Excess weight and anti-PD-1 immune checkpoint inhibitor’s outcomes in non-small cell lung cancer

Immune checkpoint inhibitors are one of the most effective treatments available in advanced non-small cell lung cancer. However, at present, there are no clinical or analytical biomarkers that define which patients benefit with certainty from these treatments. In our study, we evaluated whether excess weight could be a good predictive biomarker of benefit from these drugs.MethodsWe studied a population of 79 patients, divided into a study group with 39 patients diagnosed with non-small cell lung cancer treated with immunotherapy and 40 patients in a control group, diagnosed with different advanced cancers, treated with non-immunotherapy treatment. We analyzed according to the presence of excess weight or not, the treatment’s outcome in the study group and in the control group (objective response, and progression-free and overall survival).ResultsIn our study, we detected a better response rate to immunotherapy in patients with excess weight (62.50 vs 26.08%, OR 4.72, p = 0.02), and a better median progression-free survival (14.19 vs 5.03 months, HR 0.50, p = 0.058) and median overall survival (33.84 months vs 20.76 months, HR 0.43, p = 0.01) in the study group. These findings were specific to the immunotherapy group since in the control group, with patients who did not receive immune checkpoint inhibitors, these findings were not found.ConclusionOur study suggests that patients with excess weight who receive anti-PD-1 immune checkpoint inhibitors diagnosed with non-small cell lung cancer have a better outcome. This effect is specific to patients receiving immunotherapy. (AU)

Excess weight and anti-PD-1 immune checkpoint inhibitor's outcomes in non-small cell lung cancer.

PURPOSE: Immune checkpoint inhibitors are one of the most effective treatments available in advanced non-small cell lung cancer. However, at present, there are no clinical or analytical biomarkers that define which patients benefit with certainty from these treatments. In our study, we evaluated whether excess weight could be a good predictive biomarker of benefit from these drugs. METHODS: We studied a population of 79 patients, divided into a study group with 39 patients diagnosed with non-small cell lung cancer treated with immunotherapy and 40 patients in a control group, diagnosed with different advanced cancers, treated with non-immunotherapy treatment. We analyzed according to the presence of excess weight or not, the treatment's outcome in the study group and in the control group (objective response, and progression-free and overall survival). RESULTS: In our study, we detected a better response rate to immunotherapy in patients with excess weight (62.50 vs 26.08%, OR 4.72, p = 0.02), and a better median progression-free survival (14.19 vs 5.03 months, HR 0.50, p = 0.058) and median overall survival (33.84 months vs 20.76 months, HR 0.43, p = 0.01) in the study group. These findings were specific to the immunotherapy group since in the control group, with patients who did not receive immune checkpoint inhibitors, these findings were not found. CONCLUSION: Our study suggests that patients with excess weight who receive anti-PD-1 immune checkpoint inhibitors diagnosed with non-small cell lung cancer have a better outcome. This effect is specific to patients receiving immunotherapy.

Peripheral Blood Mononuclear Cells Predict Therapeutic Efficacy of Immunotherapy in NSCLC.

In lung cancer immunotherapy, biomarkers to guide clinical decisions are limited. We now explore whether the detailed immunophenotyping of circulating peripheral blood mononuclear cells (PBMCs) can predict the efficacy of anti-PD-1 immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC). We determined 107 PBMCs subpopulations in a prospective cohort of NSCLC patients before starting single-agent anti-PD-1 immunotherapy (study group), analyzed by flow cytometry. As a control group, we studied patients with advanced malignancies before initiating non-immunotherapy treatment. The frequency of PBMCs was correlated with treatment outcome. Patients were categorized as having either high or low expression for each biomarker, defined as those above the 55th or below the 45th percentile of the overall marker expression within the cohort. In the study group, three subpopulations were associated with significant differences in outcome: high pretreatment levels of circulating CD4+CCR9+, CD4+CCR10+, or CD8+CXCR4+ T cells correlated with poorer overall survival (15.7 vs. 35.9 months, HR 0.16, p = 0.003; 22.0 vs. NR months, HR 0.10, p = 0.003, and 22.0 vs. NR months, HR 0.29, p = 0.02). These differences were specific to immunotherapy-treated patients. High baseline levels of circulating T cell subpopulations related to tissue lymphocyte recruitment are associated with poorer outcomes of immunotherapy-treated advanced NSCLC patients.

