An Approach to the Office-Based Practice of Food Oral Immunotherapy.

Oral immunotherapy (OIT) provides an active treatment option for patients with food allergies. OIT may improve quality of life and raise the threshold at which a patient with food allergy may react to an allergen, but it is a rigorous therapy that requires a high degree of commitment by the clinician, patients, and families. Recent guidelines from the Canadian Society for Allergy and Clinical Immunology have provided a framework for the ethical, evidence-based, and patient-oriented clinical practice of OIT, and the European Academy of Allergy, Asthma, and Immunology guidelines have also recommended that OIT can be used as a potential treatment. The recent Food and Drug Administration approval of an OIT pharmaceutical has accelerated the adoption of OIT. This review provides a summary of the recent Canadian Society for Allergy and Clinical Immunology guidelines and a consensus of practical experience of clinicians across the United States and Canada related to patient selection, office and staff preparation, the general OIT process, OIT-related reaction management, and treatment outcomes.

Continuous and Daily Oral Immunotherapy for Peanut Allergy: Results from a 2-Year Open-Label Follow-On Study.

BACKGROUND: The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. OBJECTIVE: ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. METHODS: Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non-daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. RESULTS: Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. CONCLUSIONS: Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.

Burden of Asthma and Role of 2.5 µg Tiotropium Respimat® as an Add-On Therapy: A Systematic Review of Phase 2/3 Trials.

INTRODUCTION: Tiotropium, a long-acting muscarinic antagonist, is approved for maintenance treatment of asthma in patients at least 6 years of age in the USA. We systematically reviewed published evidence on the efficacy and safety of 2.5 µg tiotropium Respimat® add-on therapy to inhaled corticosteroid (ICS) with or without additional controller medication(s) in children, adolescents, and adults with asthma. METHODS: We searched PubMed from inception until October 3, 2018, for phase 2 and 3 randomized controlled trials (RCTs) evaluating the effects of 2.5 µg tiotropium Respimat® on lung function parameters in patients with asthma. We extracted adjusted mean differences for lung function data and adverse events (AEs) from relevant articles. RESULTS: Overall, 11 RCTs (three phase 2 and eight phase 3 studies) including 3244 patients (2.5 µg tiotropium Respimat®, n = 1642; placebo, n = 1602) met the predefined inclusion criteria. Once-daily 2.5 µg tiotropium Respimat® improved lung function parameters, including peak and trough forced expiratory volume in 1 s and peak and trough forced vital capacity, versus placebo. Overall, the safety profile of 2.5 µg tiotropium Respimat® was comparable to that of placebo, with the most commonly reported AEs being asthma worsening, reduction in peak expiratory rate, nasopharyngitis, and respiratory tract infections. CONCLUSION: On the basis of the results of phase 2 and 3 studies, 2.5 µg tiotropium Respimat® as add-on to ICS therapy was safe and associated with consistent improvements in lung function in patients with asthma of varying severities across different age groups. FUNDING: Development of the manuscript was funded by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI).

Tiotropium in asthma: From bench to bedside.

OBJECTIVE: Tiotropium is a long-acting muscarinic antagonist approved for maintenance treatment of asthma in children, adolescents, and adults in the United States, and recommended as add-on treatment for uncontrolled asthma despite treatment with inhaled corticosteroids and/or long-acting beta-2 agonists. This review traces the journey of tiotropium from its historical origins through early preclinical testing to human clinical trials and real-life studies. DATA SOURCES: A search was performed in PubMed using search terms 'tiotropium' and 'asthma.' Relevant references cited in those articles were reviewed. STUDY SELECTIONS: English language articles published from December 2008-December 2018 were screened. Articles evaluating the efficacy, cost-effectiveness, real-life evidence, and steroid-sparing effect of tiotropium with inadequately controlled asthma were included. RESULTS: Anticholinergics have a long history of use in the treatment of obstructive airway diseases. Evidence indicates that tiotropium's mechanism of action consists of bronchodilation and diminished mucus secretion, with preclinical evidence suggesting an anti-inflammatory effect as well. Phase 2 and 3 clinical trials have demonstrated that tiotropium is efficacious and safe, resulting in significant improvements in lung function in adults, adolescents, and children across asthma severities. Emerging evidence suggests that add-on tiotropium might potentially enable reductions in inhaled corticosteroid dose in patients with uncontrolled asthma. Further, tiotropium is a cost-effective treatment option that is also effective in the clinical practice setting. CONCLUSIONS: An increasing body of evidence indicates that tiotropium can play a significant role in the treatment of patients with uncontrolled asthma.

