Randomized trial of pharmacokinetic and pharmacodynamic effects of 13.2 mg intranasal epinephrine treatment in congestion.

BACKGROUND: Nasal congestion could affect the absorption of an epinephrine nasal spray (ENS). OBJECTIVE: To compare the pharmacokinetics of 13.2 mg ENS with nasal congestion vs without congestion and vs intramuscular (IM) treatments. METHODS: This phase I, open-label, 4-period randomized crossover study enrolled 51 healthy adults with seasonal allergies into cohorts that received a single dose of 13.2 mg ENS (NDS1C; Bryn Pharma, Lebanon, New Jersey) administered as 2 consecutive sprays in either opposite nostrils (cohort 1) or the same nostril (cohort 2). Both cohorts received 13.2 mg ENS with and without nasal allergen challenge (NAC), 0.3 mg IM epinephrine by autoinjector, and 0.5 mg IM epinephrine by manual syringe (MS). RESULTS: The ENS after NAC resulted in higher extent and peak exposures and more rapid time to maximum plasma concentration vs ENS without NAC and IM treatments. In cohort 1, the maximum observed baseline-adjusted epinephrine plasma concentration (pg/mL) of ENS with NAC, IM autoinjector, IM MS, or ENS without NAC was 458.0, 279.0, 364.2, and 270.1, respectively, and in cohort 2 was 436.3, 228.2, 322.3, and 250.8, respectively. The maximum observed baseline-adjusted epinephrine plasma concentration geometric mean ratio (90% CI) for ENS with NAC vs without NAC in cohort 1 was 170% (123%-234%), and in cohort 2 was 174% (115%-263%). In cohort 1, the time to maximum plasma concentration was 15, 21, 45, and 25 minutes, respectively, and in cohort 2 was 18, 20, 45, and 20 minutes, respectively (P < .01 for ENS with NAC vs IM MS). The postdose mean heart rate and blood pressure remained stable and relatively similar to predose values regardless of plasma epinephrine concentration. Mild nausea and headache were the most common adverse events with ENS. CONCLUSION: The 13.2 mg ENS with congestion exhibited enhanced absorption vs IM treatments and ENS without congestion and seemed to be well tolerated. There was no clinically impactful relationship between pharmacodynamic effects and plasma epinephrine concentration.

Adjunctive Treatment of Pediatric Adenoidal Hypertrophy: A Review.

Context: Adenoids play an important role in the protection of the upper respiratory tract against pathogens. Nonphysiological enlargement of adenoids is defined as adenoid hypertrophy (AH). In treating AH, physicians prefer medical therapy and often disregard adjunctive methods. Studies on the effects of adjunctive methods on adenoid tissue are quite scarce. Objective: The current review aims to examine the clinical studies that have investigated adjunctive methods-nasal irrigation, herbal therapy, bacteriotherapy, and halotherapy-used to treat AH and its associated symptoms and to evaluate their effectiveness in pediatric patients. Design: The research team performed a narrative review by searching seven electronic databases (Pubmed, Cochrane Library, Google Scholar, Web of Science, EMBASE, Science Citation Index and Elsevier) were used for the literature search. The search used the keywords adenoid hypertrophy, adjunctive treatment, nasal irrigation, herbal medications, bacteriotherapy and halotherapy. Setting: This study was took place in Department of Anatomy, Medicine Faculty, Istanbul Medeniyet University. Results: The nasal irrigation with hypertonic solution decreased to size of enlarged adenoid tissue. The bacteriotherapy used with nasal spray and tablet form decreased to surgery rate and adenoid size.The adenoid and/or tonsillar hypertrophy were decreased by halotherapy used with micronized, iodized-salt aerosol. Conclusions: A review of studies on this matter indicates that the studied adjunctive methods can be used safely in the treatment of AH, either separately or in combination with conventional medical treatment. However further clinical studies are needed on this topic.

The independent role of nasal obstruction in resistant hypertension for uncontrolled hypertensive patients with obstructive sleep apnea.

PURPOSE: To determine the independent predictive role of nasal obstruction in resistant hypertension (RH) in uncontrolled hypertensive patients with obstructive sleep apnea (OSA). METHODS: This prospective cohort study comprised of 236 OSA patients with uncontrolled blood pressure (BP) using 1 or 2 classes of antihypertensive drugs visiting Sleep Medicine Center from April 2021 to March 2022. Information on demographic characteristics, comorbidities, BP control and classes of antihypertensive medication, sleep-related symptoms, Nasal Obstruction Symptom Evaluation (NOSE) Scale and sleep parameters was collected. RH incidence according to the BP control and classes of antihypertensive drugs data during the 5 month follow-up was collected. RESULTS: After 5 month follow-up, 217 participants were included for final data analysis. Ninety-five subjects had nocturnal nasal obstruction with a higher proportion of RH (36.8% vs. 17.2%, p = 0.001) compared to those without nocturnal nasal obstruction. After adjustment for demographic characteristics, sleep-related symptoms and OSA severity, multinomial logistic regression models showed that nocturnal nasal obstruction (all ORs > 2.5, p < 0.05) or NOSE ≥ 8 (all ORs > 4.5, p < 0.05) was independently associated with a higher odds of RH. Nasal obstruction treatment improved NOSE score significantly, but did not reduce the incidence of RH significantly. Effective nasal obstruction treatment was associated with antihypertensive drugs reduction (OR 4.43; 95% CI 1.20-16.27). CONCLUSIONS: Nasal obstruction is an independent predictor of RH in uncontrolled hypertensive patients with OSA. In addition to the treatment of OSA, assessment and treatment of nasal obstruction should be considered in the management of uncontrolled hypertensive patients with OSA.

