[The diagnostic approach to difficult-to-treat asthma and severe asthma]. / Abordaje diagnóstico del asma difícil de tratar y asma grave.

Difficult-to-treat asthma refers to asthma that is not controlled despite high or medium doses of inhaled steroids or in which high doses of treatment are required to maintain an adequate control of the symptoms and to reduce the risk of exacerbations. An inadequate technique to use the inhaler, poor adherence to treatment, smoking, comorbidities, or an incorrect diagnosis should be considered. In severe asthma, despite adherence to treatment with optimized maximum doses and the management of factors that could contribute, multiple medications in maximum doses are required to have an adequate therapeutic control or this is not achieved. The approach to these patients involves a meticulous process due to the multiple factors that can influence poor asthma control and that can lead to a misclassification of the disease when, in reality, the patient can be presenting different comorbidities whose treatment could decrease the severity of asthma symptoms and modify the prognosis. The objective of this document is to make the approach to patients with difficult-to-treat asthma and severe asthma known, as well as the most frequent comorbidities. A search was made in PubMed with the purpose of identifying the main pathologies that may be present in patients and, based on what is described in the literature, to propose a diagnostic approach. 100 studies were comprised in this review, including clinical guidelines such as GINA, GEMA, and ERS/ATS.

El asma difícil de tratar es la que no se controla a pesar de las dosis altas o medias de esteroides inhalados o la que requiere altas porciones para mantener un control adecuado de los síntomas y reducir el riesgo de exacerbaciones. Se deben tener en cuenta las fallas en la técnica del uso del inhalador, la pobre adherencia al tratamiento, el tabaquismo, las comorbilidades o el diagnóstico incorrecto. En el asma grave, a pesar de la adherencia al tratamiento con dosis optimizadas y el manejo de los factores contribuyentes, se requieren múltiples medicamentos en dosis máximas para tener un adecuado control, si no es así este no se logra. La dirección de estos pacientes implica un proceso minucioso, dados los múltiples factores que pueden influir en el mal control del asma y que pueden llevar a una inadecuada clasificación de la enfermedad, cuando en realidad puedan estar cursando con diferentes comorbilidades cuyo tratamiento puede disminuir la severidad de los síntomas del asma y modificar el pronóstico. El objetivo de esta investigación es dar a conocer el manejo de los pacientes con asma difícil de tratar y asma grave, así como las comorbilidades más frecuentes. Se realizó una búsqueda en Pubmed con el propósito de identificar las principales patologías que puedan estar presentes y, con base en la literatura, proponer un abordaje diagnóstico. Se incluyeron 100 estudios, incluidas las guías clínicas GINA, GEMA y ERS/ATS.

Genetic, Immunological, and Clinical Features of the First Mexican Cohort of Patients with Chronic Granulomatous Disease.

PURPOSE: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019. METHODS: Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds. RESULTS: Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (n = 6), DHR (n = 27), and NBT plus DHR (n = 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17 months (range, 0-186 months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to CYBB (n = 64), NCF1 (n = 7), NCF2 (n = 7), and CYBA (n = 5) mutations. CONCLUSIONS: The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of CYBA and NCF2 mutations were identified, expanding the spectrum of known causal mutations.

Effect of cigarette smoke on counts of immunoreactive cells to eotaxin-1 and eosinophils on the nasal mucosa in young patients with perennial allergic rhinitis / Efeito do tabagismo nas contagens de células imunorreativas a eotaxina-1 e eosinófilos na mucosa nasal em pacientes jovens com rinite alérgica perene