Device mechanics and evaluation of inspiratory flow rate required of the beclomethasone dipropionate breath-actuated inhaler.

Background: Approximately 80% of patients with asthma and chronic obstructive pulmonary disease incorrectly use a metered-dose inhaler and, therefore, fail to obtain full benefit from their inhaler medication. Beclomethasone dipropionate (BDP) hydrofluoroalkane, an inhalation aerosol administered via a breath-actuated inhaler (BAI) has been designed to improve ease of use over press-and-breathe metered-dose inhalers by eliminating the need for hand-breath coordination. Objective: To present the mechanics of the BAI device, assess the minimum reliable inspiratory flow rate required to trigger an actuation, and evaluate if intended users can safely and effectively use the BDP BAI according to the instructions for use (IFU). Methods: Six random batches (three batches each of 40 µg and 80 µg) of 10 inhalers were evaluated for the minimum inspiratory flow rate required for actuation trigger. Each inhaler was tested for actuation at five flow rates: 12, 14, 16, 18, and 20 L/min. Simulated-use testing was conducted with 91 participants from six representative user groups in the United States to assess the use of a placebo-filled production-equivalent BDP BAI according to the IFU. Results: Across the 40-µg batches, 83% of the devices actuated at 16 L/min and 100% actuated at 18 and 20 L/min. For the 80-µg batches, 67% and 100% actuated at 18 L/min and 20 L/min, respectively. All the participants demonstrated successful use of the BDP BAI during the study session. Isolated safety-critical errors with the potential for no-dose delivery were recorded for 15 participants but were considered unrelated to the design of the IFU. Conclusion: The BDP BAI consistently triggered actuation at an airflow rate of 20 L/min and was successfully used based on guidance from the IFU only. This device provides an alternative for patients who find it difficult to use metered-dose inhaler devices correctly.

Tiotropium Is Efficacious in 6- to 17-Year-Olds with Asthma, Independent of T2 Phenotype.

BACKGROUND: Tiotropium add-on therapy has demonstrated efficacy and safety in 6- to 17-year-olds with symptomatic asthma despite treatment with inhaled corticosteroids (ICSs), with or without additional controllers. Pediatric patients often have a significant allergic component to their asthma. OBJECTIVE: To explore whether responses to tiotropium add-on were influenced by patients' type 2 status, assessed by serum IgE levels and blood eosinophil counts. METHODS: Data from 2 phase III trials in symptomatic moderate asthma (CanoTinA-asthma; RubaTinA-asthma) and 2 phase III trials in symptomatic severe asthma (VivaTinA-asthma; PensieTinA-asthma) were pooled by severity. Patients were treated with tiotropium 5 µg, tiotropium 2.5 µg, or placebo (2 puffs once daily via Respimat inhaler), as add-on to ICSs, with or without additional controllers. Modeling of efficacy outcomes was performed over the whole range of baseline IgE levels and blood eosinophil counts, and the treatment effect of the tiotropium doses was presented graphically. RESULTS: Improvements with tiotropium in peak FEV1 within 3 hours postdose, trough FEV1, forced expiratory flow at 25% to 75% of the pulmonary volume, and FEV1/forced vital capacity responses were generally consistent across the range of baseline IgE levels and blood eosinophil counts. Risk of exacerbations and improvement in Asthma Control Questionnaire responder rates with tiotropium were also largely independent of IgE levels or eosinophil counts. CONCLUSIONS: This exploratory analysis suggests that improvements with tiotropium as add-on to ICSs, with or without additional controllers, in 6- to 17-year-olds with symptomatic asthma do not vary according to systemic markers of T2 inflammation, namely, total IgE and blood eosinophil counts.