A Differential Signature of Circulating miRNAs and Cytokines Between COVID-19 and Community-Acquired Pneumonia Uncovers Novel Physiopathological Mechanisms of COVID-19.

Coronavirus Disease 2019 (COVID-19) pneumonia is a life-threatening infectious disease, especially for elderly patients with multiple comorbidities. Despite enormous efforts to understand its underlying etiopathogenic mechanisms, most of them remain elusive. In this study, we compared differential plasma miRNAs and cytokines profiles between COVID-19 and other community-acquired pneumonias (CAP). A first screening and subsequent validation assays in an independent cohort of patients revealed a signature of 15 dysregulated miRNAs between COVID-19 and CAP patients. Additionally, multivariate analysis displayed a combination of 4 miRNAs (miR-106b-5p, miR-221-3p, miR-25-3p and miR-30a-5p) that significantly discriminated between both pathologies. Search for targets of these miRNAs, combined with plasma protein measurements, identified a differential cytokine signature between COVID-19 and CAP that included EGFR, CXCL12 and IL-10. Significant differences were also detected in plasma levels of CXCL12, IL-17, TIMP-2 and IL-21R between mild and severe COVID-19 patients. These findings provide new insights into the etiopathological mechanisms underlying COVID-19.

Usefulness of circulating microRNAs miR-146a and miR-16-5p as prognostic biomarkers in community-acquired pneumonia.

INTRODUCTION: Patients with community-acquired pneumonia (CAP) undergo a dysregulated host response that is related to mortality. MicroRNAs (miRNAs) participate in this response, but their expression pattern and their role as biomarkers in CAP have not been fully characterized. METHODS: A prospective observational study was performed in a cohort of 153 consecutive patients admitted to hospital with CAP. Clinical and analytical variables were collected, and the main outcome variable was 30-day mortality. Small RNA was purified from plasma of these patients obtained on the first day of admission, and miRNA expression was analyzed by RT-PCR. Univariate and multivariate analyses were carried out through the construction of a logistic regression model. The proposed model was compared with established prognostic clinical scales using ROC curve analysis. RESULTS: The mean age of the patients included was 74.7 years [SD 15.9]. Their mean PSI was 100.9 [SD 34.6] and the mean modified Charlson index was 2.9 [SD 3.0]. Both miR-146a and miR-16-5p showed statistically significant association with 30-day mortality after admission due to CAP (1.10 vs. 0.23 and 51.74 vs. 35.23, respectively), and this association remained for miR-16-5p in the multivariate analysis adjusted for age, gender and history of bronchoaspiration (OR 0.95, p = 0.021). The area-under-the-curve (AUC) of our adjusted multivariate model (AUC = 0.954 95%CI [0.91-0.99]), was better than those of prognostic scales such as PSI (AUC = 0.799 [0.69-0.91]) and CURB-65 (AUC = 0.722 [0.58-0.86]). CONCLUSIONS: High levels of miR-146a-5p and miR-16-5p upon admission due to CAP are associated with lower mortality at 30 days of follow-up. Both miRNAs could be used as biomarkers of good prognosis in subjects hospitalized with CAP.

Effect of excess weight and immune-related adverse events on the efficacy of cancer immunotherapy with anti-PD-1 antibodies.

Immunotherapy is an effective treatment in advanced cancer, although predictors of response are limited. We studied whether excess weight influences the efficacy outcomes of immunotherapy. We have also evaluated the combined prognostic effect of excess weight and immune-related adverse events (irAEs). Efficacy of anti-PD-1 treatment was evaluated with both objective radiological response (ORR) rate and progression-free survival (PFS), and toxicity with irAEs. We studied the association between excess weight and ORR, PFS or irAEs. 132 patients diagnosed with advanced cancer were included. Median body mass index (BMI) was 24.9 kg/m2. 64 patients had normal weight (BMI<25 kg/m2), and 64 patients had excess weight (BMI≥25 kg/m2). Four patients had underweight and were excluded from further analysis. ORR was achieved in 50 patients (38.0%), median PFS was 6 months. 44 patients developed irAEs (33.3%). ORR was higher in excess weight patients than in patients with normal weight (51.6% vs 25.0%; OR 3.45, p = .0009). PFS was improved in patients with excess weight (7.25 months vs 4 months, HR 1.72, p = .01). The incidence of IrAEs was not different in patients with excess weight (54.5% vs 43.2%, p = .21). When high BMI and irAEs were combined, we observed a marked prognostic trend in ORR rate (87.5% vs 6.2%; OR 161.0, p < .00001), and in PFS (14 months vs 3 months; HR 5.89, p < .0001). Excess weight patients with advanced cancer that receive single-agent anti-PD-1 antibody therapy exhibit a significantly improved clinical outcome compared with normal BMI patients. This association was especially marked when BMI and irAEs were considered combined.

