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Purpose of the Review: Thymic stromal lymphopoietin (TSLP) is increasingly recognized for its pivotal role in the pathogenesis of various epithelial-driven chronic inflammatory diseases. This review navigates the existing evidence on TSLP, with a particular focus on asthma, before delving into the current understanding of its role in chronic rhinosinusitis with nasal polyps (CRSwNP). We explore the role of TSLP in the pathogenesis of asthma and CRSwNP, two conditions often interconnected and collectively referred to as"Global Airway Disease". Additionally, this review assesses the therapeutic potential of TSLP inhibition as a treatment option for both CRSwNP and asthma. A systematic literature search was conducted; selected publications were used to describe the biology of TSLP, including its expression and diverse effects on inflammation., Recent Findings: The role of TSLP in asthma is well established and supported by the efficacy of tezepelumab, the first anti-TSLP monoclonal antibody approved for both type 2 (T2)-high and T2-low severe asthma. TSLP may be a key contributor to CRSwNP pathogenesis as evidenced by genetic and mechanistic studies in which TSLP has been shown to regulate T2 inflammation and influence non-T2 responses. Preliminary data from the NAVIGATOR trial indicate that tezepelumab may reduce CRSwNP symptoms in patients with comorbid asthma. While further research is required to clarify the extent of TSLP contribution in CRSwNP, this review highlights the potential of anti-TSLP therapies as a novel approach for managing severe, uncontrolled CRSwNP. If these preliminary findings are confirmed, targeting TSLP could become a promising strategy to treat CRSwNP with or without comorbid asthma., Competing Interests: Declarations. Human and Animal Rights Statement: This article does not contain any studies with human or animal subjects performed by any of the authors. Competing Interests: E. De Corso received lecture fees and participated to advisory boards for Sanofi, GSK, Regeneron, Astrazeneca. P. W. Hellings has received unrestricted research grants from Sanofi/Regeneron, Viatris and GSK, and honoraria for lectures and/or advisory boards by Sanofi/Regeneron, GSK, and AstraZeneca. W. J. Fokkens received consultation and/or speaker fees from Dianosic, GSK, Menarini, Novartis, Sanofi-Aventis/Regeneron and AstraZeneca. The department of Otorhinolaryngology of the Amsterdam University Medical Centre, location AMC, received grants for research in Rhinology from: Novartis, EU, GSK, and Sanofi-Aventis. L. Klimek reports grants from Allergopharma, MEDA/Mylan, ALK Abelló, LETI Pharma, Stallergenes, Sanofi, ASIT biotech, Lofarma Quintiles, AstraZeneca, GSK, and Inmunotk; and personal fees from Allergopharma, MEDA/Mylan, HAL Allergie, LETI Pharma, Sanofi, Allergy Therapeut, and Cassella Med, outside the submitted work. A. T. Peters has received research grants from Sanofi/Regeneron and AstraZeneca. She has served as a consultant for GSK, Chiesi, Merck, Sanofi Regeneron, Eli Lilly and AstraZeneca. G. K. Scadding received honoraria for articles, speaker and advisory boards: ALK, Bayer, Chiesi, GSK, Haleon, Noucor, Sanofi- Regeneron, and Viatris. Chair of BSACI rhinitis guidelines, Scientific Chief Editor, Rhinology Section of Frontiers in Allergy, Vice President and AR lead for EUFOREA, and Chair/ member Data Monitoring Committees on SLIT for ALK. M. Desrosiers received fee for consultation, speaker activity, advisory board by sanofi/ Regeneron, GSK. He also received research support from Sanofi/Regeneron, GSK. Equity holder, Probionase Therapies Inc. S. E. Lee has received clinical trial funding and served on advisory boards for AstraZeneca, Genentech, Lyra Therapeutics, GSK, Optinose, Sanofi Regeneron, Upstream Bio and holds equity in Diceros Therapeutics. J. Mullol reports personal fees and other from SANOFI-GENZYME & REGENERON, personal fees and other from NOVARTIS, grants, personal fees and other from VIATRIS / MEDA Pharma, grants and personal fees from NOUCOR / URIACH Group, personal fees from Menarini, personal fees from UCB, personal fees and other from AstraZeneca, grants, personal fees and other from GSK, personal fees from MSD, personal fees and other from Lilly, personal fees and other from GLENMARK, outside the submitted work. J. Mullol is a Section Editor of Current Allergy and Asthma Reports and was not involved in the peer-review or handling of the manuscript., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: We aimed to review the latest evidence regarding the value of tissue histopathological analysis in chronic rhinosinusitis with nasal polyps (CRSwNP) and to facilitate tissue analysis by proposing a pragmatic checklist for clinical settings., Recent Findings: CRSwNP is a chronic inflammatory disease that severely impairs the patient's quality of life. The severity of the disease can be correlated with nasal polyps enriched in eosinophils/IL-5 and, although ≥ 10 eosinophils per high power field are considered enough to determine an eosinophilic CRS, this cut-off value, the biopsy method, and the sampling location are still a matter of debate. Besides, tissue eosinophil values might also have some added value when combined with other cellular counts (e.g., eosinophil-to-lymphocyte ratio, Charcot-Leyden crystals). Structured histopathology analysis of sinonasal tissue-including, for instance, tissue remodelling biomarkers, fibrosis, and eosinophilic aggregates-has proven to be a valuable tool for healthcare professionals to identify different pheno-endotypes of CRSwNP and to improve the prioritisation of candidates to targeted therapies. Patients with CRSwNP are treated according to their severity with corticosteroids (intranasal and systemic), endoscopic sinus surgery, and/or biological therapy. A panel of expert ear, nose, and throat specialists and pathologists proposed a pragmatic checklist to improve the clinical practice around tissue analysis in CRSwNP, to facilitate communication between hospital-based healthcare professionals, and to standardize the evaluation of inflammatory biomarkers., (© 2024. The Author(s).)

