Real-Life Effectiveness of MP-AzeFlu (Dymista®) in Swedish Patients with Persistent Allergic Rhinitis, Assessed by the Visual Analogue Scale.

Background: Many allergic rhinitis (AR) patients have moderate/severe persistent disease. MP-AzeFlu (Dymista®) comprises intranasal azelastine hydrochloride and fluticasone propionate in a novel formulation delivered in a single device. Objective: This prospective, noninterventional study assessed the effectiveness of MP-AzeFlu (one spray/nostril twice daily; azelastine hydrochloride = 548 µg; fluticasone propionate = 200 µg) on relieving AR symptom severity. Methods: A visual analogue scale (VAS; 0 mm [not at all bothersome] to 100 mm [very bothersome]) was used during a 42-day MP-AzeFlu treatment period by 161 persistent AR (PER) patients in routine clinical practice in Sweden. Patients also assessed their sleep quality. Results: VAS scores decreased from baseline during the treatment period and patients achieved a clinically relevant VAS score cutoff before Day 7, with 89.3% reporting well or partly controlled symptoms on Day 1. VAS score decreased from 61.4 ± 22.4 mm (baseline) to 32.1 ± 24.6 mm on Day 28 and 26.1 ± 24.3 mm on Day 42 (both p < 0.0001), an overall reduction from baseline on Day 42 of 38.1 ± 28.2 mm. The percentage of patients with very good/good sleep quality increased from 3.7%/28.6% on Day 0 to 16.5%/51.5% on Day 42. Conclusion: MP-AzeFlu provides effective, rapid control of PER assessed by VAS in a real-world clinical setting in Sweden. Symptom improvement was observed at Day 1, sustained for 42 days, and associated with improved sleep quality. MP-AzeFlu significantly improved the QoL of the patients and was well tolerated.

A novel and alternative therapy for persistent allergic rhinitis via intranasal acupuncture: a randomized controlled trial.

BACKGROUND: Acupuncture is used to treat allergic rhinitis (AR) in traditional Chinese medicine, and the ST2 and ST36 acupoints are generally selected in clinical practice. We report a new intranasal acupuncture method at the Neiyingxiang (EX-HN9) and Biqiu points for the treatment of persistent AR (PAR). Here, the efficacy and safety of this method were evaluated. METHODS: A total of 120 patients diagnosed with PAR were randomly allocated (2:1 ratio) to intranasal acupuncture or Western medicine groups, the basic principle of random grouping is SAS random grouping method. The applicator held a nasal endoscope and a 0.30 × 75 mm filiform needle in their left and right hands, respectively. When aiming at the Neiyingxiang or Biqiu point, the applicator quickly inserted the needle to a 20-mm depth as parallel as possible to the inferior turbinate or middle turbinate, without special reinforcing and reducing techniques (the needle remained for 20 min). The intranasal acupuncture groups received acupuncture treatment three times per week for 2 weeks. The Western medicine group was treated with budesonide nasal spray (two sprays/nostril, twice/day) and loratadine (one tablet/night) for 2 weeks. Visual analog scale (VAS) scores were the primary outcome. Quality of life, medication dosages and adverse events were secondary outcomes measured using the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). Confidence assessments were performed to evaluate data from the treatment and follow-up periods. RESULTS: The results were as follows: (1) VAS and RQLQ scores were significantly lower in the intranasal acupuncture group than in the Western medicine group on day 1 (i.e., first treatment) (P < 0.05; 95% CI - 13.1 to - 9.6 VAS points) (P < 0.05; 95% CI - 20.27 to - 12.28 RQLQ points). Overall symptoms (95% CI - 2.86 to - 1.86 points), nasal obstruction (95% CI - 6.33 to - 5.36 points), olfactory function (95% CI - 2.91 to - 1.75 points), sleep (95% CI - 5.05 to - 3.57 points), actual problems (95% CI - 2.03 to - 0.06 points), nasal symptoms (95% CI - 6.62 to - 4.5 points), and emotional problems (95% CI - 5.05 to - 3.5 points) were significantly improved. (2) VAS and RQLQ scores in the two groups were significantly improved at week 2; however, there were no significant group differences in the VAS (P > 0.05; 95% CI - 1.21 to - 1.38 points) and RQLQ (P > 0.05; 95% CI - 0.33 to - 3.46 points) scores. Olfactory function symptoms were significantly improved (95% CI - 1.58 to - 0.21 points). (3) During the follow-up period, there was a significant difference between the two groups (P < 0.05) with higher RQLQ and VAS scores in the intranasal acupuncture group than in the Western medicine group. VAS scores on rhinobyon symptoms, nasal itch, rhinorrhea and olfactory function and RQLQ scores for activities, non-nasal/eye symptoms, actual problems, nasal symptoms, and eye symptoms were significantly improved. (4) No adverse events were observed in either group during treatment. CONCLUSIONS: Intranasal acupuncture has good efficacy and safety in the treatment of PAR. Moreover, VAS and RQLQ scores were much lower in the intranasal acupuncture group than in the Western medicine group, and acupuncture had an immediate impact, especially for improving nasal congestion, olfactory function and sleep.

