[MIA 2021, Comprehensive Asthma Management. Guidelines for Mexico]. / MIA 2021, Manejo Integral del Asma. Lineamientos para México.

BACKGROUND: Asthma continues to be one of the most frequent chronic respiratory diseases in our country. New methods for diagnosis and treatment have been described; accordingly, the international guidelines were renewed. OBJECTIVE: To create a national platform for the development of updated guidelines, solidly based on evidence: Comprehensive Asthma Management (Spanish acronym: MIA). METHODS: MIA uses the ADAPTE method. The MIA development group consists of experts in pulmonology-allergology-methodology and representatives of 13 institutions and societies of specialties that manage asthma. The international reference guidelines (selected with AGREE-II): GINA 2020, GEMA 5.0, BTS/SIGN 2019 and ATS/ERS consensus document 2014-2019 on severe asthma. MIA covers suspected asthma, diagnosis, treatment, and special groups. Key clinical questions were formulated on treatment steps 1-3, biomarkers and severe asthma. RESULTS: Based on evidence, safety, cost and local reality, the core group developed responses. Through a Delphi process the broad MIA development group suggested adjustments until consensus was reached. CONCLUSION: A document was generated with multiple figures and algorithms, solidly based on evidence about asthma management, adjusted for Mexico with a broad base among different societies that participated in its development. It does not include guidelines for acute asthma.

Antecedentes: El asma sigue siendo una patología respiratoria crónica frecuente en México. Se han descrito nuevos métodos para el diagnóstico y tratamiento conforme se renuevan las guías internacionales. Objetivo: Crear la plataforma nacional Manejo Integral del Asma (MIA), para el desarrollo de lineamientos actualizados con base en evidencia. Métodos: Se utilizó el método ADAPTE. El grupo de desarrollo de MIA estuvo integrado por expertos en neumología, alergología y metodología y representantes de 13 instituciones y sociedades de especialidades que manejan asma. Las guías internacionales de referencia (seleccionadas con AGREE-II) fueron GINA 2020, GEMA 5.0, BTS/SIGN 2019 y consenso ATS/ERS 2014-2019. En MIA se aborda sospecha de asma, diagnóstico, tratamiento y grupos especiales. Se formularon preguntas clínicas clave sobre tratamiento en los pasos 1 a 3, biomarcadores y asma grave. Resultados: Con base en evidencia, seguridad, costo y realidad local, el grupo nuclear desarrolló respuestas. Mediante proceso Delphi, el grupo amplio de desarrollo sugirió ajustes hasta que se logró el consenso. Conclusión: El documento generado contiene múltiples figuras y algoritmos, está sólidamente basado en evidencia acerca del manejo del asma y fue ajustado para México con participación de diferentes sociedades para su desarrollo; no se incluyeron lineamientos para la crisis asmática.

[Expression of CD152 and CD137 on T regulatory cells in rhinitis and bronchial asthma patients]. / Expresión de CD152 y CD137 en células T reguladoras de pacientes con rinitis y asma bronquial.

BACKGROUND: Allergic rhinitis and bronchial asthma are inflammatory conditions that have increased in prevalence over the past two decades; studies of the inflammatory response in these diseases have determined that T regulatory cells (Treg) have been considered as responsible for allergens tolerance. The expression of CTLA-4 (CD152) in Treg is associated with the functional activity of this population, moreover the expression of 4-1BB (CD137) has a controversial function. OBJECTIVE: To determine the existence of CTLA-4 and 4-1BB in Treg cells in peripheral blood of patients with rhinitis and/or asthma. MATERIAL AND METHOD: A comparative cross-sectional study was done with three groups of patients: 20 subjects with allergic rhinitis, 17 subjects with bronchial asthma and 17 subjects with both disorders; 19 healthy subjects conformed the control group. The frequency of Treg (CD4+, FoxP3+ and CD25hight) and the expression of CD152 and CD137 in these cells were assessed by flow cytometry in peripheral blood. RESULTS: We found that the group of subjects with bronchial asthma (p<0.001) and allergic rhinitis bronchial asthma (p<0.001) showed a significantly lower percentage of Treg (CD4+, CD25hight and FoxP3+) in peripheral blood compared to the healthy subjects controls. Only the group of subjects with bronchial asthma showed a significantly higher percentage of CD152+ (p<0.01) and CD137+ (p<0.01) Treg compared to control group. CONCLUSIONS: Subjects with bronchial asthma and bronchial asthma and allergic rhinitis disorders have a deficiency of CD4+, CD25hight and FoxP3+ Treg in peripheral blood; however, subjects with bronchial asthma had a higher frequency of CD152+ and CD137+ Treg cells.

