The management of upper airway diseases: an ongoing challenge for the clinician.

Upper airway diseases are widespread in clinical practice. However, some aspects are still debated. The current supplement presents and discusses the most common disorders encountered in daily medical activity. The COVID-19 dramatic pandemic requires an urgent solution. Promising non-pharmacological agents are discussed. Chronic diseases are frequent in childhood, so to know risk factors is useful in their management. Allergic rhinitis and chronic rhinosinusitis should be treated with anti-inflammatory drugs, but complementary compounds should be alternated to preserve health. Empty nose syndrome is a frequent complication of nasal surgery and requires adequate staging and hydrating procedure. Lastly, laryngopharyngeal reflux is an intriguing challenge for the clinician. Alginates represent a safe and effective way to relieve LPR symptoms.

The management of chronic rhinosinusitis in clinical practice: An International Survey.

Chronic rhinosinusitis (CRS) is a common disease and is currently classified in two main phenotypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). A panel of international experts conducted the present survey. A questionnaire, containing 25 questions, was completed by each member of the panel. About half of patients with suspected CRS had confirmed diagnosis. CRSwNP affected 31% of CRS patients. Endoscopy and CT were ever performed. Rhinitis and asthma were frequent comorbidities. Intranasal corticosteroids were prescribed on average in 86% of patients. Nonadrenergic compounds were prescribed by 71% of experts. Surgery for CRSwNP was performed in about half of patients; repeated intervention occurred in about one/third. In conclusion, the current survey demonstrated that CRS requires thorough diagnostic work-up, and the most common therapeutic approach is mainly based on intranasal corticosteroids, non-adrenergic decongestants, and surgery.

Prevention and treatment of upper respiratory diseases in the pandemic COVID-19 era.

In the pandemic coronavirus disease 2019 (COVID-19) era, the need to use preventive-curative treatments is compelling. A series of non-pharmacological compounds, including oligo-elements, vitamins, nutraceuticals, and bacteriotherapy, might affect the risk of COVID-19, both reinforcing the immune system and improving the inflammation resolution during respiratory infections. Non-pharmacological remedies are very popular and usually have no relevant side effects. Bacterial and natural products may potentiate the immune system against respiratory viruses. Moreover, these compounds also exert antiinflammatory and antioxidant activity. Consequently, these non-chemical remedies could be prescribed to build up the immune defence and adequately treat the upper respiratory infection. In this way, natural compounds could be used to manage people in the pandemic COVID-19 era.

Lactoferrin: a potential candidate to fight respiratory infections in the pandemic COVID-19 era.

Respiratory infections are a significant burden at any age, but especially in childhood and aging. The COVID-19 pandemic has worsened the issue since there is no specific treatment and vaccine is not available. Moreover, respiratory symptoms cause social stigma in subjects suffering from an infection of any kind. As new drugs require a very long time to be marketed, a natural compound's interest is growing. In this regard, lactoferrin is a multifunctional protein present in secretions, mainly in breast milk. Lactoferrin has marked antimicrobial activity, including antibacterial, antiviral, antiparasitic, and antifungal. Moreover, lactoferrin strongly affects immune response and cellular control activity. Therefore, this natural component could provide a promising effect in preventing respiratory infections and potentially also for COVID-19.

Glycyrrhizin for topical use and prophylaxis of COVID-19: an interesting pharmacological perspective.

COVID-19, the disease caused by the SARS - CoV - 2 pathogen, is currently a pandemic. At the moment there is not an available vaccine, so, scientific community is looking for strategies and drugs to implement prevention and prophylaxis. Several compounds are examined for this purpose. Glycyrrhizin, an alkaloid extracted from licorice plant (glycyrriza glabra), is one of the most studied molecules, both for its peculiar biological functions and for its pharmacological effects. This brief review aims to highlight the characteristics of glycyrrhizin for topical use on the nasal and ocular surfaces. The anti-inflammatory activity, the ability to inhibit the accumulation of ROS, the antiviral property, but, above all, the ability to bind the ACE receptor and the SARS - CoV-2 protein S in the extracellular environment make Glycyrrhizzin for topical use a compound with a high prophylactic potential for SARS - CoV - 2 infection, also due to its low cost and the absence of significant side effects.