Study of Allergen Patterns in Cases of Moderate to Severe Persistent Allergic Rhinitis in Central India.

The prevalence of Allergic rhinitis (AR) is associated with a variety of environmental allergens and the level of exposure is through inhalation, or ingestion. It is clear from several studies and guidelines that screening and identification of various allergens in a particular region can facilitate in diagnosing, treating and formulating preventive strategies against AR. To study the allergen patterns in patients with Moderate to severe persistent allergic rhinitis from Central India. Male/female of 6 to 63 years age group, presenting with itching of the nose, sneezing, rhinorrhoea, nasal congestion and nasal obstruction. Patients suffering from infective pathology of nose and sinuses. The study group comprised of 1350 male/female of the age group between 6 and 63 years. Modified skin prick test was performed according to the method of Pepys and Bernstein. The ratio of allergen wheal and histamine wheal was used to evaluate the results. The reactions with wheal diameter 3 mm or greater than the reading in the negative control were considered as positive reaction. Results of the study indicate that in Central India, the common allergens are pollens (78.5%), insects (64.5%), dust (38.5%), dust mites (18%) and food (10%) causing moderate to severe persistent allergic rhinitis. The study provided an insight and identified the allergen pattern in Central India. The results were of great help in counseling for avoidance therapy and for deciding allergen specific immunotherapy which is the standard treatment protocol to modify natural course of allergic rhinitis at this point of time.

Clinical study on the treatment of moderate to severe persistent allergic rhinitis by posterior nasal nerve combined with anterior ethmoid neurotomy.

Objectives: To investigate the clinical effect of posterior nasal nerve combined with anterior ethmoid neurotomy in the treatment of moderate to severe persistent allergic rhinitis. Methods: Thirty patients with moderate to severe persistent allergic rhinitis admitted to Linhai Second People's Hospital from August 2019 to June 2020 were selected as subjects for prospective study and design. All patients underwent posterior nasal neurotomy and anterior ethmoid neurotomy simultaneously. Subsequently, the efficacy of all patients at 0.5 and one year postoperatively was compared. Their symptom score preoperatively and one year postoperatively as well as their preoperative and postoperative quality of life score were compared, and related adverse reactions were collected. Results: The curative effect ratio was 60% after 0.5 years and 90.0% after one year, showing a significant increase (χ2 =12.000, P=0.007<0.05). The symptom score at one year postoperatively (1.15±0.32) was lower than that preoperatively (2.12±0.58), with a statistically significant difference (t=11.351, P=0.000<0.05); In terms of quality of life, nasal symptoms, ocular symptoms, practical difficulties, sleep disorders, emotional disorders and other symptoms were lower than those preoperatively, with statistically significant differences (P<0.05). Adverse reactions occurred in 4 patients (13.33%), but were eliminated after treatment. Conclusion: Posterior nasal nerve combined with anterior ethmoid neurotomy is a safe and reliable surgical method for the treatment of moderate to severe persistent allergic rhinitis, boasting a variety of benefits such as symptomatic relief, improved quality of life, and reduced adverse reactions, which is worthy of clinical promotion.

Effect of acupuncture therapy combined with fluticasone propionate in the treatment of persistent allergic rhinitis: study protocol for a randomized controlled trial.

BACKGROUND: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory response. Persistent allergic rhinitis (PAR) is a subtype of AR, but the treatment of PAR is still a problem. Acupuncture is used as an alternative therapy for AR in clinical practice. The aim of this study is to evaluate the effectiveness of acupuncture therapy combined with fluticasone propionate nasal spray in comparison to fluticasone propionate nasal spray alone in the relief of symptoms for PAR. METHODS: This study is a multicenter, single-blind, randomized controlled trial. A total of 260 eligible patients will be randomly assigned into the treatment group or the control group. The treatment group will receive the nasal fluticasone propionate combined with acupuncture, and the control group will receive fluticasone propionate nasal spray alone for 6 weeks. The primary outcome is the change in the Reflective Total Nasal Symptom Score (rTNSS) from baseline to the end of treatment, and the Total Non Nasal Symptom Score (TNNSS), reflective total ocular symptom score (rTOSS), Rhinitis Quality of Life Questionnaire (RQLQ), use of antiallergic drugs, and the Rhinitis Control Assessment Test (RCAT) are used as secondary outcomes. The participants will be followed up for another 24 weeks after treatment. DISCUSSION: This clinical trial will be able to provide high level evidence on the acupuncture therapy combined with fluticasone propionate nasal spray in the treatment of PAR. TRIAL REGISTRATION: ISRCTN Registry, ID: ISRCTN44040506 . Registered on 22 July 2020.

