Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Charcot-Leyden crystals: An ancient but never so current discovery.

From the first description of Charcot-Leyden crystals (CLCs) to the present, many steps have been taken to understand the mechanisms underlying their formation. In particular, to date not only eosinophils but also mast cells are known to be responsible for the production of CLCs, which represent the crystallized form of Galectin-10. Due to their characteristics, CLCs typically induce a crystallopathy and are responsible for an exacerbation of inflammation. Nasal cytology (NC) has allowed to better understand the correlation between the severity of several rhinopaties and the presence of CLCs in NC samples, which is strictly correlated with an eosinophiles and mast cells infiltration. As a matter of fact, rhinopaties with a mixed eosinophilic-mast cell inflammatory infiltrate, characterized by the presence of abundant CLCs, show a worse prognosis and a higher risk of relapse. This could have important therapeutic implications, since the treatments available today could be exploited to target both eosinophils and mast cells, to reduce the damage induced by CLCs.

General classification of rhinopaties: the need for standardization according to etiology and nasal cytology.

BACKGROUND: Rhinitis is as an inflammation of the nasal mucosa, characterized by high prevalence, widespread morbidity, and a significant financial burden on health care systems. Nevertheless, it is often considered as no more than a mere annoyance. This point of view has progressively led to underestimate and trivialize the disease. Therefore, there are numerous, mostly overlapping classifications of rhinopaties, but clear and standardized guidelines for diagnosis and treatment are still lacking. In the context of Precision Medicine, the development of a classification system focused on the endotypes of rhinitis to be widely adopted appears of utmost importance, also by virtue of study of the nasal immunophlogosis that, thanks to nasal cytology (NC), has recently allowed to better define the different forms of rhinitis, giving a new nosological dignity to several rhinopaties. AIM: We aimed to summarize the current knowledge regarding rhinitis and to propose a systematic classification of rhinitis, based on both etiology and cytological findings.

Nasal disorders and cardiovascular damage: flow-mediated dilation and intima-media thickness as risk parameters.

Nasal disorders and cardiovascular damage: flow-mediated dilation and intima-media thickness as risk parameters.

A probiotic mixture in patients with upper respiratory diseases: the point of view of the otorhinolaringologist.

Upper respiratory infections are widespread in clinical practice. Antibiotics are frequently used in the management of patients with airways infection. However, antibiotics can induce intestinal and respiratory dysbiosis that, in turn, worsens respiratory symptoms. Moreover, respiratory infections per se can cause dysbiosis. Consequently, probiotics may counterbalance the disturbed microbiota. The current clinical experience evaluated the efficacy and safety of an oral nutraceutical containing a probiotic mixture with Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million living cells), and Lactobacillus delbrueckii subspecies delbrueckii LDD01 (200 million living cells), in 2928 outpatients with an upper respiratory infection and treated with antibiotics. Patients took one stick/daily for four weeks. Simultaneously, 2877 patients with an upper respiratory infection and treated with antibiotics were recruited as control. This probiotic mixture significantly diminished the presence and the severity of respiratory symptoms at the end of the probiotic course and, more evidently, after a 3-month follow-up. In conclusion, the current clinical experience suggested that this probiotic mixture may be considered an effective and safe therapeutic option in managing patients with an upper respiratory infection and treated with antibiotics.

Probiotics in the add-on treatment of rhinosinusitis: a clinical experience

Rhinosinusitis (RS) affects the nose and the paranasal sinus and is characterized by nasal and systemic symptoms. It may be classified as acute or chronic, based on duration. Rhinosinusitis may be clinically suspected, but the diagnosis is usually based on the endoscopy. Antibiotic therapy is frequently used for RS patients in clinical practice. However, antibiotics often induce intestinal dysbiosis associated with some clinical problems and respiratory microbiota impairment. The current clinical experience was conducted in patients with pharyngotonsillitis and treated with antibiotics. A one-month course of a probiotic mixture (Abincol® containing Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million living cells), and Lactobacillus delbrueckii LDD01 (200 million living cells), was prescribed in the Group A, and was compared with no addon treatment, such as the Group B. Patients were evaluated at baseline (T0), at the end of antibiotic treatment (T1), at the end of probiotic course (T2), and at the end of 3-month follow-up (T3).

Probiotics in the add-on treatment of laryngotracheitis: a clinical experience.

