Is the long-term mortality similar in COVID-19 and community-acquired pneumonia?

Introduction: There are no data on the association of type of pneumonia and long-term mortality by the type of pneumonia (COVID-19 or community-acquired pneumonia [CAP]) on long-term mortality after an adjustment for potential confounding variables. We aimed to assess the type of pneumonia and risk factors for long-term mortality in patients who were hospitalized in conventional ward and later discharged. Methods: Retrospective analysis of two prospective and multicentre cohorts of hospitalized patients with COVID-19 and CAP. The main outcome under study was 1-year mortality in hospitalized patients in conventional ward and later discharged. We adjusted a Bayesian logistic regression model to assess associations between the type of pneumonia and 1-year mortality controlling for confounders. Results: The study included a total of 1,693 and 2,374 discharged patients in the COVID-19 and CAP cohorts, respectively. Of these, 1,525 (90.1%) and 2,249 (95%) patients underwent analysis. Until 1-year follow-up, 69 (4.5%) and 148 (6.6%) patients from the COVID-19 and CAP cohorts, respectively, died (p = 0.008). However, the Bayesian model showed a low probability of effect (PE) of finding relevant differences in long-term mortality between CAP and COVID-19 (odds ratio 1.127, 95% credibility interval 0.862-1.591; PE = 0.774). Conclusion: COVID-19 and CAP have similar long-term mortality after adjusting for potential confounders.

Aspiration pneumonia: A renewed perspective and practical approach.

Aspiration pneumonia (AP) is a sub-type of community-acquired pneumonia (CAP) still poorly recognized especially in the absence of an aspiration event. A further difficulty is the differentiation between AP and aspiration pneumonitis. From a clinical perspective, AP is becoming increasingly relevant as a potential cause of severe and life-threatening respiratory infection among frail and very old patients, particularly among those with CAP requiring inpatient care. Moreover, AP is frequently underdiagnosed and a clear-cut definition of this pathological entity is lacking. There are different factors that increase the risk for aspiration, but other common factors influencing oral colonization such as malnutrition, smoking, poor oral hygiene or dry mouth, are also important in the pathogenesis of AP and should be considered. While there is no doubt in the diagnosis of AP in cases of a recent witnessed aspiration of oropharyngeal or gastric content, we here proposed a definition of AP that also includes silent unobserved aspirations. For this reason, the presence of one or more risk factors of oropharyngeal aspiration is required together with one or more risk factors for oral bacterial colonization. This proposed definition based on expert opinion not only unifies the diagnostic criteria of AP, but also provides the possibility to devise easily applicable strategies to prevent oral colonization.

Validation of a Prediction Score for Drug-Resistant Microorganisms in Community-acquired Pneumonia.

Rationale: Recommended initial empiric antimicrobial treatment covers the most common bacterial pathogens; however, community-acquired pneumonia (CAP) may be caused by microorganisms not targeted by this treatment. Developed in 2015, the PES (Pseudomonas aeruginosa, extended-spectrum ß-lactamase-producing Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus) score was developed in 2015 to predict the microbiological etiology of CAP caused by PES microorganisms.Objective: To validate the usefulness of the PES score for predicting PES microorganisms in two cohorts of patients with CAP from Valencia and Mataró.Methods: We analyzed two prospective observational cohorts of patients with CAP from Valencia and Mataró. Patients in the Mataró cohort were all admitted to an intensive care unit (ICU).Results: Of the 1,024 patients in the Valencia cohort, 505 (51%) had a microbiological etiology and 31 (6%) had a PES microorganism isolated. The area under the receiver operating characteristic curve was 0.81 (95% confidence interval [95% CI], 0.74-0.88). For a PES score ≥5, sensitivity, specificity, the negative and positive predictive values as well as the negative and positive likelihood ratios were 72%, 74%, 98%, 14%, 0.38, and 2.75, respectively. Of the 299 patients in the Mataró cohort, 213 (71%) had a microbiological etiology and 11 (5%) had a PES microorganism isolated. The area under the receiver operating characteristic curve was 0.73 (95% CI 0.61-0.86). For a PES score ≥ 5, sensitivity, specificity, the negative and positive predictive values, and the negative and positive likelihood ratios were 36%, 83%, 96%, 11%, 0.77, and 2.09, respectively. The best cutoff for patients admitted to the ICU was 4 points, which improved sensitivity to 86%. The hypothetical application of the PES score showed high rates of overtreatment in both cohorts (26% and 35%, respectively) and similar rates of undertreatment.Conclusions: The PES score showed good accuracy in predicting the risk for microorganisms that required different empirical therapy; however, its use as a single strategy for detecting noncore pathogens could lead to high rates of overtreatment. Given its high negative predictive value, the PES score may be used as a first step of a wider strategy that includes subsequent advanced diagnostic tests.