Step-up and step-down treatments for optimal asthma control in children and adolescents.

OBJECTIVE: To review therapeutic options for stepwise management of pediatric asthma in the context of this population's unique needs such as potential effects of asthma, treatments, or both on growth and psychosocial development, and caregiver involvement. DATA SOURCES AND STUDY SELECTION: We conducted PubMed searches to identify relevant articles then reviewed resultant articles, guidelines for asthma management in children, and articles from personal files. RESULTS: Stepwise management of asthma, similar to adults, is recommended for children in current global and US guidelines. Treatment may be stepped up or stepped down temporarily or long-term based on response over time. Inhaled corticosteroids remain the recommended treatment for persistent childhood asthma and any potential small effects on growth are considered relatively minor compared with their benefit. Controller medication options for patients <18 years old are limited, especially for Global Initiative for Asthma Steps 2-5. The long-acting antimuscarinic antagonist tiotropium (Steps 4/5, patients aged ≥12 years) and in certain circumstances (Step 5), anti-immunoglobulin E (aged ≥6 years) and interleukin-5 antibodies (aged ≥12 years) are newer treatment options. Tiotropium is indicated in the United States and Europe for patients ≥6 years old. Stepping down treatment, which is recommended but infrequently practiced, can maintain symptom control and minimize adverse events while substantially reducing costs. Patient education and better monitoring remain important for self-management and optimum outcomes. CONCLUSION: A need exists to target individual treatment goals for children with asthma by using step-up and step-down approaches to maximize treatment benefits and minimize potential adverse effects.

Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Benralizumab is a humanised, anti-interleukin 5 receptor α monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma. The objective of this trial was to assess the safety and efficacy of benralizumab for patients with mild to moderate, persistent asthma. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients aged 18-75 years, weighing at least 40 kg, and with a postbronchodilator reversibility in forced expiratory volume in 1 s (FEV1) of at least 12% at screening, from 52 clinical research centres in six countries. Patients must have been receiving either low- to medium-dosage inhaled corticosteroids (ICS) or low-dosage ICS plus long-acting ß2 agonist fixed-combination therapy at screening, had a morning prebronchodilator FEV1 of more than 50% to 90% predicted at screening, and had one or more of the following symptoms within the 7 days before randomisation: a daytime or night-time asthma symptom score of at least 1 for at least 2 days, rescue short-acting ß2 agonist use for at least 2 days, or night-time awakenings due to asthma for at least one night. We converted patients' ICS treatments to 180 µg or 200 µg budesonide dry powder inhaler twice daily for the entire duration of the study using the approved dosages in the patients' respective countries and randomly allocated them (1:1; stratified by blood eosinophil count [<300 cells per µL vs ≥300 cells per µL] and region [USA vs the rest of the world]) with an interactive web-based voice response system to receive subcutaneous placebo or benralizumab 30 mg injections every 4 weeks for 12 weeks. All patients and investigators involved in patient treatment or clinical assessment and those assessing outcomes were masked to treatment allocation. The primary endpoint was change from baseline prebronchodilator FEV1 at week 12. Efficacy analyses used an intention to treat approach. This trial is registered with ClinicalTrials.gov, number NCT02322775. FINDINGS: Between Feb 2, 2015, and April 24, 2015, we enrolled 351 patients, with 211 (60%) randomly assigned (105 [50%] to placebo and 106 [50%] to benralizumab). Benralizumab resulted in an 80 mL (95% CI 0-150; p=0·04) greater improvement (least-squares mean difference) in prebronchodilator FEV1 after 12 weeks than did placebo (placebo group: 2246 mL [SD 768] at baseline vs 2261 mL [796] at week 12, change from baseline of 0 mL; benralizumab group: 2248 mL [606] vs 2310 mL [670], 70 mL). 44 (42%) patients in the benralizumab group had adverse events compared with 49 (47%) in the placebo group. The most common adverse events for both groups were nasopharyngitis (eight [8%] patients in each group) and upper respiratory tract infections (five [5%] patients in each group). Serious adverse events occurred in two (2%) patients each in the benralizumab (pancytopenia and a suicide attempt, both considered unrelated to treatment) and placebo (cervix carcinoma and colon adenoma) groups. INTERPRETATION: This study suggests that active and modifiable disease processes might be ongoing in patients with mild to moderate, persistent asthma receiving ICS. Although the lung function improvement observed does not warrant use of benralizumab in this population because it did not reach the minimum clinically important difference of 10%, further studies to assess this finding should be considered. FUNDING: AstraZeneca.

