Short-term influence of Immufen™ on mild allergic rhinitis: a randomized, double-blind, placebo-controlled study.

Introduction: Allergic rhinitis (AR) is an IgE-mediated reaction to inhaled allergens, and is a prominent health concern affecting approximately 400 million people worldwide. A comprehensive understanding of AR's pathophysiology is imperative for developing novel therapies, especially considering its frequent co-morbidity with asthma and conjunctivitis. The escalating prevalence of AR is correlated with increased urbanization and environmental pollutants, recognized as prominent contributing factors. Dysregulation in immune networks, Th1/Th2 cytokine imbalance, activation of mast cells and eosinophils are implicated in AR progression. Classic AR symptoms include nasal congestion, nasal itching, rhinorrhea, and sneezing which significantly impact the quality of life, social interactions, and workplace productivity. Methods: This randomized, double-blind, placebo-controlled, three-arm, three-sequence study was aimed to assess the efficacy of supplementation of a co-delivery form of turmeric extract with ashwagandha extract (CQAB) in comparison with a bioavailable curcumin (CGM) and placebo in alleviating AR symptoms and enhancing the quality of life in individuals with mild AR. Participants received either placebo, CGM, or CQAB twice/day for 28 days, and subjective measures were recorded at the baseline and at the end of study. Results: CQAB supplementation demonstrated a significant (P < 0.05) improvement in Total Nasal Symptom Score (TNSS) compared to placebo and CGM. Furthermore, CQAB administration resulted in enhanced sleep quality (P < 0.05) as evaluated by the BIS questionnaire, heightened energy levels, and decreased fatigue and overall mood disturbance (POMS-SF) compared to both placebo and CGM. Conclusion: The results suggests that CQAB has the potential to be used as a dietary supplement in alleviating AR discomforts. Clinical Trial Registration: https://ctri.nic.in/Clinicaltrials/login.php; Identifier CTRI/2021/01/030355.

The burden of allergic rhinitis is undermanaged in a large proportion of Chinese young adults from Singapore.

Background: Allergic rhinitis (AR) is a nasal disorder characterized by the simultaneous manifestation of at least 2 out of 4 possible symptoms: rhinorrhea, nasal itching, nasal pruritus, and sneezing. Presently, among Chinese young adults from Singapore, we characterised AR phenotypes, established Total Nasal Symptom Score (TNSS) baselines, and examined the management of AR. Methods: Participants completed an investigator-administered International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and underwent a skin prick test (SPT). Individuals exhibiting sensitization during the SPT while having at least 2 rhinitis symptoms were identified as AR cases, then categorized into Allergic Rhinitis in Asthma (ARIA) classifications. Results: There were 9323 subjects analyzed. AR prevalence was estimated at 35.4%. Rhinorrhea was perceived as the most severe (mean Nasal Symptom Score (mNSS) ± SD: 1.42 ± 0.74), while nasal pruritus was the least severe (mNSS ± SD: 1.24 ± 0.68). Among moderate-severe AR (68.1%), most were affected by either troublesome symptoms (27.7%) or sleep disturbances (18.4%). By ARIA classes, 26.6% were mild intermittent, 5.4% were mild persistent, 50.3% were moderate-severe intermittent, and 17.6% were moderate-severe persistent. The mean TNSS (mTNSS) of AR cases was 4.43 (SD = 2.49) and between AR classifications, the mTNSS was significantly different. Notably, a large proportion of AR cases remained undiagnosed (85.2%), untreated (72.5%), or both (65.4%); 19.8% self-medicated for AR. Conclusions: There was a significant difference in TNSS of the AR phenotypes, and among phenotypes with a higher mTNSS, a large proportion remained untreated, undiagnosed, or both. The evidence indicates an existing burden of AR among Chinese young adults in Singapore which is notably undermanaged.

Real-World Evaluation of the Safety and Effectiveness of 2.3% Hypertonic Saline Soft Mist Spray for Sino-Nasal Symptoms.

