Ignazio La Mantia

Background: Persistent laryngopharyngeal symptoms are frequently managed empirically in otolaryngological practice, although symptom-based diagnosis and treatment responses are nonspecific. This multicentre, uncontrolled practice-based cohort describes symptom scores during a predefined sequence of esomeprazole followed by use of an alginate-containing food supplement (Gastrolaryn^® Stick). Methods: Seventeen Italian otolaryngologists enrolled 261 adults and recorded Reflux Symptom Index (RSI) assessments at baseline (T0), after eight weeks of esomeprazole 40 mg daily (T1), and after eight additional weeks during which the supplement was prescribed (T2). Analyses were descriptive and used visit-specific available observations. Results: A baseline total RSI was reported for 260 participants; follow-up observations were available for 161 at T1 and 167 at T2. Mean RSI scores (±SD) were 20.4 ± 6.3, 9.8 ± 6.5, and 8.4 ± 6.6, respectively. The 1.4-point difference between T1 and T2 is a comparison of different available-case samples, not a paired within-patient change. No adverse events attributed to the supplement were recorded in the available follow-up reports. Conclusions: Symptom scores were lower at follow-up than at baseline in the observed samples. Without a comparable untreated group, linked repeated measurements, or complete follow-up, the contribution of the supplement to the symptom trajectory cannot be established.

Background: Symptom management after proton pump inhibitor (PPI) treatment remains an important issue in gastroesophageal reflux disease (GERD). Objective: To describe symptom distributions during a sequential PPI and Gastrolaryn^® Stick management pathway in routine outpatient practice. Methods: In a multicenter, prospective observational survey, 263 GERD patient records were collected at baseline (T0) by 17 gastroenterologists. The intended management sequence comprised 8 weeks of esomeprazole 40 mg daily (T0–T1) followed by 8 weeks of Gastrolaryn^® Stick (one stick twice daily; T1–T2). Outcomes included GERD Impact Scale (GIS) response distributions and routine-care characteristics. Analyses were descriptive and based on available records at each survey timepoint. Results: Records were available for 124 patients at T1 (47.1% of baseline) and 112 at T2 (42.6%). Across recorded GIS item responses, the proportion rated “every day” was 12.8%, 0.9%, and 0.3% at T0, T1, and T2, respectively; the corresponding “never” proportions were 24.8%, 44.5%, and 58.4%. These are unpaired, timepoint-specific descriptive summaries and do not establish individual improvement. Investigators submitting records declined from 17 to 11 and 7. Conclusions: Among available records, symptom-frequency distributions were more favorable at later survey timepoints. Substantial missing follow-up, changing site participation, the lack of a comparator and unavailable patient-level paired analyses prevent causal attribution, assessment of relapse prevention, or definitive conclusions about maintenance effectiveness. The survey nevertheless documents management and follow-up patterns encountered in routine practice.