Purpose of Review: To present current evidence in long-term (> 5 years) results after endoscopic sinus surgery (ESS) focusing on Patients Reported Outcome Measures (PROMs) and other sinonasal outcomes while assessing the role of ESS in the treatment of CRSwNP, and identifying outcomes which affect the results of ESS and defining recommendations for future studies., Recent Findings: Long-term results of ESS in CRSwNP can be branched in PROMs and other objective measurements. Despite the heterogeneity of reported outcomes make it difficult to perform comparisons and meta-analysis, ESS improves PROMs, including symptoms, QOL and olfaction. Objectives outcomes such as NPS, LMS, type of surgery, or recurrence and revision surgery don't have a clear role in long-term results. Clustering patients suggest asthma, N-ERD, allergy, eosinophil count and IL-5 could have a role in predicting recurrence and severe disease. Long-term studies of CRSwNP treated with ESS are scarce. There is a significant need to standardize the report of results. The use of tools as SNOT-22, NPS, validated smell tests, defined criteria for disease recurrence and control and ESS extension in a unified systematic way could allow better comparisons between treatments in the new era of biologics., (© 2024. The Author(s).)

Purpose of Review: Neurogenesis occurring in the olfactory epithelium is critical to continuously replace olfactory neurons to maintain olfactory function, but is impaired during chronic type 2 and non-type 2 inflammation of the upper airways. In this review, we describe the neurobiology of olfaction and the olfactory alterations in chronic rhinosinusitis with nasal polyps (type 2 inflammation) and post-viral acute rhinosinusitis (non-type 2 inflammation), highlighting the role of immune response attenuating olfactory neurogenesis as a possibly mechanism for the loss of smell in these diseases., Recent Findings: Several studies have provided relevant insights into the role of basal stem cells as direct participants in the progression of chronic inflammation identifying a functional switch away from a neuro-regenerative phenotype to one contributing to immune defense, a process that induces a deficient replacement of olfactory neurons. The interaction between olfactory stem cells and immune system might critically underlie ongoing loss of smell in type 2 and non-type 2 inflammatory upper airway diseases. In this review, we describe the neurobiology of olfaction and the olfactory alterations in type 2 and non-type 2 inflammatory upper airway diseases, highlighting the role of immune response attenuating olfactory neurogenesis, as a possibly mechanism for the lack of loss of smell recovery., (© 2024. The Author(s).)