[Adjuvant treatment of penetrating moxibustion at governor vessel for persistent allergic rhinitis of deficiency-cold syndrome].

OBJECTIVE: To explore the efficacy and action mechanism of penetrating moxibustion at governor vessel for persistent allergic rhinitis of deficiency-cold syndrome. METHODS: Ninety patients with persistent allergic rhinitis of deficiency-cold syndrome were randomly divided into an observation group (n = 45) and a control group (n = 45). The patients in the control group were treated with momethasone furoate nasal spray, 2 sprays per side per time, once a day. On the basis of treatment in the control group, the patients in the observation group were additionally treated with penetrating moxibustion at governor vessel, 2 h per treatment, once a week. Both groups were treated for 4 weeks. The TCM symptom score, visual analogue scale (VAS) score and rhinoconjunctivitis quality of life questionnaire (RQLQ) score were observed in the two groups before and after treatment. The serum level of immunoglobulin E (IgE) and complete blood count of eosinophil (EOS) were measured before and after treatment, and the clinical effects were compared. RESULTS: Compared before treatment, the TCM symptom scores, VAS scores, RQLQ scores, serum levels of IgE and complete blood count of EOS in the two groups were all reduced after treatment (P<0.05), and those in the observation group were lower than those in the control group (P<0.05). The total effective rate in the observation group was 95.6% (43/45), which was higher than 82.2% (37/45) in the control group (P<0.05). CONCLUSION: Based on the momethasone furoate nasal spray, the adjuvant treatment of penetrating moxibustion at governor vessel could significantly improve the clinical symptoms in patients with persistent allergic rhinitis of deficiency-cold syndrome, and its mechanism may be related to the regulation of immune disorder.

Adjuvant treatment of penetrating moxibustion at governor vessel for persistent allergic rhinitis of deficiency-cold syndrome / 中国针灸

OBJECTIVE@#To explore the efficacy and action mechanism of penetrating moxibustion at governor vessel for persistent allergic rhinitis of deficiency-cold syndrome.@*METHODS@#Ninety patients with persistent allergic rhinitis of deficiency-cold syndrome were randomly divided into an observation group (@*RESULTS@#Compared before treatment, the TCM symptom scores, VAS scores, RQLQ scores, serum levels of IgE and complete blood count of EOS in the two groups were all reduced after treatment (@*CONCLUSION@#Based on the momethasone furoate nasal spray, the adjuvant treatment of penetrating moxibustion at governor vessel could significantly improve the clinical symptoms in patients with persistent allergic rhinitis of deficiency-cold syndrome, and its mechanism may be related to the regulation of immune disorder.

The effect of medical treatment on nasal exhaled nitric oxide (NO) in patients with persistent allergic rhinitis: A randomized control study.

PURPOSE: This study aimed to evaluate the role of nasal nitric oxide (NO) in the management of patients with persistent allergic rhinitis (PER). METHODS: It was a randomized and comparative study. The study subjects were classified as controls (healthy subjects) or patients with PER based on defined criteria. All clinical, functional and biological data were collected for analyzing. Nasal fractional exhaled nitric oxide (FENO) was measured by electroluminescence device. Patients with PER were randomized for treatment with antihistamine (ATH) combined with leukotriene receptor antagonists (LRA) or only with intranasal steroids (INS). RESULTS: During two years, 501 subjects were included: 234 control subjects and 267 patients with PER. The levels of nasal NO, total IgE, blood eosinophil counts, and apnea-hypopnea index (AHI) in patients with PER were higher than controls (P < 0.001; P < 0.05; P < 0.05; P < 0.01; respectively). There were statistically significant correlations between nasal NO, nasal peak flows, total IgE, and blood eosinophil counts in patients with PER (R = -0.687 and P = 0.0012; R = -0.643 and P = 0.0018; R = 0.432 and P = 0.0024; R = 0.445 and P = 0.002; respectively). After 6 months of treatment, patients treated with INS had greater improvement of clinical symptoms and reduction of nasal NO values than patients treated with ATH + LRA (985 ± 253 vs. 732 ± 298 ppb; P < 0.05). CONCLUSION: Nasal NO measurement is a useful tool for the follow-up of patients with PER. It also helps clinicians to estimate the level of response to treatment in patients with PER.