A 6-month safety and efficacy study of fluticasone propionate and fluticasone propionate/salmeterol multidose dry powder inhalers in persistent asthma.

BACKGROUND: A novel multidose dry powder inhaler (MDPI) that is breath actuated, easy, and intuitive to use has been developed for administering fluticasone propionate (Fp) and Fp/salmeterol (FS). OBJECTIVE: To assess the safety and efficacy of Fp MDPI versus Fp hydrofluoroalkane (HFA) and FS MDPI versus FS dry-powder inhaler (DPI). METHODS: This phase III, 26-week, open-label, active drug-controlled study enrolled subjects ≥12 years old with persistent asthma. Based on entry controller medication (inhaled corticosteroid [ICS] or ICS/long-acting beta-agonist), the subjects were randomized to twice-daily mid-strength Fp MDPI 100 µg or Fp HFA 220 µg, high-strength Fp MDPI 200 µg or Fp HFA 440 µg, mid-strength FS MDPI 100/12.5 µg or FS DPI 250/50 µg, or high-strength FS MDPI 200/12.5 µg or FS DPI 500/50 µg in a 3:1 MDPI to Fp HFA or FS DPI ratio. Safety and efficacy were assessed by adverse events (AE) and pulmonary function and asthma symptoms, respectively. RESULTS: A total of 674 subjects were randomized. The AE incidence was similar across treatment groups (upper respiratory tract infections, sinusitis, and nasopharyngitis were most frequent). A higher percentage of subjects in the Fp HFA 440 µg and FS DPI 500/50 µg groups had oral candidiasis versus those who received Fp MDPI 200 µg or FS MDPI 200/12.5 µg, respectively. Serious AEs were similar between the treatments, with no unexpected findings. The incidence of asthma exacerbations was low and generally similar between the groups. Noninferiority was established for all Fp MDPI and FS MDPI doses compared with Fp HFA and FS DPI, respectively, for forced expiratory volume in 1 second. Changes in peak expiratory flow, rescue albuterol use, and symptoms were similar between treatments. CONCLUSION: The safety and efficacy profiles of Fp MDPI and FS MDPI administered at lower doses were generally comparable with those of Fp HFA and FS DPI, respectively, after 26 weeks of treatment.The ClinicalTrials.gov identifier is NCT02175771.

Beclomethasone HFA for the treatment of allergic rhinitis.

INTRODUCTION: Allergic rhinitis (AR) is a common chronic disorder, affecting 10 -30% of populations. AR has significant morbidity and expense. AR patients treat themselves with over-the-counter medications. However the usual H1 antihistamines are often inadequate. Intranasal corticosteroids effectively diminish AR symptoms. Beclomethasonedipropionate (BDP) was reported to effectively treat adults and children with AR. BDP was a chlorofluorocarbon (CFC) propellant pressurized metered dose inhaler (pMDI). Subsequently BDP appeared in an aqueous format. Some patients preferred the dryer sensation of pMDI to aqueous formulations. The protocol of Montréal, removed CFC devices from medical practice. The remaining intranasal steroids were in aqueous format. Many patients did not like the sensory perceptions using liquids intranasal. They were unlikely to be compliant. BDP hydrofluoroalkanepMDI (BDP HFA) was developed. AREAS COVERED: The need of active treatment of AR will be reviewed. Chemistry, pharmacokinetics and pharmacodynamics of BDP HFA will be presented. Clinical efficacy studies and safety data which led to the approval of BDP for use in adults and children will be reviewed. EXPERT OPINION: BDP HFA is an option to treat AR, demonstrating a favorable therapeutic index in large double-blind placebo-controlled studies. BDP HFA appeals to select AR patients.

