ABSTRACT
In Latin America, asthma is a public health problem with a significant impact on both patients and health systems. The greater understanding of the pathophysiology and the recognition of the central role that inflammation has in the severity of asthma has favored the development of monoclonal antibodies that have IL-5, IL-4, IL-13 and IgE as therapeutic targets. Although these therapeutic alternatives promote better control of the disease, not all patients respond favorably to these treatments. Therefore, it is of particular interest to explore monoclonal antibodies such as Tezepelumab, directed against thymic stromal lymphopoietin (TSLP), an alarmin (epithelial cytokine) that participates in the initiation and perpetuation of inflammation in Asthma. Therefore, in this review, we will show the clinical efficacy of tezepelumab in reducing the annual rate of exacerbations, improving lung function, and reducing bronchial hyperreactivity, regardless of the patient's baseline biomarker levels. Therefore, this new molecule is a highly effective therapeutic option for patients with severe asthma.
En Latinoamérica, el asma es un problema de salud pública con un impacto importante tanto para los pacientes como para los sistemas de salud. El mayor entendimiento de la fisiopatología y el reconocimiento del papel central que tiene la inflamación en la severidad del asma ha favorecido el desarrollo de anticuerpos monoclonales que tienen como blancos terapéuticos a la IL-5, IL-4, IL-13 y la IgE. Si bien estas alternativas terapéuticas favorecen un mejor control de la enfermedad, no todos los pacientes responden favorablemente a esos tratamientos. Por lo que resulta de particular interés explorar anticuerpos monoclonales como el Tezepelumab, dirigido contra la linfopoyetina estromal tímica (TSLP) una alarmina (citocina epitelial) que participa en el inicio y la perpetuación de la inflamación en el Asma. Por lo que, en esta revisión, mostraremos la eficacia clínica del tezepelumab en la disminución de la tasa anual de exacerbaciones, mejora en la función pulmonar y en la disminución en la hiperreactividad bronquial, independientemente de los niveles de biomarcadores basales que el paciente presente. Por lo que esta nueva molécula es una opción terapéutica altamente eficaz para el paciente con asma grave.
Subject(s)
Asthma , Humans , Asthma/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Cytokines/therapeutic use , Antibodies, Monoclonal/therapeutic use , InflammationABSTRACT
OBJECTIVES: Lung metastasizing leiomyomatosis (LML) is an infrequently diagnosed pathology developed after sexual maturation, commonly preceded by uterine myomas. Symptoms can include difficulties to breathe, cough, dyspnea and pain, because of mechanical obstruction exerted by expanding local growing leiomyomas. Lung leiomyomas are normally detected by imaging studies, but nowadays the precise diagnosis demands histological characterization of biopsies obtained from the affected tissues. The purpose of the present study was to determine the presence of genomic alterations in circulating cells of LML. METHODS: Immunohistochemical characterization of a lung biopsy extracted by thoracoscopy was performed. Pathologic proliferative smooth muscle cells were observed in a major lung metastasizing nodule, with a growing pattern similar to a uterine myoma. The presence of cellular linages different to smooth muscle cells was discarded by testing the presence of a battery of molecular markers. Also, a normal karyotype was determine by GTG-banding cytogenetic study, but a high density microarray analysis revealed six submicroscopic chromosomal regions displaying genomic abnormalities: microduplications were detected on chromosomes 4, 14, 17 and 22; and microdeletions on chromosomes 8 and 10. CONCLUSION: This study remarks the relevance of submicroscopic chromosomal analysis of unusual pathologic conditions such as Benign Metastasizing Leiomyomatosis. This propitiate a better understanding of the molecular basis on the development of the pathology, in order to reckon on minimally invasive diagnostic methods, and to design appropriate treatments.