Background: Allergic rhinitis (AR) represents a significant burden in Ear Nose Throat (ENT) practice and markedly affects quality‐of‐life and work productivity of AR patients. The fixed combination of intranasal azelastine and fluticasone propionate (AzeFlu) has emerged as a valuable therapeutic option for moderate‐to‐severe AR. Recent updates to international guidelines and real‐world evidence warrant a comprehensive review of its role in ENT practice, with particular attention to both seasonal and perennial AR. Methods: This narrative review synthesises evidence from the ARIA‐EAACI 2024–2025 guidelines, systematic reviews and network meta‐analyses of randomised controlled trials, pharmacovigilance data, and results from an Italian multidisciplinary inter‐societal Delphi Consensus. We evaluated efficacy, safety, patient acceptability and implementation considerations specific to otorhinolaryngology practice. Results: Network meta‐analyses demonstrate that AzeFlu provides superior symptom control compared to monotherapy for both nasal and ocular symptoms in seasonal and perennial AR, with a rapid onset of action (15–30 min). The combination shows particular efficacy in patients with moderate‐to‐severe symptoms inadequately controlled by monotherapy. Safety profiles are comparable to those of monotherapy, with no significant effects on growth or the HPA axis in children. Real‐world data indicate high treatment satisfaction and adherence. The Italian Delphi Consensus achieved > 80% agreement on key management principles, particularly emphasising control of Type 2 inflammation and the role of combination therapy in treatment algorithms. Evidence for perennial AR remains more limited, and future primary research specifically targeting perennial rhinitis populations is warranted. Conclusions: Azelastine‐fluticasone combination therapy represents an evidence‐based, guideline‐recommended option for moderate‐to‐severe AR in ENT practice. Its dual mechanism, rapid onset, favourable safety profile and high patient acceptability support its integration into contemporary treatment algorithms, particularly for patients requiring enhanced symptom control beyond monotherapy. The combination represents a meaningful therapeutic advancement, and further research is needed to fully characterise its role in perennial AR management.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly debilitating airway disease primarily characterized by type 2 inflammation and eosinophilic infiltration. Among the key cytokines involved, Interleukin-5 (IL-5) plays a relevant role in eosinophil biology and contributes, together with other mediators of type 2 inflammation, to epithelial barrier dysfunction, immune dysregulation, mucus hypersecretion, and tissue remodeling. Therapies targeting this cytokine have demonstrated both efficacy and safety in patients with CRSwNP. This narrative commentary summarizes current evidence in understanding IL-5’s role in CRSwNP, integrating insights from an Italian otolaryngology expert panel, with a particular focus on the patient journey in Italy. Available evidence suggests that IL-5 is associated with disease severity and may contribute to multiple aspects of CRSwNP pathophysiology beyond eosinophilia. Targeting the IL-5 pathway has been shown to improve clinical outcomes, including nasal polyp burden, symptom control, olfactory function, and quality of life, in selected patients. From a clinical perspective, the expert panel highlighted several critical unmet needs in the Italian setting, including diagnostic delay, heterogeneous implementation of care pathways, suboptimal patient selection, and limited adherence to long-term management strategies. The importance of structured diagnostic work-up, endotyping, multidisciplinary management, and patient awareness was emphasized. The implementation of shared Diagnostic and Therapeutic Care Pathways (PDTA) and network-based models may support more standardized and timely management, although further evidence is needed to define their impact on clinical outcomes. Overall, improving the understanding of IL-5–driven mechanisms and addressing organizational gaps may contribute to optimizing the management of CRSwNP in clinical practice.

Background/Objectives: Intranasal carboxymethyl-β-glucan (CMBG)-resveratrol represents an innovative therapeutic approach for upper airway diseases, combining antimicrobial, anti-inflammatory, antioxidant, immunomodulatory, and antiallergic properties. Despite growing preclinical and clinical evidence, consensus on its clinical applications remains poorly defined. To establish evidence-based recommendations for the clinical use of intranasal CMBG-resveratrol through a multidisciplinary Delphi Consensus process. Methods: A two-round Delphi Consensus was conducted. In the first round, an expert board prepared, reviewed, and validated 22 statements based on current scientific evidence from preclinical and clinical studies. In the second round, 38 multidisciplinary experts evaluated each statement using a 5-point Likert scale (from 5 = strongly agree to 1 = strongly disagree). Consensus was defined as ≥80% agreement (scores 4 + 5). Results: All 22 statements achieved consensus (range: 83–100%). Strong agreement (≥90%) was reached for statements regarding the pathophysiological rationale (infection-inflammation-oxidative stress cycle), resveratrol’s pleiotropic mechanisms of action, the role of CMBG in enhancing stability and bioavailability, and clinical efficacy in respiratory infections and allergic rhinitis. The mean scores ranged from 4.2 to 4.9, indicating high expert agreement across all domains. Conclusions: This multidisciplinary Delphi Consensus provides evidence-based recommendations for the use of intranasal CMBG-resveratrol to manage upper airway diseases, particularly respiratory infections and allergic rhinitis. The formulation’s multitarget approach addresses the complex pathophysiology of these conditions through simultaneous antimicrobial (mainly antiviral), anti-inflammatory, and immunomodulatory effects.

