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1.
Emerg Med Clin North Am ; 40(1): 119-133, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34782083

RESUMO

Scombroid poisoning, systemic mastocytosis, and hereditary alpha tryptasemia all present with episodes that resemble allergic reactions. Knowledge regarding systemic mastocytosis and hereditary alpha tryptasemia is quickly evolving. Epidemiology, pathophysiology, and strategies to identify and diagnose are discussed. Evidence-based management in the emergency setting and beyond is also explored and summarized. Key differences are described between these events and allergic reactions.


Assuntos
Angioedema/diagnóstico , Hipersensibilidade/diagnóstico , Toxinas Marinhas/biossíntese , Angioedema/fisiopatologia , Mimetismo Biológico , Humanos , Hipersensibilidade/fisiopatologia , Toxinas Marinhas/metabolismo , Triptases/análise , Triptases/deficiência
2.
Emerg Med Clin North Am ; 40(1): 1-17, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34782082

RESUMO

Allergic reactions and anaphylaxis occur on a severity continuum from mild and self-limited to potentially life-threatening or fatal reactions. Anaphylaxis is typically a multiorgan phenomenon involving a broad range of effector cells and mediators. Emergency department visits for anaphylaxis are increasing, especially among children. There is a broad differential diagnosis for anaphylaxis, and the diagnosis of anaphylaxis can be aided by the use of the National Institutes of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network clinical diagnostic criteria. Risk factors for severe anaphylaxis include older age, delayed epinephrine administration, and cardiopulmonary comorbidities.


Assuntos
Anafilaxia/fisiopatologia , Hipersensibilidade/fisiopatologia , Anafilaxia/diagnóstico , Epinefrina/uso terapêutico , Humanos , Hipersensibilidade/diagnóstico , Fatores de Risco
3.
Molecules ; 26(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071080

RESUMO

The main purpose of this study was to investigate whether the blockade of the interaction between the receptor activator of nuclear factor-κB (NF-ĸB) ligand (RANKL) and its receptor RANK as well as the blockade of NF-κB inhibitor kinase (IKK) and of NF-κB translocation have the potential to suppress the pathogenesis of allergic asthma by inhibition and/or enhancement of the production by CD4+ and CD8+ T cells of important cytokines promoting (i.e., IL-4 and IL-17) and/or inhibiting (i.e., IL-10 and TGF-ß), respectively, the development of allergic asthma. Studies using ovalbumin(OVA)-immunized mice have demonstrated that all the tested therapeutic strategies prevented the OVA-induced increase in the absolute number of IL-4- and IL-17-producing CD4+ T cells (i.e., Th2 and Th17 cells, respectively) indirectly, i.e., through the inhibition of the clonal expansion of these cells in the mediastinal lymph nodes. Additionally, the blockade of NF-κB translocation and RANKL/RANK interaction, but not IKK, prevented the OVA-induced increase in the percentage of IL-4-, IL-10- and IL-17-producing CD4+ T cells. These latter results strongly suggest that both therapeutic strategies can directly decrease IL-4 and IL-17 production by Th2 and Th17 cells, respectively. This action may constitute an important mechanism underlying the anti-asthmatic effect induced by the blockade of NF-κB translocation and of RANKL/RANK interaction. Thus, in this context, both these therapeutic strategies seem to have an advantage over the blockade of IKK. None of the tested therapeutic strategies increased both the absolute number and frequency of IL-10- and TGF-ß-producing Treg cells, and hence they lacked the potential to inhibit the development of the disease via this mechanism.


Assuntos
Asma/imunologia , Asma/metabolismo , Animais , Asma/fisiopatologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Hipersensibilidade/fisiopatologia , Imunoglobulina E/imunologia , Interleucina-17/imunologia , Interleucina-4/imunologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Células Th17/efeitos dos fármacos , Células Th2/efeitos dos fármacos
4.
PLoS One ; 16(5): e0251885, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34003868

