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.

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.

[Radiographic changes in children with primary immunodeficiency]. / Alteraciones radiográficas en niños con inmunodeficiencia primaria.

BACKGROUND: Although we have epidemiological information on primary immunodeficiencies (PID), the available information is meager in Mexico. OBJECTIVE: To provide epidemiological information on the delay in the diagnosis of PID and its correlation to chronic lung damage. MATERIAL AND METHOD: A retrospective, analytical study was done in patients 0-18 year old age diagnosed with PID for 11 years at the HIMFG (Hospital Infantil de Mexico Federico Gomez). The variables studied were: age at symptom onset, age at diagnosis, time from onset of symptoms to diagnosis, number of previous pneumonias and studies with radiographic chronic lung damage data. RESULTS: 48 patients were obtained after meeting inclusion criteria; 33 showed lung damage at diagnosis, antibody deficiency being the most affected group. Relating age of onset of symptoms and the time difference of the onset of symptoms to diagnosis showed a strong correlation (p < 0.001, Rho > 0.80). A moderate correlation between the observed time difference vs number of pneumonias (p=0.005, Rho=0.495) and correlation between number of pneumonia and lung damage was highly significant (p <0.001, Rho=0.704). CONCLUSION: A strong relationship between the elapsed time from onset of symptoms and the number of pneumonia with lung injury time was found. So, the recurrent pneumonia (> 2) must make suspect the diagnosis of PID, as recommended in the literature.

Antecedentes: si bien se cuenta con información epidemiológica de las inmunodeficiencias primarias, la información disponible en México es escasa. Objetivos: dar información epidemiológica del retraso del diagnóstico de las inmunodeficiencias primarias y de su correlación con daño pulmonar crónico. Material y método: estudio retrospectivo, analítico, efectuado en pacientes de 0 a 18 años de edad con diagnóstico de inmunodeficiencias primarias durante 11 años en el Hospital Infantil de México Federico Gómez; las variables estudiadas fueron: edad al inicio de los síntomas, edad al diagnóstico, tiempo desde el inicio de los síntomas al diagnóstico, número de neumonías previas y estudios radiográficos con datos de daño pulmonar crónico. Resultados: se incluyeron 48 pacientes que cumplieron los criterios de inclusión; 33 tenían daño pulmonar al diagnóstico, el déficit de anticuerpos fue el grupo con mayor afectación. Al correlacionar la edad de inicio de los síntomas y la diferencia de tiempo del inicio de los síntomas al diagnóstico se obtuvo una fuerte correlación (p <0.001, Rho > 0.80). Se observó una correlación moderada entre la diferencia en tiempo vs número de neumonías (p=0.005, Rho=0.495) y la correlación entre número de neumonías y daño pulmonar mostró significación alta (p <0.001, Rho=0.704). Conclusión: se encontró una relación estrecha entre el tiempo transcurrido desde el inicio de los síntomas y el número de neumonías con el daño pulmonar, por lo que las neumonías de repetición (más de dos) deben hacer sospechar el diagnóstico de inmunodeficiencia primaria, como se recomienda en la bibliografía mundial.

[Frequency of allergy to cow's milk proteins and its association to other allergic diseases in patients of Hospital Infantil de Mexico Federico Gomez]. / Frecuencia de alergia a las proteínas de la leche de vaca y su asociación con otras enfermedades alérgicas en pacientes del Hospital Infantil de México Federico Gómez.

BACKGROUND: The cow's milk protein allergy is the most common food allergy among children under two years and is associated with other atopic diseases. OBJECTIVES: To evaluate cow's milk protein allergy frequency in patients sensitized to them, attended at the consultation of Immunology and Allergy in the Hospital Infantil de México Federico Gómez, and its association with other atopic diseases. MATERIAL AND METHOD: A cross-sectional, analytical and descriptive study that reviewed medical records of patients aged 0-19 years, attended at the consultation of Immunology and Allergy in the Hospital Infantil de México Federico Gómez, from January 2010 to January 2013, sensitized to the cow's milk protein by in vitro or in vivo studies, mediated or not by IgE, to determine its association with other atopic diseases during the course of their clinical evolution. RESULTS: We included 252 patients with symptoms suggestive of cow's milk protein allergy, which was diagnosed only in 15.1% by oral challenge. In relation to respiratory symptoms, about two-thirds of patients had rhinorrhea, nasal obstruction and nasal itching. Regarding gastrointestinal symptoms, about a third had abdominal pain, diarrhea and abdominal distension, being statistically significant. The most common dermatologic symptom, statistically significant, was xerosis. The most frequently associated atopic diseases were food allergy (76.3%), allergic rhinitis (65.8%), asthma (47.4%) and atopic dermatitis (23%). CONCLUSIONS: The cow's milk protein allergy can be associated with other atopic diseases, such as allergy to other foods, allergic rhinitis, asthma and atopic dermatitis.