Estudio del porcentaje de neutrófilos y el cociente de neutrófilos-linfocitos como marcadores pronósticos en pacientes hospitalizados por neumonía adquirida en la comunidad / Neutrophil Count Percentage and Neutrophil-Lymphocyte Ratio as Prognostic Markers in Patients Hospitalized for Community-Acquired Pneumonia

Introducción: La neumonía adquirida en la comunidad (NAC) es una infección frecuente y grave. El objetivo de este trabajo es estudiar la utilidad pronóstica del porcentaje de neutrófilos (NCP) y del cociente neutrófilos/linfocitos (NLR) en pacientes con NAC. Métodos: Estudio retrospectivo de pacientes hospitalizados por NAC con analítica al ingreso y una segunda extracción de control a los 3-5 días. Se consideraron variables desenlace la mortalidad a 30 y 90 días. Resultados: Se incluyó a 209 pacientes. Los pacientes que sobrevivieron redujeron significativamente el NCP y el NLR entre la analítica al diagnóstico y la de control (desde el 85,8 hasta el 65,4% para NCP y de 10,1 a 3,2 para NLR). Fallecieron 25 pacientes en los primeros 90 días. En ellos hubo un menor descenso no significativo para el NCP (del 84,8 al 74,0%) y para NLR (de 9,9 a 6,9). Los valores de NCP y NLR en la analítica de control fueron significativamente mayores en los pacientes fallecidos que en los supervivientes. Aquellos pacientes que presentaron en la analítica de control un NCP superior al 85% o un NLR superior a 10, presentaron un riesgo de mortalidad superior tras ajuste multivariable (HR para NCP 12 y para NLR 6,5). Conclusión: NCP y NLR son parámetros sencillos y de bajo coste, con utilidad pronóstica especialmente al medirse a los 3-5 días del diagnóstico de NAC. Niveles altos de NLR o NCP se asocian con mayor riesgo de mortalidad a los 90 días

Introduction: Community-acquired pneumonia (CAP) is a common serious infection. This study aimed to evaluate the prognostic utility of neutrophil count percentage (NCP) and neutrophil-lymphocyte ratio (NLR) in patients with CAP. Methods: Retrospective study of hospitalized patients with CAP. Patients had a blood test at admission and 3-5 days after hospitalization (early-stage test). The main outcome variables were 30-day and 90-day mortality. Results: Two hundred and 9 patients were included. Patients who survived had significant reductions in both NCP and NLR between admission and the day 3-5 blood tests (from 85.8% to 65.4% for NCP and from 10.1 to 3.2 for NLR). Twenty-five patients died in the first 90 days. Patients who died had lower, non-significant reductions in NCP (from 84.8% to 74%) and NLR (from 9.9 to 6.9) and significantly higher early-stage NCP and NLR than those who survived. NCP values higher than 85% and NLR values higher than 10 in the early-stage blood test were associated with a higher risk of mortality, even after multivariate adjustment (HR for NCP: 12; HR for NLR: 6.5). Conclusion: NCP and NLR are simple, low-cost parameters with prognostic utility, especially when measured 3-5 days after CAP diagnosis. High NLR and/or NCP levels are associated with a greater risk of mortality at 90 days

Neutrophil Count Percentage and Neutrophil-Lymphocyte Ratio as Prognostic Markers in Patients Hospitalized for Community-Acquired Pneumonia. / Estudio del porcentaje de neutrófilos y el cociente de neutrófilos-linfocitos como marcadores pronósticos en pacientes hospitalizados por neumonía adquirida en la comunidad.

