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Patients and families living with food allergy may experience significant burdens, including social isolation, impaired quality of life, and anxiety. Allergists/immunologists play a critical role in educating families living with food allergies about risk, particularly with regard to the rarity of fatal food allergy. Appropriate risk framing can greatly decrease the fear-based burden of disease. In 2024, an increasing complex fabric of food allergy treatments has emerged that includes oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and omalizumab, with the promise of additional treatments, including epicutaneous immunotherapy and oral mucosal immunotherapy in the near future. Younger children may be most likely to benefit from OIT and SLIT, with some evidence that suggests the possibility of an immunomodulatory effect. Omalizumab, approved in 2024 for use in conjunction with strict avoidance, increases the threshold of reactivity before a moderate-to-severe reaction for many, but not all, patients. There is no evidence to date that omalizumab has an immunomodulatory effect, and young children treated with omalizumab monotherapy may bear a lost opportunity cost from possible immunomodulation would they have been treated with OIT or SLIT instead; however, within a shared decision-making paradigm, beyond label use of omalizumab may include treatment with OIT or SLIT. Fortunately, the co-evolution of shared decision-making with modern food allergy treatments will facilitate the critical preference-sensitive care that must be characteristic of all decisions surrounding active food allergy management.

Background: Chronic spontaneous urticaria (CSU) is a common disease with complex pathogenesis. Patients' clinical characteristics and responses to treatment vary. Objective: We aimed to investigate the role of data obtained from routinely recommended tests in predicting the response to omalizumab, the only biologic agent approved for treatment, and in defining the clinical characteristics of the patients. Methods: A retrospective study of patients who started omalizumab treatment for CSU between 2015 and 2022 at the Department of Dermatology, Pamukkale University, was conducted. Response criteria were based on the urticaria control test, and patients with a urticaria control test score <12 at 6 months were considered treatment non-responders. Eosinophil and basophil counts, neutrophil-lymphocyte ratio (NLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and total immunoglobulin E (IgE) levels of the patients were evaluated before treatment and at the sixth month of treatment. Results: A total of 23.1% of the patients were unresponsive to omalizumab. The response rate to the omalizumab treatment of the patients with a total IgE level ≤ 30 IU/L (n = 4 [5.7%]) was significantly lower than patients with total IgE level > 30 IU/L (n = 66 [94.3%]) (p = 0.015). The mean ± standard deviation SIRI levels were significantly higher in non-responders versus responders (1.53 ± 1.03 versus 1.15 ± 7.76; p = 0.026). Eosinophil counts positively correlated with basophil counts (r = 587; p < 0.001) and IgE levels (r = 0.290; p = 0.005) but a negative correlation was found with levels of NLR (r = -0.475; p < 0.001), SIRI (r = -0.259; p = 0.013), and SII (r = -0.285; p = 0.006). NLR levels were lower in CSU patients with atopy, than in those without atopy (1.9 ± 0.9 vs 2.9 ± 2.1, p = 0.022). Conclusion: We suggest that eosinopenia and high NLR levels are linked to autoimmune CSU. Predicting a poor response to omalizumab seems possible with total IgE levels < 30 IU/L and high SIRI levels.

Background: Endothelin-1 (ET-1) and interleukin-33 (IL-33) can modulate the activation of mast cells and basophils in the pathophysiology of allergic diseases, interplaying with other mediators of "low-grade inflammation." Objective: To compare ET-1, IL-33, the neutrophil-lymphocyte ratio (NLR), eosinophil-lymphocyte ratio (ELR), platelet-lymphocyte ratio (PLR), eosinophil-basophil ratio (EBR), systemic immune inflammation index (SII), and system inflammation response index (SIRI) in patients with chronic spontaneous urticaria (CSU) and are antihistamine sensitive (AHS), antihistamine resistant (AHR), omalizumab sensitive (OmS), and omalizumab resistant (OmR). Methods: A prospective observational study enrolled 68 consecutive patients with CSU diagnosed and managed according to the dermatology section of the European Academy of Allergology and Clinical Immunology (EAACI), the European Union funded network of excellence, the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF), and the World Allergy Organization guidelines. Patients with a urticaria control test score of >12 are considered treatment sensitive, and ≤ 12 are considered resistant. The control group consisted of 20 sex-matched subjects without urticarial diseases. Total immunoglobulin E (IgE), antinuclear antibodies (ANA), thyroid stimulating hormone, antithyroid peroxidase, mean platelet volume (MPV), NLR, ELR, PLR, EBR, SII, SIRI, ET-1, and IL-33 were measured at the study entry and compared between the study groups. Results: Thirty AHS group, 38 AHR group, and 20 control group patients were included. The AHS, AHR, and control groups did not differ in demographic parameters, but the CSU groups were characterized by higher indicators of inflammation. In comparison with the AHS group, the AHR group was characterized by higher levels of IL-33 (p = 0.007), ET-1 (p = 0.032), C-reactive protein (p = 0.016), MPV (p = 0.002), and higher rates of positive ANA (p = 0.019). Of the 38 patients from the AHR group, 30 (79%) were included in the OmS group and 8 (21%) were included in the OmR group. The OmR group was characterized by higher levels of C-reactive protein (p = 0.022), EBR (p < 0.001), higher rates of ANA (p = 0.004), and lower levels of ET-1 (p = 0.025) than the OmS group. Conclusion: Our study did not confirm NRL, PRL, SII, and SIRI, PLR as the biomarkers of treatment response to antihistamines and/or omalizumab in CSU. Higher blood levels of IL-33 and ET-1 characterize AHR CSU.

Background: Chronic urticaria (CU), characterized by ≥6 weeks of intense pruritus, remains a debilitating condition for patients. New and safe treatments are needed to manage CU recalcitrant to standard therapy. Objective: A review of the current literature of standard and novel therapeutics in the management of CU was conducted. Methods: A literature search via a medical literature data base and clinical trial data base was conducted to identify treatment options for CU and current clinical trials. Results: Second-generation antihistamines, omalizumab, and cyclosporine remain the most proven therapeutic options for CU. Dupilumab, mepolizumab, benralizumab, tezepelumab, and CDX-0159 are all undergoing clinical trials for CU. Although ligelizumab demonstrated initial promising results, a phase III study was discontinued due to a nonsuperior clinical impact compared with omalizumab. Conclusion: Novel therapies are needed for the treatment of recalcitrant CU. With a deeper understanding of the pathophysiology of CU, promising therapeutics are in clinical trials for CU.

Background: Biomarkers of resistance to H 1 -antihistamines (AH) and omalizumab in chronic spontaneous urticaria (CSU) are still a matter of debate. Objective: To identify clinical and laboratory attributes of the patient that may be predictive of AH and omalizumab resistance in CSU. Methods: We conducted a retrospective observational study by using the electronic patient record data base of patients with CSU and of sex- and age-matched controls. Patients with CSU were divided into three study groups: the CSU group, patients who responded to AHs; the antihistamine-resistant CSU (AH-CSU) group, patients refractory to a fourfold AH dose; and the control group, composed of a random sample of age- and sex-matched subjects, with a case-control ratio of 1:2. The patients in the AH-CSU group treated with omalizumab were compared according to the response or resistance to omalizumab. Results: A total of 106 subjects in the AH-CSU group, 483 in the CSU group, and 1198 in the control group were compared. Both AH-CSU (112.7 ± 43.1 kU/mL) and CSU (129.5 ± 52.4 kU/mL) groups were associated with higher plasma total IgE levels than control group (103.2 ± 49.5 kU/mL; p < 0.001). The AH-CSU group was characterized by a higher plasma high-sensitivity C-reactive protein level (6.4 ± 3.7 mg/L) than the CSU group (4.3 ± 1.4 mg/L; p < 0.001) and the control group (3.1 ± 1.8 mg/L; p < 0.001). The AH-CSU and CSU groups were characterized by a lower mean ± standard deviation basophil counts (0.18 ± 0.16 cells ×10 9 /L and 0.19 ± 0.11 cells ×10 9 /L, respectively) than the control group (0.22 ± 0.09 cells ×10 9 /L; p < 0.001). The mean platelet volume w as higher in the AH-CSU group (11.2 ± 0.3 fL) than in the CSU group (11.1 ± 0.4 fL; p = 0.002) and in the control group (10.3 ± 0.4 fL; p < 0.001). There were no significant differences in the mean levels of lymphocytes, monocytes, eosinophils, basophils, and platelets, and the rates of eosinopenia and basopenia between the patients in the AH-CSU group who responded to and those who were resistant to omalizumab. Conclusion: This study provided additional data of interest to examine the pathophysiologic role of low-grade inflammation and basopenia in patients with CSU and resistant to AHs and omalizumab.