Pediatric obstructive sleep apnea (OSA) is a prevalent and underdiagnosed condition associated with significant neurocognitive, behavioral, and systemic consequences. Sleep-related breathing disorders (SRBDs) in children range from primary snoring to OSA, with even mild forms increasingly linked to adverse outcomes. Given their frequent contact with pediatric patients, pediatric dentists and orthodontists are uniquely positioned to contribute to early identification and management within a multidisciplinary framework. Objectives: This narrative review aimed to summarize and critically appraise current evidence to clarify the clinical role, scope of practice, and responsibilities of pediatric dentists and orthodontists within the multidisciplinary management of pediatric obstructive sleep apnea. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and EMBASE up to 1 November 2025. Review articles addressing the involvement of pediatric dentists and orthodontists in pediatric OSA were included. No restriction was applied to language or publication year. Two authors independently performed study selection and data extraction. The methodological quality and data extraction of the studies were structured according to the SANRA scale. Ten studies were deemed suitable for inclusion in the current review. After examination of the full texts, the available evidence was filtered into specific clinical domains aimed at clarifying the role of the pediatric dentist and orthodontist in the management of pediatric obstructive sleep apnea (OSA). Qualitative thematic analysis of the included studies identified three main areas in which pediatric dentists and orthodontists contribute to the management of pediatric OSA. The first area involves screening through recognition of clinical signs and symptoms, use of validated questionnaires, and identification of craniofacial and occlusal features associated with increased airway risk. The second area concerns participation in the diagnostic–therapeutic pathway and multidisciplinary care, including timely referral, clinical documentation, and collaboration with pediatricians, otolaryngologists, and sleep specialists. The third area relates to orthodontic treatments such as rapid maxillary expansion and mandibular advancement appliances, which may provide adjunctive benefits in selected patients, although current evidence is limited by heterogeneity and growth-related confounding factors. Pediatric dentists and orthodontists play a pivotal yet complementary role in the management of pediatric OSA. In particular, all the involved specialists are encouraged to actively participate in the screening process, interdisciplinary communication, and diagnostic and therapeutic decision-making processes.

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammatory condition that significantly reduces the quality of life due to nasal obstruction, loss of smell and rhinorrhea. Although endoscopic sinus surgery offers relief of symptoms and improvement of quality of life, recurrences are common and multiple surgeries are often required. The aim of this post hoc analysis is to verify the hypothesis that previous multiple surgeries may be associated with poor outcomes with dupilumab in a real‐life setting in terms of quality of life, reduction in nasal polyps and improvement of olfaction. Methods: This is a post hoc analysis of the Phase IV real‐life multicentre DUPIREAL study in patients with severe uncontrolled CRSwNP treated with dupilumab 300 mg every 2 weeks for 12 months. Inclusion criteria included adherence to treatment and olfactory evaluation measured by Sniffin' Sticks Identification Test 16 (SSIT‐16). Statistical analyses included multivariate regression, evaluating correlations between baseline factors and poor outcomes in terms of NPS ≥ 4, SNOT‐22 ≥ 30 and SSIT‐16 ≤ 12. Results: Higher NPS at baseline was associated with an increased risk of NPS > 4 at 12 months, whereas a higher number of previous surgeries is associated with a higher probability of lower NPS. Notably, a greater number of previous surgeries was independently associated with incomplete recovery of smell, and surgery‐naïve patients had a higher likelihood of achieving complete olfactory recovery. Dupilumab treatment led to a remarkable improvement in olfactory function, with anosmia rates decreasing from 60.2% to 3.3% after 1 year, although in our series, nearly half of the patients still exhibited residual olfactory impairment. Conclusions: This post hoc analysis highlights the efficacy of dupilumab for the treatment of CRSwNP in real life. Multivariate analysis revealed that multiple prior surgeries negatively impact outcomes with dupilumab during the first year of treatment, especially in terms of olfactory recovery.

