Project description:Asthma is multi-factorial disorder, and microbial dysbiosis enhances lung inflammation and asthma-related symptoms. Probiotics has shown anti-inflammatory effect and could regulate the gut-lung axis. Thus, a three-month randomized, double-blind, and placebo-controlled human trial was performed to investigate the adjunctive efficacy of probiotics in managing asthma.
Project description:The Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy (GRASS) study was a randomized, double-blind, placebo-controlled trial of individuals with timothy grass allergy who received 2 years of placebo, subcutaneous (SCIT), or sublingual immunotherapy (SLIT) and were followed for a total of 3 years. Here we utilized longitudinal transcriptomic profiling of nasal brush and peripheral blood mononuclear cell (PBMC) samples after allergen provocation collected in the GRASS study to uncover airway and systemic expression pathways mediating responsiveness to immunotherapy.
Project description:The Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy (GRASS) study was a randomized, double-blind, placebo-controlled trial of individuals with timothy grass allergy who received 2 years of placebo, subcutaneous (SCIT), or sublingual immunotherapy (SLIT) and were followed for a total of 3 years. Here we utilized longitudinal transcriptomic profiling of nasal brush and peripheral blood mononuclear cell (PBMC) samples after allergen provocation collected in the GRASS study to uncover airway and systemic expression pathways mediating responsiveness to immunotherapy.
Project description:We profiled genome-wide gene expression in nasal scrapes following grass pollen challenge and Prednisone treatment. It was a randomized, double-blind, placebo-controlled, three-period, cross-over trial to evaluate the effects of single oral doses of 10 mg and 25 mg of prednisone on inflammatory mediators measured in nasal exudates after nasal allergen challenge in susceptible individuals with allergic rhinitis. It examined the ability to quantify responses to allergen challenge and resolve dose responsive treatment effects of prednisone.
Project description:We conducted a randomized, double-blind, placebo-controlled trial in adults with moderate-to-severe AD to test the efficacy of JAK/SYK-inhibitor ASN002. ASN002 significantly suppressed key AD inflammatory pathways, corresponding to clinical response, and may be an effective novel therapeutic agent for moderate-to-severe AD.
Project description:Background Atopic diseases, resulting from hypersensitivity to a wide variety of allergens, affect 10-20% of the population. Immunotherapy is an effective treatment for atopic diseases, but its mechanisms are not fully understood. Objective We studied gene expression profiles in the peripheral blood mononuclear cells and examined whether the individuals with allergic rhinitis have a unique gene expression profile and how the immunotherapy affect the gene expression profiles. Method We used cDNA microarray and â??Expression Analysis Systemic Explorerâ?? to examine the gene expression profiles in the peripheral blood mononuclear cells of atopic subjects and other groups. Results We identified a highly conserved gene expression profile in atopic subjects that permitted their accurate segregation from control or autoimmune subjects. A major feature of this profile was the under-expression of a variety of genes that encode proteins required for apoptosis and over-expression of genes that encode proteins critical for stress responses and signal transduction. We also identified 563 genes that can segregate individuals with allergic rhinitis based upon receipt of immunotherapy. Conclusion There is a highly conserved gene expression profile in the peripheral blood mononuclear cells of individuals with allergic rhinitis. This profile can be used to identify individuals with allergic rhinitis and to evaluate responses to immunotherapy. Quantitative endpoints, such as gene expression, may assist clinicians faced with clinical decisions in the diagnosis of patients and the evaluation of response to therapy. The knowledge of the possible genetic basis for immunotherapy efficacy may also lead to novel therapeutic approaches for atopic diseases.
Project description:A Randomized, Placebo-Controlled Trial of Intradermal Allergen Immunotherapy for Grass Pollen Allergy Background: Repeated intradermal injection of grass pollen (nanograms of allergen) suppresses allergen-induced cutaneous late phase responses, in keeping with effects of conventional high dose subcutaneous and sublingual immunotherapy. We evaluated the efficacy and safety of grass pollen intradermal immunotherapy for treatment of allergic rhinitis.Methods: We randomly assigned 93 adults with grass pollen allergic rhinitis to receive 7 pre-seasonal Intradermal allergen immunotherapy injections (containing 7 ng of Phl p 5 major allergen) or histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season. Skin biopsies were taken after the pollen season following an intradermal allergen challenge. Cutaneous late phase responses were measured 4 and either 7, 10 or 13 months post-treatment. Results No difference in the primary endpoint was observed between treatment arms (median difference, 14; 95% confidence interval [CI], -172.5 to 215.1; P=0.80). Amongst secondary endpoints, nasal symptoms measured with daily scores (median difference, 35; 95% CI, 4.0 to 67.5; P=0.03) and visual-analogue scales (median difference, 53; 95% CI, -11.6 to 125.2; P=0.05) were higher in the intradermal treatment group. Intradermal immunotherapy increased serum Phl p-specific IgE (P=0.001) compared to the control arm and T cells cultured from biopsies showed higher and lower surface of surface markers for Type 2 (P=0.04) and Type 1 (P=0.01) T-helper cells, respectively, Interleukin-5 was differentially expressed by microarray (P=0.03). Late phase responses were still inhibited 7 months after treatment (P=0.03) but not at 10-13 months. Conclusions Grass pollen intradermal allergen immunotherapy was not clinically effective but resulted in immunological priming and worsening of allergic rhinitis symptoms.
Project description:The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium. We used micro array to profile gene expression of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. 17 subjects were included in a cross-sectional study (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). RNA was extracted from isolated and cultured epithelial cells from bronchial brushes and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array).
Project description:Background: In asthma, airway epithelium remodeling can already be detected during childhood, and epithelial cells are more susceptible to virus and oxidative stress. Their exact role in natural history and severity of children allergic respiratory disease remains however surprisingly unexplored. Aim: To analyze dysfunctions of epithelium in dust mite allergic respiratory disease (rhinitis ± asthma) in children. Methods: Expression profilings of nasal epithelial cells collected by brushing were performed on Affymetrix Hugene 1.0 ST arrays. All allergic patients were sensitized to dust mite. 19 patients had an isolated allergic rhinitis (AR). 14 patients had AR associated with asthma. Patients were compared to 12 controls, their severity and control being assessed according to NAEPP and ARIA criteria. Infections by respiratory viruses were excluded by real-time PCR measurements. Results: 61 probes were able to distinguish allergic rhinitis children from healthy controls. A majority of these probes was under the control of Th2 cytokines, as evidenced by parallel experiments performed on primary cultures of nasal epithelial cells. In uncontrolled asthmatic patients, we observed not only an enhanced expression of these Th2-responsive transcripts, but also a down-regulation of interferon-responsive genes. Conclusion: Our study identifies a Th2 driven epithelial phenotype common to all dust mite allergic children. Besides, it suggests that epithelium is involved in the severity of the disease. Expression profiles observed in uncontrolled asthmatic patients suggest that severity of asthma is linked at the same time to atopy and to impaired viral response. Nasal epithelium gene expression profiling of dust mite allergic children with isolated rhinitis, rhinitis associated with asthma and controls. 38 samples classified in 4 categories : 14 isolated rhinitis (R), 6 rhinitis with uncontrolled asthma (UA), 7 rhinitis with controlled asthma (CA) and 11 healthy subjects (C )