Showing papers by "William W. Busse published in 2009"

An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice.

Abstract: Background: The assessment of asthma control is pivotal to the evaluation of treatment response in individuals and in clinical trials. Previously, asthma control, severity, and exacerbations were defined and assessed in many different ways.Purpose: The Task Force was established to provide recommendations about standardization of outcomes relating to asthma control, severity, and exacerbations in clinical trials and clinical practice, for adults and children aged 6 years or older.Methods: A narrative literature review was conducted to evaluate the measurement properties and strengths/weaknesses of outcome measures relevant to asthma control and exacerbations. The review focused on diary variables, physiologic measurements, composite scores, biomarkers, quality of life questionnaires, and indirect measures.Results: The Task Force developed new definitions for asthma control, severity, and exacerbations, based on current treatment principles and clinical and research relevance. In view of current knowledge ...

A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma.

Abstract: Rationale The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-alpha, in severe persistent asthma is unknown. Objectives To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma. Methods From 2004 to 2006, 309 patients with severe and uncontrolled asthma, despite high-dose inhaled corticosteroids and long-acting beta(2) agonists, were randomized 1:1:1:1 to monthly subcutaneous injections of placebo or golimumab (50, 100, or 200 mg) through Week 52. Coprimary endpoints were the change from baseline through Week 24 in prebronchodilator percent-predicted FEV(1) and the number of severe asthma exacerbations through Week 24. Measurements and main results No significant differences were observed for the change in percent-predicted FEV1 (least squares mean: placebo, 2.44 [95% confidence interval (CI) -0.574 to 5.461]; combined 100-mg and 200-mg, 2.91 [0.696-5.116]) or severe exacerbations (mean +/- SD: placebo, 0.5 +/- 1.07 vs. combined 100-mg and 200-mg 0.5 +/- 0.97) through week 24. Through Week 24, 2.6% of patients treated with placebo vs. 19.5% of those treated with golimumab discontinued the study agent, and 1.3% and 7.8% discontinued study participation, respectively. An unfavorable risk-benefit profile led to early discontinuation of study-agent administration after the Week-24 database lock. Through Week 76, 20.5% of patients treated with placebo and 30.3% of patients treated with golimumab experienced serious adverse events, with serious infections occurring more frequently in golimumab-treated patients. One death and all eight malignancies occurred in the active groups. Conclusions Overall, treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients with severe persistent asthma. Clinical trial registered with www.clinicaltrials.gov (NCT00207740).

Severe exacerbations and decline in lung function in asthma.

Abstract: Rationale: To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma.Objectives: To determine whether severe asthma exacerbations are associated with a persistent decline in lung function.Methods: The START (inhaled steroid treatment as regular therapy in early asthma) study was a 3-year, randomized, double-blind study of 7,165 patients (5–66 yr) with persistent asthma for less than 2 years, to determine whether early intervention with low-dose inhaled budesonide prevents severe asthma-related events (exacerbations requiring hospitalization or emergency treatment) and decline in lung function.Measurements and Main Results: There were 315 patients who experienced at least one severe asthma exacerbation, of which 305 were analyzable, 190 in the placebo group and 115 in the budesonide group. In the placebo group, the change in post-bronchodilator ...

The Urban Environment and Childhood Asthma (URECA) birth cohort study: design, methods, and study population

Abstract: The incidence and morbidity of wheezing illnesses and childhood asthma is especially high in poor urban areas. This paper describes the study design, methods, and population of the Urban Environment and Childhood Asthma (URECA) study, which was established to investigate the immunologic causes of asthma among inner-city children. URECA is an observational prospective study that enrolled pregnant women in central urban areas of Baltimore, Boston, New York City, and St. Louis and is following their offspring from birth through age 7 years. The birth cohort consists of 560 inner-city children who have at least one parent with an allergic disease or asthma, and all families live in areas in which at least 20% of the population has incomes below the poverty line. In addition, 49 inner-city children with no parental history of allergies or asthma were enrolled. The primary hypothesis is that specific urban exposures in early life promote a unique pattern of immune development (impaired antiviral and increased Th2 responses) that increases the risk of recurrent wheezing and allergic sensitization in early childhood, and of asthma by age 7 years. To track immune development, cytokine responses of blood mononuclear cells stimulated ex vivo are measured at birth and then annually. Environmental assessments include allergen and endotoxin levels in house dust, pre- and postnatal maternal stress, and indoor air nicotine and nitrogen dioxide. Nasal mucous samples are collected from the children during respiratory illnesses and analyzed for respiratory viruses. The complex interactions between environmental exposures and immune development will be assessed with respect to recurrent wheeze at age 3 years and asthma at age 7 years. The overall goal of the URECA study is to develop a better understanding of how specific urban exposures affect immune development to promote wheezing illnesses and asthma.