Purpose of Review: To review the effects of endoscopic sinus surgery and endonasal approaches to the skull base on olfaction., Recent Findings: Advancements in endonasal endoscopic approaches to the sinuses and skull base allow for direct treatment of a variety of sinonasal and skull base diseases. However, these extended approaches will often require manipulation of normal anatomical structures and the olfactory neuroepithelium. Depending on the planned procedure and extent of disease, the prognosis of olfactory perception can vary significantly among patients. Endoscopic sinonasal surgical procedures may impact olfaction. Optimizing olfactory function requires proper surgical techniques, gentle handling of tissue, and perioperative care. Surgeons must discuss objectives and manage patient expectations. Routine olfactory assessment is crucial in surgical work-up and follow-up. Preserving anatomical structures while addressing the obstruction of the olfactory cleft helps to prevent decreased olfactory threshold. However, smell identification and discrimination do not always correlate with sinonasal anatomy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Mechanical nasal obstruction (MNO) is a prevalent condition with a high impact on patient's quality-of-life (QoL) and socio-economic burden. The aim of this study was to determine the usefulness of both subjective and objective criteria in the appropriate management of MNO, either alone or associated to upper airway inflammatory diseases such as allergic rhinitis (AR) or chronic rhinosinusitis with nasal polyps (CRSwNP)., Recent Findings: A long debate persists about the usefulness of subjective and objective methods for making decisions on the management of patients with nasal obstruction. Establishing standards and ranges of symptom scales and questionnaires is essential to measure the success of an intervention and its impact on QoL. To our knowledge this is the first real-life study to describe the management of MNO using both subjective and objective criteria in MNO isolated or associated to upper airway inflammatory diseases (AR or CRSwNP). Medical treatment (intranasal corticosteroids) has a minor but significant improvement in MNO subjective outcomes (NO, NOSE, and CQ7) with no changes in loss of smell and objective outcomes. After surgery, all MNO patients reported a significant improvement in both subjective and objective outcomes, this improvement being higher in CRSwNP. We concluded that in daily clinical practice, the therapeutic recommendation for MNO should be based on both subjective and objective outcomes, nasal corrective surgery being the treatment of choice in MNO, either isolated or associated to upper airway inflammatory diseases, AR or CRSwNP., (© 2023. The Author(s).)

