Rhinosinusal Inflammation and High Mobility Group Box 1 Protein: A New Target for Therapy.

BACKGROUND/AIMS: High mobility group box 1 (HMGB1) is a protein belonging to the class of damage-associated molecular pattern molecules, which activates innate immunity and powerful inflammatory factors. The aim of this review is to show the importance of HMGB1 in the pathogenesis of nasal inflammatory diseases and to suggest that inhibition of HMGB1 may be an innovative therapeutic target. METHODS: We used immunohistochemistry to study whether HMGB1 increases in chronic rhinosinusitis with nasal polyps and whether its expression is associated with eosinophils and inflammatory cytokines. Using primary cultures of human nasal epithelial cells, we localised lipopolysaccharide-induced active translocation and release of HMGB1 by immunofluorescence assay and Western blot. RESULTS: Patients with severe symptoms have the highest HMGB1 serum levels. Glycyrrhetic acid inhibits the chemotactic and mitogenic function of HMGB1, binding to the hydrophobic residues that delimit the pockets in box A and B. CONCLUSIONS: Chronic inflammatory diseases of the nose and paranasal sinuses are increasingly prevalent and are a financial burden for society. HMGB1 has been shown to play a role in several inflammatory diseases of otolaryngological interest. The inhibition of HMGB1 may be an innovative therapeutic target for patients with chronic upper airway inflammatory diseases having nasal obstruction as a major symptom.

A prospective open-label study to assess the efficacy and safety of a herbal medicinal product (Sinupret) in patients with acute rhinosinusitis.

AIMS: We present a multicenter, prospective, open-label study to assess the efficacy and safety of a phytomedicine. The aim of the research was to evaluate the efficacy and safety of 14 days of treatment with Sinupret for acute rhinosinusitis. Sinupret is a herbal preparation used to restore and maintain the physiological function of the membranes in the sinus cavity. METHODS: Sixty patients with acute rhinosinusitis based on the EPOS guidelines were enrolled in the study. Thirty patients were treated with Sinupret Forte, while 30 patients were treated with intranasal fluticasone furoate. The criteria for the evaluation of efficacy were the major symptom scores according to the investigator and the Health-Related Quality of Life score. The criteria used to evaluate safety were the number of patients with adverse events, the patients' vital signs, and laboratory safety. RESULTS: All patients considered showed significant improvements in symptoms. Among the patients treated with Sinupret, none had an adverse event, while 3 patients treated with fluticasone furoate had minor adverse events. The patients' vital signs and laboratory values were normal. CONCLUSIONS: The results of this study suggest that this phytomedicinal preparation has a significant level of efficacy in acute rhinosinusitis and that treatment is safe.

PLUNC proteins positivity in patients with chronic rhinosinusitis: a case-control study.

INTRODUCTION: Innate immunity is the first protection against microorganisms. Nowadays, there is a growing interest in innate immune molecule known as palate, lung, nasal epithelial clone (PLUNC). PLUNC is a specific product of the airways, of approximately 25 kDa, encoded by adjacent genes found within a 300 kb region of chromosome 20; these proteins must be detected predominantly in the upper respiratory tract. MATERIALS AND METHODS: We performed a case-control study to investigate the presence of this protein in nasal tissue of patients affected by chronic rhinosinusitis. 59 patients were enrolled (44 cases, 15 controls). We have examined the correlation between the presence of pathology and the PLUNC proteins positivity. RESULTS: 100% of controls have a +++ rated PLUNC proteins positivity, while cases have a lower percentage of positivity. We used χ (2) statistical test to analyze the results of the study and there is a difference statistically significant between cases and controls in PLUNC proteins positivity. CONCLUSIONS: These observations suggest that, in response to agents or chemical factors, nasal mucosal epithelium will react and produce PLUNC proteins. So PLUNC proteins have a protective function on upper airways mucosa, as we can see by evaluating the high positivity in control group.

Local allergic rhinitis: considerations.

The term "local allergic rhinitis" has gained popularity as a clinical entity in recent years. Despite the apparent contradiction in the definitions of "nasal" and "local," we offer insights based on our extensive experience in the field. Local allergic rhinitis has been recognized and treated for many years, so it is not a new discovery. The nasal provocation test, which was introduced in the 1980s, was critical in identifying allergic rhinitis cases with suggestive symptoms but negative allergy tests. Our reflections aim to contribute to a precise terminological decision that is consistent with various points of view.

Rhinosinusitis: clinical-based phenotyping.