Introduction and aims Mildly hypertonic saline is more effective in relieving symptoms of nasal congestion compared to placebo or isotonic saline. Recently, a unique device, delivering a soft mist of 2.3% hypertonic sea-salt saline (Nasoclear PureHaleTM; Zydus Healthcare Ltd., India) has been introduced in India. The device uses a power-less manual technique to release the saline as a soft mist at 1 ml/min. Methods This is a retrospective, multi-centric, single-arm study to evaluate the safety and effectiveness of 2.3% hypertonic sea-salt saline nasal irrigation delivered through a soft mist device in patients with sino-nasal symptoms. This is an analysis of data of 130 patients collected from the medical records of 11 practicing pediatricians across India. Results The mean age of the patients was 5.23 ± 4.24 years; 63 % were boys and 37% were girls (n = 130). The mean reduction in total nasal symptom score (TNSS) at follow-up from baseline was 6.28 ± 0.18 (median days = 7) (95% CI = 5.92 to 6.64; p<0.0001; mean TNSS at baseline = 7.75 ± 2.01, mean TNSS at follow-up = 1.47± 1.30). Out of 130 patients, 33 patients (25.3%) showed complete improvement in TNSS, 93 patients (71.5%) had ≥ 50% improvement in TNSS while 4 patients (3.07%) showed <50% improvement in TNSS. The effectiveness of the device was rated as excellent (75%-100% improvement) and very good (50%-75% improvement) in 41 and 74 patients, respectively. It was rated as very easy to use and easy to use by 62 patients and 57 patients, respectively. One hundred nineteen patients (91.5%) were compliant with the prescribed frequency of the device and 110 patients (84.6%) were compliant with the prescribed duration of use of the device. No serious adverse events were reported; two patients reported mild side effects - stinging and irritation of the throat. Conclusions The 2.3% hypertonic sea-salt saline nasal irrigation delivered through the soft mist device was found to be well-tolerated and effective in patients with sino-nasal symptoms in real-world clinical settings. Clinical trial number The clinical trial number of this study is CTRI/2022/07/043751.

Proof of Efficacy Study to Evaluate an Ayurvedic Formulation in the Treatment of Allergic Rhinitis: An Open Label Randomized Controlled Clinical Trial.

BACKGROUND: Allergic rhinitis is largely treated by using antihistamines and nasal sprays, either alone or in combination. However, these measures ease out the symptoms but do not address causative factors, and have their share of side effects and limitations. An Ayurvedic herbo-mineral formulation, IMMBO, has been reported to be effective in treating allergic rhinitis. OBJECTIVE: The present study was carried out to evaluate the efficacy, safety, and tolerability of the Ayurvedic herbo-mineral formulation in comparison with a fixed-dose combination of levocetirizine and montelukast. METHOD: This was a randomized, comparative, clinical study carried out on 250 patients at a medical college in India. The patients were enrolled according to the eligibility criteria of the study and randomized into two groups, to receive either Ayurvedic herbo-mineral formulation, IMMBO, or a combination of levocetirizine and montelukast for 28 days. Total nasal symptom score (TNSS) and Immunoglobulin E (IgE) were calculated for evaluation of efficacy parameters.  Result: At the end of therapy both IMMBO and levocetirizine and montelukast combination showed significant improvement in TNSS in both treated population and per protocol population. The IMMBO group had a statistically higher reduction in TNSSs compared to the levocetirizine + montelukast group (-5.70 vs. -3.31; p<0.01). There was a statistically significant difference in the reduction of IgE levels between the groups (-351.54 vs. -208.79; p<0.05).  Conclusion: The findings of this study establish prima facie evidence about the efficacy and safety of Ayurvedic formulation. However, the said Ayurvedic formulation needs to be further developed scientifically.

A Clinical Study to Evaluate the Role of Vitamin D3 in Allergic Rhinitis.

