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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. Summary: 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. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

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). Summary: 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. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

There is increasing preclinical and clinical data supporting a potential association between Traumatic Brain Injury (TBI) and Parkinson's disease (PD). It has been suggested that the glutamate-induced excitotoxicity underlying TBI secondary neuronal degeneration (SND) might be associated with further development of PD. Interestingly, an accumulation of extracellular glutamate and olfactory dysfunction are both sharing pathological conditions in TBI and PD. The possible involvement of glutamate excitotoxicity in olfactory dysfunction has been recently described, however, the role of olfactory bulbs (OB) glutamate excitotoxicity as a possible mechanism involved in the association between TBI and PD-related neurodegeneration has not been investigated yet. We examined the number of nigral dopaminergic neurons (TH +), nigral α-synuclein expression, the striatal dopamine transporter (DAT) expression, and motor performance after bilateral OB N-Methyl-D-Aspartate (NMDA)-induced excitotoxic lesions in rodents. Bulbar NMDA administration induced a decrease in the number of correct choices in the discrimination tests one week after lesions (p < 0.01) and a significant decrease in the number of nigral DAergic neurons (p < 0.01) associated with an increase in α-synuclein expression (p < 0.01). No significant striatal changes in DAT expression or motor alterations were observed. Our results show an association between TBI-induced SND and PD-related neurodegeneration suggesting that the OB excitotoxicity occurring in TBI SND may be a filling gap mechanism underlying the link between TBI and PD-like pathology. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

Background: Since the outbreak in China due to coronavirus disease 2019 (COVID-19) various studies have been published describing olfactory and gustatory dysfunction (OGD). Objective: The aim was to investigate the frequency and severity of OGD in SARS-CoV-2 (+) out-patients compared to controls with common cold/flu like symptoms and two negative RT-PCR. Methods: A multicenter cross-sectional study on SARS-CoV-2-positive out-patients (n = 197) and controls (n = 107) from five Spanish Hospitals. Severity of OGD was categorized by visual analogue scale (VAS). Frequency and severity of the chemosensory impairment were analyzed. Results: The frequencies of smell (70.1%) and taste loss (65%) were significantly higher among COVID-19 subjects than in the controls (20.6% and 19.6%, respectively). Simultaneous OGD was more frequent in the COVID-19 group (61.9% vs 10.3%) and they scored higher in VAS for severity of OGD than controls. In the COVID-19 group, OGD was predominant in young subjects 46.5 ± 14.5 and females (63.5%). Subjects with severe loss of smell were younger (42.7 years old vs 45.5 years old), and recovered later (median = 7, IQR = 5.5 vs median = 4, IQR = 3) than those with mild loss of smell. Subjects with severe loss of taste, recovered later in days (median = 7, IQR = 6 vs median = 2, IQR = 2), compared to those with mild loss. Conclusion: OGD is a prevalent symptom in COVID-19 subjects with significant differences compared to controls. It was predominant in young and females subjects. Stratified analysis by the severity of OGD showed that more than 60% of COVID-19 subjects presented a severe OGD who took a longer time to recover compared to those with mild symptoms. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

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. Summary: This review provides a comprehensive overview of the current studies regarding the chemosensory dysfunction during the COVID-19 worldwide outbreak. [ABSTRACT FROM AUTHOR]

Background: Idiopathic hyposmia (IH) is a prodromal marker of Parkinson disease (PD). However, IH is common in the general population and only a minority will develop PD. Identification of individuals with IH at prodromal stage of PD would serve to select them to implement neuroprotective agents, when available. Objective: To identify prodromal PD in IH patients using the Movement Disorders Society (MDS) research criteria for prodromal PD. Methods: We applied the MDS research criteria for prodromal PD to 25 consecutive patients older than 50 years who were self-referred for smell loss and had IH, and to 18 controls. A number of risk and prodromal PD markers were assessed in all participants including REM sleep behavior disorder (RBD) by video-polysomnography and nigrostriatal dopaminergic dysfunction by DAT-SPECT. After follow-up of 4.7 ± 2.2 years, participants were re-assessed to look for incident PD. Results: Prodromal PD probability was higher in patients than in controls (19.45 ± 34.9% versus 1.74 ± 4.48%; p = 0.019). Four (16%) patients met the criteria of prodromal PD surpassing 80% probability (99.8%, 99.5%, 88.3%, 86.4%). Three (12%) patients had RBD and four (16%) abnormal DAT-SPECT. At the end of follow-up, one (4%) IH patient who had RBD and baseline prodromal PD probability of 86.4% developed PD, while all controls remained disease free. Conclusions: Prodromal PD is infrequent among IH patients. MDS research criteria for prodromal PD are useful to identify a subgroup of IH patients at high risk of PD when RBD is assessed by video-polysomnography and nigrostriatal dopamine deficiency with DAT-SPECT. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