Abstract Introduction: In teenagers with perennial allergic rhinitis, exposure to tobacco cigarette smoke increases the count of eosinophils in the nasal mucosa; the recruitment of eosinophils arises from the combined action of a number of cellular and molecular signals, including eotaxin. Objective: To assess the effect of exposure to tobacco cigarette smoke on the count of immunoreactive cells to eotaxin-1 and eosinophils on the nasal mucosa of children and teenagers with perennial allergic rhinitis. Methods: In a cross-sectional study, forty-four patients were evaluated (aged 7-19 years old): 22 with and 22 with no exposure to tobacco cigarette smoke. After replying to 2 validated questionnaires, on Asthma and Allergies in Childhood and on the severity of nasal symptoms, nasal mucosal samples were obtained by scraping the middle one-third of the inferior turbinates. Then counts of immunoreactive cells to eotaxin-1 and eosinophils were assessed by immunohistochemistry. Results: Patients with exposure to tobacco cigarette smoke showed higher cell counts of both eotaxin-1 and eosinophils than patients with no exposure to the smoke, with no correlation between the two variables. However, both counts, of eotaxin-1 and eosinophils, were related to the cotinine/creatinine ratio. Conclusions: Exposure to tobacco cigarette smoke can increase eotaxin-1 and the count of eosinophils in the nasal mucosa of young patients with perennial allergic rhinitis.

Resumo Introdução: Em adolescentes com rinite alérgica perene, a exposição à fumaça do cigarro de tabaco aumenta a contagem de eosinófilos na mucosa nasal. O recrutamento de eosinófilos surge da ação combinada de alguns sinais celulares e moleculares, inclusive a eotaxina. Objetivo: Avaliar o efeito da exposição à fumaça do cigarro de tabaco na contagem de células imunorreativas a eotaxina-1 e eosinófilos na mucosa nasal de crianças e adolescentes com rinite alérgica perene. Método: Em um estudo transversal, 44 pacientes foram avaliados (entre sete e 19 anos): 22 com e 22 sem exposição à fumaça do cigarro de tabaco. Depois de responder a dois questionários validados, sobre asma e alergias na infância e sobre a gravidade dos sintomas nasais, as amostras de mucosa nasal foram obtidas por meio de raspagem do terço médio das conchas inferiores. Em seguida, as contagens de células imunorreativas para eotaxina-1 e eosinófilos foram avaliadas por imuno-histoquímica. Resultados: Os pacientes com exposição à fumaça do cigarro de tabaco apresentaram contagens de células mais elevadas tanto para eotaxina-1 como para eosinófilos em comparação com os pacientes sem exposição à fumaça, sem correlação entre as duas variáveis. No entanto, ambas as contagens, de eotaxina-1 e eosinófilos foram relacionadas com a razão cotinina/creatinina. Conclusões: A exposição à fumaça do cigarro de tabaco pode aumentar a eotaxina-1 e a contagem de eosinófilos na mucosa nasal de pacientes jovens com rinite alérgica perene.

Effect of cigarette smoke on counts of immunoreactive cells to eotaxin-1 and eosinophils on the nasal mucosa in young patients with perennial allergic rhinitis.

INTRODUCTION: In teenagers with perennial allergic rhinitis, exposure to tobacco cigarette smoke increases the count of eosinophils in the nasal mucosa; the recruitment of eosinophils arises from the combined action of a number of cellular and molecular signals, including eotaxin. OBJECTIVE: To assess the effect of exposure to tobacco cigarette smoke on the count of immunoreactive cells to eotaxin-1 and eosinophils on the nasal mucosa of children and teenagers with perennial allergic rhinitis. METHODS: In a cross-sectional study, forty-four patients were evaluated (aged 7-19 years old): 22 with and 22 with no exposure to tobacco cigarette smoke. After replying to 2 validated questionnaires, on Asthma and Allergies in Childhood and on the severity of nasal symptoms, nasal mucosal samples were obtained by scraping the middle one-third of the inferior turbinates. Then counts of immunoreactive cells to eotaxin-1 and eosinophils were assessed by immunohistochemistry. RESULTS: Patients with exposure to tobacco cigarette smoke showed higher cell counts of both eotaxin-1 and eosinophils than patients with no exposure to the smoke, with no correlation between the two variables. However, both counts, of eotaxin-1 and eosinophils, were related to the cotinine/creatinine ratio. CONCLUSIONS: Exposure to tobacco cigarette smoke can increase eotaxin-1 and the count of eosinophils in the nasal mucosa of young patients with perennial allergic rhinitis.