Similar colds in subjects with allergic asthma and nonatopic subjects after inoculation with rhinovirus-16

Abstract: Background Rhinovirus infections are frequent causes of asthma exacerbations. Objective This study was conducted to test whether subjects with and without allergic asthma have different responses to infection and to identify baseline patient risk factors that predict cold outcomes. Methods Twenty subjects with mild persistent allergic asthma and 18 healthy subjects were experimentally inoculated with rhinovirus-16. Subjects were evaluated at baseline, during the acute infection, and during recovery for asthma and cold symptoms by using a validated questionnaire. Sputum and nasal lavage fluid were evaluated for viral shedding, cytokines, and cellular inflammation. Results There were no group-specific significant differences in peak cold symptom scores (10.0 ± 5.8 vs 11.1 ± 6.2, asthmatic vs healthy subjects), peak nasal viral titers (log 10 4.3 ± 0.8 vs 3.7 ± 1.4 50% tissue culture infective dose/mL, respectively), or changes in peak flow during the study (10% ± 10% vs 8% ± 6%, respectively). Rhinovirus-16 infection increased peak asthma index values in the asthmatic group (median, 6 → 13; P = .003) but only marginally in the healthy group (median, 4 → 7; P = .09). More asthmatic subjects had detectable eosinophils in nasal lavage and sputum samples at baseline and during infection, but otherwise, cellular and cytokine responses were similar. Baseline sputum eosinophilia and CXCL8 (IL-8) levels were positively associated with cold symptoms, whereas CCL2 (monocyte chemotactic protein 1) levels were inversely associated with nasal viral shedding. Conclusions These findings suggest that subjects with mild allergic asthma and healthy subjects have similar cold symptoms and inflammatory and antiviral responses. In addition, eosinophilia and other selective baseline measures of airway inflammation in subjects with or without asthma might predict respiratory outcomes with rhinovirus infection.

Three-dimensional imaging of ventilation dynamics in asthmatics using multiecho projection acquisition with constrained reconstruction.

Abstract: The purpose of this work is to detect dynamic gas trapping in three dimensions during forced exhalation at isotropic high spatial resolution and high temporal resolution using hyperpolarized helium-3 MRI. Ten subjects underwent hyperpolarized helium-3 MRI and multidetector CT. MRI was performed throughout inspiration, breath-hold, and forced expiration. A multiecho three-dimensional projection acquisition was used to improve data collection efficiency and an iterative constrained reconstruction was implemented to improve signal to noise ratio (SNR) and increase robustness to motion. Two radiologists evaluated the dynamic MRI and breath-held multidetector CT data for gas and air trapping, respectively. Phantom studies showed the proposed technique significantly improved depiction of moving objects compared to view-sharing methods. Gas trapping was detected using MRI in five of the six asthmatic subjects who displayed air trapping with multidetector CT. Locations in disagreement were found to represent small to moderate regions of air trapping. The proposed technique provides whole-lung three-dimensional imaging of respiration dynamics at high spatial and temporal resolution and compares well to the current standard, multidetector CT. While multidetector CT can provide information about static regional air trapping, it is unable to depict dynamics in a setting more comparable to a spirometry maneuver and explore the longitudinal time evolution of the trapped regions.

