Search Results (46)

Intranasal corticosteroids (INCS) remain the cornerstone of pharmacologic treatment for allergic rhinitis (AR) because of their well-established anti-inflammatory efficacy and generally favorable benefit–risk profile. Nevertheless, concerns regarding local and systemic corticosteroid-related adverse events (AEs) continue to influence patient adherence, prescribing practices, and long-term treatment acceptance. In routine clinical practice, safety perception and corticosteroid-related concerns frequently influence adherence and formulation selection to a greater extent than differences in clinical efficacy, particularly in pediatric populations and in patients requiring prolonged continuous therapy. Differences in pharmacokinetic and pharmacodynamic properties, including systemic bioavailability, glucocorticoid receptor affinity, lipophilicity, protein binding, and extent of first-pass metabolism, are considered important safety profile determinants of currently available INCS formulations. Available evidence indicates that local AEs, particularly epistaxis, nasal irritation, dryness, and sensory discomfort, represent the most frequently reported treatment-related AEs across INCS formulations, although these events are generally mild, self-limiting, and infrequently treatment-limiting. Clinically significant structural nasal complications, including septal perforation or progressive mucosal injury, appear uncommon in currently available studies. Systemic AEs, including hypothalamic–pituitary–adrenal (HPA) axis suppression, ocular toxicity, growth impairment, or clinically meaningful effects on bone metabolism, have not been consistently demonstrated with currently used low-systemic-exposure formulations administered at recommended therapeutic doses. Although systemic glucocorticoid exposure has been associated with alterations in lipid metabolism, adipose tissue function, and metabolic homeostasis, currently available intranasal corticosteroids demonstrate minimal systemic exposure, making clinically relevant metabolic effects unlikely under recommended therapeutic conditions. Formulations such as mometasone furoate, fluticasone propionate, fluticasone furoate, and ciclesonide exhibit pharmacokinetic characteristics associated with minimal systemic exposure because of extensive first-pass metabolism and low oral bioavailability. Although substantial pharmacokinetic differences exist between currently available INCS formulations, direct comparative evidence demonstrating clinically meaningful superiority in systemic safety outcomes remains limited. Current evidence suggests that formulation-dependent differences are clinically more relevant with respect to local tolerability, sensory characteristics, patient preference, and long-term adherence than major systemic safety outcomes. Pediatric evidence is generally reassuring, although historical concerns regarding growth suppression associated with earlier corticosteroid formulations continue to influence clinical practice. Currently available evidence supports the use of modern INCS as effective and generally well-tolerated therapeutic options across adult and pediatric populations. Full article

Chronic rhinosinusitis (CRS) constitutes a multicausal inflammatory disease of the nose and paranasal sinuses, often associated with olfactory dysfunction (OD), a symptom that significantly impacts patients’ quality of life. OD in CRS was traditionally thought to be related to mechanical obstruction of the olfactory cleft, but is now considered to be multifactorial, involving conductive, inflammatory, and sensorineural mechanisms as well. Type-2 inflammatory response (high interleukins IL-4, IL-5, IL-13), eosinophilia, and increased IgE are involved in epithelial damage, impaired neurogenesis, and persistent olfactory loss, especially in chronic rhinosinusitis with nasal polyps (CRSwNP). In addition, peripheral chronic inflammation may also play a role in central neural remodeling, which may potentially affect olfactory function. Objective psychophysical testing is necessary to accurately assess olfactory function because self-reports may lack reliability. Management strategies aim at reducing inflammation and restoring sinonasal ventilation. First-line therapy with intranasal corticosteroids and short courses of systemic corticosteroids may be useful for symptomatic relief. Biologic agents directed against type-2 inflammation have demonstrated significant benefits in selected cases. Functional Endoscopic Sinus Surgery (FESS) plays an important role in the treatment of refractory CRS to restore the airflow and to improve the delivery of topical drugs. Olfactory outcomes following surgery, however, are variable and often incomplete, reflecting underlying inflammation and neuroepithelial damage. Disease recurrence, especially in type-2–driven CRS, affects long-term outcomes, underscoring the necessity to incorporate surgery in an individualized, endotype-informed treatment strategy. Full article

