In situ hydrogel containing diazepam-loaded nanostructured lipid carriers (DZP-NLC) for nose-to-brain delivery: development, characterization and deposition studies in a 3D-printed human nasal cavity model.

The nasal route has been investigated as a promising alternative for drug delivery to the central nervous system, avoiding passage through the blood-brain barrier and improving bioavailability. In this sense, it is necessary to develop and test the effectiveness of new formulations proposed for the management of neurological disorders. Thereby, the aim of this work was to develop and characterize an ion sensitive in situ hydrogel containing diazepam-loaded nanostructured lipid carriers (DZP-NLC) for nasal delivery in the treatment of epilepsy. Physical characterization of the developed formulations was performed and included the evaluation of rheological features, particle size, polydispersity index (PDI) and zeta potential (ZP) of an in situ hydrogel containing DZP-NLC. Afterwards, in vitro drug release, in vitro mucoadhesion and biocompatibility studies with RPMI 2650 nasal cells were performed. The in situ hydrogel containing DZP-NLC was aerosolized with a nasal spray device specifically designed for nose-to-brain delivery (VP7 multidose spray pump with a 232 N2B actuator) and characterized for droplet size distribution and spray cone angle. Finally, the deposition pattern of this hydrogel was evaluated in a 3D-printed human nasal cavity model. The developed in situ hydrogel containing DZP-NLC presented adequate characteristics for nasal administration, including good gelling ability, mucoadhesiveness and prolonged drug release. In addition, after inclusion in the hydrogel net, the particle size (81.79 ± 0.53 nm), PDI (0.21 ± 0.10) and ZP (-30.90 ± 0.10 mV), of the DZP-NLC remained appropriate for nose-to-brain delivery. Upon aerosolization in a nasal spray device, a suitable spray cone angle (22.5 ± 0.2°) and adequate droplet size distribution (Dv (90) of 317.77 ± 44.12 µm) were observed. Biocompatibility studies have shown that the developed formulation is safe towards RPMI 2650 cells in concentrations up to 100 µg/mL. Deposition studies on a 3D-printed human nasal cavity model revealed that the best nasal deposition profile was obtained upon formulation administration without airflow and at an angle from horizontal plane of 75°, resulting in 47% of administered dose deposited in the olfactory region and 89% recovery. The results of this study suggested that the intranasal administration of the developed in situ hydrogel containing DZP-NLC could be a promising alternative to the conventional treatments for epilepsy.

Chitosan-Based Thermogelling System for Nose-to-Brain Donepezil Delivery: Optimising Formulation Properties and Nasal Deposition Profile.

Donepezil nasal delivery strategies are being continuously investigated for advancing therapy in Alzheimer's disease. The aim of this study was to develop a chitosan-based, donepezil-loaded thermogelling formulation tailored to meet all the requirements for efficient nose-to-brain delivery. A statistical design of the experiments was implemented for the optimisation of the formulation and/or administration parameters, with regard to formulation viscosity, gelling and spray properties, as well as its targeted nasal deposition within the 3D-printed nasal cavity model. The optimised formulation was further characterised in terms of stability, in vitro release, in vitro biocompatibility and permeability (using Calu-3 cells), ex vivo mucoadhesion (using porcine nasal mucosa), and in vivo irritability (using slug mucosal irritation assay). The applied research design resulted in the development of a sprayable donepezil delivery platform characterised by instant gelation at 34 °C and olfactory deposition reaching a remarkably high 71.8% of the applied dose. The optimised formulation showed prolonged drug release (t1/2 about 90 min), mucoadhesive behaviour, and reversible permeation enhancement, with a 20-fold increase in adhesion and a 1.5-fold increase in the apparent permeability coefficient in relation to the corresponding donepezil solution. The slug mucosal irritation assay demonstrated an acceptable irritability profile, indicating its potential for safe nasal delivery. It can be concluded that the developed thermogelling formulation showed great promise as an efficient donepezil brain-targeted delivery system. Furthermore, the formulation is worth investigating in vivo for final feasibility confirmation.

ASSOCIATION BETWEEN SYMPTOM SEVERITY AND INTENSITY OF ACUTE PSYCHOLOGICAL DISTRESS IN NEWLY DIAGNOSED PATIENTS WITH CHRONIC RHINITIS AND CHRONIC RHINOSINUSITIS.