Attenuated P2X7 Pore Function as a Risk Factor for Virus-induced Loss of Asthma Control

Abstract: Rationale: Upper respiratory tract infection is a guideline accepted risk domain for the loss of asthma control. The ionotrophic nucleotide receptor P2X7 regulates compartmentalized acute inflammation and the immune response to airway pathogens. Objectives: We hypothesized that variability in P2X7 function contributes to neutrophilic airway inflammation during a cold and thereby is linked to acute asthma. Methods: Research volunteers with asthma were enrolled at the onset of a naturally occurring cold and monitored through convalescence, assessing symptoms, lung function, and airway inflammation. P2X7 pore activity in whole blood samples was measured using a genomically validated flow cytometric assay. Measurements and Main Results: Thirty-five participants with mild to moderate allergic asthma were enrolled and 31 completed all visits. P2X7 pore function correlated with the change in nasal lavage neutrophil counts during the cold (Rs = 0.514, P = 0.004) and was inversely related to the change in asthma symptoms (Rs = −0.486, P = 0.009). The change in peak expiratory flow recordings, precold use of inhaled corticosteroids, and P2X7 pore function were multivariate predictors of asthma symptoms (P = 0.001, < 0.001 and = 0.003 respectively). Attenuated P2X7 activity was associated with the risk of losing asthma control (crude odds ratio, 11.0; 95% confidence interval, 1.1–106.4) even after adjustment for inhaled corticosteroids and rhinovirus (odds ratio, 15.0). Conclusions: A whole blood P2X7 pore assay robustly identifies participants with loss-of-function genotypes. Using this assay as an epidemiologic tool, attenuated P2X7 pore activity may be a novel biomarker of virus-induced loss of asthma control.

Asthma morbidity among inner-city adolescents receiving guidelines-based therapy: Role of predictors in the setting of high adherence

Abstract: Background With the expanding effort to provide guidelines-based therapy to adolescents with asthma, attention must be directed to evaluating which factors predict future asthma control when guidelines-based management is applied. Objective We evaluated the role of fraction of exhaled nitric oxide in parts per billion, markers of allergic sensitization, airway inflammation, and measures of asthma severity in determining future risk of asthma symptoms and exacerbations in adolescents and young adults participating in the Asthma Control Evaluation study. Methods Five hundred forty-six inner-city residents, ages 12 through 20 years, with persistent asthma were extensively evaluated at study entry for predictors of future symptoms and exacerbations over the subsequent 46 weeks, during which guidelines-based, optimal asthma management was offered. Baseline measurements included fraction of exhaled nitric oxide in parts per billion, total IgE, allergen-specific IgE, allergen skin test reactivity, asthma symptoms, lung function, peripheral blood eosinophils, and, for a subset, airway hyperresponsiveness and sputum eosinophils. Results The baseline characteristics we examined accounted for only a small portion of the variance for future maximum symptom days and exacerbations—11.4% and 12.6%, respectively. Future exacerbations were somewhat predicted by asthma symptoms, albuterol use, previous exacerbations, and lung function, whereas maximum symptom days were predicted, also to a modest extent, by symptoms, albuterol use, and previous exacerbations, but not lung function. Conclusion Our findings demonstrate that the usual predictors of future disease activity have little predictive power when applied to a highly adherent population with persistent asthma that is receiving guidelines-based care. Thus, new predictors need to be identified that will be able to measure the continued fluctuation of disease that persists in highly adherent, well-treated populations such as the one studied.

Is intrinsic asthma synonymous with infection

Abstract: Rackemann described the 'intrinsic asthma' population over 50 years ago as a unique subgroup that was characterized by onset of progressive loss of lung function beginning later in life, possibly after a respiratory infection. It has also been associated with a female predominance, aspirin-sensitive bronchospasm, and nasal polyposis. While the aetiology is not understood, we propose that persistent respiratory infections play a central role in the development of intrinsic asthma.

Safety of Binodenoson, a Selective Adenosine A2A Receptor Agonist Vasodilator Pharmacological Stress Agent, in Healthy Subjects With Mild Intermittent Asthma