Background: The aim of this study was to evaluate the efficacy of mepolizumab as add-on therapy to intranasal corticosteroids (INCSs) for the treatment of severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNPs) in a real-life setting. Methods: This prospective observational study included 60 patients with severe uncontrolled CRSwNP who received mepolizumab. Follow-up assessments were performed at baseline (T0), 3 months (T1), and 6 months (T2). At each time point, patients underwent nasal endoscopy, completed the sinonasal outcome test-22 (SNOT-22), visual analogue scales (VAS) for smell, nasal obstruction and rhinorrhoea and facial pain. Nasal secretion and blood eosinophil counts (BECs) were also evaluated. The levels of eosinophil cationic protein (ECP) in nasal secretions were measured using an enzyme-linked immunosorbent assay (ELISA). Results: Both patient- and physician-derived outcome measures showed significant improvements from baseline to 3 months, and the benefits were maintained at 6 months. No major adverse events were reported. Conclusions: Mepolizumab was associated with improvements in nasal obstruction and sense of smell, based on both patient- and physician-derived outcome measures. However, due to the single-arm design and modest sample size, these findings should be considered hypothesis-generating rather than confirmatory. Full article

Background: Allergic rhinitis (AR) is commonly treated with intranasal and oral pharmacotherapy or allergen immunotherapy (AIT), each associated with distinct safety considerations. This study aimed to systematically evaluate and compare the safety profiles of these therapeutic approaches by analysing adverse events (AEs) reported in completed randomised controlled trials (RCTs). Methods: A meta-epidemiological analysis was conducted using completed RCTs registered in ClinicalTrials.gov up to 20 October 2023. Trials investigating intranasal drugs, oral medications, or AIT for AR were identified using predefined search terms. Adverse events were manually extracted and categorised according to treatment class and dosage. Other adverse events (OAEs) were classified using Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) and Medical Dictionary for Regulatory Activities (MedDRA) terminology. Meta-analyses compared OAE incidence across treatment groups, including standard-dose, higher-dose, and placebo arms. Results: A total of 216 RCTs were included. Intranasal therapies accounted for 55.56% of trials, predominantly intranasal corticosteroids (INCS) and intranasal antihistamines (INAH). OAE incidence was 16.37% for INCS, 29.43% for INAH, and 8.71% for combination therapy. INAH was associated with higher rates of dysgeusia and nasal discomfort, while higher INCS doses were linked to an increased risk of urinary tract infections. AIT trials comprised 22.69% of studies and demonstrated higher OAE rates, particularly for sublingual immunotherapy (64.96%), followed by subcutaneous (53.98%) and intralymphatic immunotherapy (62.50%). Oropharyngeal AEs were most frequent with sublingual immunotherapy. Oral medications (18.06%) showed the lowest OAE incidence, with upper respiratory tract infections occurring more frequently with oral antihistamines. Conclusions: Among intranasal therapies, INCS demonstrated the most favourable safety profile. Sublingual immunotherapy was associated with a higher frequency of OAEs compared with other AIT modalities. Combination oral antihistamine and leukotriene receptor antagonist therapy appeared to be the safest oral treatment option. Further well-designed studies are needed to refine comparative safety assessments across AR treatments. Full article

