anti-IgE Antibody Research Articles

Allergen-specific immunotherapy, novel drugs and biologicals: hopes from the difficult-to-treat allergic child

In the last decades, significant progresses have been reached in the management of atopic diseases in childhood. Several approaches have been proposed in patients affected by moderate-to-severe atopic diseases. Severe asthma and atopic dermatitis are poorly known with different underlying phenotypes and endotypes, and they may require further cares with biological therapies. Omalizumab, anti-IgE monoclonal antibody, is effective and safe in patients with atopic diseases, especially uncontrolled asthma and chronic urticaria. Anti-IL-5 drugs including mepolizumab, reslizumab and benralizumab are effective in resistant eosinophilic asthma. In patients with uncontrolled atopic dermatitis, dupilumab is of benefit. Allergen-specific immunotherapy (AIT) represents the only treatment attaining immunologic tolerance and sustaining improvement in symptoms. Both subcutaneous and sublingual immunotherapies are characterized by a short-term and a long-term efficacy, as demonstrated by a reduced immunologic reactivity after discontinuation. Component-resolved diagnosis has been found an essential diagnostic tool potentially able to increase the efficacy of AIT in polysensitized children, establishing a precise AIT prescription for patient genuinely sensitized to allergens. The future care of allergic diseases in childhood requires an individualized approach to achieve a patient-tailored therapy for difficult-to-treat atopic diseases.

IgE Antibodies: From Structure to Function and Clinical Translation.

Immunoglobulin E (IgE) antibodies are well known for their role in mediating allergic reactions, and their powerful effector functions activated through binding to Fc receptors FcεRI and FcεRII/CD23. Structural studies of IgE-Fc alone, and when bound to these receptors, surprisingly revealed not only an acutely bent Fc conformation, but also subtle allosteric communication between the two distant receptor-binding sites. The ability of IgE-Fc to undergo more extreme conformational changes emerged from structures of complexes with anti-IgE antibodies, including omalizumab, in clinical use for allergic disease; flexibility is clearly critical for IgE function, but may also be exploited by allosteric interference to inhibit IgE activity for therapeutic benefit. In contrast, the power of IgE may be harnessed to target cancer. Efforts to improve the effector functions of therapeutic antibodies for cancer have almost exclusively focussed on IgG1 and IgG4 subclasses, but IgE offers an extremely high affinity for FcεRI receptors on immune effector cells known to infiltrate solid tumours. Furthermore, while tumour-resident inhibitory Fc receptors can modulate the effector functions of IgG antibodies, no inhibitory IgE Fc receptors are known to exist. The development of tumour antigen-specific IgE antibodies may therefore provide an improved immune functional profile and enhanced anti-cancer efficacy. We describe proof-of-concept studies of IgE immunotherapies against solid tumours, including a range of in vitro and in vivo evaluations of efficacy and mechanisms of action, as well as ex vivo and in vivo safety studies. The first anti-cancer IgE antibody, MOv18, the clinical translation of which we discuss herein, has now reached clinical testing, offering great potential to direct this novel therapeutic modality against many other tumour-specific antigens. This review highlights how our understanding of IgE structure and function underpins these exciting clinical developments.

Current Strategies to Inhibit High Affinity FcεRI-Mediated Signaling for the Treatment of Allergic Disease.

Allergies and asthma are a major cause of chronic disease whose prevalence has been on the rise. Allergic disease including seasonal rhinitis, atopic dermatitis, urticaria, anaphylaxis, and asthma, are associated with activation of tissue-resident mast cells and circulating basophils. Although these cells can be activated in different ways, allergic reactions are normally associated with the crosslinking of the high affinity Fc receptor for Immunoglobulin E, FcεRI, with multivalent antigen. Inflammatory mediators released from cytoplasmic granules, or biosynthesized de novo, following FcεRI crosslinking induce immediate hypersensitivity reactions, including life-threatening anaphylaxis, and contribute to prolonged inflammation leading to chronic diseases like asthma. Thus, inappropriate or unregulated activation of mast cells and basophils through antigenic crosslinking of FcεRI can have deleterious, sometimes deadly, consequences. Accordingly, FcεRI has emerged as a viable target for the development of biologics that act to inhibit or attenuate the activation of mast cells and basophils. At the forefront of these strategies are (1) Anti-IgE monoclonal antibody, namely omalizumab, which has the secondary effect of reducing FcεRI surface expression, (2) Designed Ankyrin Repeat Proteins (DARPins), which take advantage of the most common structural motifs in nature involved in protein-protein interactions, to inhibit FcεRI-IgE interactions, and (3) Fusion proteins to co-aggregate FcεRI with the inhibitory FcγRIIb. This review presents the published research studies that support omalizumab, DARPins, and fusion proteins as, arguably, the three most currently viable strategies for inhibiting the expression and activation of the high affinity FcεRI on mast cells and basophils.