Background/Objectives: Inhalable Microparticles (IMPs) are part of a currently invading field of medicine. In fact, the anatomical district of Rhinopharynx represents a bed for many different pathologies and infections, where the dimension of drug aerosol Microparticles (MPs) represents a discriminating factor to success therapy. The aims of the present work are to demonstrate the efficacy of a new device and its aerosol reproducibility in the nebulization of suspensions to be deposited in the retropharynx. Materials and Methods: The Low-Angle Laser Light Scattering (LALLS) method was used to evaluate both the dimension and distribution of MPs. Six different APIs, used usually in Rhinopharynx pathology, were compared in order to investigate the dimension of MP emissions using four different devices. The results of a retrospective study including 74 subjects treated with standard therapy (ST) and the inhalation of nebulized Sobrerol (NS) were performed. Data regarding the persistence of clinical symptoms (i.e., cough and nasal constipation) were acquired. Results: No significant statistical differences among all the products tested (p > 0.05) were found. One device, Rinubes, demonstrated efficacy and robustness in the fine nebulization of all the pharmaceutical products analyzed. Rinubes delivered an aerosol cloud with significantly lower MMD (66.3 µm) than Mad Nasal and Spray-sol (142.1 and 116.0 µm, respectively), which would allow a higher fraction of drugs to be deposited in the retropharynx. The retrospective clinical study revealed that NS treatment showed higher odds of cough resolution (OR 9.18; p < 0.001) with respect to control ST and showed higher odds of nasal symptom resolution (OR 6.7; p = 0.043). Conclusions: Improved techniques for the administration of inhalable MPs (INPAD) represent significant progress in overcoming the biological and the anatomical barriers in controlling drug release at a specific site. The challenges of nasopharyngeal pathologies offer promising opportunities for the development of non-invasive drug delivery.

Background: Dupilumab is an effective treatment for severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Most real‐life studies have been conducted on small patient cohorts for up to 1 year. Methods: This ambispective, multicentric, 2‐year‐long study evaluated dupilumab effectiveness (including treatment response, disease control, and remission) and safety in severe, uncontrolled CRSwNP patients from the DUPIREAL Italian study centers. Results: The study involved 926 patients. At 24 months, median nasal polyp score (NPS), nasal obstruction visual analogue scale (VAS), Sino‐nasal Outcome Test‐22 (SNOT‐22), and olfaction improved from baseline (all p < 0.0001). Patients with NPS > 4, and/or SNOT‐22 > 30, and/or Sniffin’ Sticks Identification Test‐16 (SSIT‐16) < 12 at 12 months demonstrated improvements in these outcomes over the second year. Overall, 18.7% of patients extended the dupilumab interdose interval to every 4 weeks (q4w). Notably, 91.2% of patients were “good‐to‐excellent” responders based on EPOS/Euforea criteria. Given the absence of standardized definitions for disease control and remission, we proposed different sets of criteria reporting results from different scenarios. Remission analysis is clinically important as it helps define treatment success and long‐term therapeutic goals. Most adverse events were mild‐to‐moderate; 2.4% of patients discontinued treatment due to safety concerns. Conclusions: This is the largest real‐life study evaluating dupilumab in CRSwNP over 2 years. Dupilumab showed sustained effectiveness, with progressive improvements across all clinical outcomes. Dupilumab tapering did not compromise outcomes; treatment continuation allowed meaningful clinical benefits in late responders. Two‐year rates of disease control and remission are clinically relevant, although standardized criteria to assess these outcomes are needed.