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- Abnormal Chemokine Receptor Profile on Circulating T Lymphocytes from Nonallergic Asthma Patients. [JOURNAL ARTICLE]
- Int Arch Allergy Immunol 2014 Aug 21; 164(3):228-236.
Background: T lymphocytes are involved in the pathogenesis of nonallergic asthma. The objective of this study was to characterize the subset distribution and pattern of chemokine receptor expression in circulating T lymphocyte subsets from nonallergic asthma patients. Methods: Forty stable nonallergic asthma patients and 16 sex- and age-matched healthy donors were studied. Twelve patients did not receive inhaled steroids (untreated patients), 16 received 50-500 μg b.i.d. of inhaled fluticasone propionate (FP) (standard-dose patients), and 12 received over 500 μg b.i.d. of inhaled FP (high-dose patients) for at least 12 months prior to the beginning of this study and were clinically well controlled. Flow cytometry was performed using a panel of monoclonal antibodies (4 colors). Results: Nonallergic asthma patients treated with high doses of inhaled FP showed a significant reduction in the percentages of CD3+ T lymphocytes compared to healthy controls. Untreated patients showed a significant increase in CCR6 expression in CD8+CD25+ and CD8+CD25+bright T cells compared to healthy controls. The results were similar for CXCR3 and CCR5 expression. In patients treated with standard doses of FP, CCR5 expression was significantly increased in CD3+ T lymphocytes relative to healthy controls. Conclusions: The different groups of clinically stable nonallergic asthmatic patients showed distinct patterns of alterations in subset distribution as well as CCR6, CXCR3, and CCR5 expression on circulating T lymphocytes. © 2014 S. Karger AG, Basel.
- Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. [JOURNAL ARTICLE]
- Cochrane Database Syst Rev 2014 Sep 1.:CD001288.
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major cause of hospital admission and mortality. They contribute to long-term decline in lung function, physical capacity and quality of life. The most common causes are infective, and treatment includes antibiotics, bronchodilators and systemic corticosteroids as anti-inflammatory agents.To assess the effects of corticosteroids administered orally or parenterally for treatment of acute exacerbations of COPD, and to compare the efficacy of parenteral versus oral administration.We carried out searches using the Cochrane Airways Group Specialised Register of Trials, MEDLINE and CENTRAL (Cochrane Central Register of Controlled Trials), and checked references of included studies and trials registries. We conducted the last search in May 2014.Randomised controlled trials comparing corticosteroids administered orally or parenterally with an appropriate placebo, or comparing oral corticosteroids with parenteral corticosteroids in the treatment of people with acute exacerbations of COPD. Other interventions (e.g. bronchodilators and antibiotics) were standardised for both groups. We excluded clinical studies of acute asthma.We used standard methodological procedures expected by The Cochrane Collaboration.Sixteen studies (n = 1787) met inclusion criteria for the comparison systemic corticosteroid versus placebo and 13 studies contributed data (n = 1620). Four studies (n = 298) met inclusion criteria for the comparison oral corticosteroid versus parenteral corticosteroid and three studies contributed data (n = 239). The mean age of participants with COPD was 68 years, median proportion of males 82% and mean forced expiratory volume in one second (FEV1) per cent predicted at study admission was 40% (6 studies; n = 633). We judged risk of selection, detection, attrition and reporting bias as low or unclear in all studies. We judged risk of performance bias high in one study comparing systemic corticosteroid with control and in two studies comparing intravenous corticosteroid versus oral corticosteroid.Systemic corticosteroids reduced the risk of treatment failure by over half compared with placebo in nine studies (n = 917) with median treatment duration 14 days, odds ratio (OR) 0.48 (95% confidence interval (CI) 0.35 to 0.67). The evidence was graded as high quality and it would have been necessary to treat nine people (95% CI 7 to 14) with systemic corticosteroids to avoid one treatment failure. There was moderate-quality evidence for a lower rate of relapse by one month for treatment with systemic corticosteroid in two studies (n = 415) (hazard ratio (HR) 0.78; 95% CI 0.63 