Background: Allergic rhinitis (AR) is the most common chronic noncommunicable disease worldwide that affects any age during the human life span but raises particular concerns among the parents and caregivers of the children who are affected. H 1 -receptor antagonists and corticosteroids provide the most effective way of bringing the condition under control. Intranasal application of these medications has the advantage of a faster onset of action and avoids systemic unwanted adverse effects. The only combination treatment, which comprises azelastine hydrochloride and fluticasone propionate, so far in a single advanced delivery system has proven its efficacy and safety in clinical trials of adult patients with AR. Objective: To critically review and identify gaps in the existing data for children in all different strata of pediatric ages. Methods: We searched the specialized medical literature for publications on the efficacy and safety of the combined formulation of azelastine and fluticasone in a single delivery device in adolescents (ages < 18 years) and children (ages < 12 years). Results: Altogether, 12 peer-reviewed articles have been published about trials that also involved subjects in different strata of the pediatric ages, seven of the articles pooled adolescents and adults. Three articles presented the results of studies in children ages 4 to 11 years specifically designed to overcome the difficulties that children experience in expressing themselves verbally. Conclusion: All the trials with the novel combination product that involved young children and adolescents documented its efficacy, effectiveness, and safety. However, the numbers of the youngest children (ages 4 and 5 years) were low, which suggested that further data about safety and efficacy in this age group are needed.

Background: Cold-induced urticaria can take place either due to direct cold exposure, cryoglobulinemia, or genetic component (such as cryopyrin-associated periodic syndrome), which leads to the rapid onset of urticaria and/or angioedema. It is more common in younger patients and more likely to affect females compared with males. Objective: To increase awareness of such systemic reactions of anaphylaxis and provide a focused review of the differential diagnosis, underlying mechanisms, broad workup, and management of this disease process for allergy/immunology fellows, residents, general physicians, and general practitioners. Methods: Pertinent information was included from the patient's clinical course. Also, a review of the available literature to include additional references that were obtained by using the works cited in the most up-to-date reviews was completed. Results: A case of a patient with cold-induced urticaria with common sequela was presented, followed by a discussion of the pathophysiology, diagnosis and its differential diagnosis, workup, and management. Conclusion: Cold-induced urticaria is a complex disease with several different catalysts. Providers should be aware of the different forms of cold-induced urticaria and recognize the risk for anaphylaxis in this patient population. Pearls and pitfalls of the diagnosis and management are provided.

Background: The current treatment for patients with aspirin-exacerbated respiratory disease (AERD) who have uncontrolled asthma or chronic rhinosinusitis is aspirin desensitization. For patients who are unable to undergo or do not benefit from aspirin desensitization, treatment with biologics is an option, although efficacy data for AERD is scarce. Objective: We reported a series of patients with AERD who were started on omalizumab and measured the outcomes to assess improvement. Methods: Adult patients with AERD who were initiated on omalizumab from January 2007 to January 2018 were included. We compared outcomes 6-12 months before initiating biologic therapy and during the last 6-12 months while they were on biologic therapy. Our study investigated the number of oral steroid courses, short-acting beta-agonists (SABA), antibiotics for sinusitis or pneumonia, emergency department visits, hospitalizations, pulmonary function tests, and changes in controller medications. Results: Twenty-nine patients were placed on omalizumab. Sixty-two percent demonstrated a reduction in the number of steroid courses (p = 0.0014) and number of SABA canisters used (p = 0.0005) during their last 12 months while on omalizumab. Eighty-six percent of the patients with AERD and on omalizumab demonstrated either a decrease in the number of steroid courses or number of SABA canisters used in the last year of the study. The patients with AERD and with concomitant immunoglobulin E (IgE) mediated respiratory disease showed a statistically significant reduction in the number of steroid courses and number of SABA canisters used while on omalizumab for 1 year (p = 0.002 and p = 0.005, respectively), whereas those without concomitant IgE-mediated respiratory disease did not have a substantial reduction in steroids or SABA canisters used. Conclusion: Our case series reported that omalizumab could effectively be used as an adjunct treatment for AERD, but additional larger and longitudinal studies are needed to corroborate these findings.

Background: GSP301 is an investigational fixed-dose combination nasal spray that contains the antihistamine, olopatadine hydrochloride (HCl), and the corticosteroid, mometasone furoate. Objective: To evaluate the efficacy and safety of GSP301 in patients with seasonal allergic rhinitis (SAR). Methods: In this double-blind, randomized, parallel-group study, patients (≥12 years of age) with SAR were equally randomized to intranasal GSP301 (olopatadine 665 μg and mometasone 25 μg), olopatadine HCl (665 μg), mometasone furoate (25 μg), or placebo for 14 days of twice-daily treatment. The primary end point was the mean change from baseline in the average A.M. and P.M. 12-hour reflective Total Nasal Symptom Score (rTNSS) analyzed by using mixed-effect model repeated measures ( p < 0.05 indicates statistical significance). Additional assessments included instantaneous TNSS (iTNSS), individual nasal symptoms, reflective Total Ocular Symptom Score (rTOSS) and instantaneous Total Ocular Symptom Score (iTOSS), onset of action, Physician-assessed Nasal Symptom Score (PNSS), quality of life, and adverse events (AE). Results: A total of 1180 patients were randomized. Over 14 days of treatment, GSP301 significantly improved average A.M. and P.M. rTNSS versus placebo (least squares mean difference -0.98 [95% confidence interval, -1.38 to -0.57]; p < 0.001) and versus olopatadine (p = 0.003), and approached statistical significance versus mometasone (p = 0.059). GSP301 also significantly improved average A.M. and P.M. iTNSS versus placebo and both monotherapies (p < 0.05, all). Further, GSP301 significantly improved individual nasal symptoms, overall ocular symptoms (rTOSS and iTOSS), and overall quality of life versus placebo (p < 0.01, all). Onset of action for GSP301 was observed within 15 minutes and was maintained at all subsequent time points assessed. Results for the PNSS also were significant for GSP301 versus placebo (p < 0.001). The percentages of patients with treatment-emergent AEs treated with GSP301, olopatadine, mometasone, and placebo were 12.9, 12.5, 7.1, and 9.4%, respectively. Conclusion: GSP301 was efficacious and well tolerated for the treatment of SAR symptoms compared with placebo, with a rapid onset of action of 15 minutes in patients ≥12 years of age.Clinical trial NCT02631551, www.clinicaltrials.gov.

Background: Omalizumab resistance (OmR) in chronic spontaneous urticaria (CSU) remains poorly understood. Objective: To identify clinical and laboratory attributes of patients that may be predictive of OmR in CSU. Methods: We conducted a retrospective observational study by using an electronic patient record data base of patients with severe CSU refractory to a fourfold H 1 -antihistamine dose, treated with omalizumab 300 mg every 4 weeks for at least 24 weeks. Complete response (CR) was defined as the reduction of baseline urticaria activity score by ≥ 90%, partial response (PR) by ≥ 30% to <90%, and OmR by <30% at 24 weeks. The patient characteristics of the CR, PR, and OmR groups were compared. Results: Sixty-three patients (58.9%) had a complete remission at 24 weeks of omalizumab therapy, and 16 patients (14.9%) had OmR. The patients who were OmR were characterized by a higher rate of arterial hypertension 7 (43.8%), higher mean ± standard deviation (SD) high-sensitivity C-reactive protein (hs-CRP) level (10.3 ± 8.2 mg/L), mean ± SD white blood cell (WBC) count (9.1 ± 2.8 × 10³ cells/mL), and higher mean ± SD C3 level (164.3 ± 45.4 mg/dL) at baseline than the patients with CR (arterial hypertension, 9 [13.1%], p = 0.009; mean ± SD hs-CRP, 3.4 ± 10.1, p = 0.014; mean ± SD WBC count, 6.5 ± 3.8 × 10³ cells/mL, p = 0.012; and mean ± SD C3 level, 121.8 ± 42.1 m/dL, p < 0.001). In multivariable analysis adjusted for age, sex, and body mass index, OmR was associated with an hs-CRP level of >3.0 mg/L (odds ratio 1.94 [95% confidence interval, 1.28-3.15], p = 0.009) and with C3 > 160 mg/dL (odds ratio 1.54 [95% confidence interval, 1.05-2.36], p = .017). Conclusion: Obesity, arterial hypertension, high plasma C3 level, and high-CRP level were associated with OmR in severe CSU.

Background: Atopic dermatitis (AD) is a common inflammatory skin disorder with a multitude of highly characterized comorbidities that affect infants, children, and adults worldwide. Despite its high prevalence and health burden, our armamentarium to treat AD in its severe form has remained lacking. For decades, the only Food and Drug Administration approved systemic treatment options for AD had been limited to corticosteroids. Methods: We conducted a nonsystematic review of the new and emerging drugs for the treatment of AD. Results: The recent emergence of dupilumab, a monoclonal antibody that selectively inhibits the type 2 cytokines that are integral to the pathogenesis of AD has provided dermatologists and allergists with a safe and effective targeted therapy to manage patients with moderate-to-severe disease. Numerous other drugs, both topical and systemic, are currently in development for the treatment of AD and have shown promise in their early phase trials. These agents include monoclonal antibodies that target various mediators relevant for a type 2 immune response, small-molecule inhibitors that block signaling through the Janus kinase pathway, and other agents that are aimed at addressing the symptomatology of itch. Conclusion: When anticipating the successful development and release of these drugs in the near future, it will be imperative for providers to review the available data, including the efficacy and adverse effects profile of each agent to determine the best treatment approach for each individual patient with AD.