Allergic rhinitis is a common and chronic immunoglobulin E-mediated inflammation of nasal mucosa induced after allergen exposure. Allergic rhinitis is a global health problem that causes major illness and affects patient's social life, sleep, school and work performance. Various studies have implicated the association between low serum vitamin D levels and allergic diseases. Active form of Vitamin D3 has been shown to have immunoregulatory effect on both innate and adaptive immunity, which can significantly affect the outcome of allergic responses in allergic rhinitis. The study aims to evaluate effectiveness of Oral Vitamin D3 supplementation as an adjunct to standard therapy, in the management of allergic rhinitis. The present study is a prospective study in which 80 subjects were recruited and were randomly divided into two groups. The study group received oral vitamin D3 (60,000 IU) along with intranasal steroid spray while control group received only intranasal steroid spray for 4 weeks. The response in both the groups was compared by evaluating total nasal symptom score (TNSS). Subjects of allergic rhinitis showed deficiency in vitamin D indicated by mean serum vitamin D levels of 15 ± 2.42 ng/ml in the study group and 14.72 ± 2.64 ng/ml in the control group. The pre treatment mean TNSS score was 10.45 ± 3.1 in the study group and 11.43 ± 2.35 in the control group. The post treatment mean TNSS score was 2.1 ± 0.21 in the study group and 3.85 ± 0.76 in the control group. A significant reduction in symptoms score was observed after 4 weeks of oral vitamin D3 supplementation. The difference between two groups was found to be statistically significant (p value < 0.05).

Defining the Efficacy of Omalizumab in Nasal Polyposis: A POLYP 1 and POLYP 2 Subgroup Analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with variable underlying pathophysiologies. Numerous patient factors have been linked to differences in disease severity, control, and response to treatment, including asthma status, aspirin sensitivity, previous sinonasal surgery, and blood eosinophil levels. OBJECTIVE: The present study examines the efficacy of the anti-immunoglobulin E therapy, omalizumab, versus placebo in patients with CRSwNP from the replicate POLYP 1 (NCT03280550) and POLYP 2 (NCT03280537) trials, grouped by inherent patient characteristics to determine the response to therapy. METHODS: Patients in prespecified subgroups from POLYP 1 and POLYP 2 (studies pooled for analysis) were examined. Subgroups included blood eosinophil count at baseline (>300 or ≤300 cells/µL), previous sinonasal surgery (yes or no), asthma status (yes or no), and aspirin sensitivity status (yes or no). Subgroups were examined for subgroup-specific adjusted mean difference (95% confidence interval [CI]) (omalizumab-placebo) in change from baseline at week 24 in Nasal Congestion Score (NCS), Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), Total Nasal Symptom Score (TNSS), and University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: Adjusted mean difference (95% CI) (omalizumab-placebo) in NCS, NPS, SNOT-22, TNSS, and UPSIT change from baseline at week 24 consistently favored omalizumab treatment over placebo in patients with blood eosinophil count >300 and ≤300 cells/µL, with or without previous sinonasal surgery, asthma, and aspirin sensitivity. CONCLUSION: Together, these data suggest broad efficacy of omalizumab across clinical and patient-reported outcomes in patients with CRSwNP, independent of the underlying patient factors examined, including those with high eosinophil levels and those who have undergone previous surgery, which are associated with high recurrence. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: POLYP 1: ClinicalTrials.gov identifier NCT03280550 (https://clinicaltrials.gov/ct2/show/NCT03280550); POLYP 2: ClinicalTrials.gov identifier NCT03280537 (https://clinicaltrials.gov/ct2/show/NCT03280537).

Efficacy of Vitamin D Supplementation in Allergic Rhinitis.