A Comparison of Intradermal Skin Testing and Serum Insect Allergen-specific IgE Determination in Horses With Insect Bite Hypersensitivity From 2008 to 2016

New techniques in equine veterinary allergy testing include multiple allergen simultaneous tests (MASTs) that cover insect bite hypersensitivity (IBH), respiratory and atopic allergic diseases. The in vivo intradermal test (IDT) method is one of the most widely used techniques in veterinary practice, but recently, in vitro methods have been introduced as possible alternatives. This study was designed to assess the correlation between IDTs and MASTs based on IgE determination in serum. The study was performed on Malopolski breed horses with IBH (n = 26). IDTs were performed, and allergen-specific IgE serum concentrations were measured using a monoclonal anti-IgE antibody during the years 2008–2016. An allergen panel containing Tabanus spp., Culicoides nubeculosus, mosquito (Culex spp.), Simulium equinum, and Stomoxys calcitrans was used. This study shows good agreement and correlation (correlation coefficient rho, 0.413–0.589) between the two tests for four (Tabanus spp, Culicoides nubeculosus, Culex spp., Simulium equinum) of the five tested allergens in horses with IBH. The overall sensitivity (Se) of the allergen-specific IgE insect horse panel was 72.6% (range, 30.8%–91.3%), the specificity (Sp) was 63.6% (range, 50%–70.1%), and the accuracy (Acc) was 73.3% (range, 48%–88.5%) compared with IDTs. This study found good agreement and correlation between IDTs and serological MASTs based on monoclonal antibodies for most of the determined allergens for horses with IBH.

A “Stadium” Urticaria, Cold Urticaria is Still a Mostly Unknown Disease, with a Wide Spectrum of Severity Degrees and Few Therapeutic Certainties: Is Omalizumab one of These? Reflections from a Clinical Case Report

Introduction: One of the most common forms of physical urticaria is the cold urticaria. It can be a medical emergency, since it can induce anaphylaxis and edema of the glottis, and in any case, it is a condition that reduces the quality of life of the affected subjects forced to significantly limit their normal activities. Moreover, since the symptoms are triggered by exposure to cold, which is difficult (if not impossible) to avoid in everyday life, a safe and effective therapy appears to be essential. Unfortunately, traditional therapies often cannot provide adequate and safe answers. Case Presentation: The current study reported the case of a 52-year-old female patient manifesting the first symptoms after going to the stadium to watch football games while sitting in the stands. On such occasions, her buttocks would begin to itch, and started swelling and reddening. These manifestations then occurred on other occasions of exposure to the cold, and in other body areas. The patient visited the outpatient clinic of Allergy and Clinical Immunology Unit, Teramo General Hospital (Teramo, Italy), and was treated with sedating and non-sedating H1-blocking antihistamines (Rupatadine, Cetirizine), a leukotriene antagonist, and oral steroids with no success; therefore, it was decided to treat her with Omalizumab, an anti-IgE antibody. Conclusions: The satisfactory response to Omalizumab in the patient, after the failure of previous standard therapeutic strategies, confirmed the effectiveness of this molecule to treat cold urticaria, which despite what reported in several studies, is not yet recognized and authorized by the competent health authorities in the treatment of this condition.