Antecedentes: la rinitis alérgica y el asma bronquial son enfermedades inflamatorias cuya prevalencia ha aumentado en las últimas dos décadas. Los estudios de la respuesta inflamatoria en estas enfermedades muestran que las células T reguladoras (Treg) participan en la tolerancia inmunológica. La expresión de CTLA-4 (CD152) se asocia con la actividad funcional de esta población y la expresión de 4-1BB (CD137) tiene un papel controvertido. Objetivo: determinar la existencia de CTLA-4 y 4-1BB en las células Treg en sangre periférica de pacientes con rinitis, asma, o ambas. Material y método: estudio transversal comparativo en el que se reclutaron tres grupos de pacientes: 20 sujetos con rinitis alérgica, 17 sujetos con asma bronquial y 17 con ambos padecimientos. Se formó un grupo control de 19 sujetos sanos. Se analizó la frecuencia de células Treg en sangre periférica y la expresión de CD152 y CD137 en los diferentes grupos mediante citometría de flujo. Resultados: se encontró menor frecuencia estadísticamente significativa de células Treg (CD4+, CD25altas y FoxP3+) en los grupos de sujetos con: asma bronquial (p<0.001) y en el grupo de rinitis alérgica con asma bronquial (p<0.05) respecto del grupo de sujetos sanos. Los pacientes con asma bronquial únicamente tuvieron mayor frecuencia de células Treg que expresan CD152 (p <0.01) y CD137 (p<0.01) respecto del grupo control. Conclusiones: los sujetos con asma bronquial y rinitis alérgica y asma bronquial únicamente tienen deficiencia de Treg CD4+, CD25altas y FoxP3+ en sangre periférica y los sujetos con asma bronquial tienen mayor frecuencia de células Treg que expresan CD152 y CD137.

In the (sub)tropics allergic rhinitis and its impact on asthma classification of allergic rhinitis is more useful than perennial-seasonal classification.

BACKGROUND: Two different allergic rhinitis (AR) symptom phenotype classifications exist. Treatment recommendations are based on intermittent-persistent (INT-PER) cataloging, but clinical trials still use the former seasonal AR-perennial AR (SAR-PAR) classification. This study was designed to describe how INT-PER, mild-moderate/severe and SAR-PAR of patients seen by allergists are distributed over the different climate zones in a (sub)tropical country and how these phenotypes relate to allergen sensitization patterns. METHODS: Six climate zones throughout Mexico were determined, based on National Geographic Institute (Instituto Nacional de Estadística y Geografía) data. Subsequent AR patients (2-68 years old) underwent a blinded, standardized skin-prick test and filled out a validated questionnaire phenotyping AR. RESULTS: Five hundred twenty-nine subjects participated in this study. In the tropical zone with 87% house-dust mite sensitization, INT (80.9%; p < 0.001) and PAR (91%; p = 0.04) were more frequent than in the subtropics. In the central high-pollen areas, there was less moderate/severe AR (65.5%; p < 0.005). Frequency of comorbid asthma showed a clear north-south gradient, from 25% in the dry north to 59% in the tropics (p < 0.005). No differences exist in AR cataloging among patients with different sensitization patterns, with two minor exceptions (more PER in tree sensitized and more PAR in mold positives; p < 0.05). CONCLUSION: In a (sub)tropical country the SAR-PAR classification seems of limited value and bears poor relation with the INT-PER classification. INT is more frequent in the tropical zone. Because PER has been shown to relate to AR severity, clinical trials should select patients based on INT-PER combined with the severity cataloging because these make for a better treatment guide than SAR-PAR.

