Hipertensión pulmonar: Correlación de los marcadores plasmáticos con la supervivencia de los pacientes

<b>Background:</b> Recent studies have provided evidence for an important contribution of the immune system in the pathophysiology of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we investigated whether the inflammatory profile of pulmonary hypertension patients changes over time and correlates with patient WHO subgroups or survival. <b>Methods:</b> 50 PAH patients (16 idiopathic (I)PAH, 24 Connective Tissue Disease (CTD)-PAH and 10 Congenital Heart Disease (CHD)-PAH), 37 CTEPH patients and 18 healthy controls (HCs) were included in the study. Plasma inflammatory markers at baseline and after 1-year follow-up were measured using ELISAs. Subsequently, correlations with hemodynamic parameters and survival were explored and data sets were subjected to unbiased multivariate analyses. <b>Results:</b> At diagnosis, we found that plasma levels of interleukin-6 (IL-6) and the chemokines (C-X3-C) motif legend CXCL9 and CXCL13 in CTD-PAH patients were significantly increased, compared with HCs. In idiopathic PAH patients the levels of tumor growth factor-β (TGFβ), IL-10 and CXCL9 were elevated, compared with HCs. The increased CXCL9 and IL-8 concentrations in CETPH patients correlated significantly with decreased survival, suggesting that CXCL9 and IL-8 may be prognostic markers. After one year of treatment, IL-10, CXCL13 and TGFβ levels changed significantly in the PAH subgroups and CTEPH patients. Unbiased multivariate analysis revealed clustering of PH patients based on inflammatory mediators and clinical parameters, but did not separate the WHO subgroups. Importantly, these multivariate analyses separated patients with &#x3c;3 years and &#x3e;3 years survival, in particular when inflammatory mediators were combined with clinical parameters. <b>Discussion:</b> Our study revealed elevated plasma levels of inflammatory mediators in different PAH subgroups and CTEPH at baseline and at 1-year follow-up, whereby CXCL9 and IL-8 may prove to be prognostic markers for CTEPH patients. While this study is exploratory and hypothesis generating, our data indicate an important role for IL-8 and CXCL9 in CHD and CTEPH patients considering the increased plasma levels and the observed correlation with survival. <b>Conclusion:</b> In conclusion, our studies identified an inflammatory signature that clustered PH patients into WHO classification-independent subgroups that correlated with patient survival.

Deterioro en la actividad ventilatoria hipóxica inducido por neuropatía autonómica diabética, una causa de diagnóstico erróneo de eventos cardiacos graves: breve reporte de dos casos

<b>Resumen:</b> La ocurrencia de muerte súbita cardiaca es dos veces más frecuente en pacientes diabéticos con neuropatía autonómica. La etiología de la muerte súbita cardiaca aún no está clara, y no existen recomendaciones para identificar factores asociados con el paro cardiorrespiratorio en pacientes diabéticos. Proponemos la hipótesis, con base en dos casos clínicos, de que un deterioro en la actividad respiratoria hipóxica, inducido por la neuropatía autonómica diabética, es una causa del diagnóstico erróneo de eventos cardiacos graves. <b>Presentación de casos:</b> Describimos los casos de dos pacientes con baja saturación sanguínea aislada, medida con oxímetro de pulso durante la revisión rutinaria (77% y 85%, respectivamente), que contrasta con la ausencia de molestias como disnea, polipnea u otros signos de insuficiencia respiratoria durante el examen clínico. La gasometría arterial confirmó subsecuentemente la baja saturación de oxígeno en la sangre, y que ambas pacientes se hallaban hipoxémicas. La paciente 1 sufría una sobrecarga vascular complicada con paro cardiaco causado por hipoxemia, en vista de la rápida recuperación observada después de la ventilación. En la paciente 2 se diagnosticó edema pulmonar. El denominador común en los dos casos descritos en este breve reporte es la ausencia de signos clínicos de insuficiencia respiratoria y su contraste con la presencia confirmada de hipoxemia. Asimismo, en ambos casos, la ausencia de dichos signos precursores parece deberse a un deterioro en la actividad ventilatoria hipóxica, que resultó en hipoxemia. Ésta parece estar relacionada con la neuropatía autonómica diabética encontrada en estas dos pacientes. <b>Conclusiones:</b> Por tanto, en este breve reporte señalamos a la neuropatía autonómica cardiaca como una causa de deterioro en la actividad respiratoria hipóxica, vinculado con eventos cardiorrespiratorios agudos y severos en dos pacientes con diabetes tipo 1. Asumimos que una respuesta alterada a la hipoxemia debida a la neuropatía autonómica cardiaca y un comando respiratorio neurológico central no-funcional podría tener un papel clave en la muerte súbita entre pacientes diabéticos. Un punto importante es que es fácil pasar por alto la hipoxemia, puesto que no se reportan signos de insuficiencia respiratoria en estos dos casos clínicos. Es necesario aplicar una búsqueda sistemática de neuropatía autonómica cardiaca y detectar de manera proactiva el deterioro en la actividad respiratoria hipóxica en pacientes diabéticos, para garantizar un manejo temprano de la condición (p. ej., dando tratamiento a la hipoxia) y prevenir consecuencias dramáticas, como el paro cardiorrespiratorio y la muerte.