Glutamatergic excitotoxicity is involved in pathologies affecting the central nervous system, including traumatic brain injury (TBI) and neurodegenerative diseases, such as Parkinson's disease (PD), in which olfactory dysfunction is an early symptom. Interestingly, our group has recently shown that bilateral administration of the glutamate agonist, N-methyl-d-aspartate (NMDA) in the olfactory bulbs (OBs) induces an olfactory dysfunction 1 week after lesions. Although a wide range of treatments have been attempted, no standard therapy has been established to treat olfactory disorders. Increasing evidence suggests a beneficial effect of olfactory training (OT) in olfactory function. However, the mechanisms underlying OT effects remain unknown. We investigated the effects of OT on the olfactory dysfunction induced by excitotoxicity in bilateral OB NMDA–lesioned animals. We compared OT effects with the ones obtained with neuroprotective therapies (pramipexole and MK801). We studied the underlying mechanisms involved in OT effects investigating the changes in the subventricular zone (SVZ) neurogenesis and in the number of periglomerular dopaminergic interneurons. One week after lesion, NMDA decreased the number of correct trials in the olfactory discrimination tests in the non-trained group (p < 0.01). However, OT performed for 1 week after lesions prevented olfactory dysfunction (p < 0.01). Pramipexole did not prevent olfactory dysfunction, whereas MK801 treatment showed a partial recovery (p < 0.05). An increase in SVZ neurogenesis (p < 0.05) associated with an increase in OB dopaminergic interneurons (p < 0.05) was related to olfactory function prevention induced by OT. The present results suggest a role for dopaminergic OB interneurons underlying the beneficial effects of OT improving olfactory dysfunction in bilaterally OB NMDA–lesioned animals. [ABSTRACT FROM AUTHOR]

Excitotoxicity consists in a cascade of intracellular events initiated by an excessive release of glutamate and hyperactivation of glutamatergic receptors that is involved in several pathologies, including traumatic brain injury and neurodegenerative diseases such as Parkinson's disease. Both disorders are a common cause of olfactory dysfunction. We previously reported a role for glutamate excitotoxicity in olfactory dysfunction showing an olfactory deficit 1 week after lesion and a spontaneous recovery 2 weeks after excitotoxicity lesion of the olfactory bulbs (OBs). The olfactory dysfunction recovery was associated with an increase in subventricular zone neurogenesis and an increase in the OB glomerular dopaminergic interneurons. However, the underlying molecular mechanisms involved in the OB dopaminergic differentiation and olfactory recovery are still unknown. To investigate the role of silent information regulator family proteins sirtuins (SIRTs), a family of NAD+-dependent histone deacetylases, on the olfactory function recovery, we examined the OB SIRT (SIRT1, SIRT2, and SIRT4) expressions after OB excitotoxic lesions in rodents. N-methyl-d-aspartate (NMDA) OB administration induced a decrease in the number of correct choices in the discrimination tests 1 week after lesions (p < 0.01) and a spontaneous recovery of the olfactory deficit 2 weeks after lesions (p < 0.01) associated with an increase in OB SIRT1 and SIRT4 expression. Our results point out for the first time the association between recovery of olfactory function and the increase in bulbar SIRT1 and SIRT4 expression suggesting a role for these SIRTs in the pathophysiology of recovery of loss of smell. [ABSTRACT FROM AUTHOR]

