Asthma Phenotypes in the Era of Personalized Medicine.

Asthma is a widespread disease affecting approximately 300-million people globally. This condition leads to significant morbidity, mortality, and economic strain worldwide. Recent clinical and laboratory research advancements have illuminated the immunological factors contributing to asthma. As of now, asthma is understood to be a heterogeneous disease. Personalized medicine involves categorizing asthma by its endotypes, linking observable characteristics to specific immunological mechanisms. Identifying these endotypic mechanisms is paramount in accurately profiling patients and tailoring therapeutic approaches using innovative biological agents targeting distinct immune pathways. This article presents a synopsis of the key immunological mechanisms implicated in the pathogenesis and manifestation of the disease's phenotypic traits and individualized treatments for severe asthma subtypes.

Biomarcadores y endotipos en la sepsis. Nuevas evidencias.

ANTECEDENTES: La sepsis es una causa importante de enfermedad y muerte en todo el mundo, y es un proceso complejo y heterogéneo. Ahora se reconoce que los marcadores biológicos mejoran la clasificación de la sepsis y pueden facilitar la identificación de distintas subclases o endotipos de pacientes. OBJETIVO: Analizar los conceptos actuales en biología traslacional que ayudan a entender la heterogeneidad en la respuesta del paciente con sepsis. CONCLUSIONES: Hay una serie de biomarcadores que podrían ser útiles para construir endotipos compuestos que predicen resultados no complicados en la sepsis. Estos endotipos podrían ayudar a identificar a los pacientes que merecen el inicio temprano de antimicrobianos o la interrupción de estos. BACKGROUND: Sepsis is an important cause of disease and death worldwide, and it has a complex and heterogeneous disease process. It is now recognized that biological markers improve sepsis classification and may facilitate the identification of different subclasses or endotypes of patients. OBJECTIVE: To analyze the current concepts in translational biology that help to understand the heterogeneity in the response of the patient with sepsis. CONCLUSIONS: There are a number of biomarkers that could be useful for constructing endo-compound types that predict uncomplicated results in sepsis. These endotypes could help identify patients who deserve early antimicrobial onset or discontinuation.

Identifying pathophysiological bases of disease in COVID-19.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus that can affect lung physiology encompassing a wide spectrum of severities, ranging from asymptomatic and mild symptoms to severe and fatal cases; the latter including massive neutrophil infiltration, stroke and multiple organ failure. Despite many recents findings, a clear mechanistic description underlying symptomatology is lacking. In this article, we thoroughly review the available data involving risk factors, age, gender, comorbidities, symptoms of disease, cellular and molecular mechanisms and the details behind host/pathogen interaction that hints at the existence of different pathophysiological mechanisms of disease. There is clear evidence that, by targeting the angiotensin-converting enzyme II (ACE2) -its natural receptor-, SARS-CoV-2 would mainly affect the renin-angiotensin-aldosterone system (RAAS), whose imbalance triggers diverse symptomatology-associated pathological processes. Downstream actors of the RAAS cascade are identified, and their interaction with risk factors and comorbidities are presented, rationalizing why a specific subgroup of individuals that present already lower ACE2 levels is particularly more susceptible to severe forms of disease. Finally, the notion of endotype discovery in the context of COVID-19 is introduced. We hypothesize that COVID-19, and its associated spectrum of severities, is an umbrella term covering different pathophysiological mechanisms (endotypes). This approach should dramatically accelerate our understanding and treatment of disease(s), enabling further discovery of pathophysiological mechanisms and leading to the identification of specific groups of patients that may benefit from personalized treatments.

Genomic mosaicism: A neglected factor that promotes variability in asthma diagnosis.

To elucidate the genetic architecture of asthma continues to be a challenge for molecular biologists and medical researchers. However, powerful genomic technologies are at disposal to help decipher complete human genomes; the genetic variability in asthma hinders the discovery of common molecular markers for this disease. In this context, we purpose to explore genomic mosaicism on asthma cells' biology as a strategy to discover key mechanisms, which can complement or re-define asthma diagnosis. Recent evidences showed that genomic mosaicism could be a normal event. In brains, each neuron may harbor hundreds of genetic alterations, which may contribute to neuronal diversity. Thus, can mosaicism be a natural motor of diversity in asthma? Why this genetic event is little described in scientific literature? To discuss these questions, we perform a critical review about the normality of genomic mosaicism; moreover, we examine the difficulty of current experimental approaches to detect different genotypes in cell populations of one individual.