[Sensitization to Blomia tropicalis and Dermatophagoides pteronyssinus, farinae and siboney prevalence in patients with rhinitis, allergic asthma, or both, in a population of a metropolitan area of Mexico City]. / Prevalencia de la sensibilización a Blomia tropicalis y Dermatophagoides pteronyssinus, farinae y siboney en pacientes con rinitis o asma alérgica (o ambas) en una población de la zona metropolitana de la Ciudad de México.

BACKGROUND: The increased prevalence of asthma has been associated with an increase in atopic sensitization, and it is parallel with similar increases in other allergic diseases. In United States, Blomia tropicalis has the fourth place between the most known types of house dust mites, and is the most common in the southern subtropical states. In Mexico there have been few studies to investigate sensitization to this mite. OBJECTIVE: To identify the prevalence of sensitization to Blomia tropicalis and Dermatophagoides in patients with rhinitis and/or allergic bronchial asthma in a population of the metropolitan area of Mexico. PATIENTS AND METHOD: We selected 334 patients with a diagnosis of rhinitis and/or bronchial asthma, 149 men and 185 women, aged between 3 and 74 years, of which 189 had positive skin tests to at least one of the mites (Dermatophagoides and/or Blomia tropicalis). We measured the wheal area and compared the averages of the surface of the wheal and correlations were made of the results using the Pearson correlation coefficient. RESULTS: The total number of patients who presented positive skin test to Blomia tropicalis in association with other mites was 53 (28.0%) and the total number of patients who presented positive skin test to only Blomia tropicalis was 23 (12.1%). Correlations of r = 0.45, 0.45 and 0.68 (statistically significant, p < 0.05) were found between the three species of Dermatophagoides, while there was no correlation between positive dermoreactions of Blomia tropicalis with those of Dermatophagoides. CONCLUSIONS: In the metropolitan area of Mexico City, while not having a tropical or sub-tropical weather, it is important to include Blomia tropicalis in diagnostic panels of allergens.

Increased expression of CD30 and CD57 molecules on CD4(+) T cells from children with atopic asthma: a preliminary report.

T helper type 2 (Th2) cells play an important role in the onset and persistence of allergic airway inflammation. Consequently, many authors have attempted to identify cell surface markers associated with a Th2 phenotype. This work was aimed at correlating CD30 and CD57 expression on CD4(+) T cells with interleukin (IL)-4 production in peripheral blood mononuclear cells (PBMCs) from allergic patients. PBMCs from 17 children with atopic asthma and 12 nonatopic healthy control children were analyzed. The CD28, CD30, CD40L, CD57, CD62L, CD69, IL-4, and IFN-gamma expressions on CD4(+) T cells were determined by double immunofluorescence and flow cytometry in PBMCs ex vivo and after phorbol-12-myristate-13-acetate plus ionomycin (PMA/I) stimulation. An increased percentage of peripheral CD4(+)CD30(+) T cells was observed in asthmatic patients (p < 0.001). In addition, the percentage of CD4(+) T cells expressing IL-4, IFN-gamma, CD30, CD40L, CD57, or CD69 significantly increased (p < 0.01) after PMA/I stimulation, in asthmatic patients. The CD30 expression on CD4(+) T cells from asthmatic patients, after stimulation, correlated with both IL-4 and IFN-gamma production, whereas CD57 expression only correlated with IL-4 production. These data suggest that the expression of CD30 and CD57 cell markers on T cells could reflect circulating effector T cell early activation in the allergic airway disease.

[Hematopoietic steam cell transplantation in the management of systemic lupus erythematosus resistant to treatment]. / Trasplante de células madre hematopoyéticas en el manejo del lupus eritematoso sistémico resistente al tratamiento.

Recently stem cell transplantation has been suggested like novel treatment in some severe auto-immune diseases, specifically in severe and refractory to conventional treatment in systemic lupus erythematosus patients. Autologus hematopoietic steam cell transplantation has been used in systemic lupus erythematosus, because it does not represent risk of development in graft versus host disease, which is the most common and severe complication in alogenic transplant. This type of transplant is poorly used because of the difficulty to get donors and laboratory background. Patients under this type of treatment received high dosage of chemotherapy, followed by alogenic hematopoietic steam cell transplantation with or without T cell depletion. Most of cases have successes in treatment and some patients get clinical and serological remission even for 34 months. However, a longer following is necessary to obtain concluding results. This paper reviews those treatments in clinical cases reported in the literature.

