RESUMEN
BACKGROUND: Although remission occur, childhood-onset asthma may persist until adulthood. Since few longitudinal population-based studies have followed a cohort from childhood until adulthood, the knowledge on predictors of persistence of asthma is sparse. AIM: To estimate persistence of asthma from 8 to 28 years and its associated factors. METHODS: Within the OLIN (Obstructive Lung Disease in Northern Sweden) studies, a cohort was recruited in 1996 (age 8y, n = 3430) and followed annually with questionnaires about asthma and risk factors until 19y. Clinical examinations included skin prick tests (at 8, 12 and 19y) and lung function tests (17 and 19y) whereof a subsample performed bronchial hyperreactivity test. We identified n = 248 with asthma at 8y whereof 170 (69%) participated in a follow-up at 28y (73% of possible to invite). RESULTS: Of the 170 participants at 28y, 105 (61.8%) had persistent asthma (women: 49/76, 64.5%; men: 56/94, 59.6%, p = 0.513). Factors collected at recruitment: allergic sensitization (OR7.8, 95%CI 3.0-20.2), severe respiratory infection (OR2.6, 95%CI 1.1-6.3) and higher asthma severity score (OR1.6, 95%CI 1.1-2.4) were associated with asthma at 28y after adjustment for sex, family history of asthma, breastfeeding <3 months and eczema. Replacing allergic sensitization with rhinoconjunctivitis in the model yielded OR3.4 (95%CI 1.5-8.0). Bronchial hyperreactivity at age 17y associated with asthma at 28y (OR9.0, 95%CI 1.7-47.0). CONCLUSIONS: Among children with asthma onset by 8y, 62% still had asthma at age 28 years. Persistent asthma was associated with allergic sensitization, rhinoconjunctivitis, severe respiratory infection, a more severe asthma and bronchial hyperreactivity.
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Asma , Hiperreactividad Bronquial , Eccema , Infecciones del Sistema Respiratorio , Masculino , Niño , Humanos , Femenino , Adulto , Adolescente , Hiperreactividad Bronquial/epidemiología , Hiperreactividad Bronquial/complicaciones , Factores de Riesgo , Pruebas Cutáneas , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/complicacionesRESUMEN
BACKGROUND: Allergic rhinitis can be associated with bronchial hyperreactivity (BHR) and create an increased risk for allergic asthma development. We aimed to investigate the effects of subcutaneous immunotherapy (SCIT) on BHR and asthma development in adult patients with allergic rhinitis. METHODS: The retrospective case-control study was carried out between November 2018 and May 2019 in Süreyyapasa Chest Diseases and Thoracic Surgery Training and Research Hospital. In this study, data was recorded for patients with a mite and/or grasses/cereals pollen allergy who were tested for BHR before planned SCIT, and who had allergic rhinitis, with or without asthma. The SCIT group was selected as those who received SCIT for at least one year. The control group was selected from those who were scheduled to receive SCIT but were waived and still receiving medication. Symptom scores, prick test results, PC20 levels (methacholine challenge that is a provocative concentration causing a 20% fall in FEV1), and the presence of asthma were recorded and compared with data from at least one year after treatment. RESULTS: A total of sixty-eight subjects (22 males, 46 females; mean age 40.54 ± 12.27 years; SCIT: 40, Control: 28) were enrolled.Although the changes in log PC20 levels were not statistically significant in both SCIT and control groups after an average of 30-35 months of treatment, it was found to be significant in favor of the SCIT group when two groups were compared in terms of the change in log PC20 (p = 0.026). The development and improvement of asthma were not significantly different between the SCIT and control group but tended to increase in the control group. The percentage of patients with progressed/BHR was significantly higher in the controls (70.6% vs. 38.1%, p = 0.046). DISCUSSION: In our real life study we have demonstrated the preventative effect of SCIT on BHR, but not on asthma developmen.
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Asma , Hiperreactividad Bronquial , Rinitis Alérgica , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Hiperreactividad Bronquial/complicaciones , Estudios de Casos y Controles , Estudios Retrospectivos , Rinitis Alérgica/terapia , Asma/terapia , Asma/complicaciones , InmunoterapiaRESUMEN
Asthma is a T helper 2 (Th2) cell-associated chronic inflammatory diseases characterized with airway obstruction, increased mucus production, and eosinophil infiltration. Conventional medications for asthma treatment cannot fully control the symptoms, and potential side effects are also the concerns. Thus, complement or alternative medicine (CAM) became a new option for asthma management. Ding Chuan Tang (DCT) is a traditional Chinese herbal decoction applied mainly for patients with coughing, wheezing, chest tightness, and asthma. Previously, DCT has been proved to improve children airway hyperresponsiveness (AHR) in a randomized and double-blind clinical trial. However, the mechanisms of how DCT alleviates AHR remain unclear. Since asthmatic features such as eosinophil infiltration, IgE production, and mucus accumulation are relative with Th2 responses, we hypothesized that DCT may attenuate asthma symptoms through regulating Th2 cells. Ovalbumin (OVA) was used as a stimulant to sensitize BALB/c mice to establish an asthmatic model. AHR was detected one day before sacrifice. BALF and serum were collected for immune cell counting and antibody analysis. Splenocytes were cultured with OVA in order to determine Th2 cytokine production. Lung tissues were collected for histological and gene expression analyses. Our data reveal that DCT can attenuate AHR and eosinophil accumulation in the 30-day sensitization asthmatic model. Histological results demonstrated that DCT can reduce cell infiltration and mucus production in peribronchial and perivascular site. In OVA-stimulated splenocyte cultures, a significant reduction of IL-5 and IL-13 in DCT-treated mice suggests that DCT may alleviate Th2 responses. In conclusion, the current study demonstrates that DCT has the potential to suppress allergic responses through the reduction of mucus production, eosinophil infiltration, and Th2 activity in asthma.