Laryngotracheitis is a common disease, mainly characterized by dysphonia, cough, and sore throat. The diagnosis is usually based on the clinical ground, and antibiotic therapy is frequently used in clinical practice. However, antibiotics frequently induce intestinal dysbiosis associated with some clinical problems. The current clinical experience was conducted in patients with pharyngotonsillitis and treated with antibiotics. A one-month course of a probiotic mixture (Abincol® containing Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million living cells), and Lactobacillus delbrueckii LDD01 (200 million living cells), was prescribed in the Group A, and was compared with no add-on treatment, such as the Group B. Patients were evaluated at baseline (T0), at the end of antibiotic treatment (T1), at the end of probiotic course (T2), and at the end of 3-month follow-up (T3). Globally, 833 outpatients with laryngotracheitis were enrolled: 425 in Group A and 408 in Group B. All of them were treated with a 7-10-day course of antibiotic therapy. The probiotic mixture reduced the duration of symptoms associated with antibiotic therapy already at the end of the antibiotic cycle. The intergroup comparison showed that probiotic group patients experienced less fever, tiredness, headache, pain, malaise, diarrhea, and nausea (p<0.001 for all) than control patients at T1. The probiotic course reduced the possible clinical relapse, and the use of additional medications at T2 and T3. In conclusion, the present clinical experience demonstrated that a probiotic mixture containing Lactobacillus plantarum LP01, Lactobacillus lactis subspecies cremoris LLC02, and Lactobacillus delbrueckii subspecies delbrueckii, was able to rapidly reduce symptoms associated with antibiotic therapy in patients with laryngotracheitis.

Probiotics in the add-on treatment of pharyngotonsillitis: a clinical experience.

Pharyngotonsillitis is a common disease, mainly characterized by a sore throat. It may be classified as acute or chronic, based on duration. The diagnosis is usually performed on the clinical ground, and antibiotic therapy is frequently used in clinical practice. However, antibiotics frequently induce intestinal dysbiosis associated with some clinical problems. Therefore, probiotics are commonly prescribed in patients treated with antibiotics. The current clinical experience was conducted in patients with pharyngotonsillitis and treated with antibiotics. A one-month course of a probiotic mixture (Abincol® containing Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million of living cells), and Lactobacillus delbrueckii subspecies delbrueckii LDD01 (200 million of living cells), was prescribed in the Group A, and was compared with no add-on treatment, such as the Group B. Patients were evaluated at baseline (T0), at the end of antibiotic treatment (T1), at the end of probiotic course (T2), and at the end of 3-month follow-up (T3). Globally, 1118 outpatients were enrolled. Acute pharyngotonsillitis affected 795 subjects: 396 in Group A and 399 in Group B. Chronic pharyngotonsillitis affected 323 outpatients: 158 in Group A and 165 in Group B. All patients were usually treated with a 7-10-day course of antibiotic therapy. In patients with acute pharyngotonsillitis, the probiotic mixture significantly reduced the duration of all the symptoms (p<0.001 for all), except for the urinary tract infection, associated with antibiotic therapy which was already at the end of the antibiotic cycle (T1). The intergroup analysis showed that patients with chronic pharyngotonsillitis in Group A had significantly less tiredness, pain, and malaise (p<0.001 for all) than patients in Group B at T1. The probiotic course reduced the possible clinical relapse, and the use of additional medications at T2 and T3 in patients with both acute and chronic pharyngotonsillitis. In conclusion, the present clinical experience demonstrated that a probiotic mixture containing Lactobacillus plantarum LP01, Lactobacillus lactis subspecies cremoris LLC02, and Lactobacillus delbrueckii, was able to quickly reduce symptoms, possible relapse, and use of additional medications, associated with antibiotic therapy, in patients with both acute and chronic pharyngotonsillitis.

Probiotics in the add-on treatment of otitis media in clinical practice.

Otitis media (OM) affects the middle ear and is typically characterized by earache. OM may be classified as acute (AOM) or chronic (COM), based on symptom duration. OM may be clinically suspected, but the diagnosis is usually confirmed by the otoscopy. Antibiotic therapy is frequently used in clinical practice. However, antibiotics often induce intestinal and respiratory dysbiosis associated with some clinical problems. A one-month course of a probiotic mixture (Abincol® containing Lactobacillus plantarum LP01 (1 billion of living cells), Lactobacillus lactis subspecies cremoris LLC02 (800 million living cells), and Lactobacillus delbrueckii LDD01 (200 million living cells), was prescribed in the Group A, and was compared with no addon treatment, such as the Group B. Patients were evaluated at baseline (T0), at the end of antibiotic treatment (T1), at the end of probiotic course (T2), and at the end of 3-month follow-up (T3).