[The Th2 theory in allergy: present and future directions]. / Teoría Th2 en alergia: actualidades y futuras direcciones.

Allergic diseases have been a model study for Th2 cells polarization and it is well known that the synthesis of the human IgE results from collaboration between Th2 and B cells through the cytokines such as IL-4 and IL-13 and surface molecules (CD40-CD40L). In the last decade, some surface molecules have been associated with human Th2 cells. Although recent studies suggest that the receptors of chemokines are the most related markers of Th2 cells, so far it has not found a specific marker to discriminate Th2 cells. The most recent studies suggest that Th1 and Th2 cells are not derived from different cellular lineages, but rather they can be derived from the same precursory Th cell and, under the influence of genetic environmental factors, they can be polarized. Also, some genes conferring susceptibility to production of Th2 cytokines have been located.

[Use of cyclosporin A in patients with severe, active, treatment-resistant rheumatoid arthritis ]. / Uso de la ciclosporina A en pacientes con artritis reumatoide con actividad severa y resistentes al tratamiento.

BACKGROUND: Rheumatoid arthritis (RA) is a multisystemic and chronic disease whose etiology still remains to know. RA and their complications implicate a huge cost, calculated in 1% of total national internal product in US. OBJECTIVE: To evaluate the use of cyclosporine A in RA patients refractory to conventional treatment. MATERIAL AND METHODS: Several improvement variables were used, such as Ritchie index, modified Sharp radiological scale, functional status, HAQ index, analog scale of pain, and PCR. 13 female were included with a mean age of 44 years (range 30-50), with a mean of RA evolution of 6 years (range 0.5-22); each patient received an initial dosage of 2.5 mg/day by oral microemulsion of cyclosporine A, with increasing dosage of 0.5 mg/kg/day, adjusting by seric values of creatinine. RESULTS: RA patients were evaluated, initially and after three and six months. Data were analyzed using Mann-Whitney U and Kruskal Wallis tests. In three months evaluation there was an improvement in functional status (p = 0.009). In six months evaluation there was an improvement in painful joints (p = 0.006), functional status (p = 0.007) and general comfort sensation (p = 0.014). CONCLUSION: The cyclosporine use is considered an effective therapy, like disease modifier in RA refractory patients to conventional treatment in at least six months of the treatment.

Estudio de Marcadores de superficie celular en pacientes con rinitis alérgica frente a reto con Der p y Der f / Estudy of the markers of cellular surface in patients with allergic rinitis forehead to challenge with Der p and Der f

Los padecimientos alérgicos están genéticamente determinados y afectan del 20 al 30 por ciento de la población general en países desarrollados; en la última década la prevalencia se ha incrementado. El desequilibrio manifiesto en los padecimientos atópicos se encuentra en las células presentadoras de antígeno (monocitos y células B) y en los linfocitos T CD4+. La asociación de moléculas como CD80, CD 86 (moléculas co-estimulatorias) en monocitos y células B; y CD30, CD62L, ALL, CD11a, CD28, CD124 y CD152 en CD4+, ha demostrado ser de particular interés en padecimientos atópicos. Sin embargo, no se encontró una diferencia estadísticamente significativa entre pacientes y controles y entre reto nasal con solución salina y alergeno. Por esto se sugiere que los cambios en la activación, proliferación y cooperación se dan en el sitio de la lesión, sin una aparente repercusión en las células de la sangre periférica.