Lower Respiratory Tract Infection and Short-Term Outcome in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVE: To assess whether ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with mortality in critically ill patients with acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: Post hoc analysis of prospective cohort study including mechanically ventilated patients from a multicenter prospective observational study (TAVeM study); VA-LRTI was defined as either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP) based on clinical criteria and microbiological confirmation. Association between intensive care unit (ICU) mortality in patients having ARDS with and without VA-LRTI was assessed through logistic regression controlling for relevant confounders. Association between VA-LRTI and duration of mechanical ventilation and ICU stay was assessed through competing risk analysis. Contribution of VA-LRTI to a mortality model over time was assessed through sequential random forest models. RESULTS: The cohort included 2960 patients of which 524 fulfilled criteria for ARDS; 21% had VA-LRTI (VAT = 10.3% and VAP = 10.7%). After controlling for illness severity and baseline health status, we could not find an association between VA-LRTI and ICU mortality (odds ratio: 1.07; 95% confidence interval: 0.62-1.83; P = .796); VA-LRTI was also not associated with prolonged ICU length of stay or duration of mechanical ventilation. The relative contribution of VA-LRTI to the random forest mortality model remained constant during time. The attributable VA-LRTI mortality for ARDS was higher than the attributable mortality for VA-LRTI alone. CONCLUSION: After controlling for relevant confounders, we could not find an association between occurrence of VA-LRTI and ICU mortality in patients with ARDS.

Early and Late Cardiovascular Events in Patients Hospitalized for Community-Acquired Pneumonia. / Eventos cardiovasculares tempranos y tardíos en pacientes ingresados por neumonía adquirida en la comunidad.

INTRODUCTION: Community-acquired pneumonia increases the risk of cardiovascular events (CVE). The objective of this study was to analyze host, severity, and etiology factors associated with the appearance of early and late events and their impact on mortality. METHOD: Prospective multicenter cohort study in patients hospitalized for pneumonia. CVE and mortality rates were collected at admission, 30-day follow-up (early events), and one-year follow-up (late events). RESULTS: In total, 202 of 1,967 (10.42%) patients presented early CVE and 122 (6.64%) late events; 16% of 1-year mortality was attributed to cardiovascular disease. The host risk factors related to cardiovascular complications were: age ≥65 years, smoking, and chronic heart disease. Alcohol abuse was a risk factor for early events, whereas obesity, hypertension, and chronic renal failure were related to late events. Severe sepsis and Pneumonia Severity Index (PSI) ≥3 were independent risk factors for early events, and only PSI ≥3 for late events. Streptococcus pneumoniae was the microorganism associated with most cardiovascular complications. Developing CVE was an independent factor related to early (OR 2.37) and late mortality (OR 4.05). CONCLUSIONS: Age, smoking, chronic heart disease, initial severity, and S. pneumoniae infection are risk factors for early and late events, complications that have been related with an increase of the mortality risk during and after the pneumonia episode. Awareness of these factors can help us make active and early diagnoses of CVE in hospitalized CAP patients and design future interventional studies to reduce cardiovascular risk.