Evaluating treatment response to mepolizumab in patients with severe CRSwNP.

BACKGROUND: The SYNAPSE study (NCT03085797) demonstrated that mepolizumab decreased nasal polyp (NP) size and nasal obstruction in patients with chronic rhinosinusitis with NP (CRSwNP). METHODS: SYNAPSE, a randomized, double-blind study, included patients with recurrent, refractory, severe CRSwNP, eligible for repeated surgery despite receiving standard of care (SoC). Patients received 4-weekly mepolizumab 100 mg or placebo subcutaneously plus SoC for 52 weeks. This post hoc analysis further characterized treatment responses and association with patient characteristics. The proportion of patients meeting any and each of five response criteria indicating improvement in disease-specific quality of life, NP size, nasal obstruction, loss of smell, and overall symptoms at Weeks 24 and 52, were assessed in subgroups: 1) no surgery; 2) neither surgery nor systemic corticosteroids (SCS). RESULTS: Of 407 patients in the intention-to-treat population, 381 and 343 patients had no sinus surgery by Weeks 24 and 52, respectively. More mepolizumab- versus placebo-treated patients without surgery by Weeks 24 and 52 met each response criteria. Of the mepolizumab-treated patients without surgery by Week 24, 109 (55%) responded across >=3 criteria, increasing to 126 (67%) by Week 52. Similar response trends were seen for patients with neither surgery nor SCS by Weeks 24 and 52. At either timepoint, there were no major differences in baseline characteristics between mepolizumab-treated full- (5/5 categories) and non-responders (0/5 categories). CONCLUSIONS: Most patients who completed SYNAPSE required neither surgery nor SCS use and in addition achieved a progressive and sustained clinical response to mepolizumab underscoring the therapeutic benefits of mepolizumab in severe CRSwNP.

Mepolizumab for chronic rhinosinusitis with nasal polyps: Treatment efficacy by comorbidity and blood eosinophil count.

BACKGROUND: In the phase III SYNAPSE study, mepolizumab reduced nasal polyp (NP) size and nasal obstruction in chronic rhinosinusitis with NP. OBJECTIVE: We sought to assess the efficacy of mepolizumab in patients from SYNAPSE grouped by comorbid asthma, aspirin-exacerbated respiratory disease (AERD), and baseline blood eosinophil count (BEC). METHODS: SYNAPSE, a randomized, double-blind, 52-week study (NCT03085797), included patients with severe bilateral chronic rhinosinusitis with NP eligible for surgery despite intranasal corticosteroid treatment. Patients received 4-weekly subcutaneous mepolizumab 100 mg or placebo plus standard of care for 52 weeks. Coprimary end points were change in total endoscopic NP score (week 52) and nasal obstruction visual analog scale score (weeks 49-52). Subgroup analyses by comorbid asthma and AERD status, and post hoc by BEC, were exploratory. RESULTS: Analyses included 407 patients (289 with asthma; 108 with AERD; 371 and 278 with BEC counts ≥150 or ≥300 cells/µL, respectively). The proportion of patients with greater than or equal to 1-point improvement from baseline in NP score was higher with mepolizumab versus placebo across comorbid diseases (asthma: 52.9% vs 29.5%; AERD: 51.1% vs 20.6%) and baseline BEC subgroups (<150 cells/µL: 55.0% vs 31.3%; ≥150 cells/µL: 49.5% vs 28.1%; <300 cells/µL: 50.7% vs 29.0%; ≥300 cells/µL: 50.4% vs 28.1%). A similar trend was observed in patients without comorbid asthma or AERD. More patients had more than 3-point improvement in nasal obstruction VAS score with mepolizumab versus placebo across comorbid subgroups. CONCLUSIONS: Mepolizumab reduced polyp size and nasal obstruction in chronic rhinosinusitis with NP regardless of the presence of comorbid asthma or AERD.

Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial.

BACKGROUND: Eosinophilic inflammation has been implicated in the pathogenesis, severity, and treatment responsiveness of chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: We sought to assess the efficacy and safety of benralizumab-mediated eosinophil depletion for treating CRSwNP. METHODS: The phase 3 OSTRO study enrolled patients with severe CRSwNP who were symptomatic despite treatment with intranasal corticosteroids and who had a history of systemic corticosteroid (SCS) use and/or surgery for nasal polyps (NP). Patients were randomized 1:1 to treatment with benralizumab 30 mg or placebo every 4 weeks for the first 3 doses and every 8 weeks thereafter. Coprimary end points were change from baseline to week 40 in NP score (NPS) and patient-reported mean nasal blockage score reported once every 2 weeks. RESULTS: The study population comprised 413 randomized patients (207 in the benralizumab group and 206 in the placebo group). Benralizumab significantly improved NPS and nasal blockage score compared to placebo at week 40 (P ≤ .005). Improvements in Sinonasal Outcome Test 22 score at week 40, time to first NP surgery and/or SCS use for NP, and time to first NP surgery were not statistically significant between treatment groups. Nominal significance was obtained for improvement in difficulty in sense of smell score at week 40 (P = .003). Subgroup analyses suggested influences of comorbid asthma, number of NP surgeries, sex, body mass index, and baseline blood eosinophil count on treatment effects. Benralizumab was safe and well tolerated. CONCLUSION: Benralizumab, when added to standard-of-care therapy, reduced NPS, decreased nasal blockage, and reduced difficulty with sense of smell compared to placebo in patients with CRSwNP. TRIAL REGISTRATION: ClinicalTrials.gov NCT03401229.