Omalizumab in children with severe allergic disease: a case series

BackgroundCurrently, severe allergic asthma and food allergy in children represent an important public health problem with medical, psychosocial and economic impacts. Omalizumab is a humanized monoclonal anti-IgE antibody, approved for refractory allergic asthma and chronic urticaria. It has been widely used in clinical practice as add-on therapy in patients with severe uncontrolled allergic asthma. In recent years there has seen the emergence of an allergic epidemic with increasing food allergy, which represents the main cause of anaphylaxis in children. The standard of care for food allergy is strictly dietary allergen avoidance and emergency treatment, but recent clinical trials have suggested that omalizumab may have a role to play as an adjuvant to oral immunotherapy (OIT). We present a case series of patients treated at our institution with omalizumab for severe allergic asthma and food allergy.MethodsPatients received omalizumab according to a standard reference nomogram after failing standard therapies. In children with comorbid severe food allergy, omalizumab was administered in conjunction with an oral immunotherapy protocol.ResultsOmalizumab was effective in controlling symptoms of allergic asthma, allergic rhinitis and rhinosinusitis, but not eosinophilic esophagitis, while aiding successful oral desensitization of comorbid severe food allergies.ConclusionsOmalizumab appears to be an excellent therapeutic option in children with inadequately controlled severe allergic asthma, allergic rhinitis and rhinosinusitis, with or without food allergy.

Allergic activation of RBL-2H3 mast cells with L-Asparaginase and its inhibition by anti-IgE antibody

Allergic activation of RBL-2H3 mast cells with L-Asparaginase and its inhibition by anti-IgE antibody

Omalizumab as a Provoking Factor for Venous Thromboembolism

A 43-year-old man with a history of severe extrinsic allergic asthma treated with once-monthly omalizumab (600 mg) for the last 15 months. He presented to the emergency room with a 2-week history of right lower limb pain and chest pleuritic pain. Computed tomography pulmonary angiography showed bilateral pulmonary embolism with right-sided pulmonary infarction and ultrasound of right lower limb confirmed distal deep vein thrombosis. No other known risk factors were identified. Treatment with omalizumab was stopped during hospitalization. The Naranjo Adverse Drug Reaction (ADR) Probability Scale classifies this as a probable ADR (score of 6). Omalizumab is a humanized monoclonal anti-IgE antibody indicated for the treatment of persistent moderate-to-severe asthma and certain chronic refractory urticaria. The EXCELS study (The Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma), a postmarketing observational cohort study to assess clinical safety profile of omalizumab, showed a significant increase in venous thromboembolism. In conclusion, omalizumab has been associated with arterial and venous thromboembolic events, although the evidence is not definitive.

Omalizumab and unmet needs in severe asthma and allergic comorbidities in Japanese children.

Childhood asthma is one condition within a family of allergic diseases, which includes allergic rhinitis, atopic dermatitis, and food allergy, among others. Omalizumab is an anti-IgE antibody therapy that was approved in Japan for children with asthma and added to the Japanese pediatric asthma guidelines in 2017. This review highlights the Japanese clinical perspectives in pediatric allergic asthma, and consideration for allergic comorbidities, and reflects on omalizumab clinical trials in progress to present comprehensive future opportunities.

Genetically engineered drugs for treatment of bronchial asthma: recent achievements

Current population of patients with asthma is characterized by increasing resistance to standard pharmacotherapeutic agents such as inhaled corticosteroids, antileukotriene agents and anti-IgE antibodies. These findings were confirmed by international statistic data and indicate insufficient efficacy of the treatment. Asthma phenotyping encompassing a role of certain biomarkers for bronchial inflammation could contribute to achieving better response to treatment. Genetically engineered drugs could directly impact on mediators and modulators involved in the inflammation and bronchoconstriction. This is one of the most promising directions of the modern pharmacotherapy, particularly considering severe and difficult-to-treat asthma. A comparative analysis of efficacy and safety of currently available genetically engineered drug groups (monoclonal anti-IgE antibodies, monoclonal antibodies against interleukin (IL)-4/IL-13 and IL-5, and prostaglandin D2 receptor antagonists) was performed by the authors of this article on the basis of results of randomized controlled clinical trials (RCT). According to RCT results, omalizumab is still the leading genetically engineered drug. Moreover, evidence of efficacy and safety of novel agents has been published that allowed implementation these drugs in the routine clinical practice for treatment of severe eosinophilic asthma.

Effective treatment with omalizumab of a patient with spontaneous chronic urticaria and eosinophilic esophagitis

This article reports the clinical history of a patient who had been affected by chronic spontaneous urticaria for 13 years, resistant to currently recommended therapy, and who was also diagnosed eosinophilic esophagitis. The anti-IgE monoclonal antibody omalizumab was rapidly effective and induced the clinical remission of both diseases.