Can Pseudomonas aeruginosa growth be modulated by natural compounds?

Pseudomonas aeruginosa is an opportunistic human pathogen that frequently induces antibiotic resistance, as it mainly tends to form biofilms. Iron chelation may be an intriguing strategy to contrast bacterial growth. Lactoferrin is a natural compound able to chelate iron. A new multi-component medical device also contains lactoferrin. This study analyzed this compound investigating the in vitro capacity to inhibit Pseudomonas aeruginosa growth. In conclusion, this study demonstrated that a multicomponent medical device (Saflovir), also containing lactoferrin, could inhibit the in vitro growth of P. aeruginosa. This activity could be positively used in the prevention of respiratory nasal infections.

Laryngopharyngeal reflux management in clinical practice.

Laryngopharyngeal reflux (LPR) is an inflammatory reaction of the mucosa of the pharynx, larynx, and other associated upper respiratory organs, caused by a reflux of stomach contents outside the esophagus. LPR is considered a relatively new clinical entity with a vast number of clinical manifestations that are sometimes treated empirically and without a correct diagnosis. Alginate is a reasonable therapeutic option as a first-line or add-on option. A survey included 35 Italian otorhinolaryngologists. The survey considered ten practical queries. LPR is a common disease in clinical practice. History and fiber-optic endoscopy constitute the main diagnostic tools. Alginates represent a frequent medication to treat LPR both as first-line and add-on. The mean effectiveness rate is 44% for first-line choice and 76% for the add-on. In conclusion, the current survey provided exciting information about the management of LPR in clinical practice.

Magnesium alginate in patients with laryngopharyngeal reflux.

Laryngopharyngeal reflux (LPR) is a common disease caused by the leaking beck of gastric material out of the esophagus. The main symptoms are dysphonia, dysphagia, and cough. There is an established use of proton pump inhibitors (PPI) in patients with suspected LPR in common practice. This habit is translated by the standard strategy to use PPI in treating patients with gastroesophageal reflux. However, PPI can not wholly inhibit all types of reflux and are burden by adverse effects. Alginate, a derivative from algae, is devoid of side effects and effectively counteracts gastric material reflux forming a foaming gel in the stomach. The current study enrolled 100 outpatients with LPR. Alginate treatment was administered for two months. Patients underwent four visits (at baseline and 15, 30, and 60 days after treatment). A visual analog scale assessed the perception of dysphonia, dysphagia, and cough. Alginate significantly (p<0.0001) reduced all parameters. Therefore, the current study demonstrated that magnesium alginate was effective and safe in LPR treatment.

The impact of Allergic Rhinitis in clinical practice: An International Survey.

Allergic rhinitis (AR) is a frequent disease caused by an IgE-mediated inflammation of the nose and characterized by typical symptoms. Diagnostic workup is directed to document the production of specific IgE (sensitization). Clinical management aims to relieve symptoms, resolve allergic inflammation, use medications, and potentially induce allergen tolerance, using allergen immunotherapy (AIT). The current survey was conducted in 17 International ear nose throat experts using a questionnaire with 20 questions concerning the practical management of AR patients. It was administered in the 2020 summer. The large majority (94%) of participants use the ARIA classification in clinical practice. On average, subjects with suspected AR represent half of the patients who turn to the ENT experts; 80% have the confirmed diagnosis. Most of the experts use both cutaneous and serum assay to document IgE production. Antihistamines are prescribed in 59% of AR patients, intranasal corticosteroids in 69%, non-adrenergic decongestants in 88%, nasal lavage in 88%, and AIT in 22%. About 68% of AR patients had turbinate hypertrophy, which requires surgery in 62% (mostly surgical decongestion). In conclusion, the current International Survey demonstrated that AR is a common disorder worldwide, the diagnostic workup is mainly based on IgE assessment, and the therapeutic approach is also based on non-pharmacological remedies.

Glycyrrhetinic acid suppressed hmgb1 release by up-regulation of Sirt6 in nasal inflammation.