RESUMO

It is widely recognized that innate macrophage immune reactions to implant debris are central to the inflammatory responses that drive biologic implant failure over the long term. Less common, adaptive lymphocyte immune reactions to implant debris, such as delayed type hypersensitivity (DTH), can also affect implant performance. It is unknown which key patient factors, if any, mediate these adaptive immune responses that potentiate particle/macrophage mediated osteolysis. The objective of this investigation was to determine to what degree known adaptive immune responses to metal implant debris can affect particle-induced osteolysis (PIO); and if this pathomechanism is dependent on: 1) innate immune danger signaling, i.e., NLRP3 inflammasome activity, 2) sex, and/or 3) age. We used an established murine calvaria model of PIO using male and female wild-type C57BL/6 vs. Caspase-1 deficient mice as well as young (12-16 weeks old) vs. aged (18-24 months old) female and male C57BL/6 mice. After induction of metal-DTH, and Cobalt-alloy particle (ASTM F-75, 0.4um median diameter) calvaria challenge, bone resorption was assessed using quantitative micro-computed tomography (micro-CT) analysis and immune responses were assessed by measuring paw inflammation, lymphocyte transformation test (LTT) reactivity and adaptive immune cytokines IFN-gamma and IL-17 (ELISA). Younger aged C57BL/6 female mice exhibited the highest rate and severity of metal sensitivity lymphocyte responses that also translated into higher PIO compared to any other experimental group. The absence of inflammasome/caspase-1 activity significantly suppressed DTH metal-reactivity and osteolysis in both male and female Caspase-1 deficient mice. These murine model results indicate that young female mice are more predisposed to metal-DTH augmented inflammatory responses to wear debris, which is highly influenced by active NLRP3 inflammasome/caspase-1 danger signaling. If these results are clinically meaningful for orthopedic patients, then younger female individuals should be appropriately assessed and followed for DTH derived peri-implant complications.


Assuntos
Caspase 1/genética , Metais/efeitos adversos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Osteólise/genética , Próteses e Implantes/efeitos adversos , Fatores Etários , Animais , Reabsorção Óssea/etiologia , Reabsorção Óssea/genética , Reabsorção Óssea/patologia , Feminino , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/genética , Hipersensibilidade/fisiopatologia , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/genética , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Interferon gama/genética , Interleucina-17/genética , Macrófagos/efeitos dos fármacos , Masculino , Metais/uso terapêutico , Camundongos , Osteólise/induzido quimicamente , Osteólise/patologia , Caracteres Sexuais , Crânio/efeitos dos fármacos , Crânio/crescimento & desenvolvimento , Crânio/fisiopatologia , Microtomografia por Raio-X
5.
CMAJ Open ; 9(2): E394-E399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33863797

RESUMO

BACKGROUND: Penicillin is the most frequently reported drug allergen; however, most of these allergies are not true allergies and do not justify the prescription of alternative, less effective and more expensive antibiotic drugs. We aimed to show that patients at low risk of amoxicillin allergy can safely and efficiently undergo oral provocation challenge (OPC) by their primary care physician. METHODS: In this descriptive analysis, we conducted a retrospective chart review of all primary care patients who had undergone OPC from November 2017 to October 2019 in the Amoxicillin Allergy Clinic at the North Perth Family Health Team, Listowel, Ontario. Eligibility for OPC among patients 18 months and older was determined through review of a self-reported patient intake form asking about symptoms, onset, duration, history and family history of allergic reactions, as well as the patient's electronic medical record. Patients were considered to be at low risk of true penicillin allergy if there was no history of anaphylaxis or severe cutaneous reactions. Those with low-risk allergic reactions returned for testing with an OPC to amoxicillin. We collected data on clinical characteristics, antibiotic exposure, parental drug allergy, response to OPC and wait time from referral. We used t tests to describe and compare these variables. Our primary outcome was reaction to OPC by severity as categorized by the World Allergy Organization grading system. Our secondary outcome was the time from referral to completed testing. RESULTS: In total, we included 99 patients (mean age 28.3, standard deviation [SD] 21.2 yr); 72 (73%) were female. Of those tested, 97% (n = 96) completed the OPC with no reaction, 3% (n = 3) had mild immediate reactions, and no serious immediate reactions developed. Mean wait time to testing was 59.0 (SD 69.8) days, with a median (interquartile range) of 39.5 (13.5-70.0) days. INTERPRETATION: Oral provocation challenge presents a safe and accessible opportunity for primary care providers to address erroneous allergy labels to penicillin and related drugs within the primary care office setting. There could be positive public health implications if OPC to penicillin drugs is implemented in primary care.