Marcadores de superficie de linfocitos TCD4+ en asma bronquial / Surface markers of TCD4+ lymphocytes in the bronchial asthma

El asma es una enfermedad atópica caracterizada por un incremento de los eosinófilos y de la inmunoglobulina E (IgE) en la mucosa nasal y en la sangre periférica. Con los avances en el conocimiento de la fisiopatología y de las técnicas de laboratorio, en estos momentos se pueden determinar algunas proteínas de la superficie de los linfocitos T llamadas CD, por ejemplo CD62L, CD152, CD11a. Material y métodos: se reclutaron 15 sujetos distribuidos en tres grupos de cinco personas (control, asma leve y asma severa). Se determinaron CD11a, CD30, CD62L. Se efectuó un Análisis con métodos estadísticos no paramétricos. Resultados: se encontraron diferencias con respecto a CD62L (p = 0.009) relacion ndose con asma severa. Conclusión: se demuestra la existencia de un cambio en la expresión de los CD. Hace falta un número mayor de pacientes para apoyar aún más nuestros resultados.

Apoptosis en la enfermedad alérgica / Apoptosis in the allergic disease

La apoptosis (muerte celular programada) es un mecanismo que implica un suicidio fisiológico para mantener la homeostasia celular en una variedad de tejidos. Fas (APO-1; CD95) es una importante vía celular responsable de la inducción de la apoptosis en diversos tejidos. La eosinofilia en la sangre periférica y en los tejidos es característica de los padecimientos alérgicos, como el asma. En estos padecimientos, la apoptosis del eosinófilo está sobrerregulada a través de IL-5 y GM-CSF. Para inducir apoptosis en el eosinófilo se han utilizado los glucocorticoides, teofilina y algunos macrólidos, procedimiento que puede representar un mecanismo para promover la solución de la inflamación en los padecimientos alérgicos.

Participación de los linfocitos Th2 en la enfermedad alérgica / Participation of lymphocites Th2 in allergic disease

Los padecimientos alérgicos son determinados genéticamente y afectan al 20 a 30 por ciento de la población de los países desarrollados. En la última década se ha observado un incremento en la prevalencia de los mismos, caracterizado por un aumento en la capacidad de los linfocitos B para producir anticuerpos inmunoglobulinas tipo E (IgE). Esta síntesis de la IgE humana resulta de la colaboración entre los subtipos de la células T auxiliadoras (Th) CD4+ y las células B. En años recientes se han estudiado intensamente las propiedades funcionales de la células Th, particularmente las tipo 2 en el mecanismo de unión de las células B productoras de IgE, células cebadas o basófilos y eosinófilos en reacciones alérgicas. Estos conceptos son conocidos en la actualidad e alergia como la teoría Th2

Teoría Th2 en alergia / Th2 theory in allergy

Los padecimientos alérgicos están genéticamente determinados y afectan del 20 al 30 por ciento de la población general en países desarrollados. En la última década se ha observado un incremento en la prevalencia de los mismos. Estos se caracterizan por un aumento en la capacidad de los linfocitos B para producir anticuerpos inmunoglobulina Tipo E (IgE). Esta síntesis de la IgE humana resulta de la colaboración entre subtipos de células T auxiliadoras (th) CD4+ y células B. En años recientes se han estudiado intensamente las propiedades funcionales de las células Th, particularmente las tipo 2, en el mecanismo de unión de las células B propuctoras de IgE, células cebadas o basófilos y eosinófilos en reacciones alérgicas. Estos conceptos se conocen en la actualidad como la teoría Th2 en alergia

Atopia: ¿genética o medio ambiente? / Atopic: genetics or environment?

El origen de la alegria responde a diversos factores y depende de la interacción de situaciones ambientales en individuos genéticamente susceptibles. El riesgo de contraer un padecimiento alérgico y la tendencia a desarrollar alergía en forma temprana, están fuertemente influidos por factores genéticos e historia familiar de padecimientos alérgicos. La genética de la atopia, sin embargo, no se ha comprendido totalmente. Aunque se asocie con aberraciones bioquímicas e inmunológicas junto con genes en los cromosomas, 5 y 11, los factores del medio ambiente juegan un papel principal en el desarrollo del padecimiento alérgico. Los mecanismos de éstos en forma individual son desconocidos, y se necesita más información sobre la dinámica de producción y de contaminantes en interiores, tasas de descomposición y factores ambientales que favorecen o crean las fuentes de contaminación del aire en interiores