Background: Omalizumab was approved for the treatment of chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) in the United States in March 2014., Objective: This study sought to describe real-world omalizumab use, in the United States, in a large cohort of patients with CIU/CSU., Methods: Patients with CIU/CSU (ages ≥12 years) initiated on omalizumab (index date) with ≥12 months of pre- and postindex data were identified in the an insurance claims data base (January 1, 2013, to July 31, 2016). Treatment patterns, including the dosing regimen and continuous use of omalizumab (no gaps for ≥60 days), were described during the 12-month postindex follow-up period., Results: A total of 1546 patients (mean ± standard deviation [SD] ages, 44 ± 14.5 years; 73.1% women) were identified. Most of the patients (84.5%) were initiated on omalizumab 300-mg dose; 90% maintained the initial dose, 7.5% had a dose increase, and 4.6% had a dose decrease. The mean ± SD omalizumab treatment duration was 9.1 ± 3.8 months, the mean ± SD number of omalizumab administrations was 8.3 ± 4.8, and the mean ± SD administration frequency was 44 ± 29 days. A proportion of the patients continuously treated with omalizumab for 6, 9, and 12 months was 67.3, 54.8, and 47.4%, respectively. Among the patients who discontinued omalizumab for ≥3 months (39.8%), 21% restarted the treatment after a mean ± SD of 4.4 ± 1.3 months. The proportion of patients who used other CIU/CSU-related medications decreased pre- to postindex (94.8 to 81.1%), with the highest decrease observed in oral corticosteroids (75.7 to 49.9%)., Conclusion: In this large real-world study, the majority of the patients with CIU/CSU were initiated on a 300-mg omalizumab dose and treated without titration up or down for 9 months on average. Most of the patients were continuously treated with omalizumab for ≥6 months, and one-fourth of the patients who discontinued treatment resumed it. Moreover, compared with baseline levels, the use of other CIU/CSU-related medications was lower after omalizumab initiation, with the most prominent decrease observed in oral corticosteroids.

Background: The safety of a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) has been established in adults and adolescents with allergic rhinitis but not in children <12 years old., Objective: To evaluate the safety and tolerability of an intranasal formulation of AZE and FP in children ages 4-11 years with allergic rhinitis., Methods: The study was a randomized, 3-month, parallel-group, open-label design. Qualified patients were randomized in a 3:1 ratio to AZE/FP (n = 304) or fluticasone propionate (FP) (n = 101), one spray per nostril twice daily, and to one of three age groups: ≥4 to <6 years, ≥6 to <9 years, and ≥9 to <12 years. Safety was assessed by child- or caregiver-reported adverse events, nasal examinations, vital signs, and laboratory assessments., Results: The incidence of treatment-related adverse events (TRAEs) was low in both the AZE/FP (16%) and FP-only (12%) groups after 90 days' continuous use. Epistaxis was the most frequently reported TRAE in both groups (AZE/FP, 9%; FP, 9%), followed by headache (AZE/FP, 3%; FP, 1%). All other TRAEs in the AZE/FP group were reported by ≤1% of the children. The majority of TRAEs were of mild intensity and resolved spontaneously. Results of nasal examinations showed an improvement over time in both groups, with no cases of mucosal ulceration or nasal septal perforation. There were no unusual or unexpected changes in laboratory parameters or vital signs., Conclusion: The intranasal formulation of AZE and FP was safe and well tolerated after 3 months' continuous use in children with allergic rhinitis.The study was registered on ClinicalTrials.gov (NCT01794741).

Background: Pharmacologic treatment is a mainstay of allergy therapy and many caregivers use over-the-counter antihistamines for the treatment of seasonal allergic rhinitis (SAR) symptoms in children., Objective: To assess the efficacy and safety of cetirizine 10 mg syrup versus loratadine 10 mg syrup versus placebo syrup in a randomized double-blind study of children, ages 6-11 years, with SAR., Methods: This randomized, double-blind, parallel-group, placebo-controlled study was conducted at 71 U.S. centers during the spring tree and grass pollen season. After a 1-week placebo run-in period, qualified subjects were randomized to once-daily cetirizine 10 mg (n = 231), loratadine 10 mg (n = 221), and placebo (n = 231) for 2 weeks. The primary efficacy end point was change from baseline in the subject's mean reflective total symptom severity complex (TSSC) score over 14 days., Results: Children treated with cetirizine experienced significantly greater TSSC score reductions versus children treated with placebo over 14 days (least square mean change, -2.1 versus -1.6; p = 0.006). The differences in TSSC score improvement over 14 days between the cetirizine versus loratadine groups (-2.1 versus -1.8; p = 0.124) and between the loratadine versus placebo groups (-1.8 versus -1.6; p = 0.230) were not statistically significant. Predominant adverse events in the cetirizine, loratadine, and placebo groups were headache (3.5, 3.6, and 3.1%, respectively) and pharyngitis (3.5, 2.7, and 3.5%, respectively). Somnolence was reported in three subjects (1.3%) treated with cetirizine and in none of the other subjects., Conclusion: Cetirizine 10 mg was statistically significantly more efficacious than placebo in the treatment of SAR symptoms in children ages 6-11 years. Symptom improvement was not significantly different between the loratadine 10 mg and placebo groups.

Background: Omalizumab has been a valuable option for patients with severe allergic asthma, but there are only case reports regarding effectiveness of omalizumab in patients with allergic bronchopulmonary aspergillosis (ABPA)., Objective: To evaluate the clinical and functional effectiveness of omalizumab in patients with asthma and ABPA in long-term follow-up., Methods: The study was conducted as a retrospective chart review of patients with ABPA who were treated with omalizumab injections between December 2008 and June 2014. Once treatment with omalizumab was started, data were collected at three time points: at baseline, after 1 year, and, in June 2014, at the last follow-up., Results: Fourteen patients with ABPA (seven women and seven men; mean [± standard deviation (SD)] age, 44.21 ± 13.01 years) were included. The treatment period was 31.5 ± 3.99 months (mean ± SD). The difference between the baseline and the last evaluation of the mean percentage of forced expiratory volume in 1 second (FEV1) was significant (p = 0.02). The mean asthma control test score was increased at all-time points compared with the basal score (p = 0.001). After omalizumab treatment was initiated, the patients' mean oral corticosteroid dosage significantly decreased (p = 0.001). The baseline exacerbation rate was 2.7 ± 1.5/y (mean ± SD), and the hospitalization rate was 1.4/y, and both were zero at the last assessment (p = 0.001). Eleven of the patients (78.6%) responded perfectly, and three (21.4%) partially responded to treatment. The patients who had a total immunoglobulin E level of <1000 IU/mL seemed to be more responsive than those whose total immunoglobulin E level was >1000 IU/mL (p = 0.05)., Conclusion: Omalizumab provided a clinically important reduction in exacerbations and steroid requirement, and improved asthma symptoms and pulmonary function parameters in patients with asthma and ABPA who had previously shown an unsatisfactory response to Global Initiative for Asthma step 4 treatment.

The efficacy of MP29-02 (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in an advanced delivery system) has been well established in controlled clinical trials. This study was designed to assess the use of MP29-02 and its effectiveness in routine clinical practice. This was a German multicenter, prospective, noninterventional study, including 1781 allergic rhinitis (AR) patients. Eligible patients (i.e., acute AR symptoms and visual analog scale [VAS] score >50 mm) were included, assigned MP29-02 at baseline, and reassessed after ∼14 days. Patients assessed symptom control using a VAS from 0 (not at all bothersome) to 100 mm (very bothersome) in the morning before MP29-02 use, on days 0, 1, 3, and 7 and after ∼ 14 days. Patients' perceived levels of disease control were assessed on day 3. The Youden index determined patient-reported VAS score cutoffs on day 3 for "well controlled" and "partly controlled." MP29-02 reduced the VAS score from 75.4 mm (SD = 17.2) at baseline to 21.3 mm (SD = 18.3) by the last visit, a shift of 54.1 mm (SD = 24.6). One in every two patients felt their symptoms were well controlled at day 3. This perception of well-controlled symptoms at day 3 corresponded to an optimal VAS cutoff of 36 mm. On average, patients treated with MP29-02 crossed this well-controlled VAS cutoff by last visit. Similar results were found in adolescents, adults, and older adults, in those with perennial AR (PAR), seasonal AR (SAR), or PAR + SAR and in those with more and less severe disease. MP29-02 provides effective and rapid symptom control across all age groups in a real-life setting with responder rates higher than those observed in controlled clinical trials, supporting MP29-02's position as the drug of choice for the treatment for AR.