Correlation of Nasal Fluid Biomarkers and Symptoms in Patients with Persistent Allergic Rhinitis.

OBJECTIVES: This study investigated whether the biomarkers present in nasal fluid reflect the severity of symptoms in patients with persistent allergic rhinitis (PAR). METHODS: We enrolled 29 PAR patients complaining of nasal symptoms and testing positive to skin prick test. Patients' total nasal symptom score (TNSS) was measured and their nasal lavage fluid (NALF) was collected. The levels of biomarkers including Clara cell protein 16 (CC16), tryptase, and interleukin 5 (IL-5) in NALF were determined via enzyme-linked immunosorbent assay (ELISA). RESULTS: PAR patients were classified into persistent mild and persistent moderate-to-severe groups according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The CC16 alone was significantly negatively correlated with TNSS (P < .05). Further, the CC16 level was significantly lower in persistent moderate-to-severe group than persistent mild group of patients (P < .05). CONCLUSIONS: The levels of CC16 alone among several NALF biomarkers showed an inverse correlation with symptoms of PAR patients.

Real-life effectiveness of MP-AzeFlu in Irish patients with persistent allergic rhinitis, assessed by visual analogue scale and endoscopy.

INTRODUCTION: Most allergic rhinitis (AR) patients have moderate-to-severe, persistent disease. Meda Pharma's AzeFlu (MP-AzeFlu) combines intranasal azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a novel formulation in a single device to treat AR. This prospective, noninterventional study sought to assess the effectiveness of MP-AzeFlu (one spray/nostril twice daily; 548 µg AZE/200 µg FP daily dose) in relieving AR symptom severity. METHODS: A visual analogue scale (VAS) was used prior to MP-AzeFlu treatment on days 0, 1, 3, 7, 14, 21, 28, 35, and 42 by 53 persistent AR (PER) patients seen in routine clinical practice in Ireland. An endoscopy was performed on days 0 and 28, and symptoms of edema, discharge, and redness were scored on a three-point scale (for both nostrils). RESULTS: Patients using MP-AzeFlu experienced rapid VAS score reduction from 73.4 mm (standard deviation [SD], 20.3) at Day 0 to 31.5 mm (SD, 25.0) at day 28 (P < 0.0001) to 28.1 mm (SD, 24.1) at day 42 (P < 0.0001), a 45.3-mm reduction. On average, patients achieved a clinically relevant VAS score cutoff of 50 mm before Day 7. Total endoscopy score decreased from 7.5 mm (SD, 3.1) at baseline to 3.5 mm (SD, 2.5) at Day 28. The incidence of severe edema on endoscopy decreased from 53.1% at baseline to 3.8% at Day 28. A similar reduction in the incidence of thick/mucousy discharge (from 28.3% to 4.8%) and severe redness (from 34.9% to 0%) was also observed. CONCLUSIONS: MP-AzeFlu provided effective, rapid control of PER as assessed by VAS in a real-world clinical setting in Ireland. Symptom improvement was observed at Day 1, sustained for 42 days, and associated with improved mucosal appearance after 28 days. These results confirm the safety of MP-AzeFlu and exceed the efficacy demonstrated in phase 3 clinical studies for controlling AR in PER patients.

Treatment of persistent allergic rhinitis via acupuncture at the sphenopalatine acupoint: a randomized controlled trial.