Allergic Rhinitis is one of the most commonly recognised rhinitis globally. Though its not a life threatening entity but it is associated with severe impairment of quality of life along with substantial financial burden on patient. There has been a substantial rise in number of patients of allergic rhinitis over years and researchers worldwide have also found low levels of vitamin D in patients of allergic rhinitis. It is a randomised control trial with 87 subjects divided into two groups. Pre-treatment total nasal symptom score (TNSS) were recorded for these patients. The Group A was given intranasal steroidal spray while Group B was given vitamin D supplementation along with intranasal steroidal spray. Post treatment TNSS scores and rhinitis control assessment test scores were calculated and analysed. 38 patients had severe Vit D deficiency with average TNSS score as 11.3 while 49 patients had insufficient Vit D levels with average TNSS as 8.6. The pre-treatment TNSS score in Group A was 12.5 ± 2.68 while post-treatment score was 8.98 ± 1.009 with difference in both scores of Group A as 3.52. The pre-treatment TNSS score in Group B (fluticasone spay with Vit D) was 11.64 ± 3.09 while post-treatment score was 6.3 ± 1.45 with difference in both scores of Group A as 5.34. The post treatment RCAT in Group A and Group B was 19.72 ± 2.84 and 28.2 ± 1.53 respectively with difference between two groups as 8.48. Though Intranasal steroidal sprays are the first line of management of allergic rhinitis however vitamin D supplementation can have a role in better relief of symptoms when used in conjunction. More multi-institutional studies are encouraged to confirm the validity of results before it can be incorporated in standard treatment guidelines.

Translation, adaption and validation of the total nasal symptom score (TNSS) for Lithuanian population.

BACKGROUND: Allergic rhinitis is one of the most prevalent allergic diseases worldwide which diagnosis is based on typical clinical signs and positive results of allergic tests. Selection and evaluation of treatment is based mainly on subjective symptoms. Objective measurement of patients' complaints is necessary for proper documentation and follow-up. There are no short simple validated questionnaire assessing nasal symptoms in patients with allergic rhinitis in Lithuania. Total nasal symptoms score (TNSS) is a brief questionnaire which evaluate the severity of main symptoms of allergic rhinitis widely used in different countries. Our aim was to translate the TNSS in the Lithuanian language and to validate it. METHODS: Prospective cross-cultural adaption and validation study was performed. Linguistic validation of TNSS was performed and validity and reliability were assessed. Patients with chronic allergic and non-allergic rhinitis and healthy individuals were included in this study. Patients had to complete translated version of TNSS. Patients with allergic rhinitis additionally were asked to fill Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: Seventy-six individuals were involved into the study: 16 with non-allergic rhinitis (NAR) (21.1%), 49 with allergic rhinitis (AR) (64.5%) and 11 healthy individuals (14.5%). Cronbach's α was 0.87. TNSS score was significantly higher in patients with NAR and AR compared with healthy individuals (3.56 ± 2.28 vs. 4.28 ± 2.46 vs. 0.27 ± 0.91). Positive significant correlation was found between TNSS score and RQLQ score (rs = 0.77, p < 0.01). CONCLUSIONS: The Lithuanian version of the TNSS proved to be a valid instrument for assessing nasal symptoms in patients with allergic rhinitis.