Broser® (bromelain, escin and selenium), oral nutraceutical, monotherapy in patients with inflammatory otorhinolaryngological disorders.

Inflammation is a common pathogenic mechanism involved in many otorhinolaryngological (ORL) disorders. Broser® is an oral nutraceutical currently containing bromelain 100 mg, escin 30 mg, and selenium 42.5 mcg. It could exert a safe and effective anti-inflammatory activity by virtue of these components. Therefore, the aim of the current survey, conducted in clinical practice of 84 Italian ORL centers, was to evaluate its safety and efficacy in the treatment of patients.

Nasal cytology: Methodology with application to clinical practice and research.

Nasal cytology is an easy, cheap, non-invasive and point-of-care method to assess nasal inflammation and disease-specific cellular features. By means of nasal cytology, it is possible to distinguish between different inflammatory patterns that are typically associated with specific diseases (ie, allergic and non-allergic rhinitis). Its use is particularly relevant when other clinical information, such as signs, symptoms, time-course and allergic sensitizations, is not enough to recognize which of the different rhinitis phenotypes is involved; for example, it is only by means of nasal cytology that it is possible to distinguish, among the non-allergic rhinitis, those characterized by eosinophilic (NARES), mast cellular (NARMA), mixed eosinophilic-mast cellular (NARESMA) or neutrophilic (NARNE) inflammation. Despite its clinical usefulness, cheapness, non-invasiveness and easiness, nasal cytology is still underused and this is at least partially due to the fact that, as far as now, there is not a consensus or an official recommendation on its methodological issues. We here review the scientific literature about nasal cytology, giving recommendations on how to perform and interpret nasal cytology.

Gastric reflux: comparison between the gastroenterologist and the otorhinolaryngologist's approach. Pragmatic conclusive remarks.

Conclusions: Gastroesophageal reflux (GER) is a normal physiological process that usually happens after eating in healthy infants, children, young people and adults. In contrast, gastroesophageal reflux disease (GERD) occurs when the effect of GER leads to symptoms severe enough to merit medical treatment. In clinical practice, it is difficult to differentiate between GER and GERD, and health professionals and families use the terms interchangeably alike. There is no simple, reliable and accurate diagnostic test to confirm whether the condition is GER or GERD, and this in turn affects research and clinical decisions (1-6). Furthermore, the term GERD covers a number of specific conditions that have different effects and present in different ways. This makes it difficult to identify the person who genuinely has GERD, and to estimate the real prevalence and burden of the problem.

Focus on gastroesophageal reflux (GER) and laryngopharyngeal reflux (LPR): new pragmatic insights in clinical practice.

Introduction: Gastroesophageal reflux (GER) is a common disease usually limited to the oesophagus. Laryngopharyngeal reflux (LPR) is an inflammatory reaction of the mucosa of pharynx, larynx, and other associated upper respiratory organs, caused by a reflux of stomach contents outside the oesophagus. LPR is considered to be a relatively new clinical entity with a vast number of clinical manifestations which are treated sometimes empirically and without a correct diagnosis. However, there is disagreement between specialists about its definition and management: gastroenterologists consider LPR to be a substantially rare manifestation of gastroesophageal reflux disease (GERD), whereas otolaryngologists believe that LPR is an independent, but common in their practice, disorder. Patients suffering from LPR firstly consult their general practitioners, but a multidisciplinary approach may be fruitful to define a unified strategy based on specific medications and behavioural changes. The present Supplement would review the topic, considering LPR and GER characteristics, pathophysiology, diagnostic work-up, and new therapeutic strategies also comparing different specialist points of view and patient populations. In particular, new insights derive from an interesting gel compound, containing magnesium alginate and E-Gastryal® (hyaluronic acid, hydrolysed keratin, Tara gum, and Xantana gum). In particular, two very large Italian surveys were conducted in real-world setting, such as outpatient clinics. The most relevant outcomes are presented and discussed in the current Issue. Actually, laryngopharyngeal reflux (LPR) is considered an extraesophageal manifestation of the gastroesophageal reflux disease (GERD). Both GERD and its extraesophageal manifestation are very common in clinical practice. Both disorders have a relevant burden for the society: about this topic most of pharmaco-economic studies were conducted in the United States. In population-based studies, 19.8% of North Americans complain of typical symptoms of GERD (heartburn and regurgitation) at least weekly (1). Also in the late 1990s, GERD accounted for $9.3 to $12.1 billion in direct annual healthcare costs in the United States, higher than any other digestive disease. As a result, acid-suppressive agents were the leading pharmaceutical expenditure in the United States. The prevalence of GERD in the primary care setting becomes even more evident when one considers that, in the United States, 4.6 million office encounters annually are primarily for GERD, whereas 9.1 million encounters include GERD in the top 3 diagnoses for the encounter. GERD is also the most frequently first-listed gastrointestinal diagnosis in ambulatory care visits (2, 3) Extraesophageal manifestations of reflux, including LPR, asthma, and chronic cough, have been estimated to cost $5438 per patient in direct medical expenses in the first year after presentation and $13,700 for 5 years.