INTRODUCTION: Community-acquired pneumonia (CAP) is a common serious infection. This study aimed to evaluate the prognostic utility of neutrophil count percentage (NCP) and neutrophil-lymphocyte ratio (NLR) in patients with CAP. METHODS: Retrospective study of hospitalized patients with CAP. Patients had a blood test at admission and 3-5 days after hospitalization (early-stage test). The main outcome variables were 30-day and 90-day mortality. RESULTS: Two hundred and 9patients were included. Patients who survived had significant reductions in both NCP and NLR between admission and the day 3-5 blood tests (from 85.8% to 65.4% for NCP and from 10.1 to 3.2 for NLR). Twenty-five patients died in the first 90 days. Patients who died had lower, non-significant reductions in NCP (from 84.8% to 74%) and NLR (from 9.9 to 6.9) and significantly higher early-stage NCP and NLR than those who survived. NCP values higher than 85% and NLR values higher than 10 in the early-stage blood test were associated with a higher risk of mortality, even after multivariate adjustment (HR for NCP: 12; HR for NLR: 6.5). CONCLUSION: NCP and NLR are simple, low-cost parameters with prognostic utility, especially when measured 3-5 days after CAP diagnosis. High NLR and/or NCP levels are associated with a greater risk of mortality at 90 days.

Correction: Inflammation biomarkers in blood as mortality predictors in community-acquired pneumonia admitted patients: Importance of comparison with neutrophil count percentage or neutrophil-lymphocyte ratio.

[This corrects the article DOI: 10.1371/journal.pone.0173947.].

Inflammation biomarkers in blood as mortality predictors in community-acquired pneumonia admitted patients: Importance of comparison with neutrophil count percentage or neutrophil-lymphocyte ratio.

INTRODUCTION: The increase and persistence of inflammation in community-acquired pneumonia (CAP) patients can lead to higher mortality. Biomarkers capable of measuring this inadequate inflammatory response are likely candidates to be related with a bad outcome. We investigated the association between concentrations of several inflammatory markers and mortality of CAP patients. MATERIAL AND METHODS: This was a prospective study of hospitalised CAP patients in a Spanish university hospital. Blood tests upon admittance and in the early-stage evolution (72-120 hours) were carried out, where C-reactive protein, procalcitonin, proadrenomedullin, copeptin, white blood cell, Lymphocyte Count Percentage (LCP), Neutrophil Count Percentage (NCP) and Neutrophil/Lymphocyte Ratio (NLR) were measured. The outcome variable was mortality at 30 and 90 days. Statistical analysis included logistic regression, ROC analysis and area-under-curve test. RESULTS: 154 hospitalised CAP patients were included. Patients who died during follow-up had higher levels of procalcitonin, copeptin, proadrenomedullin, lower levels of LCP, and higher of NCP and NLR. Remarkably, multivariate analysis showed a relationship between NCP and mortality, regardless of age, severity of CAP and comorbidities. AUC analysis showed that NLR and NCP at admittance and during early-stage evolution achieved a good diagnostic power. ROC test for NCP and NLR were similar to those of the novel serum biomarkers analysed. CONCLUSIONS: NLR and NCP, are promising candidate predictors of mortality for hospitalised CAP patients, and both are cheaper, easier to perform, and at least as reliable as the new serum biomarkers. Future implementation of new biomarkers would require comparison not only with classic inflammatory parameters like White Blood Cell count but also with NLR and NCP.

Pneumonia presenting with organ dysfunctions: Causative microorganisms, host factors and outcome.

Community-acquired pneumonia (CAP) is a serious infection that may occasionally rapidly evolve provoking organ dysfunctions. We aimed to characterize CAP presenting with organ dysfunctions at the emergency room, with regard to host factors and causative microorganisms, and its impact on 30-day mortality. 460 of 4070 (11.3%) CAP patients had ≥2 dysfunctions at diagnosis, with a 30-day mortality of 12.4% vs. 3.4% in those with one or no dysfunctions. Among them, the most frequent causative microorganisms were Streptococcus pneumoniae, gram-negatives and polymicrobial etiology. Independent host risk factors for presenting with ≥2 dysfunctions were: liver (OR 2.97) and renal diseases (OR 3.91), neurological disorders (OR 1.86), and COPD (OR 1.30). Methicillin-resistant Staphylococcus aureus (OR 6.41) and bacteraemic episodes (OR 1.68) had the higher independent risk among microorganisms. The number of organ dysfunctions vs. none increased at 30-day mortality: three organs (OR 11.73), two organs (OR 4.29), and one organ (OR 2.42) whereas Enterobacteria (OR 3.73) were also independently related to mortality. The number of organ dysfunctions was the strongest 30-day mortality risk factor while Enterobacteriaceae was also associated with poorer outcome. The assessment of organ dysfunctions in CAP should be implemented for management, allocation and treatment decisions on initial evaluation.