Community-Acquired Pneumonia Patients at Risk for Early and Long-term Cardiovascular Events Are Identified by Cardiac Biomarkers.

BACKGROUND: Community-acquired pneumonia (CAP) increases the risk of cardiovascular complications during and following the episode. The goal of this study was to determine the usefulness of cardiovascular and inflammatory biomarkers for assessing the risk of early (within 30 days) or long-term (1-year follow-up) cardiovascular events. METHODS: A total of 730 hospitalized patients with CAP were prospectively followed up during 1 year. Cardiovascular (proadrenomedullin [proADM], pro-B-type natriuretic peptide (proBNP), proendothelin-1, and troponin T) and inflammatory (interleukin 6 [IL-6], C-reactive protein, and procalcitonin) biomarkers were measured on day 1, at day 4/5, and at day 30. RESULTS: Ninety-two patients developed an early event, and 67 developed a long-term event. Significantly higher initial levels of proADM, proendothelin-1, troponin, proBNP, and IL-6 were recorded in patients who developed cardiovascular events. Despite a decrease at day 4/5, levels remained steady until day 30 in those who developed late events. Biomarkers (days 1 and 30) independently predicted cardiovascular events adjusted for age, previous cardiac disease, Pao2/Fio2 < 250 mm Hg, and sepsis: ORs (95% CIs), proendothelin-1, 2.25 (1.34-3.79); proADM, 2.53 (1.53-4.20); proBNP, 2.67 (1.59-4.49); and troponin T, 2.70 (1.62-4.49) for early events. For late events, the ORs (95% CIs) were: proendothelin-1, 3.13 (1.41-7.80); proADM, 2.29 (1.01-5.19); and proBNP, 2.34 (1.01-5.56). Addition of IL-6 levels at day 30 to proendothelin-1 or proADM increased the ORs to 3.53 and 2.80, respectively. CONCLUSIONS: Cardiac biomarkers are useful for identifying patients with CAP at high risk for early and long-term cardiovascular events. They may aid personalized treatment optimization and for designing future interventional studies to reduce cardiovascular risk.

Impact of Lymphocyte and Neutrophil Counts on Mortality Risk in Severe Community-Acquired Pneumonia with or without Septic Shock.

BACKGROUND: Community-acquired pneumonia (CAP) is a frequent cause of death worldwide. As recently described, CAP shows different biological endotypes. Improving characterization of these endotypes is needed to optimize individualized treatment of this disease. The potential value of the leukogram to assist prognosis in severe CAP has not been previously addressed. METHODS: A cohort of 710 patients with CAP admitted to the intensive care units (ICUs) at Hospital of Mataró and Parc Taulí Hospital of Sabadell was retrospectively analyzed. Patients were split in those with septic shock (n = 304) and those with no septic shock (n = 406). A single blood sample was drawn from all the patients at the time of admission to the emergency room. ICU mortality was the main outcome. RESULTS: Multivariate analysis demonstrated that lymphopenia <675 cells/mm3 or <501 cells/mm3 translated into 2.32- and 3.76-fold risk of mortality in patients with or without septic shock, respectively. In turn, neutrophil counts were associated with prognosis just in the group of patients with septic shock, where neutrophils <8850 cells/mm3 translated into 3.6-fold risk of mortality. CONCLUSION: lymphopenia is a preserved risk factor for mortality across the different clinical presentations of severe CAP (sCAP), while failing to expand circulating neutrophils counts beyond the upper limit of normality represents an incremental immunological failure observed just in those patients with the most severe form of CAP, septic shock.

Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study).

PURPOSE: The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP). METHODS: In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L). RESULTS: Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58-78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline. CONCLUSIONS: No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation. TRIAL REGISTRATION: NCT01420744.

Initial Inflammatory Profile in Community-acquired Pneumonia Depends on Time since Onset of Symptoms.