Asunto(s)
Asma/tratamiento farmacológico , Asma/inmunología , Eosinófilos/fisiología , Inmunización , Ovalbúmina/inmunología , Extractos Vegetales/uso terapéutico , Neumonía/tratamiento farmacológico , Neumonía/inmunología , Animales , Asma/sangre , Asma/fisiopatología , Hiperreactividad Bronquial/sangre , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/fisiopatología , Líquido del Lavado Bronquioalveolar , Regulación hacia Abajo , Eosinófilos/efectos de los fármacos , Femenino , Inmunoglobulina E/sangre , Interleucina-13/biosíntesis , Interleucina-5/biosíntesis , Ratones Endogámicos BALB C , Moco/metabolismo , Extractos Vegetales/farmacología , Neumonía/complicaciones , Neumonía/fisiopatología , Bazo/patologíaRESUMEN
Exposure of the respiratory system to the Anisakis pegreffii L3 crude extract (AE) induces airway inflammation; however, the mechanism underlying this inflammatory response remains unknown. AE contains allergens that promote allergic inflammation; exposure to AE may potentially lead to asthma. In this study, we aimed to establish a murine model to assess the effects of AE on characteristic features of chronic asthma, including airway hypersensitivity (AHR), airway inflammation, and airway remodeling. Mice were sensitized for five consecutive days each week for 4 weeks. AHR, lung inflammation, and airway remodeling were evaluated 24 h after the last exposure. Lung inflammation and airway remodeling were assessed from the bronchoalveolar lavage fluid (BALF). To confirm the immune response in the lungs, changes in gene expression in the lung tissue were assessed with reverse transcription-quantitative PCR. The levels of IgE, IgG1, and IgG2a in blood and cytokine levels in the BALF, splenocyte, and lung lymph node (LLN) culture supernatant were measured with ELISA. An increase in AHR was prominently observed in AE-exposed mice. Epithelial proliferation and infiltration of inflammatory cells were observed in the BALF and lung tissue sections. Collagen deposition was detected in lung tissues. AE exposure increased IL-4, IL-5, and IL-13 expression in the lung, as well as the levels of antibodies specific to AE. IL-4, IL-5, and IL-13 were upregulated only in LLN. These findings indicate that an increase in IL-4+ CD4+ T cells in the LLN and splenocyte resulted in increased Th2 response to AE exposure. Exposure of the respiratory system to AE resulted in an increased allergen-induced Th2 inflammatory response and AHR through accumulation of inflammatory and IL-4+ CD4+ T cells and collagen deposition. It was confirmed that A. pegreffii plays an essential role in causing asthma in mouse models and has the potential to cause similar effects in humans.
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Remodelación de las Vías Aéreas (Respiratorias) , Anisakis/fisiología , Neumonía/fisiopatología , Neumonía/parasitología , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Animales , Especificidad de Anticuerpos/inmunología , Biomarcadores/metabolismo , Hiperreactividad Bronquial/sangre , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/fisiopatología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Cloruro de Metacolina/farmacología , Ratones Endogámicos BALB C , Neumonía/sangre , Neumonía/complicaciones , Células Th2/metabolismoRESUMEN
Obesity is a risk factor for the development of asthma and represents a difficult-to-treat disease phenotype. Aerobic glycolysis is emerging as a key feature of asthma, and changes in glucose metabolism are linked to leukocyte activation and adaptation to oxidative stress. Dysregulation of PKM2 (pyruvate kinase M2), the enzyme that catalyzes the last step of glycolysis, contributes to house dust mite (HDM)-induced airway inflammation and remodeling in lean mice. It remains unclear whether glycolytic reprogramming and dysregulation of PKM2 also contribute to obese asthma. The goal of the present study was to elucidate the functional role of PKM2 in a murine model of obese allergic asthma. We evaluated the small molecule activator of PKM2, TEPP46, and assessed the role of PKM2 using conditional ablation of the Pkm2 allele from airway epithelial cells. In obese C57BL/6NJ mice, parameters indicative of glycolytic reprogramming remained unchanged in the absence of stimulation with HDM. Obese mice that were subjected to HDM showed evidence of glycolytic reprogramming, and treatment with TEPP46 diminished airway inflammation, whereas parameters of airway remodeling were unaffected. Epithelial ablation of Pkm2 decreased central airway resistance in both lean and obese allergic mice in addition to decreasing inflammatory cytokines in the lung tissue. Lastly, we highlight a novel role for PKM2 in the regulation of glutathione-dependent protein oxidation in the lung tissue of obese allergic mice via a putative IFN-γ-glutaredoxin1 pathway. Overall, targeting metabolism and protein oxidation may be a novel treatment strategy for obese allergic asthma.