Age-related risk factors for bacterial aetiology in community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate the effect of age and comorbidities, smoking and alcohol use on microorganisms in patients with community-acquired pneumonia (CAP). METHODS: A prospective multicentre study was performed with 4304 patients. We compared microbiological results, bacterial aetiology, smoking, alcohol abuse and comorbidities in three age groups: young adults (<45 years), adults (45-64 years) and seniors (>65 years). RESULTS: Bacterial aetiology was identified in 1522 (35.4%) patients. In seniors, liver disease was independently associated with Gram-negative bacteria (Haemophilus influenzae and Enterobacteriaceae), COPD with Pseudomonas aeruginosa (OR = 2.69 (1.46-4.97)) and Staphylococcus aureus (OR = 2.8 (1.24-6.3)) and neurological diseases with S. aureus. In adults, diabetes mellitus (DM) was a risk factor for Streptococcus pneumoniae and S. aureus, and COPD for H. influenzae (OR = 3.39 (1.06-10.83)). In young adults, DM was associated with S. aureus. Smoking was a risk factor for Legionella pneumophila regardless of age. Alcohol intake was associated with mixed aetiology and Coxiella burnetii in seniors, and with S. pneumoniae in young adults. CONCLUSION: It should be considered that the bacterial aetiology may differ according to the patient's age, comorbidities, smoking and alcohol abuse. More extensive microbiological testing is warranted in those with risk factors for infrequent microorganisms.

Actualización sobre Aspergillus, Pneumocystis y otras micosis pulmonares oportunistas / Updates on Aspergillus, Pneumocystis and other opportunistic pulmonary mycoses

Las micosis son enfermedades graves y potencialmente letales. Con el desarrollo de terapias inmunosupresoras y técnicas de soporte vital, la inmunosupresión en sus diferentes grados es cada vez más prevalente. El deterioro de la respuesta inmune es el factor de riesgo principal para el desarrollo de las micosis oportunistas. El diagnóstico y tratamiento precoces son factores cruciales para mejorar el pronóstico de estas enfermedades. Sin embargo, los aislamientos mediante cultivos o las técnicas de detección antigénicas no son capaces de distinguir entre colonización e infección invasiva, y las biopsias rara vez se pueden realizar por la situación clínica. Ello sitúa al médico en una situación de incertidumbre en la que debe reconocer precozmente los signos clínicos y radiológicos e interpretar los resultados microbiológicos en su contexto. El objetivo de esta revisión es aportar una visión general del perfil de paciente que sufre estas infecciones, el papel de su sistema inmune, y de forma más detallada, los principales avances diagnósticos más reconocidos y recomendados por la comunidad científica

Mycoses are serious diseases with potentially fatal outcome. The introduction of immunosuppressive treatments and life support techniques has led to a growing prevalence of different degrees of immunosuppression. Compromised immune response is the primary risk factor for the development of opportunistic mycoses. Early diagnosis and treatment are crucial for improving prognosis. However, isolation in cultures or identification using antigen detection techniques cannot distinguish between colonization and invasive infection, and the clinical status of the patient often prevents biopsy sampling. Clinicians thus find themselves in an uncertain position, requiring them to quickly recognize clinical and radiological signs and interpret microbiological results in context. The aim of this review is to provide a general overview of the profile of patients susceptible to these infections, the role of the immune system and, in more detail, the major diagnostic developments that have gained most acceptance and recognition among the scientific community

Revisión sobre las infecciones no bacterianas del aparato respiratorio: neumonías víricas / Review of Non-Bacterial Infections in Respiratory Medicine: Viral Pneumonia

Aunque las bacterias son los principales patógenos involucrados en la neumonía adquirida en la comunidad, algunos virus son responsables directos o en coinfección de un importante número de neumonías adquiridas en la comunidad. La clínica de estas neumonías puede ser muy similar, en el caso de los virus afectan más frecuentemente a la población infantil y geriátrica, con frecuencia no elevan la cifra de leucocitos, la fiebre es inconstante y frecuentemente se acompañan de síntomas de vías respiratorias altas. Característicamente no elevan la procalcitonina. Durante años el diagnóstico ha recaído en cultivos celulares y en detección de antígenos; desde la incorporación en la clínica de la PCR, la identificación de estos patógenos ha aumentado, descubriéndose nuevos microorganismos como el bocavirus. En general, el virus influenza A y el virus respiratorio sincitial siguen siendo los principales virus implicados. Sin embargo, la irrupción en los últimos años de epidemias con alta letalidad de coronavirus y de zoonosis de virus influenza hace que sea necesario mostrarse alerta ante estos nuevos patógenos emergentes. Los inhibidores de la neuraminidasa para neumonías víricas han demostrado disminuir la transmisión en casos expuestos y mejorar la evolución clínica en pacientes en Cuidados Intensivos; su uso en infecciones banales no está recomendado. La ribavirina ha sido utilizada en niños con infecciones por virus respiratorio sincitial, así como en inmunodeprimidos. Fuera de estos fármacos, ningún otro antiviral ha probado su eficacia. Las medidas de prevención con vacunación para virus influenza y con anticuerpos monoclonales para virus respiratorio sincitial podrían disminuir la incidencia de neumonía

