Positioning of Tezepelumab in Severe Asthma.

Asthma is one of the most common chronic diseases and is estimated to be severe in 3%-10% of affected patients. There is a need for additional biologic treatments that are highly efficacious across the spectrum of severe uncontrolled asthma. Currently available drugs inhibit 1 or 2 specific cytokines or IgE antibodies and thus only partially suppress the complex type 2 (T2) inflammatory cascade. Biologics targeting more upstream molecules in the pathophysiological pathway of asthma could treat asthma more effectively. Tezepelumab is a human monoclonal immunoglobulin G2λ antibody that targets the cytokine thymic stromal lymphopoietin (TSLP). It is the first marketed biologic against an epithelial cell-derived cytokine, preventing binding of TSLP to its receptor and reducing the immune stimuli that TSLP can trigger in different asthma endotypes. Tezepelumab reduces downstream biomarkers of inflammation, such as blood and airway eosinophils, FeNO, IgE, IL-5, and IL-13. Tezepelumab provides a clinical benefit in severe asthma, reducing the annualized asthma exacerbation rate in patients with either high or low levels of biomarkers of T2 inflammation, although the effect is greater among those with high levels. The drug has been shown to improve asthma control, quality of life, and lung function and reduce airway hyperresponsiveness. Therefore, tezepelumab can be used across the spectrum of patients with severe uncontrolled asthma, especially in T2-high patients. This review includes a positioning statement by the authors, all of whom are members of the SEAIC Asthma Committee.

Dupilumab to induce tolerance to SLIT-Melocotón®.

Summary: Introduction. Food allergy is an increasing problem for population and treatments inducing tolerance using sublingual immunotherapy is currently under study. Case presentation. Our aim as allergists is to achieve tolerance to sublingual allergen specific immunotherapy with sublingual immunotherapy (SLIT-peach). We present a case report consisting of a 40 year old woman with anaphylactic reactions after eating fruit and other plant-foods due to sensitization to nonspecific lipid transfer proteins (nsLTP). Her diagnose, LTP-syndrome. This protein is the main panallergen in our area and causes crossed reaction to multiple plant foods. The principal allergen in this syndrome is rPru p3, present in peach and most vegetables, fruits, nuts and grains. Serum specific IgE levels were performed using microarrays and positive for seven nsLTPs: rAra h9, rCor a8, nJug r3, rPru p3, rTri a 14, nArt v3 and rPla a3. Immediate reaction to SLIT in the fourth month of maintenance-dose led us to interrupt pru p3 immunotherapy. Immediate reaction to Omalizumab in the fourth dose in Hospital consisting in anaphylaxis prompted us to switch to Dupilumab. After four months with this monoclonal antibody we reintroduced sublingual immunotherapy with pru p3 SLIT-peach® achieving maintenance dose of four drops a day with no clinical reactions. SLIT-peach® in our patient is crucial for her due to her restricted diet, the severity of reactions and lack of quality of life measured by Europevall questionnaire. Conclusions in our case our aim is to achieve SLIT. We report a case of compassionate use with Dupilumab in a patient with multiple food allergy syndrome mediated by nsLTP. There are no cases reported for Dupilumab in this use.

Omalizumab. A review of the new treatment of allergic asthma and seasonal allergic rhinitis.

The causal role of immunoglobulin E (IgE) in triggering the cascade of biochemical events leading to allergic disease is well established. Treatments that selectively inhibit IgE activity are a logical approach in managing the allergic response. Omalizumab is a recombinant humanised monoclonal antibody which specifically binds to the Cε3 domain of immunoglobulin (Ig) E, the site of high-affinity IgE receptor binding. The clinical benefit and steroid-sparing effect of treatment with the anti-immunoglobulin-E (IgE) antibody, Omalizumab, was assessed in patients with moderate-to-severe allergic asthma and seasonal allergic rhinitis. Intravenous and subcutaneous administration of anti-IgE mAb reduces circulating levels of IgE in atopic patients to low levels commonly seen in non-atopic individuals. Anti-IgE therapy offers protection against allergen-induced bronchoconstriction, reduces the need for short acting inhaled beta 2-agonist and corticosteroids among asthmatic patients and reduces severity of symptoms of allergic rhinitis. Adverse events were infrequent in clinical trials of omalizumab, and not significantly different from placebo. The most frequent drug-related event was mild to moderate urticaria. They do not induce anaphylaxis and the occurrence of antibodies against anti-IgE mAb is sporadic. The results of cited studies suggest that humanized anti-IgE monoclonal antibodies may have important immunotherapeutic benefit for treatment of allergic disorders.