RATIONALE: Assessment of the inflammatory response can help the decision-making process when diagnosing community-acquired pneumonia (CAP), but there is a lack of information about the influence of time since onset of symptoms. OBJECTIVES: We studied the impact of the number of days since onset of symptoms on inflammatory cytokines and biomarker concentrations at CAP diagnosis in hospitalized patients. METHODS: We performed a secondary analysis in two prospective cohorts including 541 patients in the derivation cohort and 422 in the validation cohort. The time since onset of symptoms was self-reported, and patients were classified as early presenters (<3 d) and nonearly presenters. Biomarkers (C-reactive protein [CRP] and procalcitonin [PCT] in both cohorts) and cytokines in the derivation cohort (IL-1, - 6, -8, -10, and tumor necrosis factor-α) were measured within 24 hours of hospital admission. MEASUREMENTS AND MAIN RESULTS: In early presenters, CRP was significantly lower, whereas PCT, IL-6, and IL-8 were higher. Nonearly presenters showed significantly lower PCT, IL-6, and IL-8 levels. In the validation cohort, CRP and PCT exhibited identical patterns: CRP levels were 36.4% greater in patients with 3 or more days since onset of symptoms than in those with less than 3 days since symptom onset in the derivation cohort and 38.2% in the validation cohort. PCT levels were 40% lower in patients with 3 or more days since onset of symptoms in the derivation cohort and 56% in the validation cohort. CONCLUSIONS: Time since symptom onset modifies the systemic inflammatory profile at CAP diagnosis. This information has relevant clinical implications for management, and it should be taken into account in the design of future clinical trials.

Oral health and risk of pneumonia in asthmatic pacients with inhaled treatment. / Salud bucodental y riesgo de neumonía en pacientes asmáticos con tratamiento inhalado.

INTRODUCTION AND OBJECTIVE: Asthma is a chronic disease requiring inhaled treatment and in addition it is a risk factor (RF) of pneumonia. In the oropharyngeal cavity there are numerous species of bacteria that could be dragged to the bronco-alveolar level. OBJECTIVE: to decide whether oral health is a community acquired pneumonia (CAP) RF in asthmatic patients who are taking inhaled treatment, and determining whether the frequency of use of inhalation devices and the type of inhaled drug are CAP RF. PATIENTS AND METHOD: Case-control study in asthmatic population with inhaled treatment. We recruited 126 asthmatic patients diagnosed with pneumonia by clinical and radiological criteria (cases) and 252 asthmatics not diagnosed with pneumonia during the last year (controls), matched by age. The main factor of study was the General Oral Health Assessment Index (GOHAI) score. RESULTS: Bivariated analysis showed a statistically significant association of CAP with a GOHAI score≤57 points (poor oral health) (OR 1.69), anticholinergic treatment (OR 2.41), 6 or more inhalations (3.23), chamber use (OR 1.62), FEV1 (OR 0.98), altered functionality (OR 2.08) and psychiatric disorders or depression (OR 0.41). The multivariated analysis shows an independent association of performing 6 or more inhalations per day (OR 2.74) and functional impairment (OR 1.67). CONCLUSIONS: The results suggest that poor oral health may be a CAP RF.

Risk Factors for Community-Acquired Pneumonia in Adults: A Systematic Review of Observational Studies.

We performed a systematic review of the literature to establish conclusive evidence of risk factors for community-acquired pneumonia (CAP). Observational studies (cross-sectional, case-control, and cohort studies) the primary outcome of which was to assess risk factors for CAP in both hospitalized and ambulatory adult patients with radiologically confirmed pneumonia were selected. The Newcastle-Ottawa Scale specific for cohort and case-control designs was used for quality assessment. Twenty-nine studies (20 case-control, 8 cohort, and 1 cross-sectional) were selected, with 44.8% of them focused on elderly subjects ≥65 years of age and 34.5% on mixed populations (participants' age >14 years). The median quality score was 7.44 (range 5-9). Age, smoking, environmental exposures, malnutrition, previous CAP, chronic bronchitis/chronic obstructive pulmonary disease, asthma, functional impairment, poor dental health, immunosuppressive therapy, oral steroids, and treatment with gastric acid-suppressive drugs were definitive risk factors for CAP. Some of these factors are modifiable. Regarding other factors (e.g., gender, overweight, alcohol use, recent respiratory tract infections, pneumococcal and influenza vaccination, inhalation therapy, swallowing disorders, renal and liver dysfunction, diabetes, and cancer) no definitive conclusion could be established. Prompt assessment and correction of modifiable risk factors could reduce morbidity and mortality among adult CAP patients, particularly among the elderly.