Chronic rhinitis and rhinosinusitis (CR and CRS) can lead to impairment of the health-related quality of life (HRQL) with higher psychological perceived distress, resulting in disease worsening and poor treatment outcomes. W aimed to evaluate the potential association between disease severity and HRQL impairment with the perceived acute psychological distress in newly diagnosed CR/CRS patients. This single-center cross-sectional study included otherwise healthy consecutive adults with newly diagnosed CR/CRS (European position paper on rhinosinusitis and nasal polyp criteria and International Consensus Statement on Allergy and Rhinology - Allergic Rhinitis criteria or non-allergic rhinitis), who were evaluated for CR/CRS symptom severity and HRQL (Sino Nasal Outcome Test 22 [SNOT-22], visual analog scale [VAS]) and acute perceived distress (Perceived Stress Scale [PSS]). Principal component analysis (SNOT-22 items, VAS) identified 6 components as CR/CRS severity indicators, i.e,, poor sleep, wakes-up tired, nasopharynx, obstruction, torment and rhinorrhea, which were evaluated for association with PSS score. Of the 63 included patients (20 men, age median 38, range 19-75 years), 27 suffered from CR and 36 from CRS. Upon adjustment for age and sex, higher total SNOT-22 (geometric means ratio [GMR]=1.04, 95% CI 1.01-1.06), higher "torment" (GMR=1.13, 1.04-1.24), higher "poor sleep" (GMR=1.11, 1.02-1.21) and higher "wakes-up tired" (GMR=1.11, 1.01-1.21) scores were each associated with a higher PSS score, overall and consistently in CR and CRS patients. In conclusion, more severe CR/CRS is associated with greater perceived psychological distress already at earlier stages of the disease. Paying attention to patient level of distress and anxiety over time may enable better understanding of the connection between exacerbations, symptom severity and psychological burden of the disease.

Tailoring functional spray-dried powder platform for efficient donepezil nose-to-brain delivery.

Shortcomings of oral donepezil administration in the treatment of Alzheimer's disease have paved the way for ongoing investigations towards more efficient and safe donepezil nose-to-brain delivery. Herein we present the development of advantageous powder platform for donepezil nose-to-brain delivery, coupling careful design of chitosan and mannitol-based carrier matrix with spray-drying technology advantages and early consideration of adequate nasal administration mode, employing QbD approach. Unprecedentedly, ultrasonic nozzle was used to atomise the drying feed in response to size-related requirements for nasal aerosol particles. The optimised spray-drying process resulted in free-flowable dry powder with a great majority of particles larger than 10 µm, ensuring localised nasal deposition upon aerosolization, as evidenced by using 3D-printed nasal cavity model. QbD approach coupling formulation, process and administration parameters enabled optimisation of drug deposition profile reaching tremendously high 65.5 % of the applied dose deposited in the olfactory region. The leading formulation exhibited favourable swelling, mucoadhesion, drug release and permeation-enhancing properties, suiting the needs for efficient brain-targeted delivery. Results of in vitro biocompatibility and physico-chemical stability studies confirmed the leading formulation potential for safe and efficient donepezil nose-to-brain delivery. The obtained results encourage extending the study to an appropriate in vivo model needed for the final proof-of-concept.

The Role of Seawater and Saline Solutions in Treatment of Upper Respiratory Conditions.

The history of saline nasal irrigation (SNI) is indeed a long one, beginning from the ancient Ayurvedic practices and gaining a foothold in the west at the beginning of the 20th century. Today, there is a growing number of papers covering the effects of SNI, from in vitro studies to randomized clinical trials and literature overviews. Based on the recommendations of most of the European and American professional associations, seawater, alone or in combination with other preparations, has its place in the treatment of numerous conditions of the upper respiratory tract (URT), primarily chronic (rhino)sinusitis, allergic rhinitis, acute URT infections and postoperative recovery. Additionally, taking into account its multiple mechanisms of action and mounting evidence from recent studies, locally applied seawater preparations may have an important role in the prevention of viral and bacterial infections of the URT. In this review we discuss results published in the past years focusing on seawater preparations and their use in clinical and everyday conditions, since such products provide the benefits of additional ions vs. saline, have an excellent safety profile and are recommended by most professional associations in the field of otorhinolaryngology.