Although bacteria are the main pathogens involved in community-acquired pneumonia, a significant number of community-acquired pneumonia are caused by viruses, either directly or as part of a co-infection. The clinical picture of these different pneumonias can be very similar, but viral infection is more common in the pediatric and geriatric populations, leukocytes are not generally elevated, fever is variable, and upper respiratory tract symptoms often occur; procalcitonin levels are not generally affected. For years, the diagnosis of viral pneumonia was based on cell culture and antigen detection, but since the introduction of polymerase chain reaction techniques in the clinical setting, identification of these pathogens has increased and new microorganisms such as human bocavirus have been discovered. In general, influenza virus type A and syncytial respiratory virus are still the main pathogens involved in this entity. However, in recent years, outbreaks of deadly coronavirus and zoonotic influenza virus have demonstrated the need for constant alert in the face of new emerging pathogens. Neuraminidase inhibitors for viral pneumonia have been shown to reduce transmission in cases of exposure and to improve the clinical progress of patients in intensive care; their use in common infections is not recommended. Ribavirin has been used in children with syncytial respiratory virus, and in immunosuppressed subjects. Apart from these drugs, no antiviral has been shown to be effective. Prevention with anti-influenza virus vaccination and with monoclonal antibodies, in the case of syncytial respiratory virus, may reduce the incidence of pneumonia

Updates on Aspergillus, Pneumocystis and other opportunistic pulmonary mycoses.

Mycoses are serious diseases with potentially fatal outcome. The introduction of immunosuppressive treatments and life support techniques has led to a growing prevalence of different degrees of immunosuppression. Compromised immune response is the primary risk factor for the development of opportunistic mycoses. Early diagnosis and treatment are crucial for improving prognosis. However, isolation in cultures or identification using antigen detection techniques cannot distinguish between colonization and invasive infection, and the clinical status of the patient often prevents biopsy sampling. Clinicians thus find themselves in an uncertain position, requiring them to quickly recognize clinical and radiological signs and interpret microbiological results in context. The aim of this review is to provide a general overview of the profile of patients susceptible to these infections, the role of the immune system and, in more detail, the major diagnostic developments that have gained most acceptance and recognition among the scientific community.

Review of Non-Bacterial Infections in Respiratory Medicine: Viral Pneumonia.

Although bacteria are the main pathogens involved in community-acquired pneumonia, a significant number of community-acquired pneumonia are caused by viruses, either directly or as part of a co-infection. The clinical picture of these different pneumonias can be very similar, but viral infection is more common in the pediatric and geriatric populations, leukocytes are not generally elevated, fever is variable, and upper respiratory tract symptoms often occur; procalcitonin levels are not generally affected. For years, the diagnosis of viral pneumonia was based on cell culture and antigen detection, but since the introduction of polymerase chain reaction techniques in the clinical setting, identification of these pathogens has increased and new microorganisms such as human bocavirus have been discovered. In general, influenza virus type A and syncytial respiratory virus are still the main pathogens involved in this entity. However, in recent years, outbreaks of deadly coronavirus and zoonotic influenza virus have demonstrated the need for constant alert in the face of new emerging pathogens. Neuraminidase inhibitors for viral pneumonia have been shown to reduce transmission in cases of exposure and to improve the clinical progress of patients in intensive care; their use in common infections is not recommended. Ribavirin has been used in children with syncytial respiratory virus, and in immunosuppressed subjects. Apart from these drugs, no antiviral has been shown to be effective. Prevention with anti-influenza virus vaccination and with monoclonal antibodies, in the case of syncytial respiratory virus, may reduce the incidence of pneumonia.

