The nomenclature proposed in the October 2003 report of the Nomenclature Review Committee of the World Allergy Organization is an update of the European Academy of Allergology and Clinical Immunology ...Revised Nomenclature for Allergy Position Statement published in 2001. The nomenclature can be used independently of target organ or patient age group and is based on the mechanisms that initiate and mediate allergic reactions. It is assumed that as knowledge about basic causes and mechanisms improves, the nomenclature will need further review.
Background
Anti‐IgE (omalizumab) has been used for the treatment of moderate‐to‐severe asthma that is not controlled by inhaled steroids. Despite its success, it does not always provide patients with ...significant clinical benefits.
Objective
To investigate the transcriptional variations between omalizumab responders and non‐responders and to study the mechanisms of action of omalizumab.
Methods
The whole blood transcriptomes of moderate‐to‐severe adult asthma patients (N = 45:34 responders and 11 non‐responders) were analysed over the course of omalizumab treatment. Non‐asthmatic healthy controls (N = 17) were used as controls.
Results
Transcriptome variations between responders and non‐responders were identified using the genes significant (FDR < 0.05) in at least one comparison of each patient response status and time point compared with control subjects. Using gene ontology and network analysis, eight clusters of genes were identified. Longitudinal analyses of individual clusters revealed that responders could maintain changes induced with omalizumab treatment and become more similar to the control subjects, while non‐responders tend to remain more similar to their pre‐treatment baseline. Further analysis of an inflammatory gene cluster revealed that genes associated with neutrophil/eosinophil activities were up‐regulated in non‐responders and, more importantly, omalizumab did not significantly alter their expression levels. The application of modular analysis supported our findings and further revealed variations between responders and non‐responders.
Conclusion and Clinical Relevance
This study provides not only transcriptional variations between omalizumab responders and non‐responders, but also molecular insights for controlling asthma by omalizumab.
MK-3641 is a short ragweed sublingual tablet under investigation for immunotherapy of ragweed pollen-induced allergic rhinitis.
To characterize the safety and tolerability of a ragweed sublingual ...tablet (Merck/ALK-Abelló) in ragweed-allergic adults with or without conjunctivitis.
Data from 4 randomized, double-blinded, placebo-controlled trials of MK-3641 (2 28-day and 2 52-week trials) were evaluated. Pooled analyses examined short-term safety over 28 days from all 4 trials and long-term safety from the 52-week trials.
Across all studies, 757, 198, 454, and 1,058 subjects were randomized to placebo or 1.5, 6, or 12 Amb a 1-U of MK-3641, respectively. Treatment-related adverse events were more frequent in the 6- and 12-Amb a 1-U MK-3641 groups than in the placebo group and were primarily local application-site reactions occurring in the first few days of treatment. There was no treatment-associated loss of asthma control or worsening of asthma associated with treatment. No swellings led to airway obstruction or respiratory compromise. No treatment-related anaphylactic shock, life-threatening, or serious treatment-related adverse events were reported for any MK-3641 dose. Of the 1,707 MK-3641-treated subjects, 1 systemic (anaphylactic) reaction was reported (0.06%). The 52-week long-term assessment was generally similar to the safety profile based on the 28-day assessment.
MK-3641 doses up to and including 12 Amb a 1-U were well tolerated, with no unexpected safety findings. Sublingual immunotherapy risks such as worsening asthma or airway swellings that could cause airway obstruction were not observed. Systemic reactions and use of epinephrine were uncommon. In these studies, after the first dose was administered in a health care setting, self-administration was well tolerated.
clinicaltrials.gov Identifiers: NCT01469182, NCT00783198, NCT00770315, and NCT00978029.
Negative binomial regression analyses were used for HRU; Generalized Linear Models with log-link for healthcare expenditures; and logistic or ordered logistic regression for health status ...questionnaires.