Effect of short-course glucocorticoid application on patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Local and systemic glucocorticoids are mainstay therapies for chronic rhinosinusitis. With respect to local glucocorticoids, nasal spray is used extensively, but some patients do not benefit from short-course treatment. Recently, some clinicians have focused on the effects of high-dose local glucocorticoids in chronic rhinosinusitis with nasal polyps (CRSwNP), such as treatment using nasal irrigation, transnasal nebulization, and nose-dripping therapy (nasal drop) with high-dose budesonide. However, there are little data comparing the effect of short-course high-dose local glucocorticoids with regular nasal spray and oral steroids in the treatment of preoperative CRSwNP patients. Furthermore, the appropriate use of different types of glucocorticoids in different endotypes of CRSwNP remains unclear. METHODS: This randomized controlled clinical research study was performed at a single academic center. Patients who satisfied the criteria of chronic rhinosinusitis with bilateral nasal polyps were randomly assigned in a 1:1:1 ratio to receive oral methylprednisolone, 24 mg/d and budesonide nasal spray, 256 µg/d, or intranasal budesonide suspension, 1 mg/d and budesonide nasal spray, 256 µg/d, or budesonide nasal spray, 256 µg/d for one week. Symptoms, endoscopic scores, and tissue and blood inflammatory cells were recorded before and after the study. Adverse events were recorded by clinicians. RESULTS: A total of 127 patients with CRSwNP underwent randomization. The total nasal symptoms scores (TNSS) decreased significantly in all groups compared to those at baseline. The assessment of the reduction in TNSS demonstrated that the change was significantly greater in the nasal drop group than in the nasal spray group (-7.47 vs -4.10, P = 0.032), and it was also greater in the oral steroid group than in the nasal spray group (-7.30 vs -4.10, P = 0.039). A similar trend also appeared in the reduction in Sinonasal-Outcome Test 22 (SNOT-22). After treatment, a significantly reduction in NP score was observed in the nasal drop group (-0.82) and oral steroid group (-0.85) compared with that in the nasal spray group (-0.10), and there was no significant difference between the nasal drop and oral steroid groups (P = 0.98). While calculating the percentage of patients who were sensitive to glucocorticoid treatment, there was 10.26% in the nasal spray group, 47.37% in the nasal drop group, and 52.50% in the oral steroid group that were sensitive to glucocorticoid treatment. The reduction in NP score was more significant in patients with eosinophilic CRSwNP in the nasal drop group and oral steroid group than in the nasal spray group. However, in patients with non-eosinophilic CRSwNP, the change in NP size was similar in the different treatment groups. CONCLUSION: Budesonide suspension nasal drop can significantly improve the quality of life and reduce the endoscopic score following short-course treatment, and the treatment effect of nasal drop was better than that of regular nasal spray. Budesonide nasal suspension can be used as a regular treatment for eosinophilic CRSwNP and can be an alternative choice for patients with a high percentage of tissue eosinophil infiltration who cannot use oral glucocorticoids.

Efficacy of Acupuncture at the Sphenopalatine Ganglion in the Treatment of Persistent Allergic Rhinitis.

Objective: The aim of this research was to explore the hypothesis that acupuncture at the sphenopalatine ganglion (SPG), a new a new method of acupuncture, would be more efficacious and safe than traditional acupuncture in the treatment of persistent allergic rhinitis (PAR). Materials and Methods: For this study, 120 patients with PAR were randomly assigned to SPG acupuncture, traditional acupuncture (Yingxiang [LI 20], Hegu [LI 4], and Yintang [Ex-HN 3]), or drug treatment (budesonide nasal spray). Efficacy was assessed by using single symptoms, including sneezing, rhinorrhea, nasal obstruction and nasal itch, a total nasal symptoms score (TNSS), and a Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) before treatment, the day treatment ended, and 4-, 8-, 12-weeks later, respectively. Results: Four weeks after treatment ended, the effectiveness rate in the SPG-acupuncture group was superior to that of the traditional-acupuncture group (P = 0.033) but was still lower than that of the drug-treatment group (P = 0.039), with mean effectiveness rates of 69.70%, 44.44%, and 71.43%, respectively. However, these rates gradually decreased in each group during weeks 8 through 16. Moreover, statistically significant improvements in TNSS', and reductions in nasal congestion and sneezing symptoms were observed in the SPG-acupuncture group, compared with those in the traditional-acupuncture group as early as the day treatment ended and this continued throughout the observation period (P < 0.05). However, the improvement did not continue for sneezing, during weeks 8 through weeks 12 after treatment ended. The RQLQ of the SPG-acupuncture group was lower than that of the traditional-acupuncture group at week 12; however, there were no differences at weeks 8 and 16. Conclusions: The data generated by this study confirmed that acupuncture at the SPG alleviated the symptoms of PAR rapidly and safely, especially nasal obstruction, and improved the patients' life quality. These results were worthy of clinical promotion.