Correlation between the reflux finding score and the reflux symptom index in patients with laryngopharyngeal reflux.

LaryngoPharyngeal Reflux (LPR) is characterized by symptoms, signs, and/or tissue damage resulting from the aggression of the gastrointestinal contents in the upper airways. The Reflux Finding Score (RFS) assesses the laryngeal signs through laryngoscopy. The Reflux Symptom Index (RSI) scores the LPR symptoms. The objective of this real-world study was to compare RFS with RSI in a cohort of Italian LPR patients. Globally, 3932 patients with LPR were evaluated and RFS and RSI were assessed in all subjects. A moderate correlation was found between RSI and RFS (r=0.484, p<0.0001). In conclusion, the RSI and RFS can easily be included in the LPR work-up as objective and consistent parameters, with low cost and high practicality. Based on these clinical outcomes, the specialist can easily use these tests in clinical practice.

Relieving laryngopharingeral reflux (RELIEF) survey in otolaryngology - the viewpoint of the otorhinolaryngologist.

Laryngopharyngeal Reflux (LPR) should be considered as part of extraesophageal reflux (EER). This reflux involves respiratory structures other than, or in addition to, the oesophagus. A new medical device for the treatment of gastric reflux, including LPR, has been launched in Italy: Marial®. Therefore, the aim of the present survey was to analyse the prescriptive behaviour both considering the past or current treatments and clinical features during a specialist routine visit. The current survey was conducted in 86 Otorhinolaryngological centers, distributed in all of Italy. Globally, 4.418 subjects [47% males and 53% females, 50.1 (14.5) years-of-age] were visited. The visits included laryngoscopy, Reflux Finding Score (RFS) and Reflux Symptom Index (RSI) questionnaires. The total RSI median score was 15 (12-19) and the total median RFS value was 10 (8-12). Interestingly, a significant change in the new drug prescription was observed (p<0.0001): over two-third of patients (67%) received Marial® as monotherapy, whereas PPI plus add-on were prescribed to almost one-third of the patients. PPI alone was prescribed in less than 1%. In conclusion, LPR is a common disorder characterized by typical signs and symptoms; LPR patients may be correctly identified and scored by evidence-based criteria. In addition, the present survey reported that LPR treatment has been considerably changed by the introduction of a new medical device.

Relieving laryngopharingeral reflux (RELIEF) survey in otolaryngology - II the viewpoint of the patient.

As LPR diagnostic work-up is complex in the absence of a definitive gold standard diagnostic test, patient symptoms have become a primary method to identify those with LPR. In this regard, Reflux Symptom Index (RSI) is a reliable self-administered questionnaire useful also to monitor changes after treatment. An Italian survey on patients with LPR evaluated the effect of treatments for LPR that were prescribed in a real-world setting, such as Otolaryngological clinics. In this part of the survey, 1,680 subjects [45.2% males, 54.8% females, 50.4 (14.7) years] were visited in the 86 Italian ORL centers. About 70% of patients were treated with Marial® alone, 27% with PPI plus add-on. RSI change assessment was the primary outcome. Both therapeutic options significantly (p<0.0001) reduced RSI score interestingly since the second week. The inter-group comparison demonstrated the Marial® monotherapy induced a greater reduction of RSI than PPI plus add-on since the second week. In conclusion, the present survey reported that a new medical device (Marial®) may be considered a valid option for the treatment of LPR.

Nasal cytology.

