals. In vitro, TNF-α was shown to disrupt the continuity of proteins associated with tight junctions and to downregulate the expression of these proteins in bronchial epithelial cells. We found that cigarette smoke disrupted the nasal mucosal barrier, and the extent of the damage was correlated with the duration of cigarette smoke exposure. We showed that TNF-α can disrupt the continuity and attenuate the expression of tight junction proteins in human bronchial epithelial cells. Therefore, cigarette smoke may induce nasal epithelial barrier dysfunction through TNF-α.

Impact of a Nursing Intervention Bundle of Care on Nasal-CPAP-Related Nasal Injuries in Preterm Infants: A Quality Improvement Initiative

AIM: The objective is to assess the effect of the application of a nasal injury prevention bundle on the incidence and severity of nasal-continuous positive airway pressure (nCPAP)-related nasal injuries in preterm infants. METHODS: We conducted a prospective controlled before-after study in a preterm neonate, <37 weeks gestation, who required nCPAP in the neonatal intensive care unit, at Mansoura University Children’s Hospital, between September 2018 through October 2019. After 2 months of nursing staff training, a nasal trauma prevention bundle was implemented. The nursing intervention bundle comprised nasal barrier dressing, regular focused checking for evolving nasal skin injury, and proper application of the CPAP device. nCPAP-related nasal injuries per 1000 days and grading of nasal injury severity were the primary outcomes. Time to onset of nasal injury after initiation of CPAP; duration of nCPAP use, duration of oxygen dependency; incidence of pneumothorax, broncho-pulmonary dysplasia; intraventricular hemorrhage; periventricular leukomalacia; late-onset sepsis; length of hospital stay; and in-hospital mortality were the secondary outcomes. RESULTS: Data from 62 preterm neonates were analyzed (31 in each group). The nasal trauma prevention bundle of care was associated with reduced nasal injury incidence per 1000 nCPAP-days (140 vs. 148.94, p = 0.03) with improved nasal injury severity staging (p = 0.003) compared to the pre-bundle era. Nasal injury developed earlier in the control group (1 [1–1] vs. 2 [1–3] days, p = 0.002) compared to the intervention group. No statistically significant differences were reported between groups regarding any of the other secondary outcomes. Longer duration of CPAP use (p = 0.009) and lack of bundle application (0.03) were the independent risk factors associated with nCPAP-related nasal injuries in preterm neonates. CONCLUSION: The implementation of a bundle of nursing interventions is associated with a substantially improved incidence and severity of nasal injuries in preterm infants receiving nCPAP.

Exploring the potential of intranasal drug delivery systems in the management of hypertension

Abstract Objectives The current review gives an overview of the anatomical and cellular structure of the nasal cavity. It presents some possibilities and different techniques to enhance the drug penetration through the nasal barrier. It comprehensively details the intranasal drug delivery system and the treatment modalities of hypertension, with an emphasis on nanotechnology-based products. Methods Gather published works about the research progression in the systemic delivery of antihypertensive drugs through the nasal epithelium, the formulation tactics and their related in vitro, ex vivo and in vivo assessment technologies in this field. Key findings Intranasal drug delivery is one of the potential routes for avoiding the first pass effect, lowering drug doses, reducing systemic side effects of most antihypertensive drugs and enhancing drug bioavailability. Conclusions Compared to oral medications, nasal medications often have better bioavailability and fewer adverse effects at the same dosage, which encourages pharmaceutical companies to manufacture additional medications in the form of nasal formulations intended for systemic treatment.

Bridging nanoplatform and vaccine delivery, a landscape of strategy to enhance nasal immunity.