Chronic spontaneous urticaria treated with omalizumab: report of two cases

Background: Chronic spontaneous urticaria (CSU) is a relatively common skin disease whose etiopathogenesis, as well as other factors influencing disease manifestations, are not fully understood. Mast cell function is recognised as having a central role in CSU signs and symptoms.Therapeutic options are limited; a number of drugs, recommended by international guidelines for the management of urticaria, lack regulatory approval for CSU and are prescribed off label.Omalizumab, a recombinant humanized anti IgE antibody, has recently received the approval for CSU treatment in Europe after an appropriate clinical development.Patients and results: Two case reports, that describes our encouraging experience with this therapeutic option in a real-life setting are discussed and deeply investigate the different scenario for the omalizumab use.Conclusion: In both cases, a complete remission of CSU symptoms after omalizumab treatment are demonstrated. Moreover, 6 months therapy gave the better results, whit a relapse, in one subject, 1 month after discontinuing omalizumab. Accordingly, a better understanding of long-term safety and efficacy should be needed to allow long-term administration in responding patients through a changing in prescription rules.

IgE blockade in autoimmunity: Omalizumab induced remission of bullous pemphigoid

Bullous pemphigoid (BP) is a blistering dermopathy and a prototypic antibody-mediated autoimmune disease. Detection of IgG autoantibodies against hemidesmosomal proteins BP180 and/or BP230 are diagnostic and levels can correlate with disease activity. Therapies include corticosteroids and oral immunosuppressants, while intravenous immunoglobulin and rituximab are reserved for treatment resistant cases. Here we describe a patient with severe BP which was refractory to standard first line therapy, intravenous immunoglobulin and rituximab induced depletion of peripheral B cells. Use of the monoclonal anti-IgE antibody omalizumab resulted in rapid resolution of blistering despite ongoing high levels of anti-skin IgG antibodies. To our knowledge this is the first case of BP responsive to omalizumab after failure of rituximab to be reported. This case adds to emerging data on omalizumab as a novel BP treatment as well as providing new evidence of an independent role for autoreactive IgE-mediated inflammation in the formation of BP skin lesions.

Predictors of response to omalizumab and relapse in chronic spontaneous urticaria: a study of 470 patients.

Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6weeks. Omalizumab is a monoclonal anti-IgE antibody effective in refractory CSU, but its mechanism of action and markers predictive of response remain not completely defined. To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and d-dimer (bd-dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal. In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bd-dimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2- and 3-month interval after a first and a second course of treatment, respectively. bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than non-responders (P=0.0002). Conversely, bd-dimer did not correlate to response. There was no correlation between both bIgE and d-dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P<0.0001 and P=0.0105, respectively), while baseline UAS7 correlated only to first relapse (P=0.0023). Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bd-dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk.

The soluble isoform of human FcɛRI is an endogenous inhibitor of IgE‐mediated mast cell responses

The soluble isoform of FcɛRI, the high-affinity IgE receptor (sFcεRI), is a protein of the IgE network with poorly defined functions. To define cellular sources and signals that result in the production of human sFcεRI and study its invivo functions. FcεRI-transfected human cell lines (MelJuso), human monocyte-derived dendritic cells (moDCs), and murine bone marrow-derived mast cells (MC) were stimulated by FcεRI cross-linking and release of sFcεRI was analyzed (ELISA, Western Blot). Lysosomal-associated membrane protein 1 degranulation assays and human basophil activation tests (BATs) were used to study IgE-dependent activation. Recombinant sFcεRI (rsFcεRI) was used to assess its role in murine models of anaphylaxis with WT (wild-type) and IgE-/- (IgE-deficient) mice. Antigen-specific cross-linking of IgE-loaded FcɛRI on MelJuso cells that express the trimeric or tetrameric receptor isoform induced the production of sFcεRI. Using MCs and moDCs, we confirmed that IgE/FcɛRI activation induces sFcɛRI release. We demonstrated that generation of sFcɛRI requires Src phosphorylation and endo/lysosomal acidification. In experimental mouse models, sFcɛRI diminishes the severity of IgE-mediated anaphylaxis. BATs confirmed that, comparable to the anti-IgE monoclonal antibody omalizumab, sFcɛRI is an inhibitor of the human innate IgE effector axis, implying that sFcɛRI and omalizumab potentially inhibit each other invivo. sFcɛRI is produced after antigen-specific IgE/FcɛRI-mediated activation signals and functions as an endogenous inhibitor of IgE loading to FcɛRI and IgE-mediated activation. Our results imply, therefore, that sFcɛRI contributes to a negative regulatory feedback loop that aims at preventing overshooting responses after IgE-mediated immune activation.