The concept of united airway disease (UAD) highlights the bidirectional relationship between inflammatory disorders of the upper airways—such as allergic rhinitis and chronic rhinosinusitis with or without nasal polyps (CRSwNP/CRSsNP)—and lower airway diseases, most notably asthma. This paradigm is supported by epidemiological, embryological, and immunological evidence demonstrating that airway inflammation represents a single, interconnected process rather than isolated compartmental pathology. Central to many UAD phenotypes is type 2 (T2) inflammation, driven by cytokines including IL-4, IL-5, and IL-13, and mediated by effector cells such as eosinophils and group 2 innate lymphoid cells (ILC2s). Epithelial barrier dysfunction often serves as the initiating trigger for this shared inflammatory cascade by production of TSLP, IL-25 and IL-33. Optimal diagnosis and management of UAD require an integrated, multidisciplinary framework. Clinical evaluation remains essential for patient characterization but must be complemented by pheno-endotypic assessment using imaging (CT), allergy testing, biomarker profiling (FeNO, blood eosinophils, IgE), and pulmonary function testing (spirometry, impulse oscillometry). Therapeutic strategies are layered, targeting both symptom control and inflammation across airway compartments. Standard approaches include intranasal and inhaled corticosteroids as well as saline irrigations, while severe T2-high disease increasingly benefits from biologic therapies (anti-IL-5/IL-5R, anti-IL-4R, anti-TSLP), which reduce dependence on systemic corticosteroids and surgical interventions such as endoscopic sinus surgery (ESS). Emerging precision-medicine models, particularly the “treatable traits” approach, further underscore the need to view the airway as a unified system. Collectively, these insights reinforce the clinical imperative of addressing upper and lower airway disease as a continuum, ensuring that inflammation in one district is neither overlooked nor treated in isolation. Full article

Background and Objectives: Parental beliefs strongly influence treatment adherence in pediatric allergic diseases. Concerns about corticosteroid therapy—known as corticophobia—may disrupt disease control and compromise child well-being. This study aimed to evaluate parental knowledge, beliefs, and concerns regarding topical, inhaled, and intranasal corticosteroid use in children, and to identify sociodemographic factors associated with corticophobia. Materials and Methods: This prospective survey was conducted in a tertiary pediatric allergy and immunology clinic. A structured questionnaire was anonymously completed by 110 parents of children receiving corticosteroid therapy. The survey assessed demographics, family history of atopy, corticosteroid use, perceived disease severity, knowledge level, concerns, and sources of information. Descriptive statistics and chi-square tests were applied (p < 0.05 significant). Results: The most frequent concerns were growth retardation, hormonal imbalance, and long-term side effects. Corticophobia was significantly more prevalent among university-educated parents (p = 0.043) and those with a family history of atopy (p = 0.017). Despite generally high adherence to prescribed regimens, nearly 60% of parents sought additional information, highlighting the impact of knowledge gaps on health-related parenting practices. Conclusions: Corticophobia remains a common parental concern in pediatric allergy care, with implications for adherence, family decision-making, and child well-being. Addressing misinformation and providing family-centered, tailored educational strategies—particularly for highly educated parents and those with an atopic background—may reduce fears, strengthen trust, and promote sustainable healthy behaviors. Full article

Background/Objectives: Black hairy tongue syndrome (BHT) is characterized by structural epithelial changes and a dark discoloration on the surface of the tongue, causing a variety of symptoms such as xerostomia, altered taste, and nausea. Methods: Herein, we report a 70-year-old female patient with a history of Sjogren’s syndrome, rheumatoid arthritis, and occasional use of intranasal and inhaled corticosteroids, who presented with BHT exacerbated by consumption of colored beverages and carbohydrates. We also provide a review of the literature on published articles reporting cases of BHT syndrome. Results: Our patient’s condition improved after implementing dietary restrictions in combination with local care. A literature review revealed that the most common reported exposures and underlying conditions in patients with BHT were the recent administration of antibiotics, solid organ or hematologic malignancy, immunosuppressants, smoking, corticosteroids, autoimmune conditions, receipt of antidepressants, local radiation therapy, proton pump inhibitors, and alcohol. The majority of cases were successfully managed with the elimination of implicated factors when possible and local hygiene. Conclusions: Different factors may contribute to the development of BHT. Discontinuation of implicated medications together with measures for topical care constitute the most effective ways to achieve resolution. Full article