Local Expression of Mucosal YKL-40; Correlation of YKL-40 with Clinical Manifestations and Immunopathogenesis of Moderate/Severe Persistent Allergic Rhinitis Patients.

YKL-40 is an important protein that plays a critical role in chronic inflammation in hypersensitivity disease. In this study, the expression of YKL-40 was investigated among patients with moderate/severe persistent allergic rhinitis (M/S PAR), patients with mild (M) PAR and healthy individuals. Moreover, the association between YKL-40 and immunopathogenesis of M/S PAR was meticulously surveyed. For this purpose, surgical samples were tested by real-time polymerase chain reaction to evaluate YKL-40 mRNA expression. The presence and location of YKL-40 protein in the tissue samples were determined by immunohistochemistry. Additionally, we measured the number of eosinophils per field in the tissue samples, blood eosinophils, total serum IgE, specific serum IgE, total nasal syndrome score (TNSS) and YKL-40 serum levels. The data indicated that production of YKL-40 in patients with M/S PAR increased significantly when compared with the control group. Furthermore, local production of YKL-40 correlated with specific IgE, nasal eosinophil count and TNSS. The results of the present study indicate that YKL-40, for its correlation with allergic clinical manifestations and symptom severity in M/S PAR patients, should be considered as a trigger factor in AR.

Comparative Study of Nasal Symptoms and Pulmonary Function Tests Post FESS in Ethmoidal Polyposis.

The objective of this study were to assess the pulmonary function in patients with ethmoidal polyposis who did not respond to medical treatment; to evaluate the effect of Functional Endoscopic Sinus Surgery on the lung function of these patients and to compare the total nasal symptom score in these patients. A prospective observational study was conducted in Department of ENT, KMC Manipal on 50 subjects with ethmoidal polyposis who were unresponsive to medical treatment and hence underwent FESS. Pulmonary function tests were assessed using spirometry and nasal symptoms were scored as per TNSS system prior to surgery and 3 months post-surgery and compared with the pre-operative values and analysed. Pre operatively majority (35 patients) had TNSS value of 6-9 whereas post operatively the score was reduced to 2-3 in many patients (38 patients). The mean TNSS was 7.24 before surgery which declined to 2.82 after surgery with a p value < 0.0001 indicating a statistically significant improvement in the nasal symptoms post FESS. The mean pre-operative FVC, FEV1, MEFR were 2.94, 2.41 and 2.51 L respectively whereas the mean post-operative values were 2.95, 2.39 and 2.49 L respectively. There was no statistically significant change in lung function tests following FESS. Our study shows that FESS benefits patients with nasal polyposis by improving the symptoms and there by the quality of life without any adverse effects on the lower airways.

Clinical validation of controlled exposure to birch pollen in the Environmental Exposure Unit (EEU).

BACKGROUND: The Environmental Exposure Unit (EEU) in Kingston, Ontario, Canada is a controlled allergen challenge facility (CACF) that has been previously clinically validated for the use of ragweed and grass pollen in clinical studies. In this study we aim to validate the use of birch pollen to challenge allergic participants. METHODS: A total of 59 volunteers were screened and 38 birch allergic participants and ten non-allergics completed the study, outside of tree pollen season. Participants had to have a minimum of 2-year history of allergic rhinoconjunctivitis during the typical tree pollen season and have a positive skin prick test to birch allergen ≥5 mm from the control. Qualified participants were exposed to birch (Betula pendula) pollen for 4 h in the EEU and recorded their symptoms of sneezing, rhinorrhea, nasal congestion, nasal itch which comprised the total nasal symptom score (TNSS), as well as itchy/watery eyes, red/burning eyes and itching of ears/palate/throat which along with the TNSS comprised the total rhinoconjunctival symptom score (TRSS) along with Peak Nasal Inspiratory Flow (PNIF) at baseline and at 30 min intervals for the duration of exposure, then hourly for up to 12 h from the start of exposure. RESULTS: Allergic participants reported a gradual rise in TNSS and TRSS, reaching a mean and standard error of the mean of 7.08 ± 0.45 and 11.58 ± 0.93 respectively by 180 min from the start of exposure. Symptoms gradually declined to near baseline values following departing from the unit, reaching 1.9 and 2.7 by 450 min. Allergic participants reported significantly higher TNSS than non-allergics starting from 30 min (p < 0.01, two-way ANOVA with Bonferroni corrections), maintaining maximum significance from 60 to 300 min (p < 0.0001) and losing significance by 420 min. TRSS and PNIF followed similar trends as those seen with TNSS. Participants were phenotyped using previously published definitions using the TNSS into Early Phase Responders (EPR, 57.8 %), protracted EPR (pEPR, 39.5 %), and Dual Phase Responders (DPR, 2.7 %). CONCLUSIONS: The EEU can competently challenge birch allergic participants and achieve statistically significant changes in symptoms and nasal airflow, while such changes are not reported in non-allergic controls. Trial registration NCT02351830 clinicaltrials.gov.