Nocturnal nasal congestion is associated with uncontrolled blood pressure in patients with hypertension comorbid obstructive sleep apnea.

OBJECTIVE: To determine the independent role of nasal obstruction on blood pressure (BP) control in patients with hypertension comorbid obstructive sleep apnea (OSA). SUBJECTS AND METHODS: This cross-sectional study comprised of 326 newly diagnosed OSA comorbid hypertension patients from March 2018 to December 2021. Sixty-six patients have controlled hypertension, two hundred and nine with uncontrolled hypertension and fifty-one with resistant hypertension. Information on demographic characteristics, sleep data, hypertension status was collected. Multivariate logistic regression models were used to determine the odds ratios (OR). RESULTS: Patients with nocturnal nasal congestion had more difficult to control blood pressure, with more numbers of antihypertensive drugs. They tended to have more severe OSA, lower nocturnal oxygen saturation and more severe sleepiness. Univariate analysis showed that nocturnal nasal congestion and Nasal Obstruction Symptom Evaluation (NOSE) Scale scores were associated with uncontrolled BP. After adjusting for age, sex, smoking, alcohol use, OSA severity and CT90, multivariate logistic analysis models showed that nocturnal nasal congestion was independently associated with uncontrolled hypertension (OR = 2.09, p = 0.023). When analyzed more severe resistant hypertension, nocturnal nasal congestion showed a higher association (OR = 2.96, p = 0.014). CONCLUSION: This cross-sectional study demonstrated that the nocturnal nasal congestion was independently associated with uncontrolled BP. The use of nasal decongestants or nasal surgery may be a potential therapeutic target for resistant hypertension in the future.

Biologics for chronic rhinosinusitis.

BACKGROUND: This living systematic review is one of several Cochrane Reviews evaluating the medical management of patients with chronic rhinosinusitis. Chronic rhinosinusitis is common. It is characterised by inflammation of the nasal and sinus linings, nasal blockage, rhinorrhoea, facial pressure/pain and loss of sense of smell. It occurs with or without nasal polyps.   'Biologics' are medicinal products produced by a biological process. Monoclonal antibodies are one type, already evaluated in other inflammatory conditions (e.g. asthma and atopic dermatitis). OBJECTIVES: To assess the effects of biologics for the treatment of chronic rhinosinusitis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; CENTRAL (2020, Issue 9); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 28 September 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) with at least three months follow-up comparing biologics (monoclonal antibodies) against placebo/no treatment in patients with chronic rhinosinusitis. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were disease-specific health-related quality of life (HRQL), disease severity and serious adverse events (SAEs). The secondary outcomes were avoidance of surgery, extent of disease (measured by endoscopic or computerised tomography (CT) score), generic HRQL and adverse effects (nasopharyngitis, including sore throat). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 10 studies. Of 1262 adult participants, 1260 had severe chronic rhinosinusitis with nasal polyps; 43% to 100% of participants also had asthma. Three biologics, with different targets, were evaluated: dupilumab, mepolizumab and omalizumab. All of the studies were sponsored or supported by industry. For this update (2021) we have included two new studies, including 265 participants, which reported data relating to omalizumab. Anti-IL-4Rα mAb (dupilumab) versus placebo/no treatment (all receiving intranasal steroids) Three studies (784 participants) evaluated dupilumab. Disease-specific HRQL was measured with the SNOT-22 (a 22-item questionnaire, with a score range of 0 to 110; minimal clinically important difference (MCID) 8.9 points). At 24 weeks, dupilumab results in a large reduction (improvement) in the SNOT-22 score (mean difference (MD) -19.61, 95% confidence interval (CI) -22.54 to -16.69; 3 studies; 784 participants; high certainty). At between 16 and 52 weeks of follow-up, dupilumab probably results in a large reduction in disease severity, as measured by a 0- to 10-point visual analogue scale (VAS) (MD -3.00, 95% CI -3.47 to -2.53; 3 studies; 784 participants; moderate certainty). This is a global symptom score, including all aspects of chronic rhinosinusitis symptoms. At between 16 and 52 weeks of follow-up, dupilumab may result in a reduction in serious adverse events compared to placebo (5.9% versus 12.5%, risk ratio (RR) 0.47, 95% CI 0.29 to 0.76; 3 studies, 782 participants; low certainty). Anti-IL-5 mAb (mepolizumab) versus placebo/no treatment (all receiving intranasal steroids) Two studies (137 participants) evaluated mepolizumab. Disease-specific HRQL was measured with the SNOT-22. At 25 weeks, the SNOT-22 score may be reduced (improved) in participants receiving mepolizumab (MD -13.26 points, 95% CI -22.08 to -4.44; 1 study; 105 participants; low certainty; MCID 8.9).  It is very uncertain whether there is a difference in disease severity at 25 weeks: on a 0- to 10-point VAS, disease severity was -2.03 lower in those receiving mepolizumab (95% CI -3.65 to -0.41; 1 study; 72 participants; very low certainty). It is very uncertain if there is a difference in the number of serious adverse events at between 25 and 40 weeks (1.4% versus 0%; RR 1.57, 95% CI 0.07 to 35.46; 2 studies; 135 participants, very low certainty). Anti-IgE mAb (omalizumab) versus placebo/no treatment (all receiving intranasal steroids) Five studies (329 participants) evaluated omalizumab. Disease-specific HRQL was measured with the SNOT-22. At 24 weeks omalizumab probably results in a large reduction in SNOT-22 score (MD -15.62, 95% CI -19.79 to -11.45; 2 studies; 265 participants; moderate certainty; MCID 8.9). We did not identify any evidence for overall disease severity. It is very uncertain whether omalizumab affects the number of serious adverse events, with follow-up between 20 and 26 weeks (0.8% versus 2.5%, RR 0.32, 95% CI 0.05 to 2.00; 5 studies; 329 participants; very low certainty). AUTHORS' CONCLUSIONS: Almost all of the participants in the included studies had nasal polyps (99.8%) and all were using topical nasal steroids for their chronic rhinosinusitis symptoms. In these patients, dupilumab improves disease-specific HRQL compared to placebo. It probably also results in a reduction in disease severity, and may result in a reduction in the number of serious adverse events. Mepolizumab may improve disease-specific HRQL. It is very uncertain if there is a difference in disease severity or the number of serious adverse events. Omalizumab probably improves disease-specific HRQL compared to placebo. It is very uncertain if there is a difference in the number of serious adverse events. There was no evidence regarding the effect of omalizumab on disease severity (using global scores that address all symptoms of chronic rhinosinusitis).