BACKGROUND: Allergic rhinitis is a common respiratory disease. Acupuncture is used to treat it in traditional Chinese medicine, and generally, the L120, ST2 and ST36 acupoints are selected in clinical practice. We report a new method of acupuncture at the sphenopalatine acupoint (SPA) for treatment of persistent allergic rhinitis (PAR). The effect of this treatment was investigated using two different needling depths. The efficacy of this treatment was associated with accurate stimulation of the sphenopalatine ganglion (SPG). METHODS/DESIGN: A total of 61 patients diagnosed with PAR were randomly allocated to either the acupuncture or the sham acupuncture group. The difference between the groups was the needle depth when acupuncture was administered, which was 50 mm and 20 mm. Alteration in total nasal symptom score (TNSS) was the primary outcome. Quality of life, medication dosages and adverse events were secondary outcomes, measured using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Confidence assessment was performed to evaluate data from the treatment and follow-up periods. RESULTS: Results were: (1) average TNSS in the treatment group was significantly lower than in the control group at week 4 (median and 25th and 75th percentiles were 5.00 (4.00, 7.00) and 8.00 (7.00, 10.00), respectively (P < 0.001)). However, scores in the two groups were not significantly different at week 12; (2) quality of life (RQLQ) was significantly improved at week 2 in the treatment group compared to the control group (scores of 35.47 ± 8.20 and 45.48 ± 8.84; P < 0.001); (3) during the follow-up period, the medication dosage in the treatment group was much lower than in the control group (3.64 ± 1.45 and 6.14 ± 2.34; P < 0.05); and (4) no adverse events were observed in either group during treatment. CONCLUSIONS: This pilot study revealed a profound effect of acupuncture at the SPA on prevention of PAR development. The TNSS in the treatment group (needle depth 50 mm), was significantly lower than in the control group (needle depth of only 20 mm). Our result demonstrates that performing acupuncture directly at the SPA to stimulate the SPG is an effective method to treat PAR. TRIAL REGISTRATION: Acupuncture Clinical Trial Registry, AMCTR-OOR-16000014 and Chinese Clinical Trial Register, ChiCTR-IOR-16009211 . Registered on 1 September 1 2016.

Chronic Rhinosinusitis Impairs Sleep Quality: Results of the GA2LEN Study.

Study objectives: To analyze the prevalence of sleep problems in subjects with Chronic rhinosinusitis (CRS) and to determine whether the disease severity of CRS affects sleep quality. Methods: Questionnaires were sent to a random sample of 45 000 adults in four Swedish cities. Questions on CRS, asthma, allergic rhinitis, co-morbidities, tobacco use, educational level, and physical activity were included. CRS was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) epidemiological criteria. The disease severity of CRS was defined by the number of reported CRS symptoms. Sleep quality was assessed using the Basic Nordic Sleep Questionnaire. Results: Of the 26 647 subjects, 2249 (8.4%) had CRS. Reported sleep problems were 50%-90% more common among subjects with CRS compared with those without or the total population. The prevalence of reported sleep problems increased in conjunction with the severity of CRS. After adjusting for gender, BMI, age, tobacco use, asthma, somatic diseases, physical activity level, and educational level, participants with four symptoms of CRS (compared with subjects without CRS symptoms) displayed a higher risk of snoring (adj. OR [95% CI]: 3.13 [2.22-4.41]), difficulties inducing sleep (3.98 [2.94-5.40]), difficulties maintaining sleep (3.44 [2.55-4.64]), early morning awakening (4.71 [3.47-6.38]) and excessive daytime sleepiness (4.56 [3.36-6.18]). The addition of persistent allergic rhinitis to CRS further increased the risk of sleep problems. Conclusions: Sleep problems are highly prevalent among subjects with CRS. The disease severity of CRS negatively affects sleep quality.

Nasal obstructive disorders impair health-related quality of life in adolescents with persistent allergic rhinitis: A real-life study.

BACKGROUND: We previously reported a higher prevalence of nasal obstructive disorders (NOD) in pediatric patients with persistent allergic rhinitis (PER) not responding to medical treatment. The aim of this study was to determine the impact of NOD on quality of life (QoL) in this population. METHODS: Real-life prospective study including 142 patients (41 children, 6-11 years old and 101 adolescents, 12-17 years old) with moderate and severe PER. After 2 months of medical treatment (intranasal steroids and antihistamines), patients were asked whether their symptoms had improved (yes/no) and classified accordingly in R, responders and NR, non-responders. Nasal symptoms (visual analog scale, VAS), NOD (nasal endoscopy), and QoL (PRQLQ, AdolQRLQ) were also assessed. RESULTS: Sixty-nine adolescents and 24 children were included in the NR group. NR presented worse QoL overall scores in adolescents (3.16±1.1 vs 1.63±0.99; P=.00001) and children (2.19±0.82 vs 1.51±0.77, P=.02). Medical treatment failure was associated with worse outcomes in QoL (adolescents OR: 1.6, P<.0001; children OR: 1.04, P=.036). Female adolescents presented worse QoL scores than males (3.19 vs 2.36, P=.001). The presence of obstructive septal deviation (OR: 1.02, P=.005), obstructive turbinate hyperplasia (OR: 1.03, P=.0006), and coexistence of both (OR=2.06, P=.001) was associated with worse QoL in adolescents. A strong and highly significant correlation was found between nasal symptoms VAS and QoL. CONCLUSION: The presence of NOD, particularly in adolescents, is associated with poor QoL outcomes. Assessment of NOD in pediatric PER should be considered an essential approach to determine the response to treatment and its impact on patient's QoL.