Nasal cytology represents a useful, inexpensive and easy-to-apply diagnostic method to better detail the phenotypic characteristics of rhinitis. In fact, it allows to detect and quantify the cell population within the nasal mucosa at a given time. The technique involves sampling, processing and microscope reading. Sampling requires the collection of cells from the surface of nasal mucosa that is usually done by a sterile disposable curette. Samples should be collected from the middle portion of the inferior turbinate where the ratio ciliate/mucinous cells is expected to be well balanced. This totally painless procedure is performed under anterior rhinoscopy, with an appropriate light source. The sample staining is executed using the common May-Grünwald-Giemsa (MGG). The stained sample is read at optical microscopy with a 1000x objective and with oil detecting the presence of inflammatory elements (eosinophils, mast cells, neutrophils and lymphocytes) in nasal mucosa, as in the case of allergic and non-allergic rhinitis. Nasal cytology is easy to perform, non-invasive, inexpensive and repeatable in the same subject, also at short time intervals. For these reasons it represents an affordable diagnostic technique that can be applied in all age ranges, to better differentiate pathological conditions and also to evaluate the effects of various stimuli (allergens, infectious, irritants) or the effect of treatments.

Internal nasal dilatator (Nas-Air®) in patients who snore.

Snoring is a very common human habit, and for this reason it is considered more a social nuisance that a disease symptom. The nasal valve area has the minimal cross-sectional area of the upper airways. A problem at this level may easily induce impaired breathing and consequently snoring, therefore nasal dilation might significantly improve this complaint. Nas-Air® is a new internal nasal dilator which was tested on 41 outpatients who snore. Snoring duration, assessed by smartphone, visual analogue scale for the perception of sleep quality were measured before and during Nas-Air® use. A significant reduction of snoring time and an improvement of sleep quality were achieved during Nas-Air® wearing. In conclusion, the present study demonstrates that Nas-Air® is an internal nasal dilator able to reduce snoring time and improve sleep quality.

Adjuvant treatment with a symbiotic in patients with inflammatory non-allergic rhinitis.

Inflammatory non-allergic rhinitis (INAR) is characterized by the presence of an inflammatory infiltrate and a non-IgE-mediated pathogenesis. This retrospective, controlled, multicentre study investigated whether a symbiotic, containing Lactobacillus acidophilus NCFM, Bifidobacterium lactis, and fructo-oligosaccharides (Pollagen®, Allergy Therapeutics, Italy), prescribed as adjunctive therapy to a standard pharmacological treatment, was able to reduce symptom severity, endoscopic features, and nasal cytology in 93 patients (49 males and 44 females, mean age 36.3±7.1 years) with INAR. The patients were treated with nasal corticosteroid, oral antihistamine, and isotonic saline. At randomization, 52 patients were treated also with symbiotic as adjunctive therapy, whereas the remaining 41 patients served as controls. Treatment lasted for 4 weeks. Patients were visited at baseline, after treatment, and after 4-week follow-up. Adjunctive symbiotic treatment significantly reduced the percentages of patients with symptoms and endoscopic signs, and diminished inflammatory cells. In conclusion, the present study demonstrates that a symbiotic was able, as adjuvant treatment, to significantly improve symptoms, endoscopic feature, and cytology in patients with INAR, and its effect may be long lasting.

Allergic and nonallergic rhinitis and skin sensitization to metals: is there a link?

SUMMARY: Background. Chromium, Cobalt and Nickel are responsible for contact dermatitis, that is largely prevalent in the general population. They can act also as irritants in the upper and lower respiratory airways. Also rhinitis (allergic and nonallergic) is a high prevalence disorder. Both diseases could share some common inflammatory mechanisms, but the clinical association between skin sensitization to metals and rhinitis was never studied. Objective. We assessed the presence of skin sensitization to metals in subjects with rhinitis. Methods. Patients suffering from rhinitis underwent a standard diagnostic procedure, including skin testing, nasal endoscopy and nasal cytology. Control healthy subjects were also included. None of the patients had skin diseases. All subjects underwent patch test with Chromium, Cobalt and Nickel. Results. None of the 26 controls had positive skin prick test or nasal cytology. The 82 rhinitis patients were subdivided into allergic (group A = 27), nonallergic (group B = 31) and overlapping (group C = 24). The prevalence of positive patch test to metals was 26% in group A, 45% in group B, 42% in group C and 31% in controls. The percentage of patch-positive subjects was significantly different between Group A and B (p = 0.0045; OR: 0.43), Group A and C (p = 0.0186; OR: 0.49), and Group B and controls (p = 0.0360; OR: 1.85). There was a significant difference between groups A + controls and B + C. Conclusion. Even in the absence of skin diseases, the prevalence of sensitization to metals (patch test) is greater in nonallergic and overlapping rhinitis, as compared to allergic rhinitis and controls.