Efficacy and Safety of Sea Salt-Derived Physiological Saline Nasal Spray as Add-On Therapy in Patients with Acute Upper Respiratory Infection: A Multicenter Retrospective Cohort Study.

BACKGROUND The purpose of this study was to assess the effects of seawater on nasal congestion and runny nose symptoms in adults with an acute upper respiratory infection (URI). MATERIAL AND METHODS This was a multicenter retrospective cohort trial of patients with acute URI and symptoms of nasal congestion and runny nose. The patients were assigned to 2 groups and were administered regular non-drug supportive treatment or supportive treatment with nasal irrigation with sea salt-derived physiological saline. The primary efficacy endpoint was the effective rate (percentage of patients with ≥30% symptom score reduction from baseline for nasal congestion and runny nose). RESULTS In total, 144 patients were enrolled, including 72 in each group, and 143 patients completed the study. Both groups had similar demographics and vital signs. The effective rates for nasal congestion and runny nose were significantly increased in the seawater group compared with patients in the control group (87.3% vs 59.7% for nasal congestion; 85.9% vs 61.1% for runny nose; both P<0.001). In addition, the 2 groups showed markedly different degrees of patient symptom score improvement in sleep quality and appetite (both P<0.01), but not in cough and fatigue (both P>0.05). There were no adverse events in either group. CONCLUSIONS The sea salt-derived physiological saline nasal spray device satisfactorily improved nasal congestion, runny nose, sleep quality, and appetite in adults with URI, with no adverse effects.

Evaluation of the intranasal steroid treatment outcomes in adenoid tissue hypertrophy with or without allergic rhinitis.

PURPOSE: To compare the intranasal steroid (INS) treatment outcomes in patients with adenoid tissue hypertrophy (ATH) with or without allergic rhinitis (AR). MATERIALS AND METHODS: Medical records of 96 children diagnosed with ATH were retrospectively examined. The pediatric version of the Score for Allergic Rhinitis (SFAR) questionnaire was used to determine the AR status of the patients and classify them. The children were divided into two groups based on the questionnaire: Group 1, low probability of AR (SFAR<9); and Group 2, high probability of AR (SFAR≥9). Intranasal mometasone furoate (100 µg/mL) was used to treat ATH for at least 3 months. The severity of nasal obstruction and snoring was evaluated using the visual analog scale (VAS) score, the adenoid/choana (A/C) ratios before and after treatment were compared, and the rate of patient referral to surgery was recorded among groups. RESULTS: The change in the A/C ratio within the group between before and after treatment was significant (both P < 0.001). However, the reduction in the adenoid size was more significant in Group 1 than in Group 2 (P = 0.025). A significant improvement in the VAS scores was observed between before and after treatment in both groups (P < 0.001). Furthermore, the rate of surgical referral of Group 1 was significantly lower than that of Group 2 (P = 0.035). CONCLUSIONS: INS treatment was found more successful for reducing A/C ratio in ATH without AR. Related with this, when considering the INS treatment for ATH, AR status should be kept in mind for predicting the treatment success.

Septoplasty versus non-surgical management for nasal obstruction in adults with a deviated septum: economic evaluation alongside a randomized controlled trial.