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Asma/enzimología , Asma/patología , Hipersensibilidad/enzimología , Hipersensibilidad/patología , Inflamación/enzimología , Inflamación/patología , Piruvato Quinasa/metabolismo , Animales , Asma/complicaciones , Asma/parasitología , Hiperreactividad Bronquial/complicaciones , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Activación Enzimática/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Glutatión/metabolismo , Glucólisis , Homeostasis/efectos de los fármacos , Hipersensibilidad/complicaciones , Hipersensibilidad/parasitología , Mediadores de Inflamación/metabolismo , Pulmón/enzimología , Pulmón/patología , Ratones Endogámicos C57BL , Ratones Obesos , Modelos Biológicos , Piridazinas/administración & dosificación , Piridazinas/farmacología , Pyroglyphidae , Pirroles/administración & dosificación , Pirroles/farmacologíaRESUMEN
Hydrogen chloride is available commercially as an anhydrous gas or an aqueous solution, hydrochloric acid. Exposure to this gas has been associated with the development of reactive airways dysfunction syndrome. However, there are few published reports. A 37-year-old woman developed progressive bronchospasm and acute respiratory failure after cleaning an enclosed space with an unknown concentration of hydrochloric acid gas from a cleaning substance. She had no prior history of asthma or atopy. Severe bronchospasm developed, leading to hypoxemia and diffuse interstitial infiltrates, necessitating orotracheal intubation and admission to the intensive care unit. Asthma-like symptoms such as cough, wheezing, and dyspnea; requiring bronchodilators, and repeated hospitalizations are persistent a year after the accident. Pulmonary function testing showed mild airflow obstruction.
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Humanos , Femenino , Adulto , Síndrome de Dificultad Respiratoria del Recién Nacido/complicaciones , Insuficiencia Respiratoria/etiología , Ácido Clorhídrico/efectos adversos , Inhalación , Hiperreactividad Bronquial/complicacionesRESUMEN
Allergic rhinitis and asthma are common chronic allergic diseases of the respiratory tract, which are accompanied by immunoglobulin E (IgE)-mediated inflammation and the involvement of type 2 T helper cells, mast cells, and eosinophils. Cordyceps sinensis (Berk.) Sacc is a fungal parasite on the larva of Lepidoptera. It has been considered to be a health-promoting food and, also, one of the best-known herbal remedies for the treatment of airway diseases, such as asthma and lung inflammation. In the present study, we demonstrated the antiallergic rhinitis effect of Cs-4, a water extract prepared from the mycelium culture of Cordyceps sinensis (Berk) Sacc, on ovalbumin (OVA)-induced allergic rhinitis in mice and the anti-asthmatic effect of Cs-4 in a rat model of asthma. Treatment with Cs-4 suppressed the nasal symptoms induced in OVA-sensitized and challenged mice. The inhibition was associated with a reduction in IgE/OVA-IgE and interleukin (IL)-4/IL-13 levels in the nasal fluid. Cs-4 treatment also decreased airway responsiveness and ameliorated the scratching behavior in capsaicin-challenged rats. It also reduced plasma IgE levels, as well as IgE and eosinophil peroxidase levels, in the bronchoalveolar fluid. Cs-4 treatment completely suppressed the increases in IL-4, IL-5, and IL-13 levels in rat lung tissue. In conclusion, our results suggest that Cs-4 has the potential to alleviate immune hypersensitivity reactions in allergic rhinitis and asthma.
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Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Cordyceps/química , Micelio/química , Rinitis Alérgica/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Asma/sangre , Asma/complicaciones , Asma/fisiopatología , Peso Corporal/efectos de los fármacos , Bronquios/efectos de los fármacos , Hiperreactividad Bronquial/sangre , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/tratamiento farmacológico , Hiperreactividad Bronquial/fisiopatología , Líquido del Lavado Bronquioalveolar , Capsaicina/farmacología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Peroxidasa del Eosinófilo/metabolismo , Femenino , Liberación de Histamina/efectos de los fármacos , Inmunización , Inmunoglobulina E/sangre , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Cloruro de Metacolina/farmacología , Ratones Endogámicos BALB C , Lavado Nasal (Proceso) , Ovalbúmina/inmunología , Ratas Sprague-Dawley , Rinitis Alérgica/sangre , Rinitis Alérgica/complicaciones , Piel/efectos de los fármacos , Piel/patología , Bazo/efectos de los fármacos , Bazo/patología , Tráquea/efectos de los fármacos , beta-N-Acetilhexosaminidasas/metabolismoRESUMEN
INTRODUCTION: Asthma afflicts more than 300 million people. Contemporary mainstay therapies (inhaled corticosteroids and bronchodilators), prescribed empirically, control symptoms resulting from airways obstruction tolerably well in many patients but it is less clear that they alter the natural history of progressive airways inflammation and remodeling resulting in severe, therapy-resistant obstruction in a significant minority (5-10%), causing lifelong symptoms and elevated risk of recurrent hospital admission and death. Furthermore, no current anti-asthma drug targets bronchial smooth muscle hyperresponsiveness, a critical contributor to airways obstruction and the fundamental physiological abnormality characterizing asthma. Recent monoclonal antibody (biological) therapies reduce obstruction and exacerbations in some, but not all treated patients to an unpredictable extent, but are further limited by administration logistics and cost. AREAS COVERED: An overview of the cellular and molecular immunopathology of asthma, highlighting the need and logic for the development of a novel, non-steroidal, small molecule drug for topical delivery targeting bronchial smooth muscle hyperresponsiveness and airways inflammation, particularly corticosteroid-refractory inflammation. EXPERT OPINION: This article elaborates evidence supporting the hypothesis that topically delivered, inhaled antagonists of the calcium-sensing receptor (CaSR) have the potential to meet these requirements, and the practicality of repurposing existing, small molecule CaSR antagonists (calcilytics) for this purpose.