Little is known about the long-term effects of either transnasal transsphenoidal endoscopic approach (TTEA) or expanded endonasal approach (EEA). This study assessed the long-term impact of endoscopic skull base surgery on olfaction, sinonasal symptoms, mucociliary clearance time (MCT), and quality of life (QoL). Patients with pituitary adenomas underwent TTEA ( n = 38), while patients with other benign parasellar tumours who underwent an EEA with vascularised septal flap reconstruction ( n = 17) were enrolled in this prospective study between 2009 and 2012. Sinonasal symptoms (Visual Analogue Scale), subjective olfactometry (Barcelona Smell Test-24, BAST-24), MCT (saccharin test), and QoL (short form SF-36, rhinosinusitis outcome measure/RSOM) were evaluated before, and 12 months after, surgery. At baseline, sinonasal symptoms, MCT, BAST-24, and QoL were similar between groups. Twelve months after surgery, both TTEA and EEA groups experienced smell impairment compared to baseline. Moreover, EEA (but not TTEA) patients reported increased posterior nasal discharge and longer MCTs compared to baseline. No significant changes in olfactometry or QoL were detected in either group 12 months after surgery. Over the long-term, expanded skull base surgery, using EEA, produced more sinonasal symptoms (including loss of smell) and longer MCTs than pituitary surgery (TTEA). EEA showed no long-term impact on smell test or QoL. Level of evidence: IIb [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Multiple chemical sensitivity (MCS) is characterized by a loss of tolerance to a variety of environmental chemicals. Multiple chemical sensitivity is frequently triggered by exposure to chemical agents, especially insecticides. The aim of the study was to measure the sense of smell and quality of life in patients with MCS compared to the control group. We studied the sense of smell, both sensitive and sensorial characteristics, in female patients with MCS ( n = 58, mean 50.5 ± 8.5 years) and healthy female volunteers without rhinosinusal pathologies ( n = 60, mean age 46 ± 10.2 years). Olfactometry (Barcelona Smell Test 24/BAST-24), sinonasal symptoms (visual analogue scale/VAS 0-100 mm), and quality of life (Quick Environmental Exposure and Sensitivity Inventory/QEESI) were assessed. Multiple chemical sensitivity patients showed a significant impairment in smell identification (19 ± 12 %; p > 0.05) and forced choice (62 ± 18 %; p > 0.05), but not in smell detection (96 ± 4 %) compared to the control group. Multiple chemical sensitivity patients reported more odours as being intense and irritating and less fresh and pleasant when compared with the control group. Patients scored a high level (40-100) on QEESI questionnaire (symptom severity, chemical intolerances, other intolerances, life impact). In MCS patients, total symptom intensity (VAS/0-700 mm) score was 202 ± 135, while disease severity score was 80 ± 23. The most frequent symptoms were itching and posterior rhinorrhea. Multiple chemical sensitivity patients have an impairment in smell cognitive abilities (odour identification and forced choice, but not for detection) with increased smell hypersensitivity and poor quality of life. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 PGE 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 GRα and GRβ, as well as their alterations in disease. GRα has a widespread distribution and is responsible for the induction and repression of target genes, whereas GRβ can act as a dominant negative inhibitor of GRα-mediated transactivation and transrepression. Very low GRβ mRNA levels have been detected in a number of cells and tissues, which often contradict GRβ protein data. Nevertheless, an association between GC insensitivity and increased GRβ expression has been reported in asthma, nasal polyposis, and ulcerative colitis, and in vitro, certain pro-inflammatory cytokines upregulate GRβ expression. However, the role of GRβ in modulating GC sensitivity in vivo has been highly debated and is as yet unclear. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Nasal polyposis is not a life-threatening disease but may have a great impact on patient's quality of life.Objective: To investigate the impact of nasal polyps on quality of life compared with the Spanish general population using the SF-36 questionnaire; and to evaluate the impact of asthma and aspirin sensitivity on quality of life in patients with nasal polyposis.Methods: We included 130 patients with nasal polyposis and evaluated nasal symptom, CT scan, polyp size, and quality of life.Results: In comparison with the Spanish general population, patients with nasal polyposis had worse scores on all SF-36 domains except for physical functioning. Asthmatic patients with nasal polyposis had worse quality of life than nonasthmatic patients on role physical, body pain, and vitality (p < 0.05). The authors found no significant differences on quality of life, nasal symptoms, polyp size, and CT scan scores between patients with aspirin-tolerant and aspirin-sensitive asthma.Conclusion: These results suggest that nasal polyposis has a considerable impact on quality of life. Moreover, asthma but not aspirin sensitivity has an additional negative impact on the quality of life of patients with nasal polyposis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

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. Summary: 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. [ABSTRACT FROM AUTHOR]

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. Summary: Pediatric AR needs to be considered in the context of a systemic disease, which requires a coordinated therapeutic strategy. [ABSTRACT FROM AUTHOR]

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.Summary: 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. [ABSTRACT FROM AUTHOR]