In situ gelling nanosuspension as an advanced platform for fluticasone propionate nasal delivery.

In this work we present the development of in situ gelling nanosuspension as advanced form for fluticasone propionate nasal delivery. Drug nanocrystals were prepared by wet milling technique. Incorporation of drug nanocrystals into polymeric in situ gelling system with pectin and sodium hyaluronate as constitutive polymers was fine-tuned attaining appropriate formulation surface tension, viscosity and gelling ability. Drug nanonisation improved the release profile and enhanced formulation mucoadhesive properties. QbD approach combining formulation and administration parameters resulted in optimised nasal deposition profile, with 51.8% of the dose deposited in the middle meatus, the critical region in the treatment of rhinosinusitis and nasal polyposis. Results obtained in biocompatibility and physico-chemical stability studies confirmed the leading formulation potential for safe and efficient nasal corticosteroid delivery.

UNILATERAL VS. DIFFUSE CHRONIC RHINOSINUSITIS.

Chronic rhinosinusitis (CRS) is a widespread disease with various symptoms. It is defined as an inflammation of the nasal mucosa and paranasal sinuses lasting for 12 weeks, with symptoms of nasal obstruction and/or congestion and facial pain and/or pressure as well as decreased sense of smell. Despite the widespread prevalence of the disease, the diagnosis and treatment of CRS are still not adequately developed, so many patients remain misdiagnosed. This study involved 150 patients who, according to EPOS guidelines, met the diagnosis of CRS without nasal polyposis. Each patient underwent a computerized tomography (CT) scan of the paranasal sinuses, which was evaluated according to the Lund-Mackay scoring system. Furthermore, patients completed a visual analog scale (VAS) score questionnaire which examined the severity of their symptoms. The aim of this study was to find an association between the degree of mucositis and the clinical symptoms reported by the patient. Our results showed a low positive correlation between nasal secretion and Lund-Mackay score for the bilateral ostiomeatal complex (OMC). Furthermore, a low positive correlation was found between the severity of reduced sense of smell and severity of anterior ethmoid and sphenoid sinusitis. The results demonstrated a low negative correlation between the severity of facial pain or pressure and the severity of inflammation of the anterior ethmoid and sphenoid sinus. The results of statistical testing did not show statistical differences in severity of subjective symptoms for almost all of the observed symptoms in persons with unilateral inflammation and persons without unilateral inflammation, except for cough. People who did not have unilateral inflammation had a more pronounced cough compared with people who had unilateral inflammation. However, these correlations were very mild and not clinically significant, so we cannot say that the distribution of sinusitis significantly affects the occurrence of characteristic symptoms in chronic rhinosinusitis.

A Dry Powder Platform for Nose-to-Brain Delivery of Dexamethasone: Formulation Development and Nasal Deposition Studies.

Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to emerge. In this work we present the development of sprayable brain targeting powder delivery platform of dexamethasone sodium phosphate (DSP). DSP-loaded microspheres, optimised employing Quality-by-Design approach, were blended with soluble inert carriers (mannitol or lactose monohydrate). Powder blends were characterized in terms of homogeneity, flow properties, sprayability, in vitro biocompatibility, permeability and mucoadhesion. Nasal deposition studies were performed using 3D printed nasal cavity model. Mannitol provided better powder blend flow properties compared to lactose. Microspheres blended with mannitol retained or enlarged their mucoadhesive properties and enhanced DSP permeability across epithelial model barrier. DSP dose fraction deposited in the olfactory region reached 17.0% revealing the potential of developed powder platform for targeted olfactory delivery. The observed impact of nasal cavity asymmetry highlighted the importance of individual approach when aiming olfactory region.

Imaging in chronic rhinosinusitis: A systematic review of MRI and CT diagnostic accuracy and reliability in severity staging.