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Obstrucción de las Vías Aéreas/tratamiento farmacológico , Antiasmáticos/farmacología , Asma/tratamiento farmacológico , Hiperreactividad Bronquial/tratamiento farmacológico , Receptores Sensibles al Calcio/antagonistas & inhibidores , Administración por Inhalación , Corticoesteroides , Obstrucción de las Vías Aéreas/complicaciones , Obstrucción de las Vías Aéreas/etiología , Antiasmáticos/administración & dosificación , Antiasmáticos/uso terapéutico , Asma/complicaciones , Hiperreactividad Bronquial/complicaciones , Broncodilatadores , Humanos , Inflamación/tratamiento farmacológicoRESUMEN
Lung immune responses to respiratory pathogens and allergens are initiated in early life which will further influence the later onset of asthma. The airway epithelia form the first mechanical physical barrier to allergic stimuli and environmental pollutants, which is also the key regulator in the initiation and development of lung immune response. However, the epithelial regulation mechanisms of early-life lung immune responses are far from clear. Our previous study found that integrin ß4 (ITGB4) is decreased in the airway epithelium of asthma patients with specific variant site. ITGB4 deficiency in adult mice aggravated the lung Th2 immune responses and enhanced airway hyper-responsiveness (AHR) with a house dust mite (HDM)-induced asthma model. However, the contribution of ITGB4 to the postnatal lung immune response is still obscure. Here, we further demonstrated that ITGB4 deficiency following birth mediates spontaneous lung inflammation with ILC2 activation and increased infiltration of eosinophils and lymphocytes. Moreover, ITGB4 deficiency regulated thymic stromal lymphopoietin (TSLP) production in airway epithelial cells through EGFR pathways. Neutralization of TSLP inhibited the spontaneous inflammation significantly in ITGB4-deficient mice. Furthermore, we also found that ITGB4 deficiency led to exaggerated lung allergic inflammation response to HDM stress. In all, these findings indicate that ITGB4 deficiency in early life causes spontaneous lung inflammation and induces exaggerated lung inflammation response to HDM aeroallergen.
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Células Epiteliales/metabolismo , Hipersensibilidad/complicaciones , Hipersensibilidad/inmunología , Integrina beta4/metabolismo , Pulmón/patología , Neumonía/complicaciones , Animales , Animales Recién Nacidos , Hiperreactividad Bronquial/complicaciones , Citocinas/metabolismo , Células Epiteliales/patología , Receptores ErbB/metabolismo , Hipersensibilidad/parasitología , Hipersensibilidad/fisiopatología , Pulmón/parasitología , Linfocitos/inmunología , Ratones Transgénicos , Fosforilación , Pyroglyphidae/fisiología , Linfopoyetina del Estroma TímicoRESUMEN
Asthma, a common disorder associated with airway inflammation and hyperresponsiveness, remains a significant clinical burden in need of novel therapeutic strategies. Patients are increasingly seeking complementary and alternative medicine approaches to control their symptoms, including the use of natural products. Ginger, a natural product that we previously demonstrated acutely relaxes airway smooth muscle (ASM), has long been reported to possess anti-inflammatory properties, although a precise mechanistic understanding is lacking. In these studies, we demonstrate that chronic administration of whole ginger extract or 6-shogaol, a bioactive component of ginger, mitigates in vivo house dust mite antigen-mediated lung inflammation in mice. We further show that this decrease in inflammation is associated with reduced in vivo airway responsiveness. Utilizing in vitro studies, we demonstrate that 6-shogaol augments cAMP concentrations in CD4 cells, consistent with phosphodiesterase inhibition, and limits the induction of nuclear factor-κB signaling and the production of proinflammatory cytokines in activated CD4 cells. Sustained elevations in cAMP concentration are well known to inhibit effector T cell function. Interestingly, regulatory T cells (Tregs) utilize cAMP as a mediator of their immunosuppressive effects, and we demonstrate here that 6-shogaol augments the Treg polarization of naïve CD4 cells in vitro. Taken together with previous reports, these studies suggest that ginger and 6-shogaol have the potential to combat asthma via two mechanisms: acute ASM relaxation and chronic inhibition of inflammation.
