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1.
J Biol Chem ; 290(38): 23124-34, 2015 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-26209637

RESUMO

Hyaluronan (HA) is a large (>1500 kDa) polysaccharide of the extracellular matrix that has been linked to severity and inflammation in asthma. During inflammation, HA becomes covalently modified with heavy chains (HC-HA) from inter-α-inhibitor (IαI), which functions to increase its avidity for leukocytes. Our murine model of allergic pulmonary inflammation suggested that HC-HA may contribute to inflammation, adversely effecting lower airway remodeling and asthma severity. Our objective was to characterize the levels of HA and HC-HA in asthmatic subjects and to correlate these levels with asthma severity. We determined the levels and distribution of HA and HC-HA (i) from asthmatic and control lung tissue, (ii) in bronchoalveolar lavage fluid obtained from non-severe and severe asthmatics and controls, and (iii) in serum and urine from atopic asthmatics after an experimental asthma exacerbation. HC-HA distribution was observed (i) in the thickened basement membrane of asthmatic lower airways, (ii) around smooth muscle cells of the asthmatic submucosa, and (iii) around reserve cells of the asthmatic epithelium. Patients with severe asthma had increased HA levels in bronchoalveolar lavage fluid that correlated with pulmonary function and nitric oxide levels, whereas HC-HA was only observed in a patient with non-severe asthma. After an experimental asthma exacerbation, serum HA was increased within 4 h after challenge and remained elevated through 5 days after challenge. Urine HA and HC-HA were not significantly different. These data implicate HA and HC-HA in the pathogenesis of asthma severity that may occur in part due to repetitive asthma exacerbations over the course of the disease.


Assuntos
alfa-Globulinas/metabolismo , Asma/metabolismo , Ácido Hialurônico/metabolismo , Pulmão/metabolismo , Miócitos de Músculo Liso/metabolismo , Mucosa Respiratória/metabolismo , Adolescente , Adulto , Animais , Asma/patologia , Modelos Animais de Doenças , Feminino , Humanos , Pulmão/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Miócitos de Músculo Liso/patologia , Mucosa Respiratória/patologia
2.
Cleve Clin J Med ; 88(2): 104-109, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526464

RESUMO

Peanut and tree-nut allergies have increased dramatically in prevalence, especially in children. Historically, children with food allergies have been treated through strict avoidance of the allergen. Recently, an oral preparation of peanut allergen (Palforzia) was approved for immunotherapy (ie, desensitization) in children 4 to 17 years old. This article reviews oral immunotherapy and its role in children with peanut allergies.


Assuntos
Hipersensibilidade a Noz , Hipersensibilidade a Amendoim , Adolescente , Alérgenos , Arachis , Criança , Pré-Escolar , Humanos , Imunoterapia , Hipersensibilidade a Amendoim/terapia
3.
Clin Chest Med ; 40(1): 107-123, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30691706

RESUMO

This article on exposome and asthma focuses on the interaction of patients and their environments in various parts of their growth, development, and stages of life. Indoor and outdoor environments play a role in pathogenesis via levels and duration of exposure, with genetic susceptibility as a crucial factor that alters the initiation and trajectory of common conditions such as asthma. Knowledge of environmental exposures globally and changes that are occurring is necessary to function effectively as medical professionals and health advocates.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Asma/genética , Asma/metabolismo , Exposição Ambiental/efeitos adversos , Expossoma , Humanos
5.
J Allergy Clin Immunol Pract ; 4(4): 691-696.e1, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27039239

RESUMO

BACKGROUND: Longitudinal variability in serum IgE levels has not been prospectively studied in people with moderate to severe allergic asthma. OBJECTIVE: We investigated change in serum IgE concentrations over 1 year, and its relationship with lung function, asthma control, asthma pharmacotherapy, allergy season, asthma exacerbations, body mass index, and demographic factors. METHODS: Seventeen patients with moderate to severe persistent allergic asthma were followed for 1 year. Variability in serum IgE level was explored using a linear mixed regression model treating a change of 10% or more in IgE concentration and combined change of 10% or more and an absolute change of 50 IU/mL as dichotomous variables. RESULTS: For consecutive visits every 2 months, the mean percent change in serum IgE level was 23 ± 3 (P < .001). Probability of having a greater than 10% change in serum IgE level in a subsequent visit was 69% (95% CI, 58%-78%; P < .001). Variability in IgE level could have affected clinical decisions for anti-IgE treatment (dosing and/or treatment candidacy) in 7 of 17 patients. There were no statistically significant associations of IgE level variability with demographic characteristics and lung function, exacerbations, allergy season, Asthma Control Test scores, peak flow rates, pharmacotherapy, or body mass index. CONCLUSIONS: Serum IgE concentrations exhibit variability over time among individuals with moderate to severe persistent allergic asthma. The factors that contribute to IgE level variability and the impact of these findings on clinical outcomes deserve further study.


Assuntos
Asma/sangue , Imunoglobulina E/sangue , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/imunologia , Feminino , Humanos , Antagonistas de Leucotrienos/uso terapêutico , Masculino , Pessoa de Meia-Idade
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