Minimal Clinically Important Difference (MCID) in Allergic Rhinitis: Agency for Healthcare Research and Quality or Anchor-Based Thresholds?

BACKGROUND: In 2013, the Agency for Healthcare Research and Quality (AHRQ) recommended that allergic rhinitis (AR) studies calculate a minimal clinically important difference (MCID) based on an estimated threshold equal to 30% of the maximum total nasal symptom score. Applying this threshold, their data showed no differences between well-established treatments, and a subsequent analysis using prescribing information found no differences between active treatments and placebo controls. OBJECTIVE: The objective of this study was to demonstrate the application of an evidence-based model to determine MCIDs for AR studies, with an absolute value for an anchor-based threshold and validated methods for calculating distribution-based thresholds. METHODS: Using the same studies as the AHRQ report, anchor- and distribution-based MCID thresholds were determined for 3 clinical comparisons identified by the AHRQ: (1) oral antihistamine+intranasal corticosteroid (INCS) versus INCS, (2) montelukast versus INCS, and (3) intranasal antihistamine+INCS in a single device versus the monotherapies. The outcomes were compared with those reported using the AHRQ threshold. RESULTS: No treatment comparison met the AHRQ-defined MCID threshold; all treatments were determined to be equivalent for all 3 queries. In contrast, the evidence-based model revealed some differences between treatments: INCS > montelukast; intranasal antihistamine+INCS > either monotherapy. No clinically relevant benefit was observed for adding an oral antihistamine to INCS, but some studies were not optimal choices for quantitative determination of MCIDs. Updating the literature search revealed no additional studies that met the AHRQ inclusion criteria. CONCLUSIONS: The evidence-based threshold for MCID determination for AR studies should supersede the threshold recommended in the AHRQ report.

Comparison of efficacy, safety, and cost-effectiveness of rupatadine and olopatadine in patients of allergic rhinitis: A prospective, randomized, double-blind, parallel group study.

OBJECTIVE: To compare the efficacy, safety, and cost-effectiveness of rupatadine and olopatadine in patients of allergic rhinitis (AR). MATERIALS AND METHODS: A 2-week, single-centered, randomized, double-blind, parallel group comparative clinical study was conducted on patients with AR. Following inclusion and exclusion criteria, 67 patients were recruited and randomized to two treatment groups and received the respective drugs for 2 weeks. At follow-up, parameters assessed were total nasal symptom score (TNSS), change in total and differential count of eosinophil. RESULTS: In olopatadine group, there was a significantly higher reduction in TNSS (P < 0.05) than that of rupatadine. Both the drugs significantly reduced the absolute eosinophil count, but olopatadine (P < 0.001) was found to be superior. The incidence of adverse effects was found to be less in olopatadine group when compared with rupatadine group. CONCLUSION: Olopatadine is a better choice in AR in comparison to rupatadine due to its better efficacy and safety profile.