To extend our understanding of previous studies on the pathogenesis and mechanism of high mobility group box 1 (HMGB1) in chronic rhinosinusitis with nasal polyps (CRSwNP), here we show that Sirtuin 6 (Sirt6), one of the Sirtuin family members which are widely studied in aging, DNA repair, metabolism, inflammation and cancer, was expressed in normal nasal mucosa using immunohistochemical staining and Western blot assay. Sirt6 expression levels were decreased in CRSwNP tissue. Sirt6 expression levels were modulated by small interfering RNA transfection in human nasal epithelial cells (HNE). We found that depletion of Sirt6 suppressed the number of human nasal epithelial cell cilia, and dramatically induced HMGB1 translocation from nucleus to cytoplasm in the HNE cells. Glycyrrhizic acid (GA) and glycyrrhetinic acid (GTA) are specific chemical compounds that may be isolated from the licorice plant. GTA has been shown to have anti-inflammatory and anti-allergic activity: it binds selectively to HMGB1 protein released extra-cellularly and inhibits its cytokine activities through a scavenger mechanism on the protein accumulation. In an in vitro study we used the 18-ß-stereoisomer of GTA to enhance Sirt6 expression levels, inhibiting through this mechanism the translocation of HMGB1 protein from nucleus and reversing its extracellular accumulation stimulated by lipopolysaccharides. These findings reveal a previously unknown role for nasal mucosa steady-state conditions in the control of Sirt6 activity, and provide evidence for a relationship between HMGB1 and Sirt6 in CRSwNP, and promising benefits of glycyrrhetinic acid for CRSwNP patients.

Managing turbinate hypertrophy: coblation vs. radiofrequency treatment.

The role of inferior turbinate hypertrophy in the reduction of nasal airflow is well established. Although chronic nasal obstruction is not life- threatening, it significantly impairs patients' quality of life, affecting many aspects of daily activities; therefore, patients seek medical intervention. 40 patients were selected (27 males and 13 females) between 27 and 64 years of age with a symptom of nasal obstruction. The patients were divided in two groups: Group 1: coblation, 25 patients (18 males and 7 females); Group 2: radiofrequency, 15 patients (7 males and 6 females). These 40 patients were followed for 3 years. Patients were analyzed using both subjective and objective methods. The visual analog scale (VAS) subjective data and objective data including both active anterior rhinomanometry and acoustic rhinometry were recorded and analyzed. Data were collected pre-operatively and at 1 and 3 years post-operatively. According to our data, both coblation and radiofrequency turbinate reduction benefit patients with good results. The complications, found during the follow-up, are limited to minimal bleeding and crusting. Coblation and radiofrequency were significantly less painful than others procedures during the early post-operative period. In our study, both coblation and radiofrequency provide an improvement in nasal airflow with a reduction in nasal obstructive symptoms in the short term, but their efficacy tended to decrease within 3 years.

Values of SP-A protein in the nasal mucosa.

The paranasal sinus epithelium is exposed to the environment and therefore to a variety of biological, chemical and mechanical insults. Surfactant protein A (SP-A) is a 34-36 kD pulmonary surfactant-associated protein that appears to play an important role in mammalian first-line host defence. Recent studies have reported the possibility of local production of SP-A in the extrapulmonary organs and tissues of the human body. However, the presence of SP-A in the human paranasal sinus mucosa is not well known. The purpose of this study was to investigate the expression of SP-A protein in human turbinate mucosa and to compare the expression of SP-A mRNA in normal turbinate mucosa and turbinate mucosa of chronic rhinosinusitis patients. Reverse transcriptase polymerase chain reaction was used to detect SP-A mRNA. Student's t test was used for statistical comparison of the SP-A/GAPDH-mRNA ratio (GAPDH: glycerinaldehyde-3-phosphate dehydrogenase) of cases and controls. We found expression of SP-A mRNA in mucosa lining the inferior turbinates of healthy patients and its up-regulation in mucosa lining the inferior turbinates of patients with chronic rhinosinusitis. These results may provide targets for new therapies for chronic rhinosinusitis.

Are HMGB1 protein expression and secretion markers of upper airways inflammatory diseases?