BACKGROUND: For years, the benefits of septoplasty have been questioned. Due to the scarce and inconclusive literature, several National Health Service (NHS) Clinical Commissioning Groups in England decided to add septal surgery to their list of restricted procedures with low clinical value. Recently, evidence was obtained that septoplasty is actually more effective than non-surgical management for nasal obstruction in adults with a deviated septum. However, the relation between costs and effects of septoplasty remains unknown. METHODS: We conducted an economic evaluation alongside an open, multicenter, pragmatic randomized controlled trial in two tertiary and 16 secondary referral hospitals in the Netherlands. Adults with nasal obstruction and a deviated septum were randomized to (1) septoplasty with or without concurrent turbinate surgery or (2) non-surgical management consisting of (a combination of) medical treatment and watchful waiting. Analyses were performed on an intention-to-treat basis. Single imputation nested in the bootstrap percentile method (using 5000 bootstrap replications) was performed to assess the effect of missing data. After 12 and 24 months, we assessed the incremental costs per quality-adjusted life year (QALY) gained from a healthcare and a societal perspective. RESULTS: A total of 203 adults were randomly assigned to septoplasty (N = 102) or non-surgical management (N = 101). After 12 months, the mean cost difference between septoplasty and non-surgical management using a healthcare or societal perspective was €1181 (95%CI €1038 to €1323) or €2192 per patient (95%CI €1714 to €2670), respectively. The mean QALY difference was 0.03 per patient (95%CI - 0.01 to 0.07). Incremental costs per QALY gained from a healthcare or societal perspective were €41,763 or €77,525, respectively. After 24 months, the mean cost difference between the two groups using a healthcare or societal perspective decreased to €936 (95%CI €719 to €1153) or €1671 per patient (95%CI €952 to €2390), respectively. The mean QALY difference increased to 0.05 per patient (95%CI - 0.03 to 0.14). Incremental costs per QALY gained from a healthcare or societal perspective became €17,374 or €31,024, respectively. Analyses of imputed data did not alter our findings. CONCLUSIONS: Depending on the selected perspective, cost-effectiveness threshold, and time horizon, septoplasty has the potential to be cost-effective. Despite considerable uncertainty, septoplasty seems to be cost-effective from a healthcare perspective, after 24 months against a threshold of €20,000 per QALY. From a societal perspective, septoplasty is not yet cost-effective after 24 months, but it comes closer to the cost-effectiveness threshold as time passes by. TRIAL REGISTRATION: Nederlands Trial Register, NTR3868 (https://www.trialregister.nl/trial/3698). Prospectively registered on February 21, 2013.

Biologics for chronic rhinosinusitis.

BACKGROUND: This living systematic review is one of several Cochrane Reviews evaluating the medical management of patients with chronic rhinosinusitis. Chronic rhinosinusitis is common. It is characterised by inflammation of the nasal and sinus linings, nasal blockage, rhinorrhoea, facial pressure/pain and loss of sense of smell. It occurs with or without nasal polyps.   'Biologics' are medicinal products produced by a biological process. Monoclonal antibodies are one type, already evaluated in related inflammatory conditions (e.g. asthma and atopic dermatitis). OBJECTIVES: To assess the effects of biologics for the treatment of chronic rhinosinusitis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; CENTRAL (2019, Issue 9); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 September 2019. SELECTION CRITERIA: Randomised controlled trials (RCTs) with at least three months follow-up comparing biologics (currently, monoclonal antibodies) against placebo/no treatment in patients with chronic rhinosinusitis. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were disease-specific health-related quality of life (HRQL), disease severity and serious adverse events (SAEs). The secondary outcomes were avoidance of surgery, extent of disease (measured by endoscopic or computerised tomography (CT) score), generic HRQL and adverse events (nasopharyngitis, including sore throat). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included eight RCTs. Of 986 adult participants, 984 had severe chronic rhinosinusitis with nasal polyps; 43% to 100% of participants also had asthma. Three biologics, with different targets, were evaluated: dupilumab, mepolizumab and omalizumab. All the studies were sponsored or supported by industry. Anti-IL-4Rα mAb (dupilumab) versusplacebo/no treatment (all receiving intranasal steroids) Three studies (784 participants) evaluated dupilumab. Disease-specific HRQL was measured with the SNOT-22 (score 0 to 110; minimal clinically important difference (MCID) 8.9 points). At 24 weeks, the SNOT-22 score was 19.61 points lower (better) in participants receiving dupilumab (mean difference (MD) -19.61, 95% confidence interval (CI) -22.54 to -16.69; 3 studies; 784 participants; high certainty). Symptom severity measured on a 0- to 10-point visual analogue scale (VAS) was 3.00 lower in those receiving dupilumab (95% CI -3.47 to -2.53; 3 studies; 784 participants; moderate certainty). The risk of serious adverse events may be lower in the dupilumab group (risk ratio (RR) 0.45, 95% CI 0.28 to 0.75; 3 studies; 782 participants; low certainty).  The number of participants requiring nasal polyp surgery (actual or planned) during the treatment period is probably lower in those receiving dupilumab (RR 0.17, 95% CI 0.05 to 0.52; 2 studies; 725 participants; moderate certainty). Change in the extent of disease using the Lund Mackay computerised tomography (CT) score (0 to 24, higher = worse) was -7.00 (95% CI -9.61 to -4.39; 3 studies; 784 participants; high certainty), a large effect favouring the dupilumab group.  The EQ-5D visual analogue scale (0 to 100, higher = better; MCID 8 points) was used to measure change in generic quality of life. The mean difference favouring dupilumab was 8.59 (95% CI 5.31 to 11.86; 2 studies; 706 participants; moderate certainty). There may be little or no difference in the risk of nasopharyngitis (RR 0.95, 95% CI 0.72 to 1.25; 3 studies; 783 participants; low certainty). Anti-IL-5 mAb (mepolizumab) versusplacebo/no treatment (all receiving intranasal steroids) Two studies (137 participants) evaluated mepolizumab. Disease-specific HRQL measured with the SNOT-22 at 25 weeks was 13.26 points lower (better) in participants receiving mepolizumab (95% CI -22.08 to -4.44; 1 study; 105 participants; low certainty; MCID 8.9).  It is very uncertain whether there is a difference in s ymptom severity: on a 0- to 10-point VAS symptom severity was -2.03 lower in those receiving mepolizumab (95% CI -3.65 to -0.41; 1 study; 72 participants; very low certainty). It is very uncertain if there is difference in the risk of serious adverse events (RR 1.57, 95% CI 0.07 to 35.46; 2 studies; 135 participants, very low certainty). It is very uncertain whether or not the overall risk that patients still need surgery at trial end is lower in the mepolizumab group (RR 0.78, 95% CI 0.64 to 0.94; 2 studies; 135 participants; very low certainty). It is very uncertain whether mepolizumab reduces the extent of disease as measured by endoscopic nasal polyps score (scale range 0 to 8). The mean difference was 1.23 points lower in the mepolizumab group (MD -1.23, 95% -1.79 to -0.68; 2 studies; 137 participants; very low certainty). The difference in generic quality of life (EQ-5D) was 5.68 (95% CI -1.18 to 12.54; 1 study; 105 participants; low certainty), favouring the mepolizumab group. This difference is smaller than the MCID of 8 points. There may be little or no difference in the risk of nasopharyngitis (RR 0.73, 95% 0.36 to 1.47; 2 studies; 135 participants; low certainty). Anti-IgE mAb (omalizumab) versus placebo/no treatment (all receiving intranasal steroids) Three very small studies (65 participants) evaluated omalizumab. We are very uncertain about the effect of omalizumab on disease-specific HRQL, severe adverse events, extent of disease (CT scan scores), generic HRQL and adverse effects. AUTHORS' CONCLUSIONS: In adults with severe chronic rhinosinusitis and nasal polyps, using regular topical nasal steroids, dupilumab improves disease-specific HRQL compared to placebo, and reduces the extent of the disease as measured on a CT scan. It probably also improves symptoms and generic HRQL and there is no evidence of an increased risk of serious adverse events. It may reduce the need for further surgery. There may be little or no difference in the risk of nasopharyngitis. In similar patients, mepolizumab may improve both disease-specific and generic HRQL. It is uncertain whether it reduces the need for surgery or improves nasal polyp scores. There may be little or no difference in the risk of nasopharyngitis. It is uncertain if there is a difference in symptom severity and the risk of serious adverse events. We are uncertain about the effects of omalizumab.