Rhinosinusitis (RS) is a common disease and is currently classified into two main types: acute RS (ARS) and chronic RS (CRS), which in turn includes CRS with or without nasal polyps. Different guidelines consider this classification. However, in clinical practice, other phenotypes exist. The current article would propose new clinical-based phenotyping of RS, including the following clinical phenotypes: simple catarrhal RS, Acute RS, acute bacterial RS, severe (complicated) acute RS, chronic RS, and recurrent chronic RS. Treatment strategy should be tailored considering the clinical phenotype and could include phytomedicines, intranasal non-pharmacological remedies, and local bacteriotherapy. In conclusion, RS requires thorough diagnostic work-up, and the therapeutic approach should be mainly based on appropriate management.

HMGB1-antagonism exerted by glycyrrhizin could be fruitful against COVID-19.

The COVID-19 pandemic era is causing a relevant issue for the health. There is no specific drug able to antagonize the SARS-CoV-2 infection. As a consequence, there is growing interest about potential molecules able to contrast infection. In this regard, HMGB, an alarmin, may play a relevant role in pathogenic mechanisms induced by SARS-CoV-2.  As HMGB1 is antagonized by glycyrrhizin, this substance could be potentially useful as ancillary treatment in COVID-19.

A randomized, double-blind, placebo- -controlled study to investigate the use of bacteriophages in patients with chronic rhinosinusitis with nasal polyps.

Background A randomized, double-blind placebo-controlled study investigated the use of bacteriophages in the treatment of chronic rhinosinusitis with nasal polyps. Materials and Methods 40 adult patients with сhronic rhinosinusitis with nasal polyps were examined. All patients underwent functional endoscopic sinus surgery. After the surgery, 20 patients got the intranasal gel with a bacteriophages mixture (Otofag, Micromir, Russia) twice a day for ten weeks, and 20 patients got a placebo. Results On the 10th day, IL-1ß secretion diminished (63 mg/ml versus 440 mg/ml in control). There was a decrease in the total number of microorganisms and Enterobacteriaceae (5.7 x 106 CFU/ml versus 1.2 x 109 CFU/ml in control), and the absence of Streptococci (versus 2.1 x 109 CFU/ml in control) on the 30th day of the treatment in the group with the bacteriophages. On the 10th day, a decrease in the activity of secretory IL-1ß and IL-8 strongly and very strongly correlated with a total number of microorganisms (r = 0.7; r = 0.9 respectively), as well as secretory IL-8 with Enterobacteriaceae (r = 0.72) and Staphylococci (r = 0.65) in the active group treated with the bacteriophages. On the 30th day, the decrease in serum IL-1ß significantly correlated with the total number of microorganisms (r = 0.80) and enterobacteria (r = 0.90) in the active group. Conclusions The administration of bacteriophages restored the balance of microorganisms in the nasal cavity and decreased the inflammatory response in chronic rhinosinusitis with nasal polyps. These changes, such as an inflammation dampening, could theoretically reduce the recurrent growth of polyp tissue in the future.

HMGB1 in nasal inflammatory diseases: a reappraisal 30 years after its discovery.

INTRODUCTION: High mobility group protein box 1 (HMGB1) is a protein belonging to the alarmin family. HMGB1 has a relevant role in starting the inflammatory cascade by means of receptors, such as RAGE and TLR. HMGB1 supports transcription of many genes in interactions with many transcription factors, including NF-kB. The axis HMGB1-RAGE-NF-kB has, therefore, a pivotal role in the inflammatory cascade. HMGB1 controls the production of several pro-inflammatory cytokines and the proliferation and activation of many inflammatory cells. AREAS COVERED: The present report concerns the role of HMGB1 in nasal inflammatory disorders, including allergic and non-allergic rhinitis, and chronic rhinosinusitis with nasal polyps. HMGB1 modulation has been the aim of several studies. The literature search included recent papers that covered this topic. EXPERT OPINION: As HMGB1 has a pivotal role in inflammatory events, its modulation could be attractive for designing new therapeutic strategies. In this regard, glycyrrhetic acid (GA), the active component of Glycyrrhiza glabra, can efficiently block HMGB1. Promising reports seem to suggest that GA could exert favorable anti-inflammatory activity in patients with nasal inflammatory disorders.

The impact of allergic rhinitis in clinical practice: an Italian Survey.