Antecedentes: la alergia a las proteínas de la leche de vaca es la alergia alimentaria más común entre los niños menores de dos años y se asocia con otras enfermedades atópicas. Objetivo: evaluar la frecuencia de alergia a las proteínas de la leche de vaca en pacientes sensibilizados a las mismas, que acuden a la consulta de Inmunología y Alergia del Hospital Infantil de México Federico Gómez, así como su asociación con otras enfermedades atópicas. Material y método: estudio retrolectivo, analítico y descriptivo en el que se revisaron los expedientes clínicos de pacientes de 0 a 19 años de edad, atendidos en la consulta de Inmunología y Alergia del Hospital Infantil de México Federico Gómez, de enero de 2010 a enero de 2013, sensibilizados a las proteínas de leche de vaca por estudios in vitro o in vivo, mediada o no mediada por IgE, para determinar su asociación con otras enfermedades atópicas durante el curso de su evolución clínica. Resultados: se incluyeron 252 pacientes con síntomas sugerentes de alergia a las proteínas de la leche de vaca, de los que sólo en 15.1% se diagnosticó por reto oral. Con respecto a los síntomas respiratorios, alrededor de 66% de los pacientes manifestó rinorrea, obstrucción y prurito nasales. En cuanto a los síntomas gastrointestinales, cerca de 30% tuvo diarrea y dolor y distensión abdominales, lo que fue estadísticamente significativo. El síntoma dermatológico más frecuente y estadísticamente significativo fue la xerosis. Las enfermedades atópicas asociadas con más frecuencia fueron: alergia alimentaria (76.3%), rinitis alérgica (65.8%), asma (47.4%) y dermatitis atópica (23%). Conclusiones: la alergia a las proteínas de la leche de vaca puede asociarse con otras enfermedades atópicas, como alergia a otros alimentos, rinitis alérgica, asma y dermatitis atópica.

High expression of Toll-like receptors 2 and 9 and Th1/Th2 cytokines profile in obese asthmatic children.

Asthma is a common pulmonary disease with chronic inflammation of the airways, and obesity is a chronic state of low-grade inflammation. Toll-like receptors (TLRs) are involved in the innate immune response. This study was designed to analyze whether obesity has an effect on the immune response of patients with asthma. We included obese asthmatic, obese, asthmatic, and healthy children. Biochemical and anthropometric analyses were performed. Interleukin (IL)-2, interferon (IFN) gamma, IL-4, IL-10, IL-1beta, and tumor necrosis factor alpha were measured. Peripheral blood mononuclear cells were analyzed by immunostaining with anti-TLR2 and anti-TLR9 antibodies. The data were expressed as means ± SEM or medians and percentiles. Kruskal-Wallis test and Dunn's multiple comparison test were applied. Asthmatic patients, both obese and nonobese, exhibited a mild asthma phenotype; none had infectious process, exacerbation, or acute symptoms during the 30 days before the inclusion in the study. The IL-2 and IFN-gamma levels in the obese asthmatic group were lower than in the other three groups. IL-4 levels in the obese asthmatic group were almost equal to those of the asthmatic group and more than in the other two groups, without significant difference. There were higher levels of TLR2 and TLR9 in obese asthmatic patients than in the other three groups. There is a decrease in Th1 cytokines in obese asthmatic patients, and we only found a trend to an increased Th2 profile. Patients studied do not appear to fit into any of the endotypes described until now. This is the first study showing the high expression of TLR2 and TLR9 in obese asthmatic patients. It is necessary to study other cytokines in obese asthmatic patients to see if it is possible to fit them into any of the already described endotypes or if it is a distinct endotype.