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Asma/tratamiento farmacológico , Catecoles/uso terapéutico , Neumonía/tratamiento farmacológico , Zingiber officinale/química , Resistencia de las Vías Respiratorias/efectos de los fármacos , Animales , Antígenos CD/metabolismo , Antígenos Dermatofagoides/inmunología , Asma/complicaciones , Asma/inmunología , Asma/fisiopatología , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/fisiopatología , Líquido del Lavado Bronquioalveolar/citología , Catecoles/administración & dosificación , Catecoles/farmacología , Recuento de Células , AMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Femenino , Interleucina-4/metabolismo , Pulmón/patología , Masculino , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Neumonía/complicaciones , Neumonía/inmunología , Neumonía/patología , Transducción de Señal/efectos de los fármacos , Linfocitos T Reguladores/efectos de los fármacosRESUMEN
The premature neonate is at high risk for childhood airway hyperreactivity and episodes of wheezing. Intermittent hypoxic events are frequently observed during the first weeks and months of life in these infants. Intermittent hypoxemia has been associated with adverse outcomes in extremely premature infants; including the diagnosis of bronchopulmonary dysplasia, reported wheezing, and use of prescription asthma medications. We review the incidence of intermittent hypoxia, their potential role in short and longer term respiratory morbidity, and the translational newborn models now being used to investigate common pathways by which intermittent hypoxia contributes to respiratory disease.
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Hiperreactividad Bronquial/epidemiología , Hipoxia/epidemiología , Enfermedades del Prematuro/epidemiología , Hiperreactividad Bronquial/complicaciones , Displasia Broncopulmonar/epidemiología , Displasia Broncopulmonar/etiología , Niño , Humanos , Hipoxia/complicaciones , Hipoxia/congénito , Incidencia , Lactante , Recien Nacido Extremadamente Prematuro , Recién Nacido , Morbilidad , Trastornos Respiratorios/epidemiología , Trastornos Respiratorios/etiología , Ruidos Respiratorios/etiologíaRESUMEN
BACKGROUND: Sensitization to allergen has long been known to be relate to childhood allergic diseases. Polysensitised children have more severe atopic diseases, whereas allergic rhinitis or asthma children with cosensitized to food and inhalant allergens were under-researched. OBJECTIVE: To realize the association between sensitization to food allergens and pediatric allergic rhinitis and asthma in Taiwan. METHODS: We included 138 participants with sensitized to allergen as assessed by serum-specific IgE. 87 of 138 participants had allergic rhinitis and 51 participants had asthma. All participants underwent a physical examination and measurement of serum total and specific IgE values. Besides, nasal peak expiratory flow rate (nPEFR) that was performed by the participants with allergic rhinitis and were requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQ). Lung function test and asthma control test (ACT)/child asthma control test (C-ACT) were performed by the participants with asthma. RESULTS: 39 of 87 allergic rhinitis participants with sensitized to food and inhalant allergens (AR food group), 48 of 87 allergic rhinitis participants with sensitized to inhalant allergen alone (AR inhalant group). The AR food group had significantly lower nPEFR values and higher total IgE values (p < 0.05) compared with the AR inhalant group. The AR food group had higher PRQLQ scores than the AR inhalant group. 24 of 51 asthma participants with sensitized to food and inhalant allergens (Asthma food group), 27 of 51 asthma participants with sensitized to inhalant allergen alone (Asthma inhalant group). The Asthma food group had significantly higher total IgE values (p < 0.05) compared with the Asthma inhalant group. The Asthma food group had lower lung function test values and asthma control test (ACT) scores than the other group. CONCLUSIONS: Children with cosensitized to food and inhalant allergens have more severe clinical symptoms and abnormal laboratory findings. Sensitization to food allergen was more related to pediatric allergic rhinitis than asthma. We may need larger, longer and extended studies to confirm these findings.
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Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/inmunología , Hipersensibilidad a los Alimentos/complicaciones , Hipersensibilidad a los Alimentos/inmunología , Adolescente , Adulto , Alérgenos , Asma/inmunología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina E/sangre , Masculino , Persona de Mediana Edad , Examen Físico , Pruebas de Función Respiratoria , Rinitis Alérgica , Encuestas y Cuestionarios , Taiwán , Adulto JovenRESUMEN
It has been recently reported that cigarette smoke exposure during allergen sensitization facilitates the development of allergic asthma; however, the underlying mechanisms remain elusive. We evaluated the role of interleukin (IL-23) in a cigarette smoke extract (CSE)-induced Dermatophagoides pteronyssinus (Dp)-allergic asthma mouse model. BALB/c mice were exposed to CSE during allergen sensitization period. Anti-IL-23p19 or IL-23R antibody was administered during the sensitization period. And we evaluated several immunological responses. The expression of IL-23 and IL-23 receptor (IL-23R) was examined in lung tissue. IL-23 and IL-23R expression was increased in the airway epithelium of Dp/CSE co-administered mice. CSE administration during the sensitization promoted Dp-allergic sensitization and the development of asthma phenotypes. Additionally, the proportion of innate lymphoid type 2 cells (ILC2) was also increased by CSE and Dp co-instillation. Anti-IL-23 or IL-23R antibody treatment during allergen sensitization significantly diminished phenotypes of allergic asthma and the ILC2 population. The levels of IL-33 and thymic stromal lymphopoietin (TSLP) were also significantly reduced by anti-IL-23 or IL-23R antibody treatment. IL-23 may thus play a significant role in cigarette smoke-induced allergic sensitization and asthma development. Clinically, the increase in allergen sensitization due to cigarette exposure causes onset of asthma, and IL-23 may be important in this mechanism. KEY MESSAGES: IL-23 and IL-23R expression was increased in the lung epithelium of Dp and CSE co-exposed mice during sensitization period. The population of ILC2s was increased in Dp and CSE co-exposed mice during sensitization period. Anti-IL23 or IL-23R antibody treatment with co-administration of CSE and HDM during sensitization period significantly suppresses ILC2. In vitro, IL-23 blockade in Dp and CSE-stimulated epithelial cells suppressed IL-13 expression in ILC2.