[Hypereosinophilic syndrome as paraneoplastic presentation in an adolescent]. / Síndrome hipereosinofílico como presentación paraneoplásica en una adolescente.

Hypereosinophilic syndrome is characterized by peripheral eosinophilia over 1,500 cell/mm3 and/or tissue eosinophilia, with dysfunction or damage to organ, once other causes were ruled out. This paper presents a case of hypereosinophilic syndrome (HS) which presented as lymphoblastic leukemia in a teenager. This is a 13 year old female, with B cell lymphoblastic leukemia at 9 years old, who received chemotherapy for 2 years achieving remission. One year after remission she presented malar rash, hair loss, arthralgias, conjuntival redness, dyspnea and thoracic oppression. The initial blood count only showed hypereosinophilia, and a bone marrow biopsy did not show blasts and had a negative immunophenotyping. Autoantibodies were negative, except for ANA (1:1,280 in one determination after one negative), complement was normal, lupic band in skin was negative for complement and immunoglobulins; serum IgG 2,195 mg/dL, IgA 231, IgM 327, IgE 109 U/mL; skin testing for aeroallergens and food allergens were negative. Prednisone was started at 1 mg/kg. Abdominal ultrasound only reported biliary sludge flow and hepatosplenomegaly; chest tomography showed centrolobullar interstitial pattern, suggesting eosinophilic pneumonitis. The patient started with a generalized dermatosis, and a biopsy reported leucocytoclastic vasculitis. Six months after the onset of symptomatology there were generalized malaise, uncontrolled fever, gingival haemorrhage, asthenia and adynamia; a blood cell count reported blasts, and bone marrow smear confirmed the diagnosis of cell B lymphoblastic leukemia. The patient deteriorated rapidly showing signs of respiratory difficulty and acute pulmonary edema, therefore chemotherapy was started without response, and finally the patient died. There are several causes of HS, yet one of the least frequent presentations in childhood is the association with neoplasms.

El síndrome hipereosinofílico se distingue por eosinofilia periférica mayor de 1,500 cel/mm3 o eosinofilia tisular (o ambas), con disfunción o daño a órgano atribuible, una vez que se han descartado otras causas. Se comunica un caso de síndrome hipereosinofílico como forma de presentación de leucemia linfoblástica en una adolescente. Se trata de una paciente de 13 años de edad, con leucemia linfoblástica de células B a los nueve años, tratada con quimioterapia durante dos años, con logro de la remisión. Un año posterior a ésta comenzó con eritema malar, caída de pelo, artralgias en las manos, los codos, las rodillas y los hombros, dolores musculares (predominantemente en los muslos), disnea, opresión torácica e inyección conjuntival. La biometría hemática sólo reportó eosinofilia, el aspirado de médula ósea sin blastos, inmunofenotipo negativo; autoanticuerpos negativos, sólo ANA 1:1,280 (patrón nuclear en una determinación, las posteriores resultaron negativas) complemento normal, banda lúpica en piel negativa, IgG 2,195, IgA 231, IgM 327, IgE 109, pruebas cutáneas a aeroalergenos y alimentos negativos. Se trató con prednisona a dosis de 1 mg/kg. El ultrasonido abdominal reportó lodo hepático y hepatoesplenomegalia, la tomografía de alta resolución de tórax mostró afección intersticial centroloblillar, a considerar neumonitis eosinofílica. Posteriormente tuvo una dermatosis generalizada con pápulas no pruriginosas, de 1 x 1 cm, confluentes; la biopsia de piel reportó vasculitis leucocitoclástica. Seis meses después del inicio de los síntomas tuvo ataque al estado general, fiebre no controlable, hemorragia gingival, astenia y adinamia; la biometría hemática reportó blastos, y el aspirado de médula ósea confirmó el diagnóstico de leucemia linfoblástica de células B. La paciente experimentó deterioro acelerado, datos de dificultad respiratoria y edema agudo pulmonar. Se le inició quimioterapia, sin lograr respuesta, hasta que sobrevino la muerte. Existen varias causas del síndrome hipereosinofílico y una de las presentaciones menos frecuentes en niños es la asociación con procesos neoplásicos.