Efficacy of the oral chemoattractant receptor homologous molecule on TH2 cells antagonist BI 671800 in patients with seasonal allergic rhinitis.

BACKGROUND: The inflammatory response in patients with seasonal allergic rhinitis (SAR) is partly mediated by the prostaglandin D2 receptor chemoattractant receptor homologous molecule on T(H)2 cells (CRTH2). OBJECTIVE: We sought to investigate the efficacy and safety of the oral CRTH2 antagonist BI 671800 (50, 200, and 400 mg twice daily), fluticasone propionate nasal spray (200 µg once daily), or oral montelukast (10 mg once daily) administered for 2 weeks in patients with SAR. METHODS: In this randomized, double-blind, placebo-controlled, partial-crossover study, participants aged 18 to 65 years with a positive skin prick test to Dactylis glomerata pollen were exposed to out-of-season allergen in the environmental challenge chamber for 6 hours. The primary efficacy variable was the total nasal symptom score assessed as the area under the curve (AUC)(0-6h). RESULTS: In total, 146 patients (63.7% male; mean age, 36.1 years) were randomized. The adjusted mean total nasal symptom score AUC(0-6h) was significantly reduced versus placebo with 200 mg of BI 671800 (absolute difference, -0.85; percentage difference, -17%; P = .0026), montelukast (absolute difference, -0.74; percentage difference, -15%; P = .0115), and fluticasone propionate (absolute difference, -1.64; percentage difference, -33%; P < .0001). Compared with placebo, BI 671800 significantly reduced nasal eosinophil values (P < .05 for all doses), significantly inhibited nasal inflammatory cytokine levels (IL-4 and eotaxin, P < .05; 200 mg twice daily), and induced a dose-related reduction in ex vivo prostaglandin D2-mediated eosinophil shape change. CONCLUSION: Two hundred milligrams of BI 671800 twice daily demonstrated efficacy in treating SAR symptoms induced by environmental challenge chamber allergen exposure and had a favorable safety profile.

A proof-of-concept study of the effect of a novel H3-receptor antagonist in allergen-induced nasal congestion.

BACKGROUND: H1-receptor inverse agonists are used effectively for treating several symptoms of allergic rhinitis, including nasal itching, rhinorrhea, and sneezing, although most agents are not very effective in treating nasal congestion. OBJECTIVE: This study evaluated the relative efficacy of a novel selective H3-receptor antagonist, JNJ-39220675, in preventing nasal congestion induced by exposing participants with ragweed allergy to ragweed allergen in an environmental exposure chamber model. METHODS: In this single-dose, patient-blind, double-dummy, placebo- and active-controlled, phase IIa cross-over study, 53 participants were randomized to JNJ-39220675 plus placebo, placebo plus pseudoephedrine, or only placebo. The primary efficacy assessment was change in nasal patency assessed by measuring the minimal cross-sectional area of the nasal cavity by using acoustic rhinometry. Secondary assessment included total nasal symptom scores (TNSSs) over the 8-hour environmental exposure chamber exposure period. RESULTS: Smaller decreases in minimal cross-sectional area were observed after JNJ-39220675 (least square mean difference, -0.126; P = .06) and pseudoephedrine (least square mean difference, -0.195; P = .004) treatment compared with placebo. The means for the baseline-adjusted area under the curve of TNSSs were significantly smaller for JNJ-39220675 (P = .0003) and pseudoephedrine (P = .04) versus placebo. JNJ-39220675 was significantly effective in treating all 4 individual symptoms (P ≤ .05 for all scores) compared with placebo, whereas pseudoephedrine only showed a trend for improvement in individual symptom scores of the TNSS. Insomnia was the most frequent adverse event (17.3%) associated with JNJ-39220675 treatment. CONCLUSION: Prophylactic treatment with the H3-antagonist JNJ-39220675 relieved allergen-induced nasal congestion by using standard nasal symptom scoring; however, in contrast to pseudoephedrine, it only showed a trend for increasing nasal patency by using objective measures.