Vaccination is an urgently needed and effective option to address epidemic, cancers, allergies, and other diseases. Nasal administration of vaccines offers many benefits over needle-based injection including high compliance and less risk of infection. Inactivated or attenuated vaccines as convention vaccine present potential risks of pathogenic virulence reversal, the focus of nasal vaccine development has shifted to the use of next-generation (subunit and nucleic acid) vaccines. However, subunit and nucleic acid vaccine intranasally have numerous challenges in development and utilization due to mucociliary clearance, mucosal epithelial tight junction, and enzyme/pH degradation. Nanoplatforms as ideal delivery systems, with the ability to enhance the retention, penetration, and uptake of nasal mucosa, shows great potential in improving immunogenic efficacy of nasal vaccine. This review provides an overview of delivery strategies for overcoming nasal barrier, including mucosal adhesion, mucus penetration, targeting of antigen presenting cells (APCs), enhancement of paracellular transportation. We discuss methods of enhancing antigen immunogenicity by nanoplatforms as immune-modulators or multi-antigen co-delivery. Meanwhile, we describe the application status and development prospect of nanoplatforms for nasal vaccine administration. Development of nanoplatforms for vaccine delivery via nasal route will facilitate large-scale and faster global vaccination, helping to address the threat of epidemics.

Clinical Pearls.

Injuries from medical devices account for about 30% of all hospital-acquired pressure injuries. Although several professional organizations prioritize early identification and treatment of pressure injuries, those caused by endotracheal tubes (ETTs) continue to occur.Moser and colleagues examined the current evidence to identify the reported incidence of ETT-related pressure injuries and evaluate the effectiveness of prevention methods. They found Although further study with standardized measures in various patient populations is warranted, the authors recommend use of Anchor-Fast and nasal barrier dressings to reduce the incidence of pressure-related ETT injuries.See Article, pp 416-424Research has shown that use of a checklist during intensive care patient rounds can improve quality of care and reduce the incidence of adverse events. However, difficulties with interprofessional communication during rounds may contribute to differences in patients’ plans of care.Alves and colleagues developed and validated a checklist of care to improve interprofessional communication during rounds in a pediatric intensive care unit (PICU). After multiple phases of evaluation with many expert clinicians—physicians, nurses, and pharmacists—their findings include Findings suggest that a PICU checklist supports standardization of interprofessional rounds, improving communication between professionals from different disciplines to provide consensus on patients’ plans of care.See Article, pp 383-389Communication is a challenge for patients receiving mechanical ventilation. Although various nonverbal methods of communication are possible, these are challenging and often stressful for patients. Use of a speaking valve with patients who have a tracheostomy can restore the voice; however, information on the effectiveness of this device during invasive ventilation is limited.Sutt and colleagues evaluated the use of a speaking valve on successful communication with adult patients with a tracheostomy who are receiving mechanical ventilation. They found The authors suggest that restoring airflow to the upper airway with the speaking valve may improve patients’ progress toward decannulation. They recommend use of a speaking valve for better communication with adults receiving mechanical ventilation who have a tracheostomy.See Article, pp 411-415Critical access hospitals (CAHs) were established in the late 1990s to improve health care access for rural patients. Often CAHs have limited services and technology to care for the critically ill; however, end-of-life (EOL) care does occur in these settings. As EOL care is 1 of the 5 national nursing research priorities of the National Institute for Nursing Research, it is important to understand EOL care in CAHs.Beckstrand and colleagues surveyed nurses from 39 CAHs to understand their perceptions of the obstacles and helpful behaviors in EOL care. They found The findings show that CAH nurses believe they provide high-quality EOL care. The authors recommend further research to develop effective educational tools for CAH families.See Article, pp 375-382

Conception and Clinical Efficacy of an Osmotic, Polymeric, Stable Nasal Filmogen Barrier for Preventive Treatment of Allergen and Pollution Induced Rhinitis and Respiratory Symptoms

