Change In Total Nasal Symptom Score Research Articles

Evaluation of the reproducibility of responses to nasal allergen challenge and effects of inhaled nasal corticosteroids.

Similar immune responses in the nasal and bronchial mucosa implies that nasal allergen challenge (NAC) is a suitable early phase experimental model for drug development targeting allergic rhinitis (AR) and asthma. We assessed NAC reproducibility and the effects of intranasal corticosteroids (INCS) on symptoms, physiology, and inflammatory mediators. 20 participants with mild atopic asthma and AR underwent three single blinded nasal challenges each separated by three weeks (NCT03431961). Cohort A (n = 10) underwent a control saline challenge, followed by two allergen challenges. Cohort B (n = 10) underwent a NAC with no treatment intervention, followed by NAC with 14 days pre-treatment with saline nasal spray (placebo), then NAC with 14 days pre-treatment with INCS (220 μg triamcinolone acetonide twice daily). Nasosorption, nasal lavage, blood samples, forced expiratory volume 1 (FEV1), total nasal symptom score (TNSS), peak nasal inspiratory flow (PNIF) were collected up to 24 h after NAC. Total and active tryptase were measured as early-phase allergy biomarkers (≤30 min) and IL-13 and eosinophil cell counts as late-phase allergy biomarkers (3-7 h) in serum and nasal samples. Period-period reproducibility was assessed by intraclass correlation coefficients (ICC), and sample size estimates were performed using effect sizes measured after INCS. NAC significantly induced acute increases in nasosorption tryptase and TNSS and reduced PNIF, and induced late increases in nasosorption IL-13 with sustained reductions in PNIF. Reproducibility across NACs varied for symptoms and biomarkers, with total tryptase 5 min post NAC having the highest reproducibility (ICC = 0.91). Treatment with INCS inhibited NAC-induced IL-13 while blunting changes in TNSS and PNIF. For a similar crossover study, 7 participants per treatment arm are needed to detect treatment effects comparable to INCS for TNSS. NAC-induced biomarkers and symptoms are reproducible and responsive to INCS. NAC is suitable for assessing pharmacodynamic activity and proof of mechanism for drugs targeting allergic inflammation.

Barrier-forming, drug-free nasal spray reduces allergic symptoms induced by house dust mite allergen.

House Dust Mite (HDM) is the most common indoor allergen triggering allergic symptoms. First-line pharmacotherapy treatment is recommended in international guidelines, while the avoidance of allergens represents a still unmet guideline principle. AM-301 is a new non-pharmacological nasal spray that creates a protective gel-like barrier on the nasal mucosa, preventing the contact with the allergens. This randomized, open-label, 3-period crossover study assessed the efficacy and safety of AM-301. The objective was to determine whether AM-301 reduces allergic rhinitis (AR) symptoms in patients exposed to HDM allergens. Adults with confirmed Perennial Allergic Rhinitis (PAR; n=37) were exposed to HDM allergen in a controlled Allergen Exposure Chamber before and during a treatment course of AM-301 (in six different sequences) within 3weeks (A: One spray AM-301 per nostril/B: Two sprays AM-301 per nostril/C: no treatment). For the primary efficacy analysis, data from the total nasal symptom score (TNSS) were pooled from treatment A+B (D) and analyzed with Analysis of Covariance Model. As secondary endpoints, single time points, visits and symptoms were analyzed. The primary endpoint (overall change in TNSS from baseline over all three visits) showed significant results (p=0.0085). A comparable alleviation of all four symptoms (itchy nose, nasal congestion, runny nose, sneezing) by the protective layer started to emerge after 40min and lasted up to 180min (end of challenge). AM-301 resulted to be safe and well-tolerated. AM-301 significantly reduced HDM-related allergic symptoms in a standardized allergen challenge. Protection was observed to last up to 180min.