BACKGROUND: Computerized tomography (CT) severity scores are frequently used as an objective staging tool in chronic rhinosinusitis (CRS). Magnetic resonance imaging (MRI) has also been proposed as a valid option in CRS imaging. PURPOSE: The aim of this systematic review was to briefly present the recent developments on sinus imaging utilized in clinical practice with regard to diagnostic accuracy of imaging and severity staging in CRS according to evidence-based medicine (EBM) principles. MATERIAL AND METHODS: This review paper has been assembled following PRISMA guidelines. A PubMed and Scopus (EMBASE) search using CRS, "severity staging", "diagnostic accuracy "and "imaging "resulted with 80 results. Of these, only 12 (59%) contained original data, constituting the synthesis of best-quality available evidence. RESULTS: CT is the most commonly used imaging technique for the severity staging of CRS, but a question of higher cumulative radiation dose should be taken into consideration when repeating CT examinations in evaluating treatment efficacy. MRI may be a complementary diagnostic and staging tool, especially when repeated examinations are required, or when paediatric CRS patients are evaluated. The severity staging system may be improved to better correlate with subjective scores. CONCLUSIONS: MRI may be utilized as a staging tool with comparable diagnostic accuracy, using the same staging systems as with CT examinations.

The impact of asthma on quality of life and symptoms in patients with chronic rhinosinusitis.

Objective: The study aims to evaluate how asthma influences on clinical symptoms, imaging scores and HRQL in CRS patients.Methods: The study enrolled CRS patients and collected data about asthma status, clinical symptoms, allergic sensitization, computed tomography (CT) and 22-item SinoNasal Outcome questionnaire (SNOT-22). Matching pairs of asthmatic and non-asthmatic CRS patients were defined based on age, gender and nasal polyp presence. The difference between pairs in clinical symptoms, CT and SNOT-22 was then analyzed. The study enrolled mild to moderate asthma patients.Results: From 250 CRS patients 65 (26%) had asthma. We found 60 CRS asthma and CRS non-asthma pairs based on age, gender and nasal polyp presence. There was no difference in total SNOT-22 score between asthma (46.5) and non-asthma (43.5) CRS groups (p < .357). There were more patients with allergy positive medical history in asthma group (66.1%) when we stratified for CRS phenotypes, gender and age. Comparing visual analogue scale (VAS) scores for clinical symptoms, smell (p < .013) was the only symptom significantly worse in CRS asthma group. Although there was no difference in Lund-Mackay score, there was a slightly higher osteitis score in CRS asthma group (5.21 vs. 3.45; p = .059).Conclusion: CRS patients with asthma have significantly worse impairment of smell and taste when compared to non-asthmatic CRS patients. This is the only significant difference which is independent of nasal polyp presence, gender, age and allergy.

Effects of Environmental Factors on Severity and Mortality of COVID-19.

Background: Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. Methods: We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Findings: Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973-0.988, p < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773-0.944, p = 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Interpretation: Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.

Hierarchical clustering in evaluating inflammatory upper airway phenotypes; increased symptoms in adults with allergic multimorbidity.

BACKGROUND: Inflammatory upper airway diseases cause significant morbidity. They include phenotypes with different treatment; allergic or non-allergic rhinitis (AR, nAR), and chronic rhinosinusitis with or without nasal polyps (CRSwNP, CRSsNP). In clinical practice, these phenotypes are often difficult to distinguish and may overlap. OBJECTIVE: To evaluate if hierarchical clustering can be used to distinguish these phenotypes based on the presence of nasal polyps, off-seasonal allergic symptoms, and self-reported background characteristics - e.g. atopic dermatitis (AD); and to further analyse the obtained clusters. METHODS: We studied a random sample of 74 CRS (chronic rhinosinusitis) patients, and a control group of 80 subjects without CRS with/without AR (tertiary hospitals, 2006-2012). All underwent interview and nasal examination, and filled a questionnaire. Variables regarding demographics, off-seasonal symptoms, and clinical findings were collected. Hierarchical clustering was performed, the obtained clusters were cross-tabulated and analysed. RESULTS: Four clusters were identified; 1: "Severe symptoms and CRSwNP" (n = 29), 2: "Asymptomatic AR and controls" (n = 39), 3: "Moderate symptoms and CRSsNP" (n = 36), and 4: "Symptomatic and AD" (n = 50). Cluster 1 had most sinonasal symptoms, cluster 3 had a high prevalence of facial pain. The presence of AR did not distinguish CRS groups. Of the AR subjects, 51 % belonged to cluster 4, where AR with off-seasonal airway symptoms and AD predominated. CONCLUSIONS: Hierarchical clustering can be used to distinguish inflammatory upper airway disease phenotypes. The AR phenotype was subdivided by the presence of AD. Adult AR+ AD patients could benefit from active clinical care of the upper airways also off-season.