to 0.97). Mortality up to 30 days was not reduced by treatment with systemic corticosteroid compared with control in 12 studies (n = 1319; OR 1.00; 95% CI 0.60 to 1.66).FEV1, measured up to 72 hours, showed significant treatment benefits (7 studies; n = 649; mean difference (MD) 140 mL; 95% CI 90 to 200); however, this benefit was not observed at later time points. The likelihood of adverse events increased with corticosteroid treatment (OR 2.33; 95% CI 1.59 to 3.43). Overall, one extra adverse effect occurred for every six people treated (95% CI 4 to 10). The risk of hyperglycaemia was significantly increased (OR 2.79; 95% CI 1.86 to 4.19). For general inpatient treatment, duration of hospitalisation was significantly shorter with corticosteroid treatment (MD -1.22 days; 95% CI -2.26 to -0.18), with no difference in length of stay the intensive care unit (ICU) setting.Comparison of parenteral versus oral treatment showed no significant difference in the primary outcomes of treatment failure, relapse or mortality or for any secondary outcomes. There was a significantly increased rate of hyperglycaemia in one study (OR 4.89; 95% CI 1.20 to 19.94).There is high-quality evidence to support treatment of exacerbations of COPD with systemic corticosteroid by the oral or parenteral route in reducing the likelihood of treatment failure and relapse by one month, shortening length of stay in hospital inpatients not requiring assisted ventilation in ICU and giving earlier improvement in lung function and symptoms. There is no evidence of benefit for parenteral treatment compared with oral treatment with corticosteroid on treatment failure, relapse or mortality. There is an increase in adverse drug effects with corticosteroid treatment, which is greater with parenteral administration compared with oral treatment.
- T Lymphocyte Antigen 4-Modified Dendritic Cell Therapy for Asthmatic Mice Guided by the CCR7 Chemokine Receptor. [JOURNAL ARTICLE]
- Int J Mol Sci 2014; 15(9):15304-15319.
The CD80/CD86-CD28 axis is a critical pathway for immuno-corrective therapy, and the cytotoxic T lymphocyte antigen 4 (CTLA4) is a promising immunosuppressor targeting the CD80/CD86-CD28 axis; however, its use for asthma therapy needs further optimization. A human CTLA4 fused with the IgCγ Fc (CTLA4Ig) and mouse CC chemokine receptor type7 (CCR7) coding sequences were inserted into a recombinant adenovirus (rAdV) vector to generate rAdV-CTLA4Ig and rAdV-CCR7. The naive dendritic cells (DCs) were infected with these rAdVs to ensure CCR7 and CTLA4Ig expression. The therapeutic effects of modified DCs were evaluated. rAdV-CTLA4Ig and rAdV-CCR7 infected DCs improved all asthma symptoms. Inflammatory cell infiltration and cytokine analysis showed that rAdV-CTLA4Ig and rAdV-CCR7-modified DC therapy reduced the number of eosinophils and lymphocyte and neutrophil infiltration in the lung. Interestingly, assessment of the humoral immunity showed that the IL-4 and IFNγ levels of the rAdV-CTLA4Ig and rAdV-CCR7-modified DC-treated mice decreased significantly and did not reverse the Th1/Th2 balance. DCs expressing CCR7 displayed guidance ability for DC migration, primarily for DCs in the inflammatory lung. Additionally, the rAdVs caused an inflammatory response by inducing DC differentiation, inflammatory cell infiltration and changes in cytokines; however, mice transplanted with rAdV-green fluorescent protein (GFP)-infected DCs displayed no asthma manifestations. In conclusion, CTLA4Ig-modified DCs exhibited a therapeutic effect on asthma, and CCR7 may guide DC homing. The combination of these two molecules may be a model for precision-guided immunotherapy.
- [Gastroenteritis eosinofílica.] [JOURNAL ARTICLE]
- Rev Alerg Mex 2014 Jul-Sep; 61(3):212-8.
The eosinophilic gastroenteritis is a disease of unknown etiopathogenesis and rare presentation, with several clinical symptoms, ranging from mild episodes until nonspecific abdominal acute episodes of intestinal obstruction, which some times make it necessary urgent surgical treatment. This wide symptomatic range seems to be conditioned by the degree of eosinophilic infiltration of the intestinal wall and the number of layers involved. This paper reports the case of a patient who, due to the diagnosis difficulties, illustrates in a single patient the intestinal and respiratory anatomo-clinical diversity and the evolution of the eosinophilia both intestinal and peripheral. Patient was sent to our service with diagnoses of bronchial asthma, chronic allergic rhinitis and chronic anemia.