The Syndrome We Agreed to Call Bronchiolitis.

We are ignoring evidence suggesting that the diagnosis of bronchiolitis encompasses several diseases with distinct underlying mechanisms, considerable heterogeneity in treatment responses, and ultimately different therapeutic targets. Understanding this heterogeneity may be the only way to deliver appropriate, stratified treatments.

Can inflammatory markers in induced sputum be used to detect phenotypes and endotypes of pediatric severe therapy-resistant asthma?

BACKGROUND: The phenotypes and endotypes of severe therapy-resistant asthma (STRA) have not been fully elucidated in children. The aim of the present study was to investigate inflammatory markers in the induced sputum of children with STRA and to compare them with those present in a group of children who achieved control. METHODS: A prospective cohort of children (6-18 years of age) diagnosed with severe asthma (GINA criteria) who had undergone treatment for at least 6 months was comprehensively followed for 3 months. Inhalation technique, adherence to treatment, ACT score, and main comorbidities were assessed. Induced sputum samples were collected for cytology analysis and quantitative assessment of cytokines; the participants also underwent spirometry, plethysmography, and fractional exhaled nitric oxide (FeNO) measurement. RESULTS: Forty patients were included (average age 12.8 years; 62.5% male); of these, 13 (32.5%) were classified as STRA at the end of follow-up. There were no significant differences between the STRA and control groups in demographic data, functional test results, or FeNO levels. The eosinophilic inflammatory pattern predominated in both groups; however, the STRA group showed a proportionally higher percentage of sputum neutrophils (P < 0.05). The median sputum levels of the cytokines IL-10, GM-CSF, IFN-γ, and TNF-α were significantly higher in the STRA group (P < 0.05). GM-CSF and TNF-α levels showed inverse correlations with ACT scores. CONCLUSION: The presence of neutrophils, the cytokines IL-10, and IFN-γ and, more particularly, TNF-α, and GM-CSF in the sputum may play an important role in the pathophysiological mechanism of STRA in children and adolescents. Specific antagonists for these cytokines may represent a future therapeutic strategy.

[Updating the concept of asthma. Is asthma a syndrome?]. / Actualización del concepto de asma. ¿Es el asma un síndrome?

Several symptoms are common to different processes that affect the respiratory system and their precise assessment is key to a correct diagnosis. Amongst those symptoms, mostly dyspnoea oriented toward the possible diagnosis of asthma. Nevertheless, the concept of asthma has changed in recent times, as inflammation of the bronchial tree is valued as the pathogenic base of the process, although it can not be ignored that the bronchial hyperresponsiveness is still the basis of dyspnoea crisis. In the last years, several variants have been established, being defined as phenotypes and endotypes that can identify diverse asthmatic or pseudo-asthmatic processes, and there for it is questioned if asthma is not the only process, but a syndrome. In any case, it cannot be ignored that dyspnoea episodes can be based on bronchial hyperresponsiveness of genetic origin or due to inflammation because of unfavourable environmental conditions, as well as physical exercise or the ingestión of aspirin, processes in which other mechanisms are involved.

Diversos síntomas son comunes a los diferentes procesos que afectan el aparato respiratorio y su valoración precisa es la base para el diagnóstico correcto. Entre esos síntomas, principalmente la disnea orienta hacia el posible diagnóstico de asma. Sin embargo, el concepto de asma ha variado al estimarse la inflamación del árbol bronquial como la base patogénica del proceso, pero no hay que olvidar que la hiperreactividad bronquial sigue siendo el fundamento de las crisis de disnea. En la actualidad se distinguen diversas variantes que se han definido como fenotipos y endotipos que pueden identificar diversos procesos asmáticos o seudoasmáticos, de ahí que se plantee que el asma no es un proceso único, sino un síndrome. En todo caso, la hiperreactividad bronquial puede ser de causa genética o adquirida por la inflamación causada por el medio ambiente desfavorable, o también por ejercicio físico o por la toma de aspirina, procesos en que intervienen otros mecanismos.