Oral immunotherapy for peanut allergy: multipractice experience with epinephrine-treated reactions.

BACKGROUND: Peanut allergy creates the risk of life-threatening anaphylaxis that can disrupt psychosocial development and family life. The avoidance management strategy often fails to prevent anaphylaxis and may contribute to social dysfunction. Peanut oral immunotherapy may address these problems, but there are safety concerns regarding implementation in clinical practice. OBJECTIVE: The purpose of this report is to communicate observations about the frequency of epinephrine-treated reactions during peanut oral immunotherapy in 5 different allergy/immunology practices. METHODS: Retrospective chart review of peanut oral immunotherapy performed in 5 clinical allergy practices. RESULTS: A total of 352 treated patients received 240,351 doses of peanut, peanut butter, or peanut flour, and experienced 95 reactions that were treated with epinephrine. Only 3 patients received 2 doses of epinephrine, and no patient required more intensive treatment. A total of 298 patients achieved the target maintenance dose for a success rate of 85%. CONCLUSION: Peanut oral immunotherapy carries a risk of systemic reactions. In the context of oral immunotherapy, those reactions were recognized and treated promptly. Peanut oral immunotherapy may be a suitable therapy for patients managed by qualified allergists/immunologists.

Efficacy and safety of beclomethasone dipropionate nasal aerosol in pediatric patients with seasonal allergic rhinitis.

BACKGROUND: Aerosolized intranasal corticosteroid formulations are desirable for many patients with allergic rhinitis (AR), especially children, who wish to avoid the "wet feeling" and "drip down the throat" associated with aqueous formulations. Beclomethasone dipropionate (BDP) hydrofluoroalkane nasal aerosol has been shown to be safe and effective in adolescents and adults with AR. OBJECTIVE: To evaluate the efficacy and safety of BDP nasal aerosol in pediatric patients with moderate to severe seasonal AR. METHODS: In this double-blinded, placebo-controlled study, children (6-11 years of age) with seasonal AR were randomized to once-daily treatment with BDP nasal aerosol 80 µg (n = 239) or 160 µg (n = 242) or placebo (n = 234). The primary end point was change from baseline in average morning and evening reflective total nasal symptom score over the 2-week treatment period. RESULTS: Treatment with BDP nasal aerosol showed significantly greater improvements in average morning and evening reflective total nasal symptom score vs placebo (80 µg, -0.71; 160 µg, -0.76; P < .001 for the 2 comparisons). Similarly, significantly greater improvements in average morning and evening instantaneous total nasal symptom score were seen with BDP nasal aerosol vs placebo (80 µg, -0.63; 160 µg, -0.73; P < .001 for the 2 comparisons). The incidence of adverse events from BDP nasal aerosol was comparable to that from placebo. CONCLUSION: BDP nasal aerosol (80 or 160 µg/d) provided significant and clinically meaningful nasal symptom relief and an established overall safety profile similar to that of placebo, suggesting that it is an effective and well-tolerated treatment option for pediatric patients with moderate to severe seasonal AR. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT012073190.

Oral immunotherapy for peanut allergy in clinical practice is ready.