Taking into account the mechanisms at the origin of the airways inflammatory pathologies, our attention has been recently addressed to the study of HMGB1, a protein belonging to the group of alarmins. Alarmins are those molecules which in homeostatic conditions carry out specific metabolic and/or structural functions; furthermore, after a direct trauma or an infection, these molecules are released in the extracellular milieu becoming there activators of the innate immunity and powerful inflammatory factors. In a previous research we found in patients affected with chronic rhinosinusitis with/without nasal polyposis (CRSwNP) an increased expression of this protein in the nucleus of nasal mucosa epithelial cells. HMGB1 was overexpressed also as focal subepithelial infiltration and in the inflammatory cells of patients in comparison with controls. These results suggested a possible pathogenetic role of HMGB1 in CRSwNP. The aim of the present study was to investigate if the expression and localization (nuclear, cytoplasmic and extracellular) of the HMGB1 protein-cytokine is somehow related to the severity and complexity of the histological and clinical picture. We noticed values which have around statistical significance between nuclear HMGB1 and eosinophils infiltrate (p=0.0607) and between nuclear HMGB1 and inflammatory infiltrate (P=0.0524). Even more significant was the correlation between extra-cellular HMGB1 expression and the presence of allergic-hyper reactive conditions such as asthma, allergic rhinitis, NSADs intolerance, antibiotic allergy. HMGB1 was significantly more expressed in the nucleus (p=0.0499) and in the intercellular space (p=0.0380) in allergic patients than in non-allergic subjects and as extra-cellular infiltrate in patients with NSADs intolerance (p=0.0022). These results confirm the role of HMGB1 in the pathogenesis of chronic rhinosinusitis with/without nasal polyposis; besides the higher extra-cellular expression in patients with a more severe clinical and inflammatory picture and the presence of associated co-morbidities suggests to seek for new compounds: these compounds, decreasing the extra-cellular release of this alarmin through a scavenger mechanism, could keep under control the inflammatory process without interfering with the nuclear transcriptional messengers.

Spa therapy of upper respiratory tract inflammations.

The upper airway respiratory diseases (i.e. common cold, allergic rhinitis, nonallergic/vasomotor rhinitis, acute and chronic rhinosinusitis and nasal polyposis) in which nasal congestion is a common symptom are often undertreated due to the frequent inadequate efficacy and safety concern with current therapies. In scientific literature, few studies seem to support the hypothesis that nasal inhalatory treatment with thermal water promotes the improvement of nasal symptoms, even if the mechanisms by which the improvement from SPA therapy can be expected remain debated. A prospective comparative study with a pre-post design has been performed consecutively enrolling 33 (males 70 %) patients of both genders older than 12 years of age, affected by chronic sinonasal inflammation. All patients underwent a 14-days course of radioactive water warm vapour inhalations followed by nasal aerosol of the same thermal water 10 min each once/day at Merano Therme. At the beginning and end of the study, in all the subjects, nasal function evaluation by active anterior rhinomanometry, mucociliary transport time (MCTt) determination and nasal cytology were performed. After the inhalatory treatment, the mucociliary function was improved and the pathologic mucociliary transport times recorded at the beginning of the study being significantly reduced to physiologic ones. Besides, before treatment, the cytologic picture showed an inflammatory cell infiltration (eosinophils, neutrophils with/without bacteria, mast cells) in 37 % of patients; after therapy in 66 % of these patients, the rhinocytogram was normal. Our results suggest, according to the literature data, that SPA therapy with radioactive water could represent an alternative choice in chronic inflammatory diseases of the upper airways, nonresponsive to pharmacological therapy.

The intranasal trigeminal system: roles in rhinitis (allergic and non-allergic).

The aim of this paper is to review intranasal trigeminal system and associated reflexes. The literature survey was performed on PubMed, ProQuest Central database of Kirikkale University and Google Scholar. The intranasal trigeminal system and associated reflexes play an important role in humans in both health and disease, including in rhinitis of non-allergic and mixed type. The intranasal trigeminal nerve provides sensory perception to the lining of the nose, supplying information on how patent the nasal airway is and responding to various chemical signals. The reflexes known to exist within the intranasal trigeminal system are nasobronchial reflex, trigemino-cardiac reflex, nasogastric reflex, and nasal cycle. The intranasal trigeminal system and its reflexes play a vital role in normal human physiology. Alterations in how this system operates may underlie multiple forms of rhinitis and more research is needed to fully understand the mechanisms involved.