Abstract: Background— The pharmacological stress agents adenosine and dipyridamole are contraindicated in asthma patients because of the risk of adenosine receptor-mediated bronchospasm. Binodenoson, a selective adenosine A2A receptor agonist, produces maximal coronary hyperemia during pharmacological stress testing yet has a low affinity for the adenosine A1, A2B, and A3 receptors that are probably responsible for bronchospasm. This study was conducted to assess the safety of binodenoson in 87 healthy young adult volunteers with documented mild, intermittent asthma. Methods and Results— This study consisted of a dose-escalating, single-blinded phase and a placebo-controlled, double-blinded phase conducted in healthy, young adults with documented mild, intermittent, asthma. In the single-blinded phase, 3 sequential cohorts of 8 subjects received intravenous binodenoson (0.5, 1.0, and 1.5 μg/kg). In the double-blinded phase, commenced after medical review of results from the single-blinded phase, subjects were randomly assigned 2:1 to either binodenoson 1.5 μg/kg (n=41) or placebo (n=22). The primary end point was clinically significant bronchoconstriction, defined as a decrease in forced expiratory volume in 1 second of ≥20% from the preinjection measure. Secondary safety end points were changes from preinjection measure in forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow during the middle 50% of the forced vital capacity; vital signs; pulse oximetry; and adverse events. Binodenoson caused no clinically significant bronchoconstriction or alterations in pulmonary function parameters and transiently increased heart rate and systolic blood pressure. The most common treatment-emergent adverse events were tachycardia, dizziness, and flushing. Conclusions— Binodenoson was safe, well tolerated, and caused no clinically significant bronchoconstriction or pulmonary responses in a small population of healthy subjects with mild, intermittent asthma. Received September 18, 2008; accepted September 9, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Severe Asthma Research Program - Phenotyping and Quantification of Severe Asthma

Abstract: Summary A unique multi-center consortium of research centers, the severe asthma research program (SARP), is working to define asthma phenotypes, with a particular focus on severe asthma due to the higher prevalence of exacerbations and hospital visits in these patients. The consortium includes comprehensive studies of physiology, genotype, and inflammatory biomakers in addition to a lung imaging substudy in nearly 400 subjects. The imaging substudy is comparing quantitative computed tomography (CT) measures of airway morphology and parenchymal density to asthma severity and other makers of asthma. Results show increased wall thickness and increased regional air trapping in severe versus non-severe asthma. Image-guided bronchoscopic assessment using either CT or hyperpolarized gas magnetic resonance imaging (MRI) shows that highly diseased airways have increased wall thickness on histology and greater inflammatory cell numbers. Large scale imaging studies such as SARP may provide a means to better understand and guide effective treatment of severe asthma.

Short-term safety of somatropin inhalation powder in adults with mild to moderate asthma.

Abstract: Systemic therapeutic protein delivery through the lungs could potentially replace delivery by injection, but safety needs to be established in patients with known pulmonary disease. This study determined the short-term safety profile of recombinant human growth hormone (rhGH; somatropin) inhalation therapy in clinically stable adult subjects with mild to moderate asthma and methacholine sensitivity. This randomized, placebo-controlled study had two phases: (1) an escalating 3-dose, 4-day/dosage tolerance phase; and (2) a 14-day, crossover design comparability phase. Noninferiority in maintaining forced expiratory volume in 1 second (FEV 1 ) was tested for somatropin inhalation powder (SIP) compared with subcutaneously injected rhGH (Hsc) and inhaled placebo. Lung hyperresponsiveness was assessed by methacholine bronchoprovocative challenge, and adverse events (AEs) were recorded. Eight and 18 subjects enrolled in the first and second phases, respectively. Noninferiority of SIP compared with Hsc and placebo was established for FEV 1 after the first and last doses, and noninferiority of SIP compared with Hsc for methacholine challenge was established after the first dose. Pulmonary uptake and systemic distribution of SIP was confirmed by increased serum insulin-like growth factor I levels. Mild, nonprogressive cough and nasal congestion occurred more commonly with SIP. All other treatment-emergent AEs were mild, similar across active treatment groups, and consistent with rhGH treatment. In clinically stable adults with mild to moderate asthma, no significant changes in pulmonary function or worsening of asthma complaints occurred during SIP treatment. Future studies of SIP may enroll subjects with mild to moderate asthma for longer-term evaluation of safety and efficacy.

The placebo effect in asthma: Far more complex than simply "I shall please".