Oral immunotherapy (OIT) for peanut allergy is ready for clinical allergy practice. Some physicians, particularly at academic centers, believe that OIT is not ready for clinical practice. The shortcomings of the present general recommendations of food avoidance and provision of epinephrine autoinjectors for a select number of patients demand a different approach. In peanut-allergic patients, the rate of accidental reactions is ~10% annually. Between 1 and 2% of these reactions require epinephrine or emergency department visits. Food allergy and peanut allergy, specifically, have a large negative impact on the quality of life (QOL) for patients and their families, which can be psychosocially debilitating. These decreases in health-related QOL continue into adulthood. There is only an ~20% chance of spontaneous remission in peanut allergy. Given this climate, three private allergy practices have begun providing OIT to 150 patients with peanut anaphylaxis. One hundred eleven (74%) patients were able to tolerate eight peanuts (8 g, ~2 g of protein). During outpatient dosing, epinephrine was used at a rate of 8 per 10,000 doses. To date, there have been no long-term (>24-36 months) unexpected reactions. OIT decreases risk and in one study, conducted in a practice setting, it was shown to improve QOL. OIT is a meaningful clinical procedure that can help our patients.

Efficacy and safety of fluticasone/formoterol combination therapy in patients with moderate-to-severe asthma.

BACKGROUND: The inhaled corticosteroid, fluticasone propionate, and the long-acting ß(2)-adrenergic agonist, formoterol fumarate, are both highly effective treatments for bronchial asthma. This study (NCT00393952/EudraCT number: 2006-005989-39) compared the efficacy and safety of fluticasone/formoterol combination therapy (flutiform(®); 250/10 µg) administered twice daily (b.i.d.) via a single aerosol inhaler, with the individual components (fluticasone 250 µg b.i.d.; formoterol 10 µg b.i.d.), in adult and adolescent patients with moderate-to-severe asthma. METHODS: This was a 12-week, double-blind, randomised, parallel-group, multicentre, placebocontrolled phase 3 study. The co-primary efficacy endpoints were: i) the mean change in the forced expiratory volume in the first second (FEV(1)) from morning pre-dose at baseline to pre-dose at week 12 (fluticasone/formoterol 250/10 µg vs. formoterol), ii) the mean change in FEV(1) from morning pre-dose at baseline to 2 h post-dose at week 12 (fluticasone/formoterol 250/10 µg vs. fluticasone), and iii) the number of patients who discontinued prematurely due to lack of treatment efficacy (fluticasone/formoterol 250/10 µg vs. placebo). The secondary endpoints included measures of lung function, disease control, and asthma symptoms. Safety was assessed based on adverse events, vital signs, and clinical laboratory evaluations. RESULTS: Overall, 395 (70.9%) patients completed the study. Fluticasone/formoterol 250/10 µg b.i.d. was superior to the individual components and placebo for all three co-primary endpoints and demonstrated numerically greater improvements for multiple secondary efficacy analyses. Fluticasone/formoterol combination therapy had a good safety profile over the 12 weeks. CONCLUSION: Fluticasone/formoterol combination therapy will provide clinicians with an efficacious alternative treatment option for patients with moderate-to-severe asthma.

A valved holding chamber does not decrease the bronchodilator activity of budesonide-formoterol combination metered dose inhaler.

OBJECTIVE: Spacers and valved holding chambers (VHCs) were developed to facilitate using pressurized metered dose inhaler (pMDI) by patients who could not coordinate the actions required for successful pMDI use. There is little in vivo evidence about how VHC may affect the bronchodilation from combination drugs in pMDI. This study was to determine the effect, if any, of VHC on the bronchodilating actions of the pMDI budesonide/formoterol combination. METHODS: Sixteen adult asthmatic subjects with 15% or greater reversibility of forced expiratory volume in one second (FEV-1), 15 minutes after inhaling 180-360 µg of albuterol, participated. The study had a randomized crossover design with each subject using budesonide-formoterol pMDI as described in the product information one timeand on a second occasion using the pMDI with a VHC. Spirometry and impedance osscilometry were measured at baseline and repeatedly over a 12-hour period. This study was approved by IntegReview Institutional Review Board, Austin, TX, USA. The clinical trial number for this study was NCT 009-15538 (http://www.westernskymed.com). RESULTS: The area under the curve of FEV-1, the FEV-1, and the fraction FEV-1/FVC was similar over the 12-hour time frame with both methods. Resistance was not different at any time point. In both procedures, the onset of bronchodilation occurred rapidly within 3 to 5 minutes. CONCLUSIONS: In well-trained asthmatic subjects, both tested methods caused equivalent bronchodilation. This suggests a VHC itself has no deleterious effect on the bronchodilator activity in the combined drug. These results may not apply to patients who have coordination problems with the pMDI and further study is indicated.