Rhinophototherapy in persistent allergic rhinitis.

Previous published results have revealed that Rhinolight® intranasal phototherapy is safe and effective in intermittent allergic rhinitis. The present objective was to assess whether phototherapy is also safe and effective in persistent allergic rhinitis. Thirty-four patients with persistent allergic rhinitis were randomized into two groups; twenty-five subjects completed the study. The Rhinolight® group was treated with a combination of UV-B, UV-A, and high-intensity visible light, while the placebo group received low-intensity visible white light intranasal phototherapy on a total of 13 occasions in 6 weeks. The assessment was based on the diary of symptoms, nasal inspiratory peak flow, quantitative smell threshold, mucociliary transport function, and ICAM-1 expression of the epithelial cells. All nasal symptom scores and nasal inspiratory peak flow measurements improved significantly in the Rhinolight® group relative to the placebo group and this finding persisted after 4 weeks of follow-up. The smell and mucociliary functions did not change significantly in either group. The number of ICAM-1 positive cells decreased non-significantly in the Rhinolight® group. No severe side-effects were reported during the treatment period. These results suggest that Rhinolight® treatment is safe and effective in persistent allergic rhinitis.

Mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis: a non-inferiority study (PUMA) / Furoato de mometasona no tratamento de rinite alérgica persistente leve, moderada ou grave: estudo de não inferioridade (PUMA)

ABSTRACT INTRODUCTION: Allergic rhinitis is considered the most prevalent respiratory disease in Brazil and worldwide, with great impact on quality of life, affecting social life, sleep, and also performance at school and at work. OBJECTIVE: To compare the efficacy and safety of two formulations containing mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis after four weeks of treatment. METHODS: Phase III, randomized, non-inferiority, national, open study comparing mometasone furoate in two presentations (control drug and investigational drug). The primary endpoint was the percentage of patients with reduction of at least 0.55 in nasal index score (NIS) after four weeks of treatment. Secondary outcomes included total nasal index score score after four and 12 weeks of treatment; individual scores for symptoms of nasal obstruction, rhinorrhea, sneezing, and nasal pruritus; as well as score for pruritus, lacrimation, and ocular redness after four and 12 weeks of treatment. The study was registered at clinicaltrials.gov with the reference number NCT01372865. RESULTS: The efficacy primary analysis demonstrated non-inferiority of the investigational drug in relation to the control drug, since the upper limit of the confidence interval (CI) of 95% for the difference between the success rates after four weeks of treatment (12.6%) was below the non-inferiority margin provided during the determination of the sample size (13.7%). Adverse events were infrequent and with mild intensity in most cases. CONCLUSION: The efficacy and safety of investigational drug in the treatment of persistent allergic rhinitis were similar to the reference product, demonstrating its non-inferiority.

Resumo Introdução: A rinite alérgica é considerada a doença respiratória mais prevalente no Brasil e em todo o mundo, com grande impacto na qualidade de vida; além de, afetar a vida social, o sono e também o desempenho na escola e no trabalho. Objetivo: Comparar a eficácia e segurança de duas formulações contendo furoato de mometasona no tratamento da rinite alérgica persistente leve, moderada ou grave por um período de quatro semanas. Método: Trata-se de um estudo nacional aberto de fase III, randomizado, de não inferioridade de comparação do furoato de mometasona em duas apresentações (medicação de controle e fármaco sob investigação). O ponto final primário foi o percentual de pacientes com redução mínima de 0,55 no escore de índice nasal (EIN) após quatro semanas de tratamento. Os desfechos secundários foram: escore NIS total após 4 e 12 semanas de tratamento; escores individuais para sintomas de obstrução nasal, rinorréia, espirros e prurido nasal, bem como escores para prurido, lacrimejamento e hiperemia conjuntival após 4 e 12 semanas de tratamento. O estudo foi registrado em clinicaltrials.gov com o número de referência NCT01372865. Resultados: A análise de eficácia primária demonstrou não inferioridade do fármaco sob investigação em relação à medicação de controle, visto que o limite superior do intervalo de confiança (IC) de 95% para a diferença entre os percentuais de sucesso após quatro semanas de tratamento (12,6%) situava-se abaixo da margem de não inferioridade proporcionada durante a determinação do tamanho da amostra (13,7%). Eventos adversos foram pouco frequentes e de leve intensidade na maioria dos casos. Conclusão: A eficácia e a segurança de um fármaco experimental no tratamento da rinite alérgica persistente foram similares às do produto de referência, o que demonstrou sua não inferioridade.