- Atopic dermatitis guideline. Position paper from the Latin American Society of Allergy, Asthma and Immunology. [JOURNAL ARTICLE]
- Rev Alerg Mex 2014 Jul-Sep; 61(3):178-211.
As in other regions, the incidence of atopic dermatitis in Latin America has been increasing in recent years. Although there are several clinical guidelines, many of their recommendations cannot be universal since they depend on the characteristics of each region. Thus, we decided to create a consensus guideline on atopic dermatitis applicable in Latin America and other tropical regions, taking into account socio-economic, geographical, cultural and health care system characteristics. The Latin American Society of Allergy Asthma and Immunology (SLAAI) conducted a systematic search for articles related to the pathophysiology, diagnosis and treatment of dermatitis using various electronic resources such as Google, Pubmed, EMBASE (Ovid) and Cochrane data base. We have also looked for all published articles in Latin America on the subject using LILACS (Latin American and Caribbean Literature on Health Sciences) database. Each section was reviewed by at least two members of the committee, and the final version was subsequently approved by all of them, using the Delphi methodology for consensus building. Afterward, the final document was shared for external evaluation with physicians, specialists (allergists, dermatologists and pediatricians), patients and academic institutions such as universities and scientific societies related to the topic. All recommendations made by these groups were taken into account for the final drafting of the document. There are few original studies conducted in Latin America about dermatitis; however, we were able to create a practical guideline for Latin America taking into account the particularities of the region. Moreover, the integral management was highlighted including many of the recommendations from different participants in the health care of this disease (patients, families, primary care physicians and specialists). This practical guide presents a concise approach to the diagnosis and management of atopic dermatitis that can be helpful for medical staff, patients and their families in Latin America.
- [Effects of reforestation on tree pollen sensitization in inhabitants of Nuevo Leon, Mexico.] [JOURNAL ARTICLE]
- Rev Alerg Mex 2014 Jul-Sep; 61(3):162-7.
Climate change has implications for health, ecology and society. Urban green areas are a key element in the planning of cities, promoting citizen interaction with the environment, as well as health. Lack of planning and design of these areas as well as the selection of ornamental trees can be a trigger of pollen allergy in the surrounding population. Reforestation is among the programs implemented by the government that have an impact on allergy. Environmental reforestation programs do not take into account the allergenic potential of some species. In the last 4 years, the government of Nuevo Leon, Mexico, has planted nearly 18,000 Quercus species trees, in addition to an unknown number of Fraxinus species trees that are listed as tree species with high pollen production.To identify changes in tree pollen sensitization, based on environmental reforestation programs.A retrospective and descriptive study was done in which positive skin prick tests to pollen from trees in the interval of 2010-2014 were analyzed, correlating between tree species used for reforestation and increased sensitivity to the former.A statistically significant increase in pollen sensitization to species with which Nuevo Leon was reforested was found, along with a decrease in sensitization to the species that were not reforested.Reforestation contributes to some extent to the change in the pattern of positive skin tests and may result in more frequent exacerbations of respiratory diseases. It is an activity that should always be regulated and assisted by experts in the according field.
- Prevalence of pollinosis in patients with allergic asthma, rhinitis and conjunctivitis in the South of Mexico City 2007-2013. [JOURNAL ARTICLE]
- Rev Alerg Mex 2014 Jul-Sep; 61(3):147-52.
The prevalence of pollinosis has doubled in the past two decades. Several studies suggest that up to 50% of adult residents of Mexico City can present manifestations of respiratory allergy, and pollens from trees, grasses and weeds are a common cause. To determine the prevalence of their families and antigenic cross-reactivity allows us to offer appropriate diagnoses and treatments.To know the prevalence of sensitization of pollens to trees, grasses and weeds in adults with respiratory allergy of the South zone of Mexico City from January 2007 to December 2013.A cross-sectional, observational and prospective study was done with patients from Mexico City, referred to the National Medical Center Siglo XXI, IMSS, from 2007 to 2013 with a diagnosis of allergic rhinitis, asthma and conjunctivitis. We analyzed the results of skin prick tests to pollens from trees, grasses and weeds in selected patients. The results were analyzed using descriptive statistics.A total of 672 patients were analyzed, 70% men, the average age was 34 ± 16 years. Regarding occupation 31% were students, 48% employees and 21% housewives. Fifty-three percent had rhinitis, 47% had asthma and 40.5% had both, asthma and rhinitis. Prevalence of sensitization to weeds was 56%, 33% to trees and 11% to grasses.Sensitization to weeds is the first cause of respiratory pollinosis in the south of Mexico City, Amaranthus was the most prevalent pollen in this area. Sensitization to trees is the second cause, with a predominance of trees form Betulaceae, Fagaceae and Oleacea families. Sensitization to grass is the third cause of respiratory pollinosis. The most common are from Pooideae (Lolium perenne), Chloroideae and Cynodon/Dactylon family.