Allergic rhinitis (AR) is a very common disorder. The current Survey was conducted on a sample of about 5,000 adult subjects in 5 Italian cities. A questionnaire, containing 15 questions, was administered on the road. AR affects about 20% of the general population. The most common diagnostic test was the skin prick test, but only 12% of patients performed an allergy test to confirm the diagnosis. About 50% of patients did not take any medicine. Even about 40% of treatments were suggested by friends or pharmacists. In conclusion, the current Survey demonstrated that AR is a common disorder in Italy, the diagnostic work-up is still incorrect, and the therapeutic approach does not adhere to the guidelines. Therefore, there is a need to implement adequate information on this topic in Italy.

Chronic rhinosinusitis with nasal polyposis: the role of personalized and integrated medicine.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a frequent disorder. From a clinical and an immunopathological point of view, different phenotypes and endotypes have been identified. The frequent comorbidity with asthma allowed to pave the way to the use of biological agents for the treatment of CRSwNP. Biological agents are targeted to antagonize IgE, interleukin (IL) 4, IL-5, and IL-13 at present. However, a correct and appropriate workup is mandatory, mainly concerning the exact definition of the specific pheno-endotype. The preliminary outcomes are promising, even though there is a need for well-established indications, criteria of responsiveness, duration, and safety. On the other hand, this personalized medicine could be fruitfully integrated with gold-standard medications, such as intranasal corticosteroids. As CRSwNP is a chronic disorder, treatment should be long-lasting, so complementary anti-inflammatory treatments could be opportunely integrated and/or alternated to steroids.

A comparison between mometasone furoate nasal spray and intranasal glycyrrhetic acid in patients with allergic rhinitis: a preliminary study in clinical practice.

Allergic rhinitis (AR) is caused by an IgE-mediated inflammatory reaction consequent to the exposure to the causal allergen. Glycyrrhetic acid (GlyAc) is a natural compound extracted from the liquorice that exerts anti-inflammatory activity. This real-life study compared intranasal GlyAc, present in a medical device containing also glycerol and mannitol, with mometasone furoate nasal spray (MFNS) in 50 adult outpatients with AR. Both treatments lasted 2 months. Endoscopic signs, perception of symptom severity, assessed by VAS, and nasal function measured by rhinomanometry were evaluated at baseline (T0), after one (T1) and two (T2) months. The intergroup analysis showed that at T1 there was no significant difference between groups about the use of decongestants and antihistamines, turbinate hypertrophy and pale mucosa, perception of olfaction and snoring. At T2 there was no significant difference between groups about use of relievers, all endoscopic signs, and perception of nasal discomfort, nasal obstruction, olfaction, and snoring. The intragroup analysis showed that in MFNS group there was a significant change during the entire period of treatment for all parameters except watery rhinorrhea (sign) and ocular discomfort; in GlyAc group there was a significant change during the entire period of treatment for all parameters. In conclusion, this preliminary study, conducted in clinical practice, evidenced that intranasal CysAC plus mannitol was able to significantly improve nasal endoscopic signs, perception of symptoms, and nasal function in patients with AR. Therefore, GlyAc could be a reasonable therapeutic option to control allergic inflammation.

Preventive nasal bacteriotherapy for the treatment of upper respiratory tract infections and sleep disordered breathing in children.

OBJECTIVES: The purpose of this prospective study was to assess the effectiveness and safety of Streptococcus salivarius 24SMBc administered as a nasal spray in children affected by recurring infections of the upper airways, adenotonsillar hypertrophy, and sleep disordered breathing (SDB). METHODS: Prospective study on 42 children with SDB. Anamnestic and general examination data were collected using the 'Sleep Clinical Record' (SCR) questionnaire during the first inspection and after three months of treatment with Streptococcus salivarius 24SMBc nasal spray. Quantitative variables were statistically compared. RESULTS: After three months, the enrolled patients showed lower SCR scores than during the first inspection (6.0 vs 7.5 p < 0.000), with a significant reduction of nasal obstruction (p = 0.001) and oral breathing (p = 0.04), and a positive Brouillette Score (p = 0.001). The children and parents did not declare any adverse reactions during the three months of treatment. CONCLUSIONS: This series confirms the effectiveness and safety of Streptococcus salivarius 24SMBc treatment in children affected by recurring upper respiratory tract infections, adenotonsillar hypertrophy, and sleep disordered breathing.

HMGB1 in the Pathogenesis of Nasal Inflammatory Diseases and its Inhibition as New Therapeutic Approach: A Review from the Literature.