Recovery From Sudden Sensorineural Hearing Loss May Be Linked to Chronic Stress Levels and Steroid Treatment Resistance.

Purpose This article investigates the possible connections between the level of chronic stress and success of steroid therapy in patients with sudden sensorineural hearing loss (SSNHL). Method A single-center, retrospective, longitudinal cohort study on 55 patients in a tertiary referral otology center was examined. Patients diagnosed with SSNHL between 2014 and 2017 were asked to complete a Measure of Perceived Stress (Brajac, Tkalcic, Dragojevic, & Gruber, 2003 ) questionnaire. Inclusion criteria were patients > 18 years of age, SSNHL diagnosed within 4 previous weeks, completed steroid treatment, and complete documentation. Results There were 30 patients (55%) that showed significant improvement in their pure-tone audiogram (PTA) hearing threshold average (≥ 15 dB) after steroid treatment. Two-step cluster analysis identified 3 clusters based on average PTA hearing threshold recovery and average Measure of Perceived Stress scores. The difference between pretreatment and posttreatment hearing levels was significantly higher in the cluster with moderate stress compared to clusters with mild and high stress levels (Kruskal-Wallis test, Friedman test, p < .001). There were no significant differences in average PTA hearing threshold recovery after steroid therapy between groups of patients with mild and severe stress. Conclusion Patients with moderate stress levels show significantly better results after steroid treatment for SSNHL than patients with low or high stress levels.

Cluster Analysis of Chronic Rhinosinusitis Suggests Gender-Based Differences.

PURPOSE: We aimed to evaluate the interaction between the overall severity of chronic rhinosinusitis (CRS) before treatment and subjective improvement following surgical or medical treatment. PROCEDURES: A group of 97 patients with CRS completed the visual analog scale (VAS) symptom score and the Sino-Nasal Outcome Test 22 (SNOT-22) questionnaire in the moment of their sinus computerized tomography (CT) scan. Data were analyzed via a 2-step cluster analysis based on gender, polyp presence, CT scan, and VAS scores for symptoms. RESULTS: There were 3 clusters: the first cluster comprised 37 female patients with CRS without nasal polyps (CRSsNP), the second cluster comprised 30 patients with CRS and NP (CRSwNP; 15 males and 15 females); and third cluster had 30 male patients with CRS without NP (CRSsNP). Different symptom patterns between clusters were identified. After adjustment for polyp presence, gender, eosinophilia (p = 0.021), and the SNOT-22 score (p = 0.005) were found to be better outcome predictors than the CT score (p = 0.26). CONCLUSION: Long-term patient satisfaction is significantly associated with the subjective symptom severity prior to treatment, i.e., postnasal drip and overall disease severity (SNOT-22 score), but not with the objective severity of the disease (CT score and inflammation).

Females have stronger neurogenic response than males after non-specific nasal challenge in patients with seasonal allergic rhinitis.

Epidemiological studies show female predominance in the prevalence of non- allergic rhinitis (NAR) and local allergic rhinitis (LAR). Experimental studies show female patients with allergic rhinitis (AR) demonstrate higher levels of sensitivity to irritants and airway hyperresponsiveness than males. Bronchial asthma shows female predominance in post-puberty patients, and gender interaction with severe asthma endotypes. Fibromyalgia, chronic fatigue syndrome, migraine and chronic cough, syndromes, which are commonly related to neurokinin substance P (SP) in the literature, also show strong female predominance. Studies have demonstrated that sex hormones, primarily oestrogens, affect mast cell activation. Mast cell proteases can amplify neurogenic inflammatory responses including the release of SP. Based on human epidemiological data and animal experimental data we hypothesized that female patients have different interaction between mast cell activation and neurogenic inflammation, i.e. substance P release, resulting in a different nasal symptom profile. To test the hypothesis we performed allergen and non-specific nasal challenges in patients with seasonal allergic rhinitis (SAR) out of season and looked for gender differences in subjective and objective responses. The interaction between subjective and objective reactivity was evaluated through the comparison of subjective symptom scores, concentrations of neurokinin substance P (SP) and cellular markers in nasal lavages after low doses of nasal allergen challenges. Female allergic subjects tended to have higher substance P (SP) concentrations both before and after non-specific challenges. The difference between post-allergen and post - hypertonic saline (HTS) challenge was highly significant in female patients (p = 0.001), while insignificant in male subjects (p = 0.14). Female patients had significantly stronger burning sensation after HTS challenge than male. These data indicate difference in the interaction between inflammatory cells and the neurogenic response, which is gender- related, and which may affect symptom profiles after challenges. Different regulation of neurogenic inflammation in females may have impact on symptoms and endotyping in respiratory disorders, not only in allergic rhinitis, but also asthma, chronic rhinosinusitis and irritant -induced cough.