An open-label, multicentre, randomized comparative study of efficacy, safety and tolerability of the 5 plant - extract BNO 1012 in the Delayed Antibiotic Prescription Method in children, aged 6 to 11 years with acute viral and post-viral rhinosinusitis.

Acute rhinosinusitis (ARS) can be characterized as bacterial (ABRS) and require antibiotic therapy only in 0.5-5% of cases. In most cases, the disease is in a viral and post-viral form, which requires pathogenetic and symptomatic treatment. The study objective was to determine the efficacy of BNO 1012 extract in the technology of delayed antibiotic prescribing in children with acute rhinosinusitis. METHODS: 292 children aged 6 to 11 years with ARS were randomized in the multicenter, comparative study. They received an extract of five medicinal plants in addition to standard symptomatic therapy or standard therapy only. EVALUATION CRITERIA: reduction of the sinusitis severity according to a 4-point medical assessment scale (nasal congestion, severity of anterior and posterior rhinorrhea) at each visit, dynamics of self-scoring of rhinorrhea and headache (according to a 10-point visual analogue scale), "therapeutic benefit" in days, frequency of antibiotic prescriptions due to the use of an extract of five plants. RESULTS: The use of the 5-plant extract BNO 1012 in addition to the standard symptomatic treatment of acute rhinosinusitis provides a clinically significant, adequate reduction in the severity of rhinorrhea, nasal congestion and post-nasal drip, assessed by a physician at V2 (p < 0.005). Significant differences are noted in the patient's self-scoring of rhinorrhea on the second or third day in viral RS, and from the fourth to the eighth day in post-viral RS. Symptoms of similar intensity in control group were observed at V3. Thus, in the first week of treatment, the treatment group compared to the control one showed a "therapeutic benefit" of three days. The use of BNO 1012 in patients with acute rhinosinusitis can 1.81-fold reduce the prescription of antibacterial drugs. CONCLUSION: The combination of five medicinal plants is effective for the treatment of acute rhinosinusitis in children aged 6 to 11 years. Its use provides a significant "therapeutic benefit" when administered in addition to standard symptomatic therapy, reducing the need for antibiotic use.

[Rhinitis medicamentosa]. / Lekarstvenno-indutsirovannyi rinit.

One type of non-allergic non-infectious rhinitis is represented by a heterogeneous group of rhinitis medicamentosa, which can be divided into several pathogenetic types. The most common rebound nasal congestion associated with the use of topical decongestants. Excessive use of intranasal decongestants leads to a decrease in the number of alpha-adrenoreceptors on the surface of cell membranes and uncoupling their connection with the G-protein and the development of tachyphylaxis. To prevent the development of rebound nasal congestion caused by topical decongestants, it is important to limit the frequency of their use. In most cases, the duration of the use of vasoconstrictor drugs should be limited to 5-7 days, according to Patient information leaflets for the drugs. However, in patients who have had a history of episodes of rebound nasal congestion, which develops including the previously indicated periods, the duration of decongestant therapy should be limited to 3 days. Rhinitis associated with local inflammation is caused by the intake of acetylsalicylic acid (ASA) or other non-steroidal anti-inflammatory drugs. Currently, the so-called "aspirin triad" is well known - a combination of bronchial asthma, rhinosinusitis (often polyposis) and intolerance to ASA. Neurogenic rhinitis develops due to the use of drugs that violate vascular tone, for example, antihypertensive drugs or type 5 phosphodiesterase inhibitors. Drug-induced rhinitis has a significant impact on the patient's quality of life: nasal congestion, rhinorrhea, secondary night apnea, insomnia as a result of nasal breathing disturbances, headaches, irritability, weakness after sleepless nights disturb patients to a large extent. Timely diagnosis and withdrawal of a provocative drug, the use of topical corticosteroids in case of severe rhinitis are the basis of the treatment of rhinitis medicamentosa. In severe cases, there is a need, including surgical treatment, such as, for example, submucosal laser destruction of the lower nasal concha.