Assuntos
Amoxicilina/efeitos adversos , Hipersensibilidade a Drogas , Hipersensibilidade , Anamnese/métodos , Atenção Primária à Saúde/métodos , Avaliação de Sintomas/métodos , Adulto , Assistência Ambulatorial/métodos , Antibacterianos/efeitos adversos , Testes Diagnósticos de Rotina , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/prevenção & controle , Saúde da Família , Feminino , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/etiologia , Hipersensibilidade/fisiopatologia , Masculino , Ontário/epidemiologia , Segurança do Paciente , Medição de Risco/métodos
6.
Am J Kidney Dis ; 77(5): 796-809, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33771393

RESUMO

Since maintenance hemodialysis (HD) first became available in the United States in 1962, there has been tremendous growth in the population of patients with kidney failure. HD has become a routine treatment carried out in outpatient clinics, hospitals, nursing facilities, and in patients' homes. Although it is a complex procedure, HD is quite safe. Serious complications are uncommon due to the use of modern HD machines and water treatment systems as well as the development of strict protocols to monitor various aspects of the HD treatment. The practicing nephrologist must be knowledgeable about life-threatening complications that can occur during HD and be able to recognize, manage, and prevent them. This installment in the AJKD Core Curriculum in Nephrology reviews the pathogenesis, management, and prevention of 9 HD emergencies. The HD emergencies covered include dialyzer reactions, dialysis disequilibrium syndrome, uremic/dialysis-associated pericarditis, air embolism, venous needle dislodgement, vascular access hemorrhage, hemolysis, dialysis water contamination, and arrhythmia episodes.


Assuntos
Emergências , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , Edema Encefálico , Descontaminação , Soluções para Diálise/normas , Embolia Aérea/etiologia , Embolia Aérea/fisiopatologia , Embolia Aérea/terapia , Deslocamentos de Líquidos Corporais , Hemólise , Hemorragia/etiologia , Hemorragia/fisiopatologia , Hemorragia/terapia , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/fisiopatologia , Hipersensibilidade/terapia , Rins Artificiais/efeitos adversos , Agulhas , Nefrologia , Pericardite/etiologia , Pericardite/fisiopatologia , Pericardite/terapia , Falha de Prótese , Esterilização , Uremia/complicações , Purificação da Água/normas
7.
Allergol Immunopathol (Madr) ; 49(1): 32-39, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33528927

RESUMO

BACKGROUND: Asthma control is the goal of asthma management. A nationwide study on this aspect was launched by the Italian Society of Paediatric Allergy and Immunology (ControL'Asma study). OBJECTIVE: To define variables associated with different asthma control grades in a nationwide population of asthmatic children and adolescents. METHODS: This cross-sectional real-world study included 480 asthmatic children and adolescents (333 males, median age 11.2 years) consecutively enrolled in 10 third level pediatric allergy clinics. According to the Global Initiative for Asthma (GINA) document, history, medication use, perception of asthma symptoms assessed by visual analog scale (VAS), clinical examination, lung function, childhood asthma control test (cACT)/asthma control test (ACT), and asthma control level were evaluated. RESULTS: Considering GINA criteria, asthma was well controlled in 55% of patients, partly controlled in 32.4%, and uncontrolled in 12.6%. Regarding cACT/ACT, asthma was uncontrolled in 23.2%. Patients with uncontrolled asthma had the lowest lung function parameters and VAS scores, more frequent bronchial obstruction and reversibility, and used more oral and inhaled corticosteroids (CS). CONCLUSIONS: The ControL'Asma study, performed in a real-world setting, showed that asthma in Italian children and adolescents was usually more frequent in males. Asthmatic patients had an early onset and allergic phenotype with very frequent rhinitis comorbidity. Uncontrolled and partly controlled asthma affected about half of the subjects, and the assessment of asthma symptom perception by VAS could be a reliable tool in asthma management.


Assuntos
Asma/diagnóstico , Asma/epidemiologia , Adolescente , Asma/fisiopatologia , Criança , Estudos Transversais , Feminino , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/epidemiologia , Hipersensibilidade/fisiopatologia , Itália/epidemiologia , Masculino , Prevalência , Rinite/diagnóstico , Rinite/epidemiologia , Rinite/fisiopatologia , Escala Visual Analógica
8.
Exp Biol Med (Maywood) ; 246(10): 1210-1218, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33593110

RESUMO

Whole-body vibration (WBV), which is widely used as a type of exercise, involves the use of vibratory stimuli and it is used for rehabilitation and sports performance programmes. This study aimed to investigate the effect of WBV treatment in a chronic pain model after 10 WBV sessions. An animal model (chronic pain) was applied in 60 male Wistar rats (±180 g, 12 weeks old) and the animals were treated with low intensity exercise (treadmill), WBV (vibrating platform), and a combined treatment involving both. The controls on the platform were set to a frequency of 42 Hz with 2 mm peak-to-peak displacement, g ≈ 7, in a spiral mode. Before and after the vibration exposure, sensitivity was determined. Aß-fibers-mediated mechanical sensitivity thresholds (touch-pressure) were measured using a pressure meter. C-fibers-mediated thermal perception thresholds (hot pain) were measured with a hot plate. After each session, WBV influenced the discharge of skin touch-pressure receptors, reducing mechanical sensitivity in the WBV groups (P < 0.05). Comparing the conditions "before vs. after", thermal perception thresholds (hot pain) started to decrease significantly after the third WBV session (P < 0.05). WBV decreases mechanical hyperalgesia after all sessions and thermal sensitivity after the third session with the use of WBV.