Purpose of Review: In the clinical practice, patients affected by chronic rhinosinusitis (CRS) commonly complain of otologic symptoms. This review aims to describe the available literature evidence assessing the relationship between CRS and ear illnesses published in the last 5 years., Recent Findings: Available evidence suggests a higher prevalence of otologic symptoms in patients suffering from CRS, affecting up to 87% of patients. These symptoms may be related to Eustachian tube dysfunction, which improves after treatment for CRS. A few studies suggested a potential but not confirmed role of CRS in cholesteatoma, chronic otitis media, and sensorineural hypoacusis. A special type of otitis media with effusion (OME) may occur in patients with CRS, which seems to respond well to new biologic therapy. Ear symptoms appear to be highly prevalent in patients with CRS. So far, the available evidence is robust only for Eustachian tube dysfunction, which has been shown to be particularly impaired in CRS patients. Additionally, the Eustachian tube function appears to improve after treatment for CRS. Finally, interesting preliminary data were described for eosinophilic otitis media, as it appears to respond well to the treatment with biologics., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Antrochoanal polyps (ACPs) are benign polypoid lesions arising from the inner wall of the maxillary sinus and extending into the choana. Although the diagnosis and treatment strategies of ACP have changed since this entity was first described, the underlying pathogenic mechanism of APC is poorly understood. This article reviews the current knowledge of the etiology, inflammatory parameters, and microscopic findings of ACP., Recent Findings: The inflammatory pattern of ACP appears to center around a neutrophilic inflammation T1-dominant endotype. Apart from the inflammatory component of ACP, at the microscopic level, the presence of tissue remodeling, mostly fibrin deposition and edema, and cysts in the epithelium and lamina propria has been described. Although the origin of this T1-dominant endotype immune response of ACPs is not entirely clear, it could be related to a lymphatic obstruction mechanism. This review serves to define a phenotype of ACP with potential endotypes based on the characteristics of the inflammatory parameters, microscopic findings, and hypotheses about the pathogenesis of ACP., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Olfactory dysfunction contributes to the psychopathology of mental illness. In this review, we describe the neurobiology of olfaction, and the most common olfactory alterations in several mental illnesses. We also highlight the role, hitherto underestimated, that the olfactory pathways play in the regulation of higher brain functions and its involvement in the pathophysiology of psychiatric disorders, as well as the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in psychiatric conditions., Recent Findings: The olfactory deficits present in anxiety, depression, schizophrenia or bipolar disorder consist of specific alterations of different components of the sense of smell, mainly the identification of odours, as well as the qualifications of their hedonic valence (pleasant or unpleasant). Epidemiological findings have shown that both environmental factors, such as air pollutants, and inflammatory disease of the upper respiratory tract, can contribute to an increased risk of mental illness, at least in part, due to peripheral inflammatory mechanisms of the olfactory system. In this review, we describe the neurobiology of olfaction, and the most common olfactory function alterations in several psychiatric conditions and its role as a useful symptom for the differential diagnosis. We also highlight the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in these psychiatric conditions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: While the predominant cause for morbidity and mortality with SARS-CoV-2 infection is the lower respiratory tract manifestations of the disease, the effects of SARS-CoV-2 infection on the sinonasal tract have also come to the forefront especially with the increased recognition of olfactory symptom. This review presents a comprehensive summary of the mechanisms of action of the SARS-CoV-2 virus, sinonasal pathophysiology of COVID-19, and the correlation with the clinical and epidemiological impact on olfactory dysfunction., Recent Findings: ACE2 and TMPRSS2 receptors are key players in the mechanism of infection of SARS-CoV-2. They are present within both the nasal respiratory as well as olfactory epithelia. There are however differences in susceptibility between different groups of individuals, as well as between the different SARS-CoV-2 variants. The sinonasal cavity is an important route for SARS-CoV-2 infection. While the mechanism of infection of SARS-CoV-2 in nasal respiratory and olfactory epithelia is similar, there exist small but significant differences in the susceptibility of these epithelia and consequently clinical manifestations of the disease. Understanding the differences and nuances in sinonasal pathophysiology in COVID-19 would allow the clinician to predict and counsel patients suffering from COVID-19. Future research into molecular pathways and cytokine responses at different stages of infection and different variants of SARS-CoV-2 would evaluate the individual clinical phenotype, prognosis, and possibly response to vaccines and therapeutics., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Increasing knowledge of the pathogenesis of the SARS-CoV-2 infection and the complex interaction between host and viral factors have allowed clinicians to stratify the severity of COVID-19 infection. Epidemiological data has also helped to model viral carriage and infectivity. This review presents a comprehensive summary of the pathophysiology of COVID-19, the mechanisms of action of the SARS-CoV-2 virus, and the correlation with the clinical and biochemical characteristics of the disease., Recent Findings: ACE2 and TMPRSS2 receptors have emerged as a key player in the mechanism of infection of SARS-CoV-2. Their distribution throughout the body has been shown to impact the organ-specific manifestations of COVID-19. The immune-evasive and subsequently immunoregulative properties of SARS-CoV-2 are also shown to be implicated in disease proliferation and progression. Information gleaned from the virological properties of SARS-CoV-2 is consistent with and reflects the clinical behavior of the COVID-19 infection. Further study of specific clinical phenotypes and severity classes of COVID-19 may assist in the development of targeted therapeutics to halt progression of disease from mild to moderate-severe. As the understanding of the pathophysiology and mechanism of action of SARS-CoV-2 continues to grow, it is our hope that better and more effective treatment options continue to emerge., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: A multidisciplinary approach is regarded as the best practice for many chronic diseases, such as cancer and asthma, with well-documented value. There is also evidence that it may be beneficial to patients with chronic rhinosinusitis (CRS) and/or allergic airway disease presenting to tertiary referral centres. We discuss here whether and how organizing this kind of healthcare transition into a more integrated care pathway would benefit severe chronic upper airways disease (SCUAD) management., Recent Findings: Based on a recent related EUFOREA panel discussion, literature search, and review of the best overseas practices, an appropriate implementation strategy of multidisciplinary care and its potential results are presented. Organizational principles, hurdles, and challenges of the process, as well as envisaged solutions and results, are being reported. The efficiency of care and the quality control assessment are concepts that are currently gaining importance. At the same time, novel treatment options based on molecular and precision medicine advancements, such as biologics, are being increasingly prescribed. Appropriately organized multidisciplinary care teams can adapt to new demands, data, and discoveries to assure maximum benefit for both patients and healthcare professionals.

Purpose of Review: The aim of this study was to review and describe the main innovative surgical techniques for nasal septal perforation (NSP) repair that have been published in recent years., Recent Findings: Several techniques for NSP repair have been developed recently. The anterior ethmoidal artery (AEA) flap is a versatile technique for middle-size perforations in different locations. The greater palatine artery (GPA) flap is an excellent option for anterior-most NSPs. The lateral nasal wall flap and the pericranial flap are the most appropriate techniques for large perforations. The advent of these techniques has changed the management and has expanded the therapeutic arsenal to treat all types of NSPs according to the size, location, and osteo-cartilaginous support. However, no technique has been accepted as the gold standard. Extensive knowledge of different techniques is important to individualize the treatment, selecting the most appropriate in each case.