Efficacy and Safety of a Drug-Free, Barrier-Forming Nasal Spray for Allergic Rhinitis: Randomized, Open-Label, Crossover Noninferiority Trial

Introduction: Symptoms of allergic rhinitis can be reduced by nonpharmacological nasal sprays that create a barrier between allergens and the nasal mucosa. A new nasal spray (AM-301) containing the clay mineral bentonite was tested for its ability to reduce symptoms of grass pollen. Methods: This open-label, crossover, noninferiority trial compared the efficacy and safety of AM-301 to that of hydroxypropyl methylcellulose (HPMC; Nasaleze® Allergy Blocker), an established barrier method. Adults with seasonal allergic rhinitis were exposed to Dactylis glomerata pollen, in a controlled setting, the Fraunhofer allergen challenge chamber, first without protection and then protected by HPMC or AM-301 (7 days apart). Efficacy was assessed from total nasal symptom score (TNSS), nasal secretion weight, and subjective rating. The primary endpoint was the difference, between AM-301 and HPMC, in least square mean change in TNSS over a 4-h exposure to allergen. Results: The study enrolled 36 persons, and 35 completed all study visits. The mean TNSS was 5.91 (SD = 1.45) during unprotected exposure, 5.20 (SD = 1.70) during protection with HPMC, and 4.82 (SD = 1.74) during protection with AM-301. The difference in least square means between the two treatments was −0.39 (95% CI: −0.89 to 0.10), establishing the noninferiority of AM-301. No difference in mean weight of nasal secretions was observed between the treatments. Efficacy was rated as good or very good for AM-301 by 31% and for HPMC by 14% of subjects. Sixteen subjects reported adverse events with a relationship to AM-301 or HPMC; most adverse events were mild, and none was serious. Discussion/Conclusion: AM-301 demonstrated noninferiority toward HPMC in the primary endpoint and was perceived better in subjective secondary endpoints. Both barrier-forming products had a persisting protective effect over 4 h and were safe.

Hypochlorous Acid Versus Saline Nasal Irrigation in Allergic Rhinitis: A Multicenter, Randomized, Double-Blind, Placebo-controlled Study.

Low concentrations of hypochlorous acid (HOCl) have proven antipruritic, anti-inflammatory, and antimicrobial effects without toxicity, although the mechanism has not been fully elucidated. The aim of this study was to evaluate the effectiveness of HOCl nasal irrigation to reduce allergic rhinitis (AR) symptoms compared with saline nasal irrigation. This was multicenter, randomized, double-blind, placebo-controlled study. Initially, 139 patients with perennial AR were enrolled; however, 25 did not successfully complete the study. Patients were randomly assigned to the nasal irrigation with low-concentration HOCl (n = 55) or normal saline (n = 59) treatment groups for the 4-week study period. Participants completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at every visit (baseline, Weeks 2 and 4), and Total Nasal Symptom Score (TNSS) was determined before and after nasal irrigation every morning and evening. We found that RQLQ scores significantly decreased after 4 weeks in the HOCl and placebo groups, but the decrement of the RQLQ score was similar between the 2 groups. Additionally, TNSS improved in both groups between baseline and Week 4, whereas there were no significant differences in the change of TNSS between the 2 groups. The HOCl group did not show any clinical side effects related to nasal irrigation. Allergic symptoms significantly decreased with low-concentration HOCl nasal irrigation, without significant adverse events. However, HOCl showed no additional improvement in symptoms compared with saline nasal irrigation for patients with perennial AR.

Appropriate Antigen Concentrations and Timing of a Nasal Provocation Test.

PurposeWe aimed to determine appropriate antigen concentrations and the right time to evaluate intranasal changes when performing a nasal provocation test (NPT). Also, we sought to analyze the diagnostic usefulness of individual nasal symptom and peak nasal inspiratory flow (PNIF).Materials and MethodsWe divided 46 patients into allergic rhinitis (AR) group (n=19) and a non-allergic rhinitis (NAR) group (n=27). We performed intranasal challenge with 100 AU/mL of Dermatophagoides pteronyssinus (DP) and measured changes in nasal symptoms [scored using the visual analogue scale (VAS)] and PNIF%. If the patient showed significant changes, VAS and PNIF were assessed again after another 15 minutes. In patients without significant changes, we administered 1000 AU/mL and measured changes in nasal symptoms and PNIF% after 15 and 30 minutes.ResultsFifteen minutes after the 100 AU/mL challenge, the AR group showed more significant VAS changes in all nasal symptoms, total nasal symptom score (TNSS), and PNIF% change than the NAR group. Among the AR group, patients who did not respond to 100 AU/mL exhibited less significant differences relative to the NAR group, even after 1000 AU/mL challenge. Receiver operating characteristic curve analysis for VAS changes 15 minutes after 100 AU/mL challenge revealed that all nasal symptoms had area under the curve (AUC) values of ≥0.84 (p<0.001). TNSS change had an AUC value of 0.929 (p<0.001), while PNIF% change had an AUC value of 0.834.ConclusionWe could determine the optimal concentration (100 AU/mL), timing (15 minutes after challenge), and parameters (changes in TNSS and PNIF%) when performing NPT.