Monoclonal Antibody Consumption Pattern in a Sponsored Tertiary-Care Healthcare System in a Developing Country: A Five-Year Study From 2013 - 2017

Background: Monoclonal antibodies are increasingly being employed in oncology, toxicology, infectious diseases and rheumatology owing to unmatched efficacy and safety; nevertheless, their usage in developing countries is restricted due to high cost to the exchequer. The newer production line of monoclonal antibodies comes forth with improved efficacy and safety of the current generation monoclonal antibodies and has led to a meteoric growth in their utility. Methods: We performed a comparative analysis of consumption pattern of monoclonal antibodies in a sponsored tertiary-care healthcare system during 2013 - 2017. The humanized anti-IgE monoclonal antibody, omalizumab, was compared with various groups of drugs used for the treatment of bronchial asthma such as combination of long-acting β-agonists and inhaled corticosteroids, short-acting β-agonists and anticholinergics, and inhaled corticosteroids and leukotriene receptor antagonists. Results: The consumption pattern revealed a three-fold increase in the number of monoclonal antibodies during 2016 - 2017 compared to the three-year period from 2013 to 2015. Omalizumab incurred the highest cost burden relative to other medicines used in bronchial asthma. The comparative analysis of usage pattern of monoclonal antibodies, immunomodulators, anti-HIV drugs and all insulin preparations demonstrates annually rising cost burden of monoclonal antibodies. Conclusions: The study showed an increasing trend of healthcare costs and proportionately increasing use of monoclonal antibodies, which add to the quality of care through increased efficacy and safety. We need to accept the fact that quality comes with an additional cost burden, and costs can be optimized with economy of scale.

2-year safety and efficacy results for benralizumab

The era of biological therapies for asthma started with approval in 2003 of a humanised anti-IgE antibody, omalizumab, for the treatment of patients with severe allergic asthma. Since then, IgG antibodies targeting interleukin (IL)-5 (mepolizumab and reslizumab) and IL-5 receptor α (benralizumab) have been approved for the treatment of patients with severe eosinophilic asthma characterised by recurrent exacerbations. In 2016, two phase 3 studies 1 Bleecker ER FitzGerald JM Chanez P et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016; 388: 2115-2127 Summary Full Text Full Text PDF PubMed Scopus (850) Google Scholar , 2 FitzGerald JM Bleecker ER Nair P et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016; 388: 2128-2141 Summary Full Text Full Text PDF PubMed Scopus (870) Google Scholar showed that benralizumab had good safety and efficacy when administered over 1 year in patients with severe uncontrolled asthma, reducing asthma exacerbations and improving lung function in patients with blood eosinophil counts of 300 cells per μL or greater at baseline. Although 1-year safety results for anti-IL-5 or anti-IL-5 receptor α antibodies have generally been acceptable, 3 He LL Zhang L Jiang L Xu F Fei DS Efficacy and safety of anti-interleukin-5 therapy in patients with asthma: a pairwise and Bayesian network meta-analysis. Int Immunopharmacol. 2018; 64: 223-231 Crossref PubMed Scopus (13) Google Scholar no study has assessed their long-term safety or efficacy. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trialThe 2 years of safety results validate that observations observed in the first year of benralizumab continued through a second year of treatment. No new consequences of long-term eosinophil depletion occurred, and the incidence of other adverse events, including opportunistic infections, were similar during the second year. Full-Text PDF

Omalizumab normalizes the gene expression signature of lesional skin in patients with chronic spontaneous urticaria: A randomized, double‐blind, placebo‐controlled study