Background: Pollution induced allergic rhinitis and respiratory symptoms is becoming a major health problem in the world for which still there is no safe and preventive treatment. Objectives: Conceive and evaluate the allergen preventive properties and clinical efficacy of an osmotic, polymeric, stable filmogen spray, called PCNS. Materials and Methods: Amb A 1 (ragweed), Der P 1 and 2 (dust mite), Bet v 1 (birch), Alt a 1 (Alternaria, fungus), and Fel d 1 (cat dander) allergens were exposed at a concentration of 5µg/ml (20 µl per tube) on the polymeric test product film (120 and 240µl layer) and the allergens crossing the barrier were quantified in the agar gel beneath the film. 0.40% HPMC and PBS solutions, tested identically, served as controls. Clinical efficacy of PCNS nasal spray was evaluated in patients suffering from allergic rhinitis and/or respiratory symptoms (29 in test product v/s 15 in saline controls) for 22 days. Nasal, ocular, respiratory symptoms and Rhino conjunctivitis Quality of Life Questionnaire (RQLQ) were measured. Statistical analyses: The normality of the populations was determined by the Shapiro-Wilk test, then statistical analysis was performed by two-tailed Student’s test for comparisons between two groups and the two-way ANOVA followed by the post hoc Bonferroni’s test for comparisons of multiple groups. p<0.05 was considered statistically significant. The analyses were performed with the software GraphPad Prism (version 8.4.2, La Jolla, USA). NS indicates not significant. Results: PCNS polymeric spray blocked the diffusion of all the allergens while 0.40% HPMC was able to prevent diffusion of only Alt a 1 and Fel d 1 allergens. Mean reflective total nasal symptom scores (rTNSS), reflective total ocular symptom score (rTOSS), and respiratory symptoms including effect on wheezing, cough, dyspnea, and chest tightness were moderately improved in the control saline group, but the improvements were nearly twice better in the PCNS group. RQLQ was improved by 23% in saline spray v/s 46% PCNS group. 4/15 patients in saline group v/s 1/29 in PCNS group required rescue medication during the study. PCNS was highly effective in reducing allergen and pollution induced respiratory symptoms. Conclusion: a polymeric, osmotic, and stable nasal barrier against pollutants and allergens represents an innovative approach against pollution induced respiratory symptoms.

Protective Dressings, Injury, and Device Failure in Preterm Infants Receiving Nasal Continuous Positive Airway Pressure: A Randomized Controlled Trial.

To investigate the protective effect of a hydrocolloid nasal dressing on the incidence and severity of nasal injury and continuous positive airway pressure (CPAP) failure in preterm infants receiving nasal CPAP (N-CPAP). A randomized controlled trial was conducted over 4 months in 2019 at level 3 neonatal ICUs in two hospitals affiliated with Isfahan University of Medical Sciences, Iran. Eighty eligible infants were born at 32 weeks of gestation or younger and/or with a birth weight of 1,500 g or less and had received between 4 and 72 hours of CPAP. Infants were randomly assigned to two groups; the intervention group used a protective dressing, and the control group received routine care. Data collection tools included a demographic questionnaire and nasal injury assessment score chart. The incidence and severity of nasal injury in preterm infants undergoing N-CPAP. Infants in the intervention group had a significantly lower incidence and severity of nasal injury compared with the control group: 15 of 40 (37.5%) versus 37 of 40 (92.5%; P < .001). Overall, the injuries identified in this study were mostly mild and moderate, with only three severe injuries in the intervention group and five in the control group. No significant differences were detected in CPAP failure (P > .05). The studied nasal barrier dressing is a safe and convenient solution to reduce nasal injury in preterm infants receiving N-CPAP.

The nasal mutualist Dolosigranulum pigrum AMBR11 supports homeostasis via multiple mechanisms

SummaryComparing the nasal microbiome of healthy individuals and chronic rhinosinusitis (CRS) patients revealed Dolosigranulum pigrum as a species clearly associated with nasal health, although isolates obtained from healthy individuals are scarce. In this study, we explored the properties of this understudied lactic acid bacterium by integrating comparative genomics, habitat mining, cultivation, and functional characterization of interaction capacities. Mining 10.000 samples from the Earth Microbiome Project of 17 habitat types revealed that Dolosigranulum is mainly associated with the human nasal cavity. D. pigrum AMBR11 isolated from the nose of a healthy individual exerted antimicrobial activity against Staphylococcus aureus, decreased proinflammatory cytokine production in airway epithelial cells, and Galleria mellonella larvae mortality induced by this important nasal pathobiont. Furthermore, the strain protected the nasal barrier function in a mouse model using interleukin-4 as disruptive cytokine. Hence, D. pigrum AMBR11 is a mutualist with high potential as topical live biotherapeutic product.

Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents

Increased blood–brain barrier (BBB) permeability and extensive neuronal changes have been described earlier in both healthy and pathological aging like apolipoprotein B-100 (APOB-100) and amyloid precursor protein (APP)–presenilin-1 (PSEN1) transgenic mouse models. APOB-100 hypertriglyceridemic model is a useful tool to study the link between cerebrovascular pathology and neurodegeneration, while APP–PSEN1 humanized mouse is a model of Alzheimer’s disease. The aim of the current study was to characterize the inflammatory changes in the brain with healthy aging and in neurodegeneration. Also, the cerebro-morphological and cognitive alterations have been investigated. The nose-to-brain delivery of a P-glycoprotein substrate model drug (quinidine) was monitored in the disease models and compared with the age-matched controls. Our results revealed an inflammatory balance shift in both the healthy aged and neurodegenerative models. In normal aging monocyte chemoattractant protein-1, stem cell factor and Rantes were highly upregulated indicating a stimulated leukocyte status. In APOB-100 mice, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), and interleukin-17A (IL-17A) were induced (vascular reaction), while in APP–PSEN1 mice resistin, IL-17A and GM-CSF were mostly upregulated. The nasal drug absorption was similar in the brain and blood indicating the molecular bypass of the BBB. The learning and memory tests showed no difference in the cognitive performance of healthy aged and young animals. Based on these results, it can be concluded that various markers of chronic inflammation are present in healthy aged and diseased animals. In APOB-100 mice, a cerebro-ventricular dilation can also be observed. For development of proper anti-aging and neuroprotective compounds, further studies focusing on the above inflammatory targets are suggested.

An Instant, Safe, Antihistamine, Anti-Inflammatory and Decongestant Polymeric Nasal Barrier to Prevent and To Treat Allergic Rhinitis in Children

Introduction: Allergic rhinitis (AR) in children is a common chronic pathology with a strong impact on patient quality of life. The main physiopathology affects the nasal cavity as a multi-factorial disease involving nasal mucosa damage, nasal inflammation with high concentrations of histamine, pro-inflammatory cytokines such as histamine, TNF-α, IL-4, IL-5, IL-6, IL-10, IL-13, and IgE antibodies on the nasal mucosa. Systemic entry of these proteins through damaged nasal mucosa maintains continued inflammatory and allergen cascades. Therefore, an ideal treatment should be multitarget in order to stop allergen exposure, inflammation, and nasal mucosa barrier degradation, but such treatments are nearly impossible to conceive. We envisaged an osmotic and protective nasal barrier film, not only capable of protecting the nasal mucosa from allergen exposure but also of trapping and neutralizing selected cytokines and cleaning the nasal surface continuously without using any harmful substance for children. Materials and Methods: We associated highly osmotic glycerol solution with specific plant polymers to conceive an osmotic but stable film. As plant polymers (tannins) can bind with selective proteins, a range of glycerol binding non-cytotoxic polymers were screened using the sandwich ELISA method to select those having binding affinity for allergen induced nasal proinflammatory cytokines. After verifying cytotoxicity and irritant potential, a 15-day observational clinical study was performed with approval from the ethics committee on 30 children aged between 4-13, suffering from allergic rhinitis. The test product (TP) was supplied in 15-ml nasal sprays and applied 2-3 times per day for a period of 15 days. Saline solution served as control (CP). The scores of nasal and ocular symptoms, effect on quality of life, eosinophil count in nasal smears, and need for antihistamine treatment was evaluated at the start, at 30 minutes and on days 2, 3 and 15 of treatment. Results: A few specific polymers were able to bind with selected cytokines and histamine at adequate filmogen concentrations. The osmotic film was stable, non-irritant and was able to clean the nasal mucosa continuously for 4-6h after each application. Clinical observations of Total Nasal Symptom Score (TNSS) grouping the scores of nasal congestion, runny nose, sneezing, and itching, revealed a strong decrease right after the 1st treatment in both groups but the reduction was much stronger and faster with the TP. The mean TNSS score reduction was 44.74% in CP vs 83.53% in the TP group after 7 days of treatment (p&lt;0.001). Total Ocular Symptom Score (TOSS) was decreased by 21.13% and 51.41% in CP v/s 35.12 and 99.59% in TP group on days 2 and 7, respectively. Nasal smear eosinophil count was equally strongly reduced in the TP v/s CP group. No treatment-related side effects were recorded in any of the groups. Conclusion: Protecting the nasal mucosa against allergens, neutralizing inflammatory cytokines, and keeping the nasal surface clean with an osmotic polymeric film, constitute a major breakthrough for the treatment of allergic rhinitis in children. This simple but scientific and logical approach should avoid exposing children to chemicals and to their long-term side effects.