Assuntos
Dor Crônica/complicações , Dor Crônica/fisiopatologia , Hipersensibilidade/complicações , Hipersensibilidade/fisiopatologia , Fibras Nervosas Amielínicas/metabolismo , Sensação/fisiologia , Temperatura , Vibração , Animais , Modelos Animais de Doenças , Masculino , Pressão , Ratos Wistar , Tato
9.
J Allergy Clin Immunol ; 148(1): 128-138, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33434532

RESUMO

BACKGROUND: Wheeze and allergic sensitization are the strongest early-life predictors of childhood asthma development; the molecular origins of these early-life phenotypes are poorly understood. OBJECTIVES: We sought to identify metabolites associated with early-life wheeze, allergic sensitization, and childhood asthma. METHODS: We conducted a nested case-control study using Environmental influences on Child Health Outcomes Program cohorts for discovery and independent replication. Wheeze and allergic sensitization were defined by number of wheeze episodes and positive specific IgE at age 1 year, respectively. Asthma was defined as physician diagnosis of asthma at age 5 or 6 years. We used untargeted metabolomics, controlling for observed and latent confounding factors, to assess associations between the plasma metabolome and early-life wheeze, allergy, and childhood asthma. RESULTS: Eighteen plasma metabolites were associated with first-year wheeze in the discovery cohort (n = 338). Z,Z unconjugated bilirubin (UCB) and its related metabolites exhibited a dose-response relationship with wheeze frequency; UCB levels were 13% (ß = 0.87; 95% CI, 0.74-1.02) and 22% (ß = 0.78; 95% CI, 0.68-0.91) lower in children with 1 to 3 and 4+ wheeze episodes compared with those who never wheezed, respectively. UCB levels were also associated with childhood asthma (ß = 0.82; 95% CI, 0.68-0.98). Similar trends were observed in 2 independent cohorts. UCB was significantly negatively correlated with eicosanoid- and oxidative stress-related metabolites. There were no significant associations between metabolites and allergic sensitization. CONCLUSIONS: We identified a novel inverse, dose-dependent association between UCB and recurrent wheeze and childhood asthma. Inflammatory lipid mediators and oxidative stress byproducts inversely correlated with UCB, suggesting that UCB modulates pathways critical to the development of early-life recurrent wheeze and childhood asthma.


Assuntos
Asma/metabolismo , Asma/fisiopatologia , Bilirrubina/metabolismo , Hipersensibilidade/metabolismo , Sons Respiratórios/fisiopatologia , Estudos de Casos e Controles , Criança , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Hipersensibilidade/fisiopatologia , Masculino
10.
Nat Commun ; 12(1): 249, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431872

RESUMO

Airway mucus is essential for lung defense, but excessive mucus in asthma obstructs airflow, leading to severe and potentially fatal outcomes. Current asthma treatments have minimal effects on mucus, and the lack of therapeutic options stems from a poor understanding of mucus function and dysfunction at a molecular level and in vivo. Biophysical properties of mucus are controlled by mucin glycoproteins that polymerize covalently via disulfide bonds. Once secreted, mucin glycopolymers can aggregate, form plugs, and block airflow. Here we show that reducing mucin disulfide bonds disrupts mucus in human asthmatics and reverses pathological effects of mucus hypersecretion in a mouse allergic asthma model. In mice, inhaled mucolytic treatment loosens mucus mesh, enhances mucociliary clearance, and abolishes airway hyperreactivity (AHR) to the bronchoprovocative agent methacholine. AHR reversal is directly related to reduced mucus plugging. These findings establish grounds for developing treatments to inhibit effects of mucus hypersecretion in asthma.