Introduction This study is a systematic review on recent developments about the importance of HMGB1 protein in the pathogenesis of rhino-sinusal inflammatory diseases. We also report data on the use of 18-ß-glycyrrhetic acid (GA), which has been shown able to inhibit the pro-inflammatory activities of HMGB1, in young patients affected by allergic rhinitis and complaining of nasal obstruction as main symptom. Objectives The objective of this study was to review the literature to demonstrate the importance of HMGB1 in the pathogenesis of nasal inflammatory disorders and understand whether the inhibition of this protein may be an efficacious and innovative therapeutic strategy for patients with rhino-sinusal inflammation. Data Synthesis Authors searched for pertinent articles indexed in PubMed, Scopus, and other health journals between 2004 and 2015. In total, the authors gathered 258 articles: 219 articles through Pubmed and 39 articles from other search engines. The search terms used were as follows: HMGB1 AND "respiratory epithelium," "airway inflammation," "rhinitis," "allergic rhinitis," "rhinosinusitis," "nasal polyposis," "glycyrrhetic acid," "children." Conclusions Patients with severe symptoms have the highest serum levels and the highest extracellular expression of HMGB1. GA inhibits HMGB1 chemotactic and mitogenic function by a scavenger mechanism on extracellular HMGB1 accumulation stimulated by lipopolysaccharides in vitro. Treatment of allergic rhinitis with GA is not associated with local or systemic side effects in children and adults.

Radon-enriched hot spring water therapy for upper and lower respiratory tract inflammation.

Background Radon-222-enriched hot spring therapy, which is characterized by a safe level of radioactivity, is used for the treatment of rheumatic disorders, and its efficacy has already been studied in several clinical trials. Radon-water inhalation therapy for the treatment of upper and lower airway inflammatory diseases is used in many hot springs centers. However, its application has not been reviewed to date. Methods We systematically searched the PubMed and Scopus databases for clinical trials published in the last 20 years in which objective parameters of upper and lower airway function had been tested before and after radon-enriched inhalation treatment. Results Four prospective studies were found: 1 asthma trial, 1 placebo-controlled chronic rhinosinusitis trial, 1 upper respiratory tract inflammation with nasal obstruction trial, and 1 case-control allergic rhinitis trial. Patients were treated with nasal inhalations of radon-enriched water for 12 to 28 days and were assessed at baseline and after therapy. After 2 weeks of treatment, nasal resistance decreased, flow increased, mucociliary clearance was enhanced, ciliated-to-muciparous cell ratio increased, and %FEV1 increased in asthmatic patients. Conclusion Radon-enriched inhalation therapy improves objective indicators of nasal function in allergic rhinitis and chronic rhinosinusitis, and causes relief of pulmonary obstruction in asthma.

High-mobility group box protein 1 expression in inflammatory diseases of the middle ear.

High-mobility group box 1 (HMGB1) is a nuclear non-histone protein, playing a critical role as a mediator between innate and acquired immunity; when released extracellularly, it coordinates the cellular stress response (under necrosis, bacterial lipopolysaccharide stimulation) and acts as an inflammatory marker and cytokine. The aim of the study was to demonstrate whether HMGB1 is over-expressed in chronic middle-ear pathologies and whether the entity of expression and the localization are correlated with the degree of the inflammatory reaction, thus suggesting that HMGB1 may play a crucial role in chronic inflammatory disorders of the middle ear, as already demonstrated in other airway diseases. We analyzed 30 samples of middle-ear mucosa in patients affected by chronic suppurative otitis media with ear drum perforation with/without cholesteatoma and otosclerosis as control. The distribution of HMGB1 was evaluated as nuclear, cytoplasmic, and/or extracellular staining. The inflammatory cells observed in the biopsies were mostly lymphocytes and plasmacells. A statistically significant difference in inflammation score between otosclerosis and chronic otitis samples ( P < 0.01; Anova test) and between otosclerosis and cholesteatoma samples ( P < 0.05; Anova test) was observed; the HMGB1 positivity was in accordance with the density of the inflammatory infiltrate. HMGB1 is over-expressed in chronic middle-ear pathologies and may play a role in the progression of the inflammatory process from recurrent acute otitis media to chronic suppurative otitis media.

Nasal Muco-ciliary transport time alteration: efficacy of 18 B Glycyrrhetinic acid.