Purpose of Review: Chemosensory dysfunction in the patients with COVID-19 has been reported frequently in the studies from different regions of the world. However, the prevalence of smell and/or taste disorders presents significant ethnic and geographic variability. In addition, the pathogenesis of chemosensory dysfunction remains unclarified., Recent Findings: This is a narrative review on the recent state of the prevalence, mechanism, and diagnostic and therapeutic strategy of chemosensory dysfunction in COVID-19 patients during the global pandemic. The chemosensory dysfunction was analysis based on recent studies, which either used questionnaires, Likert scales (0-10), or smell tests to estimate the smell and taste dysfunction. The ethnic and geographic difference of the prevalence of smell and/or taste disorders and the potential underlying mechanisms have been discussed. Several suggestions on the diagnosis and treatment of COVID-19 patients with smell and taste disorders were summarized for the physicians. This review provides a comprehensive overview of the current studies regarding the chemosensory dysfunction during the COVID-19 worldwide outbreak.

Purpose of Review: To study the prevalence of olfactory loss and its associated factors in a Mexican population a cross-sectional analytical study based on a population interviewed about health, epidemiologic aspects, and sense of smell (tested with four scents: rose, banana, perfume, and gas) was conducted to evaluate olfactory detection, memory, and identification. Levels of sense of smell perception were determined when the participants detected, recognized, or identified all (normosmia), 1-3 (hyposmia), or none (anosmia) of the odorants. Associated factors of olfactory dysfunction were identified by multivariate analysis (odds ratio, 95%CI)., Recent Findings: Olfactory dysfunction is a prevalent disorder affecting up to 20% of the general population. In addition to viral infection, including COVID-19, a number of other causes and factors may also be involved. 1,956 surveys were conducted and 1,921 were analyzed. Most of the participants (62.1%) were women. The general prevalence of olfactory dysfunction, regarding detection, was 7.2% (7.1% hyposmia, 0.1% anosmia). Age-related olfactory deterioration was observed in both sexes from the 5th decade of life (OR 2.74, p = 0.0050). Women showed better olfactory identification (OR 0.73, p = 0.0010). Obesity (OR 1.97, p = 0.0070), low educational level, bad/very bad self-perceived olfactory function (OR 2.74, p = 0.0050), olfactory loss for less than one week (OR 1.35, p = 0.0030), exposure to toxics/irritants (OR 1.31, p = 0.0030), active smoking (OR 1.58, p < 0.0010), and type 2 diabetes mellitus (OR 2.68, 95%CI 1.74-4.10, p < 0.0001) were identified as factors associated with olfactory dysfunction. These results in a Mexican population suggest better olfactory identification (verbalization) in females. Age was a determining factor in the olfactory deterioration process and obesity and diabetes mellitus were also associated with olfactory disorders. Finally, these findings reinforce the differential diagnosis with other potential causes of sense of smell loss, during the COVID-19 outbreak.

Purpose of Review: Olfactory dysfunction in upper airway viral infections (common cold, acute rhinosinusitis) is common (> 60%). During the COVID-19 outbreak, frequency of sensory disorders (smell and/or taste) in affected patients has shown a high variability from 5 to 98%, depending on the methodology, country, and study., Recent Findings: A sudden, severe, isolated loss of smell and/or taste, in the absence of other upper airway inflammatory diseases (allergic rhinitis, chronic rhinosinusitis, nasal polyposis), should alert individuals and physicians on being potentially affected by COVID-19. The evaluation of smell/taste disorders with a visual analogue scale or an individual olfactory or gustatory test, at the hospital or by telemedicine, to prevent contamination might facilitate an early detection of infected patients and reduce the transmission of SARS-CoV-2. During the COVID-19 outbreak, patients with sudden loss of smell should initiate social distancing and home isolation measures and be tested for SARS-CoV-2 diagnostic test when available. Olfactory training is recommended when smell does not come back after 1 month but can be started earlier.