As-Needed Versus Regular Use of Fluticasone Furoate Nasal Spray in Patients with Moderate to Severe, Persistent, Perennial Allergic Rhinitis: A Randomized Controlled Trial

Using intranasal corticosteroid (INCS) regularly is recommended for treating perennial allergic rhinitis. However, no studies have evaluated "as-needed" use. To compare the efficacy between as-needed and regular use of INCS in patients with moderate to severe perennial allergic rhinitis. In a 6-week randomized controlled trial, participants were assigned to either fluticasone furoate (FF) nasal spray, (27.5 μg) 2 sprays once daily for 1 week, followed by as-needed use (FF-as-needed) for 5 more weeks or 2 sprays once daily for 6 weeks (FF-regular). The primary outcome was a change in the total nasal symptom score (TNSS). The secondary outcomes were the change in nasal peak inspiratory flow, Rhinoconjunctivitis Quality of Life-36 Questionnaire score, and cumulative FF dose. In total of 108 patients, 53 and 55 patients were randomized to the FF-as-needed and FF-regular group, respectively. The difference in mean change in TNSS between the 2 groups was not significant at week 6 (1.21 points; 95% CI,-0.08 to 2.49; P= .066). The FF-regular group tended toward a greater improvement in TNSS. The FF-regular group had a higher mean change in nasal peak inspiratory flow than the FF-as-needed group at week 6 (-19.21 L/min; 95% CI,-33.54 to-4.89; P= .009). Both groups had similar improvement in Rhinoconjunctivitis Quality of Life-36 Questionnaire. The mean cumulative FF dose in the FF-as-needed group was 51% that of the FF-regular group. Both as-needed and regular use of INCS had similar improvement in TNSS and RCQ-36 score in patients with perennial allergic rhinitis. As-needed use had half of INCS exposure of the regular use.

House Dust Mite Sublingual Immunotherapy in Children Versus Adults With Allergic Rhinitis.

There are only a few studies in which the clinical efficacy of SLIT has been compared between children and adults. In addition, there is a lack of research on other factors, associated with the treatment, including immunological parameters and quality of life (QOL). To compare the effects of sublingual immunotherapy (SLIT) in adults and children on various factors: clinical efficacy, quality of life (QOL), satisfaction, immunological parameters, and adverse events. Subjects who were sensitized to house dust mites and treated with SLIT for at least 2 years were enrolled. Seventy patients who completed questionnaires measuring nasal symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and underwent serologic tests for immunological parameters at initial, 1-year, and 2-year follow-up were selected and divided into two groups based on age: a child group (age 4-12 years, n = 44) and an adult group (age 19-59 years, n = 26). The Total Nasal Symptom Score (TNSS) was significantly decreased after 2 years of SLIT in both the child and adult groups (p < 0.001, both); however, changes in TNSS from baseline did not significantly differ between the two groups (p = 0.365). More patients in adult group were satisfied with SLIT than those in child group (p = 0.050), and changes in RQLQ score from baseline tended to be larger in adult group (p = 0.089). The levels of immunological parameters at baseline were significantly higher in the child group than in the adult group; however, changes in the levels of these parameters were not significantly different. Although more adult patients were satisfied with SLIT, the clinical effects of SLIT on nasal symptoms were comparable between child and adult groups. Despite different immunological values at baseline between the two groups, changing patterns of immunological parameters did not differ.