An update to the atopic dermatitis (AD) practice parameter was published in 2013 using an established grading system for determining category of evidence and strength of recommendation. Since the previous update in 2004, a number of seminal observations regarding skin barrier and immune dysregulation in AD have been made with important therapeutic implications. A key addition to the treatment algorithm based on our understanding that normal-appearing skin in patients with AD is not normal is proactive therapy. Studies with both topical steroids and a topical calcineurin inhibitor have shown that in patients with relapsing AD, if they are able to clear or almost clear their eczema, then twice-weekly proactive treatment of normal-appearing skin that tends to flare leads to better disease control. For difficult-to-manage patients, the value of wet wrap therapy is reaffirmed in the practice parameter update. In addition, allergen immunotherapy is now a consideration in select patients with AD and aeroallergen sensitivity. Beyond the practice parameter, novel approaches to filaggrin deficiency are being evaluated. With respect to immune dysregulation, dupilumab, a fully human monoclonal antibody directed at the IL-4 receptor alpha subunit was recently shown to be effective in treating adults with moderate-to-severe AD.

The effect of cetirizine on quality of life (QOL) in subjects with perennial allergic rhinitis (PAR) has been previously evaluated using generic instruments. While generic QOL tools are used across various conditions, disease-specific instruments evaluate the impact of treatment on areas that are affected by that particular condition. This study evaluated the effect of cetirizine on symptom severity and health-related QOL, using a disease-specific instrument, in adults with PAR. This randomized, double-blind, placebo-controlled study was conducted at 15 U.S. centers outside the pollen allergy season. After a 1-week placebo run-in period, qualified subjects aged 18-65 years with PAR were randomized to once-daily cetirizine 10 mg (n = 158) or placebo (n = 163) for 4 weeks. Change from baseline in total symptom severity complex (TSSC) and overall Rhinitis Quality of Life Questionnaire (RQLQ) scores were primary efficacy end points. Cetirizine produced significantly greater improvements in mean TSSC for each treatment week (p < 0.05) and for the entire 4-week treatment period (p = 0.005) compared with placebo. After 4 weeks, cetirizine-treated subjects reported significantly greater overall improvement in RQLQ scores compared with placebo-treated subjects (p = 0.004). After 1 week, cetirizine produced significant improvements in the nasal symptoms, practical problems, and activities RQLQ domain scores compared with placebo (p < 0.05). After 4 weeks, cetirizine-treated subjects reported significant reductions in these RQLQ domain scores and in emotion domain scores compared with placebo-treated subjects (p < 0.05). Cetirizine 10 mg daily produced significant improvements in symptom severity and allergic rhinitis-related QOL compared with placebo in adults with PAR.

Allergic rhinitis (AR) affects at least 60 million people in the United States each year, resulting in a major impact on patient quality of life, productivity, and direct and indirect costs. As new therapies, data, and literature emerge in the management of AR, there is a need to communicate and disseminate important information to health care professionals to advance the practice of medicine and lessen the disease burden from AR. Treatment recommendations for AR have not been updated since the 2012 Food and Drug Administration approval of nonaqueous intranasal aerosol agents using hydrofluoroalkane propellants and the first aqueous intranasal combination product. Here, we present an updated algorithm for the pharmacologic treatment of AR that includes these new treatment options. Treatment recommendations are categorized by disease severity (mild versus moderate/severe) and duration of symptoms (episodic versus nonepisodic, with episodic defined as <3 days/wk or for <3 weeks). Preferred treatments are suggested, as well as alternative options for consideration by clinicians in the context of individual patient needs. This recommendation article also outlines the importance of treatment monitoring, which can be conducted using the recently developed Rhinitis Control Assessment Test. Successful therapeutic outcomes depend on multiple factors, including use of the most effective pharmacologic agents as well as patient adherence to therapy. Therefore, it is imperative that rhinitis patients not only receive the most effective therapeutic options, but that they also understand and are able to adhere to the comprehensive treatment regimen. Successful treatment, with all of these considerations in mind, results in better disease outcomes, improved quality of life for patients, and greater economic productivity in the home and workplace.

This article intends to place new treatments in the context of allergic rhinitis (AR) treatment history. The medical literature was searched for significant advances and changes in AR treatment. Historical data on AR treatment options and management were selected. Reviews of AR management published throughout the 20th century were included to provide context for treatment advances. Modern AR treatment began in the early 20th century with immunotherapy and was soon followed by the emergence of antihistamine therapy in the 1930s. Numerous treatments for AR have been used over the ensuing decades, including decongestants, mast cell stabilizers, and leukotriene receptor antagonists. Topical corticosteroid options were developed the 1950s, and, added to baseline antihistamine therapy, became the foundation of AR treatment. Treatment options were significantly impacted after the 1987 Montreal Protocol, which phased out the use of chlorofluorocarbon propellant aerosols because of environmental concerns. From the mid-1990s until recently, this left only aqueous solution options for intranasal corticosteroids (INSs). The approval of the first hydrofluoroalkane propellant aerosol INSs for AR in 2012 restored a "dry" aerosol treatment option. The first combination intranasal antihistamine/INSs was also approved in 2012, providing a novel treatment option for AR. Treatment of AR has progressed with new therapeutic options now available. This should continue to move forward with agents to alter the allergic mechanism itself and impact the disease burden that has a significant impact on patient outcomes.

Although studies have established that adding long-acting beta agonists (LABA) to inhaled corticosteroid (ICS) monotherapy among patients with inadequately controlled asthma is associated with better outcomes than increasing ICS dosage, outcomes with ICS versus fixed-dose ICS/LABA combination among patients with recent asthma exacerbation or frequent use of rescue medication are unavailable. This study was designed to compare health-care utilization/costs among patients with recent asthma exacerbation or frequent rescue medication use who received fluticasone propionate (FP) alone versus fixed-dose FP/salmeterol combination (FSC). A retrospective cohort study was conducted using a large health insurance data set. Patients with one or more claims with asthma diagnosis, two or more prescriptions for FSC (250/50- or 100/50-mg formulations) or FP (220- or 110-mg formulations), and one or more asthma exacerbations or five or more short-acting beta agonist (SABA) prescriptions within 1 year before initial receipt of study medications were included. Health-care utilization/costs and controller therapy compliance were compared for patients receiving FSC versus FP using multivariate regression analysis controlling for FP dose and baseline characteristics. A total of 7779 patients met inclusion criteria (5769, FSC, and 2010, FP) with comparable mean follow-up (FSC, 685 days; FP, 670 days; p = 0.151). Controlling for FP dosage and baseline characteristics, FSC patients had lower risks of asthma-related exacerbations, fewer SABAs and systemic corticosteroids, higher costs of asthma medications and total asthma-related health care, and lower total asthma-related health-care costs excluding study medication cost. In asthma patients with recent exacerbation or frequent SABA use, receipt of FSC reduced asthma-related exacerbation risks and rescue medication use versus receipt of FP.

The selection of specific pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, most prominent symptoms, symptom severity, patient preference, cost, and comorbid conditions. Guidelines focus on immediate symptoms and monotherapy. However, given the often variable course of disease, understanding symptom patterns, and recommending intervention transitions among agents and classes (and from alternative single and combination medications) can aid in optimization of treatment. This review focuses on considerations for combination therapy for AR, particularly in the context of step-up and step-down treatment, and individual symptoms and comorbidities that may benefit from such treatment (e.g., asthma). Relevant clinical studies for treatment of AR and of AR with comorbid asthma and information on treatment guidelines were identified through MEDLINE searches from inception through 2012. Search terms and phrases included "allergic rhinitis," "asthma," "treatment guidelines," and "stepwise treatment." Stepped methodology is individualized according to patient-specific factors and severity of disease. A possible step-up/step-down approach might move through five stages: step 1, for mild intermittent symptoms, intranasal or oral antihistamine, as needed; step 2, daily intranasal antihistamine (an oral antihistamine or leukotriene antagonist may be considered as an alternative); step 3, daily intranasal corticosteroids (INS); step 4, combination INS and intranasal antihistamines; step 5, further add-on therapy options in severe cases. A step-up/step-down approach to AR pharmacotherapy based on patient response may hold the potential for optimal control of AR symptoms while minimizing side effects and cost of treatment.

Rush immunotherapy (RIT) accelerates the build-up phase of traditional IT. The biggest potential benefit of using RIT is decreased time to symptomatic improvement. However, aeroallergen RIT carries an increased risk of systemic reaction (SR) compared with traditional IT. This study was designed to assess the safety of a modified 1-day multiple aeroallergen RIT protocol. A retrospective chart review was performed of 138 patients from an outpatient, university-based allergy practice who underwent RIT between November 2007 and February 2011. The RIT protocol consisted of eight injections over 5 hours, and stopped at one 10-fold dilution below the maintenance vial. All patients were premedicated on the same day of RIT with prednisone and histamine 1 and 2 receptor blockers. Primary end point observed was rate of SR. One hundred thirty-eight patients received a total of 2911 RIT injections. Thirty- eight patients (28%) had SRs. The SR rate per injection was 1.3%. Most of the reactions (82%) occurred after the last dose of the protocol. No patients with SR had severe anaphylaxis requiring emergency department support or hospitalization. The post-RIT SR rate was within the range seen with traditional IT. Well-controlled asthmatic patients were not at increased risk of SR compared with nonasthmatic patients. Modification of RIT to end at one 10-fold dilution below the maintenance vial for multiple aeroallergen RIT did not significantly decrease the SR rate compared with other protocols that end at the maintenance vial. Unlike hymenoptera RIT, aeroallergen RIT continues to be associated with a high risk of SR compared with traditional IT.