Frequent exacerbations are associated with greater FEV
decline in patients with asthma. The effect of omalizumab versus placebo on lung function in patients experiencing asthma exacerbations has not ...been previously examined.
To evaluate the relationship between postbaseline (treatment phase) exacerbation status and lung function decline in children, adolescents, and adults treated with omalizumab versus placebo using data from 3 pediatric and adolescent/adult studies.
Changes in percent predicted FEV
(ppFEV
) and FEV
by treatment (omalizumab/placebo) and postbaseline exacerbation status (exacerbators/nonexacerbators) were assessed in patients aged 6 to 11 years (IA05, n = 576) and 12 to 75 years (EXTRA/INNOVATE pooled, n = 1202). Pediatric patients were examined at treatment weeks 12, 24, 28, 40, and 52, and adolescent/adult data at weeks 4, 12, 20, and 28.
Omalizumab-treated patients experienced larger increases in ppFEV
and FEV
compared with placebo-treated patients in the pediatric and pooled adolescent/adult populations. The response was observed in pediatric exacerbators, with significantly larger increases in ppFEV
and FEV
at week 12 (mean difference 95% CI, 4.11% 0.93%-7.30%, P = .011 for ppFEV
; 80 10-140 mL, P = .017 for FEV
) and week 28 (mean difference 95% CI, 3.65% 0.11%-7.19%, P = .043 for ppFEV
; 100 30-170 mL, P = .007 for FEV
). In the adolescent/adult population, both exacerbators and nonexacerbators derived similar benefit with omalizumab compared with placebo.
Findings from this post hoc analysis suggest that omalizumab may confer some protection against lung function decline among patients who experienced exacerbations during treatment.
Background Mometasone furoate nasal spray (MFNS), a potent intranasal corticosteroid with proved efficacy in relieving nasal allergic rhinitis symptoms, has demonstrated effectiveness in improving ...ocular symptoms associated with seasonal allergic rhinitis (SAR) in retrospective analyses. Objective We sought to evaluate prospectively the efficacy of MFNS in reducing total ocular symptom scores (TOSSs) and individual ocular symptoms in subjects with SAR. Methods Subjects 12 years or older (n = 429) with moderate-to-severe baseline symptoms were randomized to MFNS, 200 μg once daily, or placebo in this 15-day, double-blind, parallel-group study. Subjects evaluated morning instantaneous TOSSs and daily reflective TOSSs, total nasal symptom scores (TNSSs; both instantaneous TNSSs and reflective TNSSs, respectively), and individual ocular and nasal symptoms. Mean changes from baseline averaged over days 2 to 15 (instantaneous) and days 1 to 15 (reflective) were calculated. Quality of life was assessed by using the Rhinoconjunctivitis Quality of Life Questionnaire. Results MFNS treatment yielded significant reductions from baseline versus placebo in instantaneous TOSSs (−0.34, P = .026, coprimary end point), instantaneous TNSSs (−0.88, P < .001, coprimary end point), reflective TOSSs (−0.44, P = .005), and reflective TNSSs (−1.06, P < .001). Significant decreases in all individual reflective ocular symptoms and instantaneous eye itching/burning and eye watering/tearing were observed for MFNS versus placebo ( P < .05). Numeric improvements in instantaneous eye redness were seen but did not reach statistical significance. Improvements in Rhinoconjunctivitis Quality of Life Questionnaire total scores and individual symptom domains were achieved with MFNS treatment versus placebo ( P < .001). MFNS was well tolerated. Conclusion This prospective study demonstrates that MFNS significantly reduces ocular symptoms in subjects with SAR.
The American Academy of Otolaryngic Allergy (AAOA) convened an expert, multidisciplinary Working Group on Allergic Rhinitis to discuss patients' self-treatment behaviors and how health care providers ...approach and treat the condition. PROCEDURES AND DATA SOURCES: Co-moderators, who were chosen by the AAOA Board of Directors, were responsible for initial agenda development and selection of presenters and participants, based on their expertise in diagnosis and treatment of allergic rhinitis. Each presenter performed a literature search from which a presentation was developed, portions of which were utilized in developing this review article.