Abstract: Wise and co-investigators(1) have added to our understanding and appreciation of the complexity underlying the response to placebos in asthma. When readers now evaluate data in light of “a placebo response,” it should become insightful for them to consider many variables, i.e., the effects measured, the disease being assessed, and mode of presentation used in the trial, i.e., enhanced or neutral. Furthermore, studies evaluating placebo effects have also helped to indicate the potential involvement of brain circuitry in these responses, as well as treatment determinants. Placebo responses are complex, but an integral component of many clinical trials in asthma. To fully appreciate the impact of the placebo, aside from the “I shall please” action, it is now important to realize that a science underlies the placebo and to its response by a patient. The work of Wise and colleagues(1) has added to this information in a most meaningful way and has made us more appreciative of the response to placebos.

Learning from molecular sleuths.

Abstract: Our understanding of the biology of diseases has been advanced in a quantum fashion with the application of molecular tools. The study by Miller and colleagues is another glowing example of how molecular approaches can unravel mysteries and add to greater understanding of diseases like asthma. It is now well appreciated that rhinovirus (HRV) infections are the major cause of asthma exacerbation in children, and possibly contribute to early onset asthma. This has not always been the case. Thirty years ago the impact of HRV infections in asthma was known but underestimated because this organism is difficult to culture. However, with the advent of highly sensitive and specific molecular diagnostics tools, viruses, and most commonly HRV, were found to cause over 80% of asthma exacerbations in children. Why did it take so long to appreciate this relationship? The findings of Miller and co-workers help us to understand this delay by highlighting relationships between acute asthma and a new group of HRVs which do not grow in standard tissue culture. Their work is another example of successfully applying molecular tools to solve longstanding problems in clinical medicine. This new study represents a collaborative effort to identify viral pathogens associated with hospitalization of young children for lower respiratory infections (LRI). The original goal of the project, named the New Vaccine Surveillance Network, was to evaluate the impact of influenza vaccination on hospitalization rates in early childhood. This study had a number of notable strengths. First, it was conducted in children’s hospitals in Nashville TN and Rochester NY that are virtually the sole providers of pediatric inpatient care in the regions, which allows for accurate estimates of population-based rates for hospitalization. Second, PCR-based viral diagnostics were employed, and this is of critical importance for detecting viruses that don’t grow well in tissue culture, which we now know includes the majority of respiratory viruses. Finally, the investigators analyzed partial genetic sequences to type clinical strains of HRV. Previously published findings from this study demonstrated that HRVs were often the only pathogens detected in children hospitalized for respiratory illnesses.1 In fact, HRV were found more often (26%) than respiratory syncytial virus (RSV, 20%), parainfluenza (7%), influenza (3%), or any other single family of viruses. Risk factors for hospitalization with HRV LRI included young age and asthma, which was not a surprise given a number of surveys with similar findings from around the world. What was surprising is that most of the HRV strains that were identified by partial sequencing represented “new” strains: not new in the sense of pedigree, but rather newly discovered. HRV had been classified into 100 serotypes based on growth in tissue culture and inhibition by specific antisera, and these canonical strains were classified into groups “A” and “B” based on similarity of partial genetic sequences and responses to certain antiviral medications. Data from the study of Miller and colleagues, along with similar findings from Australia,2 Hong Kong,3 Germany,4 and other US centers5–7 demonstrate that there are a lot more HRV strains than had been previously appreciated. The new HRV add to the list of recently discovered respiratory viral pathogens (Table). One common theme that unites this diverse group is that all grow poorly or not at all using traditional tissue culture methods. This characteristic explains why the discovery of these pathogens was delayed pending the development of molecular techniques, and together with the considerable differences in sequence, suggests that HRV-C have life cycles that are distinct from group A and B viruses. Accordingly, analysis of the structural proteins indicate that newly discovered HRVs may bind to unique cellular receptors.8 What is the clinical significance of these new viruses? The findings of Miller and colleagues indicate that HRV-C can be associated with wheezing illnesses and exacerbations of asthma. In fact, in their study, group C viruses were more often associated with exacerbations of asthma than other HRV. There may be insufficient data for this conclusion, however, given the distinct complexities of HRV epidemiology. While viruses such as RSV and influenza typically have 1 or 2 serotypes circulating through a community, up to 20 strains of HRV are present in a community during a single season. Furthermore, the prevailing HRV strains differ significantly from place to place, and from season to season. Whether all HRV-C are more likely to cause more severe disease, or just the strains that were circulating in Rochester and Nashville during the study period remains to be determined. This raises an important clinical question: with so many HRV strains out there (maybe there will be 150 or 200 strains when all is said and done), what can we do about it? There are several possible strategies, and usually the first one to be summarily dismissed is vaccination. Polyvalent vaccines are a reality, but a 200-valent HRV vaccine is just not plausible. This situation could be reassessed, however, if it were possible to identify a smaller number of more virulent HRV (perhaps Group C?) that were more likely to cause more severe disease. Other approaches to HRV vaccines would require the development of new technology. The second possibility would be to develop a cure for the common cold. This has been a hope and dream of virologists, and the subject of well over 500 patents. Low tech approaches to this problem have been tried (and endlessly debated…), including vitamin C, zinc, ecchinacea, and so on. And there have been near misses in the age of biotechnology including interferon alpha, molecules that block viral attachment (soluble ICAM-1, pirodavir, pleconaril), and a key viral proteases (ruprintrivir). Each of these programs was derailed by either cost, practical issues (who wants a medicine that is administered 6 times daily), side effects (IFN-α), drug interactions (pleconaril), or marginal efficacy.2,9 Perhaps the failure to consider HRV-C viruses in drug development programs contributed to the lackluster performance of previous HRV antivirals. Finally, immunologic risk factors for more severe respiratory illnesses have been identified in various experimental models, and include allergy and reduced interferon responses.10–13 An emerging concept from these studies is that exposure to common colds in early childhood is universal and infections are common, but the severity of the clinical manifestations depends on host immune factors. Interestingly, interferon responses are deficient in newborns, and the pace of development during infancy may be affected by environmental stimuli, such as pets, endotoxin, and diet.14,15 Thinking optimistically, further definition of early life determinants of immune development, together with additional insights to link the severity of viral colds to immunologic development, may suggest new preventive strategies to nonspecifically boost innate immunity to viral respiratory infections. In summary, given that there were a large number of HRV lurking anonymously in the community, please forgive your local common cold researcher for the absence of a cure. With new diagnostic tools has come a quantum leap in identifying new viruses, and a greater appreciation of HRV infections as a cause of acute (and perhaps chronic) wheezing illnesses. Now that HRV-C has been “decloaked”, we can expect new studies to extend the findings of Miller and colleagues, and further clarify the role of specific HRV groups and strains in asthma. With the recognition of these “new” pathogens via molecular sleuthing comes renewed hope for new treatment strategies for virus-induced wheezing and exacerbations of asthma.