EPOC: Enfoque personalizado para el tratamiento según la guía GOLD 2021

<b>Background:</b> In the Phase III KRONOS study, triple therapy with budesonide/glycopyrronium/formoterol fumarate metered dose inhaler (BGF MDI) was shown to reduce exacerbations and improve lung function versus glycopyrronium/formoterol fumarate dihydrate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). However, whether the benefits related to the ICS component of BGF are driven by patients with high blood eosinophil counts (EOS) and/or airway reversibility has not been previously studied. <b>Methods:</b> KRONOS was a Phase III, double-blind, parallel-group, multicenter, randomized, controlled study of patients with moderate-to-very-severe COPD. Patients were randomized 2:2:1:1 to receive BGF 320/14.4/10 μg, GFF 14.4/10 μg, budesonide/formoterol fumarate dihydrate (BFF) MDI 320/10 μg via a single Aerosphere inhaler, or open-label budesonide/formoterol fumarate dihydrate dry powder inhaler 400/12 μg (BUD/FORM DPI; Symbicort Turbuhaler) twice-daily for 24 weeks. Efficacy outcomes included in this post-hoc analysis were change from baseline in morning pre-dose trough FEV1 over weeks 12–24 and the rate of moderate-to-severe and severe COPD exacerbations. Adverse events in the non-reversible subgroup are also reported. <b>Results:</b> Of 1896 patients analyzed, 948 (50%) were non-reversible and had EOS &#x3c;300 cells/mm³. In this group, BGF significantly improved morning pre-dose trough FEV₁ versus BFF and BUD/FORM (least squares mean treatment difference, 95% confidence interval [CI] 69 mL [39, 99], unadjusted <i>p</i> &#x3c; 0.0001 and 51 mL [20, 81], unadjusted <i>p</i> = 0.0011, respectively) and was comparable to GFF. BGF also significantly reduced annual moderate-to-severe exacerbation rates versus GFF (rate ratio [95% CI] 0.53 [0.37, 0.76], unadjusted <i>p</i> = 0.0005), with numerical reductions observed versus BFF and BUD/FORM. These results were similar for the overall study population. Safety findings were generally similar between non-reversible patients with EOS &#x3c;300 cells/mm³ and the overall population. <b>Conclusions:</b> In patients with moderate-to-very-severe COPD without airway reversibility and EOS &#x3c;300 cells/mm³, BGF significantly improved morning pre-dose trough FEV1 versus BFF and BUD/FORM and significantly reduced the rate of moderate-to-severe exacerbations versus GFF. These findings demonstrate that BGF can provide benefits for a broad range of patients with COPD, and that the overall findings of the KRONOS primary analysis were not driven by patients with reversible airflow obstruction or high eosinophil counts. <b>Trial registration:</b> ClinicalTrials.gov, NCT02497001. Registered 14 July 2015, https://clinicaltrials.gov/ct2/show/NCT02497001

Síntomas respiratorios: En busca de patrones normales de síntomas en preescolares, escolares y adolescentes

<b>Aim:</b> To study the pattern of respiratory symptoms in children in the general population. <b>Method:</b> We followed a cohort of children for up to 2 years through parents completing weekly online questionnaires in the Child-Is-Ill study («Kind-en-Ziekmeting» in Dutch); the study was running 2012–2015. Inclusion criteria were «an ordinary child» (according to the parents) and &#x3c;18 years old at inclusion. We especially encouraged participation of post-infancy children. Age at inclusion, sex, smoking exposure, allergy in the family, and frequent infections in the family were noted. Pearson’s correlation, principal component analysis, latent class analysis, latent profile analysis, linear regression, and linear mixed effects regression were used in the statistical analyses. <b>Results:</b> Data were collected on 55,524 childweeks in 755 children (50% girls; median age, 7 years; interquartile range, 4–11 years, 97% ≥2 years at inclusion), with reported symptom(s) in 8,425 childweeks (15%), leading to school absenteeism in 25%, doctor’s visits in 12%, and parental sick leave in 8%; symptoms lasting ≥3 weeks were rare (2% of episodes). Linear mixed effects regression showed significant, but only limited, effects of season on the proportion of «symptom(s) reported» per individual child. Only runny nose showed a significant, but very small, age effect. However, the variability between the children was considerable. There were no obvious subgroups of children with specific symptom combinations. <b>Conclusion:</b> In any randomly chosen week, the vast majority of children (85%) in our – mainly –post-infancy cohort derived from the general population did not have any symptom, even in the younger age group, even in winter. The children showed considerable variability; no clear subgroups of symptom patterns could be identified, underlining the difficult position of healthcare providers. These results support our opinion that post-infancy children in the general population should not be evaluated as if they are infants when they have recurrent respiratory symptoms. If they clearly deviate from the above-described most common pattern, it is wise to keep an eye on potential, maybe even rare, serious underlying causes.

