Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pra...

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Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America

Arsenic-induced oxidative stress and its reversibility

Preliminary data suggest that people with obesity are at increased risk of severe COVID-19. However, as data on metabolic parameters (such as BMI and levels of glucose and insulin) in patients with COVID-19 are scarce, increased reporting is needed to improve our understanding of COVID-19 and the care of affected patients.

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Obesity and impaired metabolic health in patients with COVID-19.

Importance In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial. Objective To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response. Design, Setting, and Participants Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150 mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012. Interventions Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission. Main Outcomes and Measures The primary outcome was treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortality was a secondary outcome and adverse events were assessed. Results There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) ( P  = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P  = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P  = .37); the difference between groups was 5% (95% CI, −6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group ( P  = .34). Conclusions and Relevance Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population. Trial Registration clinicaltrials.gov Identifier:NCT00908713

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Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With Severe Community-Acquired Pneumonia and High Inflammatory Response A Randomized Clinical Trial

Importance Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option. Objective To determine the effect of hydrocortisone on treatment failure on day 21 in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute respiratory failure. Design, Setting, and Participants Multicenter randomized double-blind sequential trial conducted in France, with interim analyses planned every 50 patients. Patients admitted to the intensive care unit (ICU) for COVID-19–related acute respiratory failure were enrolled from March 7 to June 1, 2020, with last follow-up on June 29, 2020. The study intended to enroll 290 patients but was stopped early following the recommendation of the data and safety monitoring board. Interventions Patients were randomized to receive low-dose hydrocortisone (n = 76) or placebo (n = 73). Main Outcomes and Measures The primary outcome, treatment failure on day 21, was defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. Prespecified secondary outcomes included the need for tracheal intubation (among patients not intubated at baseline); cumulative incidences (until day 21) of prone position sessions, extracorporeal membrane oxygenation, and inhaled nitric oxide; Pao2:Fio2ratio measured daily from day 1 to day 7, then on days 14 and 21; and the proportion of patients with secondary infections during their ICU stay. Results The study was stopped after 149 patients (mean age, 62.2 years; 30.2% women; 81.2% mechanically ventilated) were enrolled. One hundred forty-eight patients (99.3%) completed the study, and there were 69 treatment failure events, including 11 deaths in the hydrocortisone group and 20 deaths in the placebo group. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (difference of proportions, –8.6% [95.48% CI, –24.9% to 7.7%];P = .29). Of the 4 prespecified secondary outcomes, none showed a significant difference. No serious adverse events were related to the study treatment. Conclusions and Relevance In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped early and likely was underpowered to find a statistically and clinically important difference in the primary outcome. Trial Registration ClinicalTrials.gov Identifier:NCT02517489

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Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

It is unclear whether an ‘obesity survival paradox’ exists for pneumonia. Therefore, we conducted a meta-analysis to assess the associations between increased body mass index (BMI), pneumonia risk, and mortality risk. Cohort studies were identified from the PubMed and Embase databases. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random effects model. Thirteen cohort studies on pneumonia risk (n = 1,536,623), and ten cohort studies on mortality (n = 1,375,482) were included. Overweight and obese individuals were significantly associated with an increased risk of pneumonia (RR = 1.33, 95% CI 1.04 to 1.71, P = 0.02, I

 2
  = 87%). In the dose–response analysis, the estimated summary RR of pneumonia per 5 kg/m2 increase in BMI was 1.04 (95% CI 1.01 to 1.07, P = 0.01, I

 2
  = 84%). Inversely, overweight and obese subjects were significantly associated with reduced risk of pneumonia mortality (RR = 0.83, 95% CI 0.77 to 0.91, P < 0.01, I

 2
  = 34%). The estimated summary RR of mortality per 5 kg/m2 increase in BMI was 0.95 (95% CI 0.93 to 0.98, P < 0.01, I

 2
  = 77%). This meta-analysis suggests that an ‘obesity survival paradox’ exists for pneumonia. Because this meta-analysis is based on observational studies, more studies are required to confirm the results.

https://link.springer.com/content/pdf/10.1186%2F1741-7015-12-61.pdf

Obesity survival paradox in pneumonia: a meta-analysis

Background
The benefit of corticosteroids in community-acquired pneumonia (CAP) remains controversial. We did a meta-analysis to include all the randomized controlled trials (RCTs) which used corticosteroids as adjunctive therapy, to examine the benefits and risks of corticosteroids in the treatment of CAP in adults.

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Corticosteroids in the treatment of community-acquired pneumonia in adults: a meta-analysis.