The Nasal Mutualist &lt;i&gt;Dolosigranulum pigrum&lt;/i&gt; AMBR11 Supports Homeostasis via Multiple Mechanisms

Comparing the nasal microbiome of healthy individuals and chronic rhinosinusitis (CRS) patients revealed Dolosigranulum pigrum as a species clearly associated with nasal health, although it was not yet cultured from healthy individuals. In this study, we explored the properties of this understudied lactic acid bacterium by integrating comparative genomics, habitat mining, cultivation, and functional characterization of interaction capacities. Mining 10.000 samples from the Earth Microbiome Project of 17 habitat types revealed that Dolosigranulum is mainly associated with the human nasal cavity. D. pigrum AMBR11 isolated from the nose of a healthy individual exerted antimicrobial activity against Staphylococcus aureus , and decreased proinflammatory cytokine production in airway epithelial cells and Galleria mellonella larvae mortality induced by this important nasal pathobiont. Furthermore, the strain protected the nasal barrier function in a mouse model using interleukin-4 as disruptive cytokine. Hence, D. pigrum AMBR11 is a mutualist with high potential as topical live-biotherapeutic product.

The Microbiota/Host Immune System Interaction in the Nose to Protect from COVID-19

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by variable clinical presentation that ranges from asymptomatic to fatal multi-organ damage. The site of entry and the response of the host to the infection affect the outcomes. The role of the upper airways and the nasal barrier in the prevention of infection is increasingly being recognized. Besides the epithelial lining and the local immune system, the upper airways harbor a community of microorganisms, or microbiota, that takes an active part in mucosal homeostasis and in resistance to infection. However, the role of the upper airway microbiota in COVID-19 is not yet completely understood and likely goes beyond protection from viral entry to include the regulation of the immune response to the infection. Herein, we discuss the hypothesis that restoring endogenous barriers and anti-inflammatory pathways that are defective in COVID-19 patients might represent a valid strategy to reduce infectivity and ameliorate clinical symptomatology.

T cell engagement of cross-presenting microglia protects the brain from a nasal virus infection.

The neuroepithelium is a nasal barrier surface populated by olfactory sensory neurons that detect odorants in the airway and convey this information directly to the brain via axon fibers. This barrier surface is especially vulnerable to infection, yet respiratory infections rarely cause fatal encephalitis, suggesting a highly evolved immunological defense. Here, using a mouse model, we sought to understand the mechanism by which innate and adaptive immune cells thwart neuroinvasion by vesicular stomatitis virus (VSV), a potentially lethal virus that uses olfactory sensory neurons to enter the brain after nasal infection. Fate-mapping studies demonstrated that infected central nervous system (CNS) neurons were cleared noncytolytically, yet specific deletion of major histocompatibility complex class I (MHC I) from these neurons unexpectedly had no effect on viral control. Intravital imaging studies of calcium signaling in virus-specific CD8+ T cells revealed instead that brain-resident microglia were the relevant source of viral peptide-MHC I complexes. Microglia were not infected by the virus but were found to cross-present antigen after acquisition from adjacent neurons. Microglia depletion interfered with T cell calcium signaling and antiviral control in the brain after nasal infection. Collectively, these data demonstrate that microglia provide a front-line defense against a neuroinvasive nasal infection by cross-presenting antigen to antiviral T cells that noncytolytically cleanse neurons. Disruptions in this innate defense likely render the brain susceptible to neurotropic viruses like VSV that attempt to enter the CNS via the nose.

Does using a nasal barrier dressing prevent nasal injury inpremature infants receiving nasal continuous positive airway pressure?