The incidence of cardiovascular events after hospitalization due to CAP and their association with different inflammatory markers.

BACKGROUND: Late prognosis of Community-Acquired Pneumonia (CAP) patients is related to cardiovascular events. Persistence of inflammation-related markers, defined by high circulatory levels of interleukin 6 and 10 (IL-6/IL-10), is associated with a higher post-event mortality rate for CAP patients. However, association between these markers and other components of the immune response, and the risk of cardiovascular events, has not been adequately explored. The main objectives of this study are: 1) to quantify the incidence of cardiovascular disease, in the year post-dating their hospital admittance due to CAP and, 2) to describe the distribution patterns of a wide spectrum of inflammatory markers upon admittance to and release from hospital, and to determine their relationship with the incidence of cardiovascular disease. METHODS/DESIGN: A cohort prospective study. All patients diagnosed and hospitalized with CAP will be candidates for inclusion. The study will take place in the Universitary Hospital La Princesa, Spain, during two years. Two samples of blood will be taken from each patient: the first upon admittance and the second one prior to release, in order to analyse various immune agents. The main determinants are: pro-adrenomedullin, copeptin, IL-1, IL-6, TNF-α, IL-17, IFN-γ, IL-10 and TGF-ß, E-Selectin, ICAM-1, VCAM-1 and subpopulations of peripheral T lymphocytes (T regulator, Th1 and Th17), together with other clinical and analytical variables. Follow up will start at admittance and finish a year after discharge, registering incidence of death and cardiovascular events. The main objective is to establish the predictive power of different inflammatory markers in the prognosis of CAP, in the short and long term, and their relationship with cardiovascular disease. DISCUSSION: The level of some inflammatory markers (IL-6/IL-10) has been proposed as a means to differentiate the degree of severity of CAP, but their association with cardiovascular risk is not well established. In this study we aim to define new inflammatory markers associated with cardiovascular disease that could be helpful for the prognosis of CAP patients, by describing the distribution of a wide spectrum of inflammatory mediators and analyzing their association with the incidence of cardiovascular disease and mortality one year after release from hospital.

Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection.

INTRODUCTION: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains. METHODS: We studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection. RESULTS: Multivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A(0) were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A(1) was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A(1) haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A(0) (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO2 ratio, whereas haplotype 1A(1) was associated with a higher PaO2/FiO2 ratio (P = 0.001). CONCLUSIONS: Our data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A(1)) SP-A2 for future IAV pandemics.

Tobacco smoking increases the risk for death from pneumococcal pneumonia.

BACKGROUND: Active smoking increases the risk of developing community-acquired pneumonia (CAP) and invasive pneumococcal disease, although its impact on mortality in pneumococcal CAP outcomes remains unclear. The aim of this study was to investigate the influence of current smoking status on pneumococcal CAP mortality. METHODS: We performed a multicenter, prospective, observational cohort study in 4,288 hospitalized patients with CAP. The study group consisted of 892 patients with pneumococcal CAP: 204 current smokers (22.8%), 387 nonsmokers (43.4%), and 301 exsmokers (33.7%). RESULTS: Mortality at 30 days was 3.9%: 4.9% in current smokers vs 4.3% in nonsmokers and 2.6% in exsmokers. Current smokers with CAP were younger (51 years vs 74 years), with more alcohol abuse and fewer cardiac, renal, and asthma diseases. Current smokers had lower CURB-65 (confusion, uremia, respiratory rate, BP, age ≥ 65 years) scores, although 40% had severe sepsis at diagnosis. Current smoking was an independent risk factor (OR, 5.0; 95% CI, 1.8-13.5; P = .001) for 30-day mortality of pneumococcal CAP after adjusting for age (OR, 1.06; P = .001), liver disease (OR, 4.5), sepsis (OR, 2.3), antibiotic adherence to guidelines, and first antibiotic dose given < 6 h. The independent risk effect of current smokers remained when compared only with nonsmokers (OR, 4.0; 95% CI, 1.3-12.6; P = .015) or to exsmokers (OR, 3.9; 95% CI, 1.09-4.95; P = .02). CONCLUSIONS: Current smokers with pneumococcal CAP often develop severe sepsis and require hospitalization at a younger age, despite fewer comorbid conditions. Smoking increases the risk of 30-day mortality independently of tobacco-related comorbidity, age, and comorbid conditions. Current smokers should be actively targeted for preventive strategies.