Toward personalization of asthma treatment according to trigger factors

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.Fil: Niespodziana, Katarzyna. Vienna University of Technology; AustriaFil: Borochova, Kristina. Vienna University of Technology; AustriaFil: Pazderova, Petra. Vienna University of Technology; AustriaFil: Schlederer, Thomas. Vienna University of Technology; AustriaFil: Astafyeva, Natalia. Saratov State Medical University; RusiaFil: Baranovskaya, Tatiana. Belarusian Medical Academy of Post Diploma Studies; BielorrusiaFil: Barbouche, Mohamed Ridha. Institut Pasteur de Tunis; TúnezFil: Beltyukov, Evgeny. Ural State Medical University; RusiaFil: Berger, Angelika. Vienna University of Technology; AustriaFil: Borzova, Elena. Russian Medical Academy of Continuous Professional Education; RusiaFil: Bousquet, Jean. MACVIA; Francia. Humboldt-Universität zu Berlin; AlemaniaFil: Bumbacea, Roxana S.. University of Medicine and Pharmacy "Carol Davila"; RumaniaFil: Bychkovskaya, Snezhana. Krasnoyarsk Medical University; RusiaFil: Caraballo, Luis. Universidad de Cartagena; ColombiaFil: Chung, Kian Fan. Imperial College London; Reino Unido. MRC and Asthma UK Centre in Allergic Mechanisms of Asthma; Reino UnidoFil: Custovic, Adnan. Imperial College London; Reino Unido. MRC and Asthma UK Centre in Allergic Mechanisms of Asthma; Reino UnidoFil: Docena, Guillermo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Eiwegger, Thomas. University Of Toronto. Hospital For Sick Children; CanadáFil: Evsegneeva, Irina. Sechenov First Moscow State Medical University; RusiaFil: Emelyanov, Alexander. North-Western Medical University; RusiaFil: Errhalt, Peter. University Hospital Krems and Karl Landsteiner University of Health Sciences; AustriaFil: Fassakhov, Rustem. Kazan Federal University; RusiaFil: Fayzullina, Rezeda. Bashkir State Medical University; RusiaFil: Fedenko, Elena. NRC Institute of Immunology FMBA of Russia; RusiaFil: Fomina, Daria. Sechenov First Moscow State Medical University; RusiaFil: Gao, Zhongshan. Zhejiang University; ChinaFil: Giavina Bianchi, Pedro. Universidade de Sao Paulo; BrasilFil: Gotua, Maia. David Tvildiani Medical University; GeorgiaFil: Greber Platzer, Susanne. Vienna University of Technology; AustriaFil: Hedlin, Gunilla. Karolinska Huddinge Hospital. Karolinska Institutet; Sueci

Treatment of atopic dermatitis with upadacitinib: adcare single center experience

IntroductionThe role of upadacitinib in the management of moderate to severe atopic dermatitis seems promising, but more data on its efficacy and safety are needed. This study endeavors to assess the practical impact and safety of upadacitinib in patients with moderate to severe atopic dermatitis. The study aims to evaluate the efficacy and safety of upadacitinib in the treatment of moderate to severe atopic dermatitis, focusing on analyzing patient responses to the treatment.MethodsIn this study, adult patients diagnosed with moderate to severe atopic dermatitis received upadacitinib at daily doses of 15 mg or 30 mg, as prescribed by their attending physicians. The therapeutic efficacy of upadacitinib was meticulously assessed using established clinical metrics. Simultaneously, a comprehensive safety assessment was conducted through monthly monitoring, including the evaluation of potential effects of upadacitinib intake on hepatic function, lipid profile, and hematopoiesis using the pertinent laboratory tests.ResultsSixteen participants were enrolled in the study. At 1month follow-up, there was a significant reduction in the mean Eczema Area and Severity Index (EASI) score to 18.8 points, which further increased to 24 points at the 4-month mark. Additionally, 9 participants (56%) demonstrated an EASI-50 response after 1 month of treatment, with this response increasing to 9 participants (90%) after 4 months. Furthermore, enhanced therapeutic responses were observed at 4 months, with 6 patients (38%) achieving an EASI-75 response at 1month and 8 patients (80%) achieving this milestone at the 4-month follow-up. This study highlights the potential of upadacitinib as an effective treatment option for moderate to severe atopic dermatitis. While it demonstrates improved symptom management, close monitoring for potential adverse events, particularly infections and the known risks of Janus kinase inhibitors, is essential. Further research is essential to determine the long-term safety and efficacy of upadacitinib

Allergen-Specific Immunotherapy with Monomeric Allergoid in a Mouse Model of Atopic Dermatitis.

Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN-γ level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD

Level of Foxp3 expression.

<p>The specific mRNAs in OVA-stimulated mice splenocytes (incubated with OVA for 72hrs) were quantified by qRT-PCR. The results are presented as mean mRNA expression (mean±SE, n = 8 for each). The relative levels of Foxp3 expression were calculated by referring to the HPRT (hypoxanthine guanine phosphoribosyltransferase) in each sample. AD without ASIT: OVA-sensitized untreated mice; ASIT with OVA: OVA-sensitized mice treated by ASIT with OVA; ASIT with sOVA: OVA-sensitized mice treated by ASIT with sOVA; placebo: PBS-sensitized mice. *, p<0.05.</p

Levels of cytokines.

<p>The levels of cytokines in supernatants of OVA-stimulated mice splenocytes (incubated with OVA for 72hrs) were quantified by ELISA. The results are presented as mean IL concentration (mean±SE, n = 8 for each). AD without ASIT: OVA-sensitized untreated mice; ASIT with OVA: OVA-sensitized mice treated by ASIT with OVA; ASIT with sOVA: OVA-sensitized mice treated by ASIT with sOVA; placebo: PBS-sensitized mice. Level of (a) the IL-4, (b) IL-5, (c) IL-12, (d) IFN-γ, and (e) IL-17; (f) IL-4/IFN-γ ratio in mice with ASIT. *, p<0.05 versus “AD without ASIT”; **, p<0.05 versus “placebo”; #, p<0.05 versus “ASIT with OVA”.</p

Analysis of OVA-specific IgG.

<p>The levels of antibodies in sera obtained before, during, and after ASIT were detected and quantified by ELISA. The results are presented as mean antibodies concentrations (mean±SE, n = 8 for each). AD without ASIT: OVA-sensitized untreated mice; ASIT with OVA: OVA-sensitized mice treated by ASIT with OVA; ASIT with sOVA: OVA-sensitized mice treated by ASIT with sOVA; placebo: PBS-sensitized mice. (a) anti-OVA IgG1 response in mice with ASIT, (b) anti-OVA IgG2a response in mice with ASIT, (c) anti-OVA IgG response in mice with ASIT, (d) ratio of OVA-specific IgG1/IgG2a antibody in mice with ASIT, (*, p<0.05)</p

Histologic features of OVA- and sOVA-treated skin sites in BALB/c mice.

<p>(a) Mice sensitized with OVA and treated with PBS (“AD without ASIT”), (b) mice sensitized with OVA and treated with OVA (“ASIT with OVA”), (c) mice sensitized with OVA and treated with sOVA (“ASIT with sOVA”), and (d) mice sensitized with PBS (“placebo”). Skin sections were stained with H&E and examined at 100x. Scale bars 100 μm. There is marked hyperplasia of the epidermis, a dermal infiltrate (a-c). The cellular infiltrate consists of neutrophils, eosinophils, and lymphocytes. (e) Summary index of the main assessment criteria for histologic skin lesions.</p

Protocol of sensitization and ASIT with OVA or sOVA.

<p>Mice were sensitized with OVA (100 μg) or saline applied at 100 μl to a sterile patch. The patch was applied for 1-wk and then removed. ASIT was performed between the 1^st and 2^nd OVA applications by SC injection of increasing doses of OVA (a), sOVA (b), or PBS (as control). After ASIT, the mice had two 1-wk exposures to a patch separated by 2-wk intervals. The control group received PBS at the same time.</p