Participation of CD161(+) and invariant natural killer T cells in pediatric asthma exacerbations.

Asthma has been defined as a disease of chronic airway inflammation in which many cells and cellular products participate with variable degrees of airflow obstruction and hyperresponsiveness that lead to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. Prominent among these cellular elements are two cell types referred to as the invariant natural killer T (iNKT) cells and a subpopulation of T cells expressing the molecule CD161, which are both thought to play a role in the pathogenesis of asthma. Although the presence of iNKT and other CD161(+) cells in murine models has been associated with asthma, relatively few studies have been performed in the adult patient with asthma that have been often conflicting and even fewer studies are available in children. The present study was performed to investigate the peripheral blood frequencies of iNKT and CD161(+) T cells in children with asthma. A total of 35 children, 19 stable asthmatic patients, 6 who had experienced an asthmatic attack within 24 hours and had not received any treatment, and 10 healthy controls, aged 6-12 years, were enrolled in the study. iNKT and CD161(+) T-cell frequencies in blood were measured together with quantitative levels of IL-4 and interferon (IFN) γ using a cytofluorimetric approach. The results show that iNKT cells are increased in pediatric asthmatic patients undergoing exacerbations of asthma. These cells also produced less IFN-γ and more IL-4 than children with stable asthma and in healthy control children. These results suggest that iNKT cells might participate in the development of the asthmatic exacerbations. The increased production of IL-4 in conjunction with the decrease of IFN-γ may be mechanistically responsible, at least partially, for the heightening of the immunologic response leading to the asthmatic attack in children. Knowledge of these interactive mechanisms involving the iNKT cell and our understanding of its role in the exacerbation of asthma hold great promise in the development of better diagnostic predictive markers of disease progression as well as new forms of therapeutic interventions.

Carboplatin hypersensitivity and desensitization in an infant.

Although the reported incidence of carboplatin hypersensitivity is low, it is important to describe it because of its potentially fatal consequences. A 1-year-old Mexican girl weighing 10 kg who had optic nerve glioma was initially scheduled to receive 12 cycles of 600 mg/m2 carboplatin (CBP) as two 300-mg/m2 intravenous infusions administered over 1 hour on 2 different days and a 1-hour intravenous infusion of 1.5 mg/m2 vincristine every 4 weeks. The patient had no history of drug allergies or any type of adverse drug reaction, but she developed itchiness, maculopapular rash, sweating, respiratory distress, and anxiety during the seventh cycle of CBP. According to the algorithm developed by Naranjo et al, the adverse drug reaction was classified as definite secondary to CBP and confirmed by positive skin tests indicating hypersensitivity to the drug. After evaluating the clinical course of the adverse drug reaction and considering the need to continue cancer treatment, a decision was made to desensitize the patient to CBP. The desensitization procedure took 8 hours and was performed during each new chemotherapy cycle until the 12 cycles of chemotherapy were successfully completed. In summary, a case of CBP hypersensitivity in a 1-year-old girl who was successfully desensitized to CBP is reported.

[Allergic bronchopulmonary aspergillosis. A report of a case and literature review]. / Aspergilosis broncopulmonar alérgica. Comunicación de un caso y revisión de la bibliografía.

Allergic bronchopulmonary aspergillosis is a world rare disease with a prevalence between 1 and 2%. It presents in moderate-severe asthma and cistic fibrosis patients. The diagnosis is made in the basis of Rossenberg and Greenberg criteria that can be essential or non essential. We present the case of a 3-year-old boy with allergic bronchopulmonary aspergillosis without bronchiectasies and with a good response to corticosteroids. His mother complained of two years of nasal obstruction, purulent rinorrea, nasal pruritus, sneezing, chronic cough and recurrent wheezing, twice to thrice a month. He also occasionally had vomits and diarrhea in relation with strawberries, banana, cow's milk and chocolate. We made the diagnosis of asthma, allergic rhinitis, sinusitis, and probably food allergy. We treated him with step approach of ICS according to GINA 2006, albuterol PRN, and elimination diet, with bad response. Laboratory exams: Blood white cells with eosinophilia (6%), total serum IgE: 1684 ng/L, aspergillus skin prick test: 4mm, serum IgG-Aspergillus fumigatus: 2.3 mcg/mL, serum IgE-Aspergillus fumigatus: negative, chest roentgenographic parahiliar and apical infiltrates, and chest computed tomography without bronchiectasies. We added prednisone to the treatment for four months, and we observed a very good response; he is now in treatment as mild persistent asthma with ICS low doses. ABPA must be suspected in patients with moderate-severe persistent asthma and a skin prick test positive to Aspergillus fumigatus regardless the age. The treatment with oral corticosteroids is the mainstream of management, and most of the patients have a good response, as we observed with this patient.