Allergic conjunctivitis (AC) affects an estimated 20% of the population in the Western world, with a large fraction suffering due to seasonal or perennial allergen exposures. Bepotastine besilate ophthalmic solution (BBOS) 1.5%, a dual-acting histamine (H(1)) receptor antagonist and mast cell stabilizer, is indicated for itching associated with AC. This study was designed to evaluate the efficacy and safety of BBOS 1.5% for reducing ocular itching associated with AC in subjects enrolled in a natural exposure trial. Eligible subjects in a multicenter, double-masked, randomized, parallel-group, placebo-controlled, natural exposure clinical trial were randomly assigned to either BBOS 1.5% or placebo eyedrops on a 1:1 basis and instilled 1 drop of the test agent into both eyes twice daily for 2 weeks. The mean change from baseline in instantaneous and reflective ocular itching scores at the end of 2 weeks of treatment were evaluated based on subject-assessed severity of instantaneous and reflective itching. Subject-reported adverse events (AEs) were also recorded for safety. Treatment with BBOS 1.5% significantly reduced instantaneous and reflective ocular itching scores from baseline compared with placebo over the 2-week study period(p = 0.007 and p = 0.005, respectively). BBOS 1.5% was well tolerated, and AEs were generally transient and mild. This clinical study indicates BBOS 1.5% effectively and safely treated ocular itching in a natural exposure allergy study and is a useful treatment option for the management of ocular itching associated with AC. (ClinicalTrials.gov identifier number: NCT01174823.)

Environmental challenge chambers (ECC) have been used to expose people to pollen allergens within a stable atmosphere and to examine the efficacy of treatment. Although pollinosis is one of the typical IgE-mediated type I allergic diseases, allergic inflammation is thought to contribute to the fundamental pathogenesis and prophylactic treatment may reduce exacerbations of pollinosis. The purpose of this study was to compare the efficacy of prophylactic treatment with nasal steroid (mometasone furoate nasal spray) or an antihistamine (fexofenadine) in the control of cedar pollinosis using the ECC. In a randomized, double-blind two-way crossover study, 48 patients received nasal steroid or antihistamine for 7 consecutive days (days 1-7). On day 8, patients were exposed to cedar pollen (8000 grains/m(3)) in the ECC for 3 hours. Nasal symptoms induced by pollen exposure were assessed. Total nasal symptom scores (TNSSs) during the exposure in the ECC were not significantly different between the antihistamine and the nasal steroid groups. Nasal symptoms induced by pollen exposure using the ECC persisted for up to 3 days. TNSSs after pollen exposure on days 8-11 were significantly lower in the nasal steroid group compared with the antihistamine group. Prophylactic treatment with nasal steroid is more effective than antihistamine against pollinosis, particularly in the late phase. Clinical trial registration JAPIC CTI 101182 (www.clinicaltrials.jp/user/ctiMain&#95;e.jsp).

An aerosol formulation may be preferred by some allergic rhinitis (AR) patients, to avoid the "wet feeling" and nasal runoff associated with aqueous nasal corticosteroid sprays. Beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol is a recently developed, nonaqueous, nonchlorofluorocarbon formulation of BDP for the treatment of AR. This study was designed to evaluate the efficacy, safety, and quality-of-life benefits of BDP nasal aerosol in subjects with seasonal AR (SAR). Eligible subjects (≥12 years of age) enrolled in this 2-week study were randomized to either BDP nasal aerosol at 320 μg/day (n = 169) or placebo (n = 171). Efficacy assessments included reflective and instantaneous total nasal symptom scores (rTNSS and iTNSS, respectively), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, reflective and instantaneous total ocular symptom scores (rTOSS and iTOSS, respectively), and physician-assessed total nasal symptom score (PNSS). Safety and tolerability were also assessed. Subjects receiving BDP nasal aerosol showed a significantly greater improvement from baseline in average A.M. and P.M. rTNSS versus placebo (treatment difference, -0.91; 95% confidence interval, -1.3, -0.5; p < 0.001) over 2 weeks of treatment. Greater improvements in rTNSS with BDP nasal aerosol compared with placebo were evident by day 2 and were maintained throughout the treatment period. Similarly, significant improvements were seen with BDP nasal aerosol in iTNSS (p < 0.001) and RQLQ score (p = 0.005) compared with placebo. Treatment with BDP nasal aerosol also resulted in greater improvements in rTOSS (p = 0.002), iTOSS (p = 0.003), and PNSS (p < 0.001) relative to placebo. BDP nasal aerosol was well tolerated and the overall safety profile was similar to placebo. Results from this clinical study indicated that BDP nasal aerosol provided significant AR symptom relief and was well tolerated in patients with SAR with an overall safety profile similar to placebo. Clinicaltrials.gov identifier: NCT01024608.

Omalizumab is an anti-immunoglobulin E (anti-IgE) monoclonal antibody approved in the United States since 2003 for treatment of moderate-to-severe allergic asthma in adults and adolescents (aged ≥12 years) inadequately controlled with inhaled corticosteroids (ICSs). Current treatment guidelines recommend considering the addition of omalizumab if allergic asthma symptoms are not adequately controlled with high-dose ICS + long-acting beta-agonist (LABA) therapy. This study was designed to review the clinical efficacy and safety of omalizumab as established in previously published pivotal clinical trials used to support registration in the United States, i.e., primarily including patients receiving only concomitant ICS therapy, as well as results from the recently completed additional study, which specifically enrolled patients who were poorly controlled despite high-dose ICS + LABA therapy ± additional controllers (including oral corticosteroids [OCSs]). Summary of published omalizumab pivotal trials and associated extension trials, plus key results from the additional study, were used. Pediatric data (i.e., <12 years) were outside the scope of this article. Treatment with omalizumab significantly reduced asthma exacerbations versus placebo when added to ICS therapy during both steroid-stable and steroid-reduction phases of two pivotal trials. In the additional study, omalizumab significantly reduced asthma exacerbation rates versus placebo when added to high-dose ICS + LABA therapy with or without other controller medications. Results from the additional clinical study further support current asthma guideline recommendations to consider omalizumab in steps 5 or 6 for persistent allergic asthma patients whose symptoms are not adequately controlled despite high-dose ICS + LABA therapy ± additional controllers (including OCS).

Many patients with allergic rhinitis (AR) have uncontrolled symptoms despite available treatment options. This study was designed to evaluate the efficacy and safety of MP29-02 (a novel intranasal formulation of fluticasone propionate [FP] and azelastine [AZ] hydrochloride), compared with monotherapy with FP, AZ, and placebo sprays for the treatment of seasonal allergic rhinitis (SAR). This 2-week randomized, double-blind, placebo-controlled trial was conducted in 779 patients with moderate-to-severe SAR. Treatments were administered 1 spray/nostril twice daily in the same vehicle and delivery device. Daily doses of AZ and FP were 548 and 200 micrograms, respectively. The primary efficacy variable was the 12-hour reflective total nasal symptom score (rTNSS), consisting of nasal congestion, sneezing, itchy nose, and runny nose. Secondary efficacy variables were (1) 12-hour reflective individual nasal symptom scores; (2) onset of action; (3) 12-hour reflective total ocular symptom score (rTOSS), including itchy eyes, watery eyes, and red eyes; and (4) the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score. MP29-02 significantly reduced the mean rTNSS from baseline by -5.54 points compared with FP (-4.55; p = 0.038), AZ (-4.54; p = 0.032), and placebo (-3.03; p < 0.001), improving the rTNSS by 39% beyond the contribution of FP. All individual nasal symptoms contributed to the efficacy of MP29-02. Onset of action was within 30 minutes. MP29-02 significantly improved rTOSS compared with placebo, provided a clinically important improvement in the overall RQLQ score, and was well tolerated. In this study, MP29-02 provided more complete symptom relief than two widely used first-line AR treatments and was well tolerated.