Assuntos
Dissulfetos/metabolismo , Hipersensibilidade/fisiopatologia , Pulmão/fisiopatologia , Muco/metabolismo , Adolescente , Adulto , Animais , Asma/metabolismo , Asma/fisiopatologia , Modelos Animais de Doenças , Expectorantes/farmacologia , Feminino , Glicoproteínas/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade
12.
Ann Allergy Asthma Immunol ; 126(6): 666-673, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33465457

RESUMO

BACKGROUND: Comorbidities are common in asthma and may complicate treatment response. OBJECTIVE: To examine response to omalizumab in patients with moderate-to-severe allergic asthma by asthma-related and allergic comorbidities. METHODS: Patients aged 12 years or more from placebo-controlled 008/009 (n = 1071), EXTRA (n = 848), and INNOVATE (n = 419), and single-armed PROSPERO (n = 801) omalizumab studies were included. Poisson regression/analysis of covariance models were used to estimate adjusted exacerbation rates and forced expiratory volume in 1 second (FEV1) change from baseline after omalizumab initiation for subgroups by number of comorbidities (0, 1 [008/009]; 0, 1, ≥2 [EXTRA and INNOVATE]; 0, 1, 2, ≥3 [PROSPERO]). Self-reported comorbidities included allergic rhinoconjunctivitis, chronic rhinosinusitis, recurrent acute sinusitis, nasal polyps, atopic and contact dermatitis, urticaria, food allergy, anaphylaxis, other allergies, gastroesophageal reflux disease, eosinophilic esophagitis, and eosinophilic granulomatosis with polyangiitis. RESULTS: In the EXTRA and INNOVATE studies, no consistent pattern was observed for placebo-corrected relative rate reduction in normalized asthma exacerbations among omalizumab-treated comorbidity subgroups. In PROSPERO, on-study exacerbation rates in the comorbidity subgroups were similar (0, 0.68; 1, 0.70; 2, 0.77; ≥3, 0.80). FEV1 improvements were observed throughout the study for omalizumab vs placebo for all comorbidity subgroups. There were no consistent differences in FEV1 improvements among comorbidity subgroups in 008/009, EXTRA, or INNOVATE. Similarly, no among-group differences were observed for FEV1 change from baseline at month 12 in PROSPERO (0, 0.05 L; 1, 0.08 L; 2, 0.00 L; ≥3, 0.04 L). The 95% confidence intervals overlapped substantially in all instances. CONCLUSION: In these analyses of placebo-controlled/single-armed studies, on-study exacerbation rates and FEV1 improvements with omalizumab treatment were similar irrespective of comorbidity burden. TRIAL REGISTRATION: ClinicalTrials.gov identifiers are as follows: EXTRA, NCT00314574 (https://clinicaltrials.gov/ct2/show/NCT00314574); INNOVATE, NCT00046748 (https://clinicaltrials.gov/ct2/show/NCT00046748); and PROSPERO, NCT01922037 (https://clinicaltrials.gov/ct2/show/NCT01922037).


Assuntos
Antialérgicos/uso terapêutico , Antiasmáticos/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Omalizumab/uso terapêutico , Adolescente , Adulto , Idoso , Criança , Comorbidade , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/fisiopatologia , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/epidemiologia , Pólipos Nasais/fisiopatologia , Sinusite/tratamento farmacológico , Sinusite/epidemiologia , Sinusite/fisiopatologia , Resultado do Tratamento , Adulto Jovem
13.
J Asthma ; 58(3): 316-325, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-31709879

RESUMO

BACKGROUND: There is conflicting data regarding the role of transforming growth factor-ß1 (TGF-ß1) in the pathogenesis of airway hyper-reactivity and asthma exacerbation. OBJECTIVE: To investigate the role of exhaled-TGF-ß1 in exercise-induced bronchospasm (EIB) in asthmatic and nonasthmatic healthy children, and in asthma exacerbation and asthma control. METHODS: The exhaled-TGF-ß1 levels of 56 stable asthmatic children and 15 nonasthmatic healthy children were evaluated before and 30 min after an exercise challenge. The exhaled-TGF-ß1 levels of 20 additional children with asthma exacerbation were evaluated. RESULTS: While no significant difference in the exhaled-TGF-ß1 levels was found at the baseline, exhaled-TGF-ß1 levels after the exercise challenge were significantly higher in the non-EIB (n = 31) asthmatics when compared to the asthmatic children with EIB (n = 25) (p = 0.04). Although there was a statistically significant increase in the concentration of the exhaled-TGF-ß1 after the exercise challenge in the non-EIB asthmatics (p = 0.008), the concentration of the TGF-ß1 was not increased after the exercise challenge in EIB + asthmatics. The exhaled-TGF-ß1 was significantly correlated with the ACT score (p = 0.01, r = 0.49) and the baseline FEV1 level (p = 0.02, r = 0.35). The exhaled-TGF-ß1 levels were significantly higher in the stable asthmatic children when compared to the nonasthmatic children (p < 0.0001). There was no significant difference in exhaled-TGF-ß1 levels after the exercise challenge in the nonasthmatics. The exhaled-TGF-ß1 levels were significantly lower in those children with asthma exacerbation when compared to the stable asthmatic children (p = 0.0003). CONCLUSION: Our results suggest that TGF-ß1 may play a role in suppressing airway reactivity and its deficiency is associated with asthma exacerbation.