Asthma prevalence in children living in north Mexico City and a comparison with other Latin American cities and world regions.

Reports of previous studies done without following the international guidelines in different cities of Mexico showed a decrease in asthma prevalence. The aim of this study was to determine the prevalence and severity of asthma symptoms in children and teenagers living in north Mexico City and compare them with those of other Latin American cities and world regions. The cross-sectional survey followed the protocol of the International Study of Asthma and Allergies in Childhood IIIb phase survey. The study population included children 6-7 years old and teenagers 13-14 years old from randomly selected primary and secondary schools. There were 1629 boys and 1582 girls in the group of 6- to 7-year-old children and 2039 boys and 1860 girls in the 13- to 14-year-old group. "Wheezing or whistling in the chest at any time in the past" was present in 19.2% (95% confidence interval [CI], 17.9, 20.6) of the children and in 17.0% (95% CI, 15.8, 18.1) of the teenagers; "wheezing or whistling in the chest in the last 12 months" was reported in 6.8% (95% CI, 5.9, 7.6) of the children and 9.9% (95% CI, 9.0, 10.8) of the teenagers; "asthma ever" was claimed in 4.5% (95% CI, 3.8, 5.2) of the children and 8.0% (95% CI, 7.1, 8.8) of the teenagers. These prevalences were low compared with other ISAAC Latin American surveys and intermediate in comparison with worldwide regional prevalences reported by ISAAC surveys. The prevalence of asthma is low in Mexico City in comparison with other surveyed locations, but the number of patients with asthma makes it an important issue for Mexican public health programs.

Tipos y características de los inhaladores para el manejo de asma / Types and characteristics of devices for the treatment of asthma

El tratamiento del asma requiere del uso de medicamentos durante períodos largos para lograr el control de la enfermedad y la vía inhalada es la forma más adecuada para administrarlos. En las últimas 2 décadas se han desarrollado nuevos y mejores dispositivos para la entrega del medicamento, con marcadas diferencias respecto a su diseño, construcción, características de salida y tamaño de las partículas. El médico debe conocer los puntos tecnológicos más destacados de cada aparato para que pueda aprovechar sus ventajas y haga recomendaciones muy precisas. Existen varios dispositivos para administrar medicamentos inhalados: los más viejos y de uso cotidiano en hospitales son los nebulizadores y de manera más reciente se introdujeron los inhaladores de dosis medida presurizados o los inhaladores de polvo seco, que son más usados para el paciente ambulatorio. La condición particular de cada uno de estos dispositivos debe conocerse y aplicarse para ofrecer el máximo beneficio al paciente asmático.

Asthma management requires the use of many drugs for long time with the purpose of achieving control. Inhalator delivery of asthma medications is the best way. In the previous 2 decades, technology has improved delivery devices, changes in design, materials and outsize particles. Physicians should know all the technical points in order to take advantage of these new devises to be able to make appropriate recommendations for their use. There is a large quantity of options for the delivery of asthma medications: nebulizers, metered dose inhaler and dry powder inhalers. Particular characteristics of delivery devices should be known and applied in particular patients.The aim of this review article is assist physicians to choose the best device option.

[Chronic granulomatous disease. Report of a case and review of the literature]. / Enfermedad granulomatosa crónica. Reporte de un caso y revisión de la literatura.

Chronic granulomatous disease is a little common primary immunodeficiency affecting innate immune system. This article presents the case of an 8-year-old female patient whose disease started at three months of age with respiratory ways' infections. When she was two years old, she suffered another presentation of right basal pneumonia and right cervical mass, whose biopsy reported childhood chronic granulomatous disease. At eight years old, patient suffered bacteraemia due to Salmonella group D, thus patient started prophylaxis with trimethoprim-sulfamethoxazole and, to date, she has continued stable.