The Urticaria Patient Daily Diary, including the Urticaria Activity Score, has recently been validated in adults with chronic idiopathic urticaria (CIU), but its validity in adolescents is unknown. This study was designed to (1) assess the content validity of the Adolescent Urticaria Patient Daily Diary and, (2) collect exploratory data on symptom experiences, sleep interference, and health-related quality of life (HRQOL) of adolescents with CIU. The Urticaria Patient Daily Diary was modified to increase its relevance with an adolescent population. A qualitative, cross-sectional, multicenter study was then conducted in the United States so that adolescent subjects could provide information on the impact of urticaria on their lives and comment on the diary. Data were collected via in-person semistructured interviews with subjects 12-17 years of age with moderate-to-severe CIU. The most bothersome symptom was itching (44%). The impact of CIU on HRQOL varied. The majority of subjects (78%) reported waking up at least once a night. Overall, subjects found the diary to be clear, easy to comprehend, and easy to complete. Revisions were made to the diary based on feedback from subjects. After nine interviews, no new information was received. The symptoms of CIU are bothersome to adolescents, particularly itch, and urticaria has a negative impact on the sleep of adolescent patients. The final Adolescent Urticaria Patient Daily Diary has evidence of content validity in patients with CIU ranging from 12 to 17 years of age.

The eye has become the target of intense pharmacologic development because it represents one of the most active sites of allergic inflammation, due to it having no mechanical barrier to prevent the impact of allergens such as pollen on its surface. Over the past 20 years, we have witnessed an astonishing growth in therapeutic advances, ranging essentially from derivatives of simple aspirin to various newly developed biological immunomodulatory agents, using implantable drug delivery devices that exceed the safety and efficacy of those available for other organ systems and resorting to advanced surgical techniques for the correction of sight-threatening, disease-related complications. Overall, with the expanding knowledge base, the intricacy of ocular inflammation appears to be becoming ever more manageable and the clinical allergist/immunologist has an increasing role in the treatment outcomes of patients with anterior inflammatory disorders of the ocular surface primarily allergic conjunctivitis but also including dry eye syndromes.

Controlled clinical trials have shown the recombinant humanized monoclonal anti-IgE antibody omalizumab to improve asthma control and reduce symptom exacerbations in patients with moderate-to-severe allergic asthma who remain clinically unstable despite optimal medical therapy. An objective retrospective review compared clinical experience with the data reported in the controlled studies. Data tracking for 167 patients progressively enrolled between 2003 and 2010 treated with omalizumab included symptoms, forced expiratory volume at 1 second (FEV(1)), systemic steroid bursts, and need for short-acting bronchodilator rescue measured at the start of therapy; 3, 6, and 12 months after starting treatment, and yearly thereafter. Exacerbations were compared for the 12 months before and the 12 months after starting treatment in a subgroup of patients. Asthma control improved with omalizumab over time (up to 6 years) as indicated by fewer symptoms and less need for rescue medication (p < 0.001 for both). FEV(1) remained stable. The number of patients reporting asthma exacerbations requiring urgent care decreased by 49% during the first 12 months of treatment (p ≤ 0.01), and significant reductions in exacerbations were also evident when measured by hospitalizations or systemic corticosteroid bursts (p < 0.001 for both). This is the first long-term pragmatic review of omalizumab. Our clinical experience (up to 6 years in some patients) supports the results of earlier controlled studies, confirming the usefulness of adding omalizumab to the long-term management of patients with difficult-to-treat disease who suffer from persistent symptoms despite optimal therapy with medications.

This White Paper presents the Consensus Statements derived from a Special Issues Board (SIB) held in Chicago, IL, in October 2010. The SIB was convened to address the question of whether there is a need for both aerosol and aqueous intranasal steroids (INSs) in the treatment of allergic rhinitis (AR). The faculty reviewed the published record of efficacy and safety of aerosol and aqueous INSs, as well as patient and physician satisfaction and preferences for currently available INSs, and burden of disease. Agreement on unmet needs also included the practice experience of the faculty and their colleagues. The body of evidence indicates that INSs are equally effective and well tolerated for most patients. However, differences exist among current aqueous formulations as well as between these products and their aerosol antecedents, based on the properties of the nasal spray. Aerosol formulations, although no longer available, may be preferred for some patients with specific pathophysiology and may be preferred by some patients based on sensory perception. There are good reasons to expand the currently available options of INSs by having both aerosol and aqueous formulations.

Olopatadine hydrochloride nasal spray 0.6% (OLO) and azelastine nasal spray 137 micrograms (AZE) are effective in treating allergic rhinitis and AZE is indicated for nonallergic vasomotor rhinitis (VMR). This study evaluates the relative safety and efficacy of OLO and AZE in patients with VMR. This randomized, double-blind, parallel-group, multicenter study compared OLO (an investigational use) with AZE over 14 days in patients (n = 129) ≥12 years of age with chronic VMR. Efficacy included the severity of nasal symptom scores. Safety included adverse events (AEs) and nasal examinations. Patient perceptions of treatment satisfaction and changes in allergy condition were determined using the Treatment Satisfaction Questionnaire for Medication and Patient Global Assessment scores. In the OLO and AZE groups, reflective scores for individual nasal symptoms (nasal congestion, rhinorrhea, postnasal drip, and sneezing) and total nasal VMR symptom scores decreased significantly from baseline to day 14 (p < 0.05). No significant between-group differences were observed (p > 0.05). No serious AEs were reported in either group. Overall, 22 and 20 AEs were reported in the OLO and AZE groups, respectively. The most common AE was taste disturbance, reported by three (5.3%) and six (10.3%) patients in the OLO and AZE groups, respectively. Patients in both groups reported similar treatment satisfaction scores and a majority of patients in both groups perceived an overall improvement in their rhinitis condition. OLO has a similar efficacy and safety profile to AZE for the management of VMR in patients ≥12 years of age.

Nasal congestion is a frequent, bothersome symptom of seasonal allergic rhinitis (SAR). Mometasone furoate nasal spray (MFNS) has established efficacy in treating nasal allergy symptoms, but no study has been conducted with the primary purpose of evaluating MFNS for relief of congestion. This study assessed MFNS for congestion and other nasal symptoms in SAR. Two double-blind, placebo-controlled studies randomized symptomatic SAR patients to 15 days of MFNS, 200 micrograms, or placebo q.d. each morning. Participants scored individual components of total nasal symptom score (TNSS; congestion, rhinorrhea, sneezing, and itching) on a 4-point scale in the morning (A.M.) and evening (P.M.). Symptoms were scored for the time of assessment (NOW) and for the previous 12 hours (PRIOR). The pooled population comprised 684 patients randomized to MFNS (n = 344) or placebo (n = 340). Change from baseline in A.M./P.M. PRIOR nasal congestion score averaged over days 1-15, the primary end point, was significantly (p < 0.001) greater with MFNS than with placebo (0.68-point [25.2%] reduction versus 0.45-point [16.0%] reduction, respectively). Reduction in A.M./P.M. PRIOR TNSS averaged over days 1-15, a key secondary end point, was also superior with MFNS (2.83 points [28.5%] versus 1.79 points [17.6%]; p < 0.001). Predose A.M. NOW congestion, other nasal symptoms, and TNSS improved significantly more with MFNS, indicating 24-hour efficacy. Adverse events were infrequent and localized; the most common (epistaxis and pharyngolaryngeal pain) occurred in 1.0% of MFNS patients. MFNS q.d. provides sustained relief for nasal congestion and other SAR symptoms.

Although intranasal corticosteroids (INSs) are the first-line treatment for seasonal allergic rhinitis (SAR), some patients do not respond adequately, reflecting biological heterogeneity or confounding conditions. The objective of this study was to determine what recruitment factors identify SAR subjects who will be unresponsive to mometasone furoate (MF). We performed a 2-week, double-blind, placebo-controlled, parallel study on 40 subjects with SAR. Each subject underwent a decongestant test using oxymetazoline. Baseline nasal symptoms, nasal peak inspiratory flow (NPIF) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores were recorded. Next, subjects were randomized to either 200 μg of MF or placebo. Symptom diaries and NPIF measurements were completed twice daily. After 2 weeks, subjects repeated the RQLQ and the global assessment of symptoms. There was a significant reduction in symptoms in the MF group compared with placebo (p ≤ 0.05) in patients with baseline total symptom scores of ≥6. Multivariate analysis showed that treatment (MF versus placebo; p = 0.049) and amount of decongestion (percent change in NPIF after oxymetazoline; p = 0.008) predicted the improvement in total nasal symptoms. In clinical trials, SAR subjects must report multiple symptoms to be responsive to treatment with INSs. Our results also support the use of the decongestant test for choice of appropriate study volunteers, both to ensure participation of potentially responsive subjects and to eliminate those with confounding issues.