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Asma/patología , Fumar Cigarrillos/efectos adversos , Interleucina-23/metabolismo , Animales , Anticuerpos/farmacología , Asma/complicaciones , Asma/inmunología , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/inmunología , Citocinas/metabolismo , Células Dendríticas/efectos de los fármacos , Dermatophagoides pteronyssinus , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Epitelio/efectos de los fármacos , Epitelio/patología , Femenino , Inmunidad Innata/efectos de los fármacos , Inmunización , Interleucina-13/metabolismo , Interleucina-33/metabolismo , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Ratones Endogámicos BALB C , Fenotipo , Neumonía/complicaciones , Neumonía/inmunología , Neumonía/patología , Receptores de Interleucina/metabolismo , Linfopoyetina del Estroma TímicoRESUMEN
BACKGROUND: Stability of asthma is a clinical phenotype of the disease based on long-term evaluation of control of asthma symptoms and its exacerbations. A relationship between airway inflammation and clinical classification of asthma based on stability criterion has not been well studied. OBJECTIVES: The purpose of our study was to analyze the inflammation profile of stable and unstable asthma in adolescents treated with moderate and high doses of inhaled corticosteroids. METHODS: 139 young asthmatics of 16.8 (3.25) years were classified in the stable group (Nâ¯=â¯72) and unstable group (Nâ¯=â¯67) after a 3-month prospective observation. Inflammatory markers including cytogram of the induced sputum (IS), fractional exhaled nitric oxide (FeNO) and bronchial hyperresponsiveness (BHR) following provocation with hypertonic saline and exercises, as well as clinical and spirometric parameters in both groups were compared. RESULTS: 75% of patients with unstable asthma revealed elevated percentage of eosinophils in the induced sputum (>2.5%), and mean values were significantly higher in comparison with stable asthma: 2.0 (0,5-4,2) vs 5,5 (2,6-11,3), pâ¯<â¯0,001. Bronchial hyperresponsiveness was markedly higher in unstable asthma, especially in asthma with eosinophilic profile; statistically significant differences also related to functional pulmonary tests. In multivariate analysis, asthma instability was significantly associated with sEos (pâ¯=â¯0.005), BHR (pâ¯=â¯0.001) but not FeNO (pâ¯=â¯0.24). CONCLUSION (AND CLINICAL RELEVANCE): Eosinophilic inflammation, relatively resistant to high doses of inhaled corticosteroids, is a dominant type of inflammation in unstable asthma in adolescents. Asthma instability is also associated with higher bronchial hyperresponsiveness and lower spirometric parameters. In the light of the new studies and progress in biological methods of therapy of eosinophilic inflammation, unstable asthma, especially in case of severe course, requires extended diagnostics with determination of inflammatory phenotype.
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Remodelación de las Vías Aéreas (Respiratorias)/inmunología , Asma/tratamiento farmacológico , Asma/fisiopatología , Eosinófilos/citología , Inflamación/inmunología , Administración por Inhalación , Adolescente , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Asma/metabolismo , Biomarcadores/sangre , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/fisiopatología , Estudios Transversales , Eosinófilos/patología , Espiración , Femenino , Humanos , Masculino , Óxido Nítrico/metabolismo , Fenotipo , Estudios Prospectivos , Pruebas de Función Respiratoria/métodos , Esputo/citología , Esputo/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Studies have shown that airway obstruction and increased bronchial reactivity are present in early life in children developing asthma, which challenges the dogma that airway inflammation leads to low lung function. Further studies are needed to explore whether low lung function and bronchial hyperreactivity are inherent traits increasing the risk of developing airway inflammation and asthmatic symptoms in order to establish timely primary preventive initiatives. METHODS AND FINDINGS: We investigated 367 (89%) of the 411 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) birth cohort born to mothers with asthma, who were assessed by spirometry and bronchial reactivity to methacholine from age 1 month, plethysmography and bronchial reversibility from age 3 years, cold dry air hyperventilation from age 4 years, and exercise challenge at age 7 years. The COPSAC pediatricians diagnosed and treated asthma based on symptom load, response to inhaled corticosteroid, and relapse after treatment withdrawal according to a standardized algorithm. Repeated measures mixed models were applied to analyze lung function trajectories in children with asthma ever or never at age 1 month to 13 years. The number of children ever versus never developing asthma in their first 13 years of life was 97 (27%) versus 270 (73%), respectively. Median age at diagnosis was 2.0 years (IQR 1.2-5.7), and median remission age was 6.2 years (IQR 4.2-7.8). Children with versus without asthma had reduced lung function (z-score difference, forced expiratory volume, -0.31 [95% CI -0.47; -0.15], p < 0.001), increased airway resistance (z-score difference, specific airway resistance, +0.40 [95% CI +0.24; +0.56], p < 0.001), increased bronchial reversibility (difference in change in forced expiratory volume in the first second [ΔFEV1], +3% [95% CI +2%; +4%], p < 0.001), increased reactivity to methacholine (z-score difference for provocative dose, -0.40 [95% CI -0.58; -0.22], p < 0.001), decreased forced expiratory volume at cold dry air challenge (ΔFEV1, -4% [95% CI -7%; -1%], p < 0.01), and decreased forced expiratory volume after exercise (ΔFEV1, -4% [95% CI -7%; -1%], p = 0.02). Both airway obstruction and bronchial hyperreactivity were present before symptom debut, independent of disease duration, and did not improve with symptom remission. The generalizability of these findings may be limited by the high-risk nature of the cohort (all mothers had a diagnosis of asthma), the modest study size, and limited ethnic variation. CONCLUSIONS: Children with asthma at some point at age 1 month to 13 years had airway obstruction and bronchial hyperreactivity before symptom debut, which did not worsen with increased asthma symptom duration or attenuate with remission. This suggests that airway obstruction and bronchial hyperreactivity are stable traits of childhood asthma since neonatal life, implying that symptomatic disease may in part be a consequence of these traits but not their cause.