Immunologic modification in mono- and poly-sensitized patients after sublingual immunotherapy.

To compare immunologic modification and treatment outcomes after 2 years of sublingual immunotherapy (SLIT) with house dust mite extracts (HDM) between monosensitized and polysensitized patients with allergic rhinitis. Retrospective cohort study. Among the patients who were prospectively enrolled in the SLIT cohort study, patients with allergic rhinitis who were sensitized to HDM and treated with SLIT for at least 2 years were studied. All participants underwent serologic tests at baseline and after SLIT to evaluate changes in immunologic parameters. The total nasal symptom score (TNSS) was measured before and after SLIT, and effective and less effective responder groups were categorized depending on whether patients had a TNSS reduction of 50%, as compared with baseline. The increase in Dermatophagoides pteronyssinus and Dermatophagoides farinae specific immunoglobulin G4 levels was significantly higher in monosensitized patients than in polysensitized patients (P = .020 and P = .005, respectively). The TNSS significantly improved after SLIT in both the monosensitized and polysensitized groups (P < .001 in both groups). However, the difference in the changes in TNSS from baseline was not significant between the two groups (P = .374). This study demonstrated different immunologic modifications after SLIT between monosensitized and polysensitized patients. However, patients in the polysensitized group who were treated with single-allergen SLIT experienced clinical improvement in TNSS that was comparable with that in the monosensitized group despite demonstrating different immunologic changes. 2b Laryngoscope, 129:E170-E177, 2019.

Lack of effect of Timothy grass pollen sublingual immunotherapy tablet on birch pollen–induced allergic rhinoconjunctivitis in an environmental exposure unit

BackgroundTimothy grass pollen allergen extract tablets (Grastek) are standardized sublingual immunotherapy tablets (SLIT-T) approved for the treatment of grass pollen–induced allergic rhinitis (AR) and conjunctivitis. Many grass allergic patients are also cosensitized to birch pollen. Whether Timothy grass SLIT-T can confer symptomatic benefits for birch pollen–induced AR symptoms is unknown. ObjectiveTo evaluate the treatment effect of Timothy grass SLIT-T for birch pollen–induced AR in participants sensitized to both grass and birch pollen using an environmental exposure unit (EEU). MethodsThis study was a phase 4, randomized, double-blind, placebo-controlled, parallel-group study that enrolled participants aged 18 to 65 years allergic to both timothy grass and birch pollen. After a baseline EEU birch pollen challenge, in which a minimum total nasal symptom score (TNSS) of 6 of 12 was required for enrollment, participants were randomized to receive Timothy grass SLIT-T or placebo taken once daily for 4 months. No confirmatory grass pollen challenge was performed. The primary end point was the change in TNSS averaged from assessments from hours 2 to 5 during the posttreatment birch pollen challenge compared with baseline. The secondary and exploratory end points included temporally identical changes in total ocular symptom score (TOSS), total rhinoconjunctivitis symptom score (TRSS), and individual symptom scores. ResultsThe difference in TNSS reduction after 4 months of therapy between the Timothy grass SLIT-T and placebo group was not significant (P = .83). Reductions in TOSS (P = .19) and TRSS (P = .67) were also comparable between groups. Findings between groups for individual symptom scores were similar (all P > .40), except for watery eyes, in which symptom reduction was slightly better in the placebo arm (P = .01). Timothy grass SLIT-T was well tolerated, and no serious adverse effects occurred. ConclusionA bystander effect of grass SLIT-T on birch pollen–induced AR symptoms was not detected. Symptomatic benefits of grass SLIT-T are likely allergen specific. Trial RegistrationClinicalTrials.gov identifier: NCT02394600.