Cold urticaria associated with acute serologic toxoplasmosis.

Cold urticaria is defined as a urticarial and/or angioedematous reaction of the skin to contact with cold objects, water or air. Types of urticaria associated with infectious diseases, such as mononucleosis, rubeola, varicella, syphilis, hepatitis, and HIV infection have been reported. We present the case of a patient who developed cold urticaria associated with acute serologic toxoplasmosis. The patient was a 34-year-old man who for the previous 2 months had presented cutaneous pruritus accompanied by several papular lesions in parts of the skin exposed to cold as well as those in contact with cold water. The result of an "ice-cube test" was positive. Serologic tests for Toxoplasma gondii showed an IgG level of 68 UI/ml and were positive for IgM, while a test for cryoglobulins was positive. One month later cryoglobulins were negative and a serologic test for T. gondii showed an IgG concentration of 75 UI/ml and positive IgM. Three months later cryoglobulins were still negative, IgG for T. gondii was 84 UI/ml, and IgM was positive. After 6 months cryoglobulins were still negative, IgG level was 68 UI/ml and IgM was still slightly positive. In the final evaluation, 14 months later, IgG level was 32 UI/ml and IgM was negative. The patient continues to present clinical manifestations of cold urticaria, although he has experienced some improvement and his tolerance to cold has increased after treatment with cetirizine.

Chronic idiopathic urticaria treatment.

Chronic idiopathic urticaria (CIU) is a common skin condition that affects 0.1-3 % of people in the USA and Europe and accounts for nearly 75 % of all chronic urticaria cases. Up to 40 % of patients who have chronic urticaria for more than 6 months still have urticarial wheals 10 years later. The therapeutic management should first be oriented towards palliation of symptoms. A 2 % solution of ephedrine as a local spray is very useful for oropharyngeal edema. H1 antihistamines with a low potential for sedation are the most important first-line treatment. Combinations of various antihistamines may be useful in suppressing symptomatology. These include: a) First generation H1 antihistamines; b) Combinations of first and second generations using non-sedating agents in the morning and first generation drugs at night; c) Combinations of second generation antihistamines; d) Combination of doxepin with a first or second generation antihistamine; e) Combination of an H2 anti-receptor antihistamine (eg, cimetidine or ranitidine) with a first or second generation antihistamine. Preliminary reports suggest that desloratadine and anti-leukotrienes may be effective in treating some patients with chronic idiopathic urticaria.

[Techniques for determining case mix and their application to Allergology. 2]. / Técnicas de medición del "Case-Mix" y su aplicación a la Alergología (2a parte).

In this second part, we review the Generic Algorithms, the RUGs and the Ambulatory Visits Groups, remarking their possible application in our specialty. In an Allergology Service, most resources are spent on outpatients attendance. This fact allows us to propose that a production unit of that Service (GFH) could develop its activities, in its health area, ambulatorily. Its objectives and responsibilities, together with its human and material resources, could be clearly defined. An allergy outpatients clinic basic technological requirements are scarce, its costs being mainly determined by those of the staff. This makes possible the application of algorithms, to obtain the AVGs in Allergology, and to calculate the "cost by process", with the use of an indirect cost imputation system. The systematic use of evaluation technics in our specialty case-mix is a necessity in the present, because it permits: 1) a correct planning, fixing and ordering the objectives; 2) a better user of resources; 3) an adequate request of budgets, according to production; 4) obtaining a clinical and epidemiological data base; 5) billing the services; 6) information to the customer (patient) about the expenses his attention has generated.

[Techniques for determining case mix and their application to Allergology. 1]. / Técnicas de medición del "Case-Mix" y su aplicación a la Alergología (1a parte).