Anti-IgE in Allergic Airway Diseases: Indications and Applications

Abstract: IgE plays a role in both the initial sensitization to antigen and the subsequent effects upon repeat exposure. For sensitization, inhaled antigen is ingested by antigen presenting dendritic cells that line the airway, and then processed and presented to antigen-specific T cells. The subsequent production of cytokines stimulates B cells to produce antigen-specific IgE, which then binds to the surface of mast cells and basophils via the high-affinity receptor for IgE, namely Fc e RI [1] (Fig. 1a ). Upon repeat exposure to an inhaled antigen, there is cross-linking of IgE bound to the surface of mast cells and basophils. This interaction signals mast cells and basophils to degranulate, releasing mediators such as histamine, prostaglandin, and leukotrienes, and to stimulate chemokine and cytokine production. These mediators cause an early or acute phase reaction and, under some circumstances, can lead to a late-phase reaction. IgE is an immunoglobulin that consists of a variable and constant region. The variable region is the area that binds to the antigen. Within the constant region, CH e 3 contains the binding sites for the two different receptors, Fc e RI and Fc e RII (Fig. 2 ). Given the biological effects of IgE, a novel mechanism to treat allergic disease, including asthma, would be to block IgE and its actions. However, an antibody to IgE could either stimulate or block this molecule. The antibody could stimulate IgE if IgE were already bound to receptors on mast cells and basophils. If the antibody is subsequently attached to the bound IgE, it could cause the cross-linking of at least two IgE molecules with subsequent degranulation. Depending on the degree of degranulation, this response may result in an acute allergic reaction. However, if an antibody could block IgE from attaching to its receptors on mast cells and basophils, degranulation could be prevented. Omalizumab is such a molecule; it is an anti-IgE antibody that binds to IgE regardless of IgE specificity.