Gamma globulin fraction of the proteinogram and chronic obstructive pulmonary disease exacerbations. / Fracción gamma del proteinograma y agudizaciones de la enfermedad pulmonar obstructiva crónica.

OBJECTIVES: To evaluate the levels of the serum gamma globulin fraction in proteinograms as a biomarker to assess the severity, and to predict the mortality and new exacerbations in patients admitted for an exacerbation of a COPD. PATIENTS AND METHODS: The VIRAE study was carried out on a cohort of patients hospitalized for an exacerbation of probable infectious origin of COPD over a period of 2 years. The levels of the serum gamma globulin fraction were analyzed in the proteinogram of 120 patients. The main clinical indicators of severity were also evaluated. Key features were compared in 2 groups (gamma fraction in the proteinogram greater or less than 6.6g/dl). RESULTS: The levels of the serum gamma fraction in the proteinogram correlated with the FEV1 (P=.009), the CRP (P=.04), and the number of readmissions after 6 months of hospitalization (P=.04). We observed a good association with the GOLD scale, the BODE index and the mMRC dyspnea scale; and also with treatment with oral corticoids and home oxygen therapy. We did not find it to be a good predictor of mortality, despite observing increased mortality rates one year after hospital admission in patients with low levels of the factor. CONCLUSIONS: The levels of the gamma globulin fraction in proteinograms has a good correlation with the FEV1. In addition, they are associated with a greater severity of patients with COPD. This simple biomarker may be useful in identifying high-risk patients.

Serum levels of immunoglobulins and severity of community-acquired pneumonia.

INSTRUCTION: There is evidence of a relationship between severity of infection and inflammatory response of the immune system. The objective is to assess serum levels of immunoglobulins and to establish its relationship with severity of community-acquired pneumonia (CAP) and clinical outcome. METHODS: This was an observational and cross-sectional study in which 3 groups of patients diagnosed with CAP were compared: patients treated in the outpatient setting (n=54), patients requiring in-patient care (hospital ward) (n=173), and patients requiring admission to the intensive care unit (ICU) (n=191). RESULTS: Serum total IgG (and IgG subclasses IgG1, IgG2, IgG3, IgG4), IgA and IgM were measured at the first clinical visit. Normal cutpoints were defined as the lowest value obtained in controls (≤680, ≤323, ≤154, ≤10, ≤5, ≤30 and ≤50 mg/dL for total IgG, IgG1, IgG2, IgG3, IgG4, IgM and IgA, respectively). Serum immunoglobulin levels decreased in relation to severity of CAP. Low serum levels of total IgG, IgG1 and IgG2 showed a relationship with ICU admission. Low serum level of total IgG was independently associated with ICU admission (OR=2.45, 95% CI 1.4 to 4.2, p=0.002), adjusted by the CURB-65 severity score and comorbidities (chronic respiratory and heart diseases). Low levels of total IgG, IgG1 and IgG2 were significantly associated with 30-day mortality. CONCLUSIONS: Patients with severe CAP admitted to the ICU showed lower levels of immunoglobulins than non-ICU patients and this increased mortality.

IgG2 as an independent risk factor for mortality in patients with community-acquired pneumonia.