Assuntos
Asma Induzida por Exercício/fisiopatologia , Asma/fisiopatologia , Testes Respiratórios/métodos , Fator de Crescimento Transformador beta1/análise , Adolescente , Asma/epidemiologia , Biomarcadores , Criança , Eosinófilos/citologia , Feminino , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/fisiopatologia , Imunoglobulina E/sangue , Masculino , Testes de Função Respiratória , Índice de Gravidade de Doença
14.
J Asthma ; 58(3): 334-339, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-31868051

RESUMO

OBJECTIVE: The forced oscillation technique (FOT) is a useful diagnostic respiratory system for children. However, the final value of the FOT in the diagnosis of bronchoconstriction is still open. The aim of the study was to evaluate the sensitivity and specificity of the FOT vs. body plethysmography tests in the measure of bronchoconstriction in asthmatic children. MATERIALS AND METHODS: A total of 102 children aged 2 to 6 years diagnosed with early-onset asthma and 52 healthy controls were included in this prospective, randomized study. All asthmatic patients and healthy controls underwent a basic FOT as one measurement, according to the recommendation of the Resmon Pro FOT. Then, the reversibility test was performed 20 min after the administration of 200 mg salbutamol using the FOT and body plethysmography in all patients. RESULTS: The mean basic Rrs, Xrs and sRaw in asthmatic patients were, respectively, 11.13 ± 1.28 kPa sL-1, -4.6 ± 1.18 kPa sL-1 and 1.72 ± 0.58 kPa s. Similar parameters were significantly better in the control group (p < 0.05). A total of 73 (71.6%) asthmatic patients had a positive test using the FOT according to Calogero. In 4 (7.7%) patients in the control group, a positive test was obtained. In body plethysmography, similar results were reached, with a positive test in 76 (74.5%) study patients and 5 (9.6%) control patients. CONCLUSIONS: A bronchial reversibility test with the use of the FOT is useful for the diagnosis of bronchial asthma, especially with the use of an Rrs parameter, such as the body plethysmography test.


Assuntos
Asma/fisiopatologia , Broncoconstrição/fisiologia , Oscilometria/métodos , Pletismografia Total/métodos , Asma/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/fisiopatologia , Masculino , Oscilometria/normas , Pletismografia Total/normas , Estudos Prospectivos , Reprodutibilidade dos Testes , Testes de Função Respiratória/métodos
15.
Pharmacol Ther ; 217: 107648, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32758645

RESUMO

Atopic diseases refer to common allergic inflammatory diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and allergic asthma (AA). AD often develops in early childhood and may herald the onset of other allergic disorders such as food allergy (FA), AR, and AA. This progression of the disease is also known as the atopic march, and it goes hand in hand with a significantly impaired quality of life as well as a significant economic burden. Atopic diseases usually are considered as T helper type 2 (Th2) cell-mediated inflammatory diseases. Thymic stromal lymphopoietin (TSLP), an epithelium-derived pro-inflammatory cytokine, activates distinct immune and non-immune cells. It has been shown to be a master regulator of type 2 immune responses and atopic diseases. In experimental settings, the inhibition or knockout of TSLP signaling has shown great therapeutic potential. This, in conjunction with the increasing knowledge about the central role of TSLP in the pathogenesis of atopic diseases, has sparked an interest in TSLP as a druggable target. In this review, we will discuss the autocrine and paracrine effects of TSLP, how it regulates the tissue microenvironment and drives atopic diseases, which provide the rationale for the increasing interest in TSLP as a druggable target.


