Description of BCG and Tuberculosis Disease in a Cohort of 79 Patients with Chronic Granulomatous Disease.

PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.

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.

Asma: uso adecuado de dispositivos para inhalación.

Inhaled therapy is considered the cornerstone of asthma treatment. However, despite being the ideal form of drug delivery, it is recognized that only 70% of patients have an adequate attachment to their treatment and only 39-67% of physicians can explain the optimal inhaler technique. Inhaled therapy has very specific characteristics. Pulmonary deposit of an inhaled medication through the respiratory tract is more complex than when administered orally and depends on several factors inherent to both the medication and the administration. For successful inhaled therapy, the drug needs to be converted into particles of an appropriate size, which can enter beyond the oropharynx and larynx, and be deposited in the lungs. There are multiple devices for the administration of drugs in the lower respiratory tract, each one with a similar efficacy as long as it is used with the correct technique. The decision of which device should be used is made based on the age of the patient, the ability to coordinate between the inhalation and activation of the device, and the presence of acute symptoms. The choice of the device must be evaluated individually.

La terapia inhalada se considera la piedra angular del manejo del asma. Sin embargo, a pesar de ser la forma ideal de administración de estos medicamentos, solamente el 70% de los pacientes cumple el tratamiento adecuadamente y sólo del 39 al 67% de los médicos conocen y pueden explicar de forma adecuada las distintas técnicas de inhalación. La terapia inhalada tiene características muy particulares. El depósito pulmonar de un medicamento inhalado a través del tracto respiratorio es más complejo que cuando se administra por vía oral, y varía dependiendo de varios factores, tanto inherentes al medicamento como a la forma de administrarlo. Para que la terapia inhalada sea exitosa, se requiere que se generen partículas del medicamento de un tamaño apropiado que penetren más allá de la orofaringe y la laringe, y que puedan depositarse en los pulmones. Existen múltiples dispositivos para la administración de medicamentos en la vía respiratoria baja. Cada uno ha probado tener una eficacia similar, siempre y cuando se utilicen con la técnica correcta. La decisión para su uso se realiza con base en la edad del paciente, la capacidad de coordinar entre la inhalación y la activación del dispositivo y la presencia de síntomas agudos. La elección del dispositivo a utilizar siempre deberá hacerse de forma conjunta, evaluando pros y contras de cada uno de los dispositivos y siempre de forma individualizada.

[Laryngeal cancer in patients younger than 40 years]. / Cáncer de laringe en pacientes menores de 40 años.

BACKGROUND: We undertook this study to report demographic data of laryngeal cancer patients <40 years old and treatment results. METHODS: In a retrolective study we reviewed the clinical records of 500 patients with laryngeal cancer in the period from 1989 to 2004 and included those patients<40 years of age. RESULTS: We found 15 patients, representing 4.4% of the series. Nine (60%) were men and six (40%) were women, with a 1.5:1 ratio. Average group age was 35 years (range 21-40 and median of 37 months). Average time of evolution at the time of diagnosis was 14.4 months (range 0-36 and median of 12 months); 60% of the patients were smokers and 40% admitted to drinking alcohol; dysphonia was the main symptom found in 87% of the patients. The most frequent location was the glottis in 11 (73%) patients. Well-differentiated tumors represented 53% of the cases. Initial treatment was surgery in four (27%) patients; radiotherapy in five (33%) patients receiving an average of 63.44 Gy; concomitant chemoradiotherapy in one patient (7%) using gemcitabine; four (27%) patients were treated with neoadjuvant chemotherapy followed by radiotherapy; and one patient did not receive treatment. The average time in which the patients relapsed after the first treatment was 19.57 months (range 2-63) and four were classified as persistent. Survival time was 32 months (range 2-106 and median 27 months). Finally, organ preservation rate was obtained in 28.5%. CONCLUSIONS: Squamous cell carcinoma of the larynx is rare in patients<40 years old in our study. Gender relation seems to be equal, although a slight predominance of men does still exist. Classical risk factors were present in 60% of the cases. Prognosis for these patients was determined by the initial clinical stage.

Asma: uso adecuado de dispositivos para inhalación / Asthma: correct use of inhalation drug-delivery devices

Resumen La terapia inhalada se considera la piedra angular del manejo del asma. Sin embargo, a pesar de ser la forma ideal de administración de estos medicamentos, solamente el 70% de los pacientes cumple el tratamiento adecuadamente y sólo del 39 al 67% de los médicos conocen y pueden explicar de forma adecuada las distintas técnicas de inhalación. La terapia inhalada tiene características muy particulares. El depósito pulmonar de un medicamento inhalado a través del tracto respiratorio es más complejo que cuando se administra por vía oral, y varía dependiendo de varios factores, tanto inherentes al medicamento como a la forma de administrarlo. Para que la terapia inhalada sea exitosa, se requiere que se generen partículas del medicamento de un tamaño apropiado que penetren más allá de la orofaringe y la laringe, y que puedan depositarse en los pulmones. Existen múltiples dispositivos para la administración de medicamentos en la vía respiratoria baja. Cada uno ha probado tener una eficacia similar, siempre y cuando se utilicen con la técnica correcta. La decisión para su uso se realiza con base en la edad del paciente, la capacidad de coordinar entre la inhalación y la activación del dispositivo y la presencia de síntomas agudos. La elección del dispositivo a utilizar siempre deberá hacerse de forma conjunta, evaluando pros y contras de cada uno de los dispositivos y siempre de forma individualizada.