Background: Cystic Fibrosis (CF) is an autosomal recessive inherited disease caused by mutations of the CF–transmembrane conductance regulator (CFTR), leading to impaired chloride ion trafficking, thickened secretions, and chronic rhinosinusitis (CF-CRS). CF-CRS was historically managed with intranasal corticosteroids (INCS) and endoscopic sinus surgery (ESS). Nowadays, the triple highly effective modulator therapy elexacaftor–tezacaftor–ivacaftor (ETI) is showing promising results in improving CF-CRS. Methods: This is a monocentric, retrospective study comparing Sinonasal Outcome Test-22 (SNOT-22), Nasal Polyps Score (NPS), modified Lund–Kennedy score (mLKS), sniffin’ sticks identification test (SSIT), and Lund–Mackay score (LMS) in patients affected by CF-CRS and treated with ESS or ETI. ETI patients were further subdivided based on previous surgery. Results: A total of 25 patients were surgically treated, and 54 were treated with ETI (specifically, 17 surgically naïve and 37 post-FESS patients). Patients undergoing ESS and those receiving ETI experienced statistically significant improvements in SNOT-22, SSIT, and LMS with no differences between groups and regardless of genetic or demographic characteristics. Conversely, ESS patients experienced significantly higher mean changes in NPS and mLKS. Conclusions: ETI and FESS were safe and effective in reducing the symptomatologic burden of CF-CRS. Even in the ETI epoch, surgery may play a crucial role in managing CF-CRS, particularly in patients not eligible for ETI or experiencing severe disease not adequately controlled with medical therapy alone. Full article

Background/Objectives: Patients with severe asthma (SA) commonly present with coexisting nasal polyposis (NP), often requiring treatment with intranasal corticosteroids (INC). However, adherence to INC in this population remains inadequately characterized despite its clinical significance. This study aimed to evaluate adherence to INC in patients with SA and NP and to identify clinical and pharmacological factors associated with adherence levels. Methods: We conducted a retrospective observational study including adult patients with SA and NP treated with INC and followed at a tertiary asthma unit in Madrid during 2024. Adherence was assessed via medication possession ratio (MPR) over six months, with poor adherence defined as MPR < 50%. Pharmacological, clinical and demographic variables were analyzed for associations with adherence. Results: Of the 188 patients evaluated, 86 (45.7%) were prescribed INC. Poor adherence was observed in 53.5% of these patients. Women exhibited significantly lower adherence compared to men (p < 0.05). Fluticasone was the most commonly prescribed INC (54.6%), with no significant adherence differences across corticosteroid types. Patients on maintenance systemic corticosteroids had higher adherence (85.7%, p < 0.05), whereas those receiving biologic therapies tended toward lower adherence (51% poor adherence), though this was not statistically significant. Higher adherence was associated with increased disease severity, as indicated by multiple endoscopic sinus surgeries (p < 0.05). No significant differences were observed in spirometry or Asthma Control Test scores. Conclusions: Adherence to INC in patients with SA and NP is suboptimal, particularly among women and patients on biologics. Greater disease severity correlates with improved adherence. Targeted interventions are necessary to enhance adherence and optimize disease management in this population. Full article

