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.

Positioning of Tezepelumab in Severe Asthma / Posicionamento do Tezepelumabe na Asma Grave

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 (AU)

A asma é uma das doenças crônicas mais comuns e estima-se que seja grave em 3% a 10% dos pacientes afetados. Há necessidade de tratamentos biológicos adicionais que sejam altamente eficazes em todo o espectro da asma grave não controlada. Os medicamentos atualmente disponíveis inibem 1 ou 2 citocinas específicas ou anticorpos IgE e, portanto, suprimem apenas parcialmente a cascata inflamatória complexa tipo 2 (T2). Os produtos biológicos que visam moléculas mais a montante na via fisiopatológica da asma poderiam tratar a asma de forma mais eficaz. Tezepelumab é um anticorpo monoclonal humano imunoglobulina G2λ que tem como alvo a citocina linfopoietina estromal tímica (TSLP). É o primeiro produto biológico comercializado contra uma citocina derivada de células epiteliais, impedindo a ligação da TSLP ao seu receptor e reduzindo os estímulos imunológicos que a TSLP pode desencadear em diferentes endótipos de asma. Tezepelumabe reduz biomarcadores de inflamação a jusante, como eosinófilos no sangue e nas vias aéreas, FeNO, IgE, IL-5 e IL-13. O tezepelumab proporciona um benefício clínico na asma grave, reduzindo a taxa anualizada de exacerbação da asma em pacientes com níveis elevados ou baixos de biomarcadores de inflamação T2, embora o efeito seja maior entre aqueles com níveis elevados. Foi demonstrado que o medicamento melhora o controle da asma, a qualidade de vida e a função pulmonar e reduz a hiperresponsividade das vias aéreas. Portanto, o tezepelumabe pode ser usado em todo o espectro de pacientes com asma grave não controlada, especialmente em pacientes com T2 elevado. Esta revisão inclui uma declaração de posicionamento dos autores, todos membros do Comitê de Asma da SEAIC (AU)

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.

Analysis of response of severe eosinophilic asthmatic patients to benralizumab

Introduction Clinical trials and real-life studies have been published showing effectiveness of benralizumab in severe eosinophilic asthmatic patients. The aim of the present study is to describe super-responders to benralizumab in a series of 79 patients who completed at least 1 year of treatment, and to compare super-responders with non super-responders. Methods This is a multicenter study of the Register of Severe Asthma of the Region of Murcia (RE-ASGRAMUR) Group performed in eight hospitals under the conditions of routine clinical practice. Patients with zero exacerbations and no oral corticosteroid therapy for asthma were considered super-responders. We analyzed clinical, functional, and inflammatory parameters of selected patients. Results In all, 50 of the 79 patients (63%) met the super-responder criteria. In addition, 36% of the patients (26/71) were considered as complete responders to treatment (super--responder + Asthma Control Test [ACT] ≥ 20 + forced expiratory volume in 1 s [FEV1] ≥ 80%). The super--responders were significantly older in age (P = 0.0029), had higher eosinophils count (P = 0.0423), higher proportion of nasal polyps (P = 0.036), and they had less severe disease at baseline. After 1 year of treatment, the super-responders had higher levels of ACT questionnaire (23 vs 19, P = 0.0007) and better percentage of FEV1 (83 vs 75, P = 0.0359). Conclusion Almost two of the three patients treated with benralizumab were super--responders after 1 year of treatment and 36% had a complete response. Super-responders were associated with older age, higher eosinophils count, had nasal polyposis as comorbidity, and had less severe disease at baseline. This data illustrated the good real-life response of patients with severe eosinophilic asthma to the treatment with benralizumab (AU)

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.

Alergia al látex / Allergy to latex

No disponible

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.

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.

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.