Abstract Inhaled therapy is considered the cornerstone of asthma treatment. However, despite being the ideal form of drug delivery, it is recognized that only 70% of patients have an adequate attachment to their treatment and only 39-67% of physicians can explain the optimal inhaler technique. Inhaled therapy has very specific characteristics. Pulmonary deposit of an inhaled medication through the respiratory tract is more complex than when administered orally and depends on several factors inherent to both the medication and the administration. For successful inhaled therapy, the drug needs to be converted into particles of an appropriate size, which can enter beyond the oropharynx and larynx, and be deposited in the lungs. There are multiple devices for the administration of drugs in the lower respiratory tract, each one with a similar efficacy as long as it is used with the correct technique. The decision of which device should be used is made based on the age of the patient, the ability to coordinate between the inhalation and activation of the device, and the presence of acute symptoms. The choice of the device must be evaluated individually.

Cáncer de laringe en pacientes menores de 40 años / Laryngeal cancer in patients younger than 40 years

Objetivo: describir los datos demográficos de pacientes < 40 años de edad con diagnóstico de cáncer de laringe, y los resultados obtenidos después del tratamiento. Material y métodos: se revisaron los expedientes en forma retrolectiva, de una base de datos de 500 pacientes con cáncer de laringe atendidos entre 1989 y 2004; se incluyeron los pacientes < 40 años de edad al momento del diagnóstico, en quienes se corroboró el diagnóstico de carcinoma epidermoide. Resultados: fueron encontrados 15 pacientes (4.4 % de esta serie): nueve hombres (60 %) y seis mujeres (40 %), con una relación de 1.5:1, respectivamente. El promedio de edad para el grupo fue de 35 años. El tiempo promedio de evolución a la fecha del diagnóstico fue de 14.4 meses. El tabaquismo estuvo presente en 60 % y el alcoholismo en 40 %; la disfonía fue el síntoma cardinal en 87 %. La localización más frecuente fue la glotis (73 %). Los tumores bien diferenciados representaron 53 %. El tratamiento inicial fue cirugía en cuatro (27 %) pacientes y radioterapia en cinco (33 %), con un promedio de 63.44 Gy; un paciente (7 %) fue tratado con quimiorradioterapia concomitante con gemcitabine, cuatro (27 %) con quimioterapia neoadyuvante seguida de radioterapia, y un paciente no recibió tratamiento. El tiempo promedio de recurrencia después del primer tratamiento fue de 19.57 meses; cuatro pacientes fueron catalogados con persistencia. El tiempo promedio de supervivencia fue de 32 meses. La preservación de órgano al final fue de 28.5 %. Conclusiones: el cáncer epidermoide de laringe fue una patología rara en los pacientes < 40 años revisados. La relación de acuerdo con el sexo fue similar, con ligero predominio del masculino. Los factores de riesgo clásicos estuvieron presentes en 60 %. El pronóstico de los pacientes en esta serie estuvo determinado por el estadio clínico inicial.

BACKGROUND: We undertook this study to report demographic data of laryngeal cancer patients <40 years old and treatment results. METHODS: In a retrolective study we reviewed the clinical records of 500 patients with laryngeal cancer in the period from 1989 to 2004 and included those patients<40 years of age. RESULTS: We found 15 patients, representing 4.4% of the series. Nine (60%) were men and six (40%) were women, with a 1.5:1 ratio. Average group age was 35 years (range 21-40 and median of 37 months). Average time of evolution at the time of diagnosis was 14.4 months (range 0-36 and median of 12 months); 60% of the patients were smokers and 40% admitted to drinking alcohol; dysphonia was the main symptom found in 87% of the patients. The most frequent location was the glottis in 11 (73%) patients. Well-differentiated tumors represented 53% of the cases. Initial treatment was surgery in four (27%) patients; radiotherapy in five (33%) patients receiving an average of 63.44 Gy; concomitant chemoradiotherapy in one patient (7%) using gemcitabine; four (27%) patients were treated with neoadjuvant chemotherapy followed by radiotherapy; and one patient did not receive treatment. The average time in which the patients relapsed after the first treatment was 19.57 months (range 2-63) and four were classified as persistent. Survival time was 32 months (range 2-106 and median 27 months). Finally, organ preservation rate was obtained in 28.5%. CONCLUSIONS: Squamous cell carcinoma of the larynx is rare in patients<40 years old in our study. Gender relation seems to be equal, although a slight predominance of men does still exist. Classical risk factors were present in 60% of the cases. Prognosis for these patients was determined by the initial clinical stage.