BACKGROUND: Mucociliary clearance is the main self-clearing system of the nasal cavity and paranasal sinuses.This is a very important means of non specific defence against continuous organic and inorganic contamination conveyed by air. It works by trapping particles and microorganisms in the mucus and then by transporting the mucous film to the pharynx where it is eliminated with a cough or swallowed. Its congenital or acquired abnormalities are involved in the occurrence of widespread infectious and often severe nose and paranasal sinuses diseases; generally concerning the rhinopharyngealtubal district.Restoring mucociliary clearance of the nasal epithelium when altered thus represents a key therapeutic tool against rhinosinus chronic diseases.This study evaluates the clinical efficacy of the inhalation of a natural compound (Narivent® nasal spray) in chronic vasomotor rhinitis. METHODS: The study involved 79 patients suffering from chronic vasomotor rhinitis presenting an increased mucociliary clearance time. Patients were randomized into 2 groups: a first group of 49 subjects and a second group of 30 subjects.The first group was treated with a nasal spray (Narivent® nasal spray) (2 sprays per nostril twice a day) for 30 days.The second group was treated with a nasal spray containing isotonic solution in the same way and for the same period of the first group.Nasal Mucociliary transport time was measured in the patients of both groups before treatment, after 15 days of treatment, and at the end of the 30 days treatment. RESULTS: The study shows how one of the treatments carried out determines a major objective reduction of the mucociliary clearance time in the patients under examination, using the method which involves the use of an insoluble coloured tracer (vegetable carbon), bringing the values back within normal range. At the end of the study we objectivated an increase in the rate of mucociliary transport in 97.9% percentage of patients we enrolled. CONCLUSIONS: This study shows the effectiveness of treatment with natural extracts with nasal mucosa restoring function in the treatment of chronic vasomotor rhinitis, a nasal inflammatory disease characterized by morphological and functional alteration of the normal nasal mucosa.

Surgical treatment of nasal septal perforations: SIR (Italian Society of Rhinology) experts opinion.

BACKGROUND AND AIM: The aim of our study has been to investigate the perception of aspects related to nasal perforation among experts in Rhinology and ENT surgeons. Our aim was reporting the situations in different Countries to improve the knowledge of colleagues interested in this topic. METHODS: A panel of experts prepared a 20-question questionnaire regarding nasal perforations and their surgical repair, that were emailed to all the members of SIR (Società Italiana di Rnologia - Italian Society of Rhinology). RESULTS: Data obtained from their answers showed that Cottle technique (64%) is the most common technique to perform septoplasty worldwide. 37% of the sample reported an occurrence of nasal septal perforation in less than 1% of patients and 75% attributed this occurrence to the skill of the surgeon, to infections, to drug use and to septal deformity. Trauma, pressure and Wegener's granulomatosis were also mentioned. The most common closure technique is the mucosal flap (75%), followed by the cartilage grafts (11%). Much less common were oral flaps, septal buttons and others. The majority agreed not to suggest septal perforation surgery in minimal (less than 3-4mm) perforations (73.5%), or limiting it to symptomatic patients (43.5%). The contraindications to repair surgery were reported to be: Wegener's granulomatosis, drug abuse, non-symptomatic perforation, its dimension and age of the patient. Septal deviation, atrophic rhinitis, smoke epistaxis and systemic diseases were also claimed. Failure in repair surgery has been observed to occur in less than 30% of cases. DISCUSSION AND CONCLUSIONS: Given the great difficulty to make random studies about controversial topics and obtain statistically significant data related to that, expert opinion shall be of great value (expert opinion, level of evidence 5).

Mometasone furoate nasal spray: a systematic review.