Association between computed tomography findings and clinical symptoms in chronic rhinosinusitis with and without nasal polyps.

Objective of this study was to test whether there is a difference between chronic rhinosinusitis patients with (CRSwNP) and without (CRSsNP) nasal polyps in the association of extent of disease on CT scans with symptom severity and health-related quality-of-life (HRQL) impairment. Data sets from 271 chronic rhinosinusitis (CRS) patients who completed the Sino-Nasal Outcome Test 22 (SNOT-22) and visual analog scale (VAS) scores were subjected to principal component analysis (PCA) to identify a symptom components related to CRS. After controlling for demographics, medical therapy, and comorbidities, the association between symptom components/items excluded from PCA and Lund-Mackay score (LMS) was evaluated. No association was found between the total SNOT-22 score and LMS in CRS patients. There was an independent association between a higher "nasal" symptom component derived from SNOT-22 PCA and LMS in patients with CRSwNP (p < 0.001), but not in CRSsNP patients, with a statistically significant difference between two patient subsets (p = 0.003). In patients with CRSsNP, higher (worse) SNOT-22 "facial pain" was associated with lower LMS (p = 0.022), although the estimated change in LMS was modest. Considering VAS PCA components, higher "nasal" symptoms were associated with higher LMS in CRSwNP patients (p < 0.001) but not in CRSsNP, with a statistically significant difference between CRS groups (p = 0.024). A higher "pain" PCA component was associated with lower LMS in CRSsNP patients (p = 0.019). This study found significant differences in the relationship between symptom burden and CT scores between CRS phenotypes and no association between HRQL impairment and CT scores.

Differences in the Sino-Nasal Outcome Test 22 and visual analog scale symptom scores in chronic rhinosinusitis with and without nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) with and without polyps has a high impact on health-related quality of life (HRQL), but the difference in HRQL and symptom presentation between two clinical phenotypes of CRS has not been specifically evaluated before now. OBJECTIVE: To evaluate patterns of symptoms and HRQL disease-specific domains affected in patients with CRS by comparing differences between two clinical phenotypes, adjusted for demographics, major risk factors, comorbidities, current medical treatment, and previous surgery. METHODS: A group of 251 patients with CRS completed the visual analog scale (VAS) symptom severity score and the Sino-Nasal Outcome Test 22 (SNOT-22) questionnaire. Data sets were analyzed by using principal component analysis (PCA) to identify a set of symptom components, together with the items excluded from PCA, which were then analyzed for differences between patients with CRS with nasal polyps (CRSwNP) and patients with CRS without nasal polyps (CRSsNP). RESULTS: PCA of SNOT-22 items identified six components, three referred to CRS-specific symptoms termed "nasal"; "extranasal, rhinologic"; and "olfactory/cough"; and three referred to HRQL impairment termed "sleep disturbance," "functional disturbance," and "emotional disturbance." Nasal obstruction, ear pain, ear fullness, and fatigue were excluded from PCA and treated as separate outcomes. Patients with CRSwNP had significantly worse nasal symptoms, olfactory/cough symptoms, and nasal obstruction. Patients with CRSsNP scored significantly worse with regard to fatigue and to sleep and functional disturbances. The PCA results for VAS scores identified three symptom components: pain, nasal symptoms, and pharyngeal symptoms. Patients with CRSwNP had significantly worse VAS nasal symptoms but less pronounced VAS pain symptoms than patients with CRSsNP. The total SNOT-22 score between the groups was not significantly different. CONCLUSION: With controlling of covariates that may influence the severity of the disease, this study showed significant differences in symptom patterns and different aspects of HRQL impairment between patients with CRSwNP and patients with CRSsNP, however, with no difference in the total HRQL score.

Septoplasty in children.