Efficacy and safety of using a warming needle for persistent allergic rhinitis: study protocol for a randomized controlled trial.

BACKGROUND: Many previous studies have shown the potential therapeutic effect of acupuncture for allergic rhinitis. Most of these studies, however, were limited by the short duration of observations and lack of sham acupuncture as the control group. Our preliminary experiments showed that the use of a warm needling achieved a much more persistent effect in the treatment of allergic rhinitis (AR) compared with simple acupuncture therapy. Hence, we have designed a multicenter, randomized controlled trial (RCT) in which the first-line medication loratadine will be used as the control group, and the effect of warm needling therapy will be evaluated through long-term observation. METHODS/DESIGN: The trial is designed as a multicenter, parallel-group, randomized, single-blinded (outcome assessors), non-inferiority trial. A total of 98 patients with persistent AR will be randomly assigned into two groups. Patients in the treatment group will be treated with warm needling at GV14 and acupuncture at EX-HN3, ST2, LI20, EX-HN8, GV23, LU7, LU5 and LI4 three times a week, for a total of 4 weeks. Patients in the control group will be treated with oral loratadine 10 mg/day for 4 weeks. The primary outcome will be the change in the Total Nasal Symptom Score (TNSS) from baseline to that at 6 months after treatment during the follow-up period. The secondary outcomes will include the Total Non-nasal Symptom Score and the Rhinoconjunctivitis Quality of Life Questionnaire, changes in the TNSS from baseline to that at 2 and 4 weeks during treatment, and 3 months after treatment during the follow-up period. Outcomes will be measured at 2 and 4 weeks, and 3 and 6 months after treatment. Any side effects of treatment will be observed and recorded. DISCUSSION: We expect that the study results will provide evidence to determine the effects of warm needling compared with loratadine. Our final goal of the study is to evaluate the difference in the short-term and long-term effects between the two therapeutic methods, especially the long-term effect of warm needling. TRIAL REGISTRATION: ClinicalTrials.gov NCT02339714 . Registered on 14 January 2015.

Mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis: a non-inferiority study (PUMA).

INTRODUCTION: Allergic rhinitis is considered the most prevalent respiratory disease in Brazil and worldwide, with great impact on quality of life, affecting social life, sleep, and also performance at school and at work. OBJECTIVE: To compare the efficacy and safety of two formulations containing mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis after four weeks of treatment. METHODS: Phase III, randomized, non-inferiority, national, open study comparing mometasone furoate in two presentations (control drug and investigational drug). The primary endpoint was the percentage of patients with reduction of at least 0.55 in nasal index score (NIS) after four weeks of treatment. Secondary outcomes included total nasal index score score after four and 12 weeks of treatment; individual scores for symptoms of nasal obstruction, rhinorrhea, sneezing, and nasal pruritus; as well as score for pruritus, lacrimation, and ocular redness after four and 12 weeks of treatment. The study was registered at clinicaltrials.gov with the reference number NCT01372865. RESULTS: The efficacy primary analysis demonstrated non-inferiority of the investigational drug in relation to the control drug, since the upper limit of the confidence interval (CI) of 95% for the difference between the success rates after four weeks of treatment (12.6%) was below the non-inferiority margin provided during the determination of the sample size (13.7%). Adverse events were infrequent and with mild intensity in most cases. CONCLUSION: The efficacy and safety of investigational drug in the treatment of persistent allergic rhinitis were similar to the reference product, demonstrating its non-inferiority.

Recent pharmacological developments in the treatment of perennial and persistent allergic rhinitis.

INTRODUCTION: Allergic rhinitis (AR) has a major negative impact on patients' quality of life (QoL) and carries a high socio economic burden. This is particularly the case for patients who experience symptoms for extended periods of time (i.e. those with perennial (PAR) or persistent AR (PER), depending on the classification system used). This review covers available pharmacological advances and recent developments in the treatment of PAR or PER. AREAS COVERED: Pharmacological AR treatment is used to reduce symptom burden and help restore patients' normal daily routine. Traditionally, non-sedating antihistamines and intranasal corticosteroids (INS) were the two drug classes recommended for use first line. These, along with antileukotrienes, decongestants, mast cell stabilizers and anticholinergics, constituted the bulk of the AR treatment arsenal. MP-AzeFlu (Dymista®, Meda, Solna, Sweden) is the most recent addition to that arsenal. It is a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) delivered in a single spray and has surpassed available therapies in terms of symptom control and treatment response. Other relatively new treatments for PAR or PER include H3 antihistamines, toll-like receptor (TLR) agonists, cellulose powders and micro-emulsions, novel biomolecular formulations and omalizumab. Each of these new additions is reviewed here. EXPERT OPINION: A new AR drug class has recently been introduced (i.e. RO1AD58). Currently MP-AzeFlu is the only treatment option within this drug class. It can be estimated that combination treatments like MP-AzeFlu will become the mainstay of PAR and PER therapy since use will result in better compliance, improved efficacy over INS and a faster response together with good levels of tolerability. The challenge is to find other equally, or more effective, combination treatments, as has been the therapeutic standard in bronchial asthma for decades. The potential of biologics, as well as TLR-agonists and other new treatment options needs to be further evaluated.