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Obstrucción de las Vías Aéreas/epidemiología , Asma/epidemiología , Hiperreactividad Bronquial/epidemiología , Adolescente , Factores de Edad , Obstrucción de las Vías Aéreas/complicaciones , Asma/etiología , Hiperreactividad Bronquial/complicaciones , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Prospectivos , Pruebas de Función Respiratoria , EspirometríaRESUMEN
OBJECTIVE: To examine the effect of metanol extract of Petiveria alliacea (PM) on airway inflflammation in a murine model of chronic asthma. METHODS: Two-month-old male BALB/c mice (n=6-8/group) were sensitized on days 0 and 14 by intraperitoneal injection of 20 µg ovalbumin (OVA). On day 25, the mice received an airway challenge with OVA (3%, w/v, in phosphate buffered saline). PM was administered orally by oral gavage to mice at doses of 100, 200 and 400 mg/kg body weight once daily from days 18 to 23. Control mice were orally administered phosphate buffered saline (PBS) to induce a model of asthma. At the end of the test, respiratory reactivity was assayed, the total cell number, interleukin-4 (IL-4), IL-5, IL-13, tumor necrosis factor-alpha (TNF-α) and reactive oxygen species (ROS) in the bronchoalveolar lavage fluid (BALF) were determined and the levels of serum IgE, intercellular cell adhesion molecule 1 (ICAM-1) and eotoxin were measured. In addition, lung tissue was used to qualify the IL-4, IL-5, IL-13, TNF-α and transforming growth factor beta 1 (TGF-ß1). Histologic examination was performed to observe inflammatory cellular infiltration. RESULTS: The administration of PM in comparison with the OVA-only treated group signifificantly attenuated the infifiltration of eosinophils and other inflflammatory cells (P<0.01). Airway resistance (RI) in the OVA-only induced group was significantly higher than that of the PBS control group (P<0.01) when methacholine was added. TNF-α, IgE, TGF-ß1 and cytokine levels IL-4, IL-5, IL-13 in the BALF decreased compared to control mice (P<0.01 or P<0.05). PM treatment also inhibited the production of chemokines, eotaxin and ICAM-1 in BALF (P<0.01), which improved lung function. Histopathological examination revealed that the sensitized treated PM groups had significant lower in inflammatory scores similar to dexamethasone treatments and the untreated group. CONCLUSION: Administration of PM could inhibit airway inflammation, regulate cytokines, chemokines and enhance pulmonary conditions in allergic murine model of asthma.
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Alérgenos/inmunología , Asma/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Pulmón/patología , Ovalbúmina/inmunología , Phytolaccaceae/química , Extractos Vegetales/uso terapéutico , Células Th2/inmunología , Animales , Asma/sangre , Asma/inmunología , Asma/fisiopatología , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/tratamiento farmacológico , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/fisiopatología , Líquido del Lavado Bronquioalveolar , Quimiocinas/metabolismo , Modelos Animales de Enfermedad , Inmunoglobulina E/sangre , Inflamación/sangre , Inflamación/complicaciones , Inflamación/inmunología , Pulmón/inmunología , Pulmón/fisiopatología , Masculino , Metanol , Ratones Endogámicos BALB C , Moco/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Bronchial hyperresponsiveness (BHR) is defined as a heightened bronchoconstrictive response to airway stimuli. It complements the cardinal features in asthma, such as variable or reversible airflow limitation and airway inflammation. Although BHR is considered a pathophysiologic hallmark of asthma, it should be acknowledged that this property of the airway is dynamic, because its severity and even presence can vary over time with disease activity, triggers or specific exposure, and with treatment. In addition, it is important to recognize that there is a component that is not reflective of a specific disease entity.