Current treatment options for allergic rhinoconjunctivitis include topical antihistamines, vasoconstrictors, mast cell stabilizers, intranasal corticosteroids (INCS), and nonsteroidal anti-inflammatory drugs that are generally used as a supplement to oral or intranasal therapies, necessitating the use of multiple treatments for the different symptoms of allergic rhinitis (AR). To assess the efficacy of INCS for ocular symptoms (OS) of AR. A search was performed of clinical trials (n = 32) from 1973 to 2009 of English articles (Medline, Embase, and PubMed) using "intranasal corticosteroid," "allergic rhinitis," "ocular symptoms," "allergic conjunctivitis," and "rhinoconjunctivitis" as key words. Quality assessment for the 32 eligible studies was performed using the Jadad score. Statistical analysis for continuous data was done by weighted mean difference or standardized mean difference. Thirty-two trials were included and separated into three different groups. The overall weighted mean was obtained from the Jadad score and came out to 9.29 (95% CI, 8.7-9.88). For meta-analysis for total OS scores and individual symptoms (10 parallel studies) the weighted mean was 10.17 (95% CI, 9.34-11). In the parallel studies, meta-analysis of individual symptoms (nine studies) gave a weighted mean of 10.09 (95% CI, 9.55-10.63). For eye symptoms but no individual symptoms (13 studies), the weighted mean was 8.56 (95% CI, 7.66-9.46). To date, clinical studies conducted statistically showed the efficacy of INCS on the OS of AR as evidenced by the meta-analysis results for the studies reporting total OSs.

Intranasal corticosteroids (INCSs) are established as the first-line treatment of moderate to severe allergic rhinitis (AR) in both adults and children. Compared with other nasal allergy medications, INCSs are the most effective at providing symptom relief and increasing quality of life. Ciclesonide nasal spray is the most recently approved INCS. The formulation of ciclesonide does not contain benzylalkonium chloride or phenyl ethyl alcohol, excipients that have been associated with reduced mucociliary transport, and unpleasant sensory perceptions. Additionally, ciclesonide has been formulated in a hypotonic suspension that has been shown to optimize intranasal absorption and it has a lower volume of spray compared with most other INCS products. Systemic exposure to ciclesonide and its active metabolite desisobutyryl-ciclesonide is low after intranasal administration. High protein binding ( approximately 99%) and rapid first-pass clearance further reduce systemic exposure to the drug. Studies up to 1 year have shown that intranasal ciclesonide does not cause cortisol suppression as monotherapy and does not have an additive effect on the hypothalamic-pituitary-adrenal axis function when administered in combination with inhaled corticosteroids. The efficacy of ciclesonide, 200 microg/day, has been shown in pediatric, adolescent, and adult patients with moderate to severe seasonal AR and perennial AR treated for up to 1 year. Additionally, environmental exposure unit studies have established an onset of action as early as 1 hour after administration. Ciclesonide nasal spray has also been shown to have an acceptable safety profile in patients with AR as young as 2 years of age. Thus, intranasal ciclesonide appears to provide an additional effective treatment option for patients with AR.

Allergies in Latin America is the first cross-national survey that describes the symptoms, impact, and treatment of nasal allergies (NAs) in individuals >or=4 years old in Latin America (LA). In total, 22,012 households across the Latin American countries of Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, and Venezuela were screened for children, adolescents, and adults with a diagnosis of NA and either symptoms or treatment in the past 12 months. A total of 1088 adults and 457 children and adolescents were included and the sample was probability based to ensure valid statistical inference to the population. Approximately 7% of the LA population was diagnosed with NAs with two of three respondents stating that their allergies were seasonal or intermittent in nature. A general practice physician or otolaryngologist diagnosed the majority of individuals surveyed. Nasal congestion was the most common and bothersome symptom of NAs. Sufferers indicated that their symptoms affected productivity and sleep and had a negative impact on quality of life. Two-thirds of patients reported taking some type of medication for their NAs, with a roughly equal percentage of patients reporting taking over-the-counter versus prescription medications. Changing medications was most commonly done in those reporting inadequate efficacy. The most common reasons cited for dissatisfaction with current medications were related to inadequate effectiveness, effectiveness wearing off with chronic use, failure to provide 24-hour relief, and bothersome side effects (e.g., unpleasant taste and retrograde drainage into the esophagus). Findings from this cross-national survey on NAs have confirmed a high prevalence of physician-diagnosed NAs and a considerable negative impact on daily quality of life and work productivity as well as substantial disease management challenges in LA. Through identification of disease impact on the LA population and further defining treatment gaps, clinicians in LA may better understand and treat NAs, thus leading to improvements in overall patient satisfaction and quality of life.

A complex interplay of genetic predisposition and environmental influences results in the clinical picture of allergic asthma. This article addresses recently identified genetic markers and environmental factors that contribute to disease development in asthma. Focus is placed on aspects of the innate immune system, including inherent properties of allergens, the active role of airway epithelium, and the central importance of dendritic cells together with the pathophysiological processes in which these factors interact. Implications of these processes for asthma therapy, with a focus on anti-IgE treatment are also discussed.

Omalizumab is a novel therapy approved for treating patients with moderate to severe persistent allergic asthma with a serum IgE ranging from 30 to 700 IU/mL. We examined the efficacy of omalizumab as a treatment for IgE-mediated food allergy. An Institutional Review Board-approved prospective pilot study was performed to assess the efficacy of omalizumab in 22 patients with persistent asthma and concomitant IgE-mediated food allergy. All patients showed skin test positivity to foods and experienced allergic food reactions based on history. Patients were interviewed on unintentional and/or unauthorized exposures to sensitized foods. Thirteen female and nine male patients (range, 4-66 years old; mean, 38 years) were evaluated in a private practice setting. Mean IgE level was 1120.74 IU/mL. Sensitized allergens included fish, shellfish, peanuts, tree nuts, egg, soybean, and wheat. All 22 (100%) patients maintained significant improvement as shown by a decrease/lack of clinical symptoms on reexposure to sensitized foods. Clinical improvement by the sixth dosage of omalizumab (150-300 mg q. 2-4 weeks) was noted by history and physical examination. Eight patients noted a decrease in their food-induced atopic dermatitis, 13 patients noted a decrease in their food-induced asthma symptoms, 3 patients noted a decrease in their food-induced urticaria, 6 patients noted a decrease in their food-induced rhinosinusitis symptoms, and 9 patients showed efficacy for angioedema and/or anaphylaxis. While treating asthma patients with omalizumab, patients subjectively observed a reduction in their concomitant IgE-mediated food allergy symptoms.

Limited information exists comparing fluticasone propionate/salmeterol combination (FSC) versus montelukast (MON) in patients with coexistent asthma and allergic rhinitis. The purpose of this study was to compare the addition of MON to patients receiving FSC on asthma control while experiencing asthma and allergy symptoms. Additionally, the effect of fluticasone propionate aqueous nasal spray (FPANS) and MON were assessed in allergic rhinitis control. Symptomatic patients (n = 1385) with asthma and seasonal allergic rhinitis were randomized to receive FSC, 100/50 micrograms twice daily; FSC twice daily + FPANS, 200 micrograms once daily; FSC twice daily + MON, 10 mg once daily; or MON once daily for 4 weeks during the allergy pollen season. Patients recorded peak expiratory flow, rescue albuterol use, and asthma and rhinitis symptoms. No additional improvements in overall asthma control were seen when MON was added to FSC. Treatment with FSC produced significant (p < 0.001) improvements in all clinical and patient-reported measures versus MON. FSC + FPANS was superior to FSC + MON (p < or = 0.001) in improving daytime and nighttime total nasal symptom scores. Adverse events were similar. In patients with asthma and allergic rhinitis, adding MON to FSC provided no additional benefit in asthma control. FSC resulted in superior improvement in asthma control compared with MON. FPANS also provided superior nasal symptom control versus MON in allergic patients treated with FSC for asthma. Optimal disease control in patients with asthma and allergic rhinitis should be achieved by the most effective therapy directed toward each disease component.

With cholinergic urticaria (ChU), the ultimate diagnosis often depends on the demonstration of characteristic urticaria by appropriate provocation. Several treatment options may be helpful but traditional options (antihistamines, leukotriene inhibitors, and immunosuppressives) may be exhausted by the refractory ChU patient. Here, we describe such a case. Demonstration of immediate hypersensitivity to autologous sweat skin testing (ASwST) may provide a rationale for use of omalizumab (Xolair, Genentech Novartis, South San Francisco, CA). Patients with severe ChU may have difficulty producing sufficient quantities of sweat for ASwST given that the very effort that produces the sample exacerbates ChU. Generation of sweat by iontophoresis with pilocarpine nitrate can be performed at many large medical centers. The procedure is simple, safe, and produces varying amounts of sweat depending on the individual. This sweat can then be used for ASwST. Our patient had a positive ASwST with appropriate positive and negative controls. Our testing methods were validated by negative ASwST, saline control, and positive histamine control in a nonatopic, nonurticarial control patient. By the patient's second injection of omalizumab, her quality of life score was significantly improved, as were her daily medication scores and exercise tolerance. We describe the first case of a patient with severe refractory ChU who had a positive ASwST by a novel collection method who has been successfully treated with omalizumab. We present a novel tool for the evaluation and demonstration of sweat-specific IgE in ChU patients who are unable to provide sweat by more traditional means.