[Comparative study of the efficacy of combined nasal topical drug and topical decongestants in the treatment of acute rhinosinusitis]. / Sravnitel'noe issledovanie effektivnosti kombinirovannykh nazal'nykh topicheskikh preparatov i topicheskikh dekongestantov v lechenii ostrykh rinosinusitov.

OBJECTIVE: To evaluate the efficacy of the drug Frinozol (nasal spray phenylephrinein 0.25% + cetirizine 0.25%) comparison with Rinostop Extra (nasal spray oxymetazoline 0.05%) in relation to nasal symptoms of rhinosinusitis, evaluated on rating scales, when using these drugs intranasally for 7 days in patients with acute viral and post-viral rhinosinusitis of mild (VAS 0-3) and moderate (VAS 3-7). PATIENTS AND METHODS: The randomized open-label study included 60 ambulatory patients (men and women aged 18 to 60 years) with a verified diagnosis of acute rhinosinusitis (ARS) lasting no more than 120 hours. 1 group of patients took Frinozol (nasal spray phenylephrinein 0.25% + cetirizine 0.25%) for 2 sprays per each nostril 3 times a day for 7 days; 2 group - Rinostop Extra (nasal spray oxymetazoline 0.05%) at the same dose and the therapy regimen. We evaluated 3 visits (day 1, day 3, and day 7) with an ENT examination on each of them; questionnaires on the 1st and 3rd visits of nasal symptoms (nasal obstruction, rhinorrhea, hyposmia) on the visual analog scale (VAS) and Clinical Global Impression Scale-CGI. Active anterior rhinomanometry (AAR) was performed on the 1st, 2nd and 3rd visits using the PTS-14P-01 rhinomanometer Rinolan before and 20 minutes after the use of the drugs Frinozol and oxymetazoline 0.05%.

The effects of nasal decongestion on obstructive sleep apnoea.

BACKGROUND: Many studies have indicated associations between impaired nasal breathing and sleep disorders. However, the precise nature of the relationship between nasal patency and sleep remains unclear. PURPOSE: We analysed the effects of nasal patency on sleep architecture and breath in nasal obstruction-predominant obstructive sleep apnoea (NO-OSA) patients by applying nasal decongestant. MATERIAL AND METHODS: A randomized, placebo-controlled double-blind crossover study was performed in OSA patients with chronic nasal obstruction and without obvious pharyngeal narrowing. All OSA patients (confirmed by polysomnography) were recruited and completed 2 overnight studies (randomly applying oxymetazoline or placebo). Data collected after oxymetazoline or placebo treatments were compared. The ClinicalTrials.gov identifier is NCT03506178. RESULTS: Compared with placebo, oxymetazoline resulted in significant increase in rapid eye movement sleep (p = 0.027) and reduction of stage 1 sleep (p = 0.004), as well as arousal index (p = 0.002). Moreover, great improvements in apnoea/hypopnea index (AHI) were observed (p < 0.001); AHI in the supine position was significantly reduced (p = 0.001). Oxygen saturation during sleep was increased significantly [mean oxygen saturation (p = 0.005) and lowest oxygen saturation (p = 0.024)]. Oxygen desaturation index was significantly reduced (p < 0.001). CONCLUSIONS: Improving nasal patency by decongestant could improve sleep quality, AHI, and oxygen saturation level during sleep.

A pilot study to determine the effects of nasal co-phenylcaine on drug-induced sleep endoscopy.

PURPOSE: The use of nasal decongestant and nasal anaesthesia is currently not recommended during drug-induced sleep endoscopy (DISE) according to the European position paper. The evaluation of the effects of nasal decongestant/anaesthesia on DISE has not been performed before and our aim is to perform a pilot study to determine whether nasal decongestants/anaesthesia affects DISE outcomes. METHODS: 27 patients undergoing DISE for OSA or for simple snoring were included. On each patient, DISE was performed twice, before and approximately 10 min after the administration of two puffs of co-phenylcaine nasal spray (lidocaine hydrochloride 5%, phenylephrine 0.5%, and benzalkonium chloride 0.01%) into each nostril. A nasal peak inspiratory flow was used for the objective assessment of nasal airway obstruction. During the first and the second DISE the loudness of the snoring was also recorded. RESULTS: Change in DISE total grading after nasal spray administration was not statistically significant. For the same grading, changes in percentage of contribution to collapse were not statistically significant. Sex, AHI, BMI, tonsils grade, presence of rhinitis, turbinate hypertrophy, nasal septal deviation, or nasal peak inspiratory flow limitation had no influence on the effect of nasal spray. Co-phenylcaine did not significantly influence the loudness of snoring. CONCLUSIONS: Our pilot study supports the use of co-phenylcaine nasal spray during DISE and the positive effects of the nasal spray do not influence the grading outcome. Importantly, the decongestant enhances the nasal assessment during DISE and potentially aids in the diagnosis of nasal obstruction while the nasal anaesthetic component may be beneficial by reducing nasal discomfort during DISE and thereby helping to reduce the total dose of intravenous anaesthetic administered. However, further studies on a larger population are needed to confirm our results.