- The roles of innate lymphoid cells in the development of asthma. [Journal Article, Review]
- Immune Netw 2014 Aug; 14(4):171-81.
Asthma is a common pulmonary disease with several different forms. The most studied form of asthma is the allergic form, which is mainly related to the function of Th2 cells and their production of cytokines (IL-4, IL-5, and IL-13) in association with allergen sensitization and adaptive immunity. Recently, there have been many advances in understanding non-allergic asthma, which seems to be related to environmental factors such as air pollution, infection, or even obesity. Cells of the innate immune system, including macrophages, neutrophils, and natural killer T cells as well as the newly described innate lymphoid cells, are effective producers of a variety of cytokines and seem to play important roles in the development of non-allergic asthma. In this review, we focus on recent findings regarding innate lymphoid cells and their roles in asthma.
- Cytoprotective Effect of Kaempferol on Paraquat-Exposed BEAS-2B Cells via Modulating Expression of MUC5AC. [Journal Article]
- Biol Pharm Bull 2014; 37(9):1486-94.
Mucins are highly glycosylated secretary proteins produced by most epithelial cells. Hypersecretion of mucins is one of the prominent symptoms of several airway diseases, including asthma, cystic fibrosis, nasal allergy, rhinitis, and sinusitis. Paraquat (PQ), a common herbicide, has been associated with pulmonary damage and is a potent reactive oxygen species (ROS) producer. However, until now the role of PQ on mucin overproduction has not been studied. The aim of this study is to explore how kaempferol (KM), a widely used dietary flavonoid, affects the protection of human PQ-exposed bronchial epithelium BEAS-2B cells by suppressing Mucin gene expression via nuclear factor-kappa B (NF-κB). We observed that PQ generates intracellular ROS, and also induces lipid peroxidation in BEAS-2B cells. Additionally, we found that PQ effectively induces the expression of the MUC5AC gene; however, co-treatment of PQ with KM drastically reduces its expression. Furthermore, we observed that PQ activates NF-κB, while co-treatment with KM occludes its nuclear translocation, and additionally KM repressed the PQ phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in BEAS-2B cells. Based on our data, we believe that KM can suppress the over-expression of the MUC5AC gene. This would contribute to the protection of PQ cytotoxicity to exposed BEAS-2B cells, and allow further study toward a better understanding of ROS-associated diseases.
- Mast cells in human airways: the culprit? [REVIEW]
- Eur Respir Rev 2014 Sep; 23(133):299-307.
By virtue of their undisputed role in allergy, the study of airway mast cells has focused on nasal and bronchial mast cells and their involvement in allergic rhinitis and asthma. However, recent mechanistic and human studies suggest that peripheral mast cells also have an important role in asthma, as well as chronic obstructive pulmonary disease, respiratory infections and lung fibrosis. Pathogenic roles include immune-modulatory, pro-inflammatory and pro-fibrotic activities. Importantly, mast cells also actively downregulate inflammation and participate in the defence against respiratory infections. Another complicating factor is the notorious mast cell heterogeneity, where each anatomical compartment of the lung harbours site-specific mast cell populations. Alveolar mast cells stand out as they lack the cardinal expression of the high affinity IgE receptor. Supporting the emerging concept of alveolar inflammation in asthma, alveolar mast cells shift to a highly FcϵRI-expressing phenotype in uncontrolled asthma. Site-specific and disease-associated mast cell changes have also recently been described in most other inflammatory conditions of the lung. Thus, in the exploration of new anti-mast cell treatment strategies the search has widened to include the lung periphery and the delicate task of identifying which of the countless potential roles are the critical disease modifying ones in a given clinical situation.