Inhaled corticosteroids (ICSs) are considered the most effective therapy currently available for persistent asthma and is the guideline-recommended first-line treatment for all patients requiring controller medication; however, the potential for oropharyngeal and systemic adverse events can be a barrier to their use. Ciclesonide (CIC) is a new ICS with a unique pharmacologic profile that may confer a favorable safety profile. This study was designed to provide a comprehensive review of currently available safety data for CIC in adults and children with asthma of all severities. The literature was reviewed for all clinical trials with CIC reporting safety results (no date restrictions; English language only). Clinical trials with CIC in children and adults showed a very low occurrence of oropharyngeal adverse events (including oral candidiasis, pharyngitis, and hoarseness) and minimal systemic activity. In particular, no clinically relevant effect on cortisol levels was observed, compared with placebo or active comparators, even with high-dose CIC treatment (up to 1280 microg/day) and in asthma of all severities. Furthermore, there was no clinically relevant effect of CIC treatment on growth in children with mild asthma compared with placebo. The favorable safety profile of CIC may allay patient and physician concern regarding ICS when using this agent. Guideline-recommended use of ICS medications may help optimize treatment outcomes in asthma.

Onset of action is recognized as an important pharmacologic property of allergic rhinitis (AR) medications. This study was designed to evaluate the onset of action of loratadine/montelukast (L/M; 10 mg/10 mg) versus placebo in subjects with ragweed-induced seasonal AR (SAR). A single-center, double-blind, parallel-group study of ragweed-sensitive AR subjects (n = 310) was performed in the Environmental Exposure Unit (EEU). Subjects were exposed to ragweed pollen in the EEU and symptoms were recorded at 30, 60, 90, and 120 minutes before a single dose of L/M or placebo. After dosing, symptoms were recorded for 4 hours, at 15-minute intervals for the first 2 hours and at 30-minute intervals for the final 2 hours. The primary end point was time to onset of action of L/M, defined as the first time point at which the mean change from baseline in total symptom score (TSS) for L/M became and remained significantly better than placebo. Secondary end points included nasal congestion scores and peak nasal inspiratory flow (PNIF). The onset of action of L/M for TSS was 1 hour and 15 minutes (p = 0.005 versus placebo). L/M reduced nasal congestion as indicated by significant improvements in both the nasal congestion score (p = 0.011) and the PNIF measurements (p = 0.007) within 1 hour and 15 minutes postdose. The incidence of treatment-emergent adverse events was similar between groups. The onset of action after treatment with L/M was 1 hour and 15 minutes for TSS, as well as nasal congestion. L/M was well tolerated.

Inhaled corticosteroids (ICSs) are a first-line treatment for persistent asthma. This study was designed to compare the efficacy and safety of ciclesonide (CIC) in subjects with mild-to-moderate persistent asthma not using an ICS. This was a multicenter, double-blind, parallel-group, placebo-controlled, 16-week study in subjects who were > or =12 years old, had a > or =6-month history of persistent asthma, a forced expiratory volume in 1 second (FEV(1)) of > or =60 to < or =85% predicted, and who were not using an ICS < or =30 days before study entry. Subjects were randomized to CIC, 80 microg twice daily (CIC80 b.i.d.; n = 170); CIC, 160 microg once daily in the morning (CIC160 q.d. in the A.M.; n = 173); CIC80 b.i.d. for 4 weeks followed by CIC160 q.d. for 12 weeks (CIC80 b.i.d./CIC160 q.d.; n = 171); or placebo (n = 177). Change in FEV(1) from baseline to the average of weeks 12 and 16 (primary end point) and to week 16, A.M. peak expiratory flow, rescue albuterol use, nighttime awakenings, asthma symptom scores, and safety were evaluated. FEV(1) improved from baseline to the average of weeks 12 and 16 for CIC80 b.i.d. (+0.30L; p < 0.0001), CIC160q.d. (+0.19L; p < 0.0001), CIC80 b.i.d./CIC160 q.d. (+0.19L; p < 0.0001), and placebo (+0.06L; p = 0.0251); improvement was greatest for CIC80 b.i.d. (p < 0.01). At week 16, all CIC treatments significantly improved FEV(1) and A.M. PEF from baseline (p < 0.0001) and compared with placebo (p < or = 0.015). All treatments reduced albuterol use and nighttime awakenings and improved asthma symptom scores (p < or = 0.05 versus baseline); these improvements were greater for CIC80 b.i.d. than for placebo (p < 0.01). The incidence of adverse events was similar among treatment groups (range, 53-58%). In this study, CIC80 b.i.d. improved disease control in subjects with mild-to-moderate persistent asthma not using an ICS and provided greater improvements than CIC160 q.d.

Inhaled corticosteroids (ICSs) are recommended as first-line treatment for persistent asthma. This study was designed to evaluate the ability of ciclesonide (CIC) in subjects with stable asthma previously receiving another ICS or ICS/long-acting beta(2)-agonist (LABA) to maintain asthma disease control. In this 12-week, multicenter, double-blind, parallel-group study, subjects aged > or =12 years with stable mild-to-moderate persistent asthma were switched at randomization from an ICS or ICS/LABA to CIC, 80 microg twice daily (CIC80 b.i.d.; n = 149); CIC, 160 microg once daily (CIC160 q.d.; n = 150); or placebo (n = 147). Change in forced expiratory volume in 1 second (FEV(1); primary end point), morning peak expiratory flow (PEF), rescue albuterol use, total asthma symptom score, nighttime awakenings, and safety were evaluated. FEV(1) improved from baseline to week 12 after CIC80 b.i.d. treatment (+0.07 L; p = 0.0232), and was maintained after CIC160 q.d. (+0.01 L; p = 0.6217). FEV(1) declined from baseline after placebo (-0.12 L; p < 0.0001) and significantly versus CIC treatments (p < 0.001). At week 12, morning PEF maintained baseline values after CIC80 b.i.d. (-4.43 L/minute; p = 0.1272) and decreased after CIC160 q.d. (-5.77 L/minute; p = 0.0490) and placebo (-12.82 L/minute; p < 0.0001); the difference between CIC80 b.i.d. and placebo was significant (p = 0.035). Baseline albuterol use, total daily asthma score, and nighttime awakenings were maintained after CIC treatments (p > 0.25), but increased after placebo (p < or = 0.002); the difference between CIC80 b.i.d. and placebo was significant (p < 0.02). Incidence of adverse events was similar among treatment groups (range, 52.0-57.9%). In this study, CIC80 b.i.d. maintained asthma control in subjects with stable mild-to-moderate asthma previously treated with ICS or ICS/LABA, was well tolerated, and, in general, was better than CIC160 q.d. in maintaining disease control.

Allergic rhinitis (AR) affects approximately 500 million people worldwide, and prevalence is increasing. Second-generation nonsedating antihistamines are first-line treatments for seasonal AR (SAR). This study was performed to evaluate early SAR symptom relief with second-generation antihistamines through a retrospective analysis of previously published data. In this study, 835 subjects aged 12-60 years with a > or = 2-year history of SAR were randomized to receive loratadine, 10 mg, once daily; fexofenadine, 60 mg, twice daily; or placebo for 7 days. Each subject recorded the severity of five symptoms of SAR on a scale of 0-3. This primary post hoc efficacy analysis was the mean change from baseline in daily average A.M./P.M. reflective and instantaneous total symptom score (TSS) on days 2 and 3. Significantly greater mean reductions from baseline were shown with loratadine compared with fexofenadine in average A.M./P.M. reflective TSS on days 2 (-3.51 versus -2.84, respectively; p < 0.002) and 3 (-3.80 versus -3.19, respectively; p = 0.007) and in average A.M./P.M. instantaneous TSS on day 3 (-3.68 versus -3.15, respectively; p = 0.022). Similar results were noted in average A.M./P.M. reflective and instantaneous total nasal symptom scores and for 10 of 20 individual symptom time points (p < 0.05). Loratadine was significantly more effective than placebo for all time points (p < 0.001). Early, sustained symptom relief was seen with loratadine, suggesting that it may be more effective for treating SAR symptoms.

Treatment of patients with allergic rhinitis and asthma involves securing accurate diagnoses, avoidance measures, pharmacotherapy, and in some patients allergen immunotherapy, with consideration of immunomodulator therapy. At least 20% of patients with asthma have evidence of gastroesophageal reflux (GERD) and others have laryngeal pharyngeal reflux (LPR) also referred to as supraesophageal reflux (SERD) or "atypical reflux." The scientific foundation of subcutaneous allergen immunotherapy (SCIT) includes generation of T-reg cells, which generate IL-10 and TGF-beta and suppress T(H2) and T(H1) lymphocyte responses. SCIT alone or even to a greater degree with omalizumab has been shown to reduce the extent of "facilitated allergen presentation" of allergen-IgE complexes binding to B lymphocytes, with the implication of reducing the extent of allergen presentation by B lymphocytes to T lymphocytes. In viewing the concept of the unified airway and the multiple approaches required for optimal patient care, asthma should be considered as a syndrome, which includes the concomitant conditions of allergic rhinitis and GERD (SERD or LPR) with the possibility of intermittent or chronic rhinosinusitis.