Lung microbiome alterations in patients with anti-Jo1 antisynthetase syndrome and interstitial lung disease.

Aim: To characterize the lung microbiome in the bronchoalveolar lavage fluid (BALF) of patients with Antisynthetase Syndrome (ASSD) according to anti-Jo1 autoantibody positivity and evaluate the correlation with differential cell count and other bacterial genera in BALF. Methods: We sequenced the 16S ribosomal RNA gene in the BALF of anti-Jo1-positive (JoP, n=6) and non-Jo1-positive (NJo, n=17) patients, and the differential cell count in BALF was evaluated. The Spearman's correlation was calculated for the quantitative variables and abundance of bacterial species. Results: The Veillonella genus showed a significant decrease (p<0.01) in JoP (2.2%) in comparison to NJo (4.1%) patients. The correlation analysis showed several high (rho ≥ ± 0.7) and significant (p < 0.05) correlations. We analyzed the results obtained for the Veillonella genera and other study variables. The JoP group showed that the abundance of Veillonella had a high negative correlation with macrophages (rho = - 0.77) and a positive correlation with eosinophils (rho = 0.77), lymphocytes (rho = 0.77), and Prevotella (rho = 1). Conclusions: The lung microbiome in ASSD patients differs and may affect cell composition, contributing to lung damage mechanisms. The presence of anti-Jo1 autoantibodies showed a low abundance of Veillonella. This genus had a strong and positive correlation with Prevotella abundance and levels of eosinophils and lymphocytes, and it showed a strong negative correlation with the percentage of macrophages.

Microbiota composition in the lower respiratory tract is associated with severity in patients with acute respiratory distress by influenza.

Several factors are associated with the severity of the respiratory disease caused by the influenza virus. Although viral factors are one of the most studied, in recent years the role of the microbiota and co-infections in severe and fatal outcomes has been recognized. However, most of the work has focused on the microbiota of the upper respiratory tract (URT), hindering potential insights from the lower respiratory tract (LRT) that may help to understand the role of the microbiota in Influenza disease. In this work, we characterized the microbiota of the LRT of patients with Influenza A using 16S rRNA sequencing. We tested if patients with different outcomes (deceased/recovered) and use of antibiotics differ in their microbial community composition. We found important differences in the diversity and composition of the microbiota between deceased and recovered patients. In particular, we detected a high abundance of opportunistic pathogens such as Granulicatella, in patients either deceased or with antibiotic treatment. Also, we found antibiotic treatment correlated with lower diversity of microbial communities and with lower probability of survival in Influenza A patients. Altogether, the loss of microbial diversity could generate a disequilibrium in the community, potentially compromising the immune response increasing viral infectivity, promoting the growth of potentially pathogenic bacteria that, together with altered biochemical parameters, can be leading to severe forms of the disease. Overall, the present study gives one of the first characterizations of the diversity and composition of microbial communities in the LRT of Influenza patients and its relationship with clinical variables and disease severity.

Enhanced Activity of NLRP3 Inflammasome in the Lung of Patients with Anti-Synthetase Syndrome.

Anti-synthetase syndrome (ASSD) is an autoimmune disorder characterized by inflammatory interstitial lung disease (ILD). The main objective of this work was to quantify the concentrations of cytokines and molecules associated with inflammasome activation in bronchoalveolar lavage (BAL) of patients with ASSD and a comparison group of systemic sclerosis (SSc) patients. Cytokines and lactate dehydrogenase (LDH) were determined using the concentrated BAL protein. The activity of caspase-1 and concentration of NLRP3 with the protein purified from the cell pellet in each group of patients. We found higher caspase-1 levels in ASSD vs. SSc, 1.25 RFU vs. 0.75 RFU p = 0.003, and LDH levels at 0.15 OD vs. 0.09 OD p < 0.001. A significant difference was observed in molecules associated with inflammasome activation, IL-18: 1.42 pg/mL vs. 0.87 pg/mL p = 0.02 and IFN-γ: 0.9 pg/mL vs. 0.86 pg/mL, p = 0.01. A positive correlation was found between caspase-1 and LDH in the patients with ASSD Rho 0.58 (p = 0.008) but not in the SSc group. In patients with ASSD, greater caspase-1 and higher LDH activity were observed in BAL, suggesting cell death due to pyroptosis and activation of the inflammasome pathway.

Amino acid changes in HA and determinants of pathogenicity associated with influenza virus A H1N1pdm09 during the winter seasons 2015-2016 and 2016-2017 in Mexico.

Biennial H1N1pdm09 influenza A virus (IAV) epidemics have been associated with major severity of respiratory disease in Mexico. Atypically and in contrast with what happened in USA, Canada and Europe during 2017, an increase of infections due to the H1N1pdm09 pandemic virus instead of H3N2 was observed. In order to determine the viral contribution to severe acute respiratory disease, we characterized the pathogenicity determinants of IAV in Mexico during the 2015-2016 and 2016-2017 seasons. The RNA segments of 20 IAV samples were sequenced by NGS platform and phylogenetic analysis was conducted. The analysis of the hemagglutinin (HA) sequences established that all virus samples, except one, belong to clade (6B.1). The IAVs presented the substitution S162 N, which introduces a new glycosylation site in the hemagglutinin. We also found the D222 G substitution, which has been associated with a higher tropism towards the lower respiratory tract, and a non-reported insertion of one Ile in NS1 (Ile113). The IAVs from 2016 to 2017 in Mexico belong to the new clade 6B.1. The new glycosylation site in HA (S162 N) is a major change that may affect the efficacy of the current vaccine. We detected in several patients pathogenicity determinants associated with the severity of the respiratory disease.