Effectiveness of azelastine nasal spray compared with oral cetirizine in patients with seasonal allergic rhinitis

Azelastine nasal spray and oral cetirizine are selective histamine H(1)-receptor antagonists that are approved in the United States for the treatment of seasonal allergic rhinitis (SAR). The objective of the present study was to compare the efficacy and tolerability of azelastine nasal spray administered at the recommended dosage of 2 sprays per nostril twice daily with those of cetirizine in the treatment of moderate to severe SAR. This multicenter, randomized, double-blind, parallel-group, 2-week comparative study was conducted during the 2004 fall allergy season in patients with moderate to severe SAR. After a 1-week placebo lead-in period, patients were randomized to receive azelastine nasal spray 2 sprays per nostril twice daily plus placebo tablets or cetirizine 10-mg tablets once daily plus a placebo saline nasal spray for the 2-week double-blind treatment period. The primary efficacy variables were (1) change from baseline to day 14 in the 12-hour reflective total nasal symptom score (TNSS), which combines scores for rhinorrhea, sneezing, itchy nose, and nasal congestion, and (2) onset of action, based on the instantaneous TNSS over 4 hours after the first dose of study drug. During the double-blind treatment period, patients recorded their symptom scores on diary cards twice daily (morning and evening). Patients aged > or =18 years also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at baseline and on day 14. Three hundred seven patients were randomized to treatment, and 299 completed 2 weeks of study treatment. The age of the population ranged from 12 to 74 years (mean, 35 years), 62.9% were female, and 69.6% were white. Over 2 weeks of treatment, both groups had significant improvements in the TNSS compared with baseline (P < 0.001). The overall change in TNSS was significantly greater with azelastine nasal spray compared with cetirizine (29.3% vs 23.0% improvement, respectively; P = 0.015). In terms of onset of action, azelastine nasal spray significantly improved the instantaneous TNSS compared with cetirizine at 60 and 240 minutes after the initial dose (both, P = 0.040). Scores on each domain of the RQLQ were significantly improved in both groups compared with baseline (P < 0.001); the overall RQLQ score was significantly improved with azelastine nasal spray compared with cetirizine (P = 0.049). Both treatments were well tolerated. In this 2-week study in patients with moderate to severe SAR, azelastine nasal spray was well tolerated and produced significantly greater improvements in TNSS and total RQLQ score compared with cetirizine.

Intranasal fluticasone propionate is effective for perennial nonallergic rhinitis with or without eosinophilia

Although response to intranasal corticosteroid therapy has been reported in patients with nonallergic rhinitis with eosinophilic syndrome (NARES), efficacy specifically in non-NARES patients has not been fully characterized. To evaluate the efficacy of intranasal fluticasone propionate (FP) in the treatment of patients with perennial nonallergic rhinitis, with and without nasal eosinophilia. Data from 983 patients in three randomized, double-blind, placebo-controlled PNAR trials were integrated. Patients received a total daily dose of FP 200 microg (n = 332), FP 400 microg (n = 325), or placebo (n = 326) for 28 days. Patients were > or =12 years of age with perennial rhinitis and negative skin tests to all allergens relevant to the geographic region. Nasal eosinophils were evaluated using a five-point scale. Patients were classified as non-NARES with a point score of 0 (n = 674; 69%); patients with a point score between I and 4 were classified as NARES (n = 309; 31%). Efficacy of FP was evaluated by the mean change in total nasal symptom score (TNSS), a sum of patient ratings of nasal obstruction, postnasal drip, and rhinorrhea. Patients with either NARES or non-NARES had similar statistically significant improvement with FP 200 microg or 400 microg compared with placebo; thus, the total group comprising both varieties of rhinitis responded to FP. In the total population, both FP treatment groups showed significantly greater improvement in TNSS compared with placebo during each week of treatment (P < or = 0.002), with mean changes in TNSS for day 22 to day 28 ranging from -84 and -85 in the FP 200 microg and FP 400 microg groups, respectively, to -64 in the placebo group. The three study treatment groups had similar proportions of non-NARES (68 to 69%) and NARES (31 to 32%) patients at baseline. In the non-NARES subgroup, mean changes in TNSS for each treatment group were similar to changes seen in the total population. In the NARES subgroup, mean changes in TNSS for the FP 200 microg and placebo groups were similar to changes seen in the total population; mean change in TNSS for the FP 400 microg group was somewhat greater than changes seen in the total population. Intranasal FP is an effective treatment for perennial nonallergic rhinitis with or without nasal eosinophilia (NARES or non-NARES).