Commentary on: Imbulana DI, Owen LS, Dawson JA, Bailey JL, Davis PG, Manley B. A Randomized Controlled Trial of a Barrier Dressing to Reduce Nasal Injury in Preterm Infants Receiving Binasal Noninvasive Respi ratory Support. The Journal of Pediatrics 2018; https://doi.org/10.1016/j.jpeds.2018.05.026. Most widely used and effective interfaces to provide “non-invasive” respiratory support to infants involve binasal prongs, which rely upon a tight fit at the nares to transmit pressure to the distal airways, preventing atelectasis and maintaining functional residual capacity 1. NCPAP-related nasal injury is a common complication of these interfaces 2. Special dressings have been manufactured to prevent this complication and have been found to be effective in larger infants 3-5. The current study aimed to evaluate a barrier dressing in smaller, less mature infants. This manuscript described a single-centre, prospective, randomised trial comparing the use of a nasal barrier dressing to no dressing for the prevention of nasal injury in premature neonates (<30 weeks’ gestation and/or <1250 g) receiving NCPAP. The primary outcome was nasal injury as evaluated by the bedside nursing staff each shift using a standardised chart and staging system. Secondary outcomes included relevant respiratory outcomes as well as common neonatal morbidities and mortality. An additional secondary outcome involved assessment of nasal injury on photograph by a blinded evaluator. Although the study aimed to achieve 80% power to detect a 40% relative reduction in the primary outcome, the recruitment goal was not reached, and the study was stopped early after 16 months due to slow enrolment. No infants were lost during the follow-up period (until 36 weeks’ postmenstrual age). Despite not reaching the accrual goal, the investigators were able to demonstrate a reduction in nasal injury with the use of the dressing with a number needed to treat of five infants to prevent one injury. The cost analysis demonstrated that the intervention is cost-effective at the study centre. The study was underpowered for the subgroup analyses as reported. A weakness of the study relates to the assessment of the primary outcome. The bedside nurses documenting the presence and stage of nasal injury were not blinded to the treatment, introducing risk for bias. Additionally, their ability to assess for nasal injury was often limited by the presence of the nasal barrier, which obstructed the view of the area to be examined. Using photographs and a blinded evaluator would have helped overcome these limitations. This was attempted, but there were a limited number of photographs available for assessment, and ten infants had no photograph at all. This, along with the limited power of the study, renders the finding of no difference between groups in the incidence of nasal injury as found by the blinded observer difficult to interpret. Further research is required into the optimal material, design and protocol for the use of nasal barrier dressings in neonates receiving non-invasive respiratory support. Future studies should blind evaluators to the intervention to reduce the risk for bias. While further study is needed, three prospective trials have now demonstrated the efficacy of barrier dressings at preventing NCPAP-associated nasal injury 2-4. Therefore, consideration should be given to the immediate adoption of nasal barrier dressings as a cost-effective method to prevent nasal injury in this population. https://ebneo.org/2018/09/nasal-barrier-dressing None. None.

A Randomized Controlled Trial of a Barrier Dressing to Reduce Nasal Injury in Preterm Infants Receiving Binasal Noninvasive Respiratory Support

To determine whether the use of a hydrocolloid nasal barrier dressing during binasal continuous positive airway pressure (CPAP) therapy, compared with no barrier dressing, reduces the rate of nasal injury in very preterm and/or very low birth weight infants. A single-center randomized controlled trial conducted in the neonatal intensive care unit at The Royal Women's Hospital, Melbourne. Eligible infants were born <30 weeks of gestation and/or with birth weight <1250 g, and had received ≥4 hours, but <48 hours, of CPAP. Infants were randomly allocated to receive either a hydrocolloid nasal barrier dressing during CPAP (barrier group), or no barrier dressing (no barrier group). The primary outcome was the incidence of any nasal injury during CPAP support, until the infant was both >30 weeks of postmenstrual age and >1250 g, unless CPAP therapy was stopped earlier. Nasal injury was regularly assessed by bedside nurses using a standardized form. A total of 108 preterm infants were enrolled: 53 infants in the barrier group and 55 infants in the no barrier group. Infants in the barrier group had a significantly lower rate of nasal injury compared with the no barrier group: 18 of 53 (34%) vs 31 of 55 (56%), respectively (P = .02), number needed to treat; 5 infants. No significant differences were detected in any secondary respiratory outcomes, or in the rate of common neonatal morbidities. Prophylactic use of a nasal barrier dressing within 48 hours of commencing treatment with binasal CPAP in very preterm or very low birth weight infants reduces nasal injury. Australian and New Zealand Clinical Trials Register ACTRN12616000438459.