Obstructive sleep apnea syndrome (OSAS) in children and adolescents is a prevalent and multifactorial disorder associated with significant short- and long-term health consequences. While adenotonsillectomy (AT) remains the first-line treatment, a substantial proportion of patients—especially those with obesity, craniofacial anomalies, or comorbid conditions—exhibit persistent or recurrent symptoms, underscoring the need for individualized and multimodal approaches. This review provides an updated and comprehensive overview of current and emerging treatments for pediatric OSAS, with a focus on both surgical and non-surgical options, including pharmacological, orthodontic, and myofunctional therapies. A narrative synthesis of recent literature was conducted, including systematic reviews, randomized controlled trials, and large cohort studies published in the last 10 years. The review emphasizes evidence-based indications, mechanisms of action, efficacy outcomes, safety profiles, and limitations of each therapeutic modality. Adjunctive and alternative treatments such as rapid maxillary expansion, mandibular advancement devices, myofunctional therapy, intranasal corticosteroids, leukotriene receptor antagonists, and hypoglossal nerve stimulation show promising results in selected patient populations. Personalized treatment plans based on anatomical, functional, and developmental characteristics are essential to optimize outcomes. Combination therapies appear particularly effective in children with residual disease after AT or with specific phenotypes such as Down syndrome or maxillary constriction. Pediatric OSAS requires a tailored, multidisciplinary approach that evolves with the child’s growth and clinical profile. Understanding the full spectrum of available therapies allows clinicians to move beyond a one-size-fits-all model, offering more precise and durable treatment pathways. Emerging strategies may further redefine the therapeutic landscape in the coming years. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifaceted inflammatory disorder characterized by distinct immunopathogenic entities, including type 2 inflammation mediated by cytokines such as interleukin-4 (IL-4), IL-5, and IL-13. These cytokines contribute to eosinophilic inflammation, epithelial barrier dysfunction, and mucus overproduction, resulting in polyp formation. Advances in molecular understanding have resulted in the identification of CRSwNP endotypes, suggesting personalized treatment approaches. Conventional therapies, such as intranasal and systemic corticosteroids, provide symptom relief but are restricted by side effects and polyp recurrence, necessitating the development of novel targeted approaches. Biologic therapies represent a breakthrough in CRSwNP management. Monoclonal antibodies such as dupilumab, omalizumab, mepolizumab, and Benralizumab (IL-5 receptor alpha) target key mediators of type 2 inflammation, leading to substantial improvements in polyp size, symptom control, and quality of life. Additionally, emerging therapies like tezepelumab and brodalumab aim to address broader immune mechanisms, including type 1 and type 3 inflammation. These advancements enable tailored treatment approaches that optimize outcomes and reduce reliance on surgical interventions. Biomarker-driven research continues to refine CRSwNP classification and treatment efficacy, emphasizing precision medicine. Future efforts should focus on expanding the therapeutic landscape, investigating long-term impacts of biologics, and exploring their combinatory potential to improve disease control. This review discusses the role of innate and adaptive immunity in the pathogenesis of CRSwNP and suggests novel cytokine-targeted strategies for further considering personalized medicine in future therapeutic plans. Full article

Background/Objectives: Mometasone furoate (MF) is a topical corticosteroid used to reduce allergic and inflammation symptoms. In this study, MF was incorporated into the hydrophobic cavities of γ-cyclodextrin metal-organic frameworks (CD-MOFs) to prepare MF@MOF powders for nasal delivery. Methods: MF@MOF particles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and thermogravimetry. A transparent biomimetic model of the human nasal cavity was produced by 3D printing and used to evaluate intra-nasal depositions patterns. Results: Drug loading was optimized by incubating MF with a CD-MOF at a ratio of 4% for 1 h at 40 °C, and the cubic morphology and particle size of the nanoparticles were not altered using an incubation method. PXRD and FTIR analyses confirmed the successful loading of MF into the CD-MOF. Using a 3D biomimetic nasal cavity model, a 30° administration angle was found to result in reduced drug accumulation in the nasal vestibule and enhanced deposition in the respiratory and olfactory regions, compared with administration at 45°. Approximately 51% of the drug reached the respiratory zone in the model of the nasal cavity from male subjects, while almost 60% of the drug reached this zone in the model associated with female subjects. Compared with nasal sprays, nasal powder sprays had less deposition in the nasal vestibule and more deposits in the middle and inferior nasal concha. Conclusions: MF@MOF is suitable for intranasal administration. Delivery of MF as a nasal powder shows potential in the treatment of chronic rhinosinusitis. Full article