The use of adequate technics, in the Allergology case-mix evaluation, is a necessity in the present, and an aim to the future. Doing so, we shall be able to guarantee the quality of medical assistance. This article's objective is to introduce the reader, with a clear language, in the diverse procedures employed, in the actuality, to evaluate the diverse Health Services productive processes. We point out their advantages and disadvantages, and make a final proposal about the use of some of them in Allergology. Firstly, we analyze and describe the International Disease Classification (IDC-9-CM), the Diagnosis Related Groups (DRGs), the AS-SCORE, the Patients Severity Illness, the Staging Disease, the APACHE, and the Patients Management Categories. In the second part, we review the Generic Algorithms, the RUGs and the Ambulatory Visits Groups (AVGs). Finally, we propose some methods to improve activities in our specialty, to increase our knowledge, and to educate our colleagues under training in the basic concepts they need, to carry out their activities. In this way, we'll be able to guarantee a good assistance for the allergic patients, and to present objective data to the society, about the efficacy and efficiency with which public funds are used.

Platelet-activating factor antagonists.

Platelet-activating factor (PAF), identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, exhibits potent proinflammatory properties. PAF is produced by numerous cell types, including endothelial cells, neutrophils, monocytes, macrophages, basophils, eosinophils and mastocytes. Since the discovery and identification of the chemical structure of PAF, a large variety of specific PAF-receptor antagonists, both natural and synthetic compounds, have been described. Intensive research has been conducted and development programs set up by more 25 pharmaceutical companies world-wide, studying the therapeutic interest of more than 50 PAF-receptors antagonists in various pathophysiological conditions. Medline (1966-1996), Embase (Excerpta Medica; 1974-1996), and other biomedical and drug directory databases were searched to identify English-language articles (basic science, clinical trial research, and review articles) and abstracts of conference proceedings on PAF receptor antagonists and related terms. The most important PAF receptor antagonists are reviewed with their effectiveness in various experimental tests. Fundamentally, PAF antagonists may be divided in two groups: natural and synthetic compounds. Natural (Ginkgolides, Kadsurenone, Chantancin, Phomactin, Swietemohonin A, Prehispalone, THC-7-oic acid, Aglafoline, FR 900452, PCA 4248 and SCH 37370), and synthetic antagonists (CV-3988, CV-6209, SRI 63-072, SRI 63-441, UR-10324, UR-11353, E-5880, CL 184005, 6-Mono and Bis-aryl phosphate antagonists, TCV-309, Ro-74719, WEB 2086, Y 24180, BN 50726, BN 50727, BN 50730, BN 50739, Ro 24-4736, Ro 24-0238, RP 55778, RP 59227, RP 66681, YM 264, YM 461, SM 10661, SR 27417, UK 74505, BB 182, BB 823, BB 654, SDZ 64-412, SDZ 65-123, L 652731, L 659898, L 668750, L 671284, L680573, L 680574, CIS 19, ABT-299 and Pinusolide) have a great variability in their chemical structure that might have importance in their different pharmacological profile. The great majority of these drugs are under development, and only a few have undergone clinical trials.

Pressurised metered-dose inhalers (MDIs) versus dry powder inhalers devices (DPIs) to rapid-acting inhaled b2-agonists for asthma in children.

OBJECTIVE: To compare the clinical effectiveness of pressurized metered-dose inhalers (MDIs) with that of dry powder inhalers (DPIs) in delivering short-acting b2-agonists in children with asthma. METHODS: Searches were performed in Medline (1997-March 2002), the Cochrane Library Database and the Embase reference lists of review articles and clinical trials. In addition, the international headquarters of b2-agonist manufacturers were contacted. We performed a review of randomized controlled trials. RESULTS: Ten randomized controlled trials were included. No differences in clinical effectiveness were found between MDIs and PDIs. Two studies reported that fewer adverse events occurred when the Turbuhaler was used. Two long-term studies in children found that children preferred the MDI to the Rotohaler. CONCLUSIONS: 1) In stable asthma, short-acting b2 bronchodilators in standard MDIs are as effective as dry powder inhalers. 2) Pooling of results was limited by the small number of studies and therefore no overall conclusions could be drawn. 3) From the limited data available, we found little or no evidence for an additional clinical benefit of DPI devices over standard MDIs in children with asthma.