Purpose of Review: Olfactory functioning disturbances are common following traumatic brain injury (TBI) having a significant impact on quality of life. A spontaneous recovery of the olfactory function over time may occur in TBI patients. Although there is no standard treatment for patients with posttraumatic olfactory loss, olfactory training (OT) has shown some promise beneficial effects. However, the mechanisms underlying spontaneous recovery and olfactory improvement induced by OT are not completely known., Recent Findings: The spontaneous recovery of the olfactory function and the improvement of olfactory function after OT have recently been associated with an increase in subventricular (SVZ) neurogenesis and an increase in olfactory bulb (OB) glomerular dopaminergic (DAergic) interneurons. In addition, after OT, an increase in electrophysiological responses at the olfactory epithelium (OE) level has been reported, indicating that recovery of olfactory function not only affects olfactory processing at the central level, but also at peripheral level. However, the role of OE stem cells in the spontaneous recovery and in the improvement of olfactory function after OT in TBI is still unknown. In this review, we describe the physiology of the olfactory system, and the olfactory dysfunction after TBI. We highlight the possible role for the SVZ neurogenesis and DAergic OB interneurons in the recovery of the olfactory function. In addition, we point out the relevance of the OE neurogenesis process as a future target for the research in the pathophysiological mechanisms involved in the olfactory dysfunction in TBI. The potential of basal stem cells as a promising candidate for replacement therapies is also described.

Purpose of Review: The purposes of the review are as follows: (1) to define acute rhinosinusitis (ARS) and their phenotypes, (2) to highlight the ARS management according to international guidelines, (3) to compare the physicians' management with the ARS guideline recommendations, and (4) to report ARS socioeconomic burden., Recent Findings: Bacterial and non-bacterial ARS have similar symptoms, although they can be discriminated by using a combination of specific signs and symptoms. The prescription of antibiotics should be limited to clearly suspected bacterial ARS. There is an overuse of diagnosis tools and treatment prescriptions. The total cost per ARS episode in Europe is over €1000. ARS is mainly an inflammatory disease triggered by viral infection, and few cases end up developing bacterial infection. In most of the cases, it is a self-resolving disease which diagnosis is mainly clinical and the treatment symptomatic. The incidence of complications is low and independent of antibiotic use. There is a high socioeconomic burden associated to ARS.

Purpose of Review: Most children and adolescents with allergic rhinitis (AR) present extra-nasal multimorbid conditions, including conjunctivitis, asthma, atopic dermatitis, rhinosinusitis, or seromucous otitis. Additionally, they may present nasal obstructive disorders, such as septal deformity, turbinate enlargement, and adenoidal hyperplasia, which worsen nasal symptoms, especially nasal obstruction. This is a narrative review on the current state of the concomitant presence of AR and one or more multimorbidities., Recent Findings: The presence of AR and one or more accompanying multimorbidities is associated to a higher severity and duration of the disease, a negative impact on quality of life, with worse control and lack of improvement with medical treatment. Therefore, AR needs to be managed with a multidisciplinary collaborative approach. Pediatric AR needs to be considered in the context of a systemic disease, which requires a coordinated therapeutic strategy.

Purpose of Review: The sense of smell is today one of the focuses of interest in aging and neurodegenerative disease research. In several neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease, the olfactory dysfunction is one of the initial symptoms appearing years before motor symptoms and cognitive decline, being considered a clinical marker of these diseases' early stages and a marker of disease progression and cognitive decline. Overall and under the umbrella of precision medicine, attention to olfactory function may help to improve chances of success for neuroprotective and disease-modifying therapeutic strategies., Recent Findings: The use of olfaction, as clinical marker for neurodegenerative diseases is helpful in the characterization of prodromal stages of these diseases, early diagnostic strategies, differential diagnosis, and potentially prediction of treatment success. Understanding the mechanisms underlying olfactory dysfunction is central to determine its association with neurodegenerative disorders. Several anatomical systems and environmental factors may underlie or contribute to olfactory loss associated with neurological diseases, although the direct biological link to each disorder remains unclear and, thus, requires further investigation. In this review, we describe the neurobiology of olfaction, and the most common olfactory function measurements in neurodegenerative diseases. We also highlight the evidence for the presence of olfactory dysfunction in several neurodegenerative diseases, its value as a clinical marker for early stages of the diseases when combined with other clinical, biological, and neuroimage markers, and its role as a useful symptom for the differential diagnosis and follow-up of disease. The neuropathological correlations and the changes in neurotransmitter systems related with olfactory dysfunction in the neurodegenerative diseases are also described.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the upper airways of which two major phenotypes exist, CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). Some patients with CRS have suboptimal response to current guideline treatments. These patients remain severe and uncontrolled by treatment and have a poor quality of life. It is highly important to identify both clinical and biological markers, so-called biomarkers, in this subset of patients. The presence of nasal polyps and comorbidity with asthma and with aspirin-exacerbated respiratory disease (AERD) are the most common clinical traits that have been associated to difficult-to-treat severe CRS. In addition to clinical traits, numerous biological markers, with known etiopathogenic roles in CRS, have been associated to difficult-to-treat or recalcitrant CRS. This review summarizes the existing knowledge of the clinical and biological markers associated to difficult-to-treat or uncontrolled severe CRS.