UNLABELLED: The inflammatory diseases of the nose, rhino-pharynx and paranasal sinuses (allergic and non allergic rhinitis, NARES; rhinosinusitis with/without nasal polyposis, adenoidal hypertrophy with/without middle ear involvement) clinically manifest themselves with symptoms and complications severely affecting quality of life and health care expenditure. Intranasal administration of corticosteroids, being fast, simple, and not requiring cooperation, is the preferred way to treat the patients, to optimize their quality of life, at the same time minimizing the risk of exacerbations and complications. Among the different topical steroids available on the market, we performed a comparative analysis in terms of effectiveness and safety between mometasone furoate (MF) and its main competitors. Searching through Pub Med and Google Scholar and using as entries "mometasone furoate", "rhinitis", "sinusitis", "asthma", "polyposis", "otitis media with effusion", and "adenoid hypertrophy" we found 344 articles, 300 of which met the eligibility criteria. Taking into account relevance and date of publication, a sample of 40 articles was considered for the review. MF effectiveness for treatment and/or prophylaxis of nasal symptoms in seasonal and perennial allergic rhinitis has been fully established with a level of evidence Ia. Even though it has not been assessed for MF in particular, topical steroids are the most appropriate treatment in mixed rhinitis and NARES. In acute rhinosinusitis (ARS) evidences support their use as mono-therapy or as adjuvant to antibiotics for reducing the recurrence rate, and decrease the usage of related prescriptions and medical consultations. In chronic rhinosinusitis (CRS) with Nasal polyposis, MF reduces polyps size, nasal congestion, improves quality of life and sense of smell and it is also effective in the treatment of daytime cough. The topical use of MF has great efficacy in the management of adenoidal hypertrophy and otitis media of atopic children. As regards the safety, MF has demonstrated an excellent safety profile: pregnant women can safely use it; no systemic effects on growth velocity and adrenal suppression have been shown; no changes in epithelial thickness or atrophy have been observed after long term administration of the drug. CONCLUSIONS: MF has been demonstrated to be effective in the treatment of the inflammatory diseases of the nose and paranasal sinuses; when compared to its competitors it shows a greater symptom control; it is a reliable treatment in the long term thanks not only to its proven efficacy, but also to its safety being on the market since more than 17 years.

Radioactive Merano SPA Treatment for Allergic Rhinitis Therapy.

Allergic rhinitis is a common nasal disorder with a high impact on quality of life, high social costs in therapies, and a natural development towards asthma. Pharmacological therapy is based on several genres of medications, of which intranasal corticosteroids are currently the most widespread. Thermal water treatment has traditionally been used as adjunctive treatment for chronic rhinitis and sinusitis. The present study was carried out to assess the clinical efficacy of nasal inhalation of radioactive oligomineral water vapours from the Merano hot spring and to compare it with the clinical efficacy of mometasone furoate nasal spray. A comparative prospective study was performed in 90 allergic patients treated at Merano hot springs: a group of 54 subjects treated with radioactive thermal oligomineral water and a control group of 36 subjects treated with mometasone nasal spray. Patients of both groups were assessed before and after treatment by Sino-Nasal Outcome Test questionnaire, active anterior rhinomanometry with flow and resistance monitoring, measurement of mucociliary transport time, and cytological examination of nasal brushing/scraping. The study showed that inhalation treatment with radioactive hydrofluoric thermal water for two weeks produces an objective clinical and cytological improvement in allergic patients, similar to that obtained with mometasone furoate nasal spray.

Role of prulifloxacin in the treatment of acute rhinosinusitis.

Acute rhinosinusitis (ARS) is a very common/disease faced more often by general practitioners than ear, nose and throat specialists, pneumologists or allergologists. In an outpatients setting, upper respiratory tract infection is the third most common cause of a primary care consultation, one third of which is attributable to ARS, diagnosed upon clinical presentation. In some cases however, signs and symptoms do not allow clear differentiation from viral, post-viral or bacterial infection. This compels GPs and family doctors to make a careful choice and first use the best antimicrobial treatment to avoid recurrences or complications and the rise of antibiotic resistance. Amoxicillin, thanks to its narrow spectrum against likely respiratory pathogens, is recommended as first-line therapy to treat acute bacterial rhinosinusitis by several international guidelines, being safe at the same time. Other antibiotics (beta-lactams, macrolides and newer drugs, such as fluoroquinolones) have been evaluated in double-blind studies versus placebo or comparative studies in terms of efficacy, safety and costs. Prulifloxacin, the active metabolite of ulifloxacin, is an oral fluoroquinolone with a broad in vitro activity spectrum against Gram positive and negative bacteria and among fluoroquinolones has the lowest power of inducing resistance. In vitro and in vivo studies have shown its clinical efficacy and pathogen eradication. Ulifloxacin T(1/2) and plasma and tissue concentrations including the nose-paranasal sinuses mucosa allow once daily administration at the dosage of 600 mg. Prulifloxacin shows a high safety profile: it is the fluoroquinolone with the lowest risk of cardiac arrhythmias for prolongation of the QT interval; the CNS penetration is negligible; in women prulifloxacin does not affect the lactobacillary component of the vaginal microbiota, lowering the risk of genito-urinary tract infections. The pharmacokinetic characteristics and safety profile of prulifloxacin make it the antibiotic option with the best potential to achieve clinical cures and bacteriological eradication, well tolerated and safe without specific restriction or posologic changes in the elderly and in patients with co-morbidities in multiple treatment, hence resolving ARS reliably and being simple and easy to administer.