Allergic rhinitis is a common chronic condition that has a significant negative impact on general health, co-morbid illnesses, productivity, and quality of life. Treatment of allergic rhinitis includes avoidance of allergens, immunotherapy, and/or pharmacotherapy (ie, antihistamines, decongestants, corticosteroids, mast cell stabilizers, anti-leukotriene agents, anticholinergics). Despite abundant treatment options, 60% of all allergic rhinitis patients in an Asthma and Allergy Foundation of America survey responded that they are "very interested" in finding a new medication and 25% are "constantly" trying different medications to find one that "works." Those who were dissatisfied also said their health care provider does not understand their allergy treatment needs and does not take their allergy symptoms seriously. Dissatisfaction leads to decreased compliance and an increased reliance on multiple agents and over-the-counter products. Furthermore, a lack of effective communication between health care provider and patient leads to poor disease control, noncompliance, and unhappiness in a significant portion of patients.
Health care providers must gain a greater understanding of patient expectations to increase medication compliance and patient satisfaction and confidence.
Background: A recombinant humanized anti-IgE mAb, omalizumab, forms complexes with free IgE, blocking its interaction with mast cells and basophils; as a consequence, it might be effective in the ...treatment of asthma. Objective: The purpose of this study was to evaluate the efficacy and safety of omalizumab in the treatment of inhaled corticosteroid–dependent asthma. Methods: In this phase III, double-blinded, placebo-controlled trial, 525 subjects with severe allergic asthma requiring daily inhaled corticosteroids were randomized to receive placebo or omalizumab subcutaneously every 2 or 4 weeks, depending on baseline IgE level and body weight. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment and tapered during a further 12-week treatment period. Results: Omalizumab treatment resulted in significantly fewer asthma exacerbations per subject and in lower percentages of subjects experiencing an exacerbation than placebo treatment during the stable steroid phase (0.28 vs 0.54 P = .006 and 14.6% vs 23.3% P = .009, respectively) and during the steroid reduction phase (0.39 vs 0.66 P = .003 and 21.3% vs 32.3% P = .004, respectively). Beclomethasone dipropionate reduction was significantly greater with omalizumab treatment than with placebo (median 75% vs 50% P < .001), and beclomethasone dipropionate discontinuation was more likely with omalizumab (39.6% vs 19.1% P < .001). Improvements in asthma symptoms and pulmonary function occurred along with a reduction in rescue β-agonist use. Omalizumab was well tolerated, with an adverse-events profile similar to that of placebo. Conclusion: The addition of omalizumab to standard asthma therapy reduces asthma exacerbations and decreases inhaled corticosteroid and rescue medication use. (J Allergy Clin Immunol 2001;108:184-90.)
To review the prevalence, causes, and treatments of nasal septal perforation (NSP).
A literature search was conducted in MEDLINE to identify peer-reviewed articles related to NSP using the keywords ...nasal septal perforation and septal perforation for articles published between January 1, 1969, and December 31, 2006, and references cited therein.
Articles were selected based on their direct applicability to the subject matter.
Causes of NSPs include piercings, exposure to industrial chemicals, illicit drug use, intranasal steroid use, surgical trauma, bilateral cautery, and possibly improper use of nasal applicators. Prevalence is poorly reported. Mechanisms of substance-induced NSP formation are not understood. Progression from epistaxis to ulceration to NSP could not be substantiated by the literature.
Depending on the patient, NSP may be viewed as desirable (nose rings), problematic (whistling, congestion), or inconsequential. Understanding the pathogenesis of NSP is important for the practicing physician required to make decisions about whether to recommend surgical correction or medical treatment. Although the etiology of NSP is overwhelmingly iatrogenic, there is an association with a number of medical diseases in addition to use of illicit drugs and/or prescription nasal sprays.
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