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Asma/diagnóstico , Asma/fisiopatología , Hiperreactividad Bronquial/diagnóstico , Hiperreactividad Bronquial/fisiopatología , Pruebas de Provocación Bronquial/métodos , Asma/complicaciones , Hiperreactividad Bronquial/complicaciones , HumanosRESUMEN
Asthma is a common chronic airway inflammation disease and is considered as a major public health problem. Fisetin (3,3',4',7-tetrahydroxyflavone) is a naturally occurring flavonoid abundantly found in different vegetables and fruits. Fisetin has been reported to exhibit various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. We evaluated the effects of fisetin on allergic asthma regulation in mice. Mice were first sensitized, then airway-challenged with ovalbumin (OVA). Whether fisetin treatment attenuated OVA-induced airway inflammation was examined via inflammation inhibition through MyD88-related NF-κB (p65) signaling pathway. Mice were divided into the control (Con), OVA-induced asthma (Mod), 40 (FL) and 50 (FH) mg/kg fisetin-treated OVA-induced asthma groups. Our results found that OVA-induced airway inflammation in mice caused a significant inflammatory response via the activation of MyD88 and NF-κB signaling pathways, leading to release of pro-inflammatory cytokines. In contrast, fisetin-treated mice after OVA induction inhibited activation of MyD88 and NF-κB signaling pathways, resulting in downregulation of pro-inflammatory cytokine secretion. Further, fisetin significantly ameliorated the airway hyperresponsiveness (AHR) towards methacholine (Mch). In addition, fisetin reduced the number of eosinophil, monocyte, neutrophil and total white blood cell in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. The serum and BALF samples obtained from the OVA-induced mice with fisetin showed lower levels of pro-inflammatory cytokines. The results of our study illustrated that fisetin may be a new promising candidate to inhibit airway inflammation response induced by OVA.
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Flavonoides/uso terapéutico , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Neumonía/tratamiento farmacológico , Neumonía/metabolismo , Transducción de Señal , Resistencia de las Vías Respiratorias/efectos de los fármacos , Animales , Asma/complicaciones , Asma/fisiopatología , Hiperreactividad Bronquial/complicaciones , Hiperreactividad Bronquial/fisiopatología , Recuento de Células , Citocinas/metabolismo , Modelos Animales de Enfermedad , Flavonoides/farmacología , Flavonoles , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/farmacología , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/fisiopatología , Masculino , Ratones Endogámicos C57BL , Ovalbúmina , Neumonía/complicaciones , Neumonía/fisiopatología , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 5/metabolismoRESUMEN
Environmental factors which cause asthma are those that induce airway inflammation with eosinophils (more common) or neutrophils along with airway hyperresponsiveness (AHR). The most common of these (indeed the most common cause of asthma) are IgE-mediated inhalant allergen exposures. Allergen-induced AHR and inflammation are both associated with the allergen-induced late asthmatic response (LAR). Although allergens were previously recognized only as causes of symptoms and bronchoconstriction in asthmatics, we now appreciate them as causes of the fundamental pathophysiologic features of asthma. Low-molecular-weight chemical sensitizers, causes of occupational asthma, also cause asthma in a manner analogous to allergen. Acute irritant-induced asthma (reactive airways dysfunction syndrome) following a very heavy irritant exposure and chronic irritant-induced asthma following repeated high exposures can also induce persistent or permanent changes (inflammation and AHR) consistent with asthma. Textile dust exposure produces a different form of airway disease (byssinosis) which is less frequently observed currently. Environmental exposure to tobacco smoke facilitates the development of asthma in children. Personal smoking and environmental air pollution have an inconsistent and likely generally small effect in causing asthma.
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Asma Ocupacional/etiología , Asma/etiología , Bisinosis/etiología , Exposición a Riesgos Ambientales , Alérgenos/efectos adversos , Asma/metabolismo , Hiperreactividad Bronquial/complicaciones , Eosinófilos/metabolismo , Humanos , Inflamación/complicaciones , Irritantes/efectos adversos , Neutrófilos/metabolismo , Contaminación por Humo de Tabaco/efectos adversosRESUMEN
BACKGROUND: Filaggrin loss-of-function (FLG-LOF) mutations are an established genetic cause of eczema. These mutations have subsequently been reported to increase the risk of aeroallergen sensitization and allergic airway disease. However, it is unclear whether FLG variants require both eczema and aeroallergen sensitization to influence airway disease development long-term outcomes. OBJECTIVE: To examine the effects of FLG-LOF mutations on allergic airway disease outcomes, with eczema and aeroallergen sensitization as intermediate variables, using the Isle of Wight birth cohort. METHODS: Study participants were evaluated at ages 1, 2, 4, 10 and 18 years to ascertain the development of allergic diseases (eczema, asthma and allergic rhinitis) and aeroallergen sensitization (determined by skin prick tests). FLG-LOF mutations were genotyped in 1150 subjects. To understand the complex associations between FLG mutations, intermediate variables (eczema and aeroallergen sensitization) and airway disease, path analysis was performed. RESULTS: There were significant total effects of FLG-LOF mutations on both asthma and allergic rhinitis at all ages as well as on aeroallergen sensitization up till 10 years old. In the filaggrin-asthma analysis, a direct effect of FLG-LOF mutations was observed on early childhood eczema (age 1 and 2 years) (relative risk (RR) 2.01, 95% CI: 1.74-2.31, P < .001), and all significant indirect pathways on asthma outcomes passed through eczema at these ages. In contrast, for the filaggrin-rhinitis model, FLG-LOF mutations exerted significant direct effects on early eczema as well as rhinitis at 10 years (RR 1.99; 95% CI: 1.72-2.29, P = .002). CONCLUSION: FLG-LOF mutations are a significant risk factor for later childhood asthma and rhinitis. However, the pathway to asthma is only through early childhood eczema while a direct effect was observed for childhood rhinitis.