Background/Objectives: Paediatric Obstructive Sleep Apnoea (OSA) is characterised by recurrent episodes of upper airway obstruction during sleep, manifesting as snoring, intermittent oxygen desaturation, and frequent nocturnal awakenings. Standard treatments include surgical interventions, pharmacological therapies, intranasal corticosteroids, and oral montelukast. However, significant variability exists across studies regarding dosage and outcome assessment. This literature review systematically evaluated clinical evidence regarding the efficacy and safety of intranasal corticosteroids and oral montelukast for treating sleep-disordered breathing and its primary underlying condition, adenoid hypertrophy, in otherwise healthy children. Methods: The MEDLINE (PubMed), Scopus, and Web of Science databases were systematically searched up to 13 February 2025, using tailored search terms combining keywords and synonyms related to paediatric OSA, adenoidal hypertrophy, corticosteroids, montelukast, and randomised controlled trials. Owing to variability in outcome measures, Fisher’s method for p-value combination was employed to enable a comprehensive comparison of drug effects. Results: Available evidence shows that intranasal corticosteroids (mometasone, beclometasone, budesonide, fluticasone, and flunisolide), either as monotherapy or in combination with other agents, consistently lead to clinical and instrumental improvements in adenoid hypertrophy and related respiratory symptoms, with a generally favourable safety profile. Combining montelukast with intranasal corticosteroids appears to offer superior benefits compared with monotherapy. Nevertheless, the reviewed studies varied widely in dosage, treatment duration, design, and sample size. The reported side effects are mostly mild; however, long-term studies are lacking to establish the complete safety of these treatments in children. Conclusions: Intranasal corticosteroids and oral montelukast effectively and safely manage adenoid hypertrophy and mild-to-moderate OSA symptoms in children. Nonetheless, the heterogeneity of study designs necessitates larger prospective trials with standardised protocols and more extended follow-up periods to draw more robust conclusions. Future studies should aim to stratify treatment outcomes based on OSA severity and duration to tailor therapeutic approaches better. Full article

Background/Objectives: Nasal irrigation with isotonic seawater is a known and oft-used treatment for nasal obstruction in patients with acute and chronic nasal inflammatory disease undergoing therapy with intranasal corticosteroids and antihistamine drugs. Nasal patency in healthy athletes is extremely important; however, to date, the effect of isotonic solutions for nasal irrigation in healthy athletes has not been tested. This randomized controlled trial aimed to investigate the potential synergy of physical exercise and nasal isotonic seawater on airflow and the subjective assessment of nasal patency in healthy, high-level athletes. Methods: The intervention group included 33 healthy athletes who used an isotonic seawater nasal spray daily, with a control group including 31 healthy athletes who did not use any sprays; both groups underwent identical seven-day training periods. The primary outcome measures were subjective NOSE questionnaire scores and secondary peak nasal inspiratory flow (PNIF) measures, while anthropometric and demographic variables were covariates. Results: A significant decrease in subjective nasal resistance scores was observed in the intervention group compared to the control group (binary logistic regression model, p = 0.006, RR 7.695), both in the first and second measurement interval. This effect increased with time (Friedman’s two-way analysis of variance, p < 0.001). Peak nasal inspiratory flow is positively affected by exercise but not by isotonic seawater spray intervention. Conclusions: The effects of nasal isotonic seawater irrigation during intense athletic training are beneficial on subjective nasal patency in the short term, while the effects on objective nasal patency are less clear. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a subtype of chronic rhinosinusitis (CRS) characterized by bilateral nasal polyps, primarily affecting adults. It is often associated with hyposmia and asthma and driven by persistent Th2 inflammation, particularly in Caucasian patients. The disease is recurrent and significantly impacts quality of life, yet its pathophysiology remains poorly understood. Management includes intranasal steroids, short courses of systemic corticosteroids, surgery for refractory cases, and biologics. However, despite these treatment options, disease control remains challenging. Low vitamin D levels have been associated with worse clinical outcomes, while supplementation studies show promise in improving symptoms in deficient patients. Emerging research suggests that vitamin D modulates immunity, fibroblast activity, and epithelial integrity, potentially contributing to CRSwNP pathogenesis, though the exact mechanisms remain unclear. This review synthesizes current research on vitamin D’s role in systemic and local inflammation in CRSwNP. By highlighting its potential therapeutic implications, this work aims to guide future research and inform clinical practice. Additionally, it may serve as a foundation for understanding the broader impact of vitamin D deficiency in sinonasal diseases and other atopic conditions. Full article