The chitinase-like protein YKL-40, which binds chitin but lacks chitinase activity, has been found to be either the cause or a biomarker for asthma. The aim of our study was to investigate whether serum YKL-40 levels are increased in Chinese patients with asthma and identify its correlation to acute exacerbation, total serum immunoglobulin (Ig)E, the percentage of peripheral blood eosinophils and lung function. We quantified serum YKL-40 levels, total IgE levels and peripheral blood eosinophil percentages in patients with asthma, as well as in controls from the communities surrounding our hospital. The lung function of asthma subjects was also measured. Our data showed that the serum YKL-40 levels were significantly elevated in patients with asthma compared with controls and, when the asthma subjects were stratified, serum YKL-40 levels in the exacerbation group were higher than those in the stable and control groups. In addition, serum YKL-40 levels correlated positively with total serum IgE levels and the percentage of peripheral blood eosinophils, but correlated inversely with lung functions. Thus, we conclude that YKL-40 is found in increased quantities in the serum of Chinese patients with asthma, and its level correlates with exacerbation attacks, indicating that high levels of serum YKL-40 may be a biological characteristic of the exacerbation of asthma.

https://erj.ersjournals.com/content/erj/35/4/757.full.pdf

YKL-40 in asthmatic patients, and its correlations with exacerbation, eosinophils and immunoglobulin E

Recently, the serum levels of YKL-40, a chitinase-like glycoprotein, have been shown to be significantly elevated in asthmatics and are associated with asthma severity. Although these studies raise the possibility that YKL-40 may influence asthma, the mechanisms remain unknown. This study firstly investigated the mechanisms involved in YKL-40-mediated inflammation in human bronchial epithelial cells (HBECs) and analyzed the soluble factors secreted by bronchial epithelial cells exposed to YKL-40 that were responsible for increasing proliferation and migration of primary normal human bronchial smooth muscle cells (BSMCs). YKL-40-induced inflammation was assayed in two HBECs (BEAS-2B cell line and primary HBECs). In addition, we treated BEAS-2B cells and HBECs with YKL-40 and added the conditioned culture media to BSMCs. The proliferation and migration of BSMCs were determined by premixed WST-1 cell proliferation reagent (Clontech Laboratories) and QCM chemotaxis migration assay (Millipore), respectively. Bronchial epithelial cells treated with YKL-40 resulted in a significant increase of IL-8 production, which was dependent on MAPK (JNK and ERK) and NF-κB pathways activation. YKL-40-induced IL-8 was found to further stimulate proliferation and migration of BSMCs, and the effects were inhibited after neutralizing IL-8. Through investigating the interaction of airway epithelium and smooth muscle, our findings implicate that YKL-40 may be involved in the inflammation of asthma by induction of IL-8 from epithelium, subsequently contributing to BSMC proliferation and migration. Moreover, inhibition of IL-8 signaling is a potential therapeutic target for YKL-40-induced inflammation and remodeling of asthma.

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YKL-40 induces IL-8 expression from bronchial epithelium via MAPK (JNK and ERK) and NF-κB pathways, causing bronchial smooth muscle proliferation and migration.

OBJECTIVES Several studies have compared the clinical effect of β-lactam/macrolide (BLM) dual therapy versus β-lactam (BL) monotherapy in community-acquired pneumonia (CAP) patients. However, the results remain controversial. Thus, we did this meta-analysis to determine which treatment was more effective. METHODS Databases comprising PubMed, Embase and the Cochrane Register of Controlled Trials were searched to find relevant studies. The primary outcome was mortality. The Newcastle-Ottawa scale was used to evaluate the methodological quality of included studies. Multivariable-adjusted ORs with 95% CIs were pooled in the random effects model. RESULTS Four prospective cohort studies and 12 retrospective cohort studies were included (n = 42 942). Compared with BL monotherapy, BLM dual therapy was significantly associated with reduced mortality (adjusted OR 0.67, 95% CI 0.61-0.73, P < 0.001, I(2) = 3%). Subsequent subgroup analyses confirmed that BLM dual therapy was statistically superior to BL monotherapy in reduction of mortality. Sensitivity analyses strengthened the validity of the results. CONCLUSIONS In comparison with BL monotherapy, BLM dual therapy might reduce mortality risk in patients with CAP. Because this finding is based on observational studies, randomized controlled trials are required to demonstrate the usefulness of BLM dual therapy in the treatment of CAP.

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β-Lactam/macrolide dual therapy versus β-lactam monotherapy for the treatment of community-acquired pneumonia in adults: a systematic review and meta-analysis

Qingyu Xiu

Papers

Obesity survival paradox in pneumonia: a meta-analysis

Corticosteroids in the treatment of community-acquired pneumonia in adults: a meta-analysis.

YKL-40 in asthmatic patients, and its correlations with exacerbation, eosinophils and immunoglobulin E

YKL-40 induces IL-8 expression from bronchial epithelium via MAPK (JNK and ERK) and NF-κB pathways, causing bronchial smooth muscle proliferation and migration.

β-Lactam/macrolide dual therapy versus β-lactam monotherapy for the treatment of community-acquired pneumonia in adults: a systematic review and meta-analysis