RESUMEN

BACKGROUND: Gut microbiota-derived short-chain fatty-acid (SFCA) acetate protects mice against RSV A2 strain infection by increasing interferon-ß production and expression of interferon-stimulated genes (ISGs). However, the role of SFCA in RSV infection using strains isolated from patients is unknown. METHODS: We first used RSV clinical strains isolated from infants hospitalized with RSV bronchiolitis to investigate the effects of in vitro SCFA-acetate treatment of human pulmonary epithelial cells. We next examined whether SCFA-acetate treatment is beneficial in a mouse model of RSV infection using clinical isolates. We sought to investigate the relationship of gut microbiota and fecal acetate with disease severity among infants hospitalized with RSV bronchiolitis, and whether treating their respiratory epithelial cells with SCFA-acetate ex-vivo impacts viral load and ISG expression. We further treated epithelial cells from SARS-CoV-2 infected patients with SCFA-acetate. FINDINGS: In vitro pre-treatment of A549 cells with SCFA-acetate reduced RSV infection with clinical isolates and increased the expression of RIG-I and ISG15. Animals treated with SCFA-acetate intranasally recovered significantly faster, with reduction in the RSV clinical isolates viral load, and increased lung expression of IFNB1 and the RIG-I. Experiments in RIG-I knockout A549 cells demonstrated that the protection relies on RIG-I presence. Gut microbial profile was associated with bronchiolitis severity and with acetate in stool. Increased SCFA-acetate levels were associated with increasing oxygen saturation at admission, and shorter duration of fever. Ex-vivo treatment of patients' respiratory cells with SCFA-acetate reduced RSV load and increased expression of ISGs OAS1 and ISG15, and virus recognition receptors MAVS and RIG-I, but not IFNB1. These SCFA-acetate effects were not found on cells from SARS-CoV-2 infected patients. INTERPRETATION: SCFA-acetate reduces the severity of RSV infection and RSV viral load through modulation of RIG-I expression. FUNDING: FAPERGS (FAPERGS/MS/CNPq/SESRS no. 03/2017 - PPSUS 17/2551-0001380-8 and COVID-19 20/2551-0000258-6); CNPq 312504/2017-9; CAPES) - Finance Code 001.

Asunto(s)

Bronquiolitis , COVID-19 , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Acetatos/metabolismo , Acetatos/farmacología , Animales , Antivirales/metabolismo , Antivirales/farmacología , Antivirales/uso terapéutico , Bronquiolitis/tratamiento farmacológico , Bronquiolitis/metabolismo , Ácidos Grasos Volátiles/metabolismo , Humanos , Lactante , Pulmón/metabolismo , Ratones , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/genética , Virus Sincitial Respiratorio Humano/fisiología , SARS-CoV-2

RESUMEN

Our aim is to review current asthma epidemiology, achievements from the last 10 years, and persistent challenges of asthma management and control in low-middle income countries (LMICs). Despite global efforts, asthma continues to be an important public health problem worldwide, particularly in poorly resourced settings. Several epidemiological studies in the last decades have shown significant variability in the prevalence of asthma globally, but generally a marked increase in LMICs resulting in significant morbidity and mortality. Poverty, air pollution, climate change, exposure to indoor allergens, urbanization and diet are some of the factors that contribute to inadequate control and poor outcomes in developing countries. Although asthma guidelines have been developed to raise awareness and improve asthma diagnosis and treatment, problems with underdiagnosis and undertreatment are still common. In addition, important social, financial, cultural and healthcare barriers are common obstacles in LMICs in achieving control. Given the high burden of asthma in these countries, adaptation and implementation of national asthma guidelines tailored to local needs should be a public health priority. Governmental commitment, education, better health system infrastructure, access to care and effective asthma medications are the cornerstone of achieving success. CONCLUSION: Asthma poses significant challenges to LMICs. Whilst there are ongoing efforts in improving asthma diagnosis and decreasing asthma burden in LMICs; reasons for inadequate asthma control are also common and difficult to tackle. Improving asthma diagnosis, access to appropriate treatment and decreasing risk factors should be key goals to reduce asthma morbidity and mortality worldwide.

Asunto(s)

Asma/epidemiología , Países en Desarrollo , Contaminación del Aire/estadística & datos numéricos , Contaminación del Aire Interior/estadística & datos numéricos , Alérgenos , Asma/diagnóstico , Asma/terapia , Niño , Cambio Climático/estadística & datos numéricos , Errores Diagnósticos , Dieta/estadística & datos numéricos , Humanos , Pobreza/estadística & datos numéricos , Guías de Práctica Clínica como Asunto , Salud Pública , Política Pública , Factores de Riesgo , Urbanización/tendencias

RESUMEN

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.

Asunto(s)

Bronquiolitis/diagnóstico , Bronquiolitis/virología , Humanos , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios/patogenicidad

RESUMEN

Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), the European Academy of Allergy and Clinical Immunology (EAACI), and the World Allergy Organization (WAO), has proposed to issue an International Consensus (ICON) on the clinical consequences of mite hypersensitivity. The objectives of this document are to highlight aspects of mite biology that are clinically relevant, to update the current knowledge on mite allergens, routes of sensitization, the genetics of IgE responses to mites, the epidemiologic aspects of mite hypersensitivity, the clinical pictures induced by mites, the diagnosis, specific immunotherapeutic approaches, and prevention.

RESUMEN

In the present review, we focus on evidence-based data for the use of inhaled corticosteroids (ICS), leukotriene receptor antagonist (LTRA), long-acting beta2-agonits (LABA) and oral corticosteroids (OCS), with a special emphasis on well-performed randomized clinical trials (RCTs) and meta-analyses of such trials for the chronic management of asthma/wheeze in infants and preschoolers. RESULTS: Seven meta-analyses and 14 RCTs were reviewed. Daily ICS should be the preferred drug for infants/preschoolers with recurrent wheezing, especially in asthmatics. For those with moderate or severe episodes of EVW, the use of high intermittent ICS doses significantly reduce the use of OCS. There is no evidence of effect of intermittent ICS at low-moderate dose in preschoolers with mild EVW episodes. In preschoolers with asthma, there were no significant differences between daily vs. intermittent ICS in terms of asthma exacerbations with insufficient power to conclude to equivalence; however, for other asthma control outcomes, daily ICS works significantly better than intermittent ICS for older children. Daily ICS is superior to daily or intermittent LRTA for reducing symptoms, preventing exacerbations, and improving lung function. No RCTs testing combination therapy with ICS and LABA (or LTRA) were published in infant/preschoolers. Parent-initiation of OCS at the first sign of symptoms is not effective in children with recurrent wheezing episode. In terms of ICS safety, growth suppression is dose and molecule-dependent but it's effect is not cumulative beyond the first year of therapy and may be associated with some catch-up growth while on or off therapy. Linear growth must be monitored as individual susceptibility to ICS drugs may vary considerably.