BACKGROUND: Mortality in patients with community-acquired pneumonia (CAP) remains high despite improvements in treatment. OBJECTIVE: To determine immunoglobulin levels in patients with CAP and impact on disease severity and mortality. METHODOLOGY: Observational study. Hospitalized patients with CAP were followed up for 30 days. Levels of immunoglobulin G (IgG) and subclasses, immunoglobulin A (IgA) and immunoglobulin M (IgM) were measured in serum within 24 hours of CAP diagnosis. RESULTS: Three hundred sixty-two patients with CAP were enrolled -172 ward-treated and 190 intensive care unit-treated. Intensive care unit-treated patients had significantly lower values of IgG1, IgG2, IgG3 subclasses, and IgA than ward-treated patients. Thirty-eight patients died before 30 days. Levels of IgG2 were significantly lower in non-survivors than survivors (P=.004) and IgG2 <301 mg/dL was associated with poorer survival according to both the bivariate (hazard ratio 4.47; P<.001) and multivariate (HR 3.48; P=.003) analyses. CONCLUSIONS: Patients with CAP with IgG2 levels <301 mg/dL had a poorer prognosis and a higher risk of death. Our study suggests the usefulness of IgG2 to predict CAP evolution and to provide support measures or additional treatment.

[Epidemiology of community-acquired severe sepsis. A population-based study]. / Epidemiología de la sepsis grave adquirida en la comunidad. Estudio de base poblacional.

BACKGROUND AND OBJECTIVE: Most studies aimed at getting to know the incidence of severe sepsis have methodological limitations which condition results that are difficult to compare and are inapplicable when it comes to estimating the necessary resources. Our objective is to evaluate the incidence and epidemiological aspects of community-acquired severe sepsis which require intensive care unit admission. PATIENTS AND METHOD: Prospective observational population-based study in a population of 180,000 adults over 15 years old and a general hospital with 350 beds and 14 ICU beds. All episodes of community-acquired infection requiring admission to ICU due to severe sepsis were registered over a period of 9 years. The variables analyzed were: age, sex, SAPS II score, length of stay in ICU, type of infection, isolated microorganism, and deaths during their ICU admission. A statistical bivariate analysis and a multiple logistic regression were performed. RESULTS: Nine hundred and seventeen episodes with an average age of 65.2 years. The most frequent infectious focus was pulmonary (55.2%). The average SAPS II severity score index was 37.87 and mortality 19.7%. The annual incidence was 51.54 episodes per 100,000 adult inhabitants, meaning 1.97 ICU beds per day. In the multivariate analysis, the SAPS II score and a known aetiology were demonstrated as mortality risk factors. CONCLUSIONS: This study brings us some epidemiological data from a population-based perspective which help us to care for patients better in our geographical area. The average annual incidence is 51.5 cases per 100,000 adult inhabitants which means that 2 ICU beds per day to attend this population.

Professions and Working Conditions Associated With Community-Acquired Pneumonia.

INTRODUCTION: Community-acquired pneumonia (CAP) is not considered a professional disease, and the effect of different occupations and working conditions on susceptibility to CAP is unknown. The aim of this study is to determine whether different jobs and certain working conditions are risk factors for CAP. METHODOLOGY: Over a 1-year period, all radiologically confirmed cases of CAP (n=1,336) and age- and sex-matched controls (n=1,326) were enrolled in a population-based case-control study. A questionnaire on CAP risk factors, including work-related questions, was administered to all participants during an in-person interview. RESULTS: The bivariate analysis showed that office work is a protective factor against CAP, while building work, contact with dust and sudden changes of temperature in the workplace were risk factors for CAP. The occupational factor disappeared when the multivariate analysis was adjusted for working conditions. Contact with dust (previous month) and sudden changes of temperature (previous 3 months) were risk factors for CAP, irrespective of the number of years spent working in these conditions, suggesting reversibility. CONCLUSION: Some recent working conditions such as exposure to dust and sudden changes of temperature in the workplace are risk factors for CAP. Both factors are reversible and preventable.