Aspirin intolerance syndrome is due to disturbances in the arachidonic acid metabolism implicating both the lipoxygenase and cyclooxygenase pathways. This results in imbalances of eicosanoid, leukotriene and prostaglandin synthesis. Thus, preinflammatory cysteinyl leukotrienes increase and antiinflammatory prostaglandins (PG) such as PGE2 decrease. Clinically, intolerance reactions to nonsteroidal antiinflammatory drugs (NSAIDs) can lead to different clinical manifestations; five phenotypes of the aspirin intolerance syndrome are listed in the ENDA classification. Aspirin-exacerbated respiratory disease (AERD) is the most common phenotype characterized by an eosinophil-dominated inflammatory disease of the airways that presents clinically with nasal polyps, chronic sinusitis and bronchial asthma. About 34 % of patients with aspirin-induced asthma and rhinosinusitis are thought to have AERD. Important biochemical findings in many AERD patients are increased basal leukotriene levels (at least in cell cultures) that excessively increase after intake of COX-1 inhibitors. Aspirin desensitization uses the repetitive application of aspirin to induce a tolerance to NSAIDs, especially COX-1 inhibitors. After a dose-increase phase reaching a threshold dose, a dose-continuation phase is performed. For application, the nasal, bronchial, oral and intravenous routes have been described. Aspirin desensitization has been proven to be efficacious and safe and was able to reduce the need for other medications in AERD patients.

The united airway concept in which upper and lower respiratory conditions are present in one patient requires special consideration. There is some evidence linking chronic rhinosinusitis and asthma, but a good understanding of the pathophysiology and combined management is still lacking, a fact that leads to discussion. Bronchial asthma is more prevalent in patients who suffer chronic rhinosinusitis. On the other hand, patients with asthma have a greater prevalence of rhinosinusitis than patients without asthma. The effect of chronic rhinosinusitis in patients with or without nasal polyps on asthma treatment, whether medical or surgical, is controversial. Some studies show worsening, other trials improvement, and others no effect. Direct comparisons between surgical and medical treatments are few. Most of the current literature available about this intriguing combination does not provide a good level of evidence. Thus, randomized clinical trials should be performed to better understand the management when asthma and CRS occur together. This review aims to summarize the current state of this association regarding the effects of different types of treatment.

Allergic rhinitis (AR) is a common disorder, which represents a considerable burden both on individual patients and society. It is associated with bothersome symptoms, which may impair usual daily activities, sleep quality, and productivity. Associated with impaired sleep, quality of life is significantly impaired in AR patients. AR significantly contributes to sleep-disordered breathing through multiple mechanisms, with the greatest impact mediated through nasal obstruction. Sleep impairment is very common in AR patients and has a significant impact on disease-specific measures of general health and quality of life. The degree of sleep disturbance is directly related to the severity of the disease. Nasal congestion also demonstrates circadian rhythm and positional variability, worsening during nighttime hours and in supine position. Increased sleep disordered events lead to poor sleep with fatigue and daytime somnolence, impaired performance, productivity and social functioning, and an increased risk of associated diseases.