Infección por rinovirus: Necesidad de estudios anatomopatológicos y secuelas funcionales en niños

Rhinoviruses (RVs) are increasingly implicated not only in mild upper respiratory tract infections, but also in more severe lower respiratory tract infections; however, little is known about species diversity and viral epidemiology of RVs among the infected children. Therefore, we investigated the rhinovirus (RV) infection prevalence over a 2-year period, compared it with prevalence patterns of other common respiratory viruses, and explored clinical and molecular epidemiology of RV infections among 590 children hospitalized with acute respiratory infection in north-western and central parts of Croatia. For respiratory virus detection, nasopharyngeal and pharyngeal flocked swabs were taken from each patient and subsequently analyzed with multiplex RT-PCR. To determine the RV species in a subset of positive children, 50UTR in RV-positive samples has been sequenced. Nucleotide sequences of referent RV strains were retrieved by searching the database with Basic Local Alignment Tool and used to construct alignments and phylogenetic trees using MAFFT multiple sequence alignment tool and the maximum likelihood method, respectively. In our study population RV was the most frequently detected virus, diagnosed in 197 patients (33.4%), of which 60.4% was detected as a monoinfection. Median age of RV-infected children was 2.25 years, and more than half of children infected with RV (55.8%) presented with lower respiratory tract infections. Most RV cases were detected from September to December, and all three species co-circulated during the analyzed period (2017–2019). Sequence analysis based on 50UTR region yielded 69 distinct strains; the most prevalent was RV-C (47.4%) followed by RV-A (44.7%) and RV-B (7.9%). Most of RV-A sequences formed a distinct phylogenetic group; only strains RI/HR409–18 (along with a reference strain MF978777) clustered with RV-C strains. Strains belonging to the group C were the most diverse (41.6% identity among strains), while group B was the most conserved (71.5% identity among strains). Despite such differences in strain groups (hitherto undescribed in Croatia), clinical presentation of infected children was rather similar. Our results are consistent with newer studies that investigated the etiology of acute respiratory infections, especially those focused on children with lower respiratory tract infections, where RVs should always be considered as potentially serious pathogens.

Hallazgos similares al COVID-19 en un caso fatal de neumonía intersticial descamativa asociada con glomerulonefritis por IgA en una niña de 13 meses de edad

En la era del COVID-19, es usual sospechar que cualquier paciente con síndrome respiratorio agudo grave (SARS) esté asociado con una infección por SARS-CoV-2. El objetivo de este artículo es presentar un caso de neumonía similar al COVID, con evolución fatal. Los aspectos clínicos se correlacionan con los hallazgos en la autopsia y se discuten en el contexto de los datos más recientes en la literatura médica. Una niña de 13 meses de edad ingresó a la sala de emergencias con dificultad respiratoria aguda y opacidades pulmonares bilaterales con apariencia de vidrio molido, además del pulmón izquierdo casi completamente opacificado. El estado de la paciente se deterioró súbitamente, y se confirmó la muerte 3 h después de la admisión. En la autopsia se diagnosticó neumonía intersticial descamativa grave, y se asoció con glomerulonefritis por IgA, un hallazgo poco usual. No se detectó infección por SARS-CoV-2 en el parénquima pulmonar mediante RT-PCR. Éste es un caso muy inusual de deterioro rápido de un infante con neumonía intersticial descamativa (NID) idiopática y afectación multiorgánica. Con base en tinciones inmunohistoquímicas, proponemos la hipótesis de que, en la NID, las membranas hialinas surgen de neumocitos descamados necrotizantes. En la era de COVID-19, tales casos son extremadamente difíciles de diagnosticar, y pueden semejar las lesiones pulmonares inducidas por el SARS-CoV-2. Esta pauta de formación de membrana hialina podría explicar la falta de respuesta a la terapia con oxígeno. El presente caso resalta la importancia de la autopsia en estos casos complicados.

Tratamiento médico exitoso de neumonía necrotizante en un paciente pediátrico

La neumonía necrotizante es una complicación grave pero poco frecuente de la neumonía en niños. Presentamos el caso de una niña de 20 meses de edad con dificultad respiratoria, que más adelante se diagnosticó como neumonía necrotizante. En este artículo subrayamos el papel de estudios de imagen como la radiografía torácica, la TC torácica y la ultrasonografía pulmonar para el diagnóstico, y la importancia de la terapia intravenosa con antibióticos para un mejor resultado.

Neumonía por COVID-19 en niños: De su etiología a su manejo

El COVID-19 es menos serio en niños que en adultos. Sin embargo, las afecciones respiratorias dominan el cuadro clínico de pacientes hospitalizados por COVID-19, aun en niños. En algunas series de casos, el deterioro del estado clínico, donde la disnea, la cianosis y el inicio del síndrome de dificultad respiratoria aguda (SDRA) emergieron ∼8–10 días después del inicio de la infección por SARS-CoV-2, pudo progresar rápidamente hasta la falla multiorgánica y la muerte. Esta revisión tiene como objetivo evaluar las características de la neumonía por COVID-19 en poblaciones pediátricas, comenzando con su etiología y sus mecanismos patológicos, para cerrar con su manejo clínico.