Mechanisms and solutions for nasal drug delivery - a narrative review.

The aim of this paper is to review mechanisms and solutions for nasal drug delivery. Literature survey was performed via PubMed, Google Scholar, Google, and ProQuest Central database of Kirikkale University. The nasal lining presents a large area of endothelium of variable permeability and with a rich vascular supply. Advantages of this route include eliminating first-pass metabolism and being easily accessible. The nasal route enables some agents which are otherwise difficult to administer to enter the systemic circulation, for example, low molecular mass compounds with high polarity, peptides, or proteins. There are three principal factors that influence the extent to which drugs can be absorbed through the nasal lining, namely the physico-chemical characteristics of the drug molecule itself, the action of the mucociliary system within the nose, and the presence of any factors increasing nasal absorption. A key factor limiting the use of the intranasal route of administration is insufficient absorption through the nasal mucosa. A number of drugs in development cannot be administered intranasally because their bioavailability following nasal administration is too low. There has been considerable research focus on methods to enhance absorption via the nasal mucosa. In this chapter, we review the literature related to this problem and discuss potential solutions.

Antibacterial and antibiofilm effects of radioactive thermal water.

OBJECTIVE: Most of the infections of the upper respiratory tract are caused by biofilm-forming microorganisms belonging to the Pseudomonas, Streptococcus, Staphylococcus, and Enterobacter genus. Many of these microorganisms also show antibiotic resistance, partly related to biofilm formation. The treatment of these affections may include inhalation of radioactive thermal water (RTW). The present study aimed to evaluate the in vitro antibiofilm effect of RTW collected from Merano springs, Italy. MATERIALS AND METHODS: A series of experiments were performed evaluating the effect of RTW against planktonic cultures (1 h exposure) and on biofilms (10 min and 1 h exposure) formed by Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Viable biomass was assessed using a colorimetric assay. A model based on the infection by the same strains of a reconstituted human respiratory epithelium (RHRE) was used to morphologically evaluate the antibiofilm effect of RTW. RESULTS: RTW decreased the viability of S. aureus and S. pneumoniae planktonic cultures by about 20%. RTW also decreased biofilm viability by all strains except for E. coli at both time points. In the RHRE model, bacterial adherence and colonization occurred in all specimens, showing a particular affinity for the epithelium's cilia. Bacterial infections caused significant alterations in the epithelium structure, showing enlargement of the intercellular spaces, and damage to the cell structure. Specimens infected with S. aureus showed slightly lower colonization levels after RTW treatment. CONCLUSIONS: Results of this in vitro study showed a significant effect of RTW against Gram-positive planktonic bacterial cells as well as a significant antibiofilm activity.

Foreign bodies causing asphyxiation in children: the experience of the Buenos Aires paediatric ORL clinic.

Inhalation or aspiration of a foreign body (FB) occurs relatively frequently in young children. The size, shape, type and site of arrest of the FB lead to variability in the clinical picture. The present study included data from 65 cases of FB inhalation presenting over 1 year at the Children's Hospital Gutierrez, Buenos Aires, Argentina, compared with information from four well-known published case series chosen as representative of other cultural and geographical backgrounds: the USA, Europe, North Africa (Egypt) and Asia (India). The mean age of children studied was 4.03 years. Injuries happened mainly at home (53 cases [81.54%]) and under adult supervision (59 cases [90.77%]). The most frequently inhaled FB was nuts, however, in contrast to previous reports, the majority of incidents involved inhalation of an inorganic, rather than an organic (food) FB. Complications included pneumonia (three cases), atelectasis (two cases) and pneumonitis (one case). No deaths were recorded. These data suggest that children play with objects inappropriate for their age, such as pins and nails, that adults may not be aware of the choking risks, and that more effort is required in educating caregivers about these risks.