Longitudinal improvement in nasal obstruction symptoms of chronic rhinosinusitis directly associates with improvement in mood.

PURPOSE: The effects of nasal obstruction in patients with chronic rhinosinusitis (CRS) are associated with depressed mood. We sought to validate this finding by determining whether improvement in nasal obstruction would translate to improvement in depressed mood. METHODS: This was a prospective observational study of 150 patients undergoing medical management for CRS. Data were collected at two timepoints: enrollment and a subsequent follow-up visit 3-12 months later. Impact of nasal obstruction was measured using the Nasal Obstruction Symptom Evaluation (NOSE) instrument and depressed mood was measured using the 2-item Patient Health Questionnaire (PHQ-2). Sinonasal symptoms associated with CRS were also measured using the 22-item Sinonasal Outcome Test (SNOT-22). Clinical and demographic characteristics were collected. The relationship between changes in PHQ-2 and NOSE scores was determined with correlation and linear regression. RESULTS: Change in PHQ-2 score was significantly correlated with change in NOSE score (ρ = 0.30, p < 0.001). After controlling for covariates, change in PHQ-2 score was associated with change in NOSE score (adjusted linear regression coefficient [ß] = 0.014, 95% CI 0.006-0.022, p = 0.001). We confirmed these relationships, finding that change in PHQ-2 was associated (adjusted ß = 0.037, 95% CI 0.013-0.061, p = 0.003) with change in the nasal subdomain score of the SNOT-22. Improvement in NOSE score by greater than 22 points was predictive of improvement in PHQ-2 score with sensitivity 54.5% and 83.8% specificity (p < 0.001). CONCLUSION: These results provide evidence that improvements in nasal manifestations/symptoms of CRS translate to significant improvements in mood.

Pirometaxine™ (Narlisim™) in pediatric nasal congestion: a retrospective study.

BACKGROUND: Nasal congestion represents a troublesome health issue which is especially and invalidating in children. Effective nasal drugs, such as sympathomimetic drugs, are usually forbidden in children under 12 years of age because of their potential systemic adverse effects. Hypertonic nasal physiological solutions have recently been successfully used to decongest nasal mucosa in children: its mechanical activity has been universally recognized as safe and effective and it represents a well-established, useful treatment in children. METHODS: We have retrospectively analyzed a case series of 40 children treated for 4 days (96 hours) with a new class 1s medical device nasal hypertonic spray containing Pirometaxine™ (Narlisim™) in outpatient affected by nasal congestion due to common cold. Every child was evaluated on a 3-point symptom assessment scale (0: no symptom; 1: mild symptom; 2: moderate symptom; 3: severe symptom) at the beginning of the trial (T0) and after 48 (T1) and 96 hours (T2). The symptoms assessed were nasal obstruction, nasal secretion, headache, flash of cold, pharyngodynia, cough, and sneeze. RESULTS: The results, in terms of short-term efficacy to control nasal obstruction (T1 vs. T0: P<0.0001; T2 vs. T0: P<0.0001), nasal secretion (T1 vs. T0: P<0.0001; T2 vs. T0: P<0.0001) and all the symptoms related to common cold have supported the efficacy of this hypertonic nasal solution. No adverse events have been pointed out during the trial supporting the safety of this new nasal hypertonic approach. CONCLUSIONS: The absence of adverse events after 48-96 hours along with the short-term effectiveness of this new treatment seems to represent a new, safe option to treat children affected by nasal congestion secondary to common cold. Considering the current lack of safe treatments for children under 12 years of age, Narlisim™ can be considered as a useful short-term option to control nasal congestion in children.

The burden of allergic rhinitis and allergic rhinoconjunctivitis on adolescents: A literature review.

OBJECTIVE: To evaluate the literature regarding the burden of allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC) in adolescents (aged 10-19 years). DATA SOURCES: Searches were performed in MEDLINE, Embase, Health Technology Assessment Database, and National Health Service Economic Evaluation Database for studies that evaluated concepts of symptoms, quality of life (QOL), daily activities, sleep, examination performance, school absenteeism and presenteeism, and treatment burden in adolescents with AR or ARC. STUDY SELECTIONS: English-language journal articles indexed in the last 15 years describing noninterventional, population-based studies. Records were assessed by 2 independent reviewers. RESULTS: A total of 27 articles were identified; outcomes evaluated were symptoms (n = 6 studies), QOL (n = 9), daily activities (n = 5), emotional aspects (n = 3), sleep (n = 6), education (n = 7), and treatment burden (n = 2). AR symptoms rated most bothersome were rhinorrhea, nasal congestion, and itchy eyes. QOL was worse in adolescents with AR vs controls regardless of QOL instrument used. Nasal symptoms and nasal obstruction were more likely to be associated with poor QOL in adolescents than in adults or younger children, respectively. Daily functioning and sleep were also negatively affected by AR. In addition, a detrimental effect on absenteeism, school productivity, and academic performance was reported. CONCLUSION: Although AR and ARC are sometimes perceived as trivial conditions, this review indicates that their effect on adolescent life is negative and far-reaching. It is critical that clinicians gain a greater understanding of the unique burden of AR and ARC in adolescents to ensure they receive prompt and appropriate care and treatment to improve clinical and academic outcomes.