Allergic rhinitis (AR) is a worldwide health problem that generates a significant healthcare burden in adults, adolescents, and children. Epidemiological studies have indicated that the prevalence of AR has progressively increased over the last three decades in developed and industrialized countries. AR currently affects up to 40 % of the worldwide population, with differences between adults and children and different countries of the World. Although not life-threatening, AR symptoms are frequently bothersome, adversely affecting work and quality of life of the affected patients, and causing a significant burden on both the individual and society. The symptoms have the potential to lead to both physical and mental complications, with sleep-disordered breathing in childhood and adolescence being associated with disorders in learning performance, behavior, and attention. Clinical features and comorbidities are very important for the "allergic march", and in both adults and children there is some evidence of association between AR and asthma. ARIA classifications of both symptom duration (intermittent, persistent) and severity (mild, moderate, severe) have been validated in both adult and pediatric populations. Based on the duration and severity of patient's disease, an appropriate treatment strategy has been issued for both adults and children, which consists of patient's education, allergen avoidance, and pharmacological as well as allergen-specific immunotherapy treatment. The present review will attempt to compare the characteristics of AR between children and adults, either in the epidemiology, clinical features, impact on QOL, and management of the disease.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the nasal and paranasal sinus mucosa that, despite differing hypotheses regarding its cause, remains poorly understood. Major symptoms are nasal congestion or blockage, loss of smell, rhinorrhea, postnasal drip, and facial pain or pressure. Among the objectives of CRSwNP management are to eradicate nasal polyps from nasal and sinusal cavities, eliminate symptoms, and prevent recurrences. Corticosteroids are the mainstay of treatment and are the most effective drugs for treating CRSwNP. Other potential treatments are nasal saline irrigation and antihistamines (in allergic conditions). Endoscopic sinus surgery is recommended when medical treatment fails. After surgery, medical treatment, including nasal and oral corticosteroids, is recommended.

Cyclooxygenase (COX) enzymes catalyze the rate-limiting steps in prostaglandin synthesis. Prostaglandins have an important role in several physiological processes such as maintenance of gastrointestinal integrity and pathological processes such as inflammation and neoplasia. Several mechanisms have been proposed for the development of chronic rhinosinusitis, but the common final pathway seems to be an integrated process involving the mucosal epithelium, matrix, and inflammatory cells and mediators. Upper and lower airway pathologies coexist and share common etiopathogenic mechanisms, and nasal polyposis is often associated with asthma and aspirin sensitivity. The cellular source of COX activity in acute and chronic inflammation, as in chronic rhinosinusitis, is poorly understood. COX theory postulated that inhibition of COX broke down biochemical reactions that lead to the development of asthma attacks. This article focuses on COX in the pathogenesis of chronic rhinosinusitis and nasal polyposis.

Glucocorticoids (GCs) are the most common and effective drugs for treating inflammatory airway respiratory diseases. Despite their efficacy, some patients respond poorly to GC treatment. Alterations in the expression of the receptor that mediates GC actions, the glucocorticoid receptor (GR), are one of the potential mechanisms that would explain GC insensitivity. In this review, we present an update on the GR gene and its products, namely GRalphaand GRbeta, as well as their alterations in disease. GRalpha has a widespread distribution and is responsible for the induction and repression of target genes, whereas GRbeta can act as a dominant negative inhibitor of GRalpha-mediated transactivation and transrepression. Very low GRbeta mRNA levels have been detected in a number of cells and tissues, which often contradict GRbeta protein data. Nevertheless, an association between GC insensitivity and increased GRbeta expression has been reported in asthma, nasal polyposis, and ulcerative colitis, and in vitro, certain pro-inflammatory cytokines upregulate GRbeta expression. However, the role of GRbeta in modulating GC sensitivity in vivo has been highly debated and is as yet unclear.

Rhinitis and rhinosinusitis are often associated with airway diseases such as asthma, cystic fibrosis, and nasal polyposis. In these diseases, the alteration of both the quantity and quality of mucus results in an impaired mucociliary clearance, and this produces, in extreme cases, the airway obstruction. Mucins are the major component in mucus and are responsible for its viscoelastic properties. Mucin expression patterns have been shown to be altered in rhinitis-associated diseases. It has been proposed that this is one of the causes of hyperviscid mucus plugs in these pathologies. For this reason, the study of mucin expression and regulation in upper- and lower-airway diseases, such as asthma, cystic fibrosis, and nasal polyposis, may be crucial for the development of new therapies against mucus hypersecretion. In this review, we report major findings regarding mucin expression and regulation in rhinitis syndromes.

This article is focused on the nasal and sinusal manifestations of systemic diseases, such as infections, immunodeficiencies, chronic multisystemic disorders, inflammatory bowel diseases, deposition diseases, hematologic diseases, respiratory diseases, and smell and taste disorders. A concise review of some of the systemic diseases that commonly present complaints in the nose and paranasal sinuses, including their prevalence, sinonasal manifestations, diagnosis, and treatment, is provided.