OBJECTIVES: Physicians have long had concerns about the potential harmful effects of pediatric septoplasties on the nasoseptal growth process because septal cartilage is important for the growth and development of the face. METHODS: In this review article, pediatric septoplasty and its indications are discussed, together with a literature survey. In addition, overviews of development of the nasal skeleton from neonate to adult, nasal growth, and cartilaginous septum are presented. Important issues and comments on pediatric septoplasties are provided. RESULTS: During septoplasty procedures, elevation of the mucoperichondrium unilaterally or bilaterally does not negatively affect growth of the face. Stabilization of the septum may be easier when mucosal elevation is performed unilaterally. The nasal floor mucosa should not be elevated so to avoid damage to the incisive nerves. Corrections and limited excisions may be done from the cartilaginous septum. Separation of the septal cartilage from the perpendicular plate, especially at the dorsal part, should not be performed because this area is important for the length and height of the nasal septum and nasal dorsum. Incisions or excisions should not be performed through the growing and supporting zones, especially at the sphenoethmoid dorsal zone. CONCLUSION: If there are severe breathing problems related to the septal deviation, septoplasty should be performed. In the majority of cases, septal surgery may be conducted in 6-year-old children. However, if necessary, septal surgery may be performed in younger children and even at birth.

Nasal and ocular responses after specific and nonspecific nasal challenges in seasonal allergic rhinitis.

BACKGROUND: Different nasal challenges induce neural and immune response leading to nasal and ocular symptoms in patients with seasonal allergic rhinitis (SAR). The release of neural mediators from nasal mucosa and conjunctiva after no-specific challenges in patients with SAR remains unknown. OBJECTIVES: To compare the release of mediators from the nose and conjunctiva with symptoms after different nasal challenges in patients with SAR. METHODS: Three types of consecutive nasal challenges were performed outside the pollen season in 25 patients with SAR. Challenges consisted of 500 biological units (BU) of allergen, 80 µg of histamine, and 1 mL of 2% hypertonic saline per nostril, within 24-hour and 72-hour intervals, respectively. Before and 15 minutes after challenges, evaluation of symptoms was performed with a visual analog scale. Concentrations of tryptase, eosinophil cationic protein in nasal lavages after 15 minutes, and substance P in tears after 5 minutes were measured with enzyme immunoassays. RESULTS: Concentrations of substance P in tears were significantly higher after nonspecific challenges. Substance P concentration in tears significantly correlated with eye itchiness after histamine and hypertonic saline and with tearing after allergen. Ocular symptoms correlated significantly with tryptase concentration in nasal lavage collected 15 minutes after allergen challenge. There is a significant correlation in tear volume comparing different nasal challenges. CONCLUSIONS: Nasal challenges with allergen, histamine, or irritants outside the pollen season induce a significant increase in nasal and ocular symptoms in patients with SAR. Interaction of the early-phase response and neurogenic inflammation define the pattern and severity of eye symptoms.

Relationship between nasal septal deformity, symptoms and disease severity in chronic rhinosinusitis.

The objective of this study was to evaluate the interaction of nasal septal deformity (NSD), including the contribution of septal spurs, with the severity of subjective symptoms, impairment of health-related quality of life (HRQoL) and sinus mucosal hyperplasia in patients with chronic rhinosinusitis (CRS). One hundred seventeen patients with CRS were assigned to three groups with mild, moderate or severe NSD, according to the measured nasal septal angle, including the presence of contact septal spurs. All CRS patients completed the visual analog scale (VAS) symptom severity score and the Sino-Nasal Outcome Test (SNOT-22) questionnaire. Symptoms scores, SNOT-22 and Lund-Mackay (LM) scores among the three NSD groups were compared. Related anatomy from the study group was compared with 100 control patients. VAS score for postnasal discharge in CRS patients was significantly higher in patients with mild NSD. There was a significantly higher LM score in CRS patients with severe NSD, compared to those with mild (P = 0.001) or moderate NSD (P = 0.005). CRS patients with a contact spur demonstrated a significantly higher LM score (P = 0.006) compared to those without a contact spur, and no differences in VAS symptom scores or HRQoL scores. There was a similar prevalence of septal deformities in CRS patients and in the non-ENT population. Our results support the conclusion that in patients with CRS, associated NSD or contact septal spur do not contribute significantly to CRS symptom severity or HRQoL impairment, but may have an impact on sinus mucosal hyperplasia.