Assuntos
Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Hipersensibilidade/fisiopatologia , Fatores Etários , Produtos Biológicos/farmacologia , Microambiente Celular/fisiologia , Citocinas/genética , Progressão da Doença , Humanos , Mediadores da Inflamação/fisiologia , Janus Quinases/metabolismo , Isoformas de Proteínas , Índice de Gravidade de Doença , Transdução de Sinais/fisiologia , Células Th2/metabolismo
16.
Front Immunol ; 11: 2143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072078

RESUMO

Animals have evolved circadian rhythms to adapt to the 24-h day-night cycle. Circadian rhythms are controlled by molecular clocks in the brain and periphery, which is driven by clock genes. The circadian rhythm is propagated from the brain to the periphery by nerves and hormones. Glucocorticoids (GCs) are a class of steroid hormones produced by the adrenal cortex under the control of the circadian rhythm and the stress. GCs have both positive and negative effects on the immune system. Indeed, they are well known for their strong anti-inflammatory and immunosuppressive effects. Endogenous GCs inhibit the expression of inflammatory cytokines and chemokines at the active phase of mice, regulating the circadian rhythm of tissue inflammation. In addition, GCs induce the rhythmic expression of IL-7R and CXCR4 on T cells, which supports T cell maintenance and homing to lymphoid tissues. Clock genes and adrenergic neural activity control the T cell migration and immune response. Taken together, circadian factors shape the diurnal oscillation of innate and adaptive immunity. Among them, GCs participate in the circadian rhythm of innate and adaptive immunity by positive and negative effects.


Assuntos
Imunidade Adaptativa/fisiologia , Ritmo Circadiano/fisiologia , Citocinas/biossíntese , Glucocorticoides/fisiologia , Imunidade Inata/fisiologia , Receptores de Citocinas/biossíntese , Imunidade Adaptativa/genética , Animais , Asma/genética , Asma/imunologia , Asma/fisiopatologia , Linfócitos B/imunologia , Quimiotaxia de Leucócito/imunologia , Quimiotaxia de Leucócito/fisiologia , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/genética , Ritmo Circadiano/imunologia , Citocinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/farmacologia , Humanos , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Hipersensibilidade/fisiopatologia , Imunidade Inata/genética , Memória Imunológica/efeitos dos fármacos , Infecções/genética , Infecções/imunologia , Infecções/fisiopatologia , Camundongos , Modelos Imunológicos , Receptores CXCR4/biossíntese , Receptores CXCR4/genética , Receptores de Citocinas/genética , Receptores de Interleucina-7/biossíntese , Receptores de Interleucina-7/genética , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia
17.
Allergy Asthma Proc ; 41(5): 363-371, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32867891

RESUMO

Background: Multiple immunoglobulin E (IgE) mediated sensitizations and/or allergies often coexist in patients with allergic rhinitis (AR). Several simultaneous allergen exposures in multiple IgE-mediated sensitizations and/or allergies may increase the allergen load and be related to disease severity. No study has verified whether positive allergen serum IgE levels and allergen categories together are associated with AR severity in adults. Objective: To investigate the effects of perennial dust mites (DMs) allergy and multiple serum sIgE-mediated autumn pollen allergy coexistence on symptom severity in adult patients with AR in autumn. Methods: In total, 153 patients with AR and with autumn pollen allergy (Artemisia argyi, ragweed, and hop) with or without DMs allergy were recruited in the autumn pollen season. Symptom severity was assessed by using the Chinese version of the visual analog scale (VAS): four rhinitis symptoms (sneezing, rhinorrhea, nasal pruritus, and nasal congestion) and two ocular symptoms (ocular itching and/or grittiness and/or redness, and ocular tearing) were scored at approximately the same period. We measured allergen serum sIgE levels for the inhaled allergens. The effects of DMs allergy and multiple autumn pollen allergy coexistence on symptom severity were analyzed. Results: Neither the sum of the autumn pollen allergens categories (total number of positive autumn pollen allergens, i.e., Artemisia argyi or ragweed or hop positive: 1; Artemisia argyi and ragweed positive: 2; Artemisia argyi, ragweed, and hop positive: 3) nor serum sIgE levels( total sIgE levels of positive autumn pollen allergens) exerted any influence on the severity of nasal and ocular symptoms (p > 0.05). When the concomitant DMs allergy status was considered, the sum of the positive autumn pollen allergen categories and accumulated positive autumn pollen and DMs serum sIgE levels (total levels of serum sIgE of positive autumn pollen allergens plus the levels of serum sIgE of DMs) had no influence on patients' symptom severity (p > 0.05). Conclusion: The coexistence of perennial DMs allergy and multiple autumn pollen allergy did not affect the severity of symptoms among adult patients with AR and with autumn pollen allergy in autumn.