Omalizumab, a humanized recombinant monoclonal anti-IgE antibody, proved to be effective in patients with chronic spontaneous urticaria (CSU), including severe and treatment-refractory CSU. Here, we report omalizumab's effect on gene expression in skin biopsies from CSU patients enrolled in a double-blind, placebo-controlled study. Chronic spontaneous urticaria patients (18-75years) were randomized to either 300mg omalizumab (n=20) or placebo (n=10) administered s.c. every 4weeks for 12weeks (NCT01599637). Lesional and nonlesional skin biopsies were collected from the same area of consenting patients and assessed at baseline and on Day 85 compared with skin biopsies from the same area of 10 untreated healthy volunteers (HVs). Gene expression data were generated using Affymetrix HG-U133Plus2.0 microarrays. Statistical analyses were performed using R packages. At baseline, 63 transcripts were differentially expressed between lesional and nonlesional skin. Two-thirds of these lesional signatures were also differentially expressed between lesional and HV skin. Upon treatment with omalizumab, >75% of lesional signatures changed to reflect nonlesional skin expression levels (different vs placebo, P<0.01). Transcripts upregulated in lesional skin (vs nonlesional and/or HV skin) suggested increased mast cell/leukocyte infiltration (FCER1G, C3AR1, CD93, S100A8, and S100A9), increased oxidative stress, vascularization (CYR61), and skin repair events (KRT6A, KRT16). Lesional signatures were not modulated by treatment in nonresponders (defined based on UAS7 longitudinal changes ≥16). Omalizumab, in treatment responders, reverted transcriptional signatures associated with CSU lesion phenotype to reflect nonlesional/HV expression levels; this is consistent with observed omalizumab-mediated clinical improvement observed in patients with CSU.

Omalizumab in the Therapy of Pediatric Asthma.

Eosinophilic asthma is driven by Th2 immune response and is usually characterized by the increase of total serum IgE levels and/or specific IgE that express single or multiple allergen sensitization. In such an immuno-pathological background, the anti-IgE therapy, namely omalizumab, found its main clinical utility and recommendation to treat severe asthma. In this mini-review, we summarized the most relevant immuno-pathological and clinical evidences supporting the use of omalizumab in the therapy of pediatric asthma. Furthermore, we provided the main practical points for its use in the therapeutic management of asthmatic children. Through the binding of serum free IgE, omalizumab impairs not only the effector phase of IgE-mediated asthma, but also affects the IgE biology and the related immune response, globally. Here, the history of omalizaumab has been shortly reviewed from its preclinical development to its clinical validation in pediatric asthma. Thus, recent patents regarding anti-IgE therapy have been discussed. Omalizumab significantly improved the clinical management of severe and uncontrolled pediatric asthma; however, pre-treament IgE levels limited the use of omalizumab in some patients and the cost of the therapy is still relevant. Moreover, the optimal duration of the treatment with omalizumab in children has to be determined. Finally, the recent generation of a mutant IgE-Fc fragment being resistant to omalizumab binding might open further therapeutic applications, in addition to second generation anti-IgE antibodies.

Utility and effectiveness of Symbicort\xae Turbuhaler\xae (oral inhalation containing budesonide and formoterol) in a patient with severe asthma after permanent tracheostomy

BackgroundThe utility and effectiveness of inhalational asthma therapy in patients with a permanent tracheostomy has not been established. Previously, a few studies reported the use of nebulizer-type inhalers for treating these patients. Symbicort® Turbuhaler® (Symbicort) is an orally inhaled dry powder containing the corticosteroid budesonide and the bronchodilator formoterol. There are no reports describing the successful use of Symbicort in patients with a permanent tracheostomy.Case presentationWe describe the case of a woman with poorly controlled severe asthma after a permanent tracheostomy. She had developed thyroid cancer with tracheal invasion for which right thyroid lobectomy and tracheal and esophageal resection were performed, with subsequent construction of a permanent tracheostomy. In our case, prior to surgery, asthma control had been improved by adding a bronchodilator—the long-acting muscarinic antagonist tiotropium—and the anti-IgE antibody agent omalizumab to single maintenance and reliever therapy (SMART) using Symbicort; surgery was then performed. After surgery, asthma control worsened as a result of a change from Symbicort to budesonide nebulizer and a tulobuterol patch. In order to resume SMART therapy, an In-Check® inspiratory flow meter was used to measure and assess whether the inspiratory flow rate was sufficient for a dry-powder inhaler. Inhalation guidance was provided. On inhalation with the tracheostomy closed at the same time, the inspiratory flow rate was 43 L/min at the maximum. This was judged to be sufficient for the effect of Symbicort, and thus the inhaler was changed to Symbicort. Asthma symptoms promptly improved, and the patient was subsequently discharged.ConclusionsThe use of Symbicort resulted in improved asthma control in a patient with severe asthma following a permanent tracheostomy. Thus, it is suggested that inhalation powder could be an option for patients with permanent tracheostomy.