Evaluation of vascular endothelial growth factor-A and Endostatin levels in induced sputum and relationship to bronchial hyperreactivity in patients with persistent allergic rhinitis monosensitized to house dust.

BACKGROUND: Studies about the pathogenesis of bronchial hyperreactivity (BHR) in patients with persistent allergic rhinitis (PAR) and its relationship with lower airway remodeling are extremely limited. OBJECTIVE: This study evaluated bronchial vascular remodeling via the measurement of angiogenic factor, vascular endothelial growth factor-A (VEGF-A), and anti-angiogenic factor, Endostatin, and evaluated their relationship with BHR in patients with PAR. METHODS: The study group consisted of 30 patients with PAR monosensitized to house dust mites and 14 non-allergic healthy controls. All subjects underwent induced sputum and methacholine (M) bronchial provocation tests. VEGF-A and Endostatin levels were measured by ELISA in induced sputum supernatants. RESULTS: The percentages of eosinophils in induced sputum were significantly increased in patients with PAR compared with healthy controls. There were no significant differences between patients with PAR and healthy controls in terms of levels of VEGF (37.9pg/ml, min-max: 5-373pg/ml vs. 24.9, min-max: 8-67pg/ml, p=0.8 respectively), Endostatin (532.5pg/ml, min-max: 150-2125pg/ml vs. 644, min-max: 223-1123pg/ml, p=0.2 respectively) and VEGF/Endostatin ratio (0.057 vs. 0.045, p=0.8 respectively). In addition, there were no significant differences between patients who are BHR positive (n=8), or negative to M (n=22) in terms of levels of VEGF, Endostatin and VEGF/Endostatin ratio and no correlations among value of PD20 to M and levels of VEGF, Endostatin and VEGF/Endostatin ratio. CONCLUSION: We conclude that VEGF-A and Endostatin did not differ between patients with PAR and healthy controls regardless of BHR to M.

Intranasal budesonide in children affected by persistent allergic rhinitis and its effect on nasal patency and Nasal Obstruction Symptom Evaluation (NOSE) score.

BACKGROUND: Intranasal steroids are recognized as an effective treatment for allergic rhinitis (AR) although their effect on nasal patency has never been evaluated with an objective instrument such as anterior rhinomanometry in children. Moreover this effect has been widely assessed with total Nasal Symptom Scores (NSS) including all symptoms of allergic rhinitis and not with scores specifically focused on nasal obstruction such as the Nasal Obstruction Symptom Evaluation score (NOSE). MATERIALS AND METHODS: Sixty children (42 males and 18 female) aged 6-10 years, affected by persistent AR, were randomized and divided in two groups of 30 children to be included in an unblinded trial: one group treated with intranasal budesonide and isotonic nasal saline for 2 weeks and the other group treated only with isotonic nasal saline for 2 weeks. Each child underwent rhinomanometry and completed the NSS and the NOSE scores before and after treatment. RESULTS: At the baseline nasal patency and NSS total score, NOSE total scores were correlated (r=-0.29, p<0.001; r=-60, p<0.001). After 2 weeks of treatment improvements in nasal patency, NSS and NOSE were seen (Δ NSS 4.13 ± 1.38 vs 1.33 ± 1.93, p<0.001; Δ NOSE 34 ± 17.97 vs 9 ± 18.21, p<0.001; Δ nasal patency -26.13 ± 25.25 vs -11.83 ± 11.31, p<0.001). Correlations were found between rhinitis duration and Δ nasal patency and Δ NOSE (r=-0.84, p<0.001; r=0.43, p<0.01). CONCLUSION: Intranasal budesonide is effective in increasing nasal patency in children. Moreover the NOSE score was strongly correlated with nasal flow and, hence, this score should be regarded as a valid and reliable instrument in children.