A multiallergen and miniscreen can change primary care provider diagnosis and treatment of rhinitis.

BACKGROUND: A number of studies suggested that limited economical airborne allergy screening can successfully predict true respiratory allergy and be of use to primary care providers (PCPs) in improving the accuracy of their differential diagnosis and treatment of allergic rhinitis. More accurate diagnosis would lead to proper use of intranasal corticosteroids, intranasal antihistamines, and oral antihistamines. However, to date, there have been no reports of an actual application of the screens by PCPs. This study was designed to measure the potential impact of providing a limited multiallergen and miniscreen (MAMS) by in vitro allergy testing on PCP diagnosis and treatment of rhinitis, properly differentiating seasonal allergic rhinitis, perennial allergic rhinitis, vasomotor rhinitis, and mixed rhinitis. METHODS: Two hundred adult and adolescent patients who presented to PCPs for rhinitis symptoms were enrolled from July to November of 2007. They signed informed consent and a serum specimen for MAMS was obtained. The PCPs answered a questionnaire concerning their diagnosis and treatment before and after the MAMS results were revealed to the PCP. RESULTS: The PCPs changed or modified the original diagnosis in 139 of 200 patients. Originally, 182 subjects had an allergic rhinitis diagnosis. After the results of the MAMS were known, 113 continued with an allergic rhinitis diagnosis. Vasomotor or nonallergic rhinitis diagnoses increased from 18 to 87 cases. CONCLUSION: Use of MAMS can help PCPs make a more accurate diagnosis and offer better therapy to patients with rhinitis.

Efficacy of budesonide/formoterol pressurized metered-dose inhaler versus budesonide pressurized metered-dose inhaler alone in Hispanic adults and adolescents with asthma: a randomized, controlled trial.

BACKGROUND: Few clinical trials in asthma have focused on Hispanic populations. OBJECTIVE: To compare the efficacy and safety of budesonide/formoterol (BUD/FM) with BUD in an ethnically diverse group of Hispanic participants with asthma previously treated with inhaled corticosteroids (ICS). METHODS: This 12-week, randomized, double-blind, active-controlled study (NCT00419757) was designed to enroll Hispanic participants (self-reported) (≥12 years of age) with moderate to severe asthma requiring medium- to high-dose ICS. After a 2-week run-in period (low-dose BUD pressurized metered-dose inhaler [pMDI] 80 µg × 2 inhalations [160 µg] twice daily), participants with a symptom score greater than 0 (scale: 0-3) on 3 or more of 7 run-in days and forced expiratory volume in 1 second (FEV(1)) 45%-85% predicted were randomized to BUD/FM pMDI 160/4.5 µg × 2 inhalations (320/9 µg) twice daily or BUD pMDI 160 µg × 2 inhalations (320 µg) twice daily. RESULTS: Randomized participants (n = 127 BUD/FM; n = 123 BUD) were predominately Mexican (51%) or Puerto Rican (21%). During low-dose ICS run-in, the mean symptom score was 1.0; however, mean predose FEV(1) improved (2.10-2.21 L). During randomized treatment, small, but not statistically significant, improvements favored BUD/FM vs BUD (am peak expiratory flow [PEF; primary efficacy variable] 25.4 vs 19.9 L/min; pm PEF 20.6 vs 15.8 L/min; predose FEV(1) 0.16 vs 0.11 L; rescue medication use -0.7 vs -0.6 inhalations/d). Most adverse events were mild or moderate in intensity. CONCLUSIONS: Improvement in clinically relevant control end points occurred in both BUD/FM and BUD groups; both treatments were well tolerated in this Hispanic asthma population but were not significantly differentiated.