CHRONIC OBSTRUCTIVE PULMONARY DISEASE: PERSPECTIVES FOR PRIMARY HEALTH CARE.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has become a major health challenge worldwide due to its increasing incidence and mortality, which have serious repercussions for health-care systems. METHODS: We conducted a review of international efforts to control COPD in primary care. RESULTS: The WHO created the Alma-Ata declaration which established for the first time, access to health care as a human right. This precept led to the implementation of numerous programs including practical approach to Lung Health and variants in several countries; schemes designed to centralize medical care; and resources to improve attention of respiratory diseases by adapting approaches to the health-care needs of local populations. Primary respiratory health care should include actions for timely detection, health education, and targeted treatment, but the challenge for all health systems is to ensure that their programs function adequately, for they still show shortcomings in terms of their application. CONCLUSIONS: We conclude that offering primary health care based on models that combine opportune diagnoses with suitable treatment can positively influence the course of COPD by treating early stages, thus slowing its progression. However, more extensive education and broader dissemination of information are necessary to achieve this goal.

Chronic obstructive pulmonary disease: perspectives for primary health care

Abstract Background Chronic obstructive pulmonary disease (COPD) has become a major health challenge worldwide due to its increasing incidence and mortality, which have serious repercussions for health-care systems. Methods We conducted a review of international efforts to control COPD in primary care. Results The WHO created the Alma-Ata declaration which established for the first time, access to health care as a human right. This precept led to the implementation of numerous programs including practical approach to Lung Health and variants in several countries; schemes designed to centralize medical care; and resources to improve attention of respiratory diseases by adapting approaches to the health-care needs of local populations. Primary respiratory health care should include actions for timely detection, health education, and targeted treatment, but the challenge for all health systems is to ensure that their programs function adequately, for they still show shortcomings in terms of their application. Conclusions We conclude that offering primary health care based on models that combine opportune diagnoses with suitable treatment can positively influence the course of COPD by treating early stages, thus slowing its progression. However, more extensive education and broader dissemination of information are necessary to achieve this goal.

[Infective endocarditis. 5-years experience in a third-level reference center in Yucatan, Mexico]. / Endocarditis infecciosa. Experiencia de 5 años en un tercer nivel de referencia en Yucatán México.

BACKGROUND: Infective endocarditis is a disease with high morbidity and mortality. The clinical characteristics differ among populations. Therefore it is important to know the characteristics of the disease in our region. METHODS: This is an observational study that included all patients diagnosed with infective endocarditis from 1 January 2009 until 31 December 2014. The data are showed as frequencies and percentages altogether with medians with interquartile range. RESULTS: 10 cases were included. The median age was 34 years (IQR 26-41). Several risk factors were identified and included: previous valvular heart disease, patients with chronic kidney disease who have had a vascular access and previous history of immunological disease. The native mitral valve was the most affected. The size of vegetations had a median length of 14 mm (IQR 9.3-16). Streptococcus alpha hemolytic was the most common organism. In-hospital mortality rate was 10 %. CONCLUSIONS: The behavior of the disease is similar to other national series. We identify risk factors that could be related to the type of morbidities in the region.

Introducción: la endocarditis infecciosa es una enfermedad con elevada morbilidad y mortalidad. La expresión clínica es variable en diferentes poblaciones, por lo que es imperativo conocer las características de la enfermedad en nuestra región. Métodos: estudio observacional que incluyo la totalidad de los pacientes diagnosticados con endocarditis bacteriana entre el 1 de enero de 2009 hasta el 31 de diciembre de 2014. Los datos se presentan como frecuencias con porcentajes y medianas con rango intercuartílico, según sea el caso. Resultados: se incluyen 10 casos. La mediana de edad fue 34 años (RIC 26-41). Los factores de riesgo identificados fueron: enfermedad valvular previa, enfermedad renal crónica con acceso vascular y enfermedad inmunológica. La válvula mitral nativa fue la más afectada. La mediana de longitud de las vegetaciones fue de 14 mm (RIC 9.3-16). El estreptococo alfa hemolítico fue el microorganismo más común. La tasa de mortalidad intrahospitalaria fue del 10 %. Conclusiones: el comportamiento de la enfermedad es similar a otras series nacionales. Identificamos factores de riesgo que pueden circunscribirse a las morbilidades en la región.

Prevalence of diabetic nephropathy in Type 2 Diabetes Mellitus in rural communities of Guanajuato, Mexico. Effect after 6 months of Telmisartan treatment.

OBJECTIVE: To determine the prevalence of Diabetic Nephropathy (DN) in patients with type 2 Diabetes Mellitus (T2DM) with over 5 years of evolution in rural communities of Guanajuato, Mexico, and evaluate the effects of an ARB treatment over 6 months in patients with DN. MATERIALS AND METHODS: Patients of both sexes, 38-86 years, T2DM over 5 years of evolution and diagnosed with arterial hypertension (HT) after T2DM incidence. Monthly determination of microalbuminuria (MA), lipids, glucose, serum creatinine, and glycated hemoglobin (HbA1c). Estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) formula. A dose of 80 mg of Telmisartan was administered daily over 6 months. RESULTS: The total adult population of two rural communities (3609 subjects) was studied, 335 subjects had T2DM, among them 80 (with a prevalence of 24%) had DN and HT. Sixty-seven patients received Telmisartan, and showed significant improvement in all parameters studied. CONCLUSIONS: A higher prevalence of DN than that reported in the Mexican National Health Survey (ENSANUT) was found. Further research is required in a larger population sample in order to confirm the results of Telmisartan treatment.