Assuntos
Antígenos de Dermatophagoides/imunologia , Antígenos de Plantas/imunologia , Hipersensibilidade/fisiopatologia , Imunoglobulina E/metabolismo , Pólen/imunologia , Rinite Alérgica Sazonal/fisiopatologia , Adolescente , Adulto , Ambrosia/imunologia , Animais , Artemisia/imunologia , Feminino , Humanos , Humulus/imunologia , Hipersensibilidade/complicações , Imunização , Masculino , Pessoa de Meia-Idade , Pyroglyphidae/imunologia , Rinite Alérgica Sazonal/complicações , Estações do Ano , Índice de Gravidade de Doença , Adulto Jovem
18.
J Immunol Methods ; 487: 112870, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32961242

RESUMO

The skin prick test is used to diagnose patients' sensitization to antigens through a mediated IgE response. It is a practical and quick exam, but its diagnosis depends on instruments for measuring the allergic response and observer's interpretation. The conventional method for inferring about the allergic reaction is performed from the dimensions of the wheals, which are measured using a ruler or a caliper. To make this diagnosis less dependent on human interpretation, the present study proposes two alternative methods to infer about the allergic reaction: computational determination of the wheal area and a study of the temperature variation of the patient's skin in the puncture region. For this purpose, prick test using histamine was performed on 20 patients randomly selected. The areas were determined by the conventional method using the dimensions of the wheals measured with a digital caliper 30 min after the puncture. The wheal areas were also determined by a Python algorithm using photographs of the puncture region obtained with a smartphone. A variable named circularity deviation was also determined for each analyzed wheal. The temperature variation was monitored using an infrared temperature sensor, which collected temperature data for 30 min. All results were statistically compared or correlated. The results showed that the computational method to infer the wheal areas did not differ significantly from the areas determined by the conventional method (p-value = 0.07585). Temperature monitoring revealed that there was a consistent temperature increase in the first minutes after the puncture, followed by stabilization, so that the data could be adjusted by a logistic equation (R2 = 0.96). This adjustment showed that the optimal time to measure the temperature is 800 s after the puncture, when the temperature stabilization occurs. The results have also shown that this temperature stabilization has a significant positive correlation with wheal area (p-value = 0.0015). Thus, we concluded that the proposed computational method is more accurate to infer the wheal area when compared to the traditional method, and that the temperature may be used as an alternative parameter to infer about the allergic reaction.


Assuntos
Hipersensibilidade/diagnóstico , Interpretação de Imagem Assistida por Computador , Imunoglobulina E/imunologia , Testes Intradérmicos , Fotografação , Temperatura Cutânea , Pele/imunologia , Termografia , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Hipersensibilidade/fisiopatologia , Interpretação de Imagem Assistida por Computador/instrumentação , Testes Intradérmicos/instrumentação , Aplicativos Móveis , Fotografação/instrumentação , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Pele/patologia , Pele/fisiopatologia , Smartphone , Termografia/instrumentação , Fatores de Tempo
20.
Prostaglandins Other Lipid Mediat ; 150: 106477, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32711128

RESUMO

Polyunsaturated fatty acids (PUFAs), represented by the omega-6 fatty acid arachidonic acid (AA) and omega-3 fatty acid docosahexaenoic acid (DHA), are essential components of the human body. PUFAs are converted enzymatically into bioactive lipid mediators, including AA-derived cysteinyl leukotrienes (cys-LTs) and lipoxins and DHA-derived protectins, which orchestrate a wide range of immunological responses. For instance, eosinophils possess the biosynthetic capacity of various lipid mediators through multiple enzymes, including 5-lipoxygenase and 15-lipoxygenase, and play central roles in the regulation of allergic diseases. Dysregulated metabolism of PUFAs is reported, especially in severe asthma, aspirin-exacerbated respiratory disease, and eosinophilic chronic rhinosinusitis (ECRS), which is characterized by the overproduction of cys-LTs and impaired synthesis of pro-resolving mediators. Recently, by performing a multi-omics analysis (lipidomics, proteomics, and transcriptomics), we demonstrated the metabolic derangement of eosinophils in inflamed tissues of patients with ECRS. This abnormality occurred subsequent to altered enzyme expression of gamma-glutamyl transferase-5. In this review, we summarize the previous findings of dysregulated PUFA metabolism in allergic diseases, and discuss future prospective therapeutic strategies for correcting this imbalance.


Assuntos
Asma/fisiopatologia , Eosinófilos/imunologia , Ácidos Graxos Insaturados/metabolismo , Hipersensibilidade/fisiopatologia , Inflamação/fisiopatologia , Animais , Asma/imunologia , Asma/metabolismo , Eosinófilos